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Sample records for oxidation phenotype rs

  1. rs657075 (CSF2 Is Associated with the Disease Phenotype (BAS-G of Ankylosing Spondylitis

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    Wei-Chiao Chen

    2017-01-01

    Full Text Available Ankylosing spondylitis (AS is a systemic autoimmune disease mainly affecting the lumbar spine and sacroiliac joints, and exhibits peripheral inflammatory arthropathy. More than 25 loci have been identified as associated with AS. Because both AS and rheumatoid arthritis (RA are autoimmune diseases that may share some common genetic factors, we therefore examined if the newly identified RA genetic polymorphisms were associated with AS in a Taiwanese population. In this study, we enrolled 475 AS patients and 11,301 healthy subjects from a Taiwanese biobank as controls. Although none of single-nucleotide polymorphisms (SNPs were associated with the susceptibility to AS, the AS disease index Bath AS Global (BAS-G clinical phenotype was observed as significantly correlated to the AA genotype of rs657075 (CSF2. The significance remains after gender/age/disease duration adjustment and after group categorization by human leukocyte antigen-B 27 (HLA-B27 genotype. We further investigated the possible functions of rs657075 through bioinformatics approaches. Results revealed that polymorphism of rs657075 is able to influence the expression of acyl-CoA synthetase long-chain family member 6 (ACSL6. In conclusion, our study indicated that rs657075 (CSF2 is strongly associated with the AS disease index Bath AS Global (BAS-G clinical phenotype.

  2. Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits

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    Almind Katrine

    2008-12-01

    Full Text Available Abstract Background Several studies in multiple ethnicities have reported linkage to type 2 diabetes on chromosome 1q21-25. Both PKLR encoding the liver pyruvate kinase and NOS1AP encoding the nitric oxide synthase 1 (neuronal adaptor protein (CAPON are positioned within this chromosomal region and are thus positional candidates for the observed linkage peak. The C-allele of PKLR rs3020781 and the T-allele of NOS1AP rs7538490 are reported to strongly associate with type 2 diabetes in various European-descent populations comprising a total of 2,198 individuals with a combined odds ratio (OR of 1.33 [1.16–1.54] and 1.53 [1.28–1.81], respectively. Our aim was to validate these findings by investigating the impact of the two variants on type 2 diabetes and related quantitative metabolic phenotypes in a large study sample of Danes. Further, we intended to expand the analyses by examining the effect of the variants in relation to overweight and obesity. Methods PKLR rs3020781 and NOS1AP rs7538490 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising a total of 16,801 and 16,913 individuals, respectively. The participants were ascertained from four different study groups; the population-based Inter99 cohort (nPKLR = 5,962, nNOS1AP = 6,008, a type 2 diabetic patient group (nPKLR = 1,873, nNOS1AP = 1,874 from Steno Diabetes Center, a population-based study sample (nPKLR = 599, nNOS1AP = 596 from Steno Diabetes Center and the ADDITION Denmark screening study cohort (nPKLR = 8,367, nNOS1AP = 8,435. Results In case-control studies we evaluated the potential association between rs3020781 and rs7538490 and type 2 diabetes and obesity. No significant associations were observed for type 2 diabetes (rs3020781: pAF = 0.49, OR = 1.02 [0.96–1.10]; rs7538490: pAF = 0.84, OR = 0.99 [0.93–1.06]. Neither did we show association with overweight or obesity. Additionally, the PKLR and the NOS1AP genotypes were demonstrated not

  3. The Calcium-Sensing Receptor Gene Polymorphism rs1801725 and Calcium-Related Phenotypes in Hemodialysis Patients

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    Alicja E. Grzegorzewska

    2018-05-01

    Full Text Available Background/Aims: The calcium-sensing receptor gene (CASR rs1801725 variant is responsible for a non-conservative amino-acid change (A986S in the calcium-sensing receptor cytoplasmic tail. We hypothesized that rs1801725 polymorphism might be helpful in understanding Ca-related abnormalities in HD patients. Methods: In 1215 subjects (245 on cinacalcet, we determined the associations of rs1801725 with secondary hyperparathyroidism (sHPT-related laboratory parameters, PTH-decreasing effect of cinacalcet hydrochloride, coronary artery disease (CAD, myocardial infarction (MI, nephrolithiasis-related ESRD, and mortality. CASR rs7652589(Ars1801725(G>T haplotypes and rs1801725 epistatic interactions with vitamin D signaling pathway genes were examined for associations with selected phenotypes. Results: The rs1801725 variant allele showed an increasing independent effect on plasma PTH (Pcorrected = 0.009. CASR rs7652589_rs1801725 AT haplotype was associated with 1.7-fold higher frequency of PTH levels over 437 pg/mL than the reference haplotype GG (P = 0.001. CASR rs7652589_rs1801725 AG haplotype was 1.5-fold more frequent in nephrolithiasis-related ESRD than the GG haplotype (P = 0.004. There were no significant associations between rs1801725, CAD, MI, and response to cinacalcet. Variant homozygosity of rs1801725 correlated independently with higher infection-related mortality compared with heterozygosity (HR 7.95, 95%CI 2.15 – 29.37, P = 0.003 and major homozygosity (HR 5.89, 95%CI 1.69 – 20.55, P = 0.040. CASR rs1801725 did not show epistatic interactions with vitamin D signaling pathway genes concerning tested associations. Conclusion: The variant allele of CASR rs1801725 solely and together with the variant allele of rs7652589 increases risk of more advanced sHPT. Homozygosity of the rs1801725 variant allele contributes to infection-related mortality in HD patients.

  4. Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association of rs2470102 with Skin Pigmentation.

    Science.gov (United States)

    Mishra, Anshuman; Nizammuddin, Sheikh; Mallick, Chandana Basu; Singh, Sakshi; Prakash, Satya; Siddiqui, Niyamat Ali; Rai, Niraj; Carlus, S Justin; Sudhakar, Digumarthi V S; Tripathi, Vishnu P; Möls, Märt; Kim-Howard, Xana; Dewangan, Hemlata; Mishra, Abhishek; Reddy, Alla G; Roy, Biswajit; Pandey, Krishna; Chaubey, Gyaneshwer; Das, Pradeep; Nath, Swapan K; Singh, Lalji; Thangaraj, Kumarasamy

    2017-03-01

    Our understanding of the genetics of skin pigmentation has been largely skewed towards populations of European ancestry, imparting less attention to South Asian populations, who behold huge pigmentation diversity. Here, we investigate skin pigmentation variation in a cohort of 1,167 individuals in the Middle Gangetic Plain of the Indian subcontinent. Our data confirm the association of rs1426654 with skin pigmentation among South Asians, consistent with previous studies, and also show association for rs2470102 single nucleotide polymorphism. Our haplotype analyses further help us delineate the haplotype distribution across social categories and skin color. Taken together, our findings suggest that the social structure defined by the caste system in India has a profound influence on the skin pigmentation patterns of the subcontinent. In particular, social category and associated single nucleotide polymorphisms explain about 32% and 6.4%, respectively, of the total phenotypic variance. Phylogeography of the associated single nucleotide polymorphisms studied across 52 diverse populations of the Indian subcontinent shows wide presence of the derived alleles, although their frequencies vary across populations. Our results show that both polymorphisms (rs1426654 and rs2470102) play an important role in the skin pigmentation diversity of South Asians. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Fat phenotype, associated factors and rs9939609 polymorphism of the FTO gene

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    William Alves Lima

    2010-02-01

    Full Text Available The purpose of this work was to review the main results of studies that have analysed the relationship between the rs9939609 single nucleotide polymorphism (SNP of the FTO gene and the manifestation of overweight/obesity with its associated co-morbidity, and to discuss the interaction of this polymorphism with the other factors which cause obesity. The search was performed using the MEDLINE, Highwire, Science Direct and SciELO databases, applying the following key words: FTO rs9939609, obesity genetic, gene associated obesity, FTO contributes obesity. Inclusion criteria were: original articles where the search was performed in humans and including the rs9939609. Articles that analysed the FTO gene associated with preinstalled hormonal diseases were excluded. Of the several SNP associated with the FTO gene, rs9939609 has been the most researched (studied. This SNP comprises the A and T alleles, with the A homozygote being most susceptible to the development of overweight/obesity in all age ranges, especially in the caucasian population. In this situation, the control of environmental factors (alimentation and physical activity can prevent the excessive build up of fats. Obesity is related to the development of non-transmissible chronic illnesses. Association of rs9939609 polymorphism with the lipidic profile and glycemia were observed. The practicing of physical exercise and feeding habits seem to be the main contributors in the development of overweight/obesity and its resulting co-morbidity.

  6. Interleukin-6 Receptor rs7529229 T/C Polymorphism Is Associated with Left Main Coronary Artery Disease Phenotype in a Chinese Population

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    Feng He

    2014-04-01

    Full Text Available Left main coronary artery disease (LMCAD is a particular severe phenotype of coronary artery disease (CAD and heritability. Interleukin (IL may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD. In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS and ligation detection reaction (LDR method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR = 1.46, 95% confidence interval (CI = 1.02–2.11, p = 0.042; CC + TC vs. TT, adjusted OR = 1.31, 95% CI = 1.02–1.69, p = 0.037. None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed.

  7. The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals

    DEFF Research Database (Denmark)

    Banasik, Karina; Hollensted, Mette; Andersson, Ehm

    2012-01-01

    Variations within the FOXA family have been studied for a putative contribution to the risk of type 2 diabetes (T2D), and recently the minor T-allele of FOXA2 rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate control...... and 2) a lower risk of developing T2D. Secondly, we investigated whether rs1205923 in FOXA2 associated with other glucose-related phenotypes....... procedure to enhance the statistical power of genome wide association studies in detecting associations between low-frequency variants and a given trait.Thus, the primary aim of this study was to investigate whether the minor T-allele of rs1205923 in FOXA2 associated with 1) decreased fasting plasma glucose...

  8. Phenotypic and genomic characterization of the antimicrobial producer Rheinheimera sp. EpRS3 isolated from the medicinal plant Echinacea purpurea: insights into its biotechnological relevance.

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    Presta, Luana; Bosi, Emanuele; Fondi, Marco; Maida, Isabel; Perrin, Elena; Miceli, Elisangela; Maggini, Valentina; Bogani, Patrizia; Firenzuoli, Fabio; Di Pilato, Vincenzo; Rossolini, Gian Maria; Mengoni, Alessio; Fani, Renato

    2017-04-01

    In recent years, there has been increasing interest in plant microbiota; however, despite medicinal plant relevance, very little is known about their highly complex endophytic communities. In this work, we report on the genomic and phenotypic characterization of the antimicrobial compound producer Rheinheimera sp. EpRS3, a bacterial strain isolated from the rhizospheric soil of the medicinal plant Echinacea purpurea. In particular, EpRS3 is able to inhibit growth of different bacterial pathogens (Bcc, Acinetobacter baumannii, and Klebsiella pneumoniae) which might be related to the presence of gene clusters involved in the biosynthesis of different types of secondary metabolites. The outcomes presented in this work highlight the fact that the strain possesses huge biotechnological potential; indeed, it also shows antimicrobial effects upon well-described multidrug-resistant (MDR) human pathogens, and it affects plant root elongation and morphology, mimicking indole acetic acid (IAA) action. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  9. X-linked retinoschisis: RS1 mutation severity and age affect the ERG phenotype in a cohort of 68 affected male subjects.

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    Bowles, Kristen; Cukras, Catherine; Turriff, Amy; Sergeev, Yuri; Vitale, Susan; Bush, Ronald A; Sieving, Paul A

    2011-11-29

    To assess the effect of age and RS1 mutation on the phenotype of X-linked retinoschisis (XLRS) subjects using the clinical electroretinogram (ERG) in a cross-sectional analysis. Sixty-eight XLRS males 4.5 to 55 years of age underwent genotyping, and the retinoschisis (RS1) mutations were classified as less severe (27 subjects) or more severe (41 subjects) based on the putative impact on the protein. ERG parameters of retinal function were analyzed by putative mutation severity with age as a continuous variable. The a-wave amplitude remained greater than the lower limit of normal (mean, -2 SD) for 72% of XLRS males and correlated with neither age nor mutation class. However, b-wave and b/a-ratio amplitudes were significantly lower in the more severe than in the less severe mutation groups and in older than in younger subjects. Subjects up to 10 years of age with more severe RS1 mutations had significantly greater b-wave amplitudes and faster a-wave trough implicit times than older subjects in this group. RS1 mutation putative severity and age both had significant effects on retinal function in XLRS only in the severe mutation group, as judged by ERG analysis of the b-wave amplitude and the b/a-ratio, whereas the a-wave amplitude remained normal in most. A new observation was that increasing age (limited to those aged 55 and younger) caused a significant delay in XLRS b-wave onset (i.e., a-wave implicit time), even for those who retained considerable b-wave amplitudes. The delayed b-wave onset suggested that dysfunction of the photoreceptor synapse or of bipolar cells increases with age of XLRS subjects.

  10. The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals

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    Banasik Karina

    2012-02-01

    Full Text Available Abstract Background Variations within the FOXA family have been studied for a putative contribution to the risk of type 2 diabetes (T2D, and recently the minor T-allele of FOXA2 rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate control procedure to enhance the statistical power of genome wide association studies in detecting associations between low-frequency variants and a given trait. Thus, the primary aim of this study was to investigate whether the minor T-allele of rs1205923 in FOXA2 associated with 1 decreased fasting plasma glucose and 2 a lower risk of developing T2D. Secondly, we investigated whether rs1205923 in FOXA2 associated with other glucose-related phenotypes. Methods The variant was genotyped in Danish individuals from four different study populations using KASPar® PCR SNP genotyping system. We examined for associations of the FOXA2 genotype with fasting plasma glucose and estimates of insulin release and insulin sensitivity following an oral glucose tolerance test in 6,162 Danish individuals from the population-based Inter99 study while association with T2D risk was assessed in 10,196 Danish individuals including four different study populations. Results The FOXA2 rs1209523 was not associated with fasting plasma glucose (effect size (β = -0.03 mmol/l (95%CI: -0.07; 0.01, p = 0.2 in glucose-tolerant individuals from the general Danish population. Furthermore, when employing a case-control setting the variant showed no association with T2D (odds ratio (OR = 0.82 (95%CI: 0.62-1.07, p = 0.1 among Danish individuals. However, when we performed the analysis in a subset of 6,022 non-obese individuals (BMI 2 an association with T2D was observed (OR = 0.68 (95%CI: 0.49-0.94, p = 0.02. Also, several indices of insulin release and β-cell function were associated with the minor T-allele of FOXA2 rs1209523 in non-obese individuals. Conclusions We failed to

  11. Oxidative stress and hemoglobin-cholesterol adduct in renal patients with different LDL phenotypes.

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    Miljkovic, Milica; Kotur-Stevuljevic, Jelena; Stefanovic, Aleksandra; Zeljkovic, Aleksandra; Vekic, Jelena; Gojkovic, Tamara; Bogavac-Stanojevic, Natasa; Nikolic, Milan; Simic-Ogrizovic, Sanja; Spasojevic-Kalimanovska, Vesna; Jelic-Ivanovic, Zorana

    2016-10-01

    Unfavorable lipid profile is a major risk factor for cardiovascular disease in renal pathology. In this study, we compared chronic renal patients and healthy controls with different LDL phenotypes (A or B) in respect of various biochemical parameters related to cardiovascular disease. Oxidative stress and anti-oxidative defense parameters [thiobarbituric acid-reacting substances (TBARS), total oxidative status (TOS), total anti-oxidative status (TAS), total protein sulfhydryl (-SH) groups], as well as red blood cell cholesterol distribution were assessed in 40 renal patients and 40 control subjects by standardized assays. LDL particle diameters were determined by polyacrylamide gradient gel electrophoresis. LDL particles are subdivided according to their size into large LDL A phenotype (diameter >25.5 nm) and small LDL B phenotype (diameter ≤25.5 nm). Renal patients with LDL A phenotype had increased oxidative stress (TOS: p LDL phenotype. A notable decrease in hemoglobin-cholesterol adduct was detected in patients with LDL A phenotype (p LDL B phenotype (p LDL B phenotype was characterized with increased TBARS (p LDL A phenotype in control group. Increased oxidative stress, decreased anti-oxidative defense followed with unfavorable changes in hemoglobin-cholesterol binding capacity, could have important influence on cardiovascular disease risk in renal patients regardless of LDL phenotype.

  12. Oxidative stress at high altitude: genotype–phenotype correlations

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    Pandey P

    2014-05-01

    Full Text Available Priyanka Pandey,1,2 MA Qadar Pasha1,2 1CSIR-Institute of Genomics and Integrative Biology, Delhi, India; 2Department of Biotechnology, University of Pune, Ganeshkhind, Pune, India Abstract: It has been well-documented that the hypobaric hypoxic environment at high altitude (HA causes stress to both the permanent residents of HA and the sojourners. This oxidative stress primarily disturbs the oxygen-sensing and vascular homeostasis pathways, thereby upsetting normal human physiology, especially in sojourners. These environmental challenges have caused dynamic evolutionary changes within natives of HA, allowing them to develop adaptive plasticity. This review focuses on the genomic and biochemical features of the molecules involved in the oxygen-sensing and vascular homeostasis pathways with respect to HA pulmonary edema (HAPE and adaptation. We review the role of genetic markers such as HIF-prolyl hydroxylase 2, endothelial PAS domain-containing protein 1, endothelial nitric oxide synthase, endothelin 1, cytochrome b-245 alpha polypeptide, and glutathione S-transferase pi 1, as well as three circulatory biomarkers (nitric oxide, endothelin 1, and 8-iso-prostaglandin F2α, by highlighting approaches such as candidate gene and genome-wide, adopted in deciphering the pathways. A disagreement between the two approaches has also been highlighted. In addition, we discuss that an overrepresentation of wild-type alleles in HA natives and mutant alleles of same polymorphisms in HAPE patients implies that the allelic variants at the same locus are involved in adaptation and HAPE, respectively. Moreover, healthy sojourners present a number of genomic features similar to HA natives, further strengthening the concept of genetic predisposition. A trend in correlation between protective and risk alleles and altered levels of circulatory markers clearly documents the phenomenon of genotype–phenotype correlations. We conclude that the genetic and biochemical

  13. Fat oxidation at rest predicts peak fat oxidation during exercise and metabolic phenotype in overweight men

    DEFF Research Database (Denmark)

    Rosenkilde, M; Nordby, P; Nielsen, L B

    2010-01-01

    OBJECTIVE: To elucidate if fat oxidation at rest predicts peak fat oxidation during exercise and/or metabolic phenotype in moderately overweight, sedentary men. DESIGN: Cross-sectional study.Subjects:We measured respiratory exchange ratio (RER) at rest in 44 moderately overweight, normotensive...... the International Diabetes Federation criteria, we found that there was a lower accumulation of metabolic risk factors in L-RER than in H-RER (1.6 vs 3.5, P=0.028), and no subjects in L-RER and four of eight subjects in H-RER had the metabolic syndrome. Resting RER was positively correlated with plasma...... triglycerides (Pexercise was positively correlated with plasma free fatty acid concentration at rest (Pexercise and a healthy metabolic...

  14. Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits

    DEFF Research Database (Denmark)

    Andreasen, Camilla Helene; Mogensen, Mette S.; Borch-Johnsen, Knut

    2008-01-01

    of the variants in relation to overweight and obesity. METHODS: PKLR rs3020781 and NOS1AP rs7538490 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising a total of 16,801 and 16,913 individuals, respectively. The participants were ascertained from four different study groups...

  15. [Catalase gene rs1001179 polymorphism and oxidative stress in patients with chronic hepatitis C and ulcerative colitis].

    Science.gov (United States)

    Bulatova, I A; Tretyakova, Yu I; Shchekotov, V V; Shchekotova, A P; Ulitina, P V; Krivtsov, A V; Nenasheva, O Yu

    2015-01-01

    To study the rs1001179 polymorphism of the catalase (CAT) gene and to estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP) in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis (UC) in the Perm Territory. Ninety patients with reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined. The serum levels of catalase and GP were determined and the polymorphic variants of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were found in all the patients. In the CHC and UC groups, the levels of catalase and GP were found to be lower than that in apparently healthy individuals. Furthermore, both groups showed a direct correlation between the activities of the enzymes. In the patients with CHC and in those with UC, the spread of genotypes and alleles generally failed to virtually differ from that in the control group. The G/G genotype was prevalent in all the groups. In the patients with CHC, the minor A allele demonstrated a significant inverse correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p = 0.047). The lower serum levels of catalase and GP are indicative of oxidative stress in the patients with CHC or UC. In the patients with CHC, the significant correlation of the pathological rs1701179 A allele marker with the processes of synthesis of antioxidant enzymes may suggest that CAT gene polymorphism in the A/A homozygotes might affect the regulation mechanism involved in the antioxidant system in the liver.

  16. The joint effect of the endothelin receptor B gene (EDNRB polymorphism rs10507875 and nitric oxide synthase 3 gene (NOS3 polymorphism rs869109213 in Slovenian patients with type 2 diabetes mellitus and diabetic retinopathy

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    Dejan Bregar

    2018-02-01

    Full Text Available Increasing evidence suggests that endothelin and nitric oxide synthase genes and their products exert biological effects on the vasculature via the nitric oxide or endothelin pathway. The aim of the study was to evaluate the association of rs10507875 and rs869109213 (alone or in interaction with diabetic retinopathy (DR in subjects with type 2 diabetes mellitus (T2DM. We genotyped the single nucleotide polymorphism rs10507875 of the endothelin receptor B gene (EDNRB and variable number tandem repeats rs869109213 of the nitric oxide synthase 3 gene (NOS3 in 270 Slovenian patients with DR and T2DM and 256 controls with T2DM without clinical signs of DR. The genotyping was performed using either real-time polymerase chain reaction (PCR or standard PCR. We found a significant association between the genotypes of NOS3 rs869109213 polymorphism and the risk of DR in the co-dominant model (4a4b genotype; 1.99-fold increased risk [1.09-3.65]; 95% confidence interval [CI]; p = 0.02, co-dominant model (4a4a genotype; 4.16-fold increased risk [1.03-16.74]; 95% CI; p = 0.04, and dominant model (4a4a and 4a4b genotypes; 2.22-fold increased risk [1.26-3.92]; 95% CI; p = 0.01 compared to the 4b4b genotype. Moreover, the joint effect of the two polymorphisms on DR risk was greater than the individual effect of each polymorphism in the analyzed genetic models. Additionally, adjusted odds ratio showed an increased risk in dominant × dominant (4.15-fold [1.40-12.26]; 95% CI; p = 0.01 and recessive × dominant (2.24-fold [1.25-4.01]; 95% CI; p = 0.02 genotype combinations of the two polymorphisms. In conclusion, our results indicate that NOS3 rs869109213 polymorphism alone or in a combination with EDNRB rs10507875 polymorphism may be associated with DR in Slovenian patients with T2DM.

  17. [The influence of STAT4 rs7574865 (G/T) polymorphism on the risk of clinical and immunological phenotypes of systemic sclerosis in a Russian patient population: Results of a pilot study].

    Science.gov (United States)

    Krylov, M Yu; Ananyeva, L P; Koneva, О А; Starovoytova, M N; Desinova, O V; Ovsyannikova, O B; Aleksandrova, E N; Novikov, A A; Guseva, I A; Konovalova, N V; Varlamov, D A

    To examine the association of signal transducer and activator transcription 4 (STAT4) rs7574865 G/T polymorphism with a predisposition to systemic sclerosis (SSC) and associated clinical and autoimmune phenotypes in a Russian population. A total of 102 patients with SSC and 103 healthy individuals as controls were examined. STAT4 rs7574865 polymorphism was investigated by real-time polymerase chain reaction. The carriers of the T allele showed a statistically significant association with SSC, a diffuse form (DF), the presence of interstitial lung disease (ILD), cardiac injury (CI), and seropositivity for anti-topoisomerase I antibodies (ATA). The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.

  18. Oxidative Stress -a Phenotypic Hallmark of Fanconi Anemia and ...

    African Journals Online (AJOL)

    ... major role in the pathogenesis of leukemia.prone diseases such as Fanconi anemia (FA) and ... Aim: To explore the oxidative stress state in children with DS and FA by ... and to evaluate of the effect of antioxidant treatment on these patients.

  19. Effect of liver disease on dextromethorphan oxidation capacity and phenotype: a study in 107 patients.

    OpenAIRE

    Larrey, D; Babany, G; Tinel, M; Freneaux, E; Amouyal, G; Habersetzer, F; Letteron, P; Pessayre, D

    1989-01-01

    1. The O-demethylation of dextromethorphan to dextrorphan exhibits a genetically-controlled polymorphism, co-segregating with that of debrisoquine hydroxylation. Dextromethorphan has been proposed as a test compound to assess drug oxidation polymorphism. 2. We studied the effects of liver disease of varying severity on dextromethorphan oxidation capacity. Phenotyping was performed using the urinary dextromethorphan/dextrorphan metabolic ratio after oral administration of 40 mg dextromethorpha...

  20. Phenotypic and genomic responses to titanium dioxide and cerium oxide nanoparticles in Arabidopsis germinants

    Science.gov (United States)

    The effects of exposure to two nanoparticles (NPs) -titanium dioxide (nano-titania) and cerium oxide (nano-ceria) at 500 mg NPs L-1 on gene expression and growth in Arabidopsis thaliana germinants were studied using microarrays and phenotype studies. After 12 days post treatment,...

  1. A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni.

    Science.gov (United States)

    Dai, Lei; Sahin, Orhan; Tang, Yizhi; Zhang, Qijing

    2017-12-15

    Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress-resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX R ) in C. jejuni We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR , which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX R phenotype and facilitating Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, the same mechanism may operate in multiple bacterial species. Additionally, we developed a novel method that allows for rapid quantification of spontaneous OX R mutants in a bacterial population. This method represents a technical

  2. Fat phenotype, associated factors and rs9939609 polymorphism of the FTO gene DOI:10.5007/1980-0037.2010v12n2p164

    Directory of Open Access Journals (Sweden)

    William Alves Lima

    2010-07-01

    Full Text Available The purpose of this work was to review the main results of studies that have analysed the relationship between the rs9939609 single nucleotide polymorphism (SNP of the FTO gene and the manifestation of overweight/obesity with its associated co-morbidity, and to discuss the interaction of this polymorphism with the other factors which cause obesity. The search was performed using the MEDLINE, Highwire, Science Direct and SciELO databases, applying the following key words: FTO rs9939609, obesity genetic, gene associated obesity, FTO contributes obesity. Inclusion criteria were: original articles where the search was performed in humans and including the rs9939609. Articles that analysed the FTO gene associated with preinstalled hormonal diseases were excluded. Of the several SNP associated with the FTO gene, rs9939609 has been the most researched (studied. This SNP comprises the A and T alleles, with the A homozygote being most susceptible to the development of overweight/obesity in all age ranges, especially in the caucasian population. In this situation, the control of environmental factors (alimentation and physical activity can prevent the excessive build up of fats. Obesity is related to the development of non-transmissible chronic illnesses. Association of rs9939609 polymorphism with the lipidic profile and glycemia were observed. The practicing of physical exercise and feeding habits seem to be the main contributors in the development of overweight/obesity and its resulting co-morbidity.

  3. Loss of Trx-2 enhances oxidative stress-dependent phenotypes in Drosophila.

    Science.gov (United States)

    Tsuda, Manabu; Ootaka, Ryousuke; Ohkura, Chiaki; Kishita, Yoshihito; Seong, Ki-Hyeon; Matsuo, Takashi; Aigaki, Toshiro

    2010-08-04

    Overexpression of thioredoxin (TRX) confers oxidative stress resistance and extends lifespan in mammals and insects. However, less is known about phenotypes associated with loss of TRX. We investigated loss-of-function phenotypes of Trx-2 in Drosophila, and found that the mutant flies are hyper-susceptible to paraquat, a free radical generator, but not to hydrogen peroxide. They contain a high amount of protein carbonyl, which dramatically increases with age. Trx-2 mutants express high levels of anti-oxidant genes, such as superoxide dismutase, catalase, and glutathione synthetase. This is the first demonstration of biochemical and physiological consequences caused by loss of Trx-2 in Drosophila. Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype

    International Nuclear Information System (INIS)

    Li Jiaxin; Waters, Stephen B.; Drobna, Zuzana; Devesa, Vicenta; Styblo, Miroslav; Thomas, David J.

    2005-01-01

    Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If i As methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago

  5. Chronic exposure of zinc oxide nanoparticles causes deviant phenotype in Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Anand, Avnika Singh; Prasad, Dipti N.; Singh, Shashi Bala; Kohli, Ekta, E-mail: ektakohli@hotmail.com

    2017-04-05

    Zinc oxide nanoparticles (ZnO NPs) are commonly used nanomaterials (NMs) with versatile applications from high-end technologies to household products. This pervasive utilisation has brought human in the close interface with nanoparticles (NPs), hence questioning their safety prior to usage is a must. In this study, we have assessed the effects of chronic exposure to ZnO NPs (<50 nm) on the model organism Drosophila melanogaster. Potential toxic effects were studied by evaluating longevity, climbing ability, oxidative stress and DNA fragmentation. Ensuing exposure, the F0 (parent), F1, F2, F3 and F4 generation flies were screened for the aberrant phenotype. Flies exposed to ZnO NPs showed distinctive phenotypic changes, like deformed segmented thorax and single or deformed wing, which were transmitted to the offspring’s in subsequent generations. The unique abnormal phenotype is evident of chronic toxicity induced by ZnO NPs, although appalling, it strongly emphasize the importance to understand NPs toxicity for safer use.

  6. Regulatory role of tetR gene in a novel gene cluster of Acidovorax avenae subsp. avenae RS-1 under oxidative stress

    OpenAIRE

    Liu, He; Yang, Chun-Lan; Ge, Meng-Yu; Ibrahim, Muhammad; Li, Bin; Zhao, Wen-Jun; Chen, Gong-You; Zhu, Bo; Xie, Guan-Lin

    2014-01-01

    Acidovorax avenae subsp. avenae is the causal agent of bacterial brown stripe disease in rice. In this study, we characterized a novel horizontal transfer of a gene cluster, including tetR, on the chromosome of A. avenae subsp. avenae RS-1 by genome-wide analysis. TetR acted as a repressor in this gene cluster and the oxidative stress resistance was enhanced in tetR-deletion mutant strain. Electrophoretic mobility shift assay demonstrated that TetR regulator bound directly to the promoter of ...

  7. Biotransformation and oxidative stress responses in rat hepatic cell-line (H4IIE) exposed to racemic ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S(+)-KP).

    Science.gov (United States)

    Mennillo, Elvira; Krøkje, Åse; Pretti, Carlo; Meucci, Valentina; Arukwe, Augustine

    2018-03-30

    Pharmaceuticals such as racemate ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S(+)-KP) are highly detectable non-steroidal anti-inflammatory drugs (NSAIDs) in the aquatic environment and therefore are designated as one of the most emerging groups of pollutants that can affect environmental and human health. The potential impact of these pharmaceuticals was assessed for the first time in vitro using a rat hepatocellular carcinoma cell line (H4IIE). Cells were exposed to low and high concentrations of these drugs. Cytotoxicity was determined by MTT reduction assay; CYP1A1 transcriptional and enzymatic levels together with canonical oxidative stress responsive markers (GPx, GR, GST and CAT) were also investigated. Cells exposed to RS-KP and S(+)-KP did not show cytotoxicity effect at the concentrations tested. However, this study highlighted differences between RS-KP and S(+)-KP in most of the evaluated markers, showing compound-, concentration- and time-specific effect patterns which suggest a potential stereo-selective toxicity of these drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Association of Calpain (CAPN) 10 (UCSNP-43, rs3792267) gene polymorphism with elevated serum androgens in young women with the most severe phenotype of polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Anastasia, Karela; Koika, Vasiliki; Roupas, Nikolaos D; Armeni, Anastasia; Marioli, Dimitra; Panidis, Dimitrios; George, Adonakis; Georgopoulos, Neoklis A

    2015-01-01

    To highlight a possible association of Calpain (CAPN 10) gene UCSNP-43 polymorphism with hormonal and metabolic traits of young women with different phenotypes of polycystic ovary syndrome (PCOS). PCOS women were genotyped for the CAPN 10 gene UCSNP-43 polymorphism. A comparison of clinical and biochemical features of women with PCOS stratified on the basis of the CAPN 10 gene UCSNP-43 variants was assessed. Anthropometric, hormonal and biochemical measurements were carried out in 668 PCOS women and 200 healthy controls. Subjects were also genotyped for the CAPN 10 gene UCSNP-43 polymorphism. The genotype frequency distributions between groups and controls were compared using the chi-square test. The association of the polymorphism with the clinical and biochemical features of the study cohort was estimated as well. No association of the frequency of CAPN 10 gene UCSNP-43 polymorphism with PCOS was detected. No association of the polymorphism with the anthropometric, biochemical and hormonal features was detected both in PCOS and control women. The polymorphism was associated with serum Δ4 androstenedione (p = 0.018), as well as with 17-OH progesterone (17-hydroxyprogesterone) among women with PCOS phenotype A (p = 0.012). CAPN 10 gene polymorphism UCSNP-43 is deprived of a metabolic contribution to cardiovascular disease (CVD). However, due to its association with androgen excess in phenotype A, CAPN 10 gene polymorphism UCSNP-43 could be used as a genetic marker for CVD in young PCOS women.

  9. Regulatory role of tetR gene in a novel gene cluster of Acidovorax avenae subsp. avenae RS-1 under oxidative stress

    Directory of Open Access Journals (Sweden)

    He eLiu

    2014-10-01

    Full Text Available Acidovorax avenae subsp. avenae is the causal agent of bacterial brown stripe disease in rice. In this study, we characterized a novel horizontal transfer of a gene cluster, including tetR, on the chromosome of A. avenae subsp. avenae RS-1 by genome-wide analysis. TetR acted as a repressor in this gene cluster and the oxidative stress resistance was enhanced in tetR-deletion mutant strain. Electrophoretic mobility shift assay (EMSA demonstrated that TetR regulator bound directly to the promoter of this gene cluster. Consistently, the results of quantitative real-time PCR also showed alterations in expression of associated genes. Moreover, the proteins affected by TetR under oxidative stress were revealed by comparing proteomic profiles of wild-type and mutant strains via 1D SDS-PAGE and LC-MS/MS analyses. Taken together, our results demonstrated that tetR gene in this novel gene cluster contributed to cell survival under oxidative stress, and TetR protein played an important regulatory role in growth kinetics, biofilm-forming capability, SOD and catalase activity, and oxide detoxicating ability.

  10. Regulatory role of tetR gene in a novel gene cluster of Acidovorax avenae subsp. avenae RS-1 under oxidative stress.

    Science.gov (United States)

    Liu, He; Yang, Chun-Lan; Ge, Meng-Yu; Ibrahim, Muhammad; Li, Bin; Zhao, Wen-Jun; Chen, Gong-You; Zhu, Bo; Xie, Guan-Lin

    2014-01-01

    Acidovorax avenae subsp. avenae is the causal agent of bacterial brown stripe disease in rice. In this study, we characterized a novel horizontal transfer of a gene cluster, including tetR, on the chromosome of A. avenae subsp. avenae RS-1 by genome-wide analysis. TetR acted as a repressor in this gene cluster and the oxidative stress resistance was enhanced in tetR-deletion mutant strain. Electrophoretic mobility shift assay demonstrated that TetR regulator bound directly to the promoter of this gene cluster. Consistently, the results of quantitative real-time PCR also showed alterations in expression of associated genes. Moreover, the proteins affected by TetR under oxidative stress were revealed by comparing proteomic profiles of wild-type and mutant strains via 1D SDS-PAGE and LC-MS/MS analyses. Taken together, our results demonstrated that tetR gene in this novel gene cluster contributed to cell survival under oxidative stress, and TetR protein played an important regulatory role in growth kinetics, biofilm-forming capability, superoxide dismutase and catalase activity, and oxide detoxicating ability.

  11. Tumor cell phenotype is sustained by selective MAPK oxidation in mitochondria.

    Directory of Open Access Journals (Sweden)

    Soledad Galli

    2008-06-01

    Full Text Available Mitochondria are major cellular sources of hydrogen peroxide (H(2O(2, the production of which is modulated by oxygen availability and the mitochondrial energy state. An increase of steady-state cell H(2O(2 concentration is able to control the transition from proliferating to quiescent phenotypes and to signal the end of proliferation; in tumor cells thereby, low H(2O(2 due to defective mitochondrial metabolism can contribute to sustain proliferation. Mitogen-activated protein kinases (MAPKs orchestrate signal transduction and recent data indicate that are present in mitochondria and regulated by the redox state. On these bases, we investigated the mechanistic connection of tumor mitochondrial dysfunction, H(2O(2 yield, and activation of MAPKs in LP07 murine tumor cells with confocal microscopy, in vivo imaging and directed mutagenesis. Two redox conditions were examined: low 1 microM H(2O(2 increased cell proliferation in ERK1/2-dependent manner whereas high 50 microM H(2O(2 arrested cell cycle by p38 and JNK1/2 activation. Regarding the experimental conditions as a three-compartment model (mitochondria, cytosol, and nuclei, the different responses depended on MAPKs preferential traffic to mitochondria, where a selective activation of either ERK1/2 or p38-JNK1/2 by co-localized upstream kinases (MAPKKs facilitated their further passage to nuclei. As assessed by mass spectra, MAPKs activation and efficient binding to cognate MAPKKs resulted from oxidation of conserved ERK1/2 or p38-JNK1/2 cysteine domains to sulfinic and sulfonic acids at a definite H(2O(2 level. Like this, high H(2O(2 or directed mutation of redox-sensitive ERK2 Cys(214 impeded binding to MEK1/2, caused ERK2 retention in mitochondria and restricted shuttle to nuclei. It is surmised that selective cysteine oxidations adjust the electrostatic forces that participate in a particular MAPK-MAPKK interaction. Considering that tumor mitochondria are dysfunctional, their inability to

  12. 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

    International Nuclear Information System (INIS)

    Takala, Teemu O.; Nuutila, Pirjo; Pulkki, Kari; Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani; Savunen, Timo; Vaehaesilta, Tommi; Luotolahti, Matti; Kallajoki, Markku

    2002-01-01

    14(R,S)-[ 18 F]Fluoro-6-thia-heptadecanoic acid ([ 18 F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [ 18 F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [ 18 F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [ 18 F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [ 18 F]FTHA metabolite analysis. Fractional [ 18 F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring 18 F in the tissue samples. Fractional [ 18 F]FTHA uptake rates based on the analysis of tissue samples were 0.56±0.17 ml g -1 min -1 and 0.037±0.007 ml g -1 min -1 for myocardium and skeletal muscle (mean ± SD), respectively. The myocardial results obtained from the PET data (0.50±0.11 ml g -1 min -1 ) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%±23% (mean±SD, n=7) of the 18 F entered mitochondria in myocardium, as compared with only 36%±15% (mean±SD, n=7) in skeletal muscle. Intracellular [ 18 F]FTHA metabolite analysis showed that a major part of [ 18 F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [ 18 F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [ 18 F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only 36% of [ 18 F]FTHA accumulated in skeletal muscle appears to directly enter

  13. Exogenous oxidants activate nuclear factor kappa B through Toll-like receptor 4 stimulation to maintain inflammatory phenotype in macrophage.

    Science.gov (United States)

    Zhang, Yan; Igwe, Orisa J

    2018-01-01

    Disturbances in redox equilibrium in tissue can lead to inflammatory state, which is a mediatory factor in many human diseases. The mechanism(s) by which exogenous oxidants may activate an inflammatory response is not fully understood. Emerging evidence suggests that oxidant-induced Toll-like receptor 4 (TLR4) activation plays a major role in "sterile" inflammation. In the present study, we used murine macrophage RAW-Blue cells, which are chromosomally integrated with secreted embryonic alkaline phosphatase (SEAP) inducible by NF-κB. We confirmed the expression of TLR4 mRNA and protein in RAW-Blue cells by RT-PCR and Western blot, respectively. We showed that oxidants increased intracellular reactive oxygen species production and lipid peroxidation, which resulted in decreased intracellular total antioxidant capacity. Consistent with the actions of TLR4-specific agonist LPS-EK, exogenous oxidants increased transcriptional activity of NF-κB p65 with subsequent release of NF-κB reporter gene SEAP. These effects were blocked by pretreatment with TLR4 neutralizing pAb and TLR4 signaling inhibitor CLI-095. In addition, oxidants decreased the expression of IκBα with enhanced phosphorylation at the Tyr42 residue. Finally, oxidants and LPS-EK increased TNFα production, but did not affect IL-10 production, which may cause imbalance between pro- and anti-inflammatory processes, which CLI-095 inhibited. For biological relevance, we confirmed that oxidants increased release of TNFα and IL-6 in primary macrophages derived from TLR4-WT and TLR4-KO mice. Our results support the involvement of TLR4 mediated oxidant-induced inflammatory phenotype through NF-κB activation in macrophages. Thus exogenous oxidants may play a role in activating inflammatory phenotypes that propagate and maintain chronic disease states. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Gene expression profiles deciphering rice phenotypic variation between Nipponbare (Japonica and 93-11 (Indica during oxidative stress.

    Directory of Open Access Journals (Sweden)

    Fengxia Liu

    Full Text Available Rice is a very important food staple that feeds more than half the world's population. Two major Asian cultivated rice (Oryza sativa L. subspecies, japonica and indica, show significant phenotypic variation in their stress responses. However, the molecular mechanisms underlying this phenotypic variation are still largely unknown. A common link among different stresses is that they produce an oxidative burst and result in an increase of reactive oxygen species (ROS. In this study, methyl viologen (MV as a ROS agent was applied to investigate the rice oxidative stress response. We observed that 93-11 (indica seedlings exhibited leaf senescence with severe lesions under MV treatment compared to Nipponbare (japonica. Whole-genome microarray experiments were conducted, and 1,062 probe sets were identified with gene expression level polymorphisms between the two rice cultivars in addition to differential expression under MV treatment, which were assigned as Core Intersectional Probesets (CIPs. These CIPs were analyzed by gene ontology (GO and highlighted with enrichment GO terms related to toxin and oxidative stress responses as well as other responses. These GO term-enriched genes of the CIPs include glutathine S-transferases (GSTs, P450, plant defense genes, and secondary metabolism related genes such as chalcone synthase (CHS. Further insertion/deletion (InDel and regulatory element analyses for these identified CIPs suggested that there may be some eQTL hotspots related to oxidative stress in the rice genome, such as GST genes encoded on chromosome 10. In addition, we identified a group of marker genes individuating the japonica and indica subspecies. In summary, we developed a new strategy combining biological experiments and data mining to study the possible molecular mechanism of phenotypic variation during oxidative stress between Nipponbare and 93-11. This study will aid in the analysis of the molecular basis of quantitative traits.

  15. The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

    Directory of Open Access Journals (Sweden)

    Shüné V Oliver

    Full Text Available Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and

  16. The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

    Science.gov (United States)

    Oliver, Shüné V; Brooke, Basil D

    2016-01-01

    Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and insecticide resistance

  17. A similar local immune and oxidative stress phenotype in vitiligo and halo nevus.

    Science.gov (United States)

    Yang, Yuqi; Li, Shuli; Zhu, Guannan; Zhang, Qian; Wang, Gang; Gao, Tianwen; Li, Chunying; Wang, Lin; Jian, Zhe

    2017-07-01

    Vitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood. The aim of the current study was to investigate whether vitiligo and halo nevus share the same immunological and oxidative stress response. Infiltrations of T cells, and expressions of chemokine receptors (CXCR3, CCR4, CCR5) and cytotoxic markers (Granzyme B, Perforin) in the lesions of vitiligo and halo nevus were examined by immunohistochemistry. Enzyme-linked immunosorbent assay was performed to analyze the expressions of chemokines in the serum samples and cytotoxic markers secreted by CD8 + T cells which were sorted from the peripheral blood mononuclear cells in healthy donors, vitiligo and halo nevus patients. Tissue levels of chemokine receptors and CXCR3 ligands in healthy controls, vitiligo patients and halo nevus patients were determined by qRT-PCR analysis. The percentages of CXCR3 + CD4 + T and CXCR3 + CD8 + T cells from the peripheral blood samples were examined by flow cytometry. Tissue and serum hydrogen peroxide (H 2 O 2 ) concentrations were measured using H 2 O 2 assay kit. Immunohistochemistry revealed a significant T-cell response, with pronounced dermal infiltrates of CD8 + T cells in vitiligo and halo nevus. The inflammatory cytotoxic markers such as Granzyme B and Perforin were also elevated in vitiligo and halo nevus, suggesting inflammatory responses in situ. By qRT-PCR and ELISA assay, we found significantly increased expressions of the chemokine receptor CXCR3 and its ligands, especially the accumulated CXCL10 in the skin lesions of vitiligo and halo nevus. Moreover, the level of H 2 O 2 , a key player involved in regulation of the immune response was significantly upregulated in the skin lesions of vitiligo and halo nevus. In addition, the increased H 2 O 2 concentration correlated positively with CXCL10 level in skin

  18. Oxidative Stress ‑a Phenotypic Hallmark of Fanconi Anemia and ...

    African Journals Online (AJOL)

    Keywords: Down syndrome, Oxidative DNA damage, Oxidative stress. Access this ... higher MDA levels (P < 0.01) and non significantly lower total antioxidant .... in their study that carotenoids and carotenoid-rich foods can influence DNA ...

  19. Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype.

    Science.gov (United States)

    Isken, F; Klaus, S; Petzke, K J; Loddenkemper, C; Pfeiffer, A F H; Weickert, M O

    2010-02-01

    Exposure to high vs. low glycemic index (GI) diets increases fat mass and insulin resistance in obesity-prone C57BL/6J mice. However, the longer-term effects and potentially involved mechanisms are largely unknown. We exposed four groups of male C57BL/6J mice (n = 10 per group) to long-term (20 wk) or short-term (6 wk) isoenergetic and macronutrient matched diets only differing in starch type and as such GI. Body composition, liver fat, molecular factors of lipid metabolism, and markers of insulin sensitivity and metabolic flexibility were investigated in all four groups of mice. Mice fed the high GI diet showed a rapid-onset (from week 5) marked increase in body fat mass and liver fat, a gene expression profile in liver consistent with elevated lipogenesis, and, after long-term exposure, significantly reduced glucose clearance following a glucose load. The long-term high-GI diet also led to a delayed switch to both carbohydrate and fat oxidation in the postprandial state, indicating reduced metabolic flexibility. In contrast, no difference in carbohydrate oxidation was observed after short-term high- vs. low-GI exposure. However, fatty acid oxidation was significantly blunted as early as 3 wk after beginning of the high-GI intervention, at a time where most measured phenotypic markers including body fat mass were comparable between groups. Thus long-term high-GI feeding resulted in an obese, insulin-resistant, and metabolically inflexible phenotype in obesity-prone C57BL/6J mice. Early onset and significantly impaired fatty acid oxidation preceded these changes, thereby indicating a potentially causal involvement.

  20. RS CVn binary systems

    International Nuclear Information System (INIS)

    Linsky, J.L.

    1984-01-01

    The author attempts to place in context the vast amount of data obtained in the last few years as a result of X-ray, ultraviolet, optical, and microwave observations of RS CVn and similar spectroscopic binary systems. He concentrates on the RS CVn systems and their long-period analogs, and restricts the scope by attempting to answer on the basis of the recent data and theory following questions: (1) Are the original defining characteristics still valid and still adequate? (2) What is the evidence for discrete active regions? (3) Have we derived any meaningful physical properties for the atmospheres of RS CVn systems? (4) What are the flare observations telling us about magnetic fields in the RS CVn systems? (5) Is there evidence for systematic trends in RS CVn systems with spectral type?

  1. Oxidized LDL Induces Alternative Macrophage Phenotype through Activation of CD36 and PAFR

    Directory of Open Access Journals (Sweden)

    Francisco J. Rios

    2013-01-01

    Full Text Available OxLDL is recognized by macrophage scavenger receptors, including CD36; we have recently found that Platelet-Activating Factor Receptor (PAFR is also involved. Since PAFR in macrophages is associated with suppressor function, we examined the effect of oxLDL on macrophage phenotype. It was found that the presence of oxLDL during macrophage differentiation induced high mRNA levels to IL-10, mannose receptor, PPARγ and arginase-1 and low levels of IL-12 and iNOS. When human THP-1 macrophages were pre-treated with oxLDL then stimulated with LPS, the production of IL-10 and TGF-β significantly increased, whereas that of IL-6 and IL-8 decreased. In murine TG-elicited macrophages, this protocol significantly reduced NO, iNOS and COX2 expression. Thus, oxLDL induced macrophage differentiation and activation towards the alternatively activated M2-phenotype. In murine macrophages, oxLDL induced TGF-β, arginase-1 and IL-10 mRNA expression, which were significantly reduced by pre-treatment with PAFR antagonists (WEB and CV or with antibodies to CD36. The mRNA expression of IL-12, RANTES and CXCL2 were not affected. We showed that this profile of macrophage activation is dependent on the engagement of both CD36 and PAFR. We conclude that oxLDL induces alternative macrophage activation by mechanisms involving CD36 and PAFR.

  2. MODERN APPROACHES TO FRACTIONAL EXHALED NITRIC OXIDE AS A USEFUL BIOMARKER FOR ALLERGIC ASTHMA PHENOTYPING AND MANAGEMENT.

    Science.gov (United States)

    Mgaloblishvili, N; Gotua, M

    2017-12-01

    Asthma is a pathologically heterogeneous disease, consisting of several phenotypes. Different types of airway inflammation are the cornerstone feature of this condition. Fraction of nitric oxide in exhaled air (FENO) has been proposed as a noninvasive, specific biomarker for eosinophilic airway inflammation and has been shown to be elevated in patients with allergic asthma phenotype. More recent studies indicate that FeNO identifies T-helper cell type 2 (Th2)-mediated airway inflammation with a high predictive value for identifying inhaled corticosteroid (ICS) responsive airway inflammation. Taking into account the accumulated evidence,it is possible to consider, that FeNO testing has an important role in the assessment of patients with suspected asthma and in the management of established asthmadiagnosis. In conjunction with symptom scores and lung function tests, FeNO measurement could provide a more useful and effective approach for asthma in terms of: (1) detecting the presence of Th2-mediated airway inflammation, (2) determining the likelihood of ICS responsive (and lack of course), (3) monitoring of airway inflammation to determine risk for future impairment or loss of asthma control during reduction/cessation of ICS treatment, (4) unmasking (otherwise unsuspected) non-adherence to corticosteroid therapy and (5) in severe asthma cases tailoring treatment with biological drugs. However, more work is still needed to address outstanding questions about its exact role in guiding asthma management and better define the use of FENO in different clinical settings.

  3. Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype.

    Science.gov (United States)

    Chacon-Cabrera, Alba; Mateu-Jimenez, Mercè; Langohr, Klaus; Fermoselle, Clara; García-Arumí, Elena; Andreu, Antoni L; Yelamos, Jose; Barreiro, Esther

    2017-12-01

    Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1 -/- ) and Parp-2 -/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1 -/- , and Parp-2 -/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1 -/- and Parp-2 -/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention. © 2017 Wiley Periodicals, Inc.

  4. Role of redoximiRs in fibrogenesis.

    Science.gov (United States)

    Fierro-Fernández, Marta; Miguel, Verónica; Lamas, Santiago

    2016-04-01

    Fibrosis can be defined as an excessive accumulation of extracellular matrix (ECM) components, ultimately leading to stiffness, scarring and devitalized tissue. MicroRNAs (miRNAs) are short, 19-25 nucleotides (nt), non-coding RNAs involved in the post-transcriptional regulation of gene expression. Recently, miRNAs have also emerged as powerful regulators of fibrotic processes and have been termed "fibromiRs". Oxidative stress represents a self-perpetuating mechanism in fibrogenesis. MiRNAs can also influence the expression of genes responsible for the generation of reactive oxygen species (ROS) and antioxidant defence and are termed "redoximiRs". Here, we review the current knowledge of mechanisms by which "redoximiRs" regulate fibrogenesis. This new set of miRNAs may be called "redoxifibromiRs". Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. RS-WebPredictor

    DEFF Research Database (Denmark)

    Zaretzki, J.; Bergeron, C.; Huang, T.-W.

    2013-01-01

    Regioselectivity-WebPredictor (RS-WebPredictor) is a server that predicts isozyme-specific cytochrome P450 (CYP)-mediated sites of metabolism (SOMs) on drug-like molecules. Predictions may be made for the promiscuous 2C9, 2D6 and 3A4 CYP isozymes, as well as CYPs 1A2, 2A6, 2B6, 2C8, 2C19 and 2E1....... RS-WebPredictor is the first freely accessible server that predicts the regioselectivity of the last six isozymes. Server execution time is fast, taking on average 2s to encode a submitted molecule and 1s to apply a given model, allowing for high-throughput use in lead optimization projects.......Availability: RS-WebPredictor is accessible for free use at http://reccr.chem.rpi.edu/ Software/RS-WebPredictor....

  6. Phenotype commitment in vascular smooth muscle cells derived from coronary atherosclerotic plaques: differential gene expression of endothelial Nitric Oxide Synthase

    Directory of Open Access Journals (Sweden)

    ML Rossi

    2009-06-01

    Full Text Available Unstable angina and myocardial infarction are the clinical manifestations of the abrupt thrombotic occlusion of an epicardial coronary artery as a result of spontaneous atherosclerotic plaque rupture or fissuring, and the exposure of highly thrombogenic material to blood. It has been demonstrated that the proliferation of vascular smooth muscle cells (VSMCs and impaired bioavailabilty of nitric oxide (NO are among the most important mechanisms involved in the progression of atherosclerosis. It has also been suggested that a NO imbalance in coronary arteries may be involved in myocardial ischemia as a result of vasomotor dysfunction triggering plaque rupture and the thrombotic response. We used 5’ nuclease assays (TaqMan™ PCRs to study gene expression in coronary plaques collected by means of therapeutic directional coronary atherectomy from 15 patients with stable angina (SA and 15 with acute coronary syndromes (ACS without ST elevation. Total RNA was extracted from the 30 plaques and the cDNA was amplified in order to determine endothelial nitric oxide synthase (eNOS gene expression. Analysis of the results showed that the expression of eNOS was significantly higher (p<0.001 in the plaques from the ACS patients. Furthermore, isolated VSMCs from ACS and SA plaques confirmed the above pattern even after 25 plating passages. In situ RT-PCR was also carried out to co-localize the eNOS messengers and the VSMC phenotype.

  7. High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

  8. ROBATEL RS 24 packaging

    International Nuclear Information System (INIS)

    Robatel, M.; Bochard, C.

    1986-01-01

    The ROBATEL RS 24 packaging for light-water reactor fuel assemblies is discussed. The cask uses a strength frame of carbon steel sheets, lead gamma ray shielding, neutron shielding of aluminous concrete, a thermal protection system for the gamma shielding, and a natural convection thermal transfer system

  9. Lack of association between rheumatoid arthritis and genetic variants rs10889677, rs11209026 and rs2201841 of IL-23R gene.

    Science.gov (United States)

    Paradowska-Gorycka, Agnieszka; Malinowski, Damian; Haladyj, Ewa; Olesinska, Marzena; Safranow, Krzysztof; Pawlik, Andrzej

    2018-01-19

    Rheumatoid arthritis (RA) is an autoimmune diseases, where different genetic variants in cytokine genes may play a pathogenic role. A GWAS in autoimmune diseases highlighted the IL-23R gene as a one of the susceptibility factors. We examined three candidate single nucleotide polymorphisms (SNPs) rs10889677, rs11209026 and rs2201841 of the IL-23R gene, as well as determined their possible association with RA in a Polish population. The IL-23R gene polymorphisms were genotyped for 422 RA patients and 348 healthy individuals using TaqMan SNP genotyping assay. The genotypes frequency did not deviate from HWE in each examined group. A comparison of the allele as well as genotype frequencies of the IL-23R polymorphisms under codominant, dominant and recessive genetic model revealed no significant differences between RA patients and healthy subjects. We also demonstrated that IL-23R rs2201841 and rs11209026 as well as rs11209026 and rs10889677 were in complete linkage disequilibrium (D'=1.0). Our genotype-phenotype analysis demonstrated that in carriers of rs10889677C and/or rs2201841A allele the RF, extra-articular manifestations and erosion were more frequent present than in patients with rs10889677A and/or rs2201841A allele, although this association was not significant. Present findings indicated that the autoimmune disease-associated genetic variants in IL-23R gene are not associated with RA in the Polish population. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  10. Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655

    Directory of Open Access Journals (Sweden)

    Sang Woo Seo

    2015-08-01

    Full Text Available Three transcription factors (TFs, OxyR, SoxR, and SoxS, play a critical role in transcriptional regulation of the defense system for oxidative stress in bacteria. However, their full genome-wide regulatory potential is unknown. Here, we perform a genome-scale reconstruction of the OxyR, SoxR, and SoxS regulons in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 68 genes in 51 transcription units (TUs belong to these regulons. Among them, 48 genes showed more than 2-fold changes in expression level under single-TF-knockout conditions. This reconstruction expands the genome-wide roles of these factors to include direct activation of genes related to amino acid biosynthesis (methionine and aromatic amino acids, cell wall synthesis (lipid A biosynthesis and peptidoglycan growth, and divalent metal ion transport (Mn2+, Zn2+, and Mg2+. Investigating the co-regulation of these genes with other stress-response TFs reveals that they are independently regulated by stress-specific TFs.

  11. Association of interleukin 1 receptor-like 1 gene polymorphisms with eosinophilic phenotype in Japanese adults with asthma.

    Science.gov (United States)

    Inoue, Hideki; Ito, Isao; Niimi, Akio; Matsumoto, Hisako; Oguma, Tsuyoshi; Tajiri, Tomoko; Iwata, Toshiyuki; Nagasaki, Tadao; Kanemitsu, Yoshihiro; Morishima, Toshitaka; Hirota, Tomomitsu; Tamari, Mayumi; Wenzel, Sally E; Mishima, Michiaki

    2017-11-01

    IL1RL1 (ST2) is involved in Th2 inflammation including eosinophil activation. Single nucleotide polymorphisms (SNPs) of the IL1RL1 gene are associated with asthma development and increased peripheral blood eosinophil counts. However, the association between IL1RL1 SNPs and eosinophilic phenotype among adults with asthma remains unexplored. In a primary cohort of 110 adult Japanese patients with stable asthma, we examined the associations between IL1RL1 SNPs and clinical measurements including forced expiratory volume (FEV 1 ), airway reversibility of FEV 1 , exhaled nitric oxide (FeNO), serum soluble-ST2 (sST2) levels, peripheral blood eosinophil differentials and serum total IgE level. The findings in the primary cohort were confirmed in a validation cohort of 126 adult Japanese patients with stable asthma. Patients with minor alleles in 3 SNPs (rs17026974, rs1420101, and rs1921622) had high FeNO, blood eosinophil differentials, and reversibility of FEV 1 , but low levels of serum sST2 and FEV 1 . Minor alleles of rs1041973 were associated with low serum sST2 levels alone. In the validation cohort, minor alleles of rs1420101 were associated with high FeNO and blood eosinophil differentials, whereas minor alleles of rs17026974 and rs1921622 were associated with high blood eosinophil differentials and FeNO, respectively. Multivariate analyses revealed that the minor allele of rs1420101 additively contributed to the FeNO, blood eosinophil differentials, and reversibility of FEV 1 . The minor alleles of IL1RL1 SNPs were associated with high FeNO and peripheral blood eosinophilia among adult Japanese patients with stable asthma. IL1RL1 SNPs may characterize the eosinophilic phenotype with greater eosinophilic inflammation in the Japanese asthma cohort. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  12. Quantification of oxidative stress phenotypes based on high-throughput growth profiling of protein kinase and phosphatase knockouts

    DEFF Research Database (Denmark)

    Altıntaş, Ali; Martini, Jacopo; Mortensen, Uffe Hasbro

    2016-01-01

    Cellular responses to oxidative stress are important for restoring redox balance and ensuring cell survival. Genetic defects in response factors can lead to impaired response to oxidative damage and contribute to disease and aging. In single cell organisms, such as yeasts, the integrity of the ox...

  13. Paula, RS, Brasil

    Directory of Open Access Journals (Sweden)

    Solon Jonas Longhi

    2006-01-01

    Full Text Available The present work is part of studies and researches developed at Long Duration Ecological Project - PELD/CNPq, located in São Francisco de Paula’s National Forest (FLONA, RS. The objective of this paper was to identify and to characterize the different stages of succession in mixed rainy forest remains. The work had been accomplished in ten permanent conglomerates of 100m x 100m (10.000m2, which were divided into ten strips of 10m x 100m (1.000m2 and these ones subdivided into ten subunits of 10m x 10m (100m2. In this research, a strip of 10m x 100m was selected for each conglomerate, totaling 100 subunits (stands, where it had been installed, at DBH height, dendrometric bands in all trees with CBH ≥ 30cm, for annual diameters measurement. The cluster analysis was accomplished through the Twinspan program, using a data matrix with ninety-nine stands (one of those was unconsidered by the absence of individuals with CBH ≥ 30cm having as variable the annual increment in diameter (obtained in two years of observations of sixty nine species. Three floristic groups was obtained, indicating stages of succession in the forest: a group separated a less developed stage of succession denominated secondary forest, being Nectandra megapotamica and Cryptocaria aschersoniana the indicative species; a second group indicated an intermediate stage of succession in the forest, being Sebastiania commersoniana and Ocotea pulchella the indicative species; and a third group of primary forest, whose indicative species was Araucaria angustifolia.

  14. Interleukin-6-receptor polymorphisms rs12083537, rs2228145, and rs4329505 as predictors of response to tocilizumab in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Enevold, Christian; Baslund, Bo; Linde, Louise

    2014-01-01

    Tocilizumab (TCZ), a monoclonal antibody targeting the human interleukin-6-receptor (IL-6R), is indicated for the treatment of rheumatoid arthritis (RA). We examined whether three IL6R single-nucleotide polymorphisms rs12083537, rs2228145 (formerly rs8192284), and rs4329505 with previously report...

  15. Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

    Directory of Open Access Journals (Sweden)

    Jane L. Tarry-Adkins

    2016-10-01

    Full Text Available ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’ in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb and an increased frequency of short telomeres (4.2-1.3 kb in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1 in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria, and increased xanthine oxidase (XO, p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB. Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD, copper-zinc superoxide dismutase (CuZnSOD, catalase and heme oxygenase-1 (HO1, all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by

  16. BDNF rs6265 methylation and genotype interact on risk for schizophrenia.

    Science.gov (United States)

    Ursini, Gianluca; Cavalleri, Tommaso; Fazio, Leonardo; Angrisano, Tiziana; Iacovelli, Luisa; Porcelli, Annamaria; Maddalena, Giancarlo; Punzi, Giovanna; Mancini, Marina; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Calabrese, Francesca; Rampino, Antonio; Taurisano, Paolo; Di Giorgio, Annabella; Keller, Simona; Tarantini, Letizia; Sinibaldi, Lorenzo; Quarto, Tiziana; Popolizio, Teresa; Caforio, Grazia; Blasi, Giuseppe; Riva, Marco A; De Blasi, Antonio; Chiariotti, Lorenzo; Bollati, Valentina; Bertolino, Alessandro

    2016-01-01

    Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes.

  17. A Radish Basic Helix-Loop-Helix Transcription Factor, RsTT8 Acts a Positive Regulator for Anthocyanin Biosynthesis

    Directory of Open Access Journals (Sweden)

    Sun-Hyung Lim

    2017-11-01

    Full Text Available The MYB-bHLH-WDR (MBW complex activates anthocyanin biosynthesis through the transcriptional regulation. RsMYB1 has been identified as a key player in anthocyanin biosynthesis in red radish (Raphanus sativus L., but its partner bHLH transcription factor (TF remains to be determined. In this study, we isolated a bHLH TF gene from red radish. Phylogenetic analysis indicated that this gene belongs to the TT8 clade of the IIIF subgroup of bHLH TFs, and we thus designated this gene RsTT8. Subcellular localization analysis showed that RsTT8-sGFP was localized to the nuclei of Arabidopsis thaliana protoplasts harboring the RsTT8-sGFP construct. We evaluated anthocyanin biosynthesis and RsTT8 expression levels in three radish varieties (N, C, and D that display different red phenotypes in the leaves, root flesh, and root skins. The root flesh of the C variety and the leaves and skins of the D variety exhibit intense red pigmentation; in these tissues, RsTT8 expression showed totally positive association with the expression of RsMYB1 TF and of five of eight tested anthocyanin biosynthesis genes (i.e., RsCHS, RsCHI, RsF3H, RsDFR, and RsANS. Heterologous co-expression of both RsTT8 and RsMYB1 in tobacco leaves dramatically increased the expression of endogenous anthocyanin biosynthesis genes and anthocyanin accumulation. Furthermore, a yeast two-hybrid assay showed that RsTT8 interacts with RsMYB1 at the MYB-interacting region (MIR, and a transient transactivation assay indicated that RsTT8 activates the RsCHS and RsDFR promoters when co-expressed with RsMYB1. Complementation of the Arabidopsis tt8-1 mutant, which lacks red pigmentation in the leaves and seeds, with RsTT8 restored red pigmentation, and resulted in high anthocyanin and proanthocyanidin contents in the leaves and seeds, respectively. Together, these results show that RsTT8 functions as a regulatory partner with RsMYB1 during anthocyanin biosynthesis.

  18. High-sucrose diet induces diabetic-like phenotypes and oxidative stress in Drosophila melanogaster: Protective role of Syzygium cumini and Bauhinia forficata.

    Science.gov (United States)

    Ecker, Assis; Gonzaga, Thallita Karla Silva do Nascimento; Seeger, Rodrigo Lopes; Santos, Matheus Mulling Dos; Loreto, Julia Sepel; Boligon, Aline Augusti; Meinerz, Daiane Francine; Lugokenski, Thiago Henrique; Rocha, João Batista Teixeira da; Barbosa, Nilda Vargas

    2017-05-01

    Diet is a key component for development and longevity of organisms. Here, the fruit fly was used to evaluate the detrimental effects caused by consumption of high-sucrose diets (HSD), namely phenotypic responses linked to insulin signaling and oxidative stress. The protective effects of extracts from medicinal plants Syzygium cumini and Bauhinia forficata were investigated. HSD intake (15% and 30%) delayed the time to pupation and reduced the number of white pupae. In adult flies, the intake of diets was associated with mortality and increased levels of glucose+trehalose, triacylglycerols and hydrogen peroxide. Indeed, 30% HSD induced body-weight loss, mitochondrial dysfunction and changes in acetylcholinesterase, δ-aminolevulinate dehydratase and antioxidant enzymes activity. Catalase, superoxide dismutase, keap1, HSP70, dILP-5 and Insulin receptor mRNA levels were over-expressed in flies emerged from 30% HSD. The extract treatments blunted the developmental alterations elicited by diets. Syzygium cumini extract was more efficient than B. forficata in reducing hyperglycaemia, redox disturbances and the changes in mRNA expression of insulin receptor. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Lithium Chloride Dependent Glycogen Synthase Kinase 3 Inactivation Links Oxidative DNA Damage, Hypertrophy and Senescence in Human Articular Chondrocytes and Reproduces Chondrocyte Phenotype of Obese Osteoarthritis Patients.

    Directory of Open Access Journals (Sweden)

    Serena Guidotti

    Full Text Available Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA, but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy.In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763 were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS production (2',7'-dichlorofluorescin diacetate staining. Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21, flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining.In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10.In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via

  20. Lithium Chloride Dependent Glycogen Synthase Kinase 3 Inactivation Links Oxidative DNA Damage, Hypertrophy and Senescence in Human Articular Chondrocytes and Reproduces Chondrocyte Phenotype of Obese Osteoarthritis Patients.

    Science.gov (United States)

    Guidotti, Serena; Minguzzi, Manuela; Platano, Daniela; Cattini, Luca; Trisolino, Giovanni; Mariani, Erminia; Borzì, Rosa Maria

    2015-01-01

    Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA), but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy. In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763) were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS) production (2',7'-dichlorofluorescin diacetate staining). Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21), flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining. In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10. In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via induction of

  1. Sirtuin 1 gene rs2273773 C >T single nucleotide polymorphism and ...

    African Journals Online (AJOL)

    Background: Sirtuin-1 (SIRT-1), a protein has been found to protect the cells against oxidative stress due to its deacetylase activity. In this investigation, we aimed to study SIRT-1 gene rs2273773 C >T single nucleotide polymorphism and markers of serum protein oxidation (protein carbonyl and sulfhydryl groups) in ...

  2. Effects of composite films of silk fibroin and graphene oxide on the proliferation, cell viability and mesenchymal phenotype of periodontal ligament stem cells.

    Science.gov (United States)

    Rodríguez-Lozano, F J; García-Bernal, D; Aznar-Cervantes, S; Ros-Roca, M A; Algueró, M C; Atucha, N M; Lozano-García, A A; Moraleda, J M; Cenis, J L

    2014-12-01

    In regenerative dentistry, stem cell-based therapy often requires a scaffold to deliver cells and/or growth factors to the injured site. Graphene oxide (GO) and silk fibroin (SF) are promising biomaterials for tissue engineering as they are both non toxic and promote cell proliferation. On the other hand, periodontal ligament stem cells (PDLSCs) are mesenchymal stem cells readily accessible with a promising use in cell therapy. The purpose of this study was to investigate the effects of composite films of GO, SF and GO combined with fibroin in the mesenchymal phenotype, viability, adhesion and proliferation rate of PDLSCs. PDLSCs obtained from healthy extracted teeth were cultured on GO, SF or combination of GO and SF films up to 10 days. Adhesion level of PDSCs on the different biomaterials were evaluated after 12 h of culture, whereas proliferation rate of cells was assessed using the MTT assay. Level of apoptosis was determined using Annexin-V and 7-AAD and mesenchymal markers expression of PDLSCs were analyzed by flow cytometry. At day 7 of culture, MTT experiments showed a high rate of proliferation of PDLSCs growing on GO films compared to the other tested biomaterials, although it was slightly lower than in plastic (control). However PDLSCs growing in fibroin or GO plus fibroin films showed a discrete proliferation. Importantly, at day 10 of culture it was observed a significant increase in PDLSCs proliferation rate in GO films compared to plastic (P < 0.05), as well as in GO plus fibroin compared to fibroin alone (P < 0.001). Flow cytometry analysis showed that culture of PDLSCs in fibroin, GO or GO plus fibroin films did not significantly alter the level of expression of the mesenchymal markers CD73, CD90 or CD105 up to 168 h, being the cell viability in GO even better than obtained in plastic. Our findings suggest that the combination of human dental stem cells/fibroin/GO based-bioengineered constructs have strong potential for their therapeutic

  3. Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655

    DEFF Research Database (Denmark)

    Seo, Sang Woo; Kim, Donghyuk; Szubin, Richard

    2015-01-01

    Three transcription factors (TFs), OxyR, SoxR, and SoxS, play a critical role in transcriptional regulation of the defense system for oxidative stress in bacteria. However, their full genome-wide regulatory potential is unknown. Here, we perform a genome-scale reconstruction of the OxyR, SoxR, an...

  4. R102W mutation in the RS1 gene responsible for retinoschisis and recurrent glaucoma

    Directory of Open Access Journals (Sweden)

    Xiu-Feng Huang

    2014-02-01

    Full Text Available AIM: To identify the mutations in RS1 gene associated with typical phenotype of X-linked juvenile retinoschisis (XLRS and a rare condition of concomitant glaucoma.METHODS: Complete ophthalmic examinations were performed in the proband. The coding regions of the RS1 gene that encode retinoschisin were amplified by polymerase chain reaction and directly sequenced.RESULTS: The proband showed a typical phenotype of XLRS with large peripheral retinal schisis in both eyes, involving the macula and combined with foveal cystic change, reducing visual acuity. A typical phenotype of recurrent glaucoma with high intraocular pressure (IOP and reduced visual field was also demonstrated with the patient. Mutation analysis of RS1 gene revealed R102W (c.304C>T mutations in the affected male, and his mother was proved to be a carrier with the causative mutation and another synonymous polymorphism (c.576C>CT.CONCLUSION: We identified the genetic variations of a Chinese family with typical phenotype of XLRS and glaucoma. The severe XLRS phenotypes associated with R102W mutations reveal that the mutation determines a notable alteration in the function of the retinoschisin protein. Identification of the disease-causing mutation is beneficial for future clinical references.

  5. Associations of polymorphisms in the cytokine genes IL1β (rs16944), IL6 (rs1800795), IL12b (rs3212227) and growth factor VEGFA (rs2010963) with anthracosilicosis in coal miners in Russia and related genotoxic effects.

    Science.gov (United States)

    Volobaev, Valentin P; Larionov, Aleksey V; Kalyuzhnaya, Ekaterina E; Serdyukova, Ekaterina S; Yakovleva, Svetlana; Druzhinin, Vladimir G; Babich, Olga O; Hill, Elena G; Semenihin, Victor A; Panev, Nikolay I; Minina, Varvara I; Sivanesan, Saravana Devi; Naoghare, Pravin; da Silva, Juliana; Barcelos, Gustavo R M; Prosekov, Alexander Y

    2018-04-13

    Anthracosilicosis (AS), a prevalent form of pneumoconiosis among coal miners, results from the accumulation of carbon and silica in the lungs from inhaled coal dust. This study investigated genotoxic effects and certain cytokine genes polymorphic variants in Russian coal miners with АS. Peripheral leukocytes were sampled from 129 patients with AS confirmed by X-ray and tissue biopsy and from 164 asymptomatic coal miners. Four single-nucleotide polymorphisms were genotyped in the extracted DNA samples: IL1β T-511C (rs16944), IL6 C-174G (rs1800795), IL12b A1188C (rs3212227) and VEGFA C634G (rs2010963). Genotoxic effects were assessed by the analysis of chromosome aberrations in cultured peripheral lymphocytes. The mean frequency of chromatid-type aberrations and chromosome-type aberrations, namely, chromatid-type breaks and dicentric chromosomes, was found to be higher in AS patients [3.70 (95% confidence interval {CI}, 3.29-4.10) and 0.28 (95% CI, 0.17-0.38)] compared to the control group [2.41 (95% CI, 2.00-2.82) and 0.09 (95% CI, 0.03-0.15)], respectively. IL1β gene T/T genotype (rs16944) was associated with AS [17.83% in AS patients against 4.35% in healthy donors, odds ratio = 4.77 (1.88-12.15), P < 0.01]. A significant increase in the level of certain chromosome interchanges among AS donors is of interest because such effects are typical for radiation damage and caused by acute oxidative stress. IL1β T allele probably may be considered as an AS susceptibility factor among coal miners.

  6. Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure.

    Science.gov (United States)

    Svensson, J Peter; Quirós Pesudo, Laia; McRee, Siobhan K; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D

    2013-01-01

    Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N'-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.

  7. Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure.

    Directory of Open Access Journals (Sweden)

    J Peter Svensson

    Full Text Available Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS, N-Methyl-N-nitrosourea (MNU, N,N'-bis(2-chloroethyl-N-nitroso-urea (BCNU, N-ethylnitrosourea (ENU, two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN, benzene-1,4-diol (hydroquinone, HYQ, and two non-genotoxic (methyl carbamate (MC and dimethyl sulfoxide (DMSO compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.

  8. Common Genetic Variant of INSIG2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North India

    OpenAIRE

    Prakash, Jai; Mittal, Balraj; Srivastava, Apurva; Awasthi, Shally; Srivastava, Pranjal; Srivastava, Neena

    2017-01-01

    Background: Obesity is a very common disorder resulting from an imbalance between food intake and energy expenditure, and it has a substantial impact on the development of chronic diseases. The aim of this study was to examine the association of INSIG2 (rs7566605) gene polymorphism with obesity and obesity associated phenotypes in North Indian subjects. Methods: The variants were investigated for association in 642 obese and non-obese individuals. The genotyping of INSIG2 (rs7566605) single n...

  9. A Combination of CD28 (rs1980422 and IRF5 (rs10488631 Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study.

    Directory of Open Access Journals (Sweden)

    Lucia Vernerova

    Full Text Available The aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA and redundancy analysis (RDA.A total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601, STAT4 G/T (rs7574865, CTLA4 A/G (rs3087243, TRAF1/C5 A/G (rs3761847, IRF5 T/C (rs10488631, TNFAIP3 C/T (rs5029937, AFF3 A/T (rs11676922, PADI4 C/T (rs2240340, CD28 T/C (rs1980422, CSK G/A (rs34933034 and FCGR3A A/C (rs396991, rheumatoid factor (RF, anti-citrullinated protein antibodies (ACPA and clinical status was analysed using the LDA and RDA.HLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002. The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001. The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA.The association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA.

  10. A Combination of CD28 (rs1980422) and IRF5 (rs10488631) Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study.

    Science.gov (United States)

    Vernerova, Lucia; Spoutil, Frantisek; Vlcek, Miroslav; Krskova, Katarina; Penesova, Adela; Meskova, Milada; Marko, Andrea; Raslova, Katarina; Vohnout, Branislav; Rovensky, Jozef; Killinger, Zdenko; Jochmanova, Ivana; Lazurova, Ivica; Steiner, Guenter; Smolen, Josef; Imrich, Richard

    2016-01-01

    The aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA) and redundancy analysis (RDA). A total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE) in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601), STAT4 G/T (rs7574865), CTLA4 A/G (rs3087243), TRAF1/C5 A/G (rs3761847), IRF5 T/C (rs10488631), TNFAIP3 C/T (rs5029937), AFF3 A/T (rs11676922), PADI4 C/T (rs2240340), CD28 T/C (rs1980422), CSK G/A (rs34933034) and FCGR3A A/C (rs396991), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and clinical status was analysed using the LDA and RDA. HLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002). The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001). The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA. The association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA.

  11. Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset.

    Directory of Open Access Journals (Sweden)

    Jürgen Glas

    Full Text Available BACKGROUND: Recent studies demonstrated an association of STAT4 variants with systemic lupus erythematosus (SLE and rheumatoid arthritis (RA, indicating that multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 variants on the susceptibility and phenotype of inflammatory bowel diseases (IBD in a large patient and control cohort. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 2704 individuals of Caucasian origin including 857 patients with Crohn's disease (CD, 464 patients with ulcerative colitis (UC, and 1383 healthy, unrelated controls was analyzed for seven SNPs in the STAT4 gene (rs11889341, rs7574865, rs7568275, rs8179673, rs10181656, rs7582694, rs10174238. In addition, a detailed genotype-phenotype analysis was performed. Our analysis revealed an association of the STAT4 SNP rs7574865 with overall decreased susceptibility to CD (p = 0.047, OR 0.86 [95% CI 0.74-0.99]. However, compared to CD patients carrying the wild type genotype, the STAT4 SNP rs7574865 was significantly associated with early CD onset (p = 0.021 and colonic CD (p = 0.008; OR = 4.60, 95% CI 1.63-12.96. For two other STAT4 variants, there was a trend towards protection against CD susceptibility (rs7568275, p = 0.058, OR 0.86 [95% CI 0.74-1.00]; rs10174238, p = 0.057, OR 0.86 [95% CI 0.75-1.00]. In contrast, we did not observe any association with UC susceptibility. Evidence for weak gene-gene interaction of STAT4 with the IL23R SNP rs11209026 was lost after Bonferroni correction. CONCLUSIONS/SIGNIFICANCE: Our results identified the STAT4 SNP rs7574865 as a disease-modifying gene variant in colonic CD. However, in contrast to SLE and RA, the effect of rs7574865 on CD susceptibility is only weak.

  12. Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset.

    Science.gov (United States)

    Glas, Jürgen; Seiderer, Julia; Nagy, Melinda; Fries, Christoph; Beigel, Florian; Weidinger, Maria; Pfennig, Simone; Klein, Wolfram; Epplen, Jörg T; Lohse, Peter; Folwaczny, Matthias; Göke, Burkhard; Ochsenkühn, Thomas; Diegelmann, Julia; Müller-Myhsok, Bertram; Roeske, Darina; Brand, Stephan

    2010-04-29

    Recent studies demonstrated an association of STAT4 variants with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), indicating that multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 variants on the susceptibility and phenotype of inflammatory bowel diseases (IBD) in a large patient and control cohort. Genomic DNA from 2704 individuals of Caucasian origin including 857 patients with Crohn's disease (CD), 464 patients with ulcerative colitis (UC), and 1383 healthy, unrelated controls was analyzed for seven SNPs in the STAT4 gene (rs11889341, rs7574865, rs7568275, rs8179673, rs10181656, rs7582694, rs10174238). In addition, a detailed genotype-phenotype analysis was performed. Our analysis revealed an association of the STAT4 SNP rs7574865 with overall decreased susceptibility to CD (p = 0.047, OR 0.86 [95% CI 0.74-0.99]). However, compared to CD patients carrying the wild type genotype, the STAT4 SNP rs7574865 was significantly associated with early CD onset (p = 0.021) and colonic CD (p = 0.008; OR = 4.60, 95% CI 1.63-12.96). For two other STAT4 variants, there was a trend towards protection against CD susceptibility (rs7568275, p = 0.058, OR 0.86 [95% CI 0.74-1.00]; rs10174238, p = 0.057, OR 0.86 [95% CI 0.75-1.00]). In contrast, we did not observe any association with UC susceptibility. Evidence for weak gene-gene interaction of STAT4 with the IL23R SNP rs11209026 was lost after Bonferroni correction. Our results identified the STAT4 SNP rs7574865 as a disease-modifying gene variant in colonic CD. However, in contrast to SLE and RA, the effect of rs7574865 on CD susceptibility is only weak.

  13. (RS-Efonidipine acetone hemisolvate

    Directory of Open Access Journals (Sweden)

    Yu-Heng Liu

    2016-09-01

    Full Text Available The asymmetric unit of the title compound, C34H38N3O7P·0.5C3H6O {systematic name: (RS-2-[phenyl(phenylmethylamino]ethyl 5-(5,5-dimethyl-2-oxo-1,3-dioxa-2λ5-phosphacyclohex-2-yl-2,6-dimethyl-4-(3-nitrophenyl-1,4-dihydropyridine-3-carboxylate acetone hemisolvate}, contains one R-efonidipine molecule, one S-efonidipine molecule and half of a solvate acetone molecule. In both efonidipine molecules, the six-membered rings of the dioxaphosphinanyl moieties display a chair conformation and the dihydropyridine rings display a flattened boat conformation. In the crystal, N—H...O, C—H...O hydrogen bonds and weak C—H...π interactions link the molecules into a three-dimensional supramolecular structure. A solvent-accessible void of 199 Å3 is found in the structure; the contribution of the heavily disordered solvate molecule was suppressed by use of the SQUEEZE routine in PLATON [Spek (2015. Acta Cryst. C71, 9–18].

  14. RS CV sub n binary systems

    International Nuclear Information System (INIS)

    Linsky, J.L.

    1984-01-01

    An attempt is made to place in context the vast amount of data obtained as a result of X-ray, ultraviolet, optical, and microwave observations of RS CVn and similar spectroscopic binary systems. Emphasis is on the RS CVn systems and their long period analogs. The following questions are considered: (1) are the original defining characteristics still valid and still adequate; (2) what is the evidence for discrete active regions; (3) have any meaningful physical properties for the atmospheres of RS CVn systems been derived; (4) what do the flare observations tell about magnetic fields in RS CVn systems; (5) is there evidence for systematic trends in RS CVn systems with spectral type

  15. Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients.

    Science.gov (United States)

    D'Avolio, Antonio; De Nicolò, Amedeo; Cusato, Jessica; Ciancio, Alessia; Boglione, Lucio; Strona, Silvia; Cariti, Giuseppe; Troshina, Giulia; Caviglia, Gian Paolo; Smedile, Antonina; Rizzetto, Mario; Di Perri, Giovanni

    2013-10-01

    Functional variants rs7270101 and rs1127354 of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of no functional rs6051702 polymorphism. Since a simultaneous evaluation of the three ITPA SNPs for hemolytic anemia has not yet been investigated, we aimed to understand the contribution of each SNPs and its potential clinical use to predict anemia in HCV treated patients. A retrospective analysis included 379 HCV treated patients. The ITPA variants rs6051702, rs7270101 and rs1127354 were genotyped and tested for association with achieving anemia at week 4. We also investigated, using multivariate logistic regression, the impact of each single and paired associated polymorphism on anemia onset. All SNPs were associated with Hb decrease. The carrier of at least one variant allele in the functional ITPA SNPs was associated with a lower decrement of Hb, as compared to patients without a variant allele. In multivariate logistic regression analyses the carrier of a variant allele in the rs6051702/rs1127354 association (OR=0.11, p=1.75×10(-5)) and Hb at baseline (OR=1.51, p=1.21×10(-4)) were independently associated with protection against clinically significant anemia at week 4. All ITPA polymorphisms considered were shown to be significantly associated with anemia onset. A multivariate regression model based on ITPA genetic polymorphisms was developed for predicting the risk of anemia. Considering the characterization of pre-therapy anemia predictors, rs6051702 SNP in association to rs1127354 is more informative in order to avoid this relevant adverse event. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Role of the SaeRS two-component regulatory system in Staphylococcus epidermidis autolysis and biofilm formation

    Science.gov (United States)

    2011-01-01

    Background Staphylococcus epidermidis (SE) has emerged as one of the most important causes of nosocomial infections. The SaeRS two-component signal transduction system (TCS) influences virulence and biofilm formation in Staphylococcus aureus. The deletion of saeR in S. epidermidis results in impaired anaerobic growth and decreased nitrate utilization. However, the regulatory function of SaeRS on biofilm formation and autolysis in S. epidermidis remains unclear. Results The saeRS genes of SE1457 were deleted by homologous recombination. The saeRS deletion mutant, SE1457ΔsaeRS, exhibited increased biofilm formation that was disturbed more severely (a 4-fold reduction) by DNase I treatment compared to SE1457 and the complementation strain SE1457saec. Compared to SE1457 and SE1457saec, SE1457ΔsaeRS showed increased Triton X-100-induced autolysis (approximately 3-fold) and decreased cell viability in planktonic/biofilm states; further, SE1457ΔsaeRS also released more extracellular DNA (eDNA) in the biofilms. Correlated with the increased autolysis phenotype, the transcription of autolysis-related genes, such as atlE and aae, was increased in SE1457ΔsaeRS. Whereas the expression of accumulation-associated protein was up-regulated by 1.8-fold in 1457ΔsaeRS, the expression of an N-acetylglucosaminyl transferase enzyme (encoded by icaA) critical for polysaccharide intercellular adhesin (PIA) synthesis was not affected by the deletion of saeRS. Conclusions Deletion of saeRS in S. epidermidis resulted in an increase in biofilm-forming ability, which was associated with increased eDNA release and up-regulated Aap expression. The increased eDNA release from SE1457ΔsaeRS was associated with increased bacterial autolysis and decreased bacterial cell viability in the planktonic/biofilm states. PMID:21702925

  17. Role of the SaeRS two-component regulatory system in Staphylococcus epidermidis autolysis and biofilm formation

    Directory of Open Access Journals (Sweden)

    Francois Patrice

    2011-06-01

    Full Text Available Abstract Background Staphylococcus epidermidis (SE has emerged as one of the most important causes of nosocomial infections. The SaeRS two-component signal transduction system (TCS influences virulence and biofilm formation in Staphylococcus aureus. The deletion of saeR in S. epidermidis results in impaired anaerobic growth and decreased nitrate utilization. However, the regulatory function of SaeRS on biofilm formation and autolysis in S. epidermidis remains unclear. Results The saeRS genes of SE1457 were deleted by homologous recombination. The saeRS deletion mutant, SE1457ΔsaeRS, exhibited increased biofilm formation that was disturbed more severely (a 4-fold reduction by DNase I treatment compared to SE1457 and the complementation strain SE1457saec. Compared to SE1457 and SE1457saec, SE1457ΔsaeRS showed increased Triton X-100-induced autolysis (approximately 3-fold and decreased cell viability in planktonic/biofilm states; further, SE1457ΔsaeRS also released more extracellular DNA (eDNA in the biofilms. Correlated with the increased autolysis phenotype, the transcription of autolysis-related genes, such as atlE and aae, was increased in SE1457ΔsaeRS. Whereas the expression of accumulation-associated protein was up-regulated by 1.8-fold in 1457ΔsaeRS, the expression of an N-acetylglucosaminyl transferase enzyme (encoded by icaA critical for polysaccharide intercellular adhesin (PIA synthesis was not affected by the deletion of saeRS. Conclusions Deletion of saeRS in S. epidermidis resulted in an increase in biofilm-forming ability, which was associated with increased eDNA release and up-regulated Aap expression. The increased eDNA release from SE1457ΔsaeRS was associated with increased bacterial autolysis and decreased bacterial cell viability in the planktonic/biofilm states.

  18. Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609

    DEFF Research Database (Denmark)

    Grunnet, Louise Groth; Brøns, Charlotte; Jacobsen, Stine

    2009-01-01

    9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance and shorter recovery halftimes of phosphocreatine (PCr) and inorganic phosphate (Pi) after exercise in a primarily type I muscle. These relationships - except for fasting insulin - remained...... or mitochondrially encoded genes in skeletal muscle during rest. Conclusion. Increased energy efficiency - and potentially increased mitochondrial coupling - as suggested by faster recovery rates of PCr and Pi in oxidative muscle fibres may contribute to the increased risk of obesity and type 2 diabetes...

  19. The role of catechol-O-methyl transferase Val(108/158Met polymorphism (rs4680 in the effect of green tea on resting energy expenditure and fat oxidation: a pilot study.

    Directory of Open Access Journals (Sweden)

    Rick Hursel

    Full Text Available INTRODUCTION: Green tea(GT is able to increase energy expenditure(EE and fat oxidation(FATox via inhibition of catechol-O-methyl transferase(COMT by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMT(H(Val/Val genotype, and low-activity COMT(L(Met/Met genotype. METHODS: Fourteen Caucasian subjects (BMI: 22.2±2.3 kg/m2, age: 21.4±2.2 years of whom 7 with the COMT(H-genotype and 7 with the COMT(L-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL consumption. RESULTS: At baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p<0.05. After GT vs. PL, EE(GT: 62.2 vs. PL: 35.4 kJ.3.5 hrs; p<0.01, RQ(GT: 0.80 vs. PL: 0.83; p<0.01, FATox(GT: 18.3 vs. PL: 15.3 g/d; p<0.001 and CHOox(GT: 18.5 vs. PL: 24.3 g/d; p<0.001 were significantly different for subjects carrying the COMT(H genotype, but not for subjects carrying the COMT(L genotype (EE, GT: 60.3 vs. PL: 51.7 kJ.3.5 hrs; NS, (RQ, GT: 0.81 vs. PL: 0.81; NS, (FATox, GT: 17.3 vs. PL: 17.0 g/d; NS, (CHOox, GT: 22.1 vs. PL: 21.4 g/d; NS. CONCLUSION: Subjects carrying the COMT(H genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMT(L genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter

  20. The NOD2 Single Nucleotide Polymorphism rs72796353 (IVS4+10 A>C) Is a Predictor for Perianal Fistulas in Patients with Crohn's Disease in the Absence of Other NOD2 Mutations.

    Science.gov (United States)

    Schnitzler, Fabian; Friedrich, Matthias; Wolf, Christiane; Stallhofer, Johannes; Angelberger, Marianne; Diegelmann, Julia; Olszak, Torsten; Tillack, Cornelia; Beigel, Florian; Göke, Burkhard; Glas, Jürgen; Lohse, Peter; Brand, Stephan

    2015-01-01

    A previous study suggested an association of the single nucleotide polymorphism (SNP) rs72796353 (IVS4+10 A>C) in the NOD2 gene with susceptibility to Crohn's disease (CD). However, this finding has not been confirmed. Given that NOD2 variants still represent the most important predictors for CD susceptibility and phenotype, we evaluated the association of rs72796353 with inflammatory bowel disease (IBD) susceptibility and the IBD phenotype. Genomic DNA from 2256 Caucasians, including 1073 CD patients, 464 patients with ulcerative colitis (UC), and 719 healthy controls, was genotyped for the NOD2 SNP rs72796353 and the three main CD-associated NOD2 mutations rs2066844, rs2066845, and rs2066847. Subsequently, IBD association and genotype-phenotype analyses were conducted. In contrast to the strong associations of the NOD2 SNPs rs2066844 (p=3.51 x 10(-3)), rs2066845 (p=1.54 x 10(-2)), and rs2066847 (p=1.61 x 10(-20)) with CD susceptibility, no significant association of rs72796353 with CD or UC susceptibility was found. However, in CD patients without the three main CD-associated NOD2 mutations, rs72796353 was significantly associated with the development of perianal fistulas (p=2.78 x 10(-7), OR 5.27, [95% CI 2.75-10.12] vs. NOD2 wild-type carriers). Currently, this study represents the largest genotype-phenotype analysis of the impact of the NOD2 variant rs72796353 on the disease phenotype in IBD. Our data demonstrate that in CD patients the IVS4+10 A>C variant is strongly associated with the development of perianal fistulas. This association is particularly pronounced in patients who are not carriers of the three main CD-associated NOD2 mutations, suggesting rs72796353 as additional genetic marker for the CD disease behaviour.

  1. The NOD2 p.Leu1007fsX1008 mutation (rs2066847 is a stronger predictor of the clinical course of Crohn's disease than the FOXO3A intron variant rs12212067.

    Directory of Open Access Journals (Sweden)

    Fabian Schnitzler

    Full Text Available Very recently, a sub-analysis of genome-wide association scans revealed that the non-coding single nucleotide polymorphism (SNP rs12212067 in the FOXO3A gene is associated with a milder course of Crohn's disease (CD (Cell 2013;155:57-69. The aim of our study was to evaluate the clinical value of the SNP rs12212067 in predicting the severity of CD by correlating CD patient genotype status with the most relevant complications of CD such as stenoses, fistulas, and CD-related surgery.We genotyped 550 CD patients for rs12212067 (FOXO3A and the three common CD-associated NOD2 mutations rs2066844, rs2066847, and rs2066847 and performed genotype-phenotype analyses.No significant phenotypic differences were found between the wild-type genotype TT of the FOXO3A SNP rs12212067 and the minor genotypes TG and GG independently from NOD2 variants. The allele frequency of the minor G allele was 12.7%. Age at diagnosis, disease duration, body mass index, surgery rate, stenoses, fistula, need for immunosuppressive therapy, and disease course were not significantly different. In contrast, the NOD2 mutant p.Leu1007fsX1008 (rs2066847 was highly associated with penetrating CD (p = 0.01, the development of fistulas (p = 0.01 and stenoses (p = 0.01, and ileal disease localization (p = 0.03. Importantly, the NOD2 SNP rs2066847 was a strong separator between an aggressive and a mild course of CD (p = 2.99×10(-5, while the FOXO3A SNP rs12212067 did not separate between mild and aggressive CD behavior in our cohort (p = 0.35. 96.2% of the homozygous NOD2 p.Leu1007fsX1008 carriers had an aggressive disease behavior compared to 69.3% of the patients with the NOD2 wild-type genotype (p = 0.007.In clinical practice, the NOD2 variant p.Leu1007fsX1008 (rs2066847, in particular in homozygous form, is a much stronger marker for a severe clinical phenotype than the FOXO3A rs12212067 SNP for a mild disease course on an individual patient level despite

  2. The NOD2 p.Leu1007fsX1008 mutation (rs2066847) is a stronger predictor of the clinical course of Crohn's disease than the FOXO3A intron variant rs12212067.

    Science.gov (United States)

    Schnitzler, Fabian; Friedrich, Matthias; Wolf, Christiane; Angelberger, Marianne; Diegelmann, Julia; Olszak, Torsten; Beigel, Florian; Tillack, Cornelia; Stallhofer, Johannes; Göke, Burkhard; Glas, Jürgen; Lohse, Peter; Brand, Stephan

    2014-01-01

    Very recently, a sub-analysis of genome-wide association scans revealed that the non-coding single nucleotide polymorphism (SNP) rs12212067 in the FOXO3A gene is associated with a milder course of Crohn's disease (CD) (Cell 2013;155:57-69). The aim of our study was to evaluate the clinical value of the SNP rs12212067 in predicting the severity of CD by correlating CD patient genotype status with the most relevant complications of CD such as stenoses, fistulas, and CD-related surgery. We genotyped 550 CD patients for rs12212067 (FOXO3A) and the three common CD-associated NOD2 mutations rs2066844, rs2066847, and rs2066847 and performed genotype-phenotype analyses. No significant phenotypic differences were found between the wild-type genotype TT of the FOXO3A SNP rs12212067 and the minor genotypes TG and GG independently from NOD2 variants. The allele frequency of the minor G allele was 12.7%. Age at diagnosis, disease duration, body mass index, surgery rate, stenoses, fistula, need for immunosuppressive therapy, and disease course were not significantly different. In contrast, the NOD2 mutant p.Leu1007fsX1008 (rs2066847) was highly associated with penetrating CD (p = 0.01), the development of fistulas (p = 0.01) and stenoses (p = 0.01), and ileal disease localization (p = 0.03). Importantly, the NOD2 SNP rs2066847 was a strong separator between an aggressive and a mild course of CD (p = 2.99×10(-5)), while the FOXO3A SNP rs12212067 did not separate between mild and aggressive CD behavior in our cohort (p = 0.35). 96.2% of the homozygous NOD2 p.Leu1007fsX1008 carriers had an aggressive disease behavior compared to 69.3% of the patients with the NOD2 wild-type genotype (p = 0.007). In clinical practice, the NOD2 variant p.Leu1007fsX1008 (rs2066847), in particular in homozygous form, is a much stronger marker for a severe clinical phenotype than the FOXO3A rs12212067 SNP for a mild disease course on an individual patient level despite its

  3. A Polymorphism in Hepatocyte Nuclear Factor 1 Alpha, rs7310409, Is Associated with Left Main Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Rui Liu

    2014-01-01

    Full Text Available Coronary artery disease is the leading cause of mortality and morbidity in the world. Left main coronary artery disease (LMCAD is a particularly severe phenotypic form of CAD and has a genetic basis. We hypothesized that some inflammation- and hyperhomocysteinemia-related gene polymorphisms may contribute to LMCAD susceptibility in a Chinese population. We studied the association between polymorphisms in the genes hepatocyte nuclear factor 1 alpha (HNF1A; rs7310409, G/A, C-reactive protein (rs1800947 and rs3093059 T/C, methylenetetrahydrofolate reductase (rs1801133, C/T, and methylenetetrahydrofolate dehydrogenase (rs1076991, A/G in 402 LMCAD and 804 more peripheral CAD patients in a Chinese population. Genotyping was performed using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. When the HNF1A rs7310409 GG homozygote genotype was used as the reference group, both the individual, GA and AA, and combined GA/AA genotypes were associated with an increased risk of LMCAD. This single nucleotide polymorphism (rs7310409 is strongly associated with plasma CRP levels. In conclusion, the present study provides evidence that the HNF1A rs7310409 G/A functional polymorphism may contribute to the risk of LMCAD.

  4. FTO gene polymorphisms (rs9939609 and rs17817449) as predictors of Type 2 Diabetes Mellitus in obese Iraqi population.

    Science.gov (United States)

    Younus, Laith A; Algenabi, Abdul Hussein A; Abdul-Zhara, Mohammed S; Hussein, Majid K

    2017-09-05

    dominant, recessive and additive models (P=0.000,0.000 and 0.0001 respectively). The T allele in rs17817449 was also significantly higher (P=0.0001) in patients group (36.25%) when compared with that of the control group (27.25%). The Heterozygous genotype (TG) significantly (OR=2.24, CI 95% 1.65-3.04, P=0.000) increased the risk of T2DM more than two folds with respect to those of wild type (GG) after adjustment for age, sex and BMI, and it was significantly increased the risk in the dominant models (P=0.000). In the relation to the phenotypic parameters the two SNPs were significantly associated with increased BMI, LDL, insulin and HOMA-IR and a decrease the HDL levels. The FTO gene polymorphisms rs9939609 and rs17817449 play a role in the in the development of insulin resistance and hence occurrence of type 2 DM in obese patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. PDYN rs2281285 Variant Association with Drinking to Avoid Emotional or Somatic Discomfort

    Science.gov (United States)

    Preuss, Ulrich W.; Winham, Stacey J.; Biernacka, Joanna M.; Geske, Jennifer R.; Bakalkin, Georgy; Koller, Gabriele; Zill, Peter; Soyka, Michael; Karpyak, Victor M.

    2013-01-01

    Introduction One of the proposed psychobiological pathways of craving attributes the desire for drinking in the context of tension, discomfort or unpleasant emotions, to “negative” (or “relief”) craving. The aim of this study was to replicate a previously reported association of the PDYN rs2281285 variant with negative craving using a different phenotyping approach. Methods The TaqMan® Genotyping Assay was used to genotype the rs2281285 variant in 417 German alcohol-dependent subjects. The presence of negative/relief craving was assessed by asking if participants ever ingested alcohol to avoid unwanted emotional or somatic discomfort. Results The minor allele of rs2281285 was associated with an increased risk of drinking to avoid/escape unwanted emotional or somatic events (OR = 2.29, 95% CI = 1.08–4.85, p = 0.0298). Discussion Despite the use of a different phenotyping approach to the measurement of negative craving, our results confirm the association between negative craving and PDYN rs2281285. Genetic markers of negative craving may help to identify subgroups of alcohol-dependent individuals vulnerable to relapse in the context of negative emotions or somatic discomfort, leading to the development of specifically tailored treatment strategies. PMID:24223163

  6. PDYN rs2281285 variant association with drinking to avoid emotional or somatic discomfort.

    Directory of Open Access Journals (Sweden)

    Ulrich W Preuss

    Full Text Available One of the proposed psychobiological pathways of craving attributes the desire for drinking in the context of tension, discomfort or unpleasant emotions, to "negative" (or "relief" craving. The aim of this study was to replicate a previously reported association of the PDYN rs2281285 variant with negative craving using a different phenotyping approach.The TaqMan® Genotyping Assay was used to genotype the rs2281285 variant in 417 German alcohol-dependent subjects. The presence of negative/relief craving was assessed by asking if participants ever ingested alcohol to avoid unwanted emotional or somatic discomfort.The minor allele of rs2281285 was associated with an increased risk of drinking to avoid/escape unwanted emotional or somatic events (OR=2.29, 95% CI=1.08-4.85, p=0.0298.Despite the use of a different phenotyping approach to the measurement of negative craving, our results confirm the association between negative craving and PDYN rs2281285. Genetic markers of negative craving may help to identify subgroups of alcohol-dependent individuals vulnerable to relapse in the context of negative emotions or somatic discomfort, leading to the development of specifically tailored treatment strategies.

  7. Can rs3767140 SNP of the perlecan (HSPG2) gene affect the diabetes mellitus through the dyslipidemia?

    Science.gov (United States)

    Kurnaz-Gömleksiz, Ö; Tokat, B; Aslan, E I; Yanar, F; Ermiş-Karaali, Z; Öztürk, O; Yilmaz-Aydoğan, H

    2016-07-31

    Perlecan (HSPG2) play an important role in the lipoprotein metabolisms. The G allele of the HSPG2-rs3767140 may affect the binding of heparan sulfate (HS) chains and hence cause loss of HS from the basement membrane. HSPG2-rs3767140 was studied in 60 T2DM patients and 109 healthy controls. In diabetic patients HSPG2-rs3767140 T variant allele carriers (TT+GT) have decreased fasting plasma glucose (FPG) and serum LDL-C levels (p=0.071 and p=0.060, respectively) versus GG genotype carriers. Moreover, in both of the two groups in which the T allele carriers HDL-cholesterol levels tend to be high. We investigated that the HSPG2-rs3767140 promoted to the dyslipidemic phenotype in the type 2 diabetes mellitus (T2DM) patients. We suggest that the HSPG2-rs3767140 might be associated with the decreased FPG and LDL-C and with the increased HDL-C in diabetics. Therefore, the HSPG2-rs3767140 might be a protective for the diabetes mellitus due to its ameliorating effect on the dyslipidemic phenotype.

  8. Sirtuin 1 gene rs2273773 C>T single nucleotide polymorphism and ...

    African Journals Online (AJOL)

    Aida Abdeen Mahmoud

    2015-12-24

    Dec 24, 2015 ... Abstract Background: Sirtuin-1 (SIRT-1), a protein has been found to protect the cells against oxidative stress ... rs2273773 C > T SNP and serum markers of protein oxida- tion (protein ..... tance and pulmonary dynamic compliance. Treatment ... [4] Autiero I, Costantini S, Colonna G. Human sirt-1: molecular.

  9. Genotype-phenotype associations in obesity dependent on definition of the obesity phenotype.

    Science.gov (United States)

    Kring, Sofia Inez Iqbal; Larsen, Lesli Hingstrup; Holst, Claus; Toubro, Søren; Hansen, Torben; Astrup, Arne; Pedersen, Oluf; Sørensen, Thorkild I A

    2008-01-01

    In previous studies of associations of variants in the genes UCP2, UCP3, PPARG2, CART, GRL, MC4R, MKKS, SHP, GHRL, and MCHR1 with obesity, we have used a case-control approach with cases defined by a threshold for BMI. In the present study, we assess the association of seven abdominal, peripheral, and overall obesity phenotypes, which were analyzed quantitatively, and thirteen candidate gene polymorphisms in these ten genes in the same cohort. Obese Caucasian men (n = 234, BMI >or= 31.0 kg/m(2)) and a randomly sampled non-obese group (n = 323), originally identified at the draft board examinations, were re-examined at median ages of 47.0 or 49.0 years by anthropometry and DEXA scanning. Obesity phenotypes included BMI, fat body mass index, waist circumference, waist for given BMI, intra-abdominal adipose tissue, hip circumference and lower body fat mass (%). Using logistic regression models, we estimated the odds for defined genotypes (dominant or recessive genetic transmission) in relation to z-scores of the phenotypes. The minor (rare) allele for SHP 512G>C (rs6659176) was associated with increased hip circumference. The minor allele for UCP2 Ins45bp was associated with increased BMI, increased abdominal obesity, and increased hip circumference. The minor allele for UCP2 -866G>A (rs6593669) was associated with borderline increased fat body mass index. The minor allele for MCHR1 100213G>A (rs133072) was associated with reduced abdominal obesity. None of the other genotype-phenotype combinations showed appreciable associations. If replicated in independent studies with focus on the specific phenotypes, our explorative studies suggest significant associations between some candidate gene polymorphisms and distinct obesity phenotypes, predicting beneficial and detrimental effects, depending on compartments for body fat accumulation. Copyright 2008 S. Karger AG, Basel.

  10. Effect of ciprofibrate on lipoprotein metabolism and oxidative stress parameters in patients with type 2 diabetes mellitus and atherogenic lipoprotein phenotype

    Czech Academy of Sciences Publication Activity Database

    Rašlová, K.; Nagyová, A.; Dobiášová, Milada; Ptáčková, Kateřina; Dušinská, M.

    2000-01-01

    Roč. 37, č. 3 (2000), s. 131-134 ISSN 0940-5429 R&D Projects: GA ČR GV306/96/K220 Institutional research plan: CEZ:AV0Z5011922 Keywords : ciprofibrate * type 2 diabetes mellitus * oxidative stress Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 0.519, year: 2000

  11. Comparative genomics analysis of field isolates of Aspergillus flavus and A. parasiticus to explain phenotypic variation in oxidative stress tolerance and host preference

    Science.gov (United States)

    Aflatoxin contamination of peanut and other crops is a major concern for producers globally, and has been shown to be exacerbated by drought stress. Previous transcriptomic and proteomic examination of the responses of isolates of Aspergillus flavus to drought-related oxidative stress in vitro have ...

  12. The NC3Rs gateway: Accelerating scientific discoveries with new 3Rs models and technologies.

    Science.gov (United States)

    Percie du Sert, Nathalie; Robinson, Vicky

    2018-01-01

    This editorial introduces the NC3Rs gateway, which publishes articles and reviews on new models and technologies emerging from NC3Rs-funded research. The aim is to raise awareness about these approaches, increase confidence in their capability, and provide sufficient information to facilitate their uptake by others.

  13. A preliminary candidate genotype-intermediate phenotype study of satiation and gastric motor function in obesity.

    Science.gov (United States)

    Papathanasopoulos, Athanasios; Camilleri, Michael; Carlson, Paula J; Vella, Adrian; Nord, Sara J Linker; Burton, Duane D; Odunsi, Suwebatu T; Zinsmeister, Alan R

    2010-06-01

    Stomach motility contributes significantly to fullness sensation while eating and cessation of food intake in humans. Genes controlling adrenergic and serotonergic mechanisms (ADRA2A, GNB3, and SLC6A4) affect gastric emptying (GE), volume (GV), and satiation. Fat mass and obesity-associated gene (FTO) is linked with satiety. Our aim was to examine the association of these candidate genes with stomach functions that signal postprandial fullness: GE, GV, and maximum tolerated volume (MTV). These biomarkers constitute a component of the intermediate phenotype of satiation. A total of 62 overweight or obese participants underwent genotyping of the candidate genes, and validated measurements of GE of solids and liquids by scintigraphy, fasting and postprandial change in GV by SPECT (single photon emission computed tomography), and MTV by nutrient drink test. These markers of satiation were compared for 38 genetic variants in ADRA2A, ADR2C, ADRB3, uncoupling protein (UCP)-2 and -3, GNB3, FTO, and SLC6A4 using a recessive model of inheritance. ADRA2A, ADR2C, UCP-3, GNB3, and FTO loci were significantly associated with the intermediate phenotype markers of satiation: ADR2C (Ins-Del322_325) with accelerated GE; GNB3 (rs1047776) with delayed GE; ADRA2A (rs491589 and rs553668) and GNB3 (rs2269355, rs10849527, and rs3759348) with decreased postprandial GV; ADRA2A (rs3750625) and GNB3 (rs4963517 and rs1129649) with increased postprandial GV; UCP-3 (rs1685356) with increased MTV, and FTO (rs9939609) decreased MTV. Genetic susceptibility to postprandial satiation can be identified through intermediate phenotype markers. With independent validation, these markers may guide patient selection of weight-loss therapies directed at gastric motor functions.

  14. Soft-decision decoding of RS codes

    DEFF Research Database (Denmark)

    Justesen, Jørn

    2005-01-01

    By introducing a few simplifying assumptions we derive a simple condition for successful decoding using the Koetter-Vardy algorithm for soft-decision decoding of RS codes. We show that the algorithm has a significant advantage over hard decision decoding when the code rate is low, when two or more...

  15. Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

    Science.gov (United States)

    Raza, Syed Tasleem; Abbas, Shania; Siddiqi, Zeba; Mahdi, Farzana

    2017-01-01

    Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR , FABP2 , FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (Pgenes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE , FABP2 , FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

  16. Quantitative evaluation of pairs and RS steganalysis

    Science.gov (United States)

    Ker, Andrew D.

    2004-06-01

    We give initial results from a new project which performs statistically accurate evaluation of the reliability of image steganalysis algorithms. The focus here is on the Pairs and RS methods, for detection of simple LSB steganography in grayscale bitmaps, due to Fridrich et al. Using libraries totalling around 30,000 images we have measured the performance of these methods and suggest changes which lead to significant improvements. Particular results from the project presented here include notes on the distribution of the RS statistic, the relative merits of different "masks" used in the RS algorithm, the effect on reliability when previously compressed cover images are used, and the effect of repeating steganalysis on the transposed image. We also discuss improvements to the Pairs algorithm, restricting it to spatially close pairs of pixels, which leads to a substantial performance improvement, even to the extent of surpassing the RS statistic which was previously thought superior for grayscale images. We also describe some of the questions for a general methodology of evaluation of steganalysis, and potential pitfalls caused by the differences between uncompressed, compressed, and resampled cover images.

  17. The origin of the RS CVn binaries

    International Nuclear Information System (INIS)

    Biermann, P.

    1976-01-01

    Six possible origins for the RS CVn binaries are considered based on the following possibilities. RS CVn binaries might now be either pre-main-sequence or post-main-sequence. A pre-main-sequence binary might not always have been a binary but might have resulted from fission of a rapidly rotating single pre-main-sequence star. The main-sequence counterparts might be either single stars or binaries. To decide which of the six origins is possible, the following observed data for the RS CVn binaries are considered: total mass, total angular momentum, lack of observed connection with regions of star formation, large space density, kinematical age, and the visual companion of WW Dra. In addition lifetimes and space densities of single stars and other types of binaries are considered. The only origin possible is that the RS CVn binaries are in a thermal phase following fission of a main-sequence single star. In this explanation the single star had a rapidly rotating core which became unstable due to the core contraction which made it begin to evolve off the main sequence. The present Be stars might be examples of such parent single stars. (Auth.)

  18. Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population

    International Nuclear Information System (INIS)

    Peña-Chilet, Maria; Ribas, Gloria; Blanquer-Maceiras, Maite; Ibarrola-Villava, Maider; Martinez-Cadenas, Conrado; Martin-Gonzalez, Manuel; Gomez-Fernandez, Cristina; Mayor, Matias; Aviles, Juan Antonio; Lluch, Ana

    2013-01-01

    Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition. We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics. We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10 -4 ). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10 -4 ). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study. To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that

  19. Role of ArlRS in autolysis in methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains.

    Science.gov (United States)

    Memmi, Guido; Nair, Dhanalakshmi R; Cheung, Ambrose

    2012-02-01

    Autolysis plays an essential role in bacterial cell division and lysis with β-lactam antibiotics. Accordingly, the expression of autolysins is tightly regulated by several endogenous regulators, including ArlRS, a two component regulatory system that has been shown to negatively regulate autolysis in methicillin-sensitive Staphylococcus aureus (MSSA) strains. In this study, we found that inactivation of arlRS does not play a role in autolysis of methicillin-resistant S. aureus (MRSA) strains, such as community-acquired (CA)-MRSA strains USA300 and MW2 or the hospital-acquired (HA)-MRSA strain COL. This contrasts with MSSA strains, including Newman, SH1000, RN6390, and 8325-4, where autolysis is affected by ArlRS. We further demonstrated that the striking difference in the roles of arlRS between MSSA and MRSA strains is not due to the methicillin resistance determinant mecA. Among known autolysins and their regulators, we found that arlRS represses lytN, while no effect was seen on atl, lytM, and lytH expression in both CA- and HA-MRSA strains. Transcriptional-fusion assays showed that the agr transcripts, RNAII and RNAIII, were significantly more downregulated in the arlRS mutant of MW2 than the MSSA strain Newman. Importantly, provision of agr RNAIII in trans to the MW2 arlRS mutant via a multicopy plasmid induced autolysis in this MRSA strain. Also, the autolytic phenotype in the arlRS mutant of MSSA strain Newman could be rescued by a mutation in either atl or lytM. Together, these data showed that ArlRS impacts autolysis differently in MSSA and MRSA strains.

  20. Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis.

    Science.gov (United States)

    D'Souza, Leera; Cukras, Catherine; Antolik, Christian; Craig, Candice; Lee, Ji-Yun; He, Hong; Li, Shibo; Smaoui, Nizar; Hejtmancik, James F; Sieving, Paul A; Wang, Xinjing

    2013-01-01

    X-linked juvenile retinoschisis (XLRS) is a vitreoretinal dystrophy characterized by schisis (splitting) of the inner layers of the neuroretina. Mutations within the retinoschisis (RS1) gene are responsible for this disease. The mutation spectrum consists of amino acid substitutions, splice site variations, small indels, and larger genomic deletions. Clinically, genomic deletions are rarely reported. Here, we characterize two novel full exonic deletions: one encompassing exon 1 and the other spanning exons 4-5 of the RS1 gene. We also report the clinical findings in these patients with XLRS with two different exonic deletions. Unrelated XLRS men and boys and their mothers (if available) were enrolled for molecular genetics evaluation. The patients also underwent ophthalmologic examination and in some cases electroretinogram (ERG) recording. All the exons and the flanking intronic regions of the RS1 gene were analyzed with direct sequencing. Two patients with exonic deletions were further evaluated with array comparative genomic hybridization to define the scope of the genomic aberrations. After the deleted genomic region was identified, primer walking followed by direct sequencing was used to determine the exact breakpoints. Two novel exonic deletions of the RS1 gene were identified: one including exon 1 and the other spanning exons 4 and 5. The exon 1 deletion extends from the 5' region of the RS1 gene (including the promoter) through intron 1 (c.(-35)-1723_c.51+2664del4472). The exon 4-5 deletion spans introns 3 to intron 5 (c.185-1020_c.522+1844del5764). Here we report two novel exonic deletions within the RS1 gene locus. We have also described the clinical presentations and hypothesized the genomic mechanisms underlying these schisis phenotypes.

  1. Mediterranean Dietary Pattern Adherence Modify the Association between FTO Genetic Variations and Obesity Phenotypes

    Directory of Open Access Journals (Sweden)

    Firoozeh Hosseini-Esfahani

    2017-09-01

    Full Text Available There is increasing interest of which dietary patterns can modify the association of fat mass and obesity associated (FTO variants with obesity. This study was aimed at investigating the interaction of the Mediterranean dietary pattern (Med Diet with FTO polymorphisms in relation to obesity phenotypes. Subjects of this nested case-control study were selected from the Tehran Lipid and Glucose Study participants. Each case was individually matched with a normal weight control (n = 1254. Selected polymorphisms (rs1421085, rs1121980, rs17817449, rs8050136, rs9939973, and rs3751812 were genotyped. Genetic risk score (GRS were calculated using the weighted method. The Mediterranean dietary score (MDS was computed. Individuals with minor allele carriers of rs9939973, rs8050136, rs1781749, and rs3751812 had lower risk of obesity when they had higher MDS, compared to wild-type homozygote genotype carriers. The obesity risk was decreased across quartiles of MDS in participants with high GRS (OR: 1, 0.8, 0.79, 0.67 compared to individuals with low GRS (OR: 1.33, 1.06, 0.97, 1.12 (Pinteraction < 0.05. No significant interaction between the GRS and MDS on abdominal obesity was found. A higher Med Diet adherence was associated with lower obesity risk in subjects with more genetic predisposition to obesity, compared to those with lower adherence to the Med Diet and lower GRS.

  2. Impact of Gene rs7422339 Polymorphism in Argentine Patients With Hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Silene M. Silvera-Ruiz BSc

    2015-05-01

    Full Text Available Carbamoyl phosphate synthetase 1 ( CPS1 is a key gene in the first step of urea cycle and has been correlated with nitric oxide level and vascular smooth muscle activity. A functional single-nucleotide polymorphism C/A at position 4217 in CPS1 (National Center for Biotechnology Information SNP database no. rs7422339, T1405N was reported to be associated with high homocysteine (Hcy plasma values. Although genetic variants of methylenetetrahydrofolate reductase ( MTHFR gene are known to influence Hcy concentration, other genetic determinants of Hcy remain largely unknown. The association between the CPS1 rs7422339 and the risk of hyperhomocysteinemia in Latin American populations is unknown. Here, we study this association in 100 patients having hyperhomocysteinemia without MTHFR c.677C>T polymorphism and 100 controls. CPS1 rs7422339 was studied using polymerase chain reaction and enzymatic restriction. Comparisons of the CPS1 rs7422339 genotype distributions revealed a significant difference between groups ( P = 2.3 × 10 −3 . Patients carrying polymorphic allele showed almost 3 times higher risk (odds ratio [OR] = 2.47 of hyperhomocysteinemia than wild-type allele, suggesting that rs7422339 SNP is associated with high Hcy levels in the Argentine population.

  3. Infrared observations of RS CVn stars

    International Nuclear Information System (INIS)

    Berriman, G.; De Campli, W.M.; Werner, M.W.; Hatchett, S.P.

    1983-01-01

    Infrared photometry is presented of the RS CVn binary stars AR Lac (1.2-10 μm) and MM Her (1.2-3.5 μm) as they egressed from their primary and secondary eclipses; of the eclipsing systems RS CVn and Z Her at maximum light (1.2-10 μm) and of the non-eclipsing systems UX Ari and HR 1099 (1.2-10 μm). An analysis of these and published V data based on flux ratio diagrams (linear analogues of colour-colour diagrams) shows that G and K stars supply the infrared light of these systems. None of these systems shows infrared emission from circumstellar matter. (author)

  4. Face and emotion expression processing and the serotonin transporter polymorphism 5-HTTLPR/rs22531.

    Science.gov (United States)

    Hildebrandt, A; Kiy, A; Reuter, M; Sommer, W; Wilhelm, O

    2016-06-01

    Face cognition, including face identity and facial expression processing, is a crucial component of socio-emotional abilities, characterizing humans as highest developed social beings. However, for these trait domains molecular genetic studies investigating gene-behavior associations based on well-founded phenotype definitions are still rare. We examined the relationship between 5-HTTLPR/rs25531 polymorphisms - related to serotonin-reuptake - and the ability to perceive and recognize faces and emotional expressions in human faces. For this aim we conducted structural equation modeling on data from 230 young adults, obtained by using a comprehensive, multivariate task battery with maximal effort tasks. By additionally modeling fluid intelligence and immediate and delayed memory factors, we aimed to address the discriminant relationships of the 5-HTTLPR/rs25531 polymorphisms with socio-emotional abilities. We found a robust association between the 5-HTTLPR/rs25531 polymorphism and facial emotion perception. Carriers of two long (L) alleles outperformed carriers of one or two S alleles. Weaker associations were present for face identity perception and memory for emotional facial expressions. There was no association between the 5-HTTLPR/rs25531 polymorphism and non-social abilities, demonstrating discriminant validity of the relationships. We discuss the implications and possible neural mechanisms underlying these novel findings. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  5. A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation.

    Science.gov (United States)

    Kılıç, Ayşe; Santolini, Marc; Nakano, Taiji; Schiller, Matthias; Teranishi, Mizue; Gellert, Pascal; Ponomareva, Yuliya; Braun, Thomas; Uchida, Shizuka; Weiss, Scott T; Sharma, Amitabh; Renz, Harald

    2018-06-07

    Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune homeostasis. Since an altered expression of various miRs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRs control mechanisms ensuring Th2 stability and maintenance in the lung. We isolated murine CD4+ Th2 cells from allergic inflamed lungs and profiled gene and miR expression. Instead of focusing on the magnitude of miR differential expression, here we addressed the secondary consequences for the set of molecular interactions in the cell, the interactome. We developed the Impact of Differential Expression Across Layers, a network-based algorithm to prioritize disease-relevant miRs based on the central role of their targets in the molecular interactome. This method identified 5 Th2-related miRs (mir27b, mir206, mir106b, mir203, and mir23b) whose antagonization led to a sharp reduction of the Th2 phenotype. Overall, a systems biology tool was developed and validated, highlighting the role of miRs in Th2-driven immune response. This result offers potentially novel approaches for therapeutic interventions.

  6. Interaction between the Haptoglobin 2 Phenotype and Diabetes Mellitus on Systolic Pulmonary Arterial Pressure and Nitric Oxide Bioavailability in Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Inbal Dahan

    2015-01-01

    Full Text Available Elevated systolic pulmonary artery pressure (s-PAP, ≥35 mmHg serves as an independent predictor of mortality in hemodialysis (HD and diabetic (DM patients. A polymorphism in the antioxidant Haptoglobin (Hp gene has been shown to regulate the bioavailability of nitric oxide (NO, a major mediator of pulmonary vascular tone. We therefore set out to test the hypothesis that the Hp polymorphism may be a determinant of developing elevated s-PAP specifically in the DM state due to a decreased bioavailability of NO. To test our hypothesis we Hp typed and performed transthoracic echocardiography on a series of HD patients and stratified them into elevated and normal s-PAP groups and then evaluated whether there was a significant association between the Hp type, elevated s-PAP, and decreased NO bioavailability as defined by low plasma nitrite. We found a statistically significant interaction between the Hp type and DM on the prevalence of elevated s-PAP and lower mean nitrite levels with the combination of elevated s-PAP and low nitrite levels being significantly more prevalent in Hp 2-2 DM individuals. We conclude that the Hp 2 type is associated with elevated s-PAP levels and low plasma nitrite levels in HD patients specifically in the DM state.

  7. Association between vitamin D concentration and levels of sex hormones in an elderly Polish population with different genotypes of VDR polymorphisms (rs10735810, rs1544410, rs7975232, rs731236).

    Science.gov (United States)

    Laczmanski, Lukasz; Lwow, Felicja; Mossakowska, Malgorzata; Puzianowska-Kuznicka, Monika; Szwed, Małgorzata; Kolackov, Katarzyna; Krzyzanowska-Swiniarska, Barbara; Bar-Andziak, Ewa; Chudek, Jerzy; Sloka, Natalia; Milewicz, Andrzej

    2015-03-15

    Vitamin D co-regulates the synthesis of sex hormones in part by interaction with its nuclear receptor. The aim of this study was to determine whether there is an association of vitamin D concentration vs the level of sex hormones in elderly Polish individuals with different genotypes of the vitamin D receptor (VDR) gene. Rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum sex hormone level, free estrogen index (FEI) and free androgen index (FAI) as well as vitamin D, were evaluated in 766 persons (362 women and 404 men) selected from 5695 Polish population, aged 65-90years from the PolSenior survey. We observed that women with GG (rs731236), TT (rs7975232), BB (rs1544410) and FF (rs10735810) genotypes were characterized by a significant correlation between vitamin D vs testosterone concentration and FAI value. We found a significant correlation between testosterone level and FAI vs vitamin D concentration in men with heterozygote AG in the rs731236 polymorphism and in the GG (rs7975232), the BB (rs1544410), and the Ff (rs10735810) genotypes. In elderly selected Polish population with different genotypes of VDR polymorphisms, a statistically significant relationship between vitamin D concentration vs testosterone level was observed. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria.

    Science.gov (United States)

    Wettstein, Sarah; Underhaug, Jarl; Perez, Belen; Marsden, Brian D; Yue, Wyatt W; Martinez, Aurora; Blau, Nenad

    2015-03-01

    The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) = 0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (≈ 100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database.

  9. 40 CFR 180.1114 - Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas syringae 742RS...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas syringae 742RS; exemptions from the requirement of a tolerance... Tolerances § 180.1114 Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas syringae...

  10. COX-2 rs689466, rs5275, and rs20417 polymorphisms and risk of head and neck squamous cell carcinoma: a meta-analysis of adjusted and unadjusted data

    International Nuclear Information System (INIS)

    Leng, Wei-Dong; Wen, Xiu-Jie; Kwong, Joey S. W.; Huang, Wei; Chen, Jian-Gang; Zeng, Xian-Tao

    2016-01-01

    Numerous case–control studies have been performed to investigate the association between three cyclooxygenase-2 (COX-2) polymorphisms (rs20417 (−765G > C), rs689466 (−1195G > A), and rs5275 (8473 T > C)) and the risk of head and neck squamous cell carcinoma (HNSCC). However, the results were inconsistent. Therefore, we conducted this meta-analysis to investigate the association. We searched in PubMed, Embase, and Web of Science up to January 20, 2015 (last updated on May 12, 2016). Two independent reviewers extracted the data. Odds ratios (ORs) with their 95 % confidence intervals (CIs) were used to assess the association. All statistical analyses were performed using the Review Manager (RevMan) 5.2 software. Finally 8 case–control studies were included in this meta-analysis. For unadjusted data, an association with increased risk was observed in three genetic models in COX-2 rs689466 polymorphism; however, COX-2 rs5275 and rs20417 polymorphisms were not related to HNSCC risk in this study. The pooled results from adjusted data all revealed non-significant association between these three polymorphisms and risk of HNSCC. We also found a similar result in the subgroup analyses, based on both unadjusted data and adjusted data. Current results suggest that COX-2 rs689466, rs5275, and rs20417 polymorphisms are not associated with HNSCC. Further large and well-designed studies are necessary to validate this association

  11. Mass and Reliability System (MaRS)

    Science.gov (United States)

    Barnes, Sarah

    2016-01-01

    The Safety and Mission Assurance (S&MA) Directorate is responsible for mitigating risk, providing system safety, and lowering risk for space programs from ground to space. The S&MA is divided into 4 divisions: The Space Exploration Division (NC), the International Space Station Division (NE), the Safety & Test Operations Division (NS), and the Quality and Flight Equipment Division (NT). The interns, myself and Arun Aruljothi, will be working with the Risk & Reliability Analysis Branch under the NC Division's. The mission of this division is to identify, characterize, diminish, and communicate risk by implementing an efficient and effective assurance model. The team utilizes Reliability and Maintainability (R&M) and Probabilistic Risk Assessment (PRA) to ensure decisions concerning risks are informed, vehicles are safe and reliable, and program/project requirements are realistic and realized. This project pertains to the Orion mission, so it is geared toward a long duration Human Space Flight Program(s). For space missions, payload is a critical concept; balancing what hardware can be replaced by components verse by Orbital Replacement Units (ORU) or subassemblies is key. For this effort a database was created that combines mass and reliability data, called Mass and Reliability System or MaRS. The U.S. International Space Station (ISS) components are used as reference parts in the MaRS database. Using ISS components as a platform is beneficial because of the historical context and the environment similarities to a space flight mission. MaRS uses a combination of systems: International Space Station PART for failure data, Vehicle Master Database (VMDB) for ORU & components, Maintenance & Analysis Data Set (MADS) for operation hours and other pertinent data, & Hardware History Retrieval System (HHRS) for unit weights. MaRS is populated using a Visual Basic Application. Once populated, the excel spreadsheet is comprised of information on ISS components including

  12. Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients.

    Science.gov (United States)

    Chalikiopoulou, Constantina; Tavianatou, Anastasia-Gerasimoula; Sgourou, Argyro; Kourakli, Alexandra; Kelepouri, Dimitra; Chrysanthakopoulou, Maria; Kanelaki, Vasiliki-Kaliopi; Mourdoukoutas, Evangelos; Siamoglou, Stavroula; John, Anne; Symeonidis, Argyris; Ali, Bassam R; Katsila, Theodora; Papachatzopoulou, Adamantia; Patrinos, George P

    2016-03-01

    Hemoglobinopathies exhibit a remarkable phenotypic diversity that restricts any safe association between molecular pathology and clinical outcomes. Herein, we explored the role of genes involved in the nitric oxide biosynthesis and signaling pathway, implicated in the increase of fetal hemoglobin levels and response to hydroxyurea treatment, in 119 Hellenic patients with β-type hemoglobinopathies. We show that two ASS1 genomic variants (namely, rs10901080 and rs10793902) can serve as pharmacogenomic biomarkers to predict hydroxyurea treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients. These markers may exert their effect by inducing nitric oxide biosynthesis, either via altering splicing and/or miRNA binding, as predicted by in silico analysis, and ultimately, increase γ-globin levels, via guanylyl cyclase targeting.

  13. Infrared observations of RS CVn stars

    Science.gov (United States)

    Berriman, G.; De Campli, W. M.; Werner, M. W.; Hatchett, S. P.

    1983-01-01

    The paper presents infrared photometry of the RS CVn binary stars AR Lac (1.2-10 microns) and MM Her (1.2-3.5 microns) as they egressed from their primary and secondary eclipses; of the eclipsing systems RS CVn and Z Her at maximum light (1.2-10 microns) and of the non-eclipsing systems UX Ari and HR 1099 (1.2-10 microns). An analysis of these and published V data based on flux ratio diagrams (linear analogues of color-color diagrams) shows that G and K stars supply the infrared light of these systems. In AR Lac, the combined light of a G5-K0 subgiant and either a late F dwarf or an early F subgiant can account for the observed visual and infrared light curves. None of these systems shows infrared emission from circumstellar matter. This result is simply understood: dust grains would not be expected to form in the physical conditions surrounding the subgiant, and the corona and chromosphere (whose properties have been deduced from spectroscopic X-ray observations) should not produce appreciable infrared emission.

  14. High-Speed RaPToRS

    Science.gov (United States)

    Henchen, Robert; Esham, Benjamin; Becker, William; Pogozelski, Edward; Padalino, Stephen; Sangster, Thomas; Glebov, Vladimir

    2008-11-01

    The High-Speed Rapid Pneumatic Transport of Radioactive Samples (HS-RaPToRS) system, designed to quickly and safely move radioactive materials, was assembled and tested at the Mercury facility of the Naval Research Laboratory (NRL) in Washington D.C. A sample, which is placed inside a four-inch-diameter carrier, is activated before being transported through a PVC tube via airflow. The carrier travels from the reaction chamber to the end station where it pneumatically brakes prior to the gate. A magnetic latch releases the gate when the carrier arrives and comes to rest. The airflow, optical carrier-monitoring devices, and end gate are controlled manually or automatically with LabView software. The installation and testing of the RaPToRS system at NRL was successfully completed with transport times of less than 3 seconds. The speed of the carrier averaged 16 m/s. Prospective facilities for similar systems include the Laboratory for Laser Energetics and the National Ignition Facility.

  15. New insights into virulence mechanisms of rice pathogen Acidovorax avenae subsp. avenae strain RS-1 following exposure to ?-lactam antibiotics

    OpenAIRE

    Li, Bin; Ge, Mengyu; Zhang, Yang; Wang, Li; Ibrahim, Muhammad; Wang, Yanli; Sun, Guochang; Chen, Gongyou

    2016-01-01

    Recent research has shown that pathogen virulence can be altered by exposure to antibiotics, even when the growth rate is unaffected. Investigating this phenomenon provides new insights into understanding the virulence mechanisms of bacterial pathogens. This study investigates the phenotypic and transcriptomic responses of the rice pathogenic bacterium Acidovorax avenae subsp. avenae (Aaa) strain RS-1 to ?-lactam antibiotics especially Ampicillin (Amp). Our results indicate that exposure to A...

  16. ( pear cu (SSR) m ultivar marke rs and rs are select effect tions ive for r

    African Journals Online (AJOL)

    SAM

    the most su ers selected tter matrices y. the most im s pyrifolia, Py he terms of the can Journ rs are select. Vilela Res esquita Filho”. PR, Brazil. FLA, Lavras M. 015 in the sout ... Nations Food and. Agricultire Organization (2014), approximately 210 000 ..... Lorenzo S (2011). Genetic variability and diversification process in.

  17. Asthma phenotypes in childhood.

    Science.gov (United States)

    Reddy, Monica B; Covar, Ronina A

    2016-04-01

    This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

  18. Do plants and animals differ in phenotypic plasticity?

    Indian Academy of Sciences (India)

    Unknown

    fits, of a plastic versus non-plastic phenotype in plants and animals. [Renee M Borges ... polyphenol oxidase and other oxidative enzymes in the defence repertoire of .... males in response to environmental stress (Cremer and. Heinze 2003).

  19. RaPToRS Sample Delivery System

    Science.gov (United States)

    Henchen, Robert; Shibata, Kye; Krieger, Michael; Pogozelski, Edward; Padalino, Stephen; Glebov, Vladimir; Sangster, Craig

    2010-11-01

    At various labs (NIF, LLE, NRL), activated material samples are used to measure reaction properties. The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system quickly and safely moves these radioactive samples through a closed PVC tube via airflow. The carrier travels from the reaction chamber to the control and analysis station, pneumatically braking at the outlet. A reversible multiplexer routes samples from various locations near the shot chamber to the analysis station. Also, the multiplexer allows users to remotely load unactivated samples without manually approaching the reaction chamber. All elements of the system (pneumatic drivers, flow control valves, optical position sensors, multiplexers, Geiger counters, and release gates at the analysis station) can be controlled manually or automatically using a custom LabVIEW interface. A prototype is currently operating at NRL in Washington DC. Prospective facilities for Raptors systems include LLE and NIF.

  20. ARIES-RS safety design and analysis

    International Nuclear Information System (INIS)

    Steiner, D.; El-Guebaly, L.; Herring, S.; Khater, H.; Mogahed, E.; Thayer, R.; Tillack, M.S.

    1997-01-01

    The ARIES-RS safety design and analysis focused on achieving two objectives: (1) The avoidance of sheltering or evacuation in the event of an accident; and (2) the generation of only low-level waste, no greater than Class C. The ARIES-RS baseline design employs V-4Cr-4Ti as the blanket structural material and a low activation ferritic steel in the reflector and shield. In the event of a LOCA, the baseline design first wall maximum temperature falls in the range of 1100-1200 C. For this temperature range, the hazard assessment indicates that the dose at the site boundary will be less than 1 rem per year. Thus, no sheltering or evacuation would be required in the event of a LOCA. Although the baseline design satisfies the first safety objective noted above, a first wall maximum temperature of ∝1100-1200 C would likely compromise the integrity of the vanadium blanket structure and would require blanket replacement following such a temperature excursion. To avoid this situation, a modified blanket design incorporating supplemental heat removal is also proposed. Preliminary analysis of this modified design suggests that the first wall maximum temperature can be kept below the temperature range of concern, ∝1000-1100 C, in the event of a LOCA. When the ferritic steel used in the reflector and shield is one reduced in Ir and Ag impurities, all in-vessel components qualify for near-surface shallow land burial as Class C low-level waste. (orig.)

  1. Association of MicroRNA-146a rs2910164 Gene Polymorphism with Metabolic Syndrome.

    Science.gov (United States)

    Mehanna, E T; Ghattas, M H; Mesbah, N M; Saleh, S M; Abo-Elmatty, D M

    2015-01-01

    Alteration in microRNA-146a (miRNA-146a) expression is an important event in the pathogenesis of many human diseases. MiRNA-146a rs2910164 is a functional polymorphism that showed association with several diseases. Metabolic syndrome is an aggregation of multiple risk factors including impaired glucose tolerance, increased highdensity lipoprotein, abdominal obesity, and high blood pressure. The aim of this study was to assess the relation of miRNA-146a rs2910164 with metabolic syndrome and its component traits in Egyptian women from the Suez Canal area. The study included 100 healthy female subjects and 100 metabolic syndrome patients. The component traits of metabolic syndrome were determined and the genotypes of the polymorphisms were assessed using the polymerase chain reaction-restriction fragment length polymorphism technique using the restriction enzyme Hpy188I. The rare C allele had a significantly higher frequency in metabolic syndrome patients (P = 0.013). The heterozygote GC and the rare CC genotypes showed a significant increase in body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, systolic and diastolic blood pressure. The GC genotype was associated with higher fasting blood glucose, fasting serum insulin and insulin resistance. The carriers of CC genotype had significantly lower HDL compared with the GG genotype carriers. In conclusion, The C allele of miRNA-146a rs2910164 showed positive association with increased susceptibility to metabolic syndrome and its phenotypes in the study population.

  2. Design Report for Isolated RS-485 Bus Node

    Science.gov (United States)

    2016-07-01

    TERMS Android , RS-485, isolated, USB, smartphone 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER...controlled wired RS-485 network. The Android -based smartphone or tablet is used in conjunction with a USB to serial bridge to operate as the bus master in...the system. The Android device operates in USB Host mode and communicates to the RS-485 bus as if a single peripheral on the USB bus. 15. SUBJECT

  3. RS-SNP: a random-set method for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Mukherjee Sayan

    2011-03-01

    Full Text Available Abstract Background The typical objective of Genome-wide association (GWA studies is to identify single-nucleotide polymorphisms (SNPs and corresponding genes with the strongest evidence of association (the 'most-significant SNPs/genes' approach. Borrowing ideas from micro-array data analysis, we propose a new method, named RS-SNP, for detecting sets of genes enriched in SNPs moderately associated to the phenotype. RS-SNP assesses whether the number of significant SNPs, with p-value P ≤ α, belonging to a given SNP set is statistically significant. The rationale of proposed method is that two kinds of null hypotheses are taken into account simultaneously. In the first null model the genotype and the phenotype are assumed to be independent random variables and the null distribution is the probability of the number of significant SNPs in greater than observed by chance. The second null model assumes the number of significant SNPs in depends on the size of and not on the identity of the SNPs in . Statistical significance is assessed using non-parametric permutation tests. Results We applied RS-SNP to the Crohn's disease (CD data set collected by the Wellcome Trust Case Control Consortium (WTCCC and compared the results with GENGEN, an approach recently proposed in literature. The enrichment analysis using RS-SNP and the set of pathways contained in the MSigDB C2 CP pathway collection highlighted 86 pathways rich in SNPs weakly associated to CD. Of these, 47 were also indicated to be significant by GENGEN. Similar results were obtained using the MSigDB C5 pathway collection. Many of the pathways found to be enriched by RS-SNP have a well-known connection to CD and often with inflammatory diseases. Conclusions The proposed method is a valuable alternative to other techniques for enrichment analysis of SNP sets. It is well founded from a theoretical and statistical perspective. Moreover, the experimental comparison with GENGEN highlights that it is

  4. Clinical phenotypes of asthma

    NARCIS (Netherlands)

    Bel, Elisabeth H.

    2004-01-01

    PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

  5. Association of PTPN22 (rs2476601) and STAT4 (rs7574865) polymorphisms with Rheumatoid Arthritis in the Western Algerian population.

    Science.gov (United States)

    Fodil, M; Benzaoui, A; Zemani-Fodil, F; Aberkane, M; Boughrara, W; Saidi-Mehtar, N; Petit-Teixeira, E; Boudjema, A

    2015-01-01

    The aim of the present study was to replicate the association of five risk gene polymorphisms (PTPN22-rs2476601, STAT4-rs7574865, 6q23-rs6927172, IRF5-rs2004640 and TRAF1/C5-rs10818488) with RA in a specific population of the Western Algeria. The study group comprised 110 patients with RA and 197 ethnically matched healthy control subjects. All polymorphisms were genotyped using predesigned TaqMan® assays. Allele and genotype frequencies in patients and control subjects were compared by chi-square test and odds ratios with 95% confidence intervals. Correction for multiple testing was carried out using the Bonferroni adjustment. Statistically significant associations with RA were detected. The strongest signal was obtained for PTPN22-rs2476601 with an allelic Pvalue 3.32 x 10(-11) (OR = 9.83, 95% CI [4.28 - 22.56]). A second significant association was obtained with STAT4-rs7574865 (allelic Pvalue = 4 x 10(-3); OR = 1.75, 95% CI [1.16 - 2.63]). The third SNP, 6q23-rs6927172, showed a significant result of association with RA, but missed our criteria for significance at allelic level after Bonferroni's correction (allelic Pvalue = 0.027; OR = 0.64, 95% CI [0.42 - 0.97]). Finally, IRF5-rs2004640 and TRAF1/C5-rs10818488 showed a significant association only at genotypic level (Pvalues: 3 x 10(-4) and 2.9 x 10(-3) respectively) but did not reach statistical significance when comparing allele frequencies (Pvalues: 0.96 and 0.21 respectively). From this initial study, we can conclude that PTPN22-rs2476601 and STAT4-rs7574865 polymorphisms are clearly associated with the risk of RA in the Western Algerian population.

  6. Association of PTPN22 (rs2476601 and STAT4 (rs7574865 polymorphisms with Rheumatoid Arthritis in the Western Algerian population

    Directory of Open Access Journals (Sweden)

    Mostefa FODIL

    2015-01-01

    Full Text Available Aim: The aim of the present study was to replicate the association of five risk gene polymorphisms (PTPN22-rs2476601, STAT4-rs7574865, 6q23-rs6927172, IRF5-rs2004640 and TRAF1/C5-rs10818488 with RA in a specific population of the Western Algeria. Material and methods: The study group comprised 110 patients with RA and 197 ethnically matched healthy control subjects. All polymorphisms were genotyped using predesigned TaqMan® assays. Allele and genotype frequencies in patients and control subjects were compared by chi-square test and odds ratios with 95% confidence intervals. Correction for multiple testing was carried out using the Bonferroni adjustment. Results: Statistically significant associations with RA were detected. The strongest signal was obtained for PTPN22-rs2476601 with an allelic Pvalue 3.32 x 10-11 (OR = 9.83, 95% CI [4.28 – 22.56]. A second significant association was obtained with STAT4-rs7574865 (allelic Pvalue = 4 x 10-3; OR = 1.75, 95% CI [1.16 – 2.63]. The third SNP, 6q23-rs6927172, showed a significant result of association with RA, but missed our criteria for significance at allelic level after Bonferroni’s correction (allelic Pvalue = 0.027; OR = 0.64, 95% CI [0.42 – 0.97]. Finally, IRF5-rs2004640 and TRAF1/C5-rs10818488 showed a significant association only at genotypic level (Pvalues: 3 x 10-4 and 2.9 x 10-3 respectively but did not reach statistical significance when comparing allele frequencies (Pvalues: 0.96 and 0.21 respectively. Conclusions: From this initial study, we can conclude that PTPN22-rs2476601 and STAT4-rs7574865 polymorphisms are clearly associated with the risk of RA in the Western Algerian population.

  7. Liver X Receptor Genes Variants Modulate ALS Phenotype.

    Science.gov (United States)

    Mouzat, Kevin; Molinari, Nicolas; Kantar, Jovana; Polge, Anne; Corcia, Philippe; Couratier, Philippe; Clavelou, Pierre; Juntas-Morales, Raul; Pageot, Nicolas; Lobaccaro, Jean -Marc A; Raoul, Cedric; Lumbroso, Serge; Camu, William

    2018-03-01

    Amyotrophic lateral sclerosis (ALS) is one of the most severe motor neuron (MN) disorders in adults. Phenotype of ALS patients is highly variable and may be influenced by modulators of energy metabolism. Recent works have implicated the liver X receptors α and β (LXRs), either in the propagation process of ALS or in the maintenance of MN survival. LXRs are nuclear receptors activated by oxysterols, modulating cholesterol levels, a suspected modulator of ALS severity. In a cohort of 438 ALS patients and 330 healthy controls, the influence of LXR genes on ALS risk and phenotype was studied using single nucleotide polymorphisms (SNPs). The two LXRα SNPs rs2279238 and rs7120118 were shown to be associated with age at onset in ALS patients. Consistently, homozygotes were twice more correlated than were heterozygotes to delayed onset. The onset was thus delayed by 3.9 years for rs2279238 C/T carriers and 7.8 years for T/T carriers. Similar results were obtained for rs7120118 (+2.1 years and +6.7 years for T/C and C/C genotypes, respectively). The LXRβ SNP rs2695121 was also shown to be associated with a 30% increase of ALS duration (p = 0.0055, FDR = 0.044). The tested genotypes were not associated with ALS risk. These findings add further evidence to the suspected implication of LXR genes in the disease process of ALS and might open new perspectives in ALS therapeutics.

  8. Configuration control plan for the ports NCS IBM RS/6000

    International Nuclear Information System (INIS)

    Brown, A.S.

    1996-01-01

    This document describes the actions and responsibilities for maintaining the quality and integrity of the NS software resident on the IBM RS/6000 workstation managed by the Nuclear Criticality Safety group at the Portsmouth Gaseous Diffusion Plant. This document does not address the validation of NS software packages for the RS/6000

  9. USB and RS232 voltage datalogger

    Directory of Open Access Journals (Sweden)

    Lorenzo Hernández Tabares

    2011-01-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 st1:*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} The design and construction of a PIC microcontroller based datalogger with USB 2.0 and RS232 interfaces is presented. The datalogger has one 0 to +10VDC analogue input, 10bits ADC, Real Time Clock, 4k sample room on the microcontroller’s program flash memory and an external DC power supply. This paper proposes a cheap variant to construct such device widely used in meteorological and environmental instrumentation among others. The prototype was attached to an Ultraviolet Photometric O3 Analyzer for recording the environmental (tropospheric ozone concentration in a control station at the Havana city. Key words: datalogger, USB, enviromental ozone

  10. Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells.

    Science.gov (United States)

    Eren, Erden; Tufekci, Kemal Ugur; Isci, Kamer Burak; Tastan, Bora; Genc, Kursad; Genc, Sermin

    2018-01-01

    Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes. SFN induced translocation of Nrf2 to the nucleus via extracellular signal-regulated kinase 1/2 (ERK1/2) pathway activation. siRNA-mediated knockdown study showed that the effects of SFN on LPS-induced reactive oxygen species, reactive nitrogen species, and pro-inflammatory cytokine production and cell death are partly Nrf2 dependent. Mox phenotype is a novel microglial phenotype that has roles in oxidative stress responses. Our results suggested that SFN induced the Mox phenotype in murine microglia through Nrf2 pathway. SFN also alleviated LPS-induced expression of inflammatory microRNA, miR-155. Finally, SFN inhibits microglia-mediated neurotoxicity as demonstrated by conditioned medium and co-culture experiments. In conclusion, SFN exerts protective effects on microglia and modulates the microglial activation state.

  11. SaeRS Is Responsive to Cellular Respiratory Status and Regulates Fermentative Biofilm Formation in Staphylococcus aureus.

    Science.gov (United States)

    Mashruwala, Ameya A; Gries, Casey M; Scherr, Tyler D; Kielian, Tammy; Boyd, Jeffrey M

    2017-08-01

    Biofilms are multicellular communities of microorganisms living as a quorum rather than as individual cells. The bacterial human pathogen Staphylococcus aureus uses oxygen as a terminal electron acceptor during respiration. Infected human tissues are hypoxic or anoxic. We recently reported that impaired respiration elicits a p rogrammed c ell l ysis (PCL) phenomenon in S. aureus leading to the release of cellular polymers that are utilized to form biofilms. PCL is dependent upon the AtlA murein hydrolase and is regulated, in part, by the SrrAB two-component regulatory system (TCRS). In the current study, we report that the SaeRS TCRS also governs fermentative biofilm formation by positively influencing AtlA activity. The SaeRS-modulated factor fibronectin-binding protein A (FnBPA) also contributed to the fermentative biofilm formation phenotype. SaeRS-dependent biofilm formation occurred in response to changes in cellular respiratory status. Genetic evidence presented suggests that a high cellular titer of phosphorylated SaeR is required for biofilm formation. Epistasis analyses found that SaeRS and SrrAB influence biofilm formation independently of one another. Analyses using a mouse model of orthopedic implant-associated biofilm formation found that both SaeRS and SrrAB govern host colonization. Of these two TCRSs, SrrAB was the dominant system driving biofilm formation in vivo We propose a model wherein impaired cellular respiration stimulates SaeRS via an as yet undefined signal molecule(s), resulting in increasing expression of AtlA and FnBPA and biofilm formation. Copyright © 2017 American Society for Microbiology.

  12. Dyslexia risk variant rs600753 is linked with dyslexia-specific differential allelic expression of DYX1C1

    Directory of Open Access Journals (Sweden)

    Bent Müller

    2018-02-01

    Full Text Available Abstract An increasing number of genetic variants involved in dyslexia development were discovered during the last years, yet little is known about the molecular functional mechanisms of these SNPs. In this study we investigated whether dyslexia candidate SNPs have a direct, disease-specific effect on local expression levels of the assumed target gene by using a differential allelic expression assay. In total, 12 SNPs previously associated with dyslexia and related phenotypes were suitable for analysis. Transcripts corresponding to four SNPs were sufficiently expressed in 28 cell lines originating from controls and a family affected by dyslexia. We observed a significant effect of rs600753 on expression levels of DYX1C1 in forward and reverse sequencing approaches. The expression level of the rs600753 risk allele was increased in the respective seven cell lines from members of the dyslexia family which might be due to a disturbed transcription factor binding sites. When considering our results in the context of neuroanatomical dyslexia-specific findings, we speculate that this mechanism may be part of the pathomechanisms underlying the dyslexia-specific brain phenotype. Our results suggest that allele-specific DYX1C1 expression levels depend on genetic variants of rs600753 and contribute to dyslexia. However, these results are preliminary and need replication.

  13. The STK33-linked SNP rs4929949 is associated with obesity and BMI in two independent cohorts of Swedish and Greek children.

    Directory of Open Access Journals (Sweden)

    Mathias Rask-Andersen

    Full Text Available Recent genome wide association studies (GWAS have identified a locus on chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33, to be associated with body mass. STK33, a relatively understudied protein, has been linked to KRAS mutation-driven cancers and explored as a potential antineoplastic drug target. The strongest association with body mass observed at this loci in GWAS was rs4929949, a single nucleotide polymorphism located within intron 1 of the gene encoding STK33. The functional implications of rs4929949 or related variants have not been explored as of yet. We have genotyped rs4929949 in two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross-sectional cohort of 2308 Greek school children. We found that the minor allele of rs4929949 was associated with obesity in the cohort of Swedish children and adolescents (OR = 1.199 (95%CI: 1.002-1.434, p = 0.047, and with body mass in the cross-sectional cohort of Greek children (β = 0.08147 (95% CI: 0.1345-0.1618, p = 0.021. We observe the effects of rs4929949 on body mass to be detectable already at adolescence. Subsequent analysis did not detect any association of rs4929949 to phenotypic measurements describing body adiposity or to metabolic factors such as insulin levels, triglycerides and insulin resistance (HOMA.

  14. The STK33-linked SNP rs4929949 is associated with obesity and BMI in two independent cohorts of Swedish and Greek children.

    Science.gov (United States)

    Rask-Andersen, Mathias; Moschonis, George; Chrousos, George P; Marcus, Claude; Dedoussis, George V; Fredriksson, Robert; Schiöth, Helgi B

    2013-01-01

    Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33), to be associated with body mass. STK33, a relatively understudied protein, has been linked to KRAS mutation-driven cancers and explored as a potential antineoplastic drug target. The strongest association with body mass observed at this loci in GWAS was rs4929949, a single nucleotide polymorphism located within intron 1 of the gene encoding STK33. The functional implications of rs4929949 or related variants have not been explored as of yet. We have genotyped rs4929949 in two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross-sectional cohort of 2308 Greek school children. We found that the minor allele of rs4929949 was associated with obesity in the cohort of Swedish children and adolescents (OR = 1.199 (95%CI: 1.002-1.434), p = 0.047), and with body mass in the cross-sectional cohort of Greek children (β = 0.08147 (95% CI: 0.1345-0.1618), p = 0.021). We observe the effects of rs4929949 on body mass to be detectable already at adolescence. Subsequent analysis did not detect any association of rs4929949 to phenotypic measurements describing body adiposity or to metabolic factors such as insulin levels, triglycerides and insulin resistance (HOMA).

  15. Association of 5-HT2C (rs3813929) and UCP3 (rs1800849) gene polymorphisms with type 2 diabetes in obese women candidates for bariatric surgery.

    Science.gov (United States)

    Schnor, Noa Pereira Prada; Verlengia, Rozangela; Novais, Patrícia Fátima Sousa; Crisp, Alex Harley; Leite, Celso Vieira de Souza; Rasera-Junior, Irineu; Oliveira, Maria Rita Marques de

    2017-01-01

    Obesity can cause systemic arterial hypertension (SAH) and type 2 diabetes mellitus (DM2) factor that is also influenced by genetic variability. The present study aims to investigate the association between gene polymorphisms related with obesity on the prevalence of SAH and DM2 in the preoperative period and 1 year after Roux-en-Y gastric bypass surgery. In total, 351 obese women in a Brazilian cohort completed the study. The clinical diagnosis of SAH and DM2 was monitored from medical records. Twelve gene polymorphisms (rs26802; rs572169; rs7799039; rs1137101; rs3813929; rs659366; rs660339; rs1800849; rs7498665; rs35874116; rs9701796; and rs9939609) were determined using real-time polymerase chain reaction and TaqMan assay. In the preoperative period, prevalence of SAH and DM2 was 57% and 22%, respectively. One year postoperatively, 86.8% subjects had remission of DM2 and 99.5% had control of SAH. Subjects with T allele from the serotonin receptor gene (5-HT2C, rs3813929) had five times greater chance of DM2, and the CC genotype from uncoupling protein 3 gene (UCP3, rs1800849) had three times greater chance in the preoperative period. These findings indicate that polymorphisms rs3813929 and rs1800849 from 5-HT2C and UCP3 genes were related to DM2 prevalence among the Brazilian obese women candidates for bariatric surgery.

  16. Association analysis of APOA5 rs662799 and rs3135506 polymorphisms with obesity in Moroccan patients.

    Science.gov (United States)

    Lakbakbi El Yaagoubi, F; Charoute, H; Bakhchane, A; Ajjemami, M; Benrahma, H; Errouagui, A; Kandil, M; Rouba, H; Barakat, A

    2015-12-01

    The aim of the present study is to explore the association between the APOA5 polymorphisms and haplotypes with obesity in Moroccan patients. The study was performed in 459 subjects, Obese (n=164) and non-obese (n=295). All subjects were genotyped for the APOA5 -1131T>C (rs662799) and c.56C>G (rs3135506) polymorphisms. The contribution of APOA5 polymorphisms and haplotypes in the increased risk of obesity were explored using logistic regression analyses. The -1131T>C and c.56C>G polymorphisms were significantly associated with obesity. Both polymorphisms were strongly associated with increased BMI. Analysis of constructed haplotypes showed a significant association between CG haplotype and susceptibility to obesity (OR [95%CI]=3.09 [1.93-4.97]; P<0.001). These results support a potential role for APOA5 common variants and related haplotypes as risk factors for obesity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk

    DEFF Research Database (Denmark)

    Campa, Daniele; Hüsing, Anika; McKay, James D.

    2010-01-01

    of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC). Methods we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs......7566605 as predictor of BMI and BC risk. Results and Conclusions In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age...... fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures...

  18. Correlation of Fetuin-A gene rs1071592 and rs2593813 single nucleotide polymorphisms with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Juan YI

    2016-10-01

    Full Text Available Objective  To investigate the relations of Fetuin-A gene rs1071592 and rs2593813 single nucleotide polymorphisms (SNPs with the affect ability to polycystic ovary syndrome (PCOS and its endocrine and metabolic characteristics in Chongqing Han population. Methods  A case-control study was performed in Chinese Han subjects. The clinical data of 156 cases of normal control and 147 cases of PCOS patients were collected, and their blood glucose, lipids, sex hormone and other biochemical indexes were determined, the SNPs of rs1071592 and rs2593813 were genotyped by TaqMan SNP Genotyping Assay. Hyperinsulinemic-euglycemic clamp was performed in 147 PCOS women and 20 controls. The relative risk of developing PCOS in women with rs1071592 genotype was assessed using a binary logistic regression analysis. Results  The distribution frequency of Fetuin-A gene homozygous rs1071592 AA genotype and A allele was significantly increased in PCOS patients than in controls (Pc0.05. Binary logistic regression analysis showed that the risk of developing PCOS was 4.93 times high in women with AA genotype of rs1071592 (OR=4.933, 95%CI 1.593-15.278, P0.05. Conclusion  People with SNPs variants of rs1071592 in Fetuin-A gene may have an increased genetic susceptibility to PCOS. However, there won't be significant relationship between SNP of rs2593813 at Fetuin-A gene and PCOS. DOI: 10.11855/j.issn.0577-7402.2016.09.07

  19. Insect nicotinic acetylcholine receptors (nAChRs): Important amino ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... nAChRs within the insect central nervous system has led to the development of insecticides targeting .... binding protein (AChBP), a homopentameric structural and functional homolog of ..... of the honey bee, Apis mellifera.

  20. Assessment of river plan changes in Terengganu River using RS ...

    African Journals Online (AJOL)

    Journal of Fundamental and Applied Sciences ... The database can help in the appropriate understanding of river plan change and know ... The data collected from Geographic Information System (GIS) and Remote Sensing (RS) database.

  1. SparkRS - Spark for Remote Sensing, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is Spark-RS, an open source software project that enables GPU-accelerated remote sensing workflows in an Apache Spark distributed computing...

  2. RS-485 Bus Design of a Missile Simulation Training System

    Directory of Open Access Journals (Sweden)

    Liu Fang

    2013-07-01

    Full Text Available In a missile simulation training system with one-master and multi-slaves distributed system structure, a universal controller is necessary due to the system composed with several controllers. In this research, the designed controllers communicate with each other and upper control computer through RS-485 field bus. RS-485 bus including interface circuits, transmission protocol, Cyclic Redundancy Check (CRC method and upper control test software is designed and proposed. The universal controller adopting the designed RS-485 interface circuits is connected through twisted-pair and makes the simulation system, then the controller is tested in line. The results show that the RS-485 bus communicates effectively using the protocol and CRC method, data transmission rates reaches 115.2 kbps, and has a good stability.

  3. Four therapeutic cases of RS3PE syndrome

    International Nuclear Information System (INIS)

    Nakajima, Naoya; Fukuda, Yukiko; Yang, Kwang-Seok; Aiba, Miyoji; Tsuda, Hiroshi

    2007-01-01

    RS3PE syndrome (Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome) is one of the disorders which present as polyarthritis. It is important to be aware of RS3PE syndrome when encountering elderly patients with polyarthritis who are negative for rheumatoid factor. We report 4 cases of RS3PE syndrome. All cases shared common clinical findings, such as acute onset, symmetrical polyarthritis, pitting edema of the hands and feet, and being negative for rheumatoid factor in serum. Treatment with corticosteroid was very effective in all cases. However, two patients showed a deteriorated clinical condition during the tapering of corticosteroid. Corticosteroid should be tapered off cautiously in patients with RS3PE syndrome. (author)

  4. Blending the most fundamental Remote-Sensing principles (RS ...

    African Journals Online (AJOL)

    Blending the most fundamental Remote-Sensing principles (RS) with the most functional spatial knowledge (GIS) with the objective of the determination of the accident-prone palms and points (case study: Tehran-Hamadan Highway on Saveh Superhighway)

  5. Parallel data grabbing card based on PCI bus RS422

    International Nuclear Information System (INIS)

    Zhang Zhenghui; Shen Ji; Wei Dongshan; Chen Ziyu

    2005-01-01

    This article briefly introduces the developments of the parallel data grabbing card based on RS422 and PCI bus. It could be applied for grabbing the 14 bits parallel data in high speed, coming from the devices with RS422 interface. The methods of data acquisition which bases on the PCI protocol, the functions and their usages of the chips employed, the ideas and principles of the hardware and software designing are presented. (authors)

  6. The 3Rs principle – mind the ethical gap!

    DEFF Research Database (Denmark)

    Olsson, I. Anna S.; Franco, Nuno H.; Weary, Daniel M.

    2012-01-01

    to believe that full implementation is merely a matter of time, and once the 3Rs are widely implemented, the public will fully support any continued laboratory animal use that is deemed necessary. In this paper, we argue that these conclusions are unlikely to be correct, in part because the 3Rs are rich...... effects of repeated exposure to harmful procedures). We conclude that there is now a need for a more thorough ethical discussion on how to resolve these issues....

  7. Multirate Filter Bank Representations of RS and BCH Codes

    Directory of Open Access Journals (Sweden)

    Van Meerbergen Geert

    2008-01-01

    Full Text Available Abstract This paper addresses the use of multirate filter banks in the context of error-correction coding. An in-depth study of these filter banks is presented, motivated by earlier results and applications based on the filter bank representation of Reed-Solomon (RS codes, such as Soft-In Soft-Out RS-decoding or RS-OFDM. The specific structure of the filter banks (critical subsampling is an important aspect in these applications. The goal of the paper is twofold. First, the filter bank representation of RS codes is now explained based on polynomial descriptions. This approach allows us to gain new insight in the correspondence between RS codes and filter banks. More specifically, it allows us to show that the inherent periodically time-varying character of a critically subsampled filter bank matches remarkably well with the cyclic properties of RS codes. Secondly, an extension of these techniques toward the more general class of BCH codes is presented. It is demonstrated that a BCH code can be decomposed into a sum of critically subsampled filter banks.

  8. Multirate Filter Bank Representations of RS and BCH Codes

    Directory of Open Access Journals (Sweden)

    Marc Moonen

    2009-01-01

    Full Text Available This paper addresses the use of multirate filter banks in the context of error-correction coding. An in-depth study of these filter banks is presented, motivated by earlier results and applications based on the filter bank representation of Reed-Solomon (RS codes, such as Soft-In Soft-Out RS-decoding or RS-OFDM. The specific structure of the filter banks (critical subsampling is an important aspect in these applications. The goal of the paper is twofold. First, the filter bank representation of RS codes is now explained based on polynomial descriptions. This approach allows us to gain new insight in the correspondence between RS codes and filter banks. More specifically, it allows us to show that the inherent periodically time-varying character of a critically subsampled filter bank matches remarkably well with the cyclic properties of RS codes. Secondly, an extension of these techniques toward the more general class of BCH codes is presented. It is demonstrated that a BCH code can be decomposed into a sum of critically subsampled filter banks.

  9. The optimal algorithm for Multi-source RS image fusion.

    Science.gov (United States)

    Fu, Wei; Huang, Shui-Guang; Li, Zeng-Shun; Shen, Hao; Li, Jun-Shuai; Wang, Peng-Yuan

    2016-01-01

    In order to solve the issue which the fusion rules cannot be self-adaptively adjusted by using available fusion methods according to the subsequent processing requirements of Remote Sensing (RS) image, this paper puts forward GSDA (genetic-iterative self-organizing data analysis algorithm) by integrating the merit of genetic arithmetic together with the advantage of iterative self-organizing data analysis algorithm for multi-source RS image fusion. The proposed algorithm considers the wavelet transform of the translation invariance as the model operator, also regards the contrast pyramid conversion as the observed operator. The algorithm then designs the objective function by taking use of the weighted sum of evaluation indices, and optimizes the objective function by employing GSDA so as to get a higher resolution of RS image. As discussed above, the bullet points of the text are summarized as follows.•The contribution proposes the iterative self-organizing data analysis algorithm for multi-source RS image fusion.•This article presents GSDA algorithm for the self-adaptively adjustment of the fusion rules.•This text comes up with the model operator and the observed operator as the fusion scheme of RS image based on GSDA. The proposed algorithm opens up a novel algorithmic pathway for multi-source RS image fusion by means of GSDA.

  10. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation

    DEFF Research Database (Denmark)

    Andreasen, Camilla H; Stender-Petersen, Kirstine L; Mogensen, Mette S

    2008-01-01

    (-16)). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive...... homozygous risk A-allele carriers had a 1.95 +/- 0.3 kg/m(2) increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS: We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical......OBJECTIVE: Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes...

  11. The OSR1 rs12329305 polymorphism contributes to the development of congenital malformations in cases of stillborn/neonatal death.

    Science.gov (United States)

    Lozić, Bernarda; Krželj, Vjekoslav; Kuzmić-Prusac, Ivana; Kuzmanić-Šamija, Radenka; Čapkun, Vesna; Lasan, Ružica; Zemunik, Tatijana

    2014-08-28

    Involvement of development-related gene polymorphisms in multifactorial/polygenic etiology of stillborn/neonatal deaths due to malformations has been insufficiently tested. Since these genes showed evolutional stability and their mutations are very rare, we can assume that their polymorphic variants may be a risk factor associated with the occurrence of developmental disorders of unknown etiology or can enhance the phenotypic variability of known genetic disorders. To determine the association of 3 polymorphisms involved in the regulation of the early embryonic development of different organs, we conducted an association study of their relation to the particular malformation. We selected 140 samples of archived paraffin tissue samples from deceased patients in which fetal/neonatal autopsy examination had shown congenital abnormalities as the most likely cause of death. The polymorphisms of OSR1 rs12329305, rs9936833 near FOXF1, and HOXA1 rs10951154 were genotyped using the TaqMan allelic discrimination assay. After Bonferroni correction for multiple testing, significant allelic association with stillborn/neonatal deaths was observed for rs12329305 (p=7×10-4). In addition, association analysis for the same polymorphism was shown in the subgroup with isolated anomalies (1.25×10^-5), particularly in the subgroup of cases with kidney and heart anomalies (p=4.18×10^-5, p=5.12×10^-8, respectively). The findings of the present study showed, for the first time, the role of the OSR1 rs12329305 polymorphism in the development of congenital malformations in cases of stillborn/neonatal death, particularly in those with congenital kidney and heart developmental defects.

  12. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  13. Phenotypic Resistance to Antibiotics

    Directory of Open Access Journals (Sweden)

    Jose L. Martinez

    2013-04-01

    Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  14. RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions.

    Science.gov (United States)

    Chandna, Andrew R; Nair, Manoj; Chang, Christine; Pennington, Paul R; Yamamoto, Yasuhiko; Mousseau, Darrell D; Campanucci, Verónica A

    2015-02-01

    Autonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities and premature death. It was recently proposed that autonomic dysfunction is triggered by oxidation-mediated inactivation of neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia and resulting in autonomic failure. We investigated whether the receptor for advanced glycation end products (RAGE) and its role in the generation of reactive oxygen species (ROS) could be contributing to the events that initiate sympathetic malfunction under high glucose conditions. Using biochemical, live imaging and electrophysiological tools we demonstrated that exposure of sympathetic neurons to high glucose increases RAGE expression and oxidative markers, and that incubation with RAGE ligands (e.g. AGEs, S100 and HMGB1) mimics both ROS elevation and nAChR inactivation. In contrast, co-treatment with either antioxidants or an anti-RAGE IgG prevented the inactivation of nAChRs. Lastly, a role for RAGE in this context was corroborated by the lack of sensitivity of sympathetic neurons from RAGE knock-out mice to high glucose. These data define a pivotal role for RAGE in initiating the events associated with exposure of sympathetic neurons to high glucose, and strongly support RAGE signaling as a potential therapeutic target in the autonomic complications associated with diabetes. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    International Nuclear Information System (INIS)

    Hoobakht, Fatemeh; Ganji, Fariba; Vasheghani-Farahani, Ebrahim; Mousavi, Seyyed Mohammad

    2013-01-01

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 °C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1–4 and 20 % of loaded PB released from the nanocarriers within 100 h

  16. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    Energy Technology Data Exchange (ETDEWEB)

    Hoobakht, Fatemeh; Ganji, Fariba, E-mail: fganji@modares.ac.ir; Vasheghani-Farahani, Ebrahim [Tarbiat Modares University, Biomedical Engineering Group, Chemical Engineering Department (Iran, Islamic Republic of); Mousavi, Seyyed Mohammad [Tarbiat Modares University, Biotechnology Group, Chemical Engineering Department (Iran, Islamic Republic of)

    2013-09-15

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 Degree-Sign C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1-4 and 20 % of loaded PB released from the nanocarriers within 100 h.

  17. Poor maternal nutrition leads to alterations in oxidative stress, antioxidant defense capacity, and markers of fibrosis in rat islets: potential underlying mechanisms for development of the diabetic phenotype in later life.

    Science.gov (United States)

    Tarry-Adkins, Jane L; Chen, Jian-Hua; Jones, Richard H; Smith, Noel H; Ozanne, Susan E

    2010-08-01

    Low birth weight is associated with glucose intolerance, insulin resistance, and type 2 diabetes (T2D) in later life. Good evidence indicates that the environment plays an important role in this relationship. However, the mechanisms underlying these relationships are defined poorly. Islets are particularly susceptible to oxidative stress, and this condition combined with fibrosis is thought to be instrumental in T2D pathogenesis. Here we use our maternal low-protein (LP) rat model to determine the effect of early diet on oxidative stress and fibrosis in pancreatic islets of male offspring at 3 and 15 mo of age. Islet xanthine oxidase (XO) expression was increased in 15-mo LP offspring, which suggests increased oxidative-stress. Manganese superoxide-dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), and heme oxygenase-1 (HO-1) (antioxidant enzymes) were reduced significantly in LP offspring, which indicated impairment of oxidative defense. Expression of fibrosis markers collagen I and collagen III also increased in 15-mo LP offspring. Angiotensin II receptor type I (AT(II)R(1)), induced by hyperglycemia and oxidative-stress, was significantly up-regulated in 15-mo LP offspring. Lipid peroxidation was also increased in 15-mo LP animals. We conclude that maternal protein restriction causes age-associated increased oxidative stress, impairment of oxidative defense, and fibrosis. These findings provide mechanisms by which suboptimal early nutrition can lead to T2D development later in life.

  18. Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring

    Institute of Scientific and Technical Information of China (English)

    Yao-hua KE; Chun WANG; Yun-qiu HU; Miao LI; Yu-juan LIU; Wen-zhen FU; Zhen-lin ZHANG; Wen-jin XIAO; Jin-wei HE; Hao ZHANG; Jin-bo YU; Wei-wei HU; Jie-mei GU; Gao GAO; Hua YUE

    2012-01-01

    Aim:Genetic variation in ALOX12,which encoded human 12-lipoxygenase,was found to be associated with fat mass in young Chinese men.The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese nuclear families with male offspring.Methods:We recruited 1,296 subjects from 427 nuclear families with male offspring and genotyped five SNPs (rs9894225,rs748694,rs2619112,rs2619118,and rs916055) in the ALOX15 gene locus.The total fat mass (TFM),trunk fat mass (tFM),leg fat mass (LFM) and arm fat mass (AFM) were measured using dual-energy X-ray absorptiometry (DXA).The percentage of fat mass (PFM) was the ratio of TFM and body weight.The association between SNPs and haplotypes of ALOX15 and obesity-related phenotypic variation was measured using quantitative transmission disequilibrium test (QTDT).Results:Using QTDT to measure family-based genetic association,we found that rs916055 had a statistically significant association with PFM (P=0.038),whereas rs916055 had a marginal but statistically insignificant association with tFM (P=0.093).The multipleparameter 1000 permutations test agreed with the family-based association results:both showed that rs916055 had a statistically significant association with PFM (P=0.033).Conclusion:rs916055 in ALOX15 gene was significantly associated with the percentage of fat mass in Chinese nuclear families with male offspring in the family-based association study using QTDT approach.

  19. HLA variants rs9271366 and rs9275328 are associated with systemic lupus erythematosus susceptibility in Malays and Chinese.

    Science.gov (United States)

    Chai, H C; Phipps, M E; Othman, I; Tan, L P; Chua, K H

    2013-02-01

    Human leukocyte antigen (HLA) antigens and genes have long been reported associated with systemic lupus erythematosus (SLE) susceptibility in many populations. With the advance in technologies such as genome-wide association studies, many newly discovered SLE-associated single-nucleotide polymorphisms (SNPs) have been reported in recent years. These include HLA-DRB1/HLA-DQA1 rs9271366 and HLA-DQB1/HLA-DQA2 rs9275328. Our aim was to investigate these SNPs in a Malaysian SLE cohort. SNPs rs9271366 and rs9275328 were screened across 790 Malaysian citizens from three ethnic groups (360 patients and 430 healthy volunteers) by Taqman SNP genotyping assays. Allele and genotyping frequencies, Hardy-Weinberg equilibrium, Fisher's exact test and odds ratio were calculated for each SNP and ethnic group. Linkage disequilibrium and interaction between the two SNPs were also evaluated. The minor allele G and its homozygous genotype GG of HLA-DRB1/HLA-DQA1 rs9271366 significantly increased the SLE susceptibility in Malaysian patients, including those of Malay and Chinese ethnicity (odds ratio (OR) > 1, p < 0.05). As for HLA-DQB1/HLA-DQA2 rs9275328, the minor allele T and the heterozygous genotype CT conferred protective effect to SLE in Malaysians, as well as in Malays and Chinese, by having OR < 1 and p value <0.05. Both SNPs did not show associations to SLE in Indians. D' and r (2) values for the two SNPs in LD analysis were 0.941 and 0.065, respectively, with haplotype GC and AT being significantly associated with SLE (p < 5.0 × 10(-4)) after 10,000 permutations were performed. The MDR test clustered the genotype combinations of GG and CC, and AG and CC of rs9271366 and rs9275328, accordingly, as high-risk group, and the two SNPs interacted redundantly by removing 1.96% of the entropy. Our findings suggest that in addition to some classical HLA variants, rs9271366 and rs9275328 are additional polymorphisms worth considering in the Malaysian and possibly in

  20. Evaluation of transcobalamin II rs1801198 and transcobalamin II receptor rs2336573 gene polymorphisms in recurrent spontaneous abortion.

    Science.gov (United States)

    Hashemi, Mohammad; Mokhtari, Mojgan; Yazdani-Shahrbabaki, Vajiheh; Danesh, Hiva; Bizhani, Fatemeh; Taheri, Mohsen

    2018-03-14

    It has been proposed that transcobalamin 2 (TCN2) and the transcobalamin 2 receptor (TCN2R) are associated with idiopathic recurrent spontaneous abortion (RSA). The aim of the present study was to investigate the impact of TCN2 rs1801198 and TCN2R rs2336573 polymorphism on RSA in a sample of Iranian population. This case-control study was done on 92 RSA patients and 93 normal, fertile women. Genotyping of the TCN2 rs1801198 and TCN2R rs2336573 variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The findings showed no significant association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk/protection of RSA. Our results did not support an association between the TCN2 polymorphism and the risk of RSA in a sample of southeast Iranian population. Larger studies with different ethnicities are needed to evaluate the possible impact of TCN2 and TCN2R polymorphisms on the pathogenesis of RSA. Impact statement What is already known on this subject? Recurrent spontaneous abortion (RSA), a multifactorial condition, is one of the most common complications of pregnancy. It has been proposed that genetic polymorphisms play a role in the pathogenesis of RSA. Few studies have examined the association between TNC2 and TCN2R polymorphisms and the RSA risk and the findings were inconsistent. The aim of the current study was to determine the possible association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the RSA in a sample of the southeast Iranian population. What do the results of the study add? The findings of the present case-control study did not support an association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk of RSA in a sample of the Iranian population. What are the implications of these findings for clinical practice and future research? The findings of this study may provide a basis for future studies with larger sample sizes and different ethnicities

  1. Association of PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with rheumatoid arthritis: A meta-analysis update.

    Science.gov (United States)

    Elshazli, Rami; Settin, Ahmad

    2015-08-01

    Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The genes encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) and signal transducer and activator of transcription 4 (STAT4) have been reported to be associated with RA in several ethnic populations. This work aims to assess the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility through an updated meta-analysis of available case-control studies. A literature search of all relevant studies published from January 2007 up to December 2014 was conducted using Pubmed and Science Direct databases. The observed studies that were related to an association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility were identified. Meta-analysis of the pooled and stratified data was done and assessed using varied genetic models. Thirty-seven case-control studies with a total of 47 comparisons (29 for PTPN22 rs2476601 polymorphism and 18 for STAT4 rs7574865 polymorphism) met our inclusion criteria. The meta-analysis showed an association between PTPN22 T allele, CT+TT and TT genotypes with RA susceptibility. Furthermore, The meta-analysis showed an association between STAT4 T allele, GT+TT and TT genotypes with RA susceptibility. Stratification of RA patients according to ethnic groups showed that PTPN22 T allele, CT+TT genotypes, STAT4 T allele and STAT4 GT+TT were significantly associated with RA in European, Asian, African subjects, while PTPN22 TT genotype was significantly associated with RA in European but not in Asian and African subjects and STAT4 TT genotype was significantly associated with RA in European and Asian but not in African subject. A subgroup analysis according to the presence or absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility

  2. Association between rs6812193 polymorphism and sporadic Parkinson's disease susceptibility.

    Science.gov (United States)

    Huo, Qiang; Li, Tao; Zhao, Peiqing; Wang, Lianqing

    2015-08-01

    Recently, the association of a single nucleotide polymorphism rs6812193 C/T with sporadic Parkinson's disease (PD) susceptibility has been widely evaluated, but the results remained inconsistent. This association should be clarified because of the importance of it on human health and quality of life. We performed a comprehensive meta-analysis to evaluate the association between the rs6812193 polymorphism and sporadic PD. PubMed was used to retrieve articles published up to June 2014 for all studies evaluating the rs6812193 polymorphism and PD in humans. Ethnicity-specific subgroup analysis was also performed based on ethnicity susceptibility. A total of 17 independent study samples (15 Caucasians and 2 Asians) including 17,956 cases and 52,751 controls were used in the presented study. The MAFT (minor allele T frequency) in PD patients of European descent is obviously higher than Asian cases (p susceptibility among overall samples (OR 0.882, 95 % CI 0.856-0.908) and Caucasian population (OR 0.881, 95 % CI 0.856-0.907), but not in Asian samples (OR 0.918, 95 % CI 0.721-1.168). No evidence of publication bias was observed. Throughout our analysis, the rs6812193 polymorphism is significantly associated with sporadic PD susceptibility in Caucasian samples, and ethnicity might be the key point of inconsistency in rs6812193 studies. Further studies are warranted to re-examine the observed associations, especially in different ethnicities.

  3. The Acinetobacter baumannii Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner

    Directory of Open Access Journals (Sweden)

    Grace E. Richmond

    2016-04-01

    Full Text Available The opportunistic pathogen Acinetobacter baumannii is able to persist in the environment and is often multidrug resistant (MDR, causing difficulties in the treatment of infections. Here, we show that the two-component system AdeRS, which regulates the production of the AdeABC multidrug resistance efflux pump, is required for the formation of a protective biofilm in an ex vivo porcine mucosal model, which mimics a natural infection of the human epithelium. Interestingly, deletion of adeB impacted only on the ability of strain AYE to form a biofilm on plastic and only on the virulence of strain Singapore 1 for Galleria mellonella. RNA-Seq revealed that loss of AdeRS or AdeB significantly altered the transcriptional landscape, resulting in the changed expression of many genes, notably those associated with antimicrobial resistance and virulence interactions. For example, A. baumannii lacking AdeRS displayed decreased expression of adeABC, pil genes, com genes, and a pgaC-like gene, whereas loss of AdeB resulted in increased expression of pil and com genes and decreased expression of ferric acinetobactin transport system genes. These data define the scope of AdeRS-mediated regulation, show that changes in the production of AdeABC mediate important phenotypes controlled by AdeRS, and suggest that AdeABC is a viable target for antimicrobial drug and antibiofilm discovery.

  4. Rs9939609 Variant of the Fat Mass and Obesity-Associated Gene and Trunk Obesity in Adolescents

    Science.gov (United States)

    Mangge, Harald; Renner, Wilfried; Almer, Gunter; Weghuber, Daniel; Möller, Reinhard; Horejsi, Renate

    2011-01-01

    A common T/A polymorphism (rs9939609) in the fat mass and obesity associated (FTO) gene was found associated with early-onset and severe obesity in both adults and children. However, recent observations failed to find associations of FTO with obesity. To investigate the genetic background of early obesity, we analysed the single nucleotide polymorphism (SNP) rs9939609 of FTO in 371 styrian adolescents towards degree of obesity, subcutaneous adipose tissue (SAT)-distribution determined by lipometry, early metabolic and preatherosclerotic symptoms. The percentage of AA homozygotes for the rs9939609 SNP of FTO was significantly increased in the obese adolescents. Compared to the TT wildtype, AA homozygotes showed significantly elevated values of SAT thickness at the trunk-located lipometer measure points neck and frontal chest, body weight, body mass index, waist, and hip circumference. No associations were found with carotis communis intima media thickness, systolic, diastolic blood pressure, ultrasensitive C-reactive protein (US-CRP), homocystein, total cholesterol, triglycerides, HDL cholesterol, oxidized LDL, fasted glucose, insulin, HOMA-index, liver transaminases, uric acid, and adipokines like resistin, leptin, and adiponectin. Taken together, to the best of our knowledge we are the first to report that the rs9939609 FTO SNP is associated with trunk weighted obesity as early as in adolescence. PMID:21318054

  5. Rs9939609 Variant of the Fat Mass and Obesity-Associated Gene and Trunk Obesity in Adolescents

    Directory of Open Access Journals (Sweden)

    Harald Mangge

    2011-01-01

    Full Text Available A common T/A polymorphism (rs9939609 in the fat mass and obesity associated (FTO gene was found associated with early-onset and severe obesity in both adults and children. However, recent observations failed to find associations of FTO with obesity. To investigate the genetic background of early obesity, we analysed the single nucleotide polymorphism (SNP rs9939609 of FTO in 371 styrian adolescents towards degree of obesity, subcutaneous adipose tissue (SAT-distribution determined by lipometry, early metabolic and preatherosclerotic symptoms. The percentage of AA homozygotes for the rs9939609 SNP of FTO was significantly increased in the obese adolescents. Compared to the TT wildtype, AA homozygotes showed significantly elevated values of SAT thickness at the trunk-located lipometer measure points neck and frontal chest, body weight, body mass index, waist, and hip circumference. No associations were found with carotis communis intima media thickness, systolic, diastolic blood pressure, ultrasensitive C-reactive protein (US-CRP, homocystein, total cholesterol, triglycerides, HDL cholesterol, oxidized LDL, fasted glucose, insulin, HOMA-index, liver transaminases, uric acid, and adipokines like resistin, leptin, and adiponectin. Taken together, to the best of our knowledge we are the first to report that the rs9939609 FTO SNP is associated with trunk weighted obesity as early as in adolescence.

  6. Codificador RS(n,k basado en LFCS: caso de estudio RS(7,3

    Directory of Open Access Journals (Sweden)

    Cecilia Sandoval-Ruiz

    2012-01-01

    Full Text Available El presente artículo presenta el diseño de un codi® cador Reed Solomon basado en un circuito concurrente, LFCS - Linear Feedback Concurrent Structure- que permite la generación de los símbolos de redundancia del código de forma paralela, siempre que se le suministren los k símbolos de información a codificar de forma simultánea, el codifi cador ofrece a su salida los símbolos de redundancia correspondientes. Para lograr este desarrollo se generalizó el modelo matemáticos para la descripción del comportamiento del codificador, se realizó la configuración en lenguaje descriptor de hardware VHDL de un codificador Reed Solomon, tomando como caso de estudio el RS(7,3, se simuló el diseño propuesto validando así su funcionamiento, para finalmente realizar la comparación de la implementación del codifi cador entre la versión secuencial y la versión basada en LFCS, obteniendo una reducción de componentes hardware y optimizando la velocidad de respuesta y consumo de potencia. Concluyendo, que el diseño del codi® cador propuesto valida el modelo concurrente generalizado a partir de la correspondencia con la arquitectura del LFCS.

  7. Enhancement and feature extraction of RS images from seismic area and seismic disaster recognition technologies

    Science.gov (United States)

    Zhang, Jingfa; Qin, Qiming

    2003-09-01

    Many types of feature extracting of RS image are analyzed, and the work procedure of pattern recognizing in RS images of seismic disaster is proposed. The aerial RS image of Tangshan Great Earthquake is processed, and the digital features of various typical seismic disaster on the RS image is calculated.

  8. RS-Predictor models augmented with SMARTCyp reactivities

    DEFF Research Database (Denmark)

    Zaretzki, Jed; Rydberg, Patrik; Bergeron, Charles

    2012-01-01

    (82.3%) and merged(86.0%). Comprehensive datamining of each substrate set and careful statistical analyses of the predictions made by the different models revealed new insights into molecular features that control metabolic regioselectivity and enable accurate prospective prediction of likely SOMs.......RS-Predictor is a tool for creating pathway-independent, isozyme-specific site of metabolism (SOM) prediction models using any set of known cytochrome P450 substrates and metabolites. Until now, the RS-Predictor method was only trained and validated on CYP 3A4 data, but in the present study we...... report on the versatility the RS-Predictor modeling paradigm by creating and testing regioselectivity models for substrates of the nine most important CYP isozymes. Through curation of source literature, we have assembled 680 substrates distributed among CYPs 1A2, 2A6, 2B6, 2C19, 2C8, 2C9, 2D6, 2E1 and 3...

  9. Polymorphisms rs12998 and rs5780218 in KiSS1 Suppressor Metastasis Gene in Mexican Patients with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Edhit Guadalupe Cruz Quevedo

    2015-01-01

    Full Text Available Aims. KiSS1 is a metastasis suppressor gene associated with inhibition of cellular chemotaxis and invasion attenuating the metastasis in melanoma and breast cancer cell lines. Along the KiSS-1 gene at least 294 SNPs have been described; however the association of these polymorphisms as genetic markers for metastasis in breast cancer studies has not been investigated. Here we describe two simple PCR-RFLPs protocols to identify the rs5780218 (9DelT and the rs12998 (E20K KiSS1 polymorphisms and the allelic, genotypic, and haplotypic frequencies in Mexican general population (GP and patients with benign breast disease (BBD or breast cancer (BC. Results. The rs5780218 polymorphism was individually associated with breast cancer (P=0.0332 and the rs12998 polymorphism shows statistically significant differences when GP versus case (BC and BBD groups were compared (P<0.0001. The H1 Haplotype (G/- occurred more frequently in BC group (0.4256 whereas H2 haplotype (G/T was the most prevalent in BBD group (0.4674. Conclusions. Our data indicated that the rs5780218 polymorphism individually confers susceptibility for development of breast cancer in Mexican population and a possible role as a genetic marker in breast cancer metastasis for H1 haplotype (Wt/variant in KiSS1 gene must be analyzed in other populations.

  10. The rs7517847 polymorphism in the IL-23R gene is associated with gout in a Chinese Han male population.

    Science.gov (United States)

    Liu, Shiguo; He, Hongmei; Yu, Renchao; Han, Lin; Wang, Can; Cui, Ying; Li, Changgui

    2015-05-01

    Gout is a polygenic auto-inflammatory disease, in which inflammation plays an important role in disease pathogenesis. The cytokine interleukin (IL)-23 promotes inflammation and helps to guide inflammatory cells, while studies have shown that the IL-23R gene is associated with susceptibility to several immune-related diseases. This study aimed to determine whether the IL-23R rs7517847 (G/T) polymorphism is associated with gout in a Chinese Han male population. We recruited 400 patients with gout and 582 gout-free controls. After obtaining blood samples for DNA extraction, genotyping of the rs7517847 polymorphism was performed by fluorescence-based quantitative PCR using TaqMan probes. An association analysis was carried out using the χ(2) test. A genotype-phenotype analysis was also conducted. Both genotypic and allelic frequencies of rs7517847 differed significantly between gout patients and controls (χ(2) = 6.792, df = 2, P = 0.034 by genotype; χ(2) = 4.202, df = 1, P = 0.04 by allele). IL-23R may be associated with gout in a Chinese Han male population, although our findings should be confirmed using larger sample sizes and other independent populations.

  11. Resiliency Scale (RS): Scale Development, Reliability and Validity Study

    OpenAIRE

    GÜRGAN, Uğur

    2003-01-01

    The purpose of this study was to develop a new Resiliency Scale (RS) for Turkish samples. Various items from some major resiliency scales, most of them with some partial change, were collected and a pool of 228 items containing almost all possible resilience areas were obtained. This item-pool was administered to a college sample of 419. Resulting of analysis 50 item RS were obtained and administered to a new college sample of 112 participants. This second sample has also received the Rosenba...

  12. Crosstalk XVI, basic data communication and RS-232C

    International Nuclear Information System (INIS)

    Hwang, Hui Yung

    1988-10-01

    This book is divided into three parts, which deals with compatible software of data communication with IBM PC XT/AT. The first part consists of an introduction to crosstalk XVI, getting start for user, crosstalk practice, call with crosstalk, terminal feature, switch of communication parameter, terminal emulation, capturing data, transmission of text file answer mode, file transfer, command file and script file, command summary and examples. The second part deals with basic personal computer communication, RS-232C and explanation of communication control : RS-232C interface, transmission device and interrupt controller 8259.

  13. THE HISTORY OF LABORATORY ANIMALS AND THE 3RS

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen

    This talk will give an introduction to the history of the use of laboratory animals with focus on the history of the three Rs (3Rs). We will see how animal experimentation has been performed early in our civilization, and how the suffering of animals has been justified. This will include Rene...... Descartes´s mechanical view of animals in the seventeenth century, and Charles Darwin's ambivalent relationship to animal experimentation, which he views as cruel but necessary. In the 1870s the Danish Foundation for Protection of Animals (“Dyrenes Beskyttelse”) and Professor Peter Panum discussed the use...

  14. Validation of Omron RS8, RS6, and RS3 home blood pressure monitoring devices, in accordance with the European Society of Hypertension International Protocol revision 2010.

    Science.gov (United States)

    Takahashi, Hakuo; Yoshika, Masamichi; Yokoi, Toyohiko

    2013-01-01

    Allowing patients to measure their blood pressure at home is recognized as being of clinical value. However, it is not known how often these measurements are taken correctly. Blood pressure monitors for home use fall into two types based on the position of the cuff, ie, at the upper arm or the wrist. The latter is particularly convenient, as measurements can be taken fully clothed. This study aimed to evaluate the performance of the wrist-type blood pressure monitors Omron RS8 (HEM-6310F-E), Omron RS6 (HEM-6221-E), and Omron RS3 (HEM-6130-E). A team of three trained doctors validated the performance of these devices by comparing the measurements obtained from these devices with those taken using a standard mercury sphygmomanometer. All the devices met the validation requirements of the European Society of Hypertension International Protocol revision 2010. The difference in blood pressure readings between the tested device and the standard mercury sphygmomanometer was within 3 mmHg, which is acceptable according to the European Society of Hypertension guidelines. All the home devices tested were found to be suitable for measuring blood pressure at home because their performance fulfilled the requirement of the guidelines.

  15. The Two-Component System CprRS Senses Cationic Peptides and Triggers Adaptive Resistance in Pseudomonas aeruginosa Independently of ParRS

    DEFF Research Database (Denmark)

    Fernandez, Luca; Jenssen, Håvard; Bains, Manjeet

    2012-01-01

    dependency on the CprRS and ParRS systems in a concentration-dependent manner. It was further demonstrated that, following exposure to inducing antimicrobial peptides, cprRS mutants did not become adaptively resistant to polymyxins as was observed for wild-type cells. Our microarray studies demonstrated...

  16. Association of the matrix metalloproteinase-3 polymorphisms rs679620 and rs3025058 with ischemic stroke risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhang Q

    2018-01-01

    Full Text Available Qi-Wei Zhang Department of Neurosurgery, The Affiliated Hospital of Jilin Medical University, Jilin, People’s Republic of China Purpose: The relationship of the matrix metalloproteinase-3 (MMP-3 polymorphisms rs679620 and rs3025058 with ischemic stroke has received much attention. The aim of the present study was to perform a meta-analysis of published case–control studies to evaluate the cumulative evidence.Methods: We performed a search of ISI Web of Science, Embase, PubMed, and China National Knowledge Infrastructure databases. Pooled odds ratios (ORs were appropriately derived from fixed-effects or random-effects models.Results: We identified seven eligible studies including 5,204 subjects. The pooled analysis showed that the MMP-3 rs679620 A allele carriers had increased risk of ischemic stroke compared with homozygotes for the G allele in Asians (AA + GA vs GG: OR =1.42, 95% CI: 1.05–1.91, P=0.022. Concerning the rs3025058 polymorphism, the results did not suggest an association between rs3025058 genotypes and ischemic stroke risk (5A5A + 6A5A vs 6A6A: OR =1.04, 95% CI: 0.73–1.47, P=0.844; 5A5A vs 6A5A + 6A6A: OR =1.14, 95% CI: 0.74–1.77, P=0.556; and 5A5A vs 6A6A: OR =1.11, 95% CI: 0.68–1.80, P=0.677. In subgroup analysis by ethnicity, no statistically significant associations were demonstrated for rs3025058 in Asians and Caucasians, respectively. There was no evidence for publication bias.Conclusion: Our findings indicate that the rs679620 A allele carriers have increased risk of ischemic stroke in Asians, but there is no association between rs3025058 and ischemic stroke risk. Keywords: ischemic stroke, meta-analysis, MMP-3, polymorphism

  17. RS485 optical router for HIRFL-CSR

    International Nuclear Information System (INIS)

    Zhang Shuocheng; Wang Dan; Jing Lan; Qiao Weimin

    2007-01-01

    A communication equipment-RS485 optical router has been developed to satisfy requirements of control system communication network of HIRFL-CSR (Heavy Ion Research Facility at Lanzhou-Cooling Storage Ring). The equipment is compatible with multiple communication protocols, such as Ethernet, RS232 and RS485 standard. It can be used to setup the RS485 communication network quickly and connected to the Ethernet easily. The fiber optical interface is introduced to facilitate the connection with the network of industrial Fiber Optics Communication (FOC), which expands the application field of the equipment in a large extent. This paper introduces the details of the equipment, including the design of the circuit and software, features of the equipment and how it works in the whole control system network. Its application in the HIRFL-CSR control system shows that the equipment is in accordance with the general requirement of automatic control communication system. It could also be used in other industrial automatic control fields. (authors)

  18. CAT bags orders worth Rs 90 Crore from EU

    CERN Multimedia

    2002-01-01

    "Orders to the tune of Rs 90 crore have been received by Indore-based Centre for Advanced Technology (CAT) from laboratories in the European Union (EU) and more orders are likely to follow in the near future, according to Pune-based Patel Analog and Digital Measurement Company (PADMCO) director Madhu Patel" (1/2 page).

  19. Genetic association of polymorphism rs1333049 with gout.

    Science.gov (United States)

    Wang, Binbin; Meng, Dongmei; Wang, Jing; Liu, Shiguo; Zhou, Sirui; Miao, Zhimin; Han, Lin; Chu, Nan; Zhang, Kun; Ma, Xu; Li, Changgui

    2011-09-01

    We suspect that genes or loci that contribute to coronary artery disease (CAD) may also play a role in the pathogenesis of gout, since hyperuricaemia leads to gout, and serum uric acid (SUA) levels are potential risk factors for CAD. The single nucleotide polymorphism (SNP) rs1333049 (C/G) on chromosome 9p21 has been implicated in previous studies to be associated with CAD. The aim of this study was to evaluate the relationship between this SNP and gout pathogenesis. Nine hundred Chinese Han were recruited for this study (461 gout patients and 439 gout-free individuals). The rs1333049 SNP and surrounding sequences were PCR sequenced. There was a clear link between the rs1333049 genotypic and allelic frequencies between gout cases and controls (χ(2) = 6.81, df = 2, P = 0.033 by genotype; χ(2) = 6.63, df = 1, P = 0.01 by allele). There was a significantly increased risk of gout in carriers of the CC genotype (odds ratio = 1.43, 95% CI 1.07, 1.91). To the best of our knowledge, our findings are the first to establish an association of rs1333049 with gout in a Chinese Han population. Meanwhile, this SNP is homologous to miR-519 and miR-520.

  20. 7q21-rs6964587 and breast cancer risk

    DEFF Research Database (Denmark)

    Milne, Roger L; Lorenzo-Bermejo, Justo; Burwinkel, Barbara

    2011-01-01

    Using the Breast Cancer Association Consortium, the authors previously reported that the single nucleotide polymorphism 7q21-rs6964587 (AKAP9-M463I) is associated with breast cancer risk. The authors have now assessed this association more comprehensively using 16 independent case-control studies....

  1. Work in Progress: The Seven Rs of Team Building

    Science.gov (United States)

    Brunelli, Jean; Schneider, Elaine Fogel

    2004-01-01

    This article argues that supportive teams--including professionals, paraprofessionals, and parents--can teach staff members how to identify and implement best practices in early intervention settings. The authors describe "the seven Rs of team building" distilled from their many years of team building and maintenance: 1) Reading cues; 2) Regular…

  2. The impact of LRP5 polymorphism (rs556442) on calcium homeostasis, bone mineral density, and body composition in Iranian children.

    Science.gov (United States)

    Ashouri, Elham; Meimandi, Elham Mahmoodi; Saki, Forough; Dabbaghmanesh, Mohammad Hossein; Omrani, Gholamhossein Ranjbar; Bakhshayeshkaram, Marzieh

    2015-11-01

    Failure to achieve optimal bone mass in childhood is the primary cause of decreased adult bone mineral density (BMD) and increased bone fragility in later life. Activating and inactivating LRP5 gene mutations has been associated with extreme bone-related phenotypes. Our aim was to investigate the role of LRP5 polymorphism on BMD, mineral biochemical parameters, and body composition in Iranian children. This cross-sectional study was performed on 9-18 years old children (125 boys, 137 girls). The serum level of calcium, phosphorous, alkaline phosphatase, and vitamin D parameters were checked. The body composition and BMD variables were measured by the Hologic system DXA. The rs566442 (V1119V) coding polymorphism in exon 15 of LRP5 was performed using PCR-RFLP method. Linear regression analysis, with adjustment for age, gender, body size parameters, and pubertal status was used to determine the association between LRP5 polymorphism (rs556442) and bone and body composition parameters. The allele frequency of the rs566442 gene was 35.5 % A and 63.9 % G. Our study revealed that LRP5 (rs556442) has not any significant influence on serum calcium, phosphorus, 25OHvitD, and serum alkaline phosphatase (P > 0.05). Total lean mass was greater in GG genotype (P = 0.028). Total body less head area (P = 0.044), spine BMD (P = 0.04), and total femoral BMC (P = 0.049) were lower in AG heterozygote genotype. This study show LRP5 polymorphism may associate with body composition and BMD in Iranian children. However, further investigations should be done to evaluate the role of other polymorphism.

  3. Preparation and characterization of (R,S)-[76Br]BrQNB: an analogue of QNB for PET

    International Nuclear Information System (INIS)

    Strijckmans, V.; Loc'h, C.; Ottaviani, M.; Maziere, B.; Lee, K.S.; Zeeberg, B.R.

    1997-01-01

    (R,S)-[ 76 Br]BrQNB was prepared for imaging mAChR by PET . (R,S)QNB was labelled with bromine-76 by electrophilic substitution of the tributylstannyl precursor using peracetic acid as oxidizing agent. The exchange between bromine-76 and the leaving group occurred in 20 min at room temperature. A chemically and radiochemically pure product was obtained with a final radiolabelling yield of 30%. Preliminary evaluation of pharmacological properties was performed in rats. In brain, biodistribution and autoradiography studies showed that the preferential localization of (R,S)-[ 76 Br]BrQNB was m-AChR rich structures. 6 h p.i. the radioactivity uptake in the posterior cortex was 1% ID/g and the striatum to cerebellum radioactivity ratio was 13.5. Metabolite study revealed that the radiotracer remains unchanged in brain for at least 3 h. (Author)

  4. APOC3 rs2070666 Is Associated with the Hepatic Steatosis Independently of PNPLA3 rs738409 in Chinese Han Patients with Nonalcoholic Fatty Liver Diseases.

    Science.gov (United States)

    Zhang, Rui-Nan; Zheng, Rui-Dan; Mi, Yu-Qiang; Zhou, Da; Shen, Feng; Chen, Guang-Yu; Zhu, Chan-Yan; Pan, Qin; Fan, Jian-Gao

    2016-08-01

    The association between nonalcoholic fatty liver disease (NAFLD) and apolipoprotein C3 gene (APOC3) promoter region single-nucleotide polymorphisms (SNPs) rs2854117 and rs2854116 is controversial. The aim of this study was to investigate the relationship between other polymorphisms of APOC3 and NAFLD in Chinese. Fifty-nine liver biopsy-proven NAFLD patients and 72 healthy control subjects were recruited to a cohort representing Chinese Han population. The polymorphisms in the exons and flanking regions of APOC3 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphisms were genotyped. Among the five SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) in APOC3, only rs2070666 (c.179 + 62 T/A) was significantly different in genotype and allele frequency (both p steatosis (OR 4.986, 95 % CI 1.020-24.371), but neither to liver stiffness measurement values nor to hepatic histological activity and fibrosis in NAFLD patients. The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content in Chinese Han population.

  5. FeNO as biomarker for asthma phenotyping and management.

    Science.gov (United States)

    Ricciardolo, Fabio L M; Sorbello, Valentina; Ciprandi, Giorgio

    2015-01-01

    The current review aims to revisit literature on exhaled nitric oxide (FeNO) in asthma phenotyping and management to clarify the utility of this test in clinical practice. It is increasingly evident that multiple profiles characterize asthma as a complex disease for which is necessary to find tools able to discriminate among these phenotypes to achieve the best therapeutic strategy for all asthmatic patients. Current findings indicate that FeNO, a noninvasive and easy-to-obtain biomarker, can be considered a useful tool in predicting asthma developing and exacerbation, in identifying specific asthma phenotypes, in improving asthma diagnosis and management in a selected population, and in monitoring efficacy of standard corticosteroid and biologic therapy. Based on this evidence, FeNO might become an appropriate tool for physicians to better define specific asthma phenotypes and to better deal with asthma worsening.

  6. PARP-1 Variant Rs1136410 Confers Protection against Coronary Artery Disease in a Chinese Han Population: A Two-Stage Case-Control Study Involving 5643 Subjects

    Directory of Open Access Journals (Sweden)

    Xue-bin Wang

    2017-11-01

    Full Text Available Inhibition of poly(ADP-ribose polymerase (PARP may protect against coronary artery disease (CAD in animal models, and rs1136410, a non-synonymous single nucleotide polymorphism (SNP in PARP-1, has a potential impact on PARP activities in vitro. This two-stage case-control study, involving 2803 CAD patients and 2840 controls, aimed to investigate the associations of PARP-1 rs1136410 with CAD development, lipid levels, PARP activities, 8-hydroxy-2′-dexyguanosine (8-OHdG, and interleukin (IL-6 levels in a Chinese Han population. Assuming a recessive model, the variant genotype GG of SNP rs1136410 showed a significantly inverse association with CAD risk (adjusted odds ratio (OR = 0.73, P < 0.001, left main coronary artery (LMCA lesions (P = 0.003, vessel scores (P = 0.003, and modified Gensini scores (P < 0.001. There were significant correlations of SNP rs1136410 with higher levels of total cholesterol (TC and lower levels of high-density lipoprotein cholesterol (HDL-c. In gene-environment interaction analyses, participants with the variant genotype GG, but without smoking habit, type 2 diabetes mellitus, and hyperlipidemia, conferred an 84% (P < 0.001 decreased risk of CAD. The genotype-phenotype correlation analyses further supported the functional roles of SNP rs1136410 in decreasing PARP activities and 8-OHdG levels. Taken together, our data suggest that SNP rs1136410 may confer protection against CAD through modulation of PARP activities and gene-environment interactions in a Chinese Han population.

  7. Role of the Genes of Type VI Secretion System in Virulence of Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae Strain RS-2

    Directory of Open Access Journals (Sweden)

    Md. Mahidul Islam Masum

    2017-09-01

    Full Text Available The Type VI secretion system (T6SS is a class of macromolecular machine that is required for the virulence of gram-negative bacteria. However, it is still not clear what the role of T6SS in the virulence of rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa is. The aim of the current study was to investigate the contribution of T6SS in Aaa strain RS2 virulence using insertional deletion mutation and complementation approaches. This strain produced weak virulence but contains a complete T6SS gene cluster based on a genome-wide analysis. Here we compared the virulence-related phenotypes between the wild-type (RS-2 and 25 T6SS mutants, which were constructed using homologous recombination methods. The mutation of 15 T6SS genes significantly reduced bacterial virulence and the secretion of Hcp protein. Additionally, the complemented 7 mutations ΔpppA, ΔclpB, Δhcp, ΔdotU, ΔicmF, ΔimpJ, and ΔimpM caused similar virulence characteristics as RS-2. Moreover, the mutant ΔpppA, ΔclpB, ΔicmF, ΔimpJ and ΔimpM genes caused by a 38.3~56.4% reduction in biofilm formation while the mutants ΔpppA, ΔclpB, ΔicmF and Δhcp resulted in a 37.5~44.6% reduction in motility. All together, these results demonstrate that T6SS play vital roles in the virulence of strain RS-2, which may be partially attributed to the reductions in Hcp secretion, biofilm formation and motility. However, differences in virulence between strain RS-1 and RS-2 suggest that other factors may also be involved in the virulence of Aaa.

  8. Role of the Genes of Type VI Secretion System in Virulence of Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae Strain RS-2.

    Science.gov (United States)

    Masum, Md Mahidul Islam; Yang, Yingzi; Li, Bin; Olaitan, Ogunyemi Solabomi; Chen, Jie; Zhang, Yang; Fang, Yushi; Qiu, Wen; Wang, Yanli; Sun, Guochang

    2017-09-21

    The Type VI secretion system (T6SS) is a class of macromolecular machine that is required for the virulence of gram-negative bacteria. However, it is still not clear what the role of T6SS in the virulence of rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa) is. The aim of the current study was to investigate the contribution of T6SS in Aaa strain RS2 virulence using insertional deletion mutation and complementation approaches. This strain produced weak virulence but contains a complete T6SS gene cluster based on a genome-wide analysis. Here we compared the virulence-related phenotypes between the wild-type (RS-2) and 25 T6SS mutants, which were constructed using homologous recombination methods. The mutation of 15 T6SS genes significantly reduced bacterial virulence and the secretion of Hcp protein. Additionally, the complemented 7 mutations Δ pppA , Δ clpB , Δ hcp , Δ dotU , Δ icmF , Δ impJ , and Δ impM caused similar virulence characteristics as RS-2. Moreover, the mutant Δ pppA , Δ clpB , Δ icmF , Δ impJ and Δ impM genes caused by a 38.3~56.4% reduction in biofilm formation while the mutants Δ pppA , Δ clpB , Δ icmF and Δ hcp resulted in a 37.5~44.6% reduction in motility. All together, these results demonstrate that T6SS play vital roles in the virulence of strain RS-2, which may be partially attributed to the reductions in Hcp secretion, biofilm formation and motility. However, differences in virulence between strain RS-1 and RS-2 suggest that other factors may also be involved in the virulence of Aaa.

  9. Resistance to pentamidine is mediated by AdeAB, regulated by AdeRS, and influenced by growth conditions in Acinetobacter baumannii ATCC 17978.

    Science.gov (United States)

    Adams, Felise G; Stroeher, Uwe H; Hassan, Karl A; Marri, Shashikanth; Brown, Melissa H

    2018-01-01

    In recent years, effective treatment of infections caused by Acinetobacter baumannii has become challenging due to the ability of the bacterium to acquire or up-regulate antimicrobial resistance determinants. Two component signal transduction systems are known to regulate expression of virulence factors including multidrug efflux pumps. Here, we investigated the role of the AdeRS two component signal transduction system in regulating the AdeAB efflux system, determined whether AdeA and/or AdeB can individually confer antimicrobial resistance, and explored the interplay between pentamidine resistance and growth conditions in A. baumannii ATCC 17978. Results identified that deletion of adeRS affected resistance towards chlorhexidine and 4',6-diamidino-2-phenylindole dihydrochloride, two previously defined AdeABC substrates, and also identified an 8-fold decrease in resistance to pentamidine. Examination of ΔadeA, ΔadeB and ΔadeAB cells augmented results seen for ΔadeRS and identified a set of dicationic AdeAB substrates. RNA-sequencing of ΔadeRS revealed transcription of 290 genes were ≥2-fold altered compared to the wildtype. Pentamidine shock significantly increased adeA expression in the wildtype, but decreased it in ΔadeRS, implying that AdeRS activates adeAB transcription in ATCC 17978. Investigation under multiple growth conditions, including the use of Biolog phenotypic microarrays, revealed resistance to pentamidine in ATCC 17978 and mutants could be altered by bioavailability of iron or utilization of different carbon sources. In conclusion, the results of this study provide evidence that AdeAB in ATCC 17978 can confer intrinsic resistance to a subset of dicationic compounds and in particular, resistance to pentamidine can be significantly altered depending on the growth conditions.

  10. From metabolome to phenotype

    DEFF Research Database (Denmark)

    Khakimov, Bekzod; Rasmussen, Morten Arendt; Kannangara, Rubini Maya

    2017-01-01

    for ideal vegetable protein production and for augmented β-glucan production. Seeds from three barley lines (Bomi, lys3.a and lys5.f) were sampled eight times during grain filling and analysed for metabolites using gas chromatography-mass spectrometry (GC-MS). The lys3.a mutation disrupts a regulator gene...... their successful application to link genetic and environmental factors with the seed phenotype of unique and agro-economically important barley models for optimal vegetable protein and dietary fibre production......., causing an increase in proteins rich in the essential amino acid lysine, while lys5.f carries a mutation in an ADP-glucose transporter gene leading to a significant increase in production of mixed-linkage β-glucan at the expense of α-glucan. Unique metabolic patterns associated with the tricarboxylic acid...

  11. Deep Learning for Plant Phenotyping

    OpenAIRE

    Mori, Matteo

    2016-01-01

    Plant Phenotyping is an emerging science which provides us the knowledge to better understand plants. Indeed, the study of the link between genetic background and environment in which plants develop can help us to determine cures for plants’ sicknesses and new ways to improve yields using limited resources. In this regard, one of the main aspects of Plant Phenotyping that were studied in the past, was Root Phenotyping, which is based on the study of the root architectures. In particular, toda...

  12. Evaluation of Oxidative Stress Response Related Genetic Variants, Pro-oxidants, Antioxidants and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Nicole Lavender

    2015-09-01

    Full Text Available Background: Oxidative stress and detoxification mechanisms have been commonly studied in Prostate Cancer (PCa due to their function in the detoxification of potentially damaging reactive oxygen species (ROS and carcinogens. However, findings have been either inconsistent or inconclusive. These mixed findings may, in part, relate to failure to consider interactions among oxidative stress response related genetic variants along with pro- and antioxidant factors. Methods: We examined the effects of 33 genetic and 26 environmental oxidative stress and defense factors on PCa risk and disease aggressiveness among 2,286 men from the Cancer Genetic Markers of Susceptibility project (1,175 cases, 1,111 controls. Single and joint effects were analyzed using a comprehensive statistical approach involving logistic regression, multi-dimensionality reduction, and entropy graphs. Results: Inheritance of one CYP2C8 rs7909236 T or two SOD2 rs2758331 A alleles was linked to a 1.3- and 1.4-fold increase in risk of developing PCa, respectively (p-value = 0.006-0.013. Carriers of CYP1B1 rs1800440GG, CYP2C8 rs1058932TC and, NAT2 (rs1208GG, rs1390358CC, rs7832071TT genotypes were associated with a 1.3 to 2.2-fold increase in aggressive PCa [p-value = 0.04-0.001, FDR 0.088-0.939]. We observed a 23% reduction in aggressive disease linked to inheritance of one or more NAT2 rs4646247 A alleles (p = 0.04, FDR = 0.405. Only three NAT2 sequence variants remained significant after adjusting for multiple hypotheses testing, namely NAT2 rs1208, rs1390358, and rs7832071. Lastly, there were no significant gene-environment or gene-gene interactions associated with PCa outcomes. Conclusions: Variations in genes involved in oxidative stress and defense pathways may modify PCa. Our findings do not firmly support the role of oxidative stress genetic variants combined with lifestyle/environmental factors as modifiers of PCa and disease progression. However, additional multi

  13. MicroRNAs in Muscle: Characterizing the Powerlifter Phenotype

    Science.gov (United States)

    D'Souza, Randall F.; Bjørnsen, Thomas; Zeng, Nina; Aasen, Kirsten M. M.; Raastad, Truls; Cameron-Smith, David; Mitchell, Cameron J.

    2017-01-01

    Powerlifters are the epitome of muscular adaptation and are able to generate extreme forces. The molecular mechanisms underpinning the significant capacity for force generation and hypertrophy are not fully elucidated. MicroRNAs (miRs) are short non-coding RNA sequences that control gene expression via promotion of transcript breakdown and/or translational inhibition. Differences in basal miR expression may partially account for phenotypic differences in muscle mass and function between powerlifters and untrained age-matched controls. Muscle biopsies were obtained from m. vastus lateralis of 15 national level powerlifters (25.1 ± 5.8 years) and 13 untrained controls (24.1 ± 2.0 years). The powerlifters were stronger than the controls (isokinetic knee extension at 60°/s: 307.8 ± 51.6 Nm vs. 211.9 ± 41.9 Nm, respectively P powerlifters and five having lower expression. Established transcriptionally regulated miR downstream gene targets involved in muscle mass regulation, including myostatin and MyoD, were also differentially expressed between groups. Correlation analysis demonstrates the abundance of eight miRs was correlated to phenotype including peak strength, fiber size, satellite cell abundance, and fiber type regardless of grouping. The unique miR expression profiles between groups allow for categorization of individuals as either powerlifter or healthy controls based on a five miR signature (miR-126, -23b, -16, -23a, -15a) with considerable accuracy (100%). Thus, this unique miR expression may be important to the characterization of the powerlifter phenotype. PMID:28638346

  14. Catalase deletion promotes prediabetic phenotype in mice.

    Science.gov (United States)

    Heit, Claire; Marshall, Stephanie; Singh, Surrendra; Yu, Xiaoqing; Charkoftaki, Georgia; Zhao, Hongyu; Orlicky, David J; Fritz, Kristofer S; Thompson, David C; Vasiliou, Vasilis

    2017-02-01

    Hydrogen peroxide is produced endogenously and can be toxic to living organisms by inducing oxidative stress and cell damage. However, it has also been identified as a signal transduction molecule. By metabolizing hydrogen peroxide, catalase protects cells and tissues against oxidative damage and may also influence signal transduction mechanisms. Studies suggest that acatalasemic individuals (i.e., those with very low catalase activity) have a higher risk for the development of diabetes. We now report catalase knockout (Cat -/- ) mice, when fed a normal (6.5% lipid) chow, exhibit an obese phenotype that manifests as an increase in body weight that becomes more pronounced with age. The mice demonstrate altered hepatic and muscle lipid deposition, as well as increases in serum and hepatic triglycerides (TGs), and increased hepatic transcription and protein expression of PPARγ. Liver morphology revealed steatosis with inflammation. Cat -/- mice also exhibited pancreatic morphological changes that correlated with impaired glucose tolerance and increased fasting serum insulin levels, conditions consistent with pre-diabetic status. RNA-seq analyses revealed a differential expression of pathways and genes in Cat -/- mice, many of which are related to metabolic syndrome, diabetes, and obesity, such as Pparg and Cidec. In conclusion, the results of the present study show mice devoid of catalase develop an obese, pre-diabetic phenotype and provide compelling evidence for catalase (or its products) being integral in metabolic regulation. Copyright © 2016. Published by Elsevier Inc.

  15. Genetic polymorphisms of IL-18 rs1946518 and IL-1β rs16944 are associated with prognosis and survival of acute myeloid leukemia.

    Science.gov (United States)

    Wang, Hong; Hua, Mingqiang; Wang, Shukang; Yu, Jie; Chen, Chen; Zhao, Xueyun; Zhang, Chen; Zhong, Chaoqin; Wang, Ruiqing; He, Na; Hou, Ming; Ma, Daoxin

    2017-03-01

    Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1β (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival. IL-1β (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.

  16. Predicting pKa for proteins using COSMO-RS

    DEFF Research Database (Denmark)

    Andersson, Martin Peter; Jensen, Jan Halborg; Stipp, Susan Louise Svane

    2013-01-01

    We have used the COSMO-RS implicit solvation method to calculate the equilibrium constants, pKa, for deprotonation of the acidic residues of the ovomucoid inhibitor protein, OMTKY3. The root mean square error for comparison with experimental data is only 0.5 pH units and the maximum error 0.8 p......H units. The results show that the accuracy of pKa prediction using COSMO-RS is as good for large biomolecules as it is for smaller inorganic and organic acids and that the method compares very well to previous pKa predictions of the OMTKY3 protein using Quantum Mechanics/Molecular Mechanics. Our approach...

  17. RS Ophiuchi: The Gift that Keeps on Giving

    Science.gov (United States)

    Starrfield, S.

    2008-12-01

    RS Oph experienced its sixth recorded outburst in 2006 and was observed in virtually every wavelength region from hard X-rays to the radio. Each observation, especially those with instruments that have come online since its last outburst in 1985, provided new and exciting information about the explosion. As a result, some of us organized a second workshop on the RS Oph outburst and it was held in June 2007 at Keele University. I gave the lead off talk in which I presented a number of questions to be discussed during the workshop, a brief summary of what had been discovered in previous outbursts concentrating on the ultraviolet studies with IUE, and a few observations of the 2006 outburst concentrating on the results from Swift and HST.

  18. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Directory of Open Access Journals (Sweden)

    Hayley C Whitaker

    2010-10-01

    Full Text Available Microseminoprotein-beta (MSMB regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk.MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate.These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  19. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Science.gov (United States)

    Whitaker, Hayley C; Kote-Jarai, Zsofia; Ross-Adams, Helen; Warren, Anne Y; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J; Evans, D Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E

    2010-10-13

    Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  20. Solvation quantities from a COSMO-RS equation of state

    International Nuclear Information System (INIS)

    Panayiotou, C.; Tsivintzelis, I.; Aslanidou, D.; Hatzimanikatis, V.

    2015-01-01

    Highlights: • Extension of the successful COSMO-RS model to an equation-of-state model. • Two scaling constants, obtained from atom-specific contributions. • Overall estimation of the solvation quantities and contributions. - Abstract: This work focuses on the extension of the successful COSMO-RS model of mixtures into an equation-of-state model of fluids and its application for the estimation of solvation/hydration quantities of a variety of chemical substances. These quantities include free-energies, enthalpies and entropies of hydration as well as the separate contributions to each of them. Emphasis is given on the estimation of contributions from the conformational changes of solutes upon solvation and the associated restructuring of solvent in its immediate neighborhood. COSMO-RS is a quantum-mechanics based group/segment contribution model in which the Quasi-Chemical (QC) approach is used for the description of the non-random distribution of interacting segments in the system. Thus, the equation-of-state development is done through such a QC framework. The new model will not need any adjustable parameters for the strong specific interactions, such as hydrogen bonds, since they will be provided by the quantum-mechanics based cosmo-files – a key feature of COSMO-RS model. It will need, however, one volumetric and one energy parameter per fluid, which are scaling constants or molecular descriptors of the fluid and are obtained from rather easily available data such as densities, boiling points, vapor pressures, heats of vaporization or second virial coefficients. The performance and the potential of the new equation-of-state model to become a fully predictive model are critically discussed

  1. Spectrophotometry of RS Oph during the nebular phase

    International Nuclear Information System (INIS)

    Bohigas, J.; Echevarria, J.; Diego, F.; Sarmiento, J.A.

    1989-01-01

    Blue-wavelength spectroscopic observations of RS Oph, 201 day after the 1985 outburst are presented. An analysis of the TiO bands indicates a spectral type M4III for the secondary and a distance of 2 kpc to the system. The system of forbidden lines is excited by a shock wave, whereas Balmer emission is mainly produced by photoionization. The source of photons is probably residual thermonuclear burning occurring at the surface of the white dwarf. (author)

  2. Převodník Ethernet na RS-232

    OpenAIRE

    Dreiseitel, Jiří

    2012-01-01

    Práce je věnována problematice konstrukce převodníku Ethernet na RS-232 za pomocí jednočipového mikrokontroléru. Cílem je seznámit čtenáře se síťovou technologií Ethernet a technologií pro sériový přenos založený na protokolu RS-232 a zároveň s technologií vestavěných systémů pro konstrukci zařízení. Součástí práce je kompletní návrh převodníku Ethernet na RS-232 včetně návrhu a implementace firmware v jazyce C za využití LwIP TCP/IP stacku. Převodník je postaven na základě vývojového kitu ST...

  3. Mechanism of pyrogallol red oxidation induced by free radicals and reactive oxidant species. A kinetic and spectroelectrochemistry study.

    Science.gov (United States)

    Atala, E; Velásquez, G; Vergara, C; Mardones, C; Reyes, J; Tapia, R A; Quina, F; Mendes, M A; Speisky, H; Lissi, E; Ureta-Zañartu, M S; Aspée, A; López-Alarcón, C

    2013-05-02

    Pyrogallol red (PGR) presents high reactivity toward reactive (radical and nonradical) species (RS). This property of PGR, together with its characteristic spectroscopic absorption in the visible region, has allowed developing methodologies aimed at evaluating the antioxidant capacity of foods, beverages, and human fluids. These methods are based on the evaluation of the consumption of PGR induced by RS and its inhibition by antioxidants. However, at present, there are no reports regarding the degradation mechanism of PGR, limiting the extrapolation to how antioxidants behave in different systems comprising different RS. In the present study, we evaluate the kinetics of PGR consumption promoted by different RS (peroxyl radicals, peroxynitrite, nitrogen dioxide, and hypochlorite) using spectroscopic techniques and detection of product by HPLC mass spectrometry. The same pattern of oxidation and spectroscopic properties of the products is observed, independently of the RS employed. Mass analysis indicates the formation of only one product identified as a quinone derivative, excluding the formation of peroxides or hydroperoxides and/or chlorinated compounds, in agreement with FOX's assays and oxygen consumption experiments. Cyclic voltammetry, carried out at different pH's, shows an irreversible oxidation of PGR, indicating the initial formation of a phenoxy radical and a second charge transfer reaction generating an ortho-quinone derivative. Spectroelectrochemical oxidation of PGR shows oxidation products with identical UV-visible absorption properties to those observed in RS-induced oxidation.

  4. Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit

    Science.gov (United States)

    Klee, Eric W.; Shin, Andrea; Carlson, Paula; Li, Ying; Grover, Madhusudan; Zinsmeister, Alan R.

    2013-01-01

    The study objectives were: to mine the complete exome to identify putative rare single nucleotide variants (SNVs) associated with irritable bowel syndrome (IBS)-diarrhea (IBS-D) phenotype, to assess genes that regulate bile acids in IBS-D, and to explore univariate associations of SNVs with symptom phenotype and quantitative traits in an independent IBS cohort. Using principal components analysis, we identified two groups of IBS-D (n = 16) with increased fecal bile acids: rapid colonic transit or high bile acids synthesis. DNA was sequenced in depth, analyzing SNVs in bile acid genes (ASBT, FXR, OSTα/β, FGF19, FGFR4, KLB, SHP, CYP7A1, LRH-1, and FABP6). Exome findings were compared with those of 50 similar ethnicity controls. We assessed univariate associations of each SNV with quantitative traits and a principal components analysis and associations between SNVs in KLB and FGFR4 and symptom phenotype in 405 IBS, 228 controls and colonic transit in 70 IBS-D, 71 IBS-constipation. Mining the complete exome did not reveal significant associations with IBS-D over controls. There were 54 SNVs in 10 of 11 bile acid-regulating genes, with no SNVs in FGF19; 15 nonsynonymous SNVs were identified in similar proportions of IBS-D and controls. Variations in KLB (rs1015450, downstream) and FGFR4 [rs434434 (intronic), rs1966265, and rs351855 (nonsynonymous)] were associated with colonic transit (rs1966265; P = 0.043), fecal bile acids (rs1015450; P = 0.064), and principal components analysis groups (all 3 FGFR4 SNVs; P transit (P = 0.066). Thus exome sequencing identified additional variants in KLB and FGFR4 associated with bile acids or colonic transit in IBS-D. PMID:24200957

  5. The role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancy.

    Directory of Open Access Journals (Sweden)

    Margrit Urbanek

    Full Text Available Since mediators of inflammation are associated with insulin resistance, and the risk of developing diabetes mellitus and gestational diabetes, we hypothesized that genetic variation in members of the inflammatory gene pathway impact glucose levels and related phenotypes in pregnancy. We evaluated this hypothesis by testing for association between genetic variants in 31 inflammatory pathway genes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO cohort, a large multiethnic multicenter study designed to address the impact of glycemia less than overt diabetes on pregnancy outcome.Fasting, 1-hour, and 2-hour glucose, fasting and 1-hour C-peptide, and HbA1c levels were measured in blood samples obtained from HAPO participants during an oral glucose tolerance test at 24-32 weeks gestation. We tested for association between 458 SNPs mapping to 31 genes in the inflammatory pathway and metabolic phenotypes in 3836 European ancestry and 1713 Thai pregnant women. The strongest evidence for association was observed with TNF alpha and HbA1c (rs1052248; 0.04% increase per allele C; p-value = 4.4×10(-5, RETN and fasting plasma glucose (rs1423096; 0.7 mg/dl decrease per allele A; p-value = 1.1×10(-4, IL8 and 1 hr plasma glucose (rs2886920; 2.6 mg/dl decrease per allele T; p-value = 1.3×10(-4, ADIPOR2 and fasting C-peptide (rs2041139; 0.55 ug/L decrease per allele A; p-value = 1.4×10(-4, LEPR and 1-hour C-peptide (rs1171278; 0.62 ug/L decrease per allele T; p-value = 2.4×10(-4, and IL6 and 1-hour plasma glucose (rs6954897; -2.29 mg/dl decrease per allele G, p-value = 4.3×10(-4.Based on the genes surveyed in this study the inflammatory pathway is unlikely to have a strong impact on maternal metabolic phenotypes in pregnancy although variation in individual members of the pathway (e.g. RETN, IL8, ADIPOR2, LEPR, IL6, and TNF alpha, may contribute to metabolic phenotypes in pregnant women.

  6. 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.

  7. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  8. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  9. Association between CST3 rs2424577 polymorphism and corpulence related phenotypes during lifetime in populations of European ancestry

    DEFF Research Database (Denmark)

    Hooton, Henri; Dubern, Beatrice; Henegar, Corneliu

    2011-01-01

    Cystatin C, a protein coded by CST3 gene, is implicated in adipose tissue biology. Our hypothesis is that common variants in CST3 gene could play a role in the development of corpulence during lifetime....

  10. Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.

    Science.gov (United States)

    Meyers, Jacquelyn L; Shmulewitz, Dvora; Wall, Melanie M; Keyes, Katherine M; Aharonovich, Efrat; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Edenberg, Howard J; Gelernter, Joel; Grant, Bridget F; Hasin, Deborah

    2015-01-01

    Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors. © 2013 Society for the Study of Addiction.

  11. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study.

    Science.gov (United States)

    Lee, Sung Won; Lee, Shin Seok; Oh, Dong Ho; Park, Dong Jin; Kim, Hyun Sook; Choi, Jung Ran; Chae, Soo Cheon; Yun, Ki Jung; Chung, Won Tae; Choe, Jung Yoon; Kim, Seong Kyu

    2016-10-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.

  12. Association of the ENPP1 rs997509 polymorphism with obesity in ...

    African Journals Online (AJOL)

    ) polymorphisms have been associated with metabolic traits. There is no data on the effect of ENPP1 in South African children or adults. Objective: To investigate the role of K121Q (rs1044498), rs997509 and rs9402349 in obesity and other ...

  13. Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder.

    Science.gov (United States)

    Sun, Xiao R; Zhang, Hui; Zhao, Hong T; Ji, Mu H; Li, Hui H; Wu, Jing; Li, Kuan Y; Yang, Jian J

    2016-10-01

    Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, which is characterized by anxiety- and depression-like behaviors and cognitive impairment. However, the underlying mechanisms remain elusive. Parvalbumin (PV) interneurons that are susceptible to oxidative stress are a subset of inhibitory GABAergic neurons regulating the excitability of pyramidal neurons, while dysfunction of PV interneurons is casually linked to many mental disorders including PTSD. We therefore hypothesized that environmental enrichment (EE), a method of enhanced cognitive, sensory and motor stimulation, can reverse the behavioral impairments by normalizing PV interneurons in a rat model of PTSD induced by inescapable foot shocks (IFS). Behavioral changes were determined by the open field, elevated plus maze, fear conditioning, and Morris water maze tests. The levels of nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NOX4, PV, glutamic acid decarboxylase 67 (GAD-67), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in the hippocampus and prefrontal cortex were determined. Our results showed that in this PTSD model, rats displayed the anxiety-like behavior, enhanced fear learning behavior, and hippocampus- dependent spatial memory deficit, which were accompanied by the up-regulation of NOX2, 8-OH-dG, and down-regulation of PV and GAD-67. Notably, EE reversed all these abnormalities. These results suggest that restoration of PV interneurons by inhibiting oxidative stress in the hippocampus and prefrontal cortex might represent a mechanism through which EE reverses the behavioral impairments in a rat model of PTSD induced by IFS. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. MicroRNAs in Muscle: Characterizing the Powerlifter Phenotype

    Directory of Open Access Journals (Sweden)

    Randall F. D'Souza

    2017-06-01

    Full Text Available Powerlifters are the epitome of muscular adaptation and are able to generate extreme forces. The molecular mechanisms underpinning the significant capacity for force generation and hypertrophy are not fully elucidated. MicroRNAs (miRs are short non-coding RNA sequences that control gene expression via promotion of transcript breakdown and/or translational inhibition. Differences in basal miR expression may partially account for phenotypic differences in muscle mass and function between powerlifters and untrained age-matched controls. Muscle biopsies were obtained from m. vastus lateralis of 15 national level powerlifters (25.1 ± 5.8 years and 13 untrained controls (24.1 ± 2.0 years. The powerlifters were stronger than the controls (isokinetic knee extension at 60°/s: 307.8 ± 51.6 Nm vs. 211.9 ± 41.9 Nm, respectively P < 0.001, and also had larger muscle fibers (type I CSA 9,122 ± 1,238 vs. 4,511 ± 798 μm2p < 0.001 and type II CSA 11,100 ± 1,656 vs. 5,468 ± 1,477 μm2p < 0.001. Of the 17 miRs species analyzed, 12 were differently expressed (p < 0.05 between groups with 7 being more abundant in powerlifters and five having lower expression. Established transcriptionally regulated miR downstream gene targets involved in muscle mass regulation, including myostatin and MyoD, were also differentially expressed between groups. Correlation analysis demonstrates the abundance of eight miRs was correlated to phenotype including peak strength, fiber size, satellite cell abundance, and fiber type regardless of grouping. The unique miR expression profiles between groups allow for categorization of individuals as either powerlifter or healthy controls based on a five miR signature (miR-126, -23b, -16, -23a, -15a with considerable accuracy (100%. Thus, this unique miR expression may be important to the characterization of the powerlifter phenotype.

  15. Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

    Directory of Open Access Journals (Sweden)

    Celedón Juan C

    2011-02-01

    Full Text Available Abstract Background Prior studies suggest a role for a variant (rs5743836 in the promoter of toll-like receptor 9 (TLR9 in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts. Methods rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity. Results Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV1 and FVC (p = 0.003 and p = 0.008, respectively in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant. Conclusion Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.

  16. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

    Science.gov (United States)

    Rueda, B; Broen, J; Simeon, C; Hesselstrand, R; Diaz, B; Suárez, H; Ortego-Centeno, N; Riemekasten, G; Fonollosa, V; Vonk, M C; van den Hoogen, F H J; Sanchez-Román, J; Aguirre-Zamorano, M A; García-Portales, R; Pros, A; Camps, M T; Gonzalez-Gay, M A; Coenen, M J H; Airo, P; Beretta, L; Scorza, R; van Laar, J; Gonzalez-Escribano, M F; Nelson, J L; Radstake, T R D J; Martin, J

    2009-06-01

    The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.

  17. An intronic single-nucleotide polymorphism (rs13217795) in FOXO3 is associated with asthma and allergic rhinitis: a case-case-control study.

    Science.gov (United States)

    Amarin, Justin Z; Naffa, Randa G; Suradi, Haya H; Alsaket, Yousof M; Obeidat, Nathir M; Mahafza, Tareq M; Zihlif, Malek A

    2017-11-15

    Asthma and allergic rhinitis are respiratory diseases with a significant global burden. Forkhead box O3 (FOXO3) is a gene involved in the etiology of a number of respiratory diseases. The objective of this study is to assess the association of rs13217795, an intronic FOXO3 single-nucleotide polymorphism, with asthma and allergic rhinitis. In this case-case-control genetic association study, genotyping was conducted using the PCR-RFLP method. Genotype-based associations were investigated under the general, recessive, and dominant models of disease penetrance using binomial logistic regression; and, allele-based associations were tested using Pearson's chi-squared test. The final study population consisted of 94 controls, 124 asthmatics, and 110 allergic rhinitis patients. The general and recessive models of disease penetrance were statistically significant for both case-control comparisons. Under the general model, the odds of the asthma phenotype were 1.46 (0.64 to 3.34) and 3.42 (1.37 to 8.57) times higher in heterozygotes and derived allele homozygotes, respectively, compared to ancestral allele homozygotes. The corresponding odds ratios for the allergic rhinitis phenotype were 1.05 (0.46 to 2.40) and 2.35 (0.96 to 5.73), respectively. The dominant model of disease penetrance was not statistically significant. The minor allele in all study groups was the ancestral allele, with a frequency of 0.49 in controls. There was no deviation from Hardy-Weinberg equilibrium in controls. Both case-control allele-based associations were statistically significant. Herein we present the first report of the association between rs13217795 and allergic rhinitis, and the first independent verification of the association between rs13217795 and asthma. Marker selection in future genetic association studies of asthma and allergic rhinitis should include functional polymorphisms in linkage disequilibrium with rs13217795.

  18. Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

    KAUST Repository

    Tawe, Leabaneng

    2018-03-14

    Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

  19. Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

    KAUST Repository

    Tawe, Leabaneng; Motshoge, Thato; Ramatlho, Pleasure; Mutukwa, Naledi; Muthoga, Charles Waithaka; Dongho, Ghyslaine Bruna Djeunang; Martinelli, Axel; Peloewetse, Elias; Russo, Gianluca; Quaye, Isaac Kweku; Paganotti, Giacomo Maria

    2018-01-01

    Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

  20. Neuropsychological effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253.

    LENUS (Irish Health Repository)

    Donohoe, G

    2013-03-01

    The single-nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2, was recently identified as genome-wide significant for schizophrenia (SZ), but is of unknown function. We investigated the neurocognitive effects of this CSMD1 variant in vivo in patients and healthy participants using behavioral and imaging measures of brain structure and function. We compared carriers and non-carriers of the risk \\'A\\' allele on measures of neuropsychological performance typically impaired in SZ (general cognitive ability, episodic and working memory and attentional control) in independent samples of Irish patients (n = 387) and controls (n = 171) and German patients (205) and controls (n = 533). Across these groups, the risk \\'A\\' allele at CSMD1 was associated with deleterious effects across a number of neurocognitive phenotypes. Specifically, the risk allele was associated with poorer performance on neuropsychological measures of general cognitive ability and memory function but not attentional control. These effects, while significant, were subtle, and varied between samples. Consistent with previous evidence suggesting that CSMD1 may be involved in brain mechanisms related to memory and learning, these data appear to reflect the deleterious effects of the identified \\'A\\' risk allele on neurocognitive function, possibly as part of the mechanism by which CSMD1 is associated with SZ risk.

  1. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  2. Deep Phenotyping: Deep Learning For Temporal Phenotype/Genotype Classification

    OpenAIRE

    Najafi, Mohammad; Namin, Sarah; Esmaeilzadeh, Mohammad; Brown, Tim; Borevitz, Justin

    2017-01-01

    High resolution and high throughput, genotype to phenotype studies in plants are underway to accelerate breeding of climate ready crops. Complex developmental phenotypes are observed by imaging a variety of accessions in different environment conditions, however extracting the genetically heritable traits is challenging. In the recent years, deep learning techniques and in particular Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs) and Long-Short Term Memories (LSTMs), h...

  3. Exceptional longevity and muscle and fitness related genotypes: a functional in vitro analysis and case-control association replication study with SNPs THRH rs7832552, IL6 rs1800795 and ACSL1 rs6552828

    Directory of Open Access Journals (Sweden)

    Noriyuki eFuku

    2015-05-01

    Full Text Available There are several gene variants that are candidates to influence functional capacity in long-lived individuals. As such, their potential association with exceptional longevity (EL, i.e., reaching 100+ years deserves analysis. Among them are rs7832552 in the thyrotropin-releasing hormone receptor (TRHR gene, rs1800795 in the interleukin-6 (IL6 gene and rs6552828 in the coenzyme A synthetase long-chain 1 (ACSL1 gene. To gain insight into their functionality (which is yet unknown, here we determined for the first time luciferase gene reporter activity at the muscle tissue level in rs7832552 and rs6552828. We then compared allele/genotype frequencies of the 3 abovementioned variants among centenarians [n=138, age range 100-111 years (114 women] and healthy controls [n=334, 20-50 years (141 women] of the same ethnic and geographic origin (Spain. We also studied healthy centenarians [n=79, 100-104 years (40 women] and controls [n=316, 27-81 years (156 women] from Italy, and centenarians [n=742, 100-116 years (623 women] and healthy controls [n=499, 23-59 years (356 women] from Japan. The THRH rs7832552 T-allele and ACSL1 rs6552828 A-allele up-regulated luciferase activity compared to the C and G-allele, respectively (P≤0.001. Yet we found no significant association of EL with rs7832552, rs1800795 or rs6552828 in any of the 3 cohorts. Further research is needed with larger cohorts of centenarians of different origin as well as with younger old people.

  4. Determination of IL-1B (rs16944) and IL-6 (rs1800796) genetic polymorphisms in IgA nephropathy in a northwest Chinese Han population.

    Science.gov (United States)

    Zhang, Daofa; Xie, Maowei; Yang, Xiaohong; Zhang, Yin; Su, Yan; Wang, Yanni; Huang, Haiyang; Han, Hui; Li, Wenning; Fu, Keying; Su, Huiluan; Xu, Wentan; Han, Yeguang; Wang, Ru; Zhang, Pei; Wu, Wei; Huang, Yun; Chen, Daojun; Jin, Tianbo; Wei, Jiali

    2017-09-22

    IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, but etiology and pathogenesis continue to be poorly understood. Polymorphisms in the cytokine genes may play a role in the etiology and pathogenesis of IgAN. The incidence of different between diverse ethnic groups suggested important genetic influences on its pathogenesis. We genotype 10 single nucleotide polymorphisms (SNPs) in IL-1B and IL-6 gene using Sequenom Mass-ARRAY technology from 417 IgAN patients and 463 healthy controls of the Chinese Han population. We evaluated these SNPs associated with IgAN utilising the chi-square tests and genetic model analysis. We identified that the minor alleles of rs16944 ("A"), rs1800796 ("G") in IL-1B, IL-6 were involved in an increasingly risk of IgAN in allelic model analysis, respectively. The rs16944 in IL-1B and rs1800796 in IL-6 were associated with 1.23-fold (95% CI, 1.02-1.48, P = 0.031) and 1.33-fold (95% CI, 1.11-1.66, P = 0.003) increases in the risk of developing IgAN, respectively. There was only rs1800796 still correlated with IgAN in the allelic model after adjustment by age and gender and the Bonferroni correction. In addition, Haplotype G rs1800796 A rs2069837 G rs2069840 ( P = 0.037) and G rs1800796 A rs2069837 C rs2069840 ( P = 0.042) in IL-6 were considered to be associated with increased IgAN risk. This study verified the IL-6, IL-1B genetic variants polymorphisms contributed to IgAN susceptibility in a Chinese Han population. Although we identified SNPs susceptibility, however, replication studies and functional research are required to confirm the genetic contribution in IgAN.

  5. The protein tyrosine phosphatase, nonreceptor type 22-1858C->T (rs2476601 polymorphism is not a genetic risk factor for systemic lupus erythematosus in Indian Tamils

    Directory of Open Access Journals (Sweden)

    Panneer Devaraju

    2017-01-01

    Full Text Available Background: Systemic lupus erythematosus (SLE, a systemic autoimmune disease, occurs due to disruption of immune homeostasis against self-antigens. The etiology of SLE is complex and multiple genetic factors contribute to disease susceptibility and clinical phenotypes. Protein tyrosine phosphatase, nonreceptor type 22 (PTPN22 is a lymphoid-specific phosphatase that negatively regulates T-cell receptor signaling and is responsible for the maintenance of T-cell homeostasis. Genetic aberrations affecting the function of PTPN22 result in the proliferation of autoreactive T-cells and development of autoimmune diseases. Methods: We carried out a case–control genetic study to analyze the association of PTPN22 R620W polymorphism (rs2476601 with disease susceptibility and clinical and autoantibody profile in Indian Tamils with SLE. Three hundred SLE patients satisfying the 1997 revised American College of Rheumatology classification criteria for SLE were enrolled in the study. Disease activity was measured using the SLE Disease Activity Index. We recruited 460 age-, sex-, and ethnicity-matched individuals without a family history of autoimmune diseases as control population. Genomic DNA was extracted from the blood sample by salting-out method. The PTPN22-1858C->T (rs2476601 polymorphism was screened by polymerase chain reaction-restriction fragment length polymorphism. Results: The frequency of the ancestral allele “C” was similar in both cases and controls (99.3% and 99.8%, respectively and the mutant allele “T” was less frequent in South Indian Tamil population; it did not influence clinical or serological phenotypes. Conclusion: Our findings suggest that the PTPN22 (rs2476601 polymorphism is less frequent and did not confer a risk for lupus or its associated clinical or serological phenotypes in South Indian Tamils.

  6. Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia.

    Science.gov (United States)

    Shunmugam, Vicneswari; Say, Yee-How

    2016-02-01

    α-adrenergic receptor 2A (ADRA2A) and angiotensin-converting enzyme (ACE) genes have been variably associated with obesity and its related phenotypes in different populations worldwide. This cross-sectional study aims to investigate the association of adrenergic receptor α2A (ADRA2A) rs553668 and angiotensin-converting enzyme (ACE) I/D single nucleotide polymorphisms (SNPs) with obesity traits (body mass index-BMI; waist-hip ratio-WHR; total body fat percentage - TBF) in a Malaysian population. Demographic and clinical variables were initially collected from 230 subjects via convenience sampling among residents and workers in Setapak, Malaysia, but in the end only 214 multi-ethnic Malaysians (99 males; 45 Malays, 116 ethnic Chinese, and 53 ethnic Indians) were available for statistical analysis. Genotyping was performed by polymerase chain reaction using DNA extracted from mouthwash samples. The overall minor allele frequencies (MAFs) for ADRA2A rs553668 and ACE I/D were 0.55 and 0.56, respectively. Allele distribution of ACE I/D was significantly associated with ethnicity and WHR class. Logistic regression analysis showed that subjects with the ACE II genotype and I allele were, respectively, 2.15 and 1.55 times more likely to be centrally obese, but when adjusted for age and ethnicity, this association was abolished. Covariate analysis controlling for age, gender, and ethnicity also showed similar results, where subjects carrying the II genotype or I allele did not have significantly higher WHR. Combinatory genotype and allele analysis for ADRA2A rs553668 and ACE I/D showed that subjects with both ADRA2A rs553668 GG and ACE I/D II genotypes had significant lowest WHR compared to other genotype combinations. The ACE II genotype might be a protective factor against central adiposity risk among the Malaysian population when in combination with the ADRA2A rs553668 GG genotype.

  7. PC interfacing using Centronics, RS232 and game ports

    CERN Document Server

    An, Pei

    1998-01-01

    The main links with your PC and the outside world are the centronic port, used for connecting the printer, the RS232 port, used for the mouse, and the games port for a joystick. This book explores how these input/output (I/O) ports can be put to use through a range of other interfacing applications. This is especially useful for laptop and palmtop PCs which cannot be fitted with internal I/O cards. A novel approach is taken by this book, combining the hardware through which the ports can be explored, and the software programming needed to carry out a range of experiments.Circuits are p

  8. Impact of polymorphisms in WFS1 on prediabetic phenotypes in a population-based sample of middle-aged people with normal and abnormal glucose regulation

    DEFF Research Database (Denmark)

    Sparsø, T; Andersen, G; Albrechtsen, Anders

    2008-01-01

    AIM/HYPOTHESIS: Recently, variants in WFS1 have been shown to be associated with type 2 diabetes. We aimed to examine metabolic risk phenotypes of WFS1 variants in glucose-tolerant people and in individuals with abnormal glucose regulation. METHODS: The type 2 diabetes-associated WFS1 variant rs7...

  9. PHENOTYPIC CORRELATIONS AND BODY WEIGHTS ...

    African Journals Online (AJOL)

    Dr Osondu

    Ethiopian Journal of Environmental Studies and Management Vol. 4 No.3 2011. PHENOTYPIC ... because of its high meat quality and acceptance by her populace. The meat is ... commands high price in the restaurants and markets than other ...

  10. The peptidylglycine-α-amidating monooxygenase (PAM) gene rs13175330 A>G polymorphism is associated with hypertension in a Korean population.

    Science.gov (United States)

    Yoo, Hye Jin; Kim, Minjoo; Kim, Minkyung; Chae, Jey Sook; Lee, Sang-Hyun; Lee, Jong Ho

    2017-11-21

    Peptidylglycine-α-amidating monooxygenase (PAM) may play a role in the secretion of atrial natriuretic peptide (ANP), which is a hormone involved in the maintenance of blood pressure (BP). The objective of the present study was to determine whether PAM is a novel candidate gene for hypertension (HTN). A total of 2153 Korean participants with normotension and HTN were included. Genotype data were obtained using the Korean Chip. The rs13175330 polymorphism of the PAM gene was selected from the ten single nucleotide polymorphisms (SNPs) most strongly associated with BP. The presence of the G allele of the PAM rs13175330 A>G SNP was associated with a higher risk of HTN after adjustments for age, sex, BMI, smoking, and drinking [OR 1.607 (95% CI 1.220-2.116), p = 0.001]. The rs13175330 G allele carriers in the HTN group treated without antihypertensive therapy (HTN w/o therapy) had significantly higher systolic and diastolic BP than the AA carriers, whereas the G allele carriers in the HTN group treated with antihypertensive therapy (HTN w/ therapy) showed significantly higher diastolic BP. Furthermore, rs13175330 G allele carriers in the HTN w/o therapy group had significantly increased levels of insulin, insulin resistance, and oxidized low-density lipoprotein (LDL) and significantly decreased LDL-cholesterol levels and LDL particle sizes compared to the AA carriers. These results suggest that the PAM rs13175330 A>G SNP is a novel candidate gene for HTN in the Korean population. Additionally, the PAM rs13175330 G allele might be associated with insulin resistance and LDL atherogenicity in patients with HTN.

  11. Polymorphism of rs7688672 and rs10033237 in cGKII/PRKG2 and gout susceptibility of Han population in northern China.

    Science.gov (United States)

    Guo, Min; Cheng, Zhifeng; Li, Changgui; Li, Shanshan; Li, Ming; Wang, Mingli; Xu, Jinmei; Tang, Yingying; Wang, Yujing; Qiu, Wenli; Liu, Xiaomin

    2015-05-10

    Gout is a genetic or acquired metabolic disease caused by increase of uric acid synthesis resulted from purine metabolic abnormalities. Whether cGMP-dependent protein kinase 2 (cGKII/PRKG2) is correlated with gout remains controversial. The objective of the present study was to investigate whether there is a correlation between polymorphism of cGKII/PRKG2 and gout susceptibility of Han population in northern China. Four hundred and five male patients with gout in the case group and 429 controls in the control group were collected from the Department of Endocrinology and Metabolic Disease, the Fourth Affiliated Hospital of Harbin Medical University. A case-control study method was used to study the correlation between cGKII/PRKG2 polymorphism rs7688672 and rs10033237 and gout susceptibility. The genotype frequencies of rs7688672 and rs10033237 polymorphisms of cGKII/PRKG2 in the case group and the control group both were in accordance with Hardy-Weinberg equilibrium. There were significant differences of rs10033237 in the allele frequencies and genotype distributions (Pgout. Combined mutation sites AA(*) from rs7688672 and rs10033237 were negatively correlated with gout susceptibility, whereas haplotype GG(*) was positively correlated with gout susceptibility. In conclusion, patients with rs10033237 polymorphism of cGKII/PRKG2 gene are more likely to suffer from gout. With regard to haplotypes of rs10033237 and rs7688672, both AA(*) and GG(*) are related to gout. AA(*) is a gout susceptible gene, whereas GG(*) is a protective gene. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms influence the risk of developing juvenile idiopathic arthritis in Han Chinese patients.

    Science.gov (United States)

    Fan, Zhi-Dan; Wang, Fei-Fei; Huang, Hui; Huang, Na; Ma, Hui-Hui; Guo, Yi-Hong; Zhang, Ya-Yuan; Qian, Xiao-Qing; Yu, Hai-Guo

    2015-01-01

    Juvenile idiopathic arthritis (JIA) is a common autoimmune disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The protein tyrosine phosphatase nonreceptor 22 (PTPN22) and signal transducer and activator of transcription factor 4 (STAT4) have been recognized as susceptibility genes for numerous autoimmune diseases. Associations of STAT4 rs7574865 G/T and PTPN22 (rs2488457 G/C and rs2476601 C/T) polymorphisms with JIA have repeatedly been replicated in several Caucasian populations. The aim of this study was to investigate the influence of three polymorphisms mentioned above on the risk of developing JIA in Han Chinese patients. Genotyping was performed on a total of 137 Chinese patients with JIA (JIA group) and 150 sex and age frequency-matched healthy volunteers (Control group). The single-nucleotide polymorphisms (SNP) were determined by using direct sequencing of PCR-amplified products. There were significant differences of PTPN22 rs2488457 G/C and STAT4 rs7574865 G/T polymorphisms between both groups. However, no significant difference was observed in distribution frequencies of PTPN22 rs2476601 polymorphism. The association with the PTPN22 rs2488457 G/C polymorphism remained significant in the stratifications by age at onset, ANA status, splenomegaly, lymphadenectasis and involvement joints. As with the STAT4 rs7574865 G/T polymorphisms, the enthesitis-related arthritis and presence of hepatomegaly had strong effect on the association. Our data strengthen STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms as susceptibility factors for JIA.

  13. STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms influence the risk of developing juvenile idiopathic arthritis in Han Chinese patients.

    Directory of Open Access Journals (Sweden)

    Zhi-Dan Fan

    Full Text Available Juvenile idiopathic arthritis (JIA is a common autoimmune disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The protein tyrosine phosphatase nonreceptor 22 (PTPN22 and signal transducer and activator of transcription factor 4 (STAT4 have been recognized as susceptibility genes for numerous autoimmune diseases. Associations of STAT4 rs7574865 G/T and PTPN22 (rs2488457 G/C and rs2476601 C/T polymorphisms with JIA have repeatedly been replicated in several Caucasian populations. The aim of this study was to investigate the influence of three polymorphisms mentioned above on the risk of developing JIA in Han Chinese patients. Genotyping was performed on a total of 137 Chinese patients with JIA (JIA group and 150 sex and age frequency-matched healthy volunteers (Control group. The single-nucleotide polymorphisms (SNP were determined by using direct sequencing of PCR-amplified products. There were significant differences of PTPN22 rs2488457 G/C and STAT4 rs7574865 G/T polymorphisms between both groups. However, no significant difference was observed in distribution frequencies of PTPN22 rs2476601 polymorphism. The association with the PTPN22 rs2488457 G/C polymorphism remained significant in the stratifications by age at onset, ANA status, splenomegaly, lymphadenectasis and involvement joints. As with the STAT4 rs7574865 G/T polymorphisms, the enthesitis-related arthritis and presence of hepatomegaly had strong effect on the association. Our data strengthen STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms as susceptibility factors for JIA.

  14. Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation

    Directory of Open Access Journals (Sweden)

    Martinez Fernando J

    2010-03-01

    Full Text Available Abstract Background Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. Methods We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster. Results We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1 post-bronchodilator FEV1 percent predicted, 2 percent bronchodilator responsiveness, and quantitative CT measurements of 3 apical emphysema and 4 airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1 emphysema predominant, 2 bronchodilator responsive, with higher FEV1; 3 discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4 airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant was associated with TGFB1 SNP rs1800470. Conclusions Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies.

  15. The DBP Phenotype Gc-1f/Gc-1f Is Associated with Reduced Risk of Cancer. The Tromsø Study.

    Directory of Open Access Journals (Sweden)

    Rolf Jorde

    Full Text Available In addition to its role as a transport protein, the vitamin D binding protein (DBP may also affect lipid metabolism, inflammation and carcinogenesis. There are three common variants of the DBP, Gc1s (1s, Gc1f (1f, Gc2 (2 that result in six common phenotypes (1s/1s, 1s/1f, 1s/2, 1f/1f, 1f/2, and 2/2. These phenotypes can be identified by genotyping for the two single nucleotide polymorphisms rs7041 and rs4588 in the GC gene. The DBP variants have different binding coefficients for the vitamin D metabolites, and accordingly there may be important relations between DBP phenotypes and health.DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI, type 2 diabetes (T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2010- 2013. Genotyping was performed for rs7041 and rs4588 and serum 25-hydroxyvitamin D (25(OHD was measured.Genotyping for rs7041 and rs4588 was performed successfully in 11 704 subjects. Among these, 1660 were registered with incident MI, 958 with T2DM, 2410 with cancer and 4318 had died. Subjects with the DBP phenotype 1f/1f had 23 - 26 % reduced risk of incident cancer compared to the 1s/1s and 2/2 phenotypes (P < 0.02, Cox regression with gender as covariate. Differences in serum 25(OHD levels could not explain the apparent cancer protective effect of the DBP variant 1f. In addition to cancer and 25(OHD, there were significant associations between DBP phenotype and body height, hip circumference and serum calcium.There are important biological differences between the common DBP phenotypes. If the relation between the DBP variant 1f and cancer is confirmed in other studies, determination of DBP phenotype may have clinical importance.

  16. Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.

    Directory of Open Access Journals (Sweden)

    Guilherme Suarez-Kurtz

    Full Text Available The influence of self-reported "race/color", geographical origin and genetic ancestry on the distribution of three functional CYP3A5 polymorphisms, their imputed haplotypes and inferred phenotypes was examined in 909 healthy, adult Brazilians, self-identified as White, Brown or Black ("race/color" categories of the Brazilian census. The cohort was genotyped for CYP3A5*3 (rs776746, CYP3A5*6 (rs10264272 and CYP3A5*7 (rs41303343, CYP3A5 haplotypes were imputed and CYP3A5 metabolizer phenotypes were inferred according to the number of defective CYP3A5 alleles. Estimates of the individual proportions of Amerindian, African and European ancestry were available for the entire cohort. Multinomial log-linear regression models were applied to infer the statistical association between the distribution of CYP3A5 alleles, haplotypes and phenotypes (response variables, and self-reported Color, geographical region and ancestry (explanatory variables. We found that Color per se or in combination with geographical region associates significantly with the distribution of CYP3A5 variant alleles and CYP3A5 metabolizer phenotypes, whereas geographical region per se influences the frequency distribution of CYP3A5 variant alleles. The odds of having the default CYP3A5*3 allele and the poor metabolizer phenotype increases continuously with the increase of European ancestry and decrease of African ancestry. The opposite trend is observed in relation to CYP3A5*6, CYP3A5*7, the default CYP3A5*1 allele, and both the extensive and intermediate phenotypes. No significant effect of Amerindian ancestry on the distribution of CYP3A5 alleles or phenotypes was observed. In conclusion, this study strongly supports the notion that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies, and dealt with as a continuous variable, rather than proportioned in arbitrary categories that do not capture the

  17. Childhood asthma-predictive phenotype.

    Science.gov (United States)

    Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

    2014-01-01

    Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Association of TNF-α rs1799964 and IL-1β rs16944 polymorphisms with multiple system atrophy in Chinese Han population.

    Science.gov (United States)

    Zhou, Xin; Wang, Chunrong; Chen, Zhao; Peng, Yun; Peng, Huirong; Hou, Xuan; Ye, Wei; Qiu, Rong; Xia, Kun; Tang, Beisha; Jiang, Hong

    2018-01-07

    Recent evidence suggested that several single nucleotide polymorphisms (SNPs) of inflammation-related genes (TNF-α rs1799964, IL-1α rs1800587, IL-1β rs16944, IL-8 rs4073, ICAM-1 rs5498) were associated with multiple system atrophy (MSA). Herein, we conducted this case-control study to evaluate the possible correlation between the five SNPs related to inflammation and MSA in Chinese Han population. We recruited 154 sporadic patients with MSA and 223 health controls in this study. All subjects were genotyped for the five SNPs using polymerase chain reaction amplification and Sanger sequencing. TNF-α rs1799964, genotype distribution and minor allele frequency (MAF) showed significant differences between patients and controls, which might illustrate the minor allele C may increase the risk for MSA (genotype, P = 0.006, OR = 1.245, 95% CI = [1.066-1.455]; allele, P = 0.001, OR = 1.887, 95% CI = [1.303-2.733]). For rs16944, patients carrying AA genotype showed a nearly 5-year early age at onset (AAO) than GG genotype (50.52 ± 7.45 years vs. 54.90 ± 7.21 years, P = 0.037). No differences were found in genotype distribution and MAF of the five SNPs between patients with MSA with predominant cerebellar ataxia (MSA-C) and with predominant Parkinsonism (MSA-P). Our study suggests that rs1799964 of TNF-α may act as a risk factor for MSA and the IL-1β rs16944 might be a genetic factor that modifies the AAO in MSA. Moreover, the exact mechanism of neuroinflammatory response in MSA deserves further exploration.

  19. Vad ersätter företagets avbrottsförsäkring?

    OpenAIRE

    Rosenqvist, Felix

    2010-01-01

    I arbetet redogörs för hur en avbrottsförsäkring är uppbyggd och hur ersättningen räknas ut i praktiken. I teoridelen behandlas försäkringshistoria, de frivilliga skadeförsäkringarna och mera djupgående avbrottsförsäkringen. Skadehanteringsprocessen beskrivs också i teoridelen. För att åskådliggöra ämnet har själva resultatredovisnigen förverkligats genom en fiktiv fallstudie. Detta för att göra det enklare för läsaren att förstå hur avbrottsförsäkringen fungerar i praktiken...

  20. Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children

    Directory of Open Access Journals (Sweden)

    Liu Ailing

    2010-09-01

    Full Text Available Abstract Background Fat-mass and obesity-associated (FTO gene is a gene located in chromosome region 16q12.2. Genetic variants in FTO are associated with the obesity phenotype in European and Hispanic populations. However, this association still remains controversial in Asian population. We aimed to test the association of FTO genetic variants with obesity and obesity-related metabolic traits among children living in Beijing, China. Methods We genotyped FTO variants rs9939609 in 670 children (332 girls and 338 boys aged 8-11 years living in Beijing, and analyzed its association with obesity and obesity-related metabolic traits. Overweight and obesity were defined by age- and sex-specific BMI reference for Chinese children. Obesity-related metabolic traits included fasting plasma glucose, lipid profiles, leptin, ghrelin, adiponectin and blood pressures. Results The frequency of rs9939609 A allele was 12.2%, which was 21.9% for the heterozygote and 1.2% for the homozygote of the A allele. The obesity prevalence among the carriers of AA/AT genotypes was significantly higher than that among those with TT genotype (36.4% vs. 22.6%, P = 0.004. Compared to the carrier of TT genotype, the likelihood of obesity was 1.79 (95% confidence interval (95% CI 1.20-2.67, P = 0.004 for the carrier of AA/AT genotype, after adjustment of sex, age and puberty stages. The BMI Z-score of children with AA/AT genotype were significantly higher than that of their counterparts with the TT genotype (1.1 ± 0.1 vs. 0.8 ± 0.1, P = 0.02. The concentration of triglyceride was 1.03 ± 0.52 mmol/L among TT carrier and 1.13 ± 0.68 mmol/L among AA/AT carrier (P = 0.045. While, the concentrations of adiponectin were 18.0 ± 0.4 μg/ml among carriers of TT and 16.2 ± 0.7 μg/ml among subjects with AA/AT genotype (P = 0.03. The level of glucose marginally increased in the AA/AT genotype subjects (4.67 ± 0.40 mmol/L vs. 4.60 ± 0.35 mmol/L, P = 0.08. The evidence of association

  1. The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.

    Directory of Open Access Journals (Sweden)

    Galina Lurie

    2011-02-01

    Full Text Available Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2. This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively. In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR  = 1.17; 95% confidence interval (CI: 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI, suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68. FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

  2. The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015.

    Science.gov (United States)

    Drake, Marcus J; Morris, Nicola; Apostolidis, Apostolos; Rahnama'i, Mohammad S; Marchesi, Julian R

    2017-04-01

    The microbiome is the term used for the symbiotic microbial colonisation of healthy organs. Studies have found bacterial identifiers within voided urine which is apparently sterile on conventional laboratory culture, and accordingly there may be health and disease implications. The International Consultation on Incontinence Research Society (ICI-RS) established a literature review and expert consensus discussion focussed on the increasing awareness of the urinary microbiome, and potential research priorities. The consensus considered the discrepancy between findings of conventional clinical microbiology methods, which generally rely on culture parameters predisposed towards certain "expected" organisms. Discrepancy between selective culture and RNA sequencing to study species-specific 16S ribosomal RNA is increasingly clear, and highlights the possibility that protective or harmful bacteria may be overlooked where microbiological methods are selective. There are now strong signals of the existence of a "core" urinary microbiome for the human urinary tract, particularly emerging with ageing. The consensus reviewed the potential relationship between a patient's microbiome and lower urinary tract dysfunction, whether low-count bacteriuria may be clinically significant and mechanisms which could associate micro-organisms with lower urinary tract symptoms. Key research priorities identified include the need to establish the scope of microbiome across the range of normality and clinical presentations, and gain consensus on testing protocols. Proteomics to study enzymatic and other functions may be necessary, since different bacteria may have overlapping phenotype. Longitudinal studies into risk factors for exposure, cumulative risk, and emergence of disease need to undertaken. Neurourol. Urodynam. 36:850-853, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Relationship between Lipid Phenotypes, Overweight, Lipid Lowering Drug Response and KIF6 and HMG-CoA Genotypes in a Subset of the Brisighella Heart Study Population

    Directory of Open Access Journals (Sweden)

    Sabrina Angelini

    2017-12-01

    Full Text Available The existence of genetic traits might explain the susceptibility to develop hypercholesterolemia and the inter-individual differences in statin response. This study was performed to evaluate whether individuals’ polymorphisms in HMG-CoA and KIF6 genes are independently associated with hypercholesterolemia, other lipid-associated traits, and statin response in unselected individuals enrolled in the Brisighella heart study (Survey 2012. A total of 1622 individuals, of which 183 under statin medication, were genotyped for a total of five polymorphisms (KIF6 rs20455, rs9471077, rs9462535; HMG-CoA rs3761740, rs3846662. The relationships between the five loci and clinical characteristics were analyzed. The principal basic parameters calculated on 12 h fasting blood included total cholesterol (TC, High Density Lipoprotein Cholesterol (HDL-C, Low-Density Lipoprotein Cholesterol (LDL-C, and triglycerides (TG. Hypercholesterolemia was defined as a TC >200 mg/dL or use of lipid-lowering medication. 965 individuals were characterized by hypercholesterolemia; these subjects were significantly older (p < 0.001, with body mass index (BMI and waist circumference significantly higher (p < 0.001 compared to the others. HMG-CoA rs3846662 GG genotype was significantly over-represented in the hypercholesterolemic group (p = 0.030. HMG-CoA rs3846662 genotype was associated with the level of TC and LDL-C. Furthermore, in the same subset of untreated subjects, we observed a significant correlation between the KIF6 rs20455 and HDL-C. KIF6 variants were associated with a significantly lower (rs20455 or higher (rs9471077 and rs9462535 risk of obesity, in males only. No association between responsiveness to statins and the polymorphisms under investigation were observed. Our results showed associations between HMG-CoA rs3846662 and KIF6 rs20455 and lipid phenotypes, which may have an influence on dyslipidemia-related events. Moreover, this represents the first study

  4. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona

    2016-01-01

    OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analy...

  5. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape

  6. Delineating SPTAN1 associated phenotypes

    DEFF Research Database (Denmark)

    Syrbe, Steffen; Harms, Frederike L; Parrini, Elena

    2017-01-01

    De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutati...

  7. The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study.

    Science.gov (United States)

    Khella, Mina S; Salem, Ahmed M; Abdel-Rahman, Omar; Saad, Amr S

    2018-02-01

    Despite the established link between malignant pleural mesothelioma (MPM) and asbestos exposure, genetic risk factors may play a key role in MPM pathogenesis. The rs9939609 polymorphism in the FTO gene has recently been implicated as a risk factor for some types of cancer, such as breast, pancreatic, and prostate cancers. FTO variation is associated with altered adipocytokine expression and oxidative stress inflammation, which may influence asbestos mediated-carcinogenesis. This is the first study to investigate a possible association between this polymorphism and MPM risk. FTO rs9939609 (T >A) genotypes were screened using a TaqMan ® Genotyping Assay in a total of 235 Egyptian subjects (86 MPM patients versus 149 controls). The chi-square test and logistic regression were used to evaluate the association between the candidate variant and MPM risk using a case-control design. In the additive genetic model, the AT and AA genotypes were associated with a 2.48-fold (95% confidence intervals [CI] = 1.04-5.92, p = 0.04) and a 3.46-fold (95% CI = 0.99-12.01, p = 0.051) increase in the odds of developing MPM, respectively, when compared to the TT genotype after adjustment for body mass index, age, and gender. Additionally, in the dominant genetic model AT/AA genotypes were associated with a 2.63-fold increase in the odds of developing MPM (95% CI = 1.13-6.12, p = 0.025). The present study shows for the first time that rs9939609 polymorphism in the FTO gene may be a genetic risk factor for MPM. This study highlights the association of this genetic polymorphism with cancer susceptibility, and therefore, it should be investigated in various other populations, in relation to different types of cancer, and with larger sample sizes.

  8. Enantioselective resolution of (R,S)-1-phenylethanol catalyzed by lipases immobilized in starch films

    International Nuclear Information System (INIS)

    Hoffmann, Isabel; Silva, Vanessa D.; Nascimento, Maria da G.

    2011-01-01

    Lipases from different sources and two mycelium-bound lipases, in a free or immobilized form, in ginger starch film were screened as biocatalysts in the reaction of (R,S)-1-phenylethanol (1) with vinyl acetate and other acylating agents. The effect of various reaction parameters in the resolution of (1) catalyzed by lipase from Burkholderia cepacia (BCL) immobilized in ginger starch film was evaluated (acyl donor type, alcohol:acyl donor molar ratio, temperature and organic solvent). The catalytic efficiency of BCL immobilized in polymeric blends of ginger starch and polyethylene oxide (PEO), in different compositions, was also studied. Vinyl acetate and iso-propenyl acetate furnished the highest conversion (9%) and enantiomeric excess (> 99%) of the (R)-ester. The alcohol:acyl donor molar ratio and temperature optimum were 1:1 and 28 deg respectively. The mixture of n-hexane/glycerol (9:1 v:v) was the most adequate for this reaction (conversion 23%, E > 200). The ginger starch/PEO (7:3 m/m) blend was successfully reused six times consecutively. (author)

  9. Enantioselective resolution of (R,S)-1-phenylethanol catalyzed by lipases immobilized in starch films

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Isabel; Silva, Vanessa D.; Nascimento, Maria da G., E-mail: graca@qmc.ufsc.b [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Quimica

    2011-07-01

    Lipases from different sources and two mycelium-bound lipases, in a free or immobilized form, in ginger starch film were screened as biocatalysts in the reaction of (R,S)-1-phenylethanol (1) with vinyl acetate and other acylating agents. The effect of various reaction parameters in the resolution of (1) catalyzed by lipase from Burkholderia cepacia (BCL) immobilized in ginger starch film was evaluated (acyl donor type, alcohol:acyl donor molar ratio, temperature and organic solvent). The catalytic efficiency of BCL immobilized in polymeric blends of ginger starch and polyethylene oxide (PEO), in different compositions, was also studied. Vinyl acetate and iso-propenyl acetate furnished the highest conversion (9%) and enantiomeric excess (> 99%) of the (R)-ester. The alcohol:acyl donor molar ratio and temperature optimum were 1:1 and 28 deg respectively. The mixture of n-hexane/glycerol (9:1 v:v) was the most adequate for this reaction (conversion 23%, E > 200). The ginger starch/PEO (7:3 m/m) blend was successfully reused six times consecutively. (author)

  10. Variation in the MC4R gene is associated with bone phenotypes in elderly Swedish women.

    Directory of Open Access Journals (Sweden)

    Gaurav Garg

    Full Text Available Osteoporosis is characterized by reduced bone mineral density (BMD and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs with body composition, BMD, Ultrasound (QUS, fracture and biomarkers (Homocysteine (Hcy, folate, Vitamin D and Vitamin B12 for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R; rs7566605 (insulin induced gene 2 (INSIG2; rs9939609 and rs1121980 (fat mass and obesity associated (FTO were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n = 1061 and OPRA (age 75, n = 1044. Body mass index (BMI, total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r(2 = 0.2-0.6. MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs.100 vs. 103 vs. 103; p = 0.002; (SOS: 1521 vs. 1526 vs. 1524; p = 0.008; (Stiffness index: 69 vs. 73 vs. 74; p = 0.0006 after adjustment for confounders. They also had low folate (18 vs. 17 vs. 16; p = 0.03 and vitamin D (93 vs. 91 vs. 90; p = 0.03 and high Hcy levels (13.7 vs 14.4 vs. 14.5; p = 0.06. Fracture incidence was lower among women with the C-allele, (52% vs. 58%; p = 0.067. Variation in MC4R was not associated with BMD or body composition in either OPRA or PEAK-25. SNPs close to FTO and INSIG2 were not associated with any bone phenotypes in either cohort and FTO SNPs were only associated with body composition in PEAK-25 (p≤0.001. Our results suggest that genetic variation close to MC4R is associated with quantitative ultrasound and risk of fracture.

  11. Functional variants of the dopamine receptor D2 gene modulate prefronto-striatal phenotypes in schizophrenia.

    Science.gov (United States)

    Bertolino, Alessandro; Fazio, Leonardo; Caforio, Grazia; Blasi, Giuseppe; Rampino, Antonio; Romano, Raffaella; Di Giorgio, Annabella; Taurisano, Paolo; Papp, Audrey; Pinsonneault, Julia; Wang, Danxin; Nardini, Marcello; Popolizio, Teresa; Sadee, Wolfgang

    2009-02-01

    Dopamine D2 receptor signalling is strongly implicated in the aetiology of schizophrenia. We have recently characterized the function of three DRD2 SNPs: rs12364283 in the promoter affecting total D2 mRNA expression; rs2283265 and rs1076560, respectively in introns 5 and 6, shifting mRNA splicing to two functionally distinct isoforms, the short form of D2 (D2S) and the long form (D2L). These two isoforms differentially contribute to dopamine signalling in prefrontal cortex and in striatum. We performed a case-control study to determine association of these variants and of their main haplotypes with several schizophrenia-related phenotypes. We demonstrate that the minor allele in the intronic variants is associated with reduced expression of %D2S of total mRNA in post-mortem prefrontal cortex, and with impaired working memory behavioural performance, both in patients and controls. However, the fMRI results show opposite effects in patients compared with controls: enhanced engagement of prefronto-striatal pathways in controls and reduced activity in patients. Moreover, the promoter variant is also associated with working memory activity in prefrontal cortex and striatum of patients, and less robustly with negative symptoms scores. Main haplotypes formed by the three DRD2 variants showed significant associations with these phenotypes consistent with those of the individual SNPs. Our results indicate that the three functional DRD2 variants modulate schizophrenia phenotypes possibly by modifying D2S/D2L ratios in the context of different total D2 density.

  12. SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area.

    Science.gov (United States)

    Stanislovaitiene, Daiva; Zaliuniene, Dalia; Krisciukaitis, Algimantas; Petrolis, Robertas; Smalinskiene, Alina; Lesauskaite, Vita; Tamosiunas, Abdonas; Lesauskaite, Vaiva

    2017-01-01

    Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area. The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method. Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380-0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00-39.06) vs. 3.09 (0.02-19.30) and 0.27 (0.00-34.57) vs. 0.75 (0.00-39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49-39.06) mm 2 vs. 5.02 (0.03-37.06) mm 2 , p = 0.006). SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease-an area of macular lesion.

  13. Interoperability between phenotype and anatomy ontologies.

    Science.gov (United States)

    Hoehndorf, Robert; Oellrich, Anika; Rebholz-Schuhmann, Dietrich

    2010-12-15

    Phenotypic information is important for the analysis of the molecular mechanisms underlying disease. A formal ontological representation of phenotypic information can help to identify, interpret and infer phenotypic traits based on experimental findings. The methods that are currently used to represent data and information about phenotypes fail to make the semantics of the phenotypic trait explicit and do not interoperate with ontologies of anatomy and other domains. Therefore, valuable resources for the analysis of phenotype studies remain unconnected and inaccessible to automated analysis and reasoning. We provide a framework to formalize phenotypic descriptions and make their semantics explicit. Based on this formalization, we provide the means to integrate phenotypic descriptions with ontologies of other domains, in particular anatomy and physiology. We demonstrate how our framework leads to the capability to represent disease phenotypes, perform powerful queries that were not possible before and infer additional knowledge. http://bioonto.de/pmwiki.php/Main/PheneOntology.

  14. RsComm User Manual. Data system for the control of continuous recording measuring instruments (monitors); RsComm brukermanual. Datasystem for kontroll av kontinuerlig registrerende maaleinstrumenter (monitorer)

    Energy Technology Data Exchange (ETDEWEB)

    Marsteen, L.

    1996-02-01

    Norwegian Institute for Air Research (NILU) has, as a part of the quality control systems, developed an automatic system of data recording. This report describes the installation and use of the RsComm software. Using RsComm and a NILU data recorder it is possible to run system tests on air quality analyzers via a telephone line. Test reports are generated. 17 figs.

  15. Polymorphisms of transforming growth factor beta 1 (RS#1800468 and RS#1800471) and esophageal squamous cell carcinoma among Zhuangese population, China.

    Science.gov (United States)

    Tang, Ren-Guang; Huang, Yong-Zhi; Yao, Li-Min; Xiao, Jian; Lu, Chuan; Yu, Qian

    2013-01-01

    Epidemiological evidence has shown two polymorphisms (namely RS#1800468G>A and RS#1800471G>C) of transforming growth factor-beta 1 (TGF-β1) gene may be involved in the cancer development. However, their role in the carcinogenic process of esophageal squamous cell carcinoma (ESCC) has been less well elaborated. We conducted a hospital-based case-control study including 391 ESCC cases and 508 controls without any evidence of tumors to evaluate the association between these two polymorphisms and ESCC risk and prognosis for Zhuangese population by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS)-PCR techniques. We found that individuals with the genotypes with RS#1800471 C allele (namely RS#1800471-GC or -CC) had an increased risk of ESCC than those without above genotypes (namely RS#1800471-GG, adjusted odds ratio 3.26 and 5.65, respectively). Further stratification analysis showed that this polymorphism was correlated with tumor histological grades and TNM (tumor, node, and metastasis) stage, and modified the serum levels of TGF-β1. Additionally, RS#1800471 polymorphism affected ESCC prognosis (hazard ratio, 3.40), especially under high serum levels of TGF-β1 conditions. However, RS#1800468 polymorphism was not significantly related to ESCC risk. These findings indicated that TGF-β1 RS#1800471G>C polymorphism may be a genetic modifier for developing ESCC in Zhuangese population. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Association of FLG single nucleotide variations with clinical phenotypes of atopic dermatitis.

    Directory of Open Access Journals (Sweden)

    Myungshin Kim

    Full Text Available FLG encodes a large protein called profilaggrin, which plays a key role in maintaining an effective skin barrier against the environment. In this study, we identified FLG single nucleotide variations (FLG-SNVs and evaluated the association of FLG-SNVs with clinical phenotypes including atopic dermatitis (AD-associated minor clinical features, presence of specific allergic sensitization, and serum parameters.Eighty-one Korean patients with AD were enrolled. AD-associated minor clinical features as well as allergic rhinitis and asthma were diagnosed by specialists. FLG-SNVs were identified by Sanger sequencing of entire exons through long-range PCR. Allergic sensitization to a specific allergen was evaluated by multiple allergen simultaneous test. Serologic parameters such as serum eosinophil cationic protein (ECP and eosinophil derived neurotoxin (EDN were measured.A total of seventy-three SNVs and 4 LOF mutations were successfully genotyped. rs71626704 and rs76413899 were significantly associated with a history of asthma and cheilitis (P = 0.002 and P = 0.033, respectively, however, the associations were not found statistically significant after adjustment by multiple comparisons. In addition, we detected haplotype blocks which were correlated with non-specific hand or foot dermatitis and scalp scale. We identified FLG-SNVs which were associated with sensitization to environmental allergens; rs62623409 and rs71625199 (P = 0.038 and P = 0.008, respectively. Patients with FLG P478S TT and history of allergic rhinitis showed a higher EDN level, and among those patients, the ones with asthma showed a higher ECP level.This study revealed the association of FLG-SNVs with AD-associated minor clinical features. We firstly identified rs71625199 which was associated with higher environmental allergic sensitization. We also suggest that FLG P478S is a kind of disease modifier which affects serologic parameters such as EDN and ECP.

  17. Polymorphic Variants rs3088442 and rs2292334 in the Organic Cation Transporter 3 (OCT3) Gene and Susceptibility Against Type 2 Diabetes: Role of their Interaction.

    Science.gov (United States)

    Mahrooz, Abdolkarim; Alizadeh, Ahad; Hashemi-Soteh, Mohammad Bagher; Ghaffari-Cherati, Maryam; Hosseyni-Talei, Seyyedeh Raheleh

    2017-02-01

    In this study, we investigated whether two common variants (rs3088442G>A and rs2292334G>A) in the organic cation transporter 3 (OCT3) gene, a high-capacity transporter widely expressed in various tissues, affect susceptibility to type 2 diabetes (T2D) in patients newly diagnosed with T2D. We performed a study with 150 newly diagnosed patients with T2D and 152 controls. The genetic analyses were performed using the restricted fragment length polymorphism (RFLP) after PCR amplification. For the rs3088442G>A variant, A allele carriers had a significantly lower odds ratio (OR) vs. GG homozygotes in the BMI A variant was associated with a decreased risk of T2D (OR = 0.016, p A in the 3'-untranslated region of the OCT3 gene in susceptibility to T2D, and that the protective role is maintained in the presence of risky alleles of the variant rs2292334G>A. The association of the A allele of rs3088442G>A with T2D become weaker in obese people than that of non-obese. If confirmed in other populations, the rs3088442G>A variant as a genetic marker may potentially assist in the identification of individuals at an increased risk of T2D. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  18. Endoplasmic reticulum stress mediating downregulated StAR and 3-beta-HSD and low plasma testosterone caused by hypoxia is attenuated by CPU86017-RS and nifedipine

    Directory of Open Access Journals (Sweden)

    Liu Gui-Lai

    2012-01-01

    Full Text Available Abstract Background Hypoxia exposure initiates low serum testosterone levels that could be attributed to downregulated androgen biosynthesizing genes such as StAR (steroidogenic acute regulatory protein and 3-beta-HSD (3-beta-hydroxysteroid dehydrogenase in the testis. It was hypothesized that these abnormalities in the testis by hypoxia are associated with oxidative stress and an increase in chaperones of endoplasmic reticulum stress (ER stress and ER stress could be modulated by a reduction in calcium influx. Therefore, we verify that if an application of CPU86017-RS (simplified as RS, a derivative to berberine could alleviate the ER stress and depressed gene expressions of StAR and 3-beta-HSD, and low plasma testosterone in hypoxic rats, these were compared with those of nifedipine. Methods Adult male Sprague-Dawley rats were randomly divided into control, hypoxia for 28 days, and hypoxia treated (mg/kg, p.o. during the last 14 days with nifedipine (Nif, 10 and three doses of RS (20, 40, 80, and normal rats treated with RS isomer (80. Serum testosterone (T and luteinizing hormone (LH were measured. The testicular expressions of biomarkers including StAR, 3-beta-HSD, immunoglobulin heavy chain binding protein (Bip, double-strand RNA-activated protein kinase-like ER kinase (PERK and pro-apoptotic transcription factor C/EBP homologous protein (CHOP were measured. Results In hypoxic rats, serum testosterone levels decreased and mRNA and protein expressions of the testosterone biosynthesis related genes, StAR and 3-beta-HSD were downregulated. These changes were linked to an increase in oxidants and upregulated ER stress chaperones: Bip, PERK, CHOP and distorted histological structure of the seminiferous tubules in the testis. These abnormalities were attenuated significantly by CPU86017-RS and nifedipine. Conclusion Downregulated StAR and 3-beta-HSD significantly contribute to low testosterone in hypoxic rats and is associated with ER stress

  19. Cluster analysis of obesity and asthma phenotypes.

    Directory of Open Access Journals (Sweden)

    E Rand Sutherland

    Full Text Available Asthma is a heterogeneous disease with variability among patients in characteristics such as lung function, symptoms and control, body weight, markers of inflammation, and responsiveness to glucocorticoids (GC. Cluster analysis of well-characterized cohorts can advance understanding of disease subgroups in asthma and point to unsuspected disease mechanisms. We utilized an hypothesis-free cluster analytical approach to define the contribution of obesity and related variables to asthma phenotype.In a cohort of clinical trial participants (n = 250, minimum-variance hierarchical clustering was used to identify clinical and inflammatory biomarkers important in determining disease cluster membership in mild and moderate persistent asthmatics. In a subset of participants, GC sensitivity was assessed via expression of GC receptor alpha (GCRα and induction of MAP kinase phosphatase-1 (MKP-1 expression by dexamethasone. Four asthma clusters were identified, with body mass index (BMI, kg/m(2 and severity of asthma symptoms (AEQ score the most significant determinants of cluster membership (F = 57.1, p<0.0001 and F = 44.8, p<0.0001, respectively. Two clusters were composed of predominantly obese individuals; these two obese asthma clusters differed from one another with regard to age of asthma onset, measures of asthma symptoms (AEQ and control (ACQ, exhaled nitric oxide concentration (F(ENO and airway hyperresponsiveness (methacholine PC(20 but were similar with regard to measures of lung function (FEV(1 (% and FEV(1/FVC, airway eosinophilia, IgE, leptin, adiponectin and C-reactive protein (hsCRP. Members of obese clusters demonstrated evidence of reduced expression of GCRα, a finding which was correlated with a reduced induction of MKP-1 expression by dexamethasoneObesity is an important determinant of asthma phenotype in adults. There is heterogeneity in expression of clinical and inflammatory biomarkers of asthma across obese individuals

  20. Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10.

    Science.gov (United States)

    Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

    2014-09-01

    Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.

  1. Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.

    Science.gov (United States)

    Ferreira, Manuel A R; Matheson, Melanie C; Tang, Clara S; Granell, Raquel; Ang, Wei; Hui, Jennie; Kiefer, Amy K; Duffy, David L; Baltic, Svetlana; Danoy, Patrick; Bui, Minh; Price, Loren; Sly, Peter D; Eriksson, Nicholas; Madden, Pamela A; Abramson, Michael J; Holt, Patrick G; Heath, Andrew C; Hunter, Michael; Musk, Bill; Robertson, Colin F; Le Souëf, Peter; Montgomery, Grant W; Henderson, A John; Tung, Joyce Y; Dharmage, Shyamali C; Brown, Matthew A; James, Alan; Thompson, Philip J; Pennell, Craig; Martin, Nicholas G; Evans, David M; Hinds, David A; Hopper, John L

    2014-06-01

    To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10(-8)). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10(-6)). By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  2. Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility

    Directory of Open Access Journals (Sweden)

    Guangyuan Chen

    2015-05-01

    Full Text Available Large-scale genome-wide association studies (GWAS have revealed that rs10757278 polymorphism (or its proxy rs1333049 on chromosome 9p21 is associated with myocardial infarction (MI susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported weak or no significant association. Here, we reevaluated this association using large-scale samples by searching PubMed and Google Scholar databases. Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10−22, odds ratio (OR = 1.29, 95% confidence interval (CI 1.22–1.36 in pooled population. We further performed a subgroup analysis, and found significant association between rs10757278 polymorphism and MI in Asian and Caucasian populations. We identified that the association between rs10757278 polymorphism and MI did not vary substantially by excluding any one study. However, the heterogeneity among the selected studies varies substantially by excluding the study from the Pakistan population. We found even more significant association between rs10757278 polymorphism and MI in pooled population, p = 3.55 × 10−53, after excluding the study from the Pakistan population. In summary, previous studies reported weak or no significant association between rs10757278 polymorphism and MI. Interestingly, our analysis suggests that rs10757278 polymorphism is significantly associated with MI susceptibility by analyzing large-scale samples.

  3. Association between BDNF-rs6265 and obesity in the Boston Puerto Rican Health Study

    Science.gov (United States)

    The objective of this study is to examine a functional variant (rs6265) in the BDNF gene interacting with dietary intake modulate obesity traits in the Boston Puerto Rican Health Study population. BDNF rs6265 was genotyped in 1147 Puerto Ricans (aged 45-75 years), and examined for association with o...

  4. rs3806268 of NLRP3 gene polymorphism is associated with the development of primary gout.

    Science.gov (United States)

    Deng, Jianping; Lin, Wen; Chen, Yunpeng; Wang, Xin; Yin, Zhong; Yao, Chunhong; Liu, Tangbing; Lv, Yonghong

    2015-01-01

    The aim of the present study was to investigate the association between seven functional SNPs in NALP3 gene and the susceptibility to primary gout. A total of 247 patients with primary gout and 247 controls were selected in this study. Genotyping of NALP3 rs4612666, rs3806268, rs12239046, rs10754558, rs7512998, rs12137901 and rs12565738 was performed using the Sequenom MassARRAY platform. Comparison analysis showed that primary gout patients were more likely to have a higher body mass index, DBP, SBP, TG, urea nitrogen and uric acid (P gout when compared with the AA genotype (OR=1.83, 95% CI=1.03-3.26). However, no significant associations were identified for the remaining SNPs. In conclusion, we found a significant association between rs3806268 in NLRP3 gene and the risk of primary gout in a Chinese population. Further clinical and genetic studies are required to investigate the mechanisms underlying the association between NALP3 polymorphisms and the development of primary gout.

  5. Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus.

    Science.gov (United States)

    Sakiyama, Masayuki; Matsuo, Hirotaka; Nakaoka, Hirofumi; Yamamoto, Ken; Nakayama, Akiyoshi; Nakamura, Takahiro; Kawai, Sayo; Okada, Rieko; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-05-16

    Gout is a common disease resulting from hyperuricemia. Recently, a genome-wide association study identified an association between gout and a single nucleotide polymorphism (SNP) rs2188380, located on an intergenic region between MYL2 and CUX2 on chromosome 12. However, other genes around rs2188380 could possibly be gout susceptibility genes. Therefore, we performed a fine-mapping study of the MYL2-CUX2 region. From 8,595 SNPs in the MYL2-CUX2 region, 9 tag SNPs were selected, and genotyping of 1,048 male gout patients and 1,334 male controls was performed by TaqMan method. Eight SNPs showed significant associations with gout after Bonferroni correction. rs671 (Glu504Lys) of ALDH2 had the most significant association with gout (P = 1.7 × 10(-18), odds ratio = 0.53). After adjustment for rs671, the other 8 SNPs no longer showed a significant association with gout, while the significant association of rs671 remained. rs671 has been reportedly associated with alcohol drinking behavior, and it is well-known that alcohol drinking elevates serum uric acid levels. These data suggest that rs671, a common functional SNP of ALDH2, is a genuine gout-associated SNP in the MYL2-CUX2 locus and that "A" allele (Lys) of rs671 plays a protective role in the development of gout.

  6. The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

    DEFF Research Database (Denmark)

    Pharoah, Paul D P; Palmieri, Rachel T; Ramus, Susan J

    2011-01-01

    PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene, and is a cand...

  7. Polymorphism of glucagon-like peptide-1 receptor gene (rs1042044 ...

    African Journals Online (AJOL)

    patience

    2015-02-16

    Feb 16, 2015 ... turnover via GLP-1 receptors (GLP1Rs) in postmenopausal state. Furthermore, polymorphisms in. GLP1R gene were suggested to affect the function of GLP1Rs and be associated with many diseases. However, the relationships between GLP1R polymorphisms and osteoporosis susceptibility and bone.

  8. Polymorphism of glucagon-like peptide-1 receptor gene (rs1042044 ...

    African Journals Online (AJOL)

    Previous investigations indicated that glucagon-like peptide-1 (GLP-1) played important roles in bone turnover via GLP-1 receptors (GLP1Rs) in postmenopausal state. Furthermore, polymorphisms in GLP1R gene were suggested to affect the function of GLP1Rs and be associated with many diseases. However, the ...

  9. The Composition and Metabolic Phenotype of Neisseria gonorrhoeae Biofilms

    Directory of Open Access Journals (Sweden)

    Michael A Apicella

    2011-04-01

    Full Text Available N. gonorrhoeae has been shown to form biofilms during cervical infection. Thus, biofilm formation may play an important role in the infection of women. The ability of N. gonorrhoeae to form membrane blebs is crucial to biofilm formation. Blebs contain DNA and outer membrane structures, which have been shown to be major constituents of the biofilm matrix. The organism expresses a DNA thermonuclease that is involved in remodeling of the biofilm matrix. Comparison of the transcriptional profiles of gonococcal biofilms and planktonic runoff indicate that genes involved in anaerobic metabolism and oxidative stress tolerance are more highly expressed in biofilm. The expression of aniA, ccp, and norB, which encode nitrite reductase, cytochrome c peroxidase, and nitric oxide reductase respectively, is required for mature biofilm formation over glass and human cervical cells. In addition, anaerobic respiration occurs in the substratum of gonococcal biofilms and disruption of the norB gene required for anaerobic respiration, results in a severe biofilm attenuation phenotype. It has been demonstrated that accumulation of nitric oxide (NO contributes to the phenotype of a norB mutant and can retard biofilm formation. However, NO can also enhance biofilm formation, and this is largely dependent on the concentration and donation rate or steady state kinetics of NO. The majority of the genes involved in gonococcal oxidative stress tolerance are also required for normal biofilm formation, as mutations in the following genes result in attenuated biofilm formation over cervical cells and/or glass: oxyR, gor, prx, mntABC, trxB, and estD. Overall, biofilm formation appears to be an adaptation for coping with the environmental stresses present in the female genitourinary tract. Therefore, this review will discuss the studies, which describe the composition and metabolic phenotype of gonococcal biofilms.

  10. 'Fat mass and obesity associated' gene (FTO: No significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents

    Directory of Open Access Journals (Sweden)

    Müller Timo D

    2008-09-01

    Full Text Available Abstract Background We have previously identified strong association of six single nucleotide polymorphisms (SNPs in FTO (fat mass and obesity associated gene to early onset extreme obesity within the first genome wide association study (GWA for this phenotype. The aim of this study was to investigate whether the obesity risk allele of one of these SNPs (rs9939609 is associated with weight loss in a lifestyle intervention program. Additionally, we tested for association of rs9939609 alleles with fasting blood parameters indicative of glucose and lipid metabolism. Methods We initially analysed rs9939609 in a case-control study comprising 519 German overweight and obese children and adolescents and 178 normal weight adults. In 207 of the obese individuals who took part in the outpatient obesity intervention program 'Obeldicks' we further analysed whether carrier status of the obesity risk A-allele of rs9939609 has a differential influence on weight loss after the intervention program. Additionally, we investigated in 480 of the overweight and obese patients whether rs9939609 is associated with fasting blood levels of glucose, triglycerides and HDL and LDL-cholesterol. Genotyping was performed using allele specific polymerase chain reaction (ARMS-PCR. For the association study (case-control approach, the Cochran-Armitage trend test was applied. Blood parameters were analysed using commercially available test kits and the log10-transformed blood parameters and changes in BMI-standard deviation scores (BMI-SDS were analysed by linear regression with sex and age as covariates under an additive mode of inheritance with the rs9939609 A-allele as risk allele. Results We confirmed the association of the risk A-allele of rs9939609 with overweight and early onset obesity (one sided p = 0.036. However, we observed no association of rs9939609 alleles with weight loss or fasting levels of blood glucose, triglycerides and cholesterol. Conclusion We confirmed

  11. Pentatomids associated with different forest species in Itaara, RS, Brazil

    Directory of Open Access Journals (Sweden)

    Ervandil Corrêa Costa

    2010-03-01

    Full Text Available The objective of this study was to determine qualitatively and quantitatively the pentatomid fauna associated with the canopy of different native species during the period from September 2005 to September 2006. Insects were collected from among nine botanical species: Gochnatia polymorpha (Less. (cambará, Eugenia uniflora Berg. (pitangueira, Acca selowiana (Berg Burret (goiaba-da-serra, Psidium cattleianum Sabine (araçá, Baccharis spp., Solanaum mauritianum Scop. (fumo-bravo, Micanea cinerascens Miq. (passiquinho, Calliandra brevipes Bhent. (caliandra, and Schinus molle L. (aroeira located at Rodolfo da Costa Dam in Itaara, RS, Brazil. Samples were taken every two weeks with a conical funnel made of tin plate (2mm, 70cm in diameter at the rim and 63cm in height. One sample per botanical species for each sampling date was taken, by shaking the branches, ten times over the funnel. Samples were sent to the Entomology Laboratory of the Crop Protection Department of the Federal University of Santa Maria, where the material was analyzed. A total of nine Pentatomidae species were identified. Edessa rufomarginata (De Geer, 1773 was the species of highest ocurrence followed by Thyanta humilis (Bergroth, 1891. The botanical species S. mauritianum presented the greatest number of Pentatomidae species, with an occurrence of 26.9%.

  12. RASSF1A and the rs2073498 Cancer Associated SNP

    International Nuclear Information System (INIS)

    Donninger, Howard; Barnoud, Thibaut; Nelson, Nick; Kassler, Suzanna; Clark, Jennifer; Cummins, Timothy D.; Powell, David W.; Nyante, Sarah; Millikan, Robert C.; Clark, Geoffrey J.

    2011-01-01

    RASSF1A is one of the most frequently inactivated tumor suppressors yet identified in human cancer. It is pro-apoptotic and appears to function as a scaffolding protein that interacts with a variety of other tumor suppressors to modulate their function. It can also complex with the Ras oncoprotein and may serve to integrate pro-growth and pro-death signaling pathways. A SNP has been identified that is present in approximately 29% of European populations [rs2073498, A(133)S]. Several studies have now presented evidence that this SNP is associated with an enhanced risk of developing breast cancer. We have used a proteomics based approach to identify multiple differences in the pattern of protein/protein interactions mediated by the wild type compared to the SNP variant protein. We have also identified a significant difference in biological activity between wild type and SNP variant protein. However, we have found only a very modest association of the SNP with breast cancer predisposition.

  13. Water quality assessment of the Sinos River – RS, Brazil

    Directory of Open Access Journals (Sweden)

    C. Steffens

    Full Text Available Worldwide environmental pollution is increasing at the same rate as social and economic development. This growth, however, is disorganized and leads to increased degradation of water resources. Water, which was once considered inexhaustible, has become the focus of environmental concerns because it is essential for life and for many production processes. This article describes monitoring of the water quality at three points along the Sinos River (RS, Brazil, one in each of the upper, middle and lower stretches. The points were sampled in 2013 and again in 2014. The water samples were analyzed to determine the following physical and chemical parameters plus genotoxicity to fish: metals (Cr, Fe, Al, chemical oxygen demand, biochemical oxygen demand, chlorides, conductivity, total suspended solids, total phosphorous, total and fecal coliforms, pH, dissolved oxygen, turbidity, total Kjeldahl nitrogen nitrate and ammoniacal nitrogen. Genotoxicity was tested by exposing individuals of the species Astyanax jacuhiensis to water samples and then comparing them with a control group exposed to water from the public water supply. The results confirmed the presence of substances with genotoxic potential at the sample points located in the middle and lower stretches of the river. The results for samples from the upper stretch, at P1, did not exhibit differences in relation to the control group. The physical and chemical analyses did not detect reductions in water quality in the lower stretch, as had been expected in view of the large volumes of domestic and industrial effluents discharged into this part of the river.

  14. Performance Characterization of RaPToRS Systems

    Science.gov (United States)

    Shibata, K.; Krieger, M.; Fallica, J.; Henchen, R.; Pogozelski, E.; Padalino, S.; SUNY Geneseo Collaboration; LaboratoryLaser Energetics at University of Rochester Collaboration

    2011-10-01

    The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system can quickly and efficiently move radioactive materials from their activation site to a counting station. Facilities such as the NIF and LLE are considering these systems while NRL is currently using one. The system is essentially a 10 cm diameter pneumatic tube with a cylindrical sample carrier. The performance of the system depends on many factors, including the mass of the carrier, length of the tube, angle and difference in height of the tube's endpoints, the carrier's physical design, and the number, type, and distribution of blowers attached to the tube. These factors have been systematically examined to develop the fastest and most reliable system. The most significant factors are the mass and the vertical travel of the carrier. When the carrier mass is low, moving air supports the carrier in the tube, resulting in low friction. The terminal velocity ranges from 13.5 to 2.5 m/s for masses varying from 1 kg to 3 kg. Using a single 1100 W blower, the initial force exerted on the carrier was 11.3 N. This work was supported in part by the US Department of Energy through the LLE.

  15. Rapid Pneumatic Transport of Radioactive Samples - RaPToRS

    Science.gov (United States)

    Padalino, S.; Barrios, M.; Sangster, C.

    2005-10-01

    Some ICF neutron activation diagnostics require quick retrieval of the activated sample. Minimizing retrieval times is particularly important when the half-life of the activated material is on the order of the transport time or the degree of radioactivity is close to the background counting level. These restrictions exist in current experiments performed at the Laboratory for Laser Energetics, thus motivating the development of the RaPToRS system. The system has been designed to minimize transportation time while requiring no human intervention during transport or counting. These factors will be important if the system is to be used at the NIF where radiological hazards will be present during post activation. The sample carrier is pneumatically transported via a 4 inch ID PVC pipe to a remote location in excess of 100 meters from the activation site at a speed of approximately 7 m/s. It arrives at an end station where it is dismounted robotically from the carrier and removed from its hermetic package. The sample is then placed by the robot in a counting station. This system is currently being developed to measure back-to-back gamma rays produced by positron annihilation which were emitted by activated graphite. Funded in part by the U.S. DOE under sub contract with LLE at the University of Rochester.

  16. Diagnosis of the retail flower market of Santa Maria, RS

    Directory of Open Access Journals (Sweden)

    Janine Farias Menegaes

    2015-12-01

    Full Text Available The present study aimed to diagnose the flowers retail market and ornamental plants in Santa Maria, RS, Brazil, by means of a research in loco, from January to June of 2013, based on questionnaires and interviews applied to the managers of the establishment, as well as of an application of a visual and phytosanitary scale to other establishments that sell flowers and ornamental plants, such as agricultural shops, fairs of horticultural products, supermarkets and providers of funeral services - cemeteries and funeral homes. The diagnosis aims to know the steps of the dynamics observed from the market of flowers until the final consumer, and to segment the types of floricultures, distinguishing them according to the commercial focus — floricultures of arrangements and bouquets, and producing flowers and landscape floricultures. Based on the diagnosis it can be concluded that the Santa Maria retail flowers and ornamental plants follows the national trend of floral arrangements and bouquets shops, with the increase of the companies focused on landscaping and gardening. Among the most marketed plants are the rose as the best-selling cut flower, the begonia as potted flower, the fern for foliage arrangements, the cactus as potted plant, the raffia as garden plant and the pansy as the best-selling plant in boxes.

  17. Automated phenotyping of permanent crops

    Science.gov (United States)

    McPeek, K. Thomas; Steddom, Karl; Zamudio, Joseph; Pant, Paras; Mullenbach, Tyler

    2017-05-01

    AGERpoint is defining a new technology space for the growers' industry by introducing novel applications for sensor technology and data analysis to growers of permanent crops. Serving data to a state-of-the-art analytics engine from a cutting edge sensor platform, a new paradigm in precision agriculture is being developed that allows growers to understand the unique needs of each tree, bush or vine in their operation. Autonomous aerial and terrestrial vehicles equipped with multiple varieties of remote sensing technologies give AGERpoint the ability to measure key morphological and spectral features of permanent crops. This work demonstrates how such phenotypic measurements combined with machine learning algorithms can be used to determine the variety of crops (e.g., almond and pecan trees). This phenotypic and varietal information represents the first step in enabling growers with the ability to tailor their management practices to individual plants and maximize their economic productivity.

  18. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  19. Phenotypic deconstruction of gene circuitry

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  20. The ARIES-RS power core - recent development in Li/V designs

    International Nuclear Information System (INIS)

    Sze Dai-Kai; Billone, M.C.; Hua, T.Q.; Tillack, M.; Najmabadi, F.; Wang Xueren; Malang, S.; El-Guebaly, L.A.; Sviatoslavsky, I.N.; Blanchard, J.P.; Crowell, J.A.; Khater, H.Y.; Mogahed, E.A.; Waganer, L.M.; Lee, D.; Cole, D.

    1998-01-01

    The ARIES-RS fusion power plant design study is based on reversed-shear (RS) physics with a Li/V (lithium breeder and vanadium structure) blanket. The reversed-shear discharge has been documented in many large tokamak experiments. The plasma in the RS mode has a high beta, low current, and low current drive requirement. Therefore, it is an attractive physics regime for a fusion power plant. The blanket system based on Li/V has high temperature operating capability, good tritium breeding, excellent high heat flux removal capability, long structural life time, low activation, low after heat and good safety characteristics. For these reasons, the ARIES-RS reactor study selected Li/V as the reference blanket. The combination of attractive physics and attractive blanket engineering is expected to result in a superior power plant design. This paper summarizes the power core design of the ARIES-RS power plant study. (orig.)

  1. Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis: a meta-analysis.

    Science.gov (United States)

    Lee, Young Ho; Woo, Jin-Hyun; Choi, Seong Jae; Ji, Jong Dae; Song, Gwan Gyu

    2010-03-01

    The aim of this study was to determine whether the rs7574865 polymorphism of STAT4 (signal transducers and activators of transcription 4) confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. A meta-analysis was conducted on the T allele of the STAT4 rs7574865 polymorphism in 15 studies containing 16,088 RA patients and 16,509 normal control subjects. Meta-analysis revealed an association between RA and the STAT4 rs7574865 T allele in all subjects (OR = 1.271, 95% CI = 1.197-1.350, P rs7574865 T allele was found to be significantly associated with RA in Europeans and Asians (OR = 1.300, 95% CI = 1.195-1.414, P rs7574865 polymorphism is associated with RA susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.

  2. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  3. From plant genomes to phenotypes

    OpenAIRE

    Bolger, Marie; Gundlach, Heidrun; Scholz, Uwe; Mayer, Klaus; Usadel, Björn; Schwacke, Rainer; Schmutzer, Thomas; Chen, Jinbo; Arend, Daniel; Oppermann, Markus; Weise, Stephan; Lange, Matthias; Fiorani, Fabio; Spannagl, Manuel

    2017-01-01

    Recent advances in sequencing technologies have greatly accelerated the rate of plant genome and applied breeding research. Despite this advancing trend, plant genomes continue to present numerous difficulties to the standard tools and pipelines not only for genome assembly but also gene annotation and downstream analysis.Here we give a perspective on tools, resources and services necessary to assemble and analyze plant genomes and link them to plant phenotypes.

  4. Reduced TCA flux in diabetic myotubes: A governing influence on the diabetic phenotype?

    DEFF Research Database (Denmark)

    Gaster, Michael

    2009-01-01

    The diabetic phenotype is complex, requiring elucidation of key initiating defects. It is unknown whether the reduced tricarboxylic acid cycle (TCA) flux in skeletal muscle of obese and obese type 2 diabetic (T2D) subjects is of primary origin. Acetate oxidation (measurement of TCA-flux) was sign......The diabetic phenotype is complex, requiring elucidation of key initiating defects. It is unknown whether the reduced tricarboxylic acid cycle (TCA) flux in skeletal muscle of obese and obese type 2 diabetic (T2D) subjects is of primary origin. Acetate oxidation (measurement of TCA...

  5. Phenotypic covariance at species' borders.

    Science.gov (United States)

    Caley, M Julian; Cripps, Edward; Game, Edward T

    2013-05-28

    Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species' borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species' borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future.

  6. Adaptive evolution of molecular phenotypes

    International Nuclear Information System (INIS)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-01-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak. (paper)

  7. Study on parallel and distributed management of RS data based on spatial database

    Science.gov (United States)

    Chen, Yingbiao; Qian, Qinglan; Wu, Hongqiao; Liu, Shijin

    2009-10-01

    With the rapid development of current earth-observing technology, RS image data storage, management and information publication become a bottle-neck for its appliance and popularization. There are two prominent problems in RS image data storage and management system. First, background server hardly handle the heavy process of great capacity of RS data which stored at different nodes in a distributing environment. A tough burden has put on the background server. Second, there is no unique, standard and rational organization of Multi-sensor RS data for its storage and management. And lots of information is lost or not included at storage. Faced at the above two problems, the paper has put forward a framework for RS image data parallel and distributed management and storage system. This system aims at RS data information system based on parallel background server and a distributed data management system. Aiming at the above two goals, this paper has studied the following key techniques and elicited some revelatory conclusions. The paper has put forward a solid index of "Pyramid, Block, Layer, Epoch" according to the properties of RS image data. With the solid index mechanism, a rational organization for different resolution, different area, different band and different period of Multi-sensor RS image data is completed. In data storage, RS data is not divided into binary large objects to be stored at current relational database system, while it is reconstructed through the above solid index mechanism. A logical image database for the RS image data file is constructed. In system architecture, this paper has set up a framework based on a parallel server of several common computers. Under the framework, the background process is divided into two parts, the common WEB process and parallel process.

  8. The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility.

    Science.gov (United States)

    Rezaei, Mahnaz; Eskandari, Fatemeh; Mohammadpour-Gharehbagh, Abbas; Teimoori, Batool; Yaghmaei, Minoo; Mokhtari, Mojgan; Salimi, Saeedeh

    2018-01-01

    Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1-2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4-6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC-GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4-8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 - 2], P = 0.01). The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC-GG combined genotype and C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.

  9. mir-126 rs4636297 and TGFβRI rs334348 functional gene variants are associated with susceptibility to endometriosis and its severity.

    Science.gov (United States)

    Sepahi, Neda; Kohan, Leila; Jahromi, Athar Rasekh; Daneshbod, Yahya; Hoveidi, Elahe Nimi

    2017-06-01

    microRNAs (miRNAs) are negative regulators in a variety of cellular processes that occur in endometriosis. Therefore, functional polymorphisms in miRNA and miRNA binding sites may affect gene expression and contribute to susceptibility of endometriosis. In this study, we evaluated the association of two miRNA related polymorphisms, mir-126 rs4636297 and TGFβRI rs334348, with endometriosis risk and its severity. This case-control study was done on 157 endometriosis patients and 252 healthy women as a control group. Tetra amplification refractory mutation system-polymerase chain reaction (tetra-ARMS PCR) was designed to determine the polymorphisms. Our finding showed significant differences in genotype frequency of mir-126 rs4636297 between the groups (χ 2  = 6.26, p = 0.044). A significant protection against endometriosis was found for mir-126 rs4636297 in allele (G versus A allele: OR = 0.695, 95% CI = 0.519-0.931, p = 0.015) and genotype (GG versus AA genotype: OR = 0.451, 95%CI = 0.233-0.873, p = 0.018). Significant association was also observed between the A allele and severity of endometriosis (OR = 0.478, 95%CI = 0.297-0.768, p = 0.002). Moreover, we found a significant association between AA genotype with the risk of endometriosis (OR = 0.493, 95%CI = 0.250-0.970, p = 0.041) and its severity (OR = 0.240, 95%CI = 0.065-0.883, p = 0.032) regarding TGFβRI rs334348 polymorphism. These finding suggest that, for the first time, mir-126 rs4636297 and TGFβRI rs334348 polymorphisms may influence individual's susceptibility to endometriosis and its severity.

  10. Association of IL28B SNPs rs12979860 and rs8099917 on Hepatitis C Virus-RNA Status in Donors/Recipients of Living Donor Liver Transplantation.

    Directory of Open Access Journals (Sweden)

    King-Wah Chiu

    Full Text Available To investigate the effect of IL28B single nucleotide polymorphisms (SNPs (rs8099917 and rs12979860 in the donors and recipients on the outcome of Hepatitis C virus-RNA clearance after living donor liver transplantation (LDLT. The rs8099917 and rs12979860 genotypes in 50 donor and recipients pairs were explored on the pre-operative day (POD and post-operative day 30 (POD30. There was a significant difference in HCV-RNA clearance before (12%, 6/50 and after (48%, 24/50 liver transplantation (P < 0.001. The rs8099917 genotype TT was dominant in both the recipients (82%, 41/50 and donors (86%, 43/50, but had no significant effect on HCV-RNA clearance (87.5%, 21/24 and recurrence (76.9%, 20/26 after LDLT. One recipient was detected with genotype GG on POD, which changed to genotype GT on POD30. Prevalence of rs12979860 genotype CT was 98% (49/50 recipient and 92% (46/50 donor and prevalence of genotype CC was 2% (1/50 recipient and 8% (4/50 donor on POD and POD30, respectively. Of the 4 recipients with rs12979860 genotype CC on POD30, 3 recipients (12.5%, 3/24 exhibited HCV clearance and 1 experienced recurrence (3.9%, 1/26, however, this was not statistically significant. In conclusion, alterations in IL28B SNP genotype may occur after LDLT, leading to modifications in the host genome or donor proteome by HCV. This predicted mechanism will need to be investigated further.

  11. Relationships between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men – a preliminary study

    Directory of Open Access Journals (Sweden)

    Rotter I

    2016-11-01

    Full Text Available Iwona Rotter,1 Karolina Skonieczna-Żydecka,2 Danuta Kosik-Bogacka,3 Grażyna Adler,2 Aleksandra Rył,4 Maria Laszczyńska4 1Department of Medical Rehabilitation, 2Department of Gerontobiology, 3Department of Biology and Medical Parasitology, 4Department of Histology and Developmental Biology, Pomeranian Medical University, Szczecin, Poland Purpose: Metabolic disorders, including MetS, obesity, and lipid disorders, may be related to genetic factors. Metabolic disorders are associated with decreased TS levels in aging men. The aim of this study was to evaluate the relationship between FTO rs9939609, MC4R rs17782313, and PPARɣ rs1801282 polymorphisms and the presence of MetS and its components, the concurrent lipid disorders, as well as sex hormone concentrations. Subjects and methods: This study involved 272 men of Caucasian descent aged 50–75 years. Lipid profile, including TCh, LDL, HDL, and TG, was evaluated by spectrophotometric method. Anthropometric measurements concerned WC and blood pressure. MetS was diagnosed according to the criteria of the IDF. Sex hormone profile, including TST, FTS, E2, DHEAS, and SHBG, was examined using enzyme-linked immunosorbent assay. Polymorphisms within FTO, MC4R, and PPARɣ genes were identified using polymerase chain reaction-restriction fragments length polymorphism. Results: This study did not show links between the analyzed genetic polymorphisms and the presence of MetS, T2DM, HT, and obesity. However, higher concentrations of TCh and LDL were found in men with the FTO rs9939609 polymorphism in the recessive mode of inheritance (P=0.03 and P=0.05, respectively. Lower WC was found to be associated with MC4R rs17782313 gene inherited in the same model (P=0.005. Conclusion: FTO rs9939609, MC4R rs17782313, and PPARɣ rs1801282 polymorphisms seem to have little effect on the incidence of metabolic malfunctions and no effect on androgen-related disorders in the examined middle-aged and elderly men

  12. Early Super Soft Source Spectra in RS Oph

    Directory of Open Access Journals (Sweden)

    J.-U. Ness

    2015-02-01

    Full Text Available Recent Swift X-ray monitoring campaigns of novae have revealed extreme levels of variability during the early super-softsource (SSS phase. The first time this was observed was during the 2006 outburst of the recurrent nova RS Oph which was also extensively covered by grating observations with XMM-Newton and Chandra. I focus here on an XMM-Newton observation taken on day 26.1, just before Swift confirmed the start of the SSS phase, and a Chandra observation taken on day 39.7. The first observation probes the evolution of the shock emission produced by the collision of the nova ejecta with the stellar wind of the companion. The second observation contains bright SSS emission longwards of 15°A while at short wavelengths, the shock component can be seen to have hardly changed. On top of the SSS continuum, additional emission lines are clearly seen, and I show that they are much stronger than those seen on day 26.1, indicating line pumping caused by the SSS emission. The lightcurve on day 39.7 is highly variable on short time scales while the long-term Swift light curve was still variable. In 2007, we have shown that brightness variations are followed by hardness variations, lagging behind 1000 seconds. I show now that the hardness variations are owed to variations in the depth of the neutral hydrogen column density of order 25%, particularly affecting the oxygen K-shell ionization edge at 0.5 keV.

  13. Association of ADORA1 rs2228079 and ADORA2A rs5751876 Polymorphisms with Gilles de la Tourette Syndrome in the Polish Population.

    Directory of Open Access Journals (Sweden)

    Piotr Janik

    Full Text Available Gilles de la Tourette syndrome (GTS is a neurodevelopmental disorder characterized by motor and vocal tics. Hyperactivity of dopaminergic transmission is considered a prime abnormality in the pathophysiology of tics. There are reciprocal antagonistic interactions between adenosine and dopamine transmission. The aim of the study was to analyze the association of two polymorphisms, rs2228079 in ADORA1 and rs5751876 in ADORA2A, with the risk of GTS and co-morbid disorders.A total of 162 Polish GTS patients and 270 healthy persons were enrolled in the study. Two polymorphisms were selected on the basis of knowledge of SNPs frequencies in ADORA1 and ADORA2A. Chi-square test was used for allelic and genotypic association studies. Association of genotypes with age of tic onset was analyzed with Mann-Whitney test. Multivariate logistic regression was used to find independent predictors of GTS risk.We found that the risk of GTS was associated with rs2228079 and rs5751876 polymorphisms. The GG+GT genotypes of rs2228079 in ADORA1 were underrepresented in GTS patients (p = 0.011, whereas T allele of rs5751876 in ADORA2A was overrepresented (p = 0.017. The GG genotype of rs2228079 was associated with earlier age of tic onset (p = 0.046. We found also that the minor allele G of rs2228079 was more frequent in GTS patients with depression as compared to the patients without depression (p = 0.015. Also the genotype GG was significantly more frequent in patients with obsessive compulsive disorder/behavior (OCD/OCB, p = 0.021 and depression (p = 0.032, as compared to the patients without these co-morbidities. The minor allele T frequency of rs5751876 was lower in GTS patients with co-morbid attention deficit hyperactivity disorder (p = 0.022, and TT+TC genotypes were less frequent in the non-OCD anxiety disorder group (p = 0.045.ADORA1 and ADORA2A variants are associated with the risk of GTS, co-morbid disorders, and may affect the age of tic onset.

  14. Dinitrosyl iron complexes and S-nitrosothiols are two possible forms for stabilization and transport of nitric oxide in biological systems.

    Science.gov (United States)

    Vanin, A F

    1998-07-01

    The physicochemical properties, mechanisms of synthesis and decomposition of dinitrosyl iron complexes (DNICs) with thiol-containing ligands and of S-nitrosothiols (RS-NO), and the potential role of these compounds in storage and transport of NO in biological systems are reviewed. Special attention is given to the phenomenon of mutual transformation of DNIC and RS-NO catalyzed by Fe2+. Each Fe2+ binds two neutral NO molecules in the DNICs, catalyzes their mutual oxidation--reduction with formation of nitrous oxide and nitrosonium ions appearing in the DNICs. These ions S-nitrosate thiol-compounds with RS-NO formation. Fe2+ binds two RS-NO molecules and catalyzes their mutual oxidation--reduction followed by decomposition of the resulting molecules. Mutual conversion of DNICs and RS-NO regulated by iron, thiol, and NO levels is suggested to provide NO transport in cells and tissues.

  15. Genetic polymorphisms of surfactant protein D rs2243639, Interleukin (IL)-1β rs16944 and IL-1RN rs2234663 in chronic obstructive pulmonary disease, healthy smokers, and non-smokers.

    Science.gov (United States)

    Issac, Marianne Samir M; Ashur, Wafaa; Mousa, Heba

    2014-06-01

    Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of this study was to investigate the association between surfactant protein D (SFTPD) rs2243639, interleukin (IL)-1β rs16944 and IL-1 receptor antagonist (IL-1RN) rs2234663 gene polymorphisms and COPD susceptibility, as well as examining the association between the various IL-1RN/IL-1β haplotypes and pulmonary function tests (PFT). Secondly, we aimed to examine the influence of SFTPD rs2243639 polymorphism on serum surfactant protein D (SP-D) level. A total of 114 subjects were recruited in this study and divided into three groups: 63 COPD patients, 25 asymptomatic smokers, and 26 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for the detection of SFTPD rs2243639 and IL-1β rs16944 polymorphisms. Detection of variable numbers of an 86-bp tandem repeat (VNTR) of IL-1RN was done using PCR. Serum SP-D level was measured using enzyme linked-immunosorbent assay. PFTs were measured by spirometry. Carriers of the SFTPD AG and AA polymorphic genotypes constituted 71.4 % of COPD patients versus 48 % in asymptomatic smokers, with a statistically significant difference between the two groups (p = 0.049). Smokers who were carriers of the polymorphic SFTPD rs2243639 A allele (AG and AA genotypes) have a 2.708 times risk of developing COPD when compared with wild-type GG genotype carriers [odds ratio (OR) 2.708 (95 % CI 1.041-7.047)]. Forced expiratory flow (FEF) 25-75 % predicted was higher in IL-1RN*1/*1 when compared with *1/*2 (p = 0.013). FEF25-75 % predicted in carriers of haplotype IL-1RN *1/IL-1β T (49.21 ± 10.26) was statistically significantly higher than in carriers of IL-1RN *2/IL-1β T (39.67 ± 12.64) [p = 0

  16. Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics

    DEFF Research Database (Denmark)

    Gresner, Peter; Gromadzinska, Jolanta; Jablonska, Ewa

    2014-01-01

    affect the unselected BrC risk. Contrary to this, carriers of rs12946522, rs16943176, rs12946397 and rs17222691 rare-alleles were found to present significantly increased level of blood plasma TBARS compared to respective wild-type homozygotes (p... decreased fraction of oxidatively generated DNA damage (34% of total damaged DNA) in favor of DNA strand breakage, with no effect on total DNA damage, unlike respective wild-types, among which more evenly distributed proportions between oxidatively damaged DNA (48% of total DNA damage) and DNA strand...

  17. The TT genotype of the rs6860 polymorphism of the charged multivesicular body protein 1A gene is associated with susceptibility to fibromyalgia in southern Spanish women

    NARCIS (Netherlands)

    Estévez-López, Fernando; Aparicio, Virginia A; Ruiz, Jonatan R; Martínez-González, Luis J; Delgado-Fernández, Manuel; Álvarez-Cubero, María J

    In 2012, Barbosa et al. analysed the association between the genotype frequencies of the rs4680 and rs4818 polymorphisms of the catechol-O-methyltransferase (COMT) gene. Of note is that, in the abstract, they mentioned the rs6860 polymorphism when it should have been rs4680. Indeed, the rs6860

  18. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  19. NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping.

    Science.gov (United States)

    Laughlin, Maren R; Lloyd, K C Kent; Cline, Gary W; Wasserman, David H

    2012-10-01

    The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community's needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses.

  20. A direct comparison of remote sensing approaches for high-throughput phenotyping in plant breeding

    Directory of Open Access Journals (Sweden)

    Maria Tattaris

    2016-08-01

    Full Text Available Remote sensing (RS of plant canopies permits non-intrusive, high-throughput monitoring of plant physiological characteristics. This study compared three RS approaches using a low flying UAV (unmanned aerial vehicle, with that of proximal sensing, and satellite-based imagery. Two physiological traits were considered, canopy temperature (CT and a vegetation index (NDVI, to determine the most viable approaches for large scale crop genetic improvement. The UAV-based platform achieves plot-level resolution while measuring several hundred plots in one mission via high-resolution thermal and multispectral imagery measured at altitudes of 30-100 m. The satellite measures multispectral imagery from an altitude of 770 km. Information was compared with proximal measurements using IR thermometers and an NDVI sensor at a distance of 0.5-1m above plots. For robust comparisons, CT and NDVI were assessed on panels of elite cultivars under irrigated and drought conditions, in different thermal regimes, and on un-adapted genetic resources under water deficit. Correlations between airborne data and yield/biomass at maturity were generally higher than equivalent proximal correlations. NDVI was derived from high-resolution satellite imagery for only larger sized plots (8.5 x 2.4 m due to restricted pixel density. Results support use of UAV-based RS techniques for high-throughput phenotyping for both precision and efficiency.

  1. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage

    Science.gov (United States)

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

  2. Genetic susceptibility markers for a breast-colorectal cancer phenotype: Exploratory results from genome-wide association studies

    Science.gov (United States)

    Joon, Aron; Brewster, Abenaa M.; Chen, Wei V.; Eng, Cathy; Shete, Sanjay; Casey, Graham; Schumacher, Fredrick; Lin, Yi; Harrison, Tabitha A.; White, Emily; Ahsan, Habibul; Andrulis, Irene L.; Whittemore, Alice S.; Ko Win, Aung; Schmidt, Daniel F.; Kapuscinski, Miroslaw K.; Ochs-Balcom, Heather M.; Gallinger, Steven; Jenkins, Mark A.; Newcomb, Polly A.; Lindor, Noralane M.; Peters, Ulrike; Amos, Christopher I.; Lynch, Patrick M.

    2018-01-01

    Background Clustering of breast and colorectal cancer has been observed within some families and cannot be explained by chance or known high-risk mutations in major susceptibility genes. Potential shared genetic susceptibility between breast and colorectal cancer, not explained by high-penetrance genes, has been postulated. We hypothesized that yet undiscovered genetic variants predispose to a breast-colorectal cancer phenotype. Methods To identify variants associated with a breast-colorectal cancer phenotype, we analyzed genome-wide association study (GWAS) data from cases and controls that met the following criteria: cases (n = 985) were women with breast cancer who had one or more first- or second-degree relatives with colorectal cancer, men/women with colorectal cancer who had one or more first- or second-degree relatives with breast cancer, and women diagnosed with both breast and colorectal cancer. Controls (n = 1769), were unrelated, breast and colorectal cancer-free, and age- and sex- frequency-matched to cases. After imputation, 6,220,060 variants were analyzed using the discovery set and variants associated with the breast-colorectal cancer phenotype at Pcolorectal cancer phenotype in the discovery and replication data (most significant; rs7430339, Pdiscovery = 1.2E-04; rs7429100, Preplication = 2.8E-03). In meta-analysis of the discovery and replication data, the most significant association remained at rs7429100 (P = 1.84E-06). Conclusion The results of this exploratory analysis did not find clear evidence for a susceptibility locus with a pleiotropic effect on hereditary breast and colorectal cancer risk, although the suggestive association of genetic variation in the region of ROBO1, a potential tumor suppressor gene, merits further investigation. PMID:29698419

  3. The CHRNA3 rs578776 variant is associated with an intrinsic reward sensitivity deficit in smokers

    Directory of Open Access Journals (Sweden)

    Jason D. Robinson

    2013-09-01

    Full Text Available A compromised brain reward system has been postulated as a key feature of drug dependence. We examined whether several polymorphisms of genes found to regulate nicotinic acetylcholine receptor (nAChR and dopamine (DA expression were related to an intrinsic reward sensitivity (IRS deficit we previously identified among a subgroup of smokers using event-related potentials (ERPs. We examined genetic polymorphisms within the CHRNA5-A3-B4 gene cluster (CHRNA3 rs578776, CHRNA5 rs16969968, LOC123688 rs8034191, and CHRNA3 rs1051730, the ANKK1 gene (rs1800497, and the D2 receptor gene (DRD2 rs1079597, DRD2 rs1799732 from 104 smokers of European ancestry in a smoking cessation trial. Prior to treatment, we recorded ERPs evoked by emotional (both pleasant and unpleasant, neutral, and cigarette-related pictures. Smokers were assigned to two groups (IRS+/IRS- based on the amplitude of the late positive potential (LPP component to the pictures, a neural marker of motivational salience. Smokers (n = 42 with blunted brain responses to intrinsically rewarding (pleasant pictures and enhanced responses to cigarette pictures were assigned to the IRS- group, while smokers (n = 62 with the opposite pattern of LPP responding were assigned to the IRS+ group. Carriers of the protective minor T allele (T/T, C/T of the CHRNA3 rs578776 were less likely to be members of the IRS- group than those homozygous for the at-risk C allele (C/C. The CHRNA3 rs578776 polymorphism did not differ on questionnaires of nicotine dependence, depressed mood, or trait affective disposition and did not predict abstinence at 6 months after the quit date. These results suggest that polymorphisms of genes influencing nAChR expression are related to an endophenotype of reward sensitivity in smokers.

  4. The CHRNA3 rs578776 Variant is Associated with an Intrinsic Reward Sensitivity Deficit in Smokers.

    Science.gov (United States)

    Robinson, Jason D; Versace, Francesco; Lam, Cho Y; Minnix, Jennifer A; Engelmann, Jeffrey M; Cui, Yong; Karam-Hage, Maher; Shete, Sanjay S; Tomlinson, Gail E; Chen, Tina T-L; Wetter, David W; Green, Charles E; Cinciripini, Paul M

    2013-01-01

    A compromised brain reward system has been postulated as a key feature of drug dependence. We examined whether several polymorphisms of genes found to regulate nicotinic acetylcholine receptor (nAChR) and dopamine expression were related to an intrinsic reward sensitivity (IRS) deficit we previously identified among a subgroup of smokers using event-related potentials (ERPs). We examined genetic polymorphisms within the CHRNA5-A3-B4 gene cluster (CHRNA3 rs578776, CHRNA5 rs16969968, LOC123688 rs8034191, and CHRNA3 rs1051730), the ANKK1 gene (rs1800497), and the D2 dopamine receptor gene (DRD2 rs1079597, DRD2 rs1799732) from 104 smokers of European ancestry in a smoking cessation trial. Prior to treatment, we recorded ERPs evoked by emotional (both pleasant and unpleasant), neutral, and cigarette-related pictures. Smokers were assigned to two groups (IRS+/IRS-) based on the amplitude of the late positive potential (LPP) component to the pictures, a neural marker of motivational salience. Smokers (n = 42) with blunted brain responses to intrinsically rewarding (pleasant) pictures and enhanced responses to cigarette pictures were assigned to the IRS- group, while smokers (n = 62) with the opposite pattern of LPP responding were assigned to the IRS+ group. Carriers of the protective minor T allele (T/T, C/T) of the CHRNA3 rs578776 were less likely to be members of the IRS- group than those homozygous for the at-risk C allele (C/C). The CHRNA3 rs578776 polymorphism did not differ on questionnaires of nicotine dependence, depressed mood, or trait affective disposition and did not predict abstinence at 6 months after the quit date. These results suggest that polymorphisms of genes influencing nAChR expression are related to an endophenotype of reward sensitivity in smokers.

  5. The Human Phenotype Ontology in 2017

    International Nuclear Information System (INIS)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

    2016-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

  6. TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes.

    Science.gov (United States)

    Redondo, Maria J; Geyer, Susan; Steck, Andrea K; Sosenko, Jay; Anderson, Mark; Antinozzi, Peter; Michels, Aaron; Wentworth, John; Xu, Ping; Pugliese, Alberto

    2018-02-01

    The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 ( TCF7L2 ) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis. We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data ( n = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders. The rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old ( n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones ( n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) ( P = 0.008) and lower mean glucose AUC ( P = 0.0127). The results were similar for the rs7901695 SNP. In this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms. © 2017 by the American Diabetes Association.

  7. Phenotypic variability in Meesmann's dystrophy

    DEFF Research Database (Denmark)

    Ehlers, Niels; Hjortdal, Jesper; Nielsen, Kim

    2008-01-01

    symptoms often include blurred vision and ocular irritation. Typical cases may be entirely free of complaints. Intermittent pain episodes, such as occur in recurrent erosion syndrome, are not the rule. Genetic sequencing indicated a familial relationship with the originally described Meesmann family......'s dystrophy occurs worldwide. The largest family described is the original German one, now supplemented with a Danish branch. Despite the presence of an identical genetic defect, the clinical phenotype varies. This suggests that non-KRT12-related mechanisms are responsible for the variation....

  8. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...... of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the 45 known type 2...

  9. RS-34 (Peacekeeper Post Boost Propulsion System) Orbital Debris Application Concept Study

    Science.gov (United States)

    Esther, Elizabeth A.; Burnside, Christopher G.

    2013-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) lead a study to evaluate the Rocketdyne produced RS-34 propulsion system as it applies to an orbital debris removal design reference mission. The existing RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper ICBM program; specifically the pressure-fed storable bi-propellant Stage IV Post Boost Propulsion System. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC is working closely with the USAF to obtain all the remaining RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Concept Study, preceded by a utilization study to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions, sought to further understand application for an orbital debris design reference mission as the orbital debris removal mission was found to closely mimic the heritage RS-34 mission. The RS-34 Orbital Debris Application Concept Study sought to identify multiple configurations varying the degree of modification to trade for dry mass optimization and propellant load for overall capability and evaluation of several candidate missions. The results of the RS-34 Phoenix Utilization Study show that the system is technically sufficient to successfully support all of the missions

  10. Reductive Stress in Inflammation-Associated Diseases and the Pro-Oxidant Effect of Antioxidant Agents

    Directory of Open Access Journals (Sweden)

    Israel Pérez-Torres

    2017-10-01

    Full Text Available Abstract: Reductive stress (RS is the counterpart oxidative stress (OS, and can occur in response to conditions that shift the redox balance of important biological redox couples, such as the NAD+/NADH, NADP+/NADPH, and GSH/GSSG, to a more reducing state. Overexpression of antioxidant enzymatic systems leads to excess reducing equivalents that can deplete reactive oxidative species, driving the cells to RS. A feedback regulation is established in which chronic RS induces OS, which in turn, stimulates again RS. Excess reducing equivalents may regulate cellular signaling pathways, modify transcriptional activity, induce alterations in the formation of disulfide bonds in proteins, reduce mitochondrial function, decrease cellular metabolism, and thus, contribute to the development of some diseases in which NF-κB, a redox-sensitive transcription factor, participates. Here, we described the diseases in which an inflammatory condition is associated to RS, and where delayed folding, disordered transport, failed oxidation, and aggregation are found. Some of these diseases are aggregation protein cardiomyopathy, hypertrophic cardiomyopathy, muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, Alzheimer’s disease, and metabolic syndrome, among others. Moreover, chronic consumption of antioxidant supplements, such as vitamins and/or flavonoids, may have pro-oxidant effects that may alter the redox cellular equilibrium and contribute to RS, even diminishing life expectancy.

  11. Association of STAT4 rs7574865 and PTPN22 rs2476601 polymorphisms with rheumatoid arthritis and non-systemically reacting antibodies in Egyptian patients.

    Science.gov (United States)

    El-Lebedy, Dalia; Raslan, Hala; Ibrahim, Alshaymaa; Ashmawy, Ingy; El-Aziz, Shereen Abd; Mohammed, Asmaa M

    2017-09-01

    The aim of this study was to investigate association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid arthritis (RA) susceptibility and to assess potential association with the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and neopterin were assayed in serum of 100 unrelated RA patients and 114 controls. STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the TaqMan allelic discrimination method. The frequency of STAT4 variant allele was significantly higher in RA patients than in controls (p = 0.01), while the variant allele of PTPN22 was identified in only two RA patients, in a heterozygous form and in none of control subjects. The frequency of STAT4 variant allele carrier genotypes (GT+TT) was significantly higher among RA patients than in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and dominant models. The frequency of RF and anti-CCP positivity was significantly higher among RA patients carrying T allele genotypes compared to patients carrying wild genotype (P = 0.02 and 0.04, respectively). No significant associations between STAT4 variant and serum neopterin or disease activity parameters were identified. Our study confirmed the association of STAT4 rs7574865 polymorphism with RA and was the first to indicate an association with RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role in susceptibility to RA in Egyptian patients.

  12. Proteome oxidative carbonylation during oxidative stress-induced premature senescence of WI-38 human fibroblasts

    DEFF Research Database (Denmark)

    Le Boulch, Marine; Ahmed, Emad K; Rogowska-Wrzesinska, Adelina

    2018-01-01

    Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e. the "Oxi-pro...

  13. Vulnerabilidade Natural do Solo de Silveira Martins-RS

    Directory of Open Access Journals (Sweden)

    Franciele Francisca Marmentini Rovani

    Full Text Available A análise ambiental, com base nos processos de morfogênese e pedogênese, possibilita informações importantes para a elaboração de políticas públicas visando o uso e ocupação da paisagem de maneira sustentável. Com isso, objetivou-se identificar os diferentes níveis de vulnerabilidade natural à perda de solo do município de Silveira Martins, RS. Foi elaborado um banco de dados espaciais em um ambiente de Sistemas de Informações Geográficas (SIG com auxílio do software Spring. O zoneamento da vulnerabilidade natural à perda de solo foi elaborado com base nas informações referentes à declividade, geomorfologia, geologia e solos de acordo com o grau de vulnerabilidade de cada informação, por meio da álgebra de mapas. Para o território municipal de Silveira Martins identificou-se a ocorrência de cinco classes. Destacam-se as unidades estáveis com predomínio dos processos formadores do solo (38,08% da área municipal, e as unidades moderadamente vulneráveis, prevalecendo os processos erosivos (53,67%. As áreas classificadas como moderadamente vulnerável e vulnerável (8,25%, correspondem a áreas com inclinações superiores a 25º e com formação geológica e geomorfológica menos estáveis. Nas unidades em que predominou a vulnerabilidade natural, sugere-se especial atenção em relação ao meio natural e aos agentes que o influenciam, visando boas práticas sociais associadas às políticas ambientais no processo de tomada de decisões econômicas, possibilitando a valorização e proteção do meio natural.

  14. Investigating the Correlation between rs1049305 and ‏rs10244884 Polymorphisms of AQP-1 Gene and Menorrhagia ‎in Adolescents

    Directory of Open Access Journals (Sweden)

    S Madani

    2014-02-01

    Results: Regarding ‏‎rs1049305, the C minor allele showed more frequency in patients' group‏ (0.47 vs. 0.37.‎‎ The results revealed that GG genotype presents less probable risk ‎for menorrhagia. ‎‎ rs10244884‎ also shows the same frequency. Conclusion: It can be concluded that both variants are important in pathogenesis of menorrhagia and the results confirm the important role of Aquqporin–1 channel in menstruation as well as endometrium physiology.

  15. Association of rs6265 and rs2030324 polymorphisms in brain-derived neurotrophic factor gene with Alzheimer's disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yan Lin

    Full Text Available BACKGROUND: The association between polymorphisms rs6265 and rs2030324 in brain-derived neurotrophic factor (BDNF and Alzheimer's disease (AD has been widely reported, but the results remain controversial. METHODS: A comprehensive search of Pubmed, Web of Science, China National Knowledge Infrastructure (CNKI, Wanfang Med Online and China Biology Medical literature database (CBM was performed. Pooled odds ratios (ORs with 95% confidence intervals (CIs were calculated using fixed or random-effects models. We excluded the studies with OR>3.0 or OR<0.3 for sensitive analysis. Subgroup analysis by ethnicity, form of AD and gender was carried out. Meta-regression was conducted to explore the potential sources of between-study heterogeneity. RESULTS: 29 articles with 7548 cases and 7334 controls concerning rs6265 and 22 articles with 5796 cases and 5706 controls concerning rs2030324 were included in this meta-analysis. The combined evidence suggested rs6265 contributing significantly to the increased risk of AD in females (codominant: fixed-effects model (FEM: OR = 1.13, 95% CI = 1.04-1.23; dominant: FEM: OR = 1.17, 95% CI = 1.05-1.31, especially for Caucasian females (codominant: FEM: OR = 1.18, 95% CI = 1.03-1.34; dominant: FEM: OR = 1.18, 95% CI = 1.01-1.37 and female late-onset Alzheimer's disease (LOAD patients (codominant: FEM: OR = 1.22, 95% CI = 1.05-1.41; dominant: FEM: OR = 1.23, 95% CI = 1.03-1.46. No evidence indicated an association between rs2030324 with AD in codominant (random-effects model (REM: OR = 1.06, 95% CI = 0.89-1.26 and dominant (REM: OR = 1.05, 95% CI = 0.86-1.27 models. CONCLUSION: This meta-analysis suggested A allele of rs6265 might increase the risk of AD in Caucasian females and female LOAD patients. In addition, no evidence indicated an association between rs2030324 with AD. Further studies are needed to confirm these results.

  16. ACE phenotyping in Gaucher disease.

    Science.gov (United States)

    Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

    2018-04-01

    Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI based on the Genetic Investigation of ANthropometric Traits (GIANT consortium data and calculated a BMI genetic risk score (BMI-GRS for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO. Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively. The BMI-GRS was also positively correlated with pack-years of smoking (p<0.001 in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p<0.05, respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF achieved statistical significance after Bonferroni correction for multiple testing, and three suggestive SNPs (rs13021737, TMEM18; rs11583200, ELAVL4; and rs6990042, SGCZ achieved a nominal statistical significance. Our results suggest that there is a common genetic component between BMI and smoking, and pleiotropy analysis can be useful to identify novel genetic loci of complex phenotypes.

  18. Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.

    Directory of Open Access Journals (Sweden)

    Tamuno Alfred

    Full Text Available The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP rs1260326 (P446L in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported.As part of the Healthy Ageing across the Life Course (HALCyon collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI, blood lipid levels, lung function, and cognitive and physical capability.We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score= -0.04, p-value=0.0001, n=16,251. Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability.Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.

  19. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants

    DEFF Research Database (Denmark)

    Sandholt, Camilla Helene; Vestmar, Marie Aare; Bille, Dorthe Sadowa

    2011-01-01

    associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms. Methods: 15 gene variants in 14 loci including TMEM18 (rs7561317), SH2B1 (rs7498665), KCTD15 (rs29941), NEGR1 (rs2568958), ETV5 (rs7647305), BDNF (rs4923461, rs925946), SEC16B (rs10913469), FAIM2 (rs7138803), GNPDA2......, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI....

  20. Preparation and characterization of ketoprofen loaded eudragit RS polymeric nanoparticles for controlled release

    International Nuclear Information System (INIS)

    Tuan Anh, Nguyen; Tuyen Dao, T P; Nhan Le, N T; Mau Chien, Dang; To Hoai, Nguyen; T Chi, Nguyen; Tran, T Khai

    2012-01-01

    Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid. (paper)

  1. Association of a single-nucleotide polymorphism (rs6180) in GHR ...

    Indian Academy of Sciences (India)

    in the GHR gene and investigated an effect of SNP rs6180 on human organ weight ... and approved by the Human Ethics Committee of Shimane. University School of ..... This work was supported by JSPS KAKENHI grant number. 26713025 ...

  2. CYBRD1 as a modifier gene that modulates iron phenotype in HFE p.C282Y homozygous patients.

    Science.gov (United States)

    Pelucchi, Sara; Mariani, Raffaella; Calza, Stefano; Fracanzani, Anna Ludovica; Modignani, Giulia Litta; Bertola, Francesca; Busti, Fabiana; Trombini, Paola; Fraquelli, Mirella; Forni, Gian Luca; Girelli, Domenico; Fargion, Silvia; Specchia, Claudia; Piperno, Alberto

    2012-12-01

    Most patients with hereditary hemochromatosis in the Caucasian population are homozygous for the p.C282Y mutation in the HFE gene. The penetrance and expression of hereditary hemochromatosis differ largely among cases of homozygous p.C282Y. Genetic factors might be involved in addition to environmental factors. In the present study, we analyzed 50 candidate genes involved in iron metabolism and evaluated the association between 214 single nucleotide polymorphisms in these genes and three phenotypic outcomes of iron overload (serum ferritin, iron removed and transferrin saturation) in a large group of 296 p.C282Y homozygous Italians. Polymorphisms were tested for genetic association with each single outcome using linear regression models adjusted for age, sex and alcohol consumption. We found a series of 17 genetic variants located in different genes with possible additive effects on the studied outcomes. In order to evaluate whether the selected polymorphisms could provide a predictive signature for adverse phenotype, we re-evaluated data by dividing patients in two extreme phenotype classes based on the three phenotypic outcomes. We found that only a small improvement in prediction could be achieved by adding genetic information to clinical data. Among the selected polymorphisms, a significant association was observed between rs3806562, located in the 5'UTR of CYBRD1, and transferrin saturation. This variant belongs to the same haplotype block that contains the CYBRD1 polymorphism rs884409, found to be associated with serum ferritin in another population of p.C282Y homozygotes, and able to modulate promoter activity. A luciferase assay indicated that rs3806562 does not have a significant functional role, suggesting that it is a genetic marker linked to the putative genetic modifier rs884409. While our results support the hypothesis that polymorphisms in genes regulating iron metabolism may modulate penetrance of HFE-hereditary hemochromatosis, with emphasis on

  3. Polymorphisms in TRPV1 and TAS2Rs associate with sensations from sampled ethanol.

    Science.gov (United States)

    Allen, Alissa L; McGeary, John E; Hayes, John E

    2014-10-01

    Genetic variation in chemosensory genes can explain variability in individual's perception of and preference for many foods and beverages. To gain insight into variable preference and intake of alcoholic beverages, we explored individual variability in the responses to sampled ethanol (EtOH). In humans, EtOH elicits sweet, bitter, and burning sensations. Here, we explore the relationship between variation in EtOH sensations and polymorphisms in genes encoding bitter taste receptors (TAS2Rs) and a polymodal nociceptor (TRPV1). Caucasian participants (n = 93) were genotyped for 16 single nucleotide polymorphisms (SNPs) in TRPV1, 3 SNPs in TAS2R38, and 1 SNP in TAS2R13. Participants rated sampled EtOH on a generalized Labeled Magnitude Scale. Two stimuli were presented: a 16% EtOH whole-mouth sip-and-spit solution with a single time-point rating of overall intensity and a cotton swab saturated with 50% EtOH on the circumvallate papillae (CV) with ratings of multiple qualities over 3 minutes. Area-under-the-curve (AUC) was calculated for the time-intensity data. The EtOH whole-mouth solution had overall intensity ratings near "very strong." Burning/stinging had the highest mean AUC values, followed by bitterness and sweetness. Whole-mouth intensity ratings were significantly associated with burning/stinging and bitterness AUC values on the CV. Three TRPV1 SNPs (rs224547, rs4780521, rs161364) were associated with EtOH sensations on the CV, with 2 (rs224547 and rs4780521) exhibiting strong linkage disequilibrium. Additionally, the TAS2R38 SNPs rs713598, rs1726866, and rs10246939 formed a haplotype, and were associated with bitterness on the CV. Last, overall intensity for whole-mouth EtOH associated with the TAS2R13 SNP rs1015443. These data suggest genetic variation in TRPV1 and TAS2Rs influence sensations from sampled EtOH and may potentially influence how individuals initially respond to alcoholic beverages. Copyright © 2014 by the Research Society on Alcoholism.

  4. The prostate cancer risk stratification (ProCaRS) project: Recursive partitioning risk stratification analysis

    International Nuclear Information System (INIS)

    Rodrigues, George; Lukka, Himu; Warde, Padraig; Brundage, Michael; Souhami, Luis; Crook, Juanita; Cury, Fabio; Catton, Charles; Mok, Gary; Martin, Andre-Guy; Vigneault, Eric; Morris, Jim; Warner, Andrew; Gonzalez Maldonado, Sandra; Pickles, Tom

    2013-01-01

    Background: The Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision-making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema. Methods: The RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively. Results: The recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ⩽6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ⩾87.5% OR PSA >30). Conclusions: Proposed RS subcategories have been identified by a RPA of the ProCaRS database

  5. Description of the Implementation of Home Care Servicer at RS Murni Teguh, Medan

    OpenAIRE

    Manalu, Ayu P Sary

    2014-01-01

    Home care service constitutes providing service and nurses’ equipment for patients and their families at home in order to keep their health, education, prevention from diseases, palliative therapy, and rehabilitation. Home care service at RS Murni Teguh, Medan, has its specification in management, compared with home care service in other places. The objective of the research was to find out the description of the implementation of home care service at RS Murni Teguh, Medan. The research used ...

  6. Association between MC4R rs17782313 Polymorphism and Overeating Behaviours

    Science.gov (United States)

    Yilmaz, Zeynep; Davis, Caroline; Loxton, Natalie J.; Kaplan, Allan S.; Levitan, Robert D.; Carter, Jacqueline C.; Kennedy, James L.

    2014-01-01

    Background/Objectives Melanocortins play a crucial role in appetite and weight regulation. Although the melanocortin 4 receptor (MC4R) gene has been repeatedly linked to obesity and antipsychotic-induced weight gain, the mechanism behind how it leads to this effect in still undetermined. The goal of this study was to conduct an in-depth and sophisticated analysis of MC4R polymorphisms, body mass index (BMI), eating behaviour, and depressed mood. Subjects/Methods We genotyped 328 individuals of European ancestry on the following MC4R markers based on the relevant literature on obesity and antipsychotic-induced weight gain: rs571312, rs17782313, rs489693, rs11872992, and rs8087522. Height and weight were measured, and information on depressed mood and overeating behaviours was obtained during the in-person assessment. Results BMI was associated with rs17782313 C allele; however this finding did not survive correction for multiple testing (p=0.018). Although rs17782313 was significantly associated with depressed mood and overeating behaviours, tests of indirect effects indicated that emotional eating and food cravings, rather than depressed mood, uniquely accounted for the effect of this marker and BMI (n=152). Conclusions To our knowledge, this is the first study to investigate the link between MC4R rs17782313, mood and overeating behaviour, as well as to demonstrate possible mechanisms behind MC4R’s influence on body weight. If replicated in a larger sample, these results may have important clinical implications, including potential for the use of MC4R agonists in the treatment of obesity and disordered eating. PMID:24827639

  7. Association between MC4R rs17782313 polymorphism and overeating behaviors.

    Science.gov (United States)

    Yilmaz, Z; Davis, C; Loxton, N J; Kaplan, A S; Levitan, R D; Carter, J C; Kennedy, J L

    2015-01-01

    Melanocortins have a crucial role in appetite and weight regulation. Although the melanocortin 4 receptor (MC4R) gene has been repeatedly linked to obesity and antipsychotic-induced weight gain, the mechanism behind how it leads to this effect in still undetermined. The goal of this study was to conduct an in-depth and sophisticated analysis of MC4R polymorphisms, body mass index (BMI), eating behavior and depressed mood. We genotyped 328 individuals of European ancestry on the following MC4R markers based on the relevant literature on obesity and antipsychotic-induced weight gain: rs571312, rs17782313, rs489693, rs11872992, and rs8087522. Height and weight were measured, and information on depressed mood and overeating behaviors was obtained during the in-person assessment. BMI was associated with rs17782313 C allele; however, this finding did not survive correction for multiple testing (P = 0.018). Although rs17782313 was significantly associated with depressed mood and overeating behaviors, tests of indirect effects indicated that emotional eating and food cravings, rather than depressed mood, uniquely accounted for the effect of this marker and BMI (n = 152). To our knowledge, this is the first study to investigate the link between MC4R rs17782313, mood and overeating behavior, as well as to demonstrate possible mechanisms behind MC4R's influence on body weight. If replicated in a larger sample, these results may have important clinical implications, including potential for the use of MC4R agonists in the treatment of obesity and disordered eating.

  8. Design of Bus Protocol Intelligent Initiation System Based On RS485

    Directory of Open Access Journals (Sweden)

    Li Liming

    2017-01-01

    Full Text Available In order to design an effective and reliable RS485 bus protocol based on RS485 bus, this paper introduces the structure and transmission mode of the command frame and the response frame, and also introduce four control measures and the communication in order to process quality of this system. The communication protocol is open, tolerant, reliable and fast, and can realize ignition more reliable and accurate in the intelligent initiation system.

  9. Faktor-Faktor Yang Mempengaruhi Kejadian Insomnia di Poliklinik Saraf RS DR. M. Djamil Padang

    OpenAIRE

    Lydia Susanti

    2015-01-01

    Abstrak Faktor risiko seperti usia lanjut, jenis kelamin wanita, penyakit penyerta (depresi dan penyakit lain), status sosial ekonomi rendah menyebabkan insomnia. Penelitian mengenai prevalensi dan faktor-faktor yang mempengaruhi kejadian insomnia di Poliklinik Saraf RS DR. M. Djamil Padang belum pernah dilakukan. Tujuan penelitian ini adalah menentukan faktor-faktor yang mempengaruhi terjadinya insomnia di poliklinik saraf RS DR. M. Djamil Padang. Penelitian ini merupakan penelitian cross se...

  10. The RS-485 communication system design of the waste steel radioactivity detector system

    International Nuclear Information System (INIS)

    Zhang Yongli

    2014-01-01

    The importance and schematic structure of the waste steel radioactivity detector system is given firstly in this paper, and then the RS-485 communication system design including the circuit and program of the waste steel radioactivity detector system is provided. The test result of RS-485 communication system is also introduced, that shows the design completely meets the requirements of the waste steel radioactivity detector system. (author)

  11. Fatty acid translocase gene CD36 rs1527483 variant influences oral fat perception in Malaysian subjects.

    Science.gov (United States)

    Ong, Hing-Huat; Tan, Yen-Nee; Say, Yee-How

    2017-01-01

    We determined whether single nucleotide polymorphisms (SNPs; rs1761667 and rs1527483) in the fatty acid translocase CD36 gene - a receptor for fatty acids - is associated with oral fat perception (OFP) of different fat contents in custards and commercially-available foods, and obesity measures in Malaysian subjects (n=313; 118 males, 293 ethnic Chinese; 20 ethnic Indians). A 170-mm visual analogue scale was used to assess the ratings of perceived fat content, oiliness and creaminess of 0%, 2%, 6% and 10% fat content-by-weight custards and low-fat/regular versions of commercially-available milk, mayonnaise and cream crackers. Overall, the subjects managed to significantly discriminate the fat content, oiliness and creaminess between low-fat/regular versions of milk and mayonnaise. Females rated the perception of fat content and oiliness of both milks higher, but ethnicity, obesity and adiposity status did not seem to play a role in influencing most of OFP. The overall minor allele frequencies for rs1761667 and rs1527483 were 0.30 and 0.26, respectively. Females and individuals with rs1527483 TT genotype significantly perceived greater creaminess of 10% fat-by-weight custard. Also, individuals with rs1527483 TT genotype and T allele significantly perceived greater fat content of cream crackers, independent of fat concentration. rs1761667 SNP did not significantly affect OFP, except for cream crackers. Both gene variants were also not associated with obesity measures. Taken together, this study supports the notion that CD36 - specifically rs1527483, plays a role in OFP, but not in influencing obesity in Malaysian subjects. Besides, gender is an important factor for OFP, where females had higher sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The Use of Systematic Reviews and Reporting Guidelines to Advance the Implementation of the 3Rs

    Science.gov (United States)

    Avey, Marc T; Fenwick, Nicole; Griffin, Gilly

    2015-01-01

    In 1959, Russell and Burch published The Principles of Humane Experimental Technique, which included concrete advice on factors that they considered would govern progress in the implementation of these principles (enunciated as the 3Rs [Replacement, Reduction, and Refinement in animal-based studies]). One challenge to the implementation of the 3Rs was identified as information retrieval. Here, we further explore this challenge—the need for ‘research on research’—and the role that systematic reviews and reporting guidelines can play in implementation of the 3Rs. First, we examine the 2-fold nature of the challenge of information retrieval: 1) the identification of relevant publications spread throughout a large population of nonrelevant publications and 2) the incomplete reporting of relevant details within those publications. Second, we evaluate how systematic reviews and reporting guidelines can be used generally to address this challenge. Third, we assess the explicit reporting of the 3Rs in a cohort of preclinical animal systematic reviews. Our results show that Reduction methods are the most commonly reported by authors of systematic reviews but that, in general, reporting on how findings relate to the 3Rs is limited at best. Although systematic reviews are excellent tools for resolving the challenge of information retrieval, their utility for making progress in implementation of the 3Rs may be limited unless authors improve their reporting of these principles. PMID:25836961

  13. The common variant rs11646213 is associated with preeclampsia in Han Chinese women.

    Directory of Open Access Journals (Sweden)

    Ji-peng Wan

    Full Text Available BACKGROUND: Preeclampsia, characterized by hypertension and proteinuria, is a multifactorial disease caused by complex interactions between environmental and genetic factors. A recent genome-wide association study of blood pressure reported an association between hypertension and rs11646213. This study evaluated the association between preeclampsia and rs11646213. METHODS: A total of 454 cases and 460 controls were recruited to participate in this study. The single nucleotide polymorphism (SNP rs11646213 was genotyped by polymerase chain reaction (PCR and direct sequencing. RESULTS: The allele frequency of rs11646213 was significantly different between the preeclampsia and control groups (P = 0.017, OR = 1.36, 95% CI = 1.06-1.76. Differences were particularly significant in the severe preeclampsia subgroup (P = 0.002, OR = 1.54, 95% CI = 1.17-2.03 and the early-onset preeclampsia subgroup (P = 0.004, OR = 1.57, 95% CI = 1.16-2.13. Genotyping analysis showed that the T allele of rs11646213 could confer a risk for preeclampsia, severe preeclampsia and early-onset preeclampsia. CONCLUSIONS: Rs11646213 upstream of the CDH13 gene is associated with preeclampsia in Han Chinese women.

  14. Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis.

    Science.gov (United States)

    Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof; Pawlik, Andrzej

    2017-08-01

    Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

  15. The rs1527483, but not rs3212018, CD36 polymorphism associates with linoleic acid detection and obesity in Czech young adults

    Czech Academy of Sciences Publication Activity Database

    Plesník, J.; Šerý, Omar; Khan, A. S.; Bielik, P.; Khan, N. A.

    2018-01-01

    Roč. 119, č. 4 (2018), s. 472-478 ISSN 0007-1145 R&D Projects: GA MZd(CZ) NV16-29900A Institutional support: RVO:67985904 Keywords : CD36 * fat taste * genetic polymorphism * rs1527483 Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 3.706, year: 2016

  16. Lack of association between KCNJ11 (rs5219 and ABCC8 (rs757110 polymorphisms and sulphonylurea treatment response in type 2 diabetes patients in Novosibirsk region

    Directory of Open Access Journals (Sweden)

    Irina Arkad'evna Bondar

    2015-03-01

    Full Text Available Aim. Sulfonylureas (SU are widely used in everyday clinical practice in treatment of patients with type 2 diabetes mellitus (T2DM. There is a considerable variability in SU effects, which may be caused by psychological, social, biological and genetic factors. The aim of the study was to investigate the association between rs5219 KCNJ11 gene and rs757110 ABCC8 gene polymorphism and long-term response to SU-drugs of second and third generation in the Novosibirsk region. Materials and Methods. 326 patients with type 2 diabetes in the Novosibirsk region were examined. Patients were divided into 2 groups, depending on HbA1c level. The first group included patients with target HbA1c levels on SU monotherapy. The second group included patients who did not reach target HbA1c levels on the highest dose of SU. Genotyping of KCNJ11 (rs5219 and ABCC8 (rs757110 was performed by TaqMan real-time PCR (ICBFM SB RAS, Novosibirsk, Russia. Results. Patients with type 2 diabetes with a good response to SU-therapy compared to the group of patients with a poor response to SU-therapy were older (65.8?9.1 years vs. 61.6?7.9 years, p

  17. The gustin (CA6) gene polymorphism, rs2274333 (A/G), as a mechanistic link between PROP tasting and fungiform taste papilla density and maintenance.

    Science.gov (United States)

    Melis, Melania; Atzori, Elena; Cabras, Stefano; Zonza, Andrea; Calò, Carla; Muroni, Patrizia; Nieddu, Mariella; Padiglia, Alessandra; Sogos, Valeria; Tepper, Beverly J; Tomassini Barbarossa, Iole

    2013-01-01

    Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (pTreatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli.

  18. Two-stage gene regulation of the superoxide stress response soxRS system in Escherichia coli.

    Science.gov (United States)

    Nunoshiba, T

    1996-01-01

    All organisms have adapted to environmental changes by acquiring various functions controlled by gene regulation. In bacteria, a number of specific responses have been found to confer cell survival in various nutrient-limited conditions, and under physiological stresses such as high or low temperature, extreme pH, radiation, and oxidation (for review, see Neidhardt et al., 1987). In this article, I introduce an Escherichia coli (E. coli) global response induced by superoxide stress, the soxRS regulon. The functions controlled by this system consist of a wide variety of enzymes such as manganese-containing SOD (Mn-SOD); glucose 6-phosphate dehydrogenase (G6PD), the DNA repair enzyme endonuclease IV, fumarase C, NADPH:ferredoxin oxidoreductase, and aconitase. This response is positively regulated by a two-stage control system in which SoxR iron-sulfur protein senses exposure to superoxide and nitric oxide, and then activates transcription of the soxS gene, whose product stimulates the expression of the regulon genes. Our recent finding indicates that soxS transcription is initiated in a manner dependent on the rpoS gene encoding RNA polymerase sigma factor, theta s, in response to entering the stationary phase of growth. With this information, mechanisms for prokaryotic coordinating gene expression in response to superoxide stress and in stationary phase are discussed.

  19. A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

    Directory of Open Access Journals (Sweden)

    Johanna Hass

    Full Text Available Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328. A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170 on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10 had p-values between 6.75×10(-6 and 8.3×10(-7. Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings

  20. Coordinated Regulation of Anthocyanin Biosynthesis Genes Confers Varied Phenotypic and Spatial-Temporal Anthocyanin Accumulation in Radish (Raphanus sativus L.

    Directory of Open Access Journals (Sweden)

    Everlyne M'mbone Muleke

    2017-07-01

    Full Text Available Anthocyanins are natural pigments that have important functions in plant growth and development. Radish taproots are rich in anthocyanins which confer different taproot colors and are potentially beneficial to human health. The crop differentially accumulates anthocyanin during various stages of growth, yet molecular mechanisms underlying this differential anthocyanin accumulation remains unknown. In the present study, transcriptome analysis was used to concisely identify putative genes involved in anthocyanin biosynthesis in radish. Spatial-temporal transcript expressions were then profiled in four color variant radish cultivars. From the total transcript sequences obtained through illumina sequencing, 102 assembled unigenes, and 20 candidate genes were identified to be involved in anthocyanin biosynthesis. Fifteen genomic sequences were isolated and sequenced from radish taproot. The length of these sequences was between 900 and 1,579 bp, and the unigene coverage to all of the corresponding cloned sequences was more than 93%. Gene structure analysis revealed that RsF3′H is intronless and anthocyanin biosynthesis genes (ABGs bear asymmetrical exons, except RsSAM. Anthocyanin accumulation showed a gradual increase in the leaf of the red radish and the taproot of colored cultivars during development, with a rapid increase at 30 days after sowing (DAS, and the highest content at maturity. Spatial-temporal transcriptional analysis of 14 genes revealed detectable expressions of 12 ABGs in various tissues at different growth levels. The investigation of anthocyanin accumulation and gene expression in four color variant radish cultivars, at different stages of development, indicated that total anthocyanin correlated with transcript levels of ABGs, particularly RsUFGT, RsF3H, RsANS, RsCHS3 and RsF3′H1. Our results suggest that these candidate genes play key roles in phenotypic and spatial-temporal anthocyanin accumulation in radish through

  1. Refined Phenotyping of Modic Changes

    Science.gov (United States)

    Määttä, Juhani H.; Karppinen, Jaro; Paananen, Markus; Bow, Cora; Luk, Keith D.K.; Cheung, Kenneth M.C.; Samartzis, Dino

    2016-01-01

    Abstract Low back pain (LBP) is the world's most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese. We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting ≥30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors. In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P disability. The strength of the associations increased with the number of MC. This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP. PMID:27258491

  2. The phenotypic variance gradient - a novel concept.

    Science.gov (United States)

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  3. Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent.

    Science.gov (United States)

    Winham, Stacey J; Preuss, Ulrich W; Geske, Jennifer R; Zill, Peter; Heit, John A; Bakalkin, Georgy; Biernacka, Joanna M; Karpyak, Victor M

    2015-10-27

    We previously demonstrated that prodynorphin (PDYN) haplotypes and single nucleotide polymorphism (SNP) rs2281285 are associated with alcohol dependence and the propensity to drink in negative emotional states, and recent studies suggest that PDYN gene effects on substance dependence risk may be sex-related. We examined sex-dependent associations of PDYN variation with alcohol dependence and related phenotypes, including negative craving, time until relapse after treatment and the length of sobriety episodes before seeking treatment, in discovery and validation cohorts of European ancestry. We found a significant haplotype-by-sex interaction (p  =  0.03), suggesting association with alcohol dependence in males (p = 1E-4) but not females. The rs2281285 G allele increased risk for alcohol dependence in males in the discovery cohort (OR = 1.49, p = 0.002), with a similar trend in the validation cohort (OR = 1.35, p = 0.086). However, rs2281285 showed a trend towards association with increased negative craving in females in both the discovery (beta = 10.16, p = 0.045) and validation samples (OR = 7.11, p = 0.066). In the discovery cohort, rs2281285 was associated with time until relapse after treatment in females (HR = 1.72, p = 0.037); in the validation cohort, it was associated with increased length of sobriety episodes before treatment in males (beta = 13.49, p = 0.001). Our findings suggest that sex-dependent effects of PDYN variants in alcohol dependence are phenotype-specific.

  4. Association of calcium sensing receptor polymorphisms at rs1801725 with circulating calcium in breast cancer patients.

    Science.gov (United States)

    Wang, Li; Widatalla, Sarrah E; Whalen, Diva S; Ochieng, Josiah; Sakwe, Amos M

    2017-08-02

    Breast cancer (BC) patients with late-stage and/or rapidly growing tumors are prone to develop high serum calcium levels which have been shown to be associated with larger and aggressive breast tumors in post and premenopausal women respectively. Given the pivotal role of the calcium sensing receptor (CaSR) in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium levels in African American and Caucasian control subjects and BC cases. In this retrospective case-control study, we assessed the mean circulating calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and rs1801726 in 199 cases and 384 age-matched controls, and used multivariable regression analysis to determine whether these SNPs are associated with circulating calcium in control subjects and BC cases. We found that the mean circulating calcium levels in African American subjects were higher than those in Caucasian subjects (p calcium levels were higher in BC cases compared to control subjects (p calcium levels in BC patients were independent of race. We also show that in BC cases and control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726 (C/G, Q1011E) were common among Caucasians and African Americans respectively. Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were associated with higher calcium levels (p = 0.006) while those at rs1801726 were not. Using multivariable linear mixed-effects models and adjusting for age and race, we show that circulating calcium levels in BC cases were associated with tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). These data suggest that decreased sensitivity of the CaSR to calcium due to inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to high circulating calcium

  5. Cattle phenotypes can disguise their maternal ancestry.

    Science.gov (United States)

    Srirattana, Kanokwan; McCosker, Kieren; Schatz, Tim; St John, Justin C

    2017-06-26

    Cattle are bred for, amongst other factors, specific traits, including parasite resistance and adaptation to climate. However, the influence and inheritance of mitochondrial DNA (mtDNA) are not usually considered in breeding programmes. In this study, we analysed the mtDNA profiles of cattle from Victoria (VIC), southern Australia, which is a temperate climate, and the Northern Territory (NT), the northern part of Australia, which has a tropical climate, to determine if the mtDNA profiles of these cattle are indicative of breed and phenotype, and whether these profiles are appropriate for their environments. A phylogenetic tree of the full mtDNA sequences of different breeds of cattle, which were obtained from the NCBI database, showed that the mtDNA profiles of cattle do not always reflect their phenotype as some cattle with Bos taurus phenotypes had Bos indicus mtDNA, whilst some cattle with Bos indicus phenotypes had Bos taurus mtDNA. Using D-loop sequencing, we were able to contrast the phenotypes and mtDNA profiles from different species of cattle from the 2 distinct cattle breeding regions of Australia. We found that 67 of the 121 cattle with Bos indicus phenotypes from NT (55.4%) had Bos taurus mtDNA. In VIC, 92 of the 225 cattle with Bos taurus phenotypes (40.9%) possessed Bos indicus mtDNA. When focusing on oocytes from cattle with the Bos taurus phenotype in VIC, their respective oocytes with Bos indicus mtDNA had significantly lower levels of mtDNA copy number compared with oocytes possessing Bos taurus mtDNA (P cattle with a Bos taurus phenotype. The phenotype of cattle is not always related to their mtDNA profiles. MtDNA profiles should be considered for breeding programmes as they also influence phenotypic traits and reproductive capacity in terms of oocyte quality.

  6. Association between rs3087243 and rs231775 polymorphism within the cytotoxic T-lymphocyte antigen 4 gene and Graves' disease: a case/control study combined with meta-analyses

    Science.gov (United States)

    Dai, Yu; Zeng, Tianshu; Xiao, Fei; Chen, Lulu; Kong, Wen

    2017-01-01

    We conducted a case/control study to assess the impact of SNP rs3087243 and rs231775 within the CTLA4 gene, on the susceptibility to Graves' disease (GD) in a Chinese Han dataset (271 cases and 298 controls). The frequency of G allele for rs3087243 and rs231775 was observed to be significantly higher in subjects with GD than in control subjects (p = 0.005 and p = 0.000, respectively). After logistic regression analysis, a significant association was detected between SNP rs3087243 and GD in the additive and recessive models. Similarly, association for the SNP rs231775 could also be detected in the additive model, dominant model and recessive model. A meta-analysis, including 27 published datasets along with the current dataset, was performed to further confirm the association. Consistent with our case/control results, rs3087243 and rs231775 showed a significant association with GD in all genetic models. Of note, ethnic stratification revealed that these two SNPs were associated with susceptibility to GD in populations of both Asian and European descent. In conclusion, our data support that the rs3087243 and rs231775 polymorphisms within the CTLA4 gene confer genetic susceptibility to GD. PMID:29299173

  7. The 8q24 rs6983267G variant is associated with increased thyroid cancer risk.

    Science.gov (United States)

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Polanco Echeverry, Guadalupe; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carmona, Luis G Carvajal

    2015-10-01

    The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11-1.27, P=4.03×10(-7)), Japan (OR=1.20, 95% CI: 1.03-1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99-1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12 594 controls, confirmed the association between rs6983267G and TC (P=1.23×10(-7), OR=1.13, 95% CI: 1.08-1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by ∼13%. © 2015 Society for Endocrinology.

  8. 8q24 rs6983267G variant is associated with increased thyroid cancer risk

    Science.gov (United States)

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Echeverry, Guadalupe Polanco; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carvajal Carmona, Luis G.

    2015-01-01

    The G allele of the rs6983267 single nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in thyroid cancer susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3,067 cases and 8,575 controls. We detected significant associations between rs6983267G and thyroid cancer in the British Isles (Odds Ratio, OR= 1.19, 95% confidence interval, CI: 1.11–1.27, P= 4.03 × 10−7), Japan (OR= 1.20, 95% CI: 1.03–1.41, P= 0.022) and a borderline significant association of similar effect direction and size in Colombia (OR= 1.19, 95% CI: 0.99–1.44, P= 0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5,484 cases and 12,594 controls, confirmed the association between rs6983267G and thyroid cancer (P= 1.23 × 10−7, OR= 1.13, 95% CI: 1.07–1.18). Our results therefore support the notion that rs6983267G is a bona fide thyroid cancer risk variant that increases the risk of disease by ~13%. PMID:26290501

  9. Evaluation of IFITM3 rs12252 Association With Severe Pediatric Influenza Infection.

    Science.gov (United States)

    Randolph, Adrienne G; Yip, Wai-Ki; Allen, Emma Kaitlynn; Rosenberger, Carrie M; Agan, Anna A; Ash, Stephanie A; Zhang, Yu; Bhangale, Tushar R; Finkelstein, David; Cvijanovich, Natalie Z; Mourani, Peter M; Hall, Mark W; Su, Helen C; Thomas, Paul G

    2017-07-01

    Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  10. Phenotype variations affect genetic association studies of degenerative disc disease: conclusions of analysis of genetic association of 58 single nucleotide polymorphisms with highly specific phenotypes for disc degeneration in 332 subjects.

    Science.gov (United States)

    Rajasekaran, S; Kanna, Rishi Mugesh; Senthil, Natesan; Raveendran, Muthuraja; Cheung, Kenneth M C; Chan, Danny; Subramaniam, Sakthikanal; Shetty, Ajoy Prasad

    2013-10-01

    Although the influence of genetics on the process of disc degeneration is well recognized, in recently published studies, there is a wide variation in the race and selection criteria for such study populations. More importantly, the radiographic features of disc degeneration that are selected to represent the disc degeneration phenotype are variable in these studies. The study presented here evaluates the association between single nucleotide polymorphisms (SNPs) of candidate genes and three distinct radiographic features that can be defined as the degenerative disc disease (DDD) phenotype. The study objectives were to examine the allelic diversity of 58 SNPs related to 35 candidate genes related to lumbar DDD, to evaluate the association in a hitherto unevaluated ethnic Indian population that represents more than one-sixth of the world population, and to analyze how genetic associations can vary in the same study subjects with the choice of phenotype. A cross-sectional, case-control study of an ethnic Indian population was carried out. Fifty-eight SNPs in 35 potential candidate genes were evaluated in 342 subjects and the associations were analyzed against three highly specific markers for DDD, namely disc degeneration by Pfirrmann grading, end-plate damage evaluated by total end-plate damage score, and annular tears evaluated by disc herniations and hyperintense zones. Genotyping of cases and controls was performed on a genome-wide SNP array to identify potential associated disease loci. The results from the genome-wide SNP array were then used to facilitate SNP selection and genotype validation was conducted using Sequenom-based genotyping. Eleven of the 58 SNPs provided evidence of association with one of the phenotypes. For annular tears, rs1042631 SNP of AGC1 and rs467691 SNP of ADAMTS5 were highly significantly associated (p<.01) and SNPs in NGFB, IL1B, IL18RAP, and MMP10 were also significantly associated (p<.05). The rs4076018 SNP of NGFB was highly

  11. Genetic Polymorphisms in SOD (rs2070424, rs7880) and CAT (rs7943316, rs1001179) Enzymes Are Associated with Increased Body Fat Percentage and Visceral Fat in an Obese Population from Central Mexico.

    Science.gov (United States)

    Hernández-Guerrero, César; Hernández-Chávez, Paulina; Romo-Palafox, Inés; Blanco-Melo, Grecia; Parra-Carriedo, Alicia; Pérez-Lizaur, Ana

    2016-07-01

    Oxidative disturbance is an important factor involved in the etiology of comorbidities associated with obesity. Genetic polymorphisms such as SOD1 -251A>G, SOD2 47 C>T, CAT -21A>T and CAT -262 C>T have been described to alter the activity of antioxidant enzymes. The aim of the present work was to analyze the association of the mentioned SNPs with obesity and their relationship with anthropometric and clinical variables in this group. The study included 416 Mexican women (208 normal weight, NW and 208 subjects with obesity, OB). Dietary intake, anthropometric, biochemical and clinical features were evaluated and then analyzed in function of the genotypes. The mutated carriers (GA+GG) of SOD -251 were significantly higher in the OB group (0.24) compared to the NW group (0.08). The other SNPs showed no differences compared with control group. When comparing carrier mutated subjects with obesity vs. wild-type obese participants with the SNPs SOD1 -251, SOD2 47 and CAT -262, the carriers showed a significantly (p G is associated with obesity independent of the presence of diabetes or dyslipidemia. Mutated obese carries of SOD1 -251, SOD2 47 and CAT -262 are associated with a higher distribution of fat in comparison with obese wild-type carriers. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  12. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have

  13. Daddy issues: paternal effects on phenotype.

    Science.gov (United States)

    Rando, Oliver J

    2012-11-09

    The once popular and then heretical idea that ancestral environment can affect the phenotype of future generations is coming back into vogue due to advances in the field of epigenetic inheritance. How paternal environmental conditions influence the phenotype of progeny is now a tractable question, and researchers are exploring potential mechanisms underlying such effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Phenotypes of organ involvement in sarcoidosis

    NARCIS (Netherlands)

    Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena; Mihailović-Vučinić, Violeta; Rottoli, Paola; Grubanovic, Aleksandar; Müller, Annegret; Jochens, Arne; Tittmann, Lukas; Schnerch, Jasmin; Olivieri, Carmela; Fischer, Annegret; Jovanovic, Dragana; Filipovic, Snežana; Videnovic-Ivanovic, Jelica; Bresser, Paul; Jonkers, René; O'Reilly, Kate; Ho, Ling-Pei; Gaede, Karoline I.; Zabel, Peter; Dubaniewicz, Anna; Marshall, Ben; Kieszko, Robert; Milanowski, Janusz; Günther, Andreas; Weihrich, Anette; Petrek, Martin; Kolek, Vitezslav; Keane, Michael P.; O'Beirne, Sarah; Donnelly, Seamas; Haraldsdottir, Sigridur Olina; Jorundsdottir, Kristin B.; Costabel, Ulrich; Bonella, Francesco; Wallaert, Benoît; Grah, Christian; Peroš-Golubičić, Tatjana; Luisetti, Mauritio; Kadija, Zamir; Pabst, Stefan; Grohé, Christian; Strausz, János; Vašáková, Martina; Sterclova, Martina; Millar, Ann; Homolka, Jiří; Slováková, Alena; Kendrick, Yvonne; Crawshaw, Anjali; Wuyts, Wim; Spencer, Lisa; Pfeifer, Michael; Valeyre, Dominique; Poletti, Venerino; Wirtz, Hubertus; Prasse, Antje; Schreiber, Stefan; Krawczak, Michael; Müller-Quernheim, Joachim

    2018-01-01

    Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis. The baseline

  15. Emerging semantics to link phenotype and environment

    Directory of Open Access Journals (Sweden)

    Anne E. Thessen

    2015-12-01

    Full Text Available Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1 use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2 two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3 two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE and the Biological Collections Ontology (BCO; these provide a starting point for the development of a data model linking phenotypes and environments.

  16. Haptoglobin Phenotypes and Hypertension in Indigenous Zambians ...

    African Journals Online (AJOL)

    Haptoglobin Phenotypes and Hypertension in Indigenous Zambians at the University Teaching Hospital, Lusaka, Zambia. MM Phiri, T Kaile, FM Goma. Abstract. Objectives: The aim of the study was to investigate the association between presence of haptoglobin phenotypes and hypertension in indigenous Zambian patients ...

  17. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-01

    a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology

  18. The Neuroanatomy of the Autistic Phenotype

    Science.gov (United States)

    Fahim, Cherine; Meguid, Nagwa A.; Nashaat, Neveen H.; Yoon, Uicheul; Mancini-Marie, Adham; Evans, Alan C.

    2012-01-01

    The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X…

  19. Reduced TCA flux in diabetic myotubes: A governing influence on the diabetic phenotype?

    Science.gov (United States)

    Gaster, Michael

    2009-10-02

    The diabetic phenotype is complex, requiring elucidation of key initiating defects. It is unknown whether the reduced tricarboxylic acid cycle (TCA) flux in skeletal muscle of obese and obese type 2 diabetic (T2D) subjects is of primary origin. Acetate oxidation (measurement of TCA-flux) was significantly reduced in primary myotube cultures established from T2D versus lean subjects. Acetate oxidation was acutely stimulated by insulin and respiratory uncoupling. Inhibition of TCA flux in lean myotubes by malonate was followed by a measured decline in; acetate oxidation, complete palmitate oxidation, lipid uptake, glycogen synthesis, ATP content and increased glucose uptake, while glucose oxidation was unaffected. Acute TCA inhibition did not induce insulin resistance. Thus the reduced TCA cycle flux in T2D skeletal muscle may be of primary origin. The diabetic phenotype of increased basal glucose uptake and glucose oxidation, the reduced complete lipid oxidation and increased respiratory quotient, are likely to be adaptive responses to the reduced TCA cycle flux.

  20. Evolving phenotypic networks in silico.

    Science.gov (United States)

    François, Paul

    2014-11-01

    Evolved gene networks are constrained by natural selection. Their structures and functions are consequently far from being random, as exemplified by the multiple instances of parallel/convergent evolution. One can thus ask if features of actual gene networks can be recovered from evolutionary first principles. I review a method for in silico evolution of small models of gene networks aiming at performing predefined biological functions. I summarize the current implementation of the algorithm, insisting on the construction of a proper "fitness" function. I illustrate the approach on three examples: biochemical adaptation, ligand discrimination and vertebrate segmentation (somitogenesis). While the structure of the evolved networks is variable, dynamics of our evolved networks are usually constrained and present many similar features to actual gene networks, including properties that were not explicitly selected for. In silico evolution can thus be used to predict biological behaviours without a detailed knowledge of the mapping between genotype and phenotype. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  1. Adjusting phenotypes by noise control.

    Directory of Open Access Journals (Sweden)

    Kyung H Kim

    2012-01-01

    Full Text Available Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

  2. Federated Tensor Factorization for Computational Phenotyping

    Science.gov (United States)

    Kim, Yejin; Sun, Jimeng; Yu, Hwanjo; Jiang, Xiaoqian

    2017-01-01

    Tensor factorization models offer an effective approach to convert massive electronic health records into meaningful clinical concepts (phenotypes) for data analysis. These models need a large amount of diverse samples to avoid population bias. An open challenge is how to derive phenotypes jointly across multiple hospitals, in which direct patient-level data sharing is not possible (e.g., due to institutional policies). In this paper, we developed a novel solution to enable federated tensor factorization for computational phenotyping without sharing patient-level data. We developed secure data harmonization and federated computation procedures based on alternating direction method of multipliers (ADMM). Using this method, the multiple hospitals iteratively update tensors and transfer secure summarized information to a central server, and the server aggregates the information to generate phenotypes. We demonstrated with real medical datasets that our method resembles the centralized training model (based on combined datasets) in terms of accuracy and phenotypes discovery while respecting privacy. PMID:29071165

  3. Nordic research infrastructures for plant phenotyping

    Directory of Open Access Journals (Sweden)

    Kristiina Himanen

    2018-03-01

    Full Text Available Plant phenomics refers to the systematic study of plant phenotypes. Together with closely monitored, controlled climates, it provides an essential component for the integrated analysis of genotype-phenotype-environment interactions. Currently, several plant growth and phenotyping facilities are under establishment globally, and numerous facilities are already in use. Alongside the development of the research infrastructures, several national and international networks have been established to support shared use of the new methodology. In this review, an overview is given of the Nordic plant phenotyping and climate control facilities. Since many areas of phenomics such as sensor-based phenotyping, image analysis and data standards are still developing, promotion of educational and networking activities is especially important. These facilities and networks will be instrumental in tackling plant breeding and plant protection challenges. They will also provide possibilities to study wild species and their ecological interactions under changing Nordic climate conditions.

  4. DeAnnIso: a tool for online detection and annotation of isomiRs from small RNA sequencing data.

    Science.gov (United States)

    Zhang, Yuanwei; Zang, Qiguang; Zhang, Huan; Ban, Rongjun; Yang, Yifan; Iqbal, Furhan; Li, Ao; Shi, Qinghua

    2016-07-08

    Small RNA (sRNA) Sequencing technology has revealed that microRNAs (miRNAs) are capable of exhibiting frequent variations from their canonical sequences, generating multiple variants: the isoforms of miRNAs (isomiRs). However, integrated tool to precisely detect and systematically annotate isomiRs from sRNA sequencing data is still in great demand. Here, we present an online tool, DeAnnIso (Detection and Annotation of IsomiRs from sRNA sequencing data). DeAnnIso can detect all the isomiRs in an uploaded sample, and can extract the differentially expressing isomiRs from paired or multiple samples. Once the isomiRs detection is accomplished, detailed annotation information, including isomiRs expression, isomiRs classification, SNPs in miRNAs and tissue specific isomiR expression are provided to users. Furthermore, DeAnnIso provides a comprehensive module of target analysis and enrichment analysis for the selected isomiRs. Taken together, DeAnnIso is convenient for users to screen for isomiRs of their interest and useful for further functional studies. The server is implemented in PHP + Perl + R and available to all users for free at: http://mcg.ustc.edu.cn/bsc/deanniso/ and http://mcg2.ustc.edu.cn/bsc/deanniso/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. A Molecular Case-Control Study on the Association of Melatonin Hormone and rs#10830963 Single Nucleotide Polymorphism in its Receptor MTNR1B Gene with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Nadia A Abd El Moneim

    2015-01-01

    Full Text Available Background: The main function of the pineal hormone melatonin which is mediated via its two receptors, MTNR1A and MTNR1B, is to mediate dark signals in addition to anti-oxidation, immune system enhancement, protection from radiation, and anti-cancer functions. A common single nucleotide polymorphism in the MTNR1B gene is rs#10830963, which is well known as a risk factor for type 2 diabetes mellitus. This study intends to figure out the role of melatonin and its receptor MTNR1B gene rs#10830963 polymorphism in breast cancer incidence, diagnosis and prognosis. Methods: This study included 43 females with breast cancer and 45 apparently normal healthy females. Restriction fragment length polymorphism-PCR was used for amplification and genotyping of the MTNR1B gene rs#10830963 polymorphism in whole blood. Serum melatonin levels were measured using a ready-for-use radioimmunoassay kit. Results: For the MTNR1B gene rs#10830963 polymorphism, we observed a significantly higher GG genotype frequency among cases (72.1% than controls (13.3%, with a diagnostic sensitivity of 83.78% and specificity of 76.47%. The cases had a frequency of 11.6% for the CC genotype and 16.3% for the CG genotype which was significantly lower compared to controls that had a 44.4% frequency of the CC genotype and 42.2% frequency of the CG genotype. The GG genotype had a significant association with larger tumor volume (P=0.048. Serum melatonin levels were significantly lower among breast cancer patients than controls. Using the ROC curve analysis, serum melatonin showed a significant AUC (72.6%, P39.5 pg/ml. Conclusion: The risk for breast cancer incidence increased as the serum levels of melatonin decreased and in females homozygous for the G allele (GG genotype of the MTNR1B gene rs#10830963 polymorphism. The GG genotype was found to be associated with increased breast tumor volume as a marker of a poor prognosis breast cancer.

  6. Genetic variants and early cigarette smoking and nicotine dependence phenotypes in adolescents.

    Directory of Open Access Journals (Sweden)

    Jennifer O'Loughlin

    Full Text Available While the heritability of cigarette smoking and nicotine dependence (ND is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes.In a prospective study of 1294 adolescents aged 12-13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7-8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator.The pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1 were associated with at least one phenotype with a p-value <0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and self-medication phenotypes were both 0.076.Because the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3.Dopaminergic pathways may be salient during early smoking and the development of ND.

  7. Striatal response to reward anticipation: evidence for a systems-level intermediate phenotype for schizophrenia.

    Science.gov (United States)

    Grimm, Oliver; Heinz, Andreas; Walter, Henrik; Kirsch, Peter; Erk, Susanne; Haddad, Leila; Plichta, Michael M; Romanczuk-Seiferth, Nina; Pöhland, Lydia; Mohnke, Sebastian; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Schäfer, Axel; Cichon, Sven; Nöthen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas

    2014-05-01

    Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder. To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929). Examination of a well-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied. Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype. Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P systems-level functional phenotype is reliable (with intraclass correlation coefficients of 0.59-0.73), independent of local gray matter volume (with no corresponding group differences and no correlation to function, and with all uncorrected P values >.05), and affected by

  8. Two-Component Signal Transduction System SaeRS Positively Regulates Staphylococcus epidermidis Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Qiang Lou

    2014-01-01

    Full Text Available Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, we performed a proteomic analysis of differences in expression between the S. epidermidis 1457 wild-type and saeRS mutant to identify candidates regulated by saeRS using two-dimensional gel electrophoresis (2-DE combined with matrix-assisted laser desorption/lonization mass spectrometry (MALDI-TOF-MS. Of 55 identified proteins that significantly differed in expression between the two strains, 15 were upregulated and 40 were downregulated. The downregulated proteins included enzymes related to glycolysis and TCA cycle, suggesting that glucose is not properly utilized in S. epidermidis when saeRS was deleted. The study will be helpful for treatment of S. epidermidis infection from the viewpoint of metabolic modulation dependent on two-component signal transduction system SaeRS.

  9. FIRE, A Test Bed for ARIES-RS/AT Advanced Physics and Plasma Technology

    International Nuclear Information System (INIS)

    Meade, Dale M.

    2004-01-01

    The overall vision for FIRE [Fusion Ignition Research Experiment] is to develop and test the fusion plasma physics and plasma technologies needed to realize capabilities of the ARIES-RS/AT power plant designs. The mission of FIRE is to attain, explore, understand and optimize a fusion dominated plasma which would be satisfied by producing D-T [deuterium-tritium] fusion plasmas with nominal fusion gains ∼10, self-driven currents of ∼80%, fusion power ∼150-300 MW, and pulse lengths up to 40 s. Achieving these goals will require the deployment of several key fusion technologies under conditions approaching those of ARIES-RS/AT. The FIRE plasma configuration with strong plasma shaping, a double null pumped divertor and all metal plasma-facing components is a 40% scale model of the ARIES-RS/AT plasma configuration. ''Steady-state'' advanced tokamak modes in FIRE with high beta, high bootstrap fraction, and 100% noninductive current drive are suitable for testing the physics of the ARIES-RS/A T operating modes. The development of techniques to handle power plant relevant exhaust power while maintaining low tritium inventory is a major objective for a burning plasma experiment. The FIRE high-confinement modes and AT-modes result in fusion power densities from 3-10 MWm -3 and neutron wall loading from 2-4 MWm -2 which are at the levels expected from the ARIES-RS/AT design studies

  10. Prediction of solubilities for ginger bioactive compounds in hot water by the COSMO-RS method

    Science.gov (United States)

    Zaimah Syed Jaapar, Syaripah; Azian Morad, Noor; Iwai, Yoshio

    2013-04-01

    The solubilities in water of four main ginger bioactives, 6-gingerol, 6-shogaol, 8-gingerol and 10-gingerol, were predicted using a conductor-like screening model for real solvent (COSMO-RS) calculations. This study was conducted since no experimental data are available for ginger bioactive solubilities in hot water. The σ-profiles of these selected molecules were calculated using Gaussian software and the solubilities were calculated using the COSMO-RS method. The solubilities of these ginger bioactives were calculated at 50 to 200 °C. In order to validate the accuracy of the COSMO-RS method, the solubilities of five hydrocarbon molecules were calculated using the COSMO-RS method and compared with the experimental data in the literature. The selected hydrocarbon molecules were 3-pentanone, 1-hexanol, benzene, 3-methylphenol and 2-hydroxy-5-methylbenzaldehyde. The calculated results of the hydrocarbon molecules are in good agreement with the data in the literature. These results confirm that the solubilities of ginger bioactives can be predicted using the COSMO-RS method. The solubilities of the ginger bioactives are lower than 0.0001 at temperatures lower than 130 °C. At 130 to 200 °C, the solubilities increase dramatically with the highest being 6-shogaol, which is 0.00037 mole fraction, and the lowest is 10-gingerol, which is 0.000039 mole fraction at 200 °C.

  11. Prediction of solubilities for ginger bioactive compounds in hot water by the COSMO-RS method

    International Nuclear Information System (INIS)

    Jaapar, Syaripah Zaimah Syed; Iwai, Yoshio; Morad, Noor Azian

    2013-01-01

    The solubilities in water of four main ginger bioactives, 6-gingerol, 6-shogaol, 8-gingerol and 10-gingerol, were predicted using a conductor-like screening model for real solvent (COSMO-RS) calculations. This study was conducted since no experimental data are available for ginger bioactive solubilities in hot water. The σ-profiles of these selected molecules were calculated using Gaussian software and the solubilities were calculated using the COSMO-RS method. The solubilities of these ginger bioactives were calculated at 50 to 200 °C. In order to validate the accuracy of the COSMO-RS method, the solubilities of five hydrocarbon molecules were calculated using the COSMO-RS method and compared with the experimental data in the literature. The selected hydrocarbon molecules were 3-pentanone, 1-hexanol, benzene, 3-methylphenol and 2-hydroxy-5-methylbenzaldehyde. The calculated results of the hydrocarbon molecules are in good agreement with the data in the literature. These results confirm that the solubilities of ginger bioactives can be predicted using the COSMO-RS method. The solubilities of the ginger bioactives are lower than 0.0001 at temperatures lower than 130 °C. At 130 to 200 °C, the solubilities increase dramatically with the highest being 6-shogaol, which is 0.00037 mole fraction, and the lowest is 10-gingerol, which is 0.000039 mole fraction at 200 °C.

  12. Association of STAT4 rs7574865 with susceptibility to systemic lupus erythematosus in Iranian population.

    Science.gov (United States)

    Mirkazemi, Sedigheh; Akbarian, Mahmoud; Jamshidi, Ahmad Reza; Mansouri, Reza; Ghoroghi, Shima; Salimi, Yahya; Tahmasebi, Zahra; Mahmoudi, Mahdi

    2013-12-01

    Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with complex genetic inheritance that affecting different organs and systems. STAT4 has been newly identified as a susceptible gene in the development of SLE. According to recent studies, STAT4 has been associated with SLE in various populations. We investigated whether STAT4 single nucleotide polymorphisms (SNPs) were associated with susceptibility and clinical features of SLE in Iranian patients. The study group comprised 280 patients with SLE and 281 sex-, age-, and ethnicity-matched healthy controls of Iranian ancestry. Two SNPs (rs7574865 and rs7601754) were genotyped using the TaqMan MGB Allelic Discrimination method. Our results showed a significant association between rs7574865 T allele (odds ratio (OR) = 1.50, 95 % CI = 1.18-1.92, P = 0.002) and susceptibility to SLE. The rs7574865TT genotype (P = 0.02, OR = 1.94, 95 % CI = 1.74-3.19) and GT genotype (P = 0.008, OR = 1.71, 95 % CI = 1.19-2.45) showed a significant association with the risk of SLE in the Iranian population. We concluded that STAT4 rs7574865 is associated with SLE susceptibility in the Iranian population and this SNP might be a factor in the pathogenesis of SLE. However, further studies are required to investigate the mechanism by which polymorphisms in this gene lead to SLE.

  13. The Nature of Stable Insomnia Phenotypes

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L.

    2015-01-01

    Study Objectives: We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Design: Longitudinal. Setting: Urban, community-based. Participants: Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). Interventions: None. Measurements and results: At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the “neither criterion” phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. Conclusions: By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With

  14. Influence of VEGFA gene polymorphisms rs2010963 and rs699947 on clinical and laboratory indicators in diabetic retinopathy among patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    A.S. Gudz

    2017-10-01

    Full Text Available Background. A key factor of neoangiogenesis deve­lopment in diabetic retinopathy (DR among patients with type 2 diabetes mellitus (DM is vascular endothelial growth factor A (VEGFA. The important role of genetic polymorphisms of the VEGFA gene indicates a number of studies and meta-analyzes, that have shown their association with DR, especially with its proliferative variant, which varies in different populations. Accordingly, the purpose of this work was to find out the influence of the polymorphic genotypes rs2010963 and rs699947 of the VEGFA gene on clinical and laboratory parameters of DR in DM patients from Ukrainian population. Materials and methods. The study involved 302 patients with type 2 diabetes mellitus and DR. Diagnosis was established according to the international clinical classification adopted by the American Academy of Ophthalmology (2003. The control group consisted of 98 people who did not have DM and DR, as well as other ophthalmic diseases. All patients were operated on cataract. In the intraocular fluid collected during the surgery, the VEGFA content was determined by the immunoassay method. Analysis of the polymorphic DNA loci of the VEGFA gene: rs2010963 and rs699947 was performed in a real time polymerase chain reaction using TaqMan Mutation Detection Assays (Thermo Fisher Scientific, USA. Results. An analysis of the study results showed that rs2010963 polymorphism had an effect on the intraocular fluid VEGFA level (maximum — under the C/C risk genotype. This polymorphism was related to the sex (the genotype C/C was more common in men than in women: 3 : 1, the presence of proliferative DR (most often was determined by the presence of the genotype C/C: 45.4 % and neovascularization of the optic disc (most often determined by the pre­sence of heterozygotes G/C: 21.4 %. Polymorphism rs699947 had an effect on the visual acuity (the minimum was available in the genotype C/C, the thickness of the retina (the maximum

  15. Familjearbetaren hos en ensamförsörjare : en kvalitativ studie om ensamförsörjarens livssituation och hur familjearbetet påverkas

    OpenAIRE

    Sjöblom, Mikaela; Azimi, Diana

    2013-01-01

    Syftet med vårt lärdomsprov är att redogöra för familjearbetarnas åsikter om familjearbetet har specifika drag i utförandet av det hos familjer med en försörjare. I teoridelen tas det upp om familjepolitiken i Finland, familjearbete samt om hur en ensamförsörjares livssituation kan se ut. I undersökningen använde vi oss av kvalitativa forskningsintervjuer. Undersökningspersonerna bestod av åtta familjearbetare från fyra olika kommuner. Intervjuerna gjordes både i grupper och som individue...

  16. Role of micro RNAs (miRs) involved in hemato lymphoid differentiation and malignancy: identification of novel miRs expressed in b-, t- lymphoid and hematopoietic cells

    International Nuclear Information System (INIS)

    Bronte, V.; Zanovello, P.; Dalla Favera, R.

    2009-01-01

    Total RNA from CD14+ cells (monocytes), CD15+ cells (polymorphonuclear cells), eosinophils, CD8+ T cells, resting and activated CD4+ T cells, two HTLV-1-infected cell lines (C91PL and MT-2), and different thymocyte populations was used as a source of small RNAs for the construction of miR cDNA libraries. In the initial phase of the study, sequences were identified after cloning cDNAs into a plasmid; to expedite this analysis, the cloning step has been replaced by direct 454 sequencing of uncloned cDNAs, carried out by Drs. G. DeBellis and A. Guffanti of the CNR, Istituto di Tecnologie Biomediche (Segrate-Milano). Resulting sequences are subjected to a series of bioinformatics analysis steps designed to identify known miRs (i.e., those catalogued in the Sanger miRBASE) and sequences that represent potential new miRs

  17. Catalytic oxidation using nitrous oxide

    Directory of Open Access Journals (Sweden)

    Juan Carlos Beltran-Prieto

    2017-01-01

    Full Text Available Nitrous oxide is a very inert gas used generally as oxidant as it offers some advantage compared with other oxidants such as O2 but a considerably higher temperature (> 526 °C is often required. For particular cases such as the oxidation of sugar alcohols, especially for the oxidation of primary alcohols to aldehydes, N2O has the advantage over O2 of a higher reaction selectivity. In the present paper we present the modelling of oxidation reaction of sugar alcohols using an oxidizing agent in low concentrations, which is important to suppress subsequent oxidation reactions due to the very low residual concentrations of the oxidizing agent. For orientation experiments we chose nitrous oxide generated by thermal decomposition of ammonium nitrate. Kinetic modeling of the reaction was performed after determination of the differential equations that describe the system under study.

  18. TSHR intronic polymorphisms (rs179247 and rs12885526) and their role in the susceptibility of the Brazilian population to Graves' disease and Graves' ophthalmopathy.

    Science.gov (United States)

    Bufalo, N E; Dos Santos, R B; Marcello, M A; Piai, R P; Secolin, R; Romaldini, J H; Ward, L S

    2015-05-01

    Intronic thyroid-stimulating hormone receptor polymorphisms have been associated with the risk for both Graves' disease and Graves' ophthalmopathy, but results have been inconsistent among different populations. We aimed to investigate the influence of thyroid-stimulating hormone receptor intronic polymorphisms in a large well-characterized population of GD patients. We studied 279 Graves' disease patients (231 females and 48 males, 39.80 ± 11.69 years old), including 144 with Graves' ophthalmopathy, matched to 296 healthy control individuals. Thyroid-stimulating hormone receptor genotypes of rs179247 and rs12885526 were determined by Real Time PCR TaqMan(®) SNP Genotyping. A multivariate analysis showed that the inheritance of the thyroid-stimulating hormone receptor AA genotype for rs179247 increased the risk for Graves' disease (OR = 2.821; 95 % CI 1.595-4.990; p = 0.0004), whereas the thyroid-stimulating hormone receptor GG genotype for rs12885526 increased the risk for Graves' ophthalmopathy (OR = 2.940; 95 % CI 1.320-6.548; p = 0.0083). Individuals with Graves' ophthalmopathy also presented lower mean thyrotropin receptor antibodies levels (96.3 ± 143.9 U/L) than individuals without Graves' ophthalmopathy (98.3 ± 201.9 U/L). We did not find any association between the investigated polymorphisms and patients clinical features or outcome. We demonstrate that thyroid-stimulating hormone receptor intronic polymorphisms are associated with the susceptibility to Graves' disease and Graves' ophthalmopathy in the Brazilian population, but do not appear to influence the disease course.

  19. Percepção das paisagens da Floresta Nacional de Canela (RS pelos turistas / Landscapes perception of the of the National Forest of Canela (RS

    Directory of Open Access Journals (Sweden)

    Nara Rejane Zamberlan dos Santos

    2012-04-01

    Full Text Available ResumoUm estudo foi realizado com os turistas da cidade de Canela (RS, em quatro períodos do ano (julho-outubro, dezembro e fevereiro, com o objetivo de valorar 22 fotos (substitutos da paisagem da Floresta Nacional de Canela (RS, cuja escala de ponderação era variável de 1 a 5, correspondendo a classes de qualidade da paisagem de muito baixa a muito alta, respectivamente. Os resultados mostram que as mulheres são mais perceptivas do que os homens na análise de paisagens. Os menores valores médios valorados correspondem aos substitutos da classe baixa (2,74 e os mais altos, à classe alta de qualidade da paisagem (4,61. Por meio da Análise de Agrupamento Hierárquico, são observados dois grupos, sendo o primeiro, formado por mulheres de 15 a mais de 70 anos e jovens de 15 a 20 anos, do sexo masculino; e o segundo grupo, pelos demais homens.AbstractA study was carried out with the tourists of the city of Canela (RS, in four periods of the year (July, October, December and February, in order to value 22 photographs (landscape substitutes of the National Forest of Canela (RS, which weighting scale varied from 1 to 5. it was corresponding to very low to very high landscape classifications. The results show that women are more perceptive than men in landscape analysis. The lowest average values given correspond with low –class substitutes (2.74 and the highest with high quality landscapes (4.61. Through hierarchical group analysis were shown two groups, the first formed by women from 15 to over 70 years of age and young men of 15 to 20 years of age and second group by older men.

  20. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    AlShahrani, Mona; Hoehndorf, Robert

    2018-01-01

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  1. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    Alshahrani, Mona

    2018-04-30

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  2. ApoE rs429358 and rs7412 Polymorphism and Gender Differences of Serum Lipid Profile and Cognition in Aging Chinese Population

    Directory of Open Access Journals (Sweden)

    Jie Zhen

    2017-08-01

    Full Text Available ApoE gene polymorphism has been reportedly associated with serum lipids and cognition. However, very few studies have explored the combined effects of ApoE gene polymorphism and gender on serum lipid profile with subsequent impacts on cognition in Chinese population. A total of 1,000 Chinese community dwellers aged 55 years and above were recruited in this cross-sectional study. Demographic information of the participants was collected using well designed self-administered questionnaires. The Montreal Cognitive Assessment (MoCA test was employed to evaluate the cognitive status of the participants. Semi-quantitative food frequency questionnaire (FFQ was used to obtain the dietary intake information. Fasting venous blood samples were taken for ApoE genotyping and serum lipid measurements. Significant gender differences in cognition, serum lipid profile and dietary fat-rich foods consumption were observed (p < 0.05. Cognition of the subjects was found to be associated with ApoE genotypes (p < 0.05. ApoE rs429358 and rs7412 variants demonstrated a significant effect on cognitive performance in the male subjects; especially within the attention and language cognitive domains as well as the total MoCA score (p < 0.05, respectively. Serum lipid profile and cognition of Chinese adults are significantly linked with gender and ApoE genetic polymorphism. The ApoE variant rs429358 is found to be notably associated with cognition in aging male Chinese population.

  3. The RNA-binding protein HOS5 and serine/arginine-rich proteins RS40 and RS41 participate in miRNA biogenesis in Arabidopsis

    KAUST Repository

    Chen, Tao

    2015-07-30

    MicroRNAs are a class of small regulatory RNAs that are generated from primary miRNA (pri-miRNA) transcripts with a stem-loop structure. Accuracy of the processing of pri-miRNA into mature miRNA in plants can be enhanced by SERRATE (SE) and HYPONASTIC LEAVES 1 (HYL1). HYL1 activity is regulated by the FIERY2 (FRY2)/RNA polymerase II C-terminal domain phosphatase-like 1 (CPL1). Here, we discover that HIGH OSMOTIC STRESS GENE EXPRESSION 5 (HOS5) and two serine/arginine-rich splicing factors RS40 and RS41, previously shown to be involved in pre-mRNA splicing, affect the biogenesis of a subset of miRNA. These proteins are required for correct miRNA strand selection and the maintenance of miRNA levels. FRY2 dephosphorylates HOS5 whose phosphorylation status affects its subnuclear localization. HOS5 and the RS proteins bind both intronless and intron-containing pri-miRNAs. Importantly, all of these splicing-related factors directly interact with both HYL1 and SE in nuclear splicing speckles. Our results indicate that these splicing factors are directly involved in the biogenesis of a group of miRNA.

  4. ApoE rs429358 and rs7412 Polymorphism and Gender Differences of Serum Lipid Profile and Cognition in Aging Chinese Population.

    Science.gov (United States)

    Zhen, Jie; Huang, Xiaochen; Van Halm-Lutterodt, Nicholas; Dong, Shengqi; Ma, Weiwei; Xiao, Rong; Yuan, Linhong

    2017-01-01

    ApoE gene polymorphism has been reportedly associated with serum lipids and cognition. However, very few studies have explored the combined effects of ApoE gene polymorphism and gender on serum lipid profile with subsequent impacts on cognition in Chinese population. A total of 1,000 Chinese community dwellers aged 55 years and above were recruited in this cross-sectional study. Demographic information of the participants was collected using well designed self-administered questionnaires. The Montreal Cognitive Assessment (MoCA) test was employed to evaluate the cognitive status of the participants. Semi-quantitative food frequency questionnaire (FFQ) was used to obtain the dietary intake information. Fasting venous blood samples were taken for ApoE genotyping and serum lipid measurements. Significant gender differences in cognition, serum lipid profile and dietary fat-rich foods consumption were observed ( p < 0.05). Cognition of the subjects was found to be associated with ApoE genotypes ( p < 0.05). ApoE rs429358 and rs7412 variants demonstrated a significant effect on cognitive performance in the male subjects; especially within the attention and language cognitive domains as well as the total MoCA score ( p < 0.05), respectively. Serum lipid profile and cognition of Chinese adults are significantly linked with gender and ApoE genetic polymorphism. The ApoE variant rs429358 is found to be notably associated with cognition in aging male Chinese population.

  5. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  6. New insights into virulence mechanisms of rice pathogen Acidovorax avenae subsp. avenae strain RS-1 following exposure to ß-lactam antibiotics.

    Science.gov (United States)

    Li, Bin; Ge, Mengyu; Zhang, Yang; Wang, Li; Ibrahim, Muhammad; Wang, Yanli; Sun, Guochang; Chen, Gongyou

    2016-02-26

    Recent research has shown that pathogen virulence can be altered by exposure to antibiotics, even when the growth rate is unaffected. Investigating this phenomenon provides new insights into understanding the virulence mechanisms of bacterial pathogens. This study investigates the phenotypic and transcriptomic responses of the rice pathogenic bacterium Acidovorax avenae subsp. avenae (Aaa) strain RS-1 to ß-lactam antibiotics especially Ampicillin (Amp). Our results indicate that exposure to Amp does not influence bacterial growth and biofilm formation, but alters the virulence, colonization capacity, composition of extracellular polymeric substances and secretion of Type VI secretion system (T6SS) effector Hcp. This attenuation in virulence is linked to unique or differential expression of known virulence-associated genes based on genome-wide transcriptomic analysis. The reliability of expression data generated by RNA-Seq was verified with quantitative real-time PCR of 21 selected T6SS genes, where significant down-regulation in expression of hcp gene, corresponding to the reduction in secretion of Hcp, was observed under exposure to Amp. Hcp is highlighted as a potential target for Amp, with similar changes observed in virulence-associated phenotypes between exposure to Amp and mutation of hcp gene. In addition, Hcp secretion is reduced in knockout mutants of 4 differentially expressed T6SS genes.

  7. Polymorphism of MDM2 promoter 309 (rs 2279744) and the risk of PCOS.

    Science.gov (United States)

    Chan, Ying; Jiang, Hongguo; Yang, Xiaoling; Li, Dongya; Ma, Lan; Luo, Ying; Tang, Wenru

    2016-01-01

    This study aimed at evaluating possible association between MDM2 SNP309 polymorphism (rs 2279744) and polycystic ovary syndrome (PCOS). One hundred and twenty-five women with PCOS and two hundred and fifty women without PCOS were collected from the department of reproductive medicine of college hospital in this case-control study. Peripheral blood samples were collected from all participants and DNA was extracted, MDM2 SNP309 polymorphism (rs 2279744) was determined from the 125 cases and 250 controls. Women were grouped into PCOS (n = 125) group and control group (n = 250). Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the association between MDM2 SNP309 polymorphism (rs 2279744) and PCOS. The distribution of T allele was significant higher in PCOS cases than controls. MDM2 SNP 309 T allele is associated with PCOS.

  8. A review of research on ecosystem of arid area using RS-GIS in China

    Science.gov (United States)

    Han, Hongling

    2007-06-01

    Arid area is classical mountain-oasis-desert ecosystem in North-west China. As the ecosystem has its nature geography character obviously, it has superior to research with remote-sensing and geography information system. The study on arid ecosystem in RS-GIS' way is focused on that the landscape spatial pattern of complex MODS ecosystem, the dynamic development of Land use/land cover, the security of ecological environment of eco-tone and so on. At the same time, the research on the single system is more and more, which has provided more ways and deeper fields of arid area using RS-GIS. Through the use of RS-GIS, desertification, oasis' development, urbanization etc. can be known, which would provide precaution for human-being and suitable ways to adjust the problems.

  9. P-bRS: A Physarum-Based Routing Scheme for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Mingchuan Zhang

    2014-01-01

    Full Text Available Routing in wireless sensor networks (WSNs is an extremely challenging issue due to the features of WSNs. Inspired by the large and single-celled amoeboid organism, slime mold Physarum polycephalum, we establish a novel selecting next hop model (SNH. Based on this model, we present a novel Physarum-based routing scheme (P-bRS for WSNs to balance routing efficiency and energy equilibrium. In P-bRS, a sensor node can choose the proper next hop by using SNH which comprehensively considers the distance, energy residue, and location of the next hop. The simulation results show how P-bRS can achieve the effective trade-off between routing efficiency and energy equilibrium compared to two famous algorithms.

  10. Working in partnership to advance the 3Rs in toxicity testing

    International Nuclear Information System (INIS)

    Holmes, Anthony M.; Creton, Stuart; Chapman, Kathryn

    2010-01-01

    Toxicological assessment of pharmaceutical and non-pharmaceutical chemicals is a regulatory requirement to ensure all compounds likely to be exposed to humans or the environment are safe. These studies rely on the use of large numbers of animals and involve a number of assumptions and extrapolations that remain controversial in assuring consumer safety. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) has taken a collaborative approach to identify opportunities for implementation of the 3Rs principles (Replacement, Reduction and Refinement) to drive innovation and support animal welfare in toxicity testing. This review highlights the mechanisms by which the NC3Rs is working with the pharmaceutical and chemical industries and regulatory authorities to achieve these goals.

  11. Integrating phenotype ontologies with PhenomeNET

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel

    2017-12-19

    Background Integration and analysis of phenotype data from humans and model organisms is a key challenge in building our understanding of normal biology and pathophysiology. However, the range of phenotypes and anatomical details being captured in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization that includes as one of its components an ontology designed to integrate phenotype ontologies. While not applicable to matching arbitrary ontologies, PhenomeNET can be used to identify related phenotypes in different species, including human, mouse, zebrafish, nematode worm, fruit fly, and yeast. Results Here, we apply the PhenomeNET to identify related classes from two phenotype and two disease ontologies using automated reasoning. We demonstrate that we can identify a large number of mappings, some of which require automated reasoning and cannot easily be identified through lexical approaches alone. Combining automated reasoning with lexical matching further improves results in aligning ontologies. Conclusions PhenomeNET can be used to align and integrate phenotype ontologies. The results can be utilized for biomedical analyses in which phenomena observed in model organisms are used to identify causative genes and mutations underlying human disease.

  12. Redefining Aging in HIV Infection Using Phenotypes.

    Science.gov (United States)

    Stoff, David M; Goodkin, Karl; Jeste, Dilip; Marquine, Maria

    2017-10-01

    This article critically reviews the utility of "phenotypes" as behavioral descriptors in aging/HIV research that inform biological underpinnings and treatment development. We adopt a phenotypic redefinition of aging conceptualized within a broader context of HIV infection and of aging. Phenotypes are defined as dimensions of behavior, closely related to fundamental mechanisms, and, thus, may be more informative than chronological age. Primary emphasis in this review is given to comorbid aging and cognitive aging, though other phenotypes (i.e., disability, frailty, accelerated aging, successful aging) are also discussed in relation to comorbid aging and cognitive aging. The main findings that emerged from this review are as follows: (1) the phenotypes, comorbid aging and cognitive aging, are distinct from each other, yet overlapping; (2) associative relationships are the rule in HIV for comorbid and cognitive aging phenotypes; and (3) HIV behavioral interventions for both comorbid aging and cognitive aging have been limited. Three paths for research progress are identified for phenotype-defined aging/HIV research (i.e., clinical and behavioral specification, biological mechanisms, intervention targets), and some important research questions are suggested within each of these research paths.

  13. Evolution of molecular phenotypes under stabilizing selection

    International Nuclear Information System (INIS)

    Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

    2013-01-01

    Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes. (paper)

  14. TERT-CLPTM1 locus polymorphism (rs401681 is associated with the prognosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Lee HW

    2017-10-01

    Full Text Available Hye Won Lee,1,* Won-Jin Park,2,* Yu-Ran Heo,2 Tae In Park,3 Soo Young Park,4 Jae-Ho Lee2,* 1Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea; 2Department of Anatomy, Keimyung University School of Medicine, Daegu, Republic of Korea; 3Department of Pathology, Kyungpook National University School of Medicine, Daegu, Republic of Korea; 4Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea *These authors contributed equally to this work Abstract: Telomere length is associated with the development of hepatocellular carcinoma (HCC, and recent studies have focused on the genetic alteration or polymorphism in telomere-maintaining genes. We examined the clinicopathologic and prognostic value of rs401681 polymorphism, located in the TERT-CLPTM1L locus, in HCC. The relationship between rs401681 variants and telomere length was also analyzed in 156 HCC patients. The rs401681 polymorphism had the following genotype frequencies: C/C in 51.3% of the samples, C/T in 39.7%, and T/T in 9.0%. Telomeres in the tumor samples were 4.04-fold longer, on average, than the telomeres in matched normal samples (SD =1.32, and there were no differences in telomere length according to rs401681 polymorphism (p=0.802. Our results indicate that the rs401681 C allele was significantly associated with increased T and International Union for Cancer Control stages (p<0.01. Univariate and multivariate survival analyses showed that HCC with C allele had poorer prognosis (p<0.01. In conclusion, our findings suggest that rs401681 is a possible prognostic biomarker for HCC patients. Keywords: CLPTM1L polymorphism, hepatocellular carcinoma, TERT-CLPTM1L locus, telomere length

  15. Effects of VRK2 (rs2312147 on white matter connectivity in patients with schizophrenia.

    Directory of Open Access Journals (Sweden)

    Hoyoung Sohn

    Full Text Available Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2, in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM and white matter (WM analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part, the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.

  16. Simplified Antenna Group Determination of RS Overhead Reduced Massive MIMO for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Byung Moo Lee

    2017-12-01

    Full Text Available Massive multiple-input multiple-output (MIMO systems can be applied to support numerous internet of things (IoT devices using its excessive amount of transmitter (TX antennas. However, one of the big obstacles for the realization of the massive MIMO system is the overhead of reference signal (RS, because the number of RS is proportional to the number of TX antennas and/or related user equipments (UEs. It has been already reported that antenna group-based RS overhead reduction can be very effective to the efficient operation of massive MIMO, but the method of deciding the number of antennas needed in each group is at question. In this paper, we propose a simplified determination scheme of the number of antennas needed in each group for RS overhead reduced massive MIMO to support many IoT devices. Supporting many distributed IoT devices is a framework to configure wireless sensor networks. Our contribution can be divided into two parts. First, we derive simple closed-form approximations of the achievable spectral efficiency (SE by using zero-forcing (ZF and matched filtering (MF precoding for the RS overhead reduced massive MIMO systems with channel estimation error. The closed-form approximations include a channel error factor that can be adjusted according to the method of the channel estimation. Second, based on the closed-form approximation, we present an efficient algorithm determining the number of antennas needed in each group for the group-based RS overhead reduction scheme. The algorithm depends on the exact inverse functions of the derived closed-form approximations of SE. It is verified with theoretical analysis and simulation that the proposed algorithm works well, and thus can be used as an important tool for massive MIMO systems to support many distributed IoT devices.

  17. MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process.

    Science.gov (United States)

    Aalaei-Andabili, Seyed Hossein; Rezaei, Nima

    2016-01-01

    Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

  18. SHBG gene polymorphism (rs1799941 associates with metabolic syndrome in children and adolescents.

    Directory of Open Access Journals (Sweden)

    Marquitta J White

    Full Text Available Metabolic syndrome (MetS is a complex disorder characterized by coexistence of several cardiometabolic (CM factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD. The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs, previously shown to modulate lipid or sex hormone binding globulin (SHBG levels, with MetS in a Turkish pediatric cohort (37 cases, 323 controls.Logistic regression analysis revealed a significant association between rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006. The association with MetS remained after sequential adjustment for each CM factor included in the syndrome definition, indicating that the identified association is not being driven by any single trait. A relationship between rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS status. In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012, while in cases there was no association between rs1799941 and SHBG levels (p = 0.963.The significant association between rs1799941 and MetS in children is not contingent on any single CM trait. Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children.

  19. Polymorphisms of Interlukin-1β rs16944 confer susceptibility to myelodysplastic syndromes.

    Science.gov (United States)

    Yin, Congcong; He, Na; Li, Peng; Zhang, Chen; Yu, Jie; Hua, Mingqiang; Ji, Chunyan; Ma, Daoxin

    2016-11-15

    Genetic factors have been shown to be associated with Myelodysplastic syndromes (MDS) susceptibility. In recent years, the role of inflammation in the promotion of tumor growth is supported by a broad range of experimental and clinical evidence. But the relationship between polymorphisms in NOD-like receptor protein 3 (NLRP3) inflammasome and MDS is rarely reported. Thus, we conducted a case-control study, and genotyped five single nucleotide polymorphisms (SNPs) (NLRP3, IL-1β, IL-18, CARD8, and NF-κB) in MDS patients and healthy controls. The association of different genotypes with patient characteristics was analyzed. Comparing MDS patients with controls, GG genotype of IL-1β (rs16944) was observed to be associated with a significantly increased risk of MDS 78/166 (48.8%) vs 26/96 (27.0%), OR=2.1, CI (1.0-4.4). No significant association was identified regarding the rest of investigated polymorphisms and MDS susceptibility. Complex karyotypes were more frequent in patients with GG genotype of IL-1β (rs16944). Patients with IL-1β polymorphisms (rs16944) GG and GA had lower hemoglobin than those without. Patients with IL-1β polymorphisms (rs16944) GG had higher IPSS scores than those without IL-1β polymorphisms. In conclusion, our present data shows that the IL-1β polymorphisms (rs16944) GG were frequently occurred in MDS. IL-1β (rs16944) GG genotype might serve as a novel biomarker and potential targets for MDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The nature of stable insomnia phenotypes.

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L

    2015-01-01

    We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the 'neither criterion' phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes.

  1. Developing RESTful services with JAX-RS 2.0, WebSockets, and JSON

    CERN Document Server

    Kalali, Masoud

    2013-01-01

    Written as an easy and practical guide, this book is a crash course on using JAX-RS 2.0, JSON, and WebSockets to develop RESTful services.Getting Started with Developing RESTful Web Services using JAX-RS 2.0, JSON, and WebSockets is a perfect reading source for application developers who are familiar with Java EE and are keen to understand the new HTML5-related functionality introduced in Java EE 7 to improve productivity. To take full advantage of this book, you need to be familiar with Java EE and have some basic understanding of using the GlassFish application server.

  2. Implementation of RS-485 Communication between PLC and PC of Distributed Control System Based on VB

    Science.gov (United States)

    Lian Zhang, Chuan; Da Huang, Zhi; Qing Zhou, Gui; Chong, Kil To

    2015-05-01

    This paper focuses on achieving RS-485 communication between programmable logical controller (PLC) and PC based on visual basic 6.0 (VB6.0) on an experimental automatic production line. Mitsubishi FX2N PLCs and a PC are chosen as slave stations and main station, respectively. Monitoring software is developed using VB6.0 for data input/output, flow control and online parameters setting. As a result, all functions are fulfilled with robust performance. It is concluded from results that one PC can monitor several PLCs using RS-485 communication.

  3. Experimental research and comparison of LDPC and RS channel coding in ultraviolet communication systems.

    Science.gov (United States)

    Wu, Menglong; Han, Dahai; Zhang, Xiang; Zhang, Feng; Zhang, Min; Yue, Guangxin

    2014-03-10

    We have implemented a modified Low-Density Parity-Check (LDPC) codec algorithm in ultraviolet (UV) communication system. Simulations are conducted with measured parameters to evaluate the LDPC-based UV system performance. Moreover, LDPC (960, 480) and RS (18, 10) are implemented and experimented via a non-line-of-sight (NLOS) UV test bed. The experimental results are in agreement with the simulation and suggest that based on the given power and 10(-3)bit error rate (BER), in comparison with an uncoded system, average communication distance increases 32% with RS code, while 78% with LDPC code.

  4. Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus

    OpenAIRE

    Sakiyama, Masayuki; Matsuo, Hirotaka; Nakaoka, Hirofumi; Yamamoto, Ken; Nakayama, Akiyoshi; Nakamura, Takahiro; Kawai, Sayo; Okada, Rieko; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-01-01

    Gout is a common disease resulting from hyperuricemia. Recently, a genome-wide association study identified an association between gout and a single nucleotide polymorphism (SNP) rs2188380, located on an intergenic region between MYL2 and CUX2 on chromosome 12. However, other genes around rs2188380 could possibly be gout susceptibility genes. Therefore, we performed a fine-mapping study of the MYL2-CUX2 region. From 8,595 SNPs in the MYL2-CUX2 region, 9 tag SNPs were selected, and genotyping ...

  5. Lidt om DØRS' selvforståelse: om lønrelationerne i SMEC

    DEFF Research Database (Denmark)

    Harck, Søren H.

    1997-01-01

    at all: if the wage-to-price elasticity is taken to be equal to one (as stipulated by DØRS), the model turns out to imply, even in the long run, an old-fashioned, stable Phillips curve; and if, more realistically, this elasticity is taken to be smaller than one, the error-correction specification by DØRS...... does in fact entail a horizontal Phillips curve, the level of which is determined by the exchange rate adjusted foreign inflation rate. Evidently, the policy implications of getting the interpretation right are, potentially, huge....

  6. Propagation of ELF Radiation from RS-LC System and Red Sprites in Earth-Ionosphere Waveguide

    Directory of Open Access Journals (Sweden)

    M. K. Paras

    2012-10-01

    Full Text Available In this paper, two different mechanisms return stroke-lateral corona (RS-LC system and red sprites which excite Earth-ionosphere waveguide have been discussed. The electric and magnetic fields from RS-LC system and red spites in the Earth-ionosphere waveguide have been calculated. It has been found that red sprites contribute to the Schumann resonances (SR greatly as compared to the RS-LC system.

  7. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

    Biessels, G J; Bril, V; Calcutt, N A

    2014-01-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy...... with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence...

  8. Obesity-related polymorphisms and their associations with the ability to regulate fat oxidation in obese europeans

    DEFF Research Database (Denmark)

    Corpeleijn, Eva; Petersen, Liselotte; Holst, Claus

    2010-01-01

    for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese......Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single-nucleotide polymorphisms (SNPs) in 26 candidate genes.......01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with -174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related...

  9. PCSK1 rs6232 Is Associated with Childhood and Adult Class III Obesity in the Mexican Population

    Science.gov (United States)

    Villalobos-Comparán, Marisela; Villamil-Ramírez, Hugo; Villarreal-Molina, Teresa; Larrieta-Carrasco, Elena; León-Mimila, Paola; Romero-Hidalgo, Sandra; Jacobo-Albavera, Leonor; Liceaga-Fuentes, Adriana E.; Campos-Pérez, Francisco J.; López-Contreras, Blanca E.; Tusié-Luna, Teresa; del Río-Navarro, Blanca E.; Aguilar-Salinas, Carlos A.; Canizales-Quinteros, Samuel

    2012-01-01

    Background Common variants rs6232 and rs6235 in the PCSK1 gene have been associated with obesity in European populations. We aimed to evaluate the contribution of these variants to obesity and related traits in Mexican children and adults. Methodology/Principal Findings Rs6232 and rs6235 were genotyped in 2382 individuals, 1206 children and 1176 adults. Minor allele frequencies were 0.78% for rs6232 and 19.99% for rs6235. Rs6232 was significantly associated with childhood obesity and adult class III obesity (OR = 3.01 95%CI 1.64–5.53; P = 4×10−4 in the combined analysis). In addition, this SNP was significantly associated with lower fasting glucose levels (P = 0.01) and with increased insulin levels and HOMA-B (P = 0.05 and 0.01, respectively) only in non-obese children. In contrast, rs6235 showed no significant association with obesity or with glucose homeostasis parameters in any group. Conclusion/Significance Although rs6232 is rare in the Mexican population, it should be considered as an important risk factor for extreme forms of obesity. PMID:22737226

  10. Chemical chaperones exceed the chaperone effects of RIC-3 in promoting assembly of functional α7 AChRs.

    Directory of Open Access Journals (Sweden)

    Alexander Kuryatov

    Full Text Available Functional α7 nicotinic acetylcholine receptors (AChRs do not assemble efficiently in cells transfected with α7 subunits unless the cells are also transfected with the chaperone protein RIC-3. Despite the presence of RIC-3, large amounts of these subunits remain improperly assembled. Thus, additional chaperone proteins are probably required for efficient assembly of α7 AChRs. Cholinergic ligands can act as pharmacological chaperones to promote assembly of mature AChRs and upregulate the amount of functional AChRs. In addition, we have found that the chemical chaperones 4-phenylbutyric acid (PBA and valproic acid (VPA greatly increase the amount of functional α7 AChRs produced in a cell line expressing both α7 and RIC-3. Increased α7 AChR expression allows assay of drug action using a membrane potential-sensitive fluorescent indicator. Both PBA and VPA also increase α7 expression in the SH-SY5Y neuroblastoma cell line that endogenously expresses α7 AChRs. VPA increases expression of endogenous α7 AChRs in hippocampal neurons but PBA does not. RIC-3 is insufficient for optimal assembly of α7 AChRs, but provides assay conditions for detecting additional chaperones. Chemical chaperones are a useful pragmatic approach to express high levels of human α7 AChRs for drug selection and characterization and possibly to increase α7 expression in vivo.

  11. Common miR-590 Variant rs6971711 Present Only in African Americans Reduces miR-590 Biogenesis.

    Directory of Open Access Journals (Sweden)

    Xiaoping Lin

    Full Text Available MicroRNAs (miRNAs are recognized as important regulators of cardiac development, hypertrophy and fibrosis. Recent studies have demonstrated that genetic variations which cause alterations in miRNA:target interactions can lead to disease. We hypothesized that genetic variations in miRNAs that regulate cardiac hypertrophy/fibrosis might be involved in generation of the cardiac phenotype in patients diagnosed with hypertrophic cardiomyopathy (HCM. To investigate this question, we Sanger sequenced 18 miRNA genes previously implicated in myocyte hypertrophy/fibrosis and apoptosis, using genomic DNA isolated from the leukocytes of 199 HCM patients. We identified a single nucleotide polymorphism (rs6971711, C57T SNP at the 17th position of mature miR-590-3p (= 57th position of pre-miR-590 that is common in individuals of African ancestry. SNP frequency was higher in African American HCM patients (n = 55 than ethnically-matched controls (n = 100, but the difference was not statistically significant (8.2% vs. 6.5%; p = 0.5. Using a cell culture system, we discovered that presence of this SNP resulted in markedly lower levels of mature miR-590-5p (39 ± 16%, p<0.003 and miR-590-3p (20 ± 2%, p<0.003, when compared with wild-type (WT miR-590, without affecting levels of pri-miR-590 and pre-miR-590. Consistent with this finding, the SNP resulted in reduced target suppression when compared to WT miR-590 (71% suppression by WT vs 60% suppression by SNP, p<0.03. Since miR-590 can regulate TGF-β, Activin A and Akt signaling, SNP-induced reduction in miR-590 biogenesis could influence cardiac phenotype by de-repression of these signaling pathways. Since the SNP is only present in African Americans, population studies in this patient population would be valuable to investigate effects of this SNP on myocyte function and cardiac physiology.

  12. Does the oxytocin receptor polymorphism (rs2254298 confer 'vulnerability' for psychopathology or 'differential susceptibility'? insights from evolution

    Directory of Open Access Journals (Sweden)

    Brüne Martin

    2012-04-01

    Full Text Available Abstract The diathesis-stress model of psychiatric conditions has recently been challenged by the view that it might be more accurate to speak of 'differential susceptibility' or 'plasticity' genes, rather than one-sidedly focusing on individual vulnerability. That is, the same allelic variation that predisposes to a psychiatric disorder if associated with (developmentally early environmental adversity may lead to a better-than-average functional outcome in the same domain under thriving (or favourable environmental conditions. Studies of polymorphic variations of the serotonin transporter gene, the monoamino-oxidase-inhibitor A coding gene or the dopamine D4 receptor gene indicate that the early environment plays a crucial role in the development of favourable versus unfavourable outcomes. Current evidence is limited, however, to establishing a link between genetic variation and behavioural phenotypes. In contrast, little is known about how plasticity may be expressed at the neuroanatomical level as a 'hard-wired' correlate of observable behaviour. The present review article seeks to further strengthen the argument in favour of the differential susceptibility theory by incorporating findings from behavioural and neuroanatomical studies in relation to genetic variation of the oxytocin receptor gene. It is suggested that polymorphic variation at the oxytocin receptor gene (rs2254298 is associated with sociability, amygdala volume and differential risk for psychiatric conditions including autism, depression and anxiety disorder, depending on the quality of early environmental experiences. Seeing genetic variation at the core of developmental plasticity can explain, in contrast to the diathesis-stress perspective, why evolution by natural selection has maintained such 'risk' alleles in the gene pool of a population. Please see related manuscript: http://www.biomedcentral.com/1741-7015/10/37

  13. Sodium nitroprusside (SNP) alleviates the oxidative stress induced ...

    African Journals Online (AJOL)

    Oxidative damage is often induced by abiotic stress, nitric oxide (NO) is considered as a functional molecule in modulating antioxidant metabolism of plants. In the present study, effects of sodium nitroprusside (SNP), a NO donor, on the phenotype, antioxidant capacity and chloroplast ultrastructure of cucumber leaves were ...

  14. Phenotypic profiles of Armenian grape cultivars

    Directory of Open Access Journals (Sweden)

    Aroutiounian Rouben

    2015-01-01

    Full Text Available The conservation and sustainable use of grapevine biodiversity in Armenia is particularly important due to the large number of traditional local varieties. Being partially different from European grapevine gene pool, the material of Armenian local cultivars significantly contributes to the understanding of the genetic variation and is valuable source for target selection. During last years many Armenian grapevine cultivars have been already described and their genotypes determined, but some local varieties and wild accessions remain unidentified and their phenotypic characteristics overlooked. The comprehensive analysis of phenotypes is essential for research, including genetic association studies, cultivar evaluation and selection. The goal of our research was the phenotyping on the base of reproductive, carpological and analytical characteristics of 80 Armenian aboriginal and new grape cultivars. Description of phenotypic profiles is important step towards identification and conservation of genetic resources of Armenian grapes. In future, these data can be applied for breeding of improved grape varieties targeted to fresh consumption and wine production.

  15. Phenotypic diversity and phylogenetic relationship between the ...

    African Journals Online (AJOL)

    Phenotypic diversity and phylogenetic relationship between the Bakosi/Baweri and other pig breeds ( Sus scrofa Domesticus ) in the humid forest with monomodal rainfall agro-ecological zone of Cameroon.

  16. Mining skeletal phenotype descriptions from scientific literature.

    Directory of Open Access Journals (Sweden)

    Tudor Groza

    Full Text Available Phenotype descriptions are important for our understanding of genetics, as they enable the computation and analysis of a varied range of issues related to the genetic and developmental bases of correlated characters. The literature contains a wealth of such phenotype descriptions, usually reported as free-text entries, similar to typical clinical summaries. In this paper, we focus on creating and making available an annotated corpus of skeletal phenotype descriptions. In addition, we present and evaluate a hybrid Machine Learning approach for mining phenotype descriptions from free text. Our hybrid approach uses an ensemble of four classifiers and experiments with several aggregation techniques. The best scoring technique achieves an F-1 score of 71.52%, which is close to the state-of-the-art in other domains, where training data exists in abundance. Finally, we discuss the influence of the features chosen for the model on the overall performance of the method.

  17. Integrating phenotype ontologies with PhenomeNET

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel; Gkoutos, Georgios V.; Schofield, Paul N.; Hoehndorf, Robert

    2017-01-01

    in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization

  18. Wiedemann-Rautenstrauch syndrome: A phenotype analysis

    NARCIS (Netherlands)

    Paolacci, Stefano; Bertola, Debora; Franco, José; Mohammed, Shehla; Tartaglia, Marco; Wollnik, Bernd; Hennekam, Raoul C.

    2017-01-01

    Wiedemann-Rautenstrauch syndrome (WRS) is a neonatal progeroid disorder characterized by growth retardation, lipodystrophy, a distinctive face, and dental anomalies. Patients reported to date demonstrate a remarkable variability in phenotype, which hampers diagnostics. We performed a literature

  19. REVIEW ARTICLE One gene, many phenotypes

    African Journals Online (AJOL)

    salah

    Phenotype descriptions are valuable information right at the interface of medi- cine and biology. ... the interaction of alleles at different loci. Modifier genes. 5. ... the amount of normal protein is called ..... Institute, using computer simulations,.

  20. The spatial patterns of directional phenotypic selection

    KAUST Repository

    Siepielski, Adam M.; Gotanda, Kiyoko M.; Morrissey, Michael B.; Diamond, Sarah E.; DiBattista, Joseph; Carlson, Stephanie Marie

    2013-01-01

    the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data

  1. Phenotypic variability among strains of Pasteurella multocida ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-05-02

    May 2, 2008 ... Available online at http://www.academicjournals.org/AJB. ISSN 1684–5315 ... extended phenotypic characterization methods supported by DNA ... septicaemia African (Obudu) strain (E:2) which are currently employed as ...

  2. The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.

    LENUS (Irish Health Repository)

    Rose, Emma J

    2012-03-01

    A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N=157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the \\'G\\' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk \\'A\\' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in \\'G\\' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and\\/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.

  3. Evaluation of Biogenic and Fire Emissions in a Global Chemistry Model with NOMADSS, DC3 and SEAC4RS observations

    Science.gov (United States)

    Emmons, L. K.; Wiedinmyer, C.; Park, M.; Kaser, L.; Apel, E. C.; Guenther, A. B.

    2014-12-01

    Numerous measurements of compounds produced by biogenic and fire emissions were made during several recent field campaigns in the southeast United States, providing a unique data set for emissions and chemical model evaluation. The NCAR Community Atmosphere Model with Chemistry (CAM-chem) is coupled to the Community Land Model (CLM), which includes the biogenic emissions model MEGAN-v2.1, allowing for online calculation of emissions from vegetation for 150 compounds. Simulations of CAM-chem for summers 2012 and 2013 are evaluated with the aircraft and ground-based observations from DC3, NOMADSS and SEAC4RS. Comparison of directly emitted biogenic species, such as isoprene, terpenes, methanol and acetone, are used to evaluate the MEGAN emissions. Evaluation of oxidation products, including methyl vinyl ketone (MVK), methacrolein, formaldehyde, and other oxygenated VOCs are used to test the model chemistry mechanism. In addition, several biomass burning inventories are used in the model, including FINN, QFED, and FLAMBE, and are compared for their impact on atmospheric composition and ozone production, and evaluated with the aircraft observations.

  4. Nanofilamentary resistive switching in binary oxide system; a review on the present status and outlook

    International Nuclear Information System (INIS)

    Kim, Kyung Min; Hwang, Cheol Seong; Jeong, Doo Seok

    2011-01-01

    This review article summarized the recent understanding of resistance switching (RS) behavior in several binary oxide thin film systems. Among the various RS materials and mechanisms, TiO 2 and NiO thin films in unipolar thermo-chemical switching mode are primarily dealt with. To facilitate the discussions, the RS was divided into three parts; electroforming, set and reset steps. After short discussions on the electrochemistry of 'electrolytic' oxide materials, the general and peculiar aspects of these RS systems and mechanism are elaborated. Although the RS behaviors and characteristics of these materials are primarily dependent on the repeated formation and rupture of the conducting filaments (CFs) at the nanoscale at a localized position, this mechanism appears to offer a basis for the understanding of other RS mechanisms which were originally considered to be irrelevant to the localized events. The electroforming and set switching phenomena were understood as the process of CF formation and rejuvenation, respectively, which are mainly driven by the thermally assisted electromigration and percolation (or even local phase transition) of defects, while the reset process was understood as the process of CF rupture where the thermal energy plays a more crucial role. This review also contains several remarks on the outlook of these resistance change devices as a semiconductor memory. (topical review)

  5. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...... of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification....

  6. A Regulatory RNA Inducing Transgenerationally Inherited Phenotypes

    DEFF Research Database (Denmark)

    Jensen, Lea Møller

    . The variation in Arabidopsis enables different regulatory networks and mechanisms to shape the phenotypic characteristics. The thesis describes the identification of regulatory RNA encoded by an enzyme encoding gene. The RNA regulates by inducing transgenerationally inherited phenotypes. The function of the RNA...... is dependent on the genetic background illustrating that polymorphisms are found in either interactors or target genes of the RNA. Furthermore, the RNA provides a mechanistic link between accumulation of glucosinolate and onset of flowering....

  7. Blue eyes in lemurs and humans: same phenotype, different genetic mechanism

    DEFF Research Database (Denmark)

    Bradley, Brenda J; Pedersen, Anja; Mundy, Nicholas I

    2009-01-01

    Almost all mammals have brown or darkly-pigmented eyes (irises), but among primates, there are some prominent blue-eyed exceptions. The blue eyes of some humans and lemurs are a striking example of convergent evolution of a rare phenotype on distant branches of the primate tree. Recent work...... on humans indicates that blue eye color is associated with, and likely caused by, a single nucleotide polymorphism (rs12913832) in an intron of the gene HERC2, which likely regulates expression of the neighboring pigmentation gene OCA2. This raises the immediate question of whether blue eyes in lemurs might...... have a similar genetic basis. We addressed this by sequencing the homologous genetic region in the blue-eyed black lemur (Eulemur macaco flavifrons; N = 4) and the closely-related black lemur (Eulemur macaco macaco; N = 4), which has brown eyes. We then compared a 166-bp segment corresponding...

  8. Phenex: ontological annotation of phenotypic diversity.

    Directory of Open Access Journals (Sweden)

    James P Balhoff

    2010-05-01

    Full Text Available Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge.Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices.Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

  9. Phenex: ontological annotation of phenotypic diversity.

    Science.gov (United States)

    Balhoff, James P; Dahdul, Wasila M; Kothari, Cartik R; Lapp, Hilmar; Lundberg, John G; Mabee, Paula; Midford, Peter E; Westerfield, Monte; Vision, Todd J

    2010-05-05

    Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge. Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices. Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

  10. Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy

    Science.gov (United States)

    Alfonso-García, Alba; Smith, Tim D.; Datta, Rupsa; Luu, Thuy U.; Gratton, Enrico; Potma, Eric O.; Liu, Wendy F.

    2016-04-01

    Macrophages adopt a variety of phenotypes that are a reflection of the many functions they perform as part of the immune system. In particular, metabolism is a phenotypic trait that differs between classically activated, proinflammatory macrophages, and alternatively activated, prohealing macrophages. Inflammatory macrophages have a metabolism based on glycolysis while alternatively activated macrophages generally rely on oxidative phosphorylation to generate chemical energy. We employ this shift in metabolism as an endogenous marker to identify the phenotype of individual macrophages via live-cell fluorescence lifetime imaging microscopy (FLIM). We demonstrate that polarized macrophages can be readily discriminated with the aid of a phasor approach to FLIM, which provides a fast and model-free method for analyzing fluorescence lifetime images.

  11. Oxide ceramics

    International Nuclear Information System (INIS)

    Ryshkewitch, E.; Richerson, D.W.

    1985-01-01

    The book explores single-phase ceramic oxide systems from the standpoint of physical chemistry and technology. This second edition also focuses on advances in technology since publication of the original edition. These include improvements in raw materials and forming and sintering techniques, and the major role that oxide ceramics have had in development of advanced products and processes. The text is divided into five major sections: general fundamentals of oxide ceramics, advances in aluminum oxide technology, advances in zirconia technology, and advances in beryllium oxide technology

  12. Genetic and phenotypic variability of iris color in Buenos Aires population

    Directory of Open Access Journals (Sweden)

    Diana María Hohl

    Full Text Available Abstract The aim of this work was to describe the phenotypic and genotypic variability related to iris color for the population of Buenos Aires province (Argentina, and to assess the usefulness of current methods of analysis for this country. We studied five Single Nucleotide Polymorphisms (SNPs included in the IrisPlex kit, in 118 individuals, and we quantified eye color with Digital Iris Analysis Tool. The markers fit Hardy-Weinberg equilibrium for the whole sample, but not for rs12913832 within the group of brown eyes (LR=8.429; p=0.004. We found a remarkable association of HERC2 rs12913832 GG with blue color (p < 0.01 but the other markers did not show any association with iris color. The results for the Buenos Aires population differ from those of other populations of the world for these polymorphisms (p < 0,01. The differences we found might respond to the admixed ethnic composition of Argentina; therefore, methods of analysis used in European populations should be carefully applied when studying the population of Argentina. These findings reaffirm the importance of this investigation in the Argentinian population for people identification based on iris color.

  13. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

    NARCIS (Netherlands)

    A. Hollestelle (Antoinette); F.H. Van Der Baan (Frederieke H.); A. Berchuck (Andrew); S.E. Johnatty (Sharon); K.K.H. Aben (Katja); B.A. Agnarsson (Bjarni); K. Aittomäki (Kristiina); E. Alducci (Elisa); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); N.N. Antonenkova (Natalia); A.C. Antoniou (Antonis C.); C. Apicella (Carmel); V. Arndt (Volker); N. Arnold (Norbert); B.K. Arun (Banu); B. Arver (Brita Wasteson); A. Ashworth (Alan); L. Baglietto (Laura); R. Balleine (Rosemary); E.V. Bandera (Elisa); D. Barrowdale (Daniel); Y.T. Bean (Yukie); L. Beckmann (Lars); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berger (Andreas); R. Berger (Raanan); B. Beuselinck (B.); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); A. Bojesen (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet); B. Bonnani (Bernardo); J.S. Brand (Judith S.); H. Brauch (Hiltrud); H. Brenner (Hermann); L.A. Brinton (Louise); A. Brooks-Wilson (Angela); F. Bruinsma (Fiona); J. Brunet (Joan); T. Brüning (Thomas); A. Budzilowska (Agnieszka); C.H. Bunker (Clareann H.); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra S.); M.A. Caligo (Maria); I. Campbell (Ian); J. Carter (Jonathan); J. Chang-Claude (Jenny); S.J. Chanock (Stephen J.); K.B.M. Claes (Kathleen B.M.); J.M. Collée (Margriet); L.S. Cook (Linda S.); F.J. Couch (Fergus); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); J.M. Cunningham (Julie); C. Cybulski (Cezary); K. Czene (Kamila); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); M. de La Hoya (Miguel); A. DeFazio (Anna); J. Dennis (Joe); P. Devilee (Peter); E. Dicks (Ed); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); I. dos Santos Silva (Isabel); A. Du Bois (Andreas); M. Dumont (Martine); A.M. Dunning (Alison); M. Duran (Mercedes); D.F. Easton (Douglas F.); D. Eccles (Diana); R. Edwards (Robert); H. Ehrencrona (Hans); B. Ejlertsen (Bent); A.B. Ekici (Arif); S.D. Ellis (Steve); C. Engel (Christoph); M. Eriksson (Mikael); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); A. Fontaine (Annette); S. Fortuzzi (S.); F. Fostira (Florentia); B.L. Fridley (Brooke); M.O.W. Friebel (Mark ); E. Friedman (Eitan); G. Friel (Grace); D. Frost (Debra); J. Garber (Judy); M. García-Closas (Montserrat); S.A. Gayther (Simon); A. Gentry-Maharaj (Aleksandra); A-M. Gerdes (Anne-Marie); G.G. Giles (Graham); R. Glasspool (Rosalind); G. Glendon (Gord); A.K. Godwin (Andrew K.); M.T. Goodman (Marc T.); M. Gore (Martin); M.H. Greene (Mark H.); M. Grip (Mervi); J. Gronwald (Jacek); D. Gschwantler-Kaulich (Daphne); P. Guénel (Pascal); S.R. Guzman (Starr R.); L. Haeberle (Lothar); C.A. Haiman (Christopher A.); P. Hall (Per); S.L. Halverson (Sandra L.); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. Harter (Philipp); J.M. Hartikainen (J.); S. Healey (Sue); R. Hein (Rebecca); P.U. Heitz; B.E. Henderson (Brian); J. Herzog (Josef); M.A. T Hildebrandt (Michelle A.); C.K. Høgdall (Claus); E. Høgdall (Estrid); F.B.L. Hogervorst (Frans); J.L. Hopper (John); K. Humphreys (Keith); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny N.); C. Isaacs (Claudine); A. Jakubowska (Anna); R. Janavicius (Ramunas); K. Jaworska (Katarzyna); A. Jensen (Allan); U.B. Jensen; N. Johnson (Nichola); A. Jukkola-Vuorinen (Arja); M. Kabisch (Maria); B.Y. Karlan (Beth Y.); V. Kataja (Vesa); N. Kauff (Noah); L.E. Kelemen (Linda); M. Kerin (Michael); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); J.P. Knol-Bout (Jacoba P.); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); C. Krakstad (Camilla); V. Kristensen (Vessela); K.B. Kuchenbaecker (Karoline); J. Kupryjanczyk (Jolanta); Y. Laitman (Yael); D. Lambrechts (Diether); S. Lambrechts (Sandrina); M.C. Larson (Melissa); A. Lasa (Adriana); P. Laurent-Puig (Pierre); C. Lazaro (Conxi); N. Le (Nhu); L. Le Marchand (Loic); A. Leminen (Arto); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); D. Liang (Dong); A. Lindblom (Annika); N.M. Lindor (Noralane); J. Lissowska (Jolanta); J. Long (Jirong); K.H. Lu (Karen); J. Lubinski (Jan); L. Lundvall (Lene); G. Lurie (Galina); P.L. Mai (Phuong); A. Mannermaa (Arto); S. Margolin (Sara); F. Mariette (F.); F. Marme (Federick); J.W.M. Martens (John); L.F. Massuger (Leon); C. Maugard; S. Mazoyer (Sylvie); L. McGuffog (Lesley); W.P. McGuire; C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); F. Menegaux (Florence); P. Menéndez (Primitiva); J. Menkiszak (Janusz); U. Menon (Usha); A.R. Mensenkamp (Arjen); N. Miller (Nicola); R.L. Milne (Roger); F. Modugno (Francesmary); M. Montagna (Marco); K.B. Moysich (Kirsten B.); H. Mul̈ler (Heiko); A.-M. Mulligan (Anna-Marie); T.A. Muranen (Taru); S.A. Narod (Steven A.); K.L. Nathanson (Katherine); R.B. Ness (Roberta B.); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); P. Neven (Patrick); F. Nielsen (Finn); S.F. Nielsen (Sune); B.G. Nordestgaard (Børge); R. Nussbaum (Robert); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); S.H. Olson (Sara); J.C. Oosterwijk (Jan); I. Orlow (Irene); N. Orr (Nick); S. Orsulic (Sandra); A. Osorio (Ana); L. Ottini (Laura); J. Paul (James); C.L. Pearce (Celeste); I.S. Pedersen (Inge Sokilde); B. Peissel (Bernard); T. Pejovic (Tanja); L.M. Pelttari (Liisa); J. Perkins (Jo); J. Permuth-Wey (Jenny); P. Peterlongo (Paolo); J. Peto (Julian); C. Phelan (Catherine); K.-A. Phillips (Kelly-Anne); M. Piedmonte (Marion); M.C. Pike (Malcolm C.); R. Platte (Radka); J. Plisiecka-Halasa (Joanna); E.M. Poole (Elizabeth); B. Poppe (Bruce); K. Pykäs (Katri); P. Radice (Paolo); S.J. Ramus (Susan); R. Rebbeck (Timothy); M.W.R. Reed (Malcolm W.R.); G. Rennert (Gad); H. Risch (Harvey); M. Robson (Mark); G. Rodriguez (Gustavo); A. Romero (Atocha); M.A. Rossing (Mary Anne); J.H. Rothstein (Joseph H.); A. Rudolph (Anja); I.B. Runnebaum (Ingo); R. Salani (Ritu); H.B. Salvesen (Helga); E.J. Sawyer (Elinor); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); A. Schneeweiss (Andreas); M. Schoemaker (Minouk); A. Schrauder (André); F.R. Schumacher (Fredrick); I. Schwaab (Ira); G. Scuvera (Giulietta); T.A. Sellers (Thomas A.); G. Severi (Gianluca); C.M. Seynaeve (Caroline); M. Shah (Mitul); M. Shrubsole (Martha); N. Siddiqui (Nadeem); W. Sieh (Weiva); J. Simard (Jacques); C.F. Singer (Christian); O. Sinilnikova (Olga); D. Smeets (Dominiek); C. Sohn (Christof); M. Soller (Maria); H. Song (Honglin); P. Soucy (Penny); M.C. Southey (Melissa); C. Stegmaier (Christa); D. Stoppa-Lyonnet (Dominique); L. Sucheston (Lara); A.J. Swerdlow (Anthony ); I.L. Tangen (Ingvild L.); M.-K. Tea; P.J. Teixeira; K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); P.J. Thompson (Pamela J.); L. Tihomirova (Laima); M. Tischkowitz (Marc); A.E. Toland (Amanda); R.A.E.M. Tollenaar (Rob); I. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); H. Tsimiklis (Helen); N. Tung (Nadine); S. Tworoger (Shelley); J.P. Tyrer (Jonathan); C. Vachon (Celine); L.J. van 't Veer (Laura); A.M. van Altena (Anne); C.J. van Asperen (Christi); D. Van Den Berg (David); A.M.W. van den Ouweland (Ans); H.C. van Doorn (Helena); E. Van Nieuwenhuysen (Els); E.J. van Rensburg (Elizabeth); I. Vergote (Ignace); S. Verhoef; R.A. Vierkant (Robert); J. Vijai (Joseph); A.F. Vitonis (Allison); A. von Wachenfeldt (Anna); C.S. Walsh (Christine); Q. Wang (Qing); S. Wang-Gohrke (Shan); B. Wapenschmidt (Barbara); M. Weischer (Maren); J.N. Weitzel (Jeffrey); C. Weltens (Caroline); N. Wentzensen (N.); A.S. Whittemore (Alice S.); L.R. Wilkens (Lynne R.); R. Winqvist (Robert); A.H. Wu (Anna); X. Wu (Xifeng); H.P. Yang (Hannah P.); D. Zaffaroni (Daniela); M.P. Zamora (Pilar); W. Zheng (Wei); A. Ziogas (Argyrios); G. Chenevix-Trench (Georgia); P.D.P. Pharoah (Paul); M.A. Rookus (Matti); M.J. Hooning (Maartje); E.L. Goode (Ellen L.); Breast Cancer Family Register; EMBRACE; GENICA Network; HEBON; SWE-BRCA

    2016-01-01

    textabstractObjective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies,

  14. A Study of the Association of Polymorphism rs5860110 and its ...

    African Journals Online (AJOL)

    HP

    as multiple sclerosis [28,29] and rheumatoid arthritis [30]. However, it is first time to report the relationship between SPP1 polymorphism and. AS patients. So the research should be confirmed in large and ethnically divergent population samples to make stronger conclusion about the association between the rs5860110.

  15. The computer-controlled GPIB-RS232 interface for data transmission

    International Nuclear Information System (INIS)

    Bai Xiaowei

    1993-01-01

    A kind of RS232-GPIB interface circuit is introduced, which provides communication between the serial system and the instrument with GPIB. Port P 1 of 8031 is used to select function mode as listener, talker or others. Under the control of a personal computer, the data communication is completed both in serial and the parallel modes

  16. Aligning the 3Rs with new paradigms in the safety assessment of chemicals.

    Science.gov (United States)

    Burden, Natalie; Mahony, Catherine; Müller, Boris P; Terry, Claire; Westmoreland, Carl; Kimber, Ian

    2015-04-01

    There are currently several factors driving a move away from the reliance on in vivo toxicity testing for the purposes of chemical safety assessment. Progress has started to be made in the development and validation of non-animal methods. However, recent advances in the biosciences provide exciting opportunities to accelerate this process and to ensure that the alternative paradigms for hazard identification and risk assessment deliver lasting 3Rs benefits, whilst improving the quality and relevance of safety assessment. The NC3Rs, a UK-based scientific organisation which supports the development and application of novel 3Rs techniques and approaches, held a workshop recently which brought together over 20 international experts in the field of chemical safety assessment. The aim of this workshop was to review the current scientific, technical and regulatory landscapes, and to identify key opportunities towards reaching these goals. Here, we consider areas where further strategic investment will need to be focused if significant impact on 3Rs is to be matched with improved safety science, and why the timing is right for the field to work together towards an environment where we no longer rely on whole animal data for the accurate safety assessment of chemicals.

  17. Psychometric Properties of the Parent and Teacher ADHD Rating Scale (ADHD-RS)

    DEFF Research Database (Denmark)

    Makransky, Guido; Bilenberg, Niels

    2014-01-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in childhood and adolescence. Rating the severity of psychopathology and symptom load is essential in daily clinical practice and in research. The parent and teacher ADHD-Rating Scale (ADHD-RS) includes...

  18. COSMO-RS-based extractant screening for phenol extraction as model system

    NARCIS (Netherlands)

    Burghoff, B.; Goetheer, E.L.V.; Haan, A.B. de

    2008-01-01

    The focus of this investigation is the development of a fast and reliable extractant screening approach. Phenol extraction is selected as the model process. A quantum chemical conductor-like screening model for real solvents (COSMO-RS) is combined with molecular design considerations. For this

  19. Predicting CO2-H2O Interfacial Tension Using COSMO-RS

    DEFF Research Database (Denmark)

    Silvestri, Alessandro; Stipp, Susan Louise Svane; Andersson, Martin Peter

    2017-01-01

    us interpret results and gain insight under conditions where experiments are difficult or impossible. Here, we report predictions for CO2–water interfacial tension performed using density functional theory (DFT) combined with the COSMO-RS implicit solvent model. We predicted the IFT dependence...

  20. Association of rs662799 in APOA5 with CAD in Chinese Han population.

    Science.gov (United States)

    Chen, Hua; Ding, Shifang; Zhou, Mi; Wu, Xiayin; Liu, Xi; Wu, Yun; Liu, Dechao

    2018-01-08

    CAD (Coronary Artery Disease) is a complex disease that influenced by various environmental and genetic factors. Previous studies have found many single nucleotide polymorphisms (SNPs) associated with the risk of CAD occurrence. However, the results are inconsistent. In this study, we aim to investigate genetic etiology in Chinese Han population by analysis of 7 SNPs in lipid metabolism pathway that previously has been reported to be associated with CAD. A total of 631 samples were used in this study, including 435 CAD cases and 196 normal healthy controls. SNP genotyping were conducted via multiplex PCR amplifying followed by NGS (next-generation sequencing). Rs662799 in APOA5 (Apolipoprotein A5) gene was associated with CAD in Chinese Han population (Odds-ratio = 1.374, P-value = 0.03). No significant association was observed between the rest of SNPs and CAD. Stratified association analysis revealed rs5882 was associated with CAD in non-hypertension group (Odds-ratio = 1.593, P-value = 0.023). Rs1800588 was associated with CAD in smoking group (Odds-ratio = 1.603, P-value = 0.035). The minor allele of rs662799 was the risk factor of CAD occurrences in Chinese Han population.

  1. Lack of association between rs10491334 in the CAMK4 gene and ...

    Indian Academy of Sciences (India)

    human longevity in a Chinese population and found that the. SNP was negatively ... 10,000 inhabitants, 65 years of age or older, is in Hainan. (16.64), followed by .... ified analyses by sex and did not observe positive effect of rs10491334 in ...

  2. Effect of Tryptophan Hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression

    Directory of Open Access Journals (Sweden)

    Zhang Yuqi

    2010-08-01

    Full Text Available Abstract Background Suicide and major depressive disorders (MDD are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2 gene rs7305115 SNP may predispose to suicide attempts in MDD. Methods We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis. Results There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p p p Conclusions The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.

  3. Unravelling the Nature of HD 81032 – A New RS CVn Binary

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... ... component solar-abundance coronal plasma model, but implies either the presence of two or more plasma components, non-solar abundances, or a combination of both of these properties. All of the above properties of HD 81032 suggest that it is a newly identified, evolved RS CVn binary.

  4. Association of Lin-28A rs3811464 Variant with Susceptibility to Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Mona Khodabandeh

    2017-11-01

    Full Text Available Introduction: It has been suggested that Lin-28A and the let-7 microRNA family (Lin-28/let-7 axis play a critical role in the control of glucose metabolism, insulin sensitivity and resistance to diabetes. Aim: This case-control study aimed at evaluating the association between Lin-28 rs3811464 polymorphism and the susceptibility to Type 2 Diabetes (T2D in a sample of Iranian population. Materials and Methods: This study involved 172 T2D patients and 160 non-diabetic age and gender-matched controls. Lin 28A rs3811464 genotypes were determined by Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP technique. Results: The results showed that the frequency of the AA genotype was significantly higher in control subjects than in diabetic patients (13.12% vs. 4.65%. In addition, binary logistic regression analysis revealed that rs3811464-AA genotype was significantly associated to T2D after adjustment for BMI, age and lipid profiles. Indeed, subjects with AA genotype were less likely to develop T2D than GG and AG subjects (OR of 0.26, 95% CI 0.10-0.66, p=0.005. Conclusion: The findings of our study suggest that the Lin 28A rs3811464 is associated with type 2 diabetes susceptibility and subjects with AA genotypes were less likely to develop T2D diabetes.

  5. Significant association between RGS14 rs12654812 and nephrolithiasis risk among Guangxi population in China.

    Science.gov (United States)

    Long, Jun; Chen, Yang; Lin, Haisong; Liao, Ming; Li, Tianyu; Tong, Lei; Wei, Suchun; Xian, Xiaoying; Zhu, Jia; Chen, Jianxin; Tian, Jiarong; Wang, Qiuyan; Mo, Zengnan

    2018-03-26

    Nephrolithiasis is a worldwide health problem that affects almost all populations. This study aimed to evaluate the association between rs12654812 of regulator of G protein signaling 14 (RGS14) gene and nephrolithiasis in the Chinese population. A total of 1541 participators including 830 cases and 711 controls were included from Guangxi area in China. Age, sex, BMI, smoking status, drinking status, creatinine, uric acid, and urea nitrogen were analyzed between the case group and control group. We found that the G/A+A/A genotypes of rs12654812 had a significantly increased nephrolithiasis risk after adjusting age, sex, BMI, smoking, drinking, and hypertension, compared with G/G genotype (OR = 1.361, 95% CI = 1.033-1.794, P = .029). This hazardous effect was more pronounced in subgroup of age < 50, ever smoking, ever drinking, creatinine normal, and high uric acid. The G/A genotype of rs12654812 also had a significantly increased nephrolithiasis risk compared with G/G genotype. The A allele of rs12654812 significantly increased the risk of nephrolithiasis compared with the G allele after adjusting for age, sex, BMI, smoking, drinking and hypertension (OR = 1.277, 95% CI = 1.013-1.609, P = .038). Our results suggest that the RGS14 polymorphism is involved in the etiology of nephrolithiasis and thus may be a genetic marker for nephrolithiasis. © 2018 Wiley Periodicals, Inc.

  6. Prediction of environmental parameters of polycyclic aromatic hydrocarbons with COSMO-RS

    NARCIS (Netherlands)

    Schröder, B.; Santos, L.M.N.B.F.; Alves da Rocha, M.A.; Oliveira, M.B.; Marrucho, I.M.; Coutinho, J.A.P.

    2010-01-01

    The methodology for the prediction of properties of environmental relevance of polycyclic aromatic hydrocarbons based on the conductor-like screening model for real solvents (COSMO-RS/COSMOtherm) is presented and evaluated, with a special focus on the aqueous solubility of polycyclic aromatic

  7. Transgenic tobacco plants expressing BoRS1 gene from Brassica ...

    Indian Academy of Sciences (India)

    Water stress is by far the leading environmental stress limiting crop yields worldwide. Genetic engineering techniques hold great promise for developing crop cultivars with high tolerance to water stress. In this study, the Brassica oleracea var. acephala BoRS1 gene was transferred into tobacco through ...

  8. Design of RS232-powered controller for switched parasitic array antenna

    CSIR Research Space (South Africa)

    Mofolo, MOR

    2013-09-01

    Full Text Available It is often convenient to power up peripheral devices directly from the host device interface, without a need for additional and/or external power supply. In this paper we present a design of the RS232-powered controller for electronically...

  9. Genome sequence of the rice-pathogenic bacterium Acidovorax avenae subsp. avenae RS-1.

    Science.gov (United States)

    Xie, Guan-Lin; Zhang, Guo-Qing; Liu, He; Lou, Miao-Miao; Tian, Wen-Xiao; Li, Bin; Zhou, Xue-Ping; Zhu, Bo; Jin, Gu-Lei

    2011-09-01

    Acidovorax avenae subsp. avenae is a phytobacterium which is the causative agent of several plant diseases with economic significance. Here, we present the draft genome sequence of strain RS-1, which was isolated from rice shoots in a rice field in China. This strain can cause bacterial stripe of rice. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

  10. Genome Sequence of the Rice-Pathogenic Bacterium Acidovorax avenae subsp. avenae RS-1 ▿

    OpenAIRE

    Xie, Guan-Lin; Zhang, Guo-Qing; Liu, He; Lou, Miao-Miao; Tian, Wen-Xiao; Li, Bin; Zhou, Xue-Ping; Zhu, Bo; Jin, Gu-Lei

    2011-01-01

    Acidovorax avenae subsp. avenae is a phytobacterium which is the causative agent of several plant diseases with economic significance. Here, we present the draft genome sequence of strain RS-1, which was isolated from rice shoots in a rice field in China. This strain can cause bacterial stripe of rice.

  11. Genome Sequence of the Rice-Pathogenic Bacterium Acidovorax avenae subsp. avenae RS-1 ▿

    Science.gov (United States)

    Xie, Guan-Lin; Zhang, Guo-Qing; Liu, He; Lou, Miao-Miao; Tian, Wen-Xiao; Li, Bin; Zhou, Xue-Ping; Zhu, Bo; Jin, Gu-Lei

    2011-01-01

    Acidovorax avenae subsp. avenae is a phytobacterium which is the causative agent of several plant diseases with economic significance. Here, we present the draft genome sequence of strain RS-1, which was isolated from rice shoots in a rice field in China. This strain can cause bacterial stripe of rice. PMID:21742879

  12. The Association of FTO SNP rs9939609 with Weight Gain at University

    NARCIS (Netherlands)

    Meisel, S.F.; Beeken, R.J.; Jaarsveld, C.H.M. van; Wardle, J.

    2015-01-01

    AIM: We tested the hypothesis that the obesity-associated FTO SNP rs9939609 would be associated with clinically significant weight gain (>/= 5% of initial body weight) in the first year of university; a time identified as high risk for weight gain. METHODS: We collected anthropometric data from

  13. Genotyping Rs2274625 Marker in NPHS2 Gene Associated with Nephrotic Syndrome in Isfahan Population

    Directory of Open Access Journals (Sweden)

    L Esmaili Chamgordani

    2015-12-01

    Full Text Available Introduction: Nephrotic syndrome (NS is a genetic disease belonging to a heterogeneous group of glomerular disorders, which mainly occurs within the children. Linkage analysis using single nucleotide polymorphisms (SNP is used as an indirect method in molecular diagnosis of the disease. A large number of SNP markers have been introduced in NPHS2gene in the available electronic databases. Method: In the present study, the genotype and informative status of rs2274625 marker in NPHS2 genewas investigated in 120 unrelated healthy individuals using Tetra-primer ARMS PCR technique and newly designed primers. Allelic frequency and presence of Hardy Weinberg Equilibrium (HWE was estimated using GenePop website. Furthermore, PowerMarker software was utilized in order to compute the index of polymorphism information content (PIC. Results: The study results indicated allele frequency of 97% and 3% for C and T alleles, respectively, in regard with rs2274625 marker within Isfahan population. Moreover, the PIC for the rs2274625 marker was 0.5%, and HWE revealed the equilibruim of the study population in regard with the related marker. Conclusion: As the study findings indicated, rs2274625 could be introduced as an SNP marker in the linkage analysis in order to molecularly trace NPHS2 gene mutations in molecular NS diagnosis in Isfahan population as a representative sample of the Iranian population.

  14. Prostate Cancer Susceptibility Polymorphism rs2660753 Is Not Associated with Invasive Ovarian Cancer

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Kelemen, Linda E; Wang, Qinggang

    2011-01-01

    BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1...

  15. Do we manage incontinence in children and adults with special needs adequately? ICI-RS 2014

    NARCIS (Netherlands)

    von Gontard, Alexander; de Jong, Tom P. V. M.; Rantell, Angie; Nieuwhof-Leppink, Anka; Badawi, Jasmin Katrin; Cardozo, Linda

    2016-01-01

    To review studies on the associations of incontinence and special needs in children and adults and to outline future directions in research and clinical care. A review of literature was conducted. Open questions and future directions were discussed during the ICI-RS meeting in 2014. Special needs

  16. Ionotropic glutamate receptors (iGluRs) of the delta family (GluD1 ...

    African Journals Online (AJOL)

    ... such as Neurexin1. This review presents current knowledge regarding the expression, structure and function of Glu delta receptors (GluD1, GluD2) in brain, focusing on synapse formation, function and dysfunction. Keywords: iGluRs; GluD1; GluD2; Synaptogenesis; Autism spectrum disorder (ASD); Schizophrenia (SCZ) ...

  17. Association of OPN rs11730582 polymorphism with cancer risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    He LL

    2016-03-01

    Full Text Available Lanlan He,1,* Yong Wang2,* 1Emergency Department, Zhenjiang First People’s Hospital, Zhenjiang, People’s Republic of China; 2Department of Interventional Radiology and Vascular Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China *Both authors contributed equally to this work Purpose: Several molecular epidemiological studies have investigated the association between OPN rs11730582 C>T polymorphism and cancer risk, but the results are inconsistent. Hence, a meta-analysis was conducted to determine the association of this polymorphism with cancer risk. Materials and methods: The related articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases. Pooled odds ratios and 95% confidence intervals were calculated to evaluate the strength of the associations. A random-effects model or fixed-effects model was employed depending on the heterogeneity. Results: A total of ten case-control studies involving 2,749 cancer cases and 3,398 controls were included in the meta-analysis. In overall analysis, OPN rs11730582 C>T polymorphism was not associated with cancer risk. In a stratified analysis by cancer type, no significant association was found between OPN rs11730582 C>T polymorphism and the risk of glioma, gastric cancer, and other cancers. Conclusion: This meta-analysis suggests that OPN rs11730582 C>T polymorphism is not associated with cancer susceptibility. Keywords: osteopontin, polymorphism, cancer, risk 

  18. [Association of IL-1β-511T gene rs16944 polymorphism with febrile seizures].

    Science.gov (United States)

    Ren, Xiao-Tun; Sun, Su-Zhen; Liu, Fang; Wang, Xiao-Ming

    2014-02-01

    Despite substantial research efforts worldwide, the role of inflammatory cytokine IL-1β in the onset of febrile seizures (FS) remains controversial. The aim of this study was to assess the relationship between rs16944 polymorphism of the IL-1β-511T gene and occurrence of simple FS in a sample of Han children in northern China. The IL-1β-511T gene rs16944 was genotyped by SNaPshot SNP technique in 141 FS children and 130 healthy control subjects. The genotypic and allelic frequencies in the two groups were comparatively analyzed. There were no significant differences in genotypic and allelic frequencies of rs16944 polymorphism of the IL-1β-511T gene between FS patients and control subjects (P>0.05).When the clinical data on A/A, A/G and G/G genotypes of the rs16944 polymorphism in FS patients, there was statistically significant difference in age of first onset (χ(2)=19.491, Prs16944 polymorphism of the IL-1β-511T gene and the incidence of FS in Han children in Northern China. However, the differences in genotypes of this polymorphism might be associated with pathogenesis and prognosis of simple FS in the population studied.

  19. FTO at rs9939609, Food Responsiveness, Emotional Control and Symptoms of ADHD in Preschool Children

    NARCIS (Netherlands)

    F.P. Velders (Fleur); F.R.C. de Wit (Frank); P.W. Jansen (Pauline); V.W.V. Jaddoe (Vincent); A. Hofman (Albert); F.C. Verhulst (Frank); H.W. Tiemeier (Henning)

    2012-01-01

    textabstractThe FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg)/height (m)2) in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural

  20. Does company compliance with RS-17 influence the characterization of a casual nexus in expert testimony?

    Directory of Open Access Journals (Sweden)

    Manuela Ribeiro

    2015-02-01

    Full Text Available Objective: To examine whether company compliance with RS-17 influences the characterization of the casual nexus in physical therapists' expert reports of cumulative trauma disorders in the labor court of Pernambuco, Brazil. Method: The sample was composed of seven physical therapists who provided expert testimony regarding cumulative trauma disorder cases in the labor court of Pernambuco, Brazil. Data collection was performed across two stages. In the first stage, the experts answered a sociodemographic survey and requested the identification numbers of recent cases where expert testimony was provided to characterize the causal nexus. In the second stage, the researchers went to the labor court to collect expert testimony data. These experts indicated that of 75 total cases, 31% (N=23 of the companies fulfilled RS-17, whereas 69% (N=52 did not comply with the law. Results: Among the organizations that complied with legislation, 30% of the analyzed expert testimonies showed a positive causal nexus. However, of the companies that did not comply with RS-17, 71% of the expert testimonies revealed a causal nexus. These results indicate that the breach of the law increases the probability that a causal nexus will be determined by 54.8%. Conclusion: The results showed that failure to comply with RS-17 significantly increases the probability that a causal nexus will be determined in physical therapists' expert testimony of cumulative trauma disorders.

  1. Sex differences in microRNA regulation of gene expression: no smoke, just miRs

    Directory of Open Access Journals (Sweden)

    Morgan Christopher P

    2012-09-01

    Full Text Available Abstract Males and females differ widely in morphology, physiology, and behavior leading to disparities in many health outcomes, including sex biases in the prevalence of many neurodevelopmental disorders. However, with the exception of a relatively small number of genes on the Y chromosome, males and females share a common genome. Therefore, sexual differentiation must in large part be a product of the sex biased expression of this shared genetic substrate. microRNAs (miRs are small non-coding RNAs involved in the post-transcriptional regulation of up to 70% of protein-coding genes. The ability of miRs to regulate such a vast amount of the genome with a high degree of specificity makes them perfectly poised to play a critical role in programming of the sexually dimorphic brain. This review describes those characteristics of miRs that make them particularly amenable to this task, and examines the influences of both the sex chromosome complement as well as gonadal hormones on their regulation. Exploring miRs in the context of sex differences in disease, particularly in sex-biased neurodevelopmental disorders, may provide novel insight into the pathophysiology and potential therapeutic targets in disease treatment and prevention.

  2. Ledelse på tværs i de danske sygehuse

    DEFF Research Database (Denmark)

    Plesner, Jeppe; Christensen, Anne Birgitte; Bech, Mickael

    2012-01-01

    behovet for bedre koordinering og samarbejde på tværs af organisatoriske grænser. I kontrast hertil var ledelsestænkningen baseret på hierarkiske, positionsorienterede ledelsesdiskurser, der ikke matcher de organisatoriske behov. Sygehuse er komplekse organisationer, men en rationalistisk styrings- og...

  3. The construction of distant total distributed measuring and controlling system based on RS-232 communication

    International Nuclear Information System (INIS)

    Shi Chengying; Li Tiantuo; Zhu Wenkai; Zhang Quanhu

    1999-01-01

    The author discusses the construction of distant total distributed measuring and controlling system based on RS-232 communication. The merits of this system are simple construction, reliable performance, big communication distance, and wide covering range. The system fits in with application in radiation environment. The author also discusses the system's hardware equipment and communication protocol

  4. Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: Prospective Validation of the HeRS Score.

    Science.gov (United States)

    Marsh, Elisabeth B; Llinas, Rafael H; Schneider, Andrea L C; Hillis, Argye E; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F

    2016-01-01

    Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

  5. Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis.

    Science.gov (United States)

    Liang, Ya-Ling; Wu, Hua; Shen, Xi; Li, Pei-Qiang; Yang, Xiao-Qing; Liang, Li; Tian, Wei-Hua; Zhang, Li-Feng; Xie, Xiao-Dong

    2012-09-01

    The association between the signal transducer and activator of transcription 4 (STAT4) gene rs7574865 single nucleotide polymorphism and different autoimmune diseases remains controversial and ambiguous. We conducted this study to investigate whether combined evidence shows the association between STAT4 rs7574865 polymorphism and autoimmune diseases. Comprehensive Medline search and review of the references were used to get the relevant reports published before September 2011. Meta-analysis was conducted for genotype T/T (recessive effect), T/T + G/T (dominant effect) and T allele in random effects models. 40 studies with 90 comparisons including 32 systemic lupus erythematosus (SLE), 19 rheumatoid arthritis (RA), 3 type 1 diabetes (T1D), 11 Systemeric Sclerosis (SSc), 4 inflammatory bowed diseases (IBD), 3 Primary Sjogren's syndrome (pSS), 4 juvenile idiopathic arthritis (JIA), 2 Primary antiphospholipid syndrome (APS), 1 Autoimmune thyroid diseases, 1 multiple sclerosis, 1 Psoriasis, 1 Wegener's granulomatosis, 1 Type 2 diabetes, and 1 giant cell arteritis disease were available for this meta-analysis. The overall odds ratios for rs7574865 T-allele significantly increased in SLE, RA, T1D, SSc, JIA, and APS (OR = 1.56, 1.25, 1.13, 1.34, 1.25, and 2.15, respectively, P rs7574865 T allele confers susceptibility to SLE, RA, T1D, SSc, JIA, APS, IBD-UC, and pSS patients, supporting the hypothesis of association between STAT4 gene polymorphism and subgroup of autoimmune diseases.

  6. Phenotypic Heterogeneity of Genomically-Diverse Isolates of Streptococcus mutans

    Science.gov (United States)

    Palmer, Sara R.; Miller, James H.; Abranches, Jacqueline; Zeng, Lin; Lefebure, Tristan; Richards, Vincent P.; Lemos, José A.; Stanhope, Michael J.; Burne, Robert A.

    2013-01-01

    High coverage, whole genome shotgun (WGS) sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat) and exposure to competence stimulating peptide (CSP). Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease. PMID:23613838

  7. Phenotypic heterogeneity of genomically-diverse isolates of Streptococcus mutans.

    Directory of Open Access Journals (Sweden)

    Sara R Palmer

    Full Text Available High coverage, whole genome shotgun (WGS sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat and exposure to competence stimulating peptide (CSP. Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease.

  8. FSHD myotubes with different phenotypes exhibit distinct proteomes.

    Science.gov (United States)

    Tassin, Alexandra; Leroy, Baptiste; Laoudj-Chenivesse, Dalila; Wauters, Armelle; Vanderplanck, Céline; Le Bihan, Marie-Catherine; Coppée, Frédérique; Wattiez, Ruddy; Belayew, Alexandra

    2012-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder linked to a contraction of the D4Z4 repeat array in the 4q35 subtelomeric region. This deletion induces epigenetic modifications that affect the expression of several genes located in the vicinity. In each D4Z4 element, we identified the double homeobox 4 (DUX4) gene. DUX4 expresses a transcription factor that plays a major role in the development of FSHD through the initiation of a large gene dysregulation cascade that causes myogenic differentiation defects, atrophy and reduced response to oxidative stress. Because miRNAs variably affect mRNA expression, proteomic approaches are required to define the dysregulated pathways in FSHD. In this study, we optimized a differential isotope protein labeling (ICPL) method combined with shotgun proteomic analysis using a gel-free system (2DLC-MS/MS) to study FSHD myotubes. Primary CD56(+) FSHD myoblasts were found to fuse into myotubes presenting various proportions of an atrophic or a disorganized phenotype. To better understand the FSHD myogenic defect, our improved proteomic procedure was used to compare predominantly atrophic or disorganized myotubes to the same matching healthy control. FSHD atrophic myotubes presented decreased structural and contractile muscle components. This phenotype suggests the occurrence of atrophy-associated proteolysis that likely results from the DUX4-mediated gene dysregulation cascade. The skeletal muscle myosin isoforms were decreased while non-muscle myosin complexes were more abundant. In FSHD disorganized myotubes, myosin isoforms were not reduced, and increased proteins were mostly involved in microtubule network organization and myofibrillar remodeling. A common feature of both FSHD myotube phenotypes was the disturbance of several caveolar proteins, such as PTRF and MURC. Taken together, our data suggest changes in trafficking and in the membrane microdomains of FSHD myotubes. Finally, the adjustment of a

  9. FSHD myotubes with different phenotypes exhibit distinct proteomes.

    Directory of Open Access Journals (Sweden)

    Alexandra Tassin

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is a progressive muscle disorder linked to a contraction of the D4Z4 repeat array in the 4q35 subtelomeric region. This deletion induces epigenetic modifications that affect the expression of several genes located in the vicinity. In each D4Z4 element, we identified the double homeobox 4 (DUX4 gene. DUX4 expresses a transcription factor that plays a major role in the development of FSHD through the initiation of a large gene dysregulation cascade that causes myogenic differentiation defects, atrophy and reduced response to oxidative stress. Because miRNAs variably affect mRNA expression, proteomic approaches are required to define the dysregulated pathways in FSHD. In this study, we optimized a differential isotope protein labeling (ICPL method combined with shotgun proteomic analysis using a gel-free system (2DLC-MS/MS to study FSHD myotubes. Primary CD56(+ FSHD myoblasts were found to fuse into myotubes presenting various proportions of an atrophic or a disorganized phenotype. To better understand the FSHD myogenic defect, our improved proteomic procedure was used to compare predominantly atrophic or disorganized myotubes to the same matching healthy control. FSHD atrophic myotubes presented decreased structural and contractile muscle components. This phenotype suggests the occurrence of atrophy-associated proteolysis that likely results from the DUX4-mediated gene dysregulation cascade. The skeletal muscle myosin isoforms were decreased while non-muscle myosin complexes were more abundant. In FSHD disorganized myotubes, myosin isoforms were not reduced, and increased proteins were mostly involved in microtubule network organization and myofibrillar remodeling. A common feature of both FSHD myotube phenotypes was the disturbance of several caveolar proteins, such as PTRF and MURC. Taken together, our data suggest changes in trafficking and in the membrane microdomains of FSHD myotubes. Finally, the

  10. IL-1B rs16944 polymorphism is related to septic shock and death.

    Science.gov (United States)

    Jiménez-Sousa, María Ángeles; Medrano, Luz M; Liu, Pilar; Almansa, Raquel; Fernández-Rodríguez, Amanda; Gómez-Sánchez, Esther; Rico, Lucía; Heredia-Rodríguez, María; Gómez-Pesquera, Estefanía; Tamayo, Eduardo; Resino, Salvador

    2017-01-01

    IL-1β is a primary mediator of systemic inflammatory response syndrome (SIRS) and it may lead to shock septic. Our aim was to analyse whether IL-1B rs16944 polymorphism is associated with the onset of septic shock and death after major surgery. We performed a case-control study on 467 patients who underwent major cardiac or abdominal surgery. Of them, 205 patients developed septic shock (cases, SS group) and 262 patients developed SIRS (controls, SIRS group). The primary outcome variables were the development of septic shock and death within 90 days after diagnosis of septic shock. The IL-1B rs16944 polymorphism was genotyped by Sequenom's MassARRAY platform. The association analysis was performed under a recessive genetic model (AA vs. GG/GC). The frequency of septic shock was higher in patients with IL-1B rs16944 AA genotype than in patients with IL-1B rs16944 GG/AG genotype when all patients were taken into account (63·6% vs. 41·8%; P = 0·006), cardiac surgery (52·2% vs. 33·3%; P = 0·072) and abdominal surgery (76·2% vs. 50·2%; P = 0·023). However, the IL-1B rs16944 AA genotype was only associated with higher likelihood of septic shock in the analysis of all population [adjusted odds ratio (aOR) = 2·26 (95%CI = 1·03; 4·97; P = 0·042], but not when it was stratified by cardiac surgery (P = 0·175) or abdominal surgery (P = 0·467). Similarly, IL-1B rs16944 AA genotype was also associated with higher likelihood of septic shock-related death in all population [aOR = 2·67 (95%CI = 1·07; 4·97); P = 0·035]. IL-1B rs16944 AA genotype seems to be related to the onset of septic shock and death in patients who underwent major surgery. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  11. Beta cell 5'-shifted isomiRs are candidate regulatory hubs in type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Jeanette Baran-Gale

    Full Text Available Next-generation deep sequencing of small RNAs has unveiled the complexity of the microRNA (miRNA transcriptome, which is in large part due to the diversity of miRNA sequence variants ("isomiRs". Changes to a miRNA's seed sequence (nucleotides 2-8, including shifted start positions, can redirect targeting to a dramatically different set of RNAs and alter biological function. We performed deep sequencing of small RNA from mouse insulinoma (MIN6 cells (widely used as a surrogate for the study of pancreatic beta cells and developed a bioinformatic analysis pipeline to profile isomiR diversity. Additionally, we applied the pipeline to recently published small RNA-seq data from primary human beta cells and whole islets and compared the miRNA profiles with that of MIN6. We found that: (1 the miRNA expression profile in MIN6 cells is highly correlated with those of primary human beta cells and whole islets; (2 miRNA loci can generate multiple highly expressed isomiRs with different 5'-start positions (5'-isomiRs; (3 isomiRs with shifted start positions (5'-shifted isomiRs are highly expressed, and can be as abundant as their unshifted counterparts (5'-reference miRNAs. Finally, we identified 10 beta cell miRNA families as candidate regulatory hubs in a type 2 diabetes (T2D gene network. The most significant candidate hub was miR-29, which we demonstrated regulates the mRNA levels of several genes critical to beta cell function and implicated in T2D. Three of the candidate miRNA hubs were novel 5'-shifted isomiRs: miR-375+1, miR-375-1 and miR-183-5p+1. We showed by in silico target prediction and in vitro transfection studies that both miR-375+1 and miR-375-1 are likely to target an overlapping, but distinct suite of beta cell genes compared to canonical miR-375. In summary, this study characterizes the isomiR profile in beta cells for the first time, and also highlights the potential functional relevance of 5'-shifted isomiRs to T2D.

  12. Hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Jun Yin

    Full Text Available Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. We conducted a hospital based case-control study to evaluate the genetic susceptibility of functional single nucleotide polymorphisms (SNPs in the microRNAs on the development of esophageal cancer. A total of 629 esophageal squamous cell carcinoma (ESCC cases and 686 controls were recruited for this study. The hsa-miR-34b/c rs4938723 T>C, pri-miR-124-1 rs531564 C>G, pre-miR-125a rs12975333 G>T and hsa-miR-423 rs6505162 C>A genotypes were determined using Ligation Detection Reaction (LDR method. Our results demonstrated that hsa-miR-34b/c rs4938723 CC genotype had a decreased risk of ESCC. The association was evident among patients who never drinking. Hsa-miR-423 rs6505162 C>A might associated with a significantly increased risk of ESCC in patients who smoking. These findings indicated that functional polymorphisms hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A might alter individual susceptibility to ESCC. However, our results were obtained with a limited sample size. Future larger studies with other ethnic populations are required to confirm current findings.

  13. Genetic and phenotypic heterogeneity in tropical calcific pancreatitis.

    Science.gov (United States)

    Paliwal, Sumit; Bhaskar, Seema; Chandak, Giriraj R

    2014-12-14

    Tropical calcific pancreatitis (TCP) is a form of chronic non-alcoholic pancreatitis initially reported in the developing parts of the tropical world. The clinical phenotype of TCP has undergone marked changes since its first description in 1968. The disease is now seen in relatively older people with less severe symptoms. In addition, there are varying reports on the proportion of cases presenting with imaging abnormalities like calcification, ductal dilation, and glandular atrophy. Significant progress has also been made in understanding the etiopathology of TCP. The role of malnutrition and cassava toxicity in its pathogenesis is disproven and few studies have focused on the role of micronutrient deficiency and oxidative stress in the etiopathogenesis of TCP. Emerging evidence support an important role for genetic risk factors in TCP. Several studies have shown that, rather than mutations in trypsinogens, variants in serine protease inhibitor kazal type 1, cathepsin B, chymotrypsin C, cystic fibrosis transmembrane regulator, and carboxypeptidase A1, predict risk of TCP. These studies also provided evidence of mutational heterogeneity between TCP and chronic pancreatitis in Western populations. The current review summarizes recent advances that have implications in the understanding of the pathophysiology and thus, heterogeneity in genotype-phenotype correlations in TCP.

  14. Interleukin 1 gene cluster SNPs (rs1800587, rs1143634) influences post-orthodontic root resorption in endodontic and their contralateral vital control teeth differently.

    Science.gov (United States)

    Iglesias-Linares, A; Yañez-Vico, R M; Ballesta, S; Ortiz-Ariza, E; Mendoza-Mendoza, A; Perea, E; Solano-Reina, E

    2012-11-01

    To investigate whether the genetic variants of the interleukin-1 gene cluster (IL1) are associated with a possible genetically induced variability in post-orthodontic external apical root resorption (EARR) in root filled teeth and their control counterparts with vital pulps. One hundred and forty-six maxillary premolars were evaluated radiographically following orthodontic treatment. Genetic screening was performed on orthodontic patients for two single-nucleotide polymorphisms (SNPs: rs1800587 and rs1143634) in the IL1 gene cluster. Subjects were divided into two groups according to the presence or absence of radiographic post-orthodontic EARR (>2 mm) in root filled teeth and their controls with vital pulps. Logistic regression analysis was performed to obtain an adjusted estimation between EARR and IL1 polymorphisms. Allelic frequencies, genotype distributions, and adjusted odds ratio (OR), at 95% confidence interval, were also calculated. Whilst no clear statistical association was found for gene variations in IL1A, a sound association was found in the comparative analysis of subjects homozygous [2/2(TT)] for the IL1B gene, which resulted in a two times increased risk of suffering post-orthodontic EARR in root filled teeth [OR, 2.032 (P = 0.031); CI,1.99-14.77] when compared with their controls with vital pulps. There was, however, a shared predisposition to EARR in controls with vital pulps and root filled teeth of subjects homozygous for allele 1 [OR, 5.05 (P = 0.002)] and [OR, 2.77 (P = 0.037)], respectively. Genetic variations in the interleukin-1β gene (rs1143634) predispose root filled teeth to EARR for matched pairs secondary to orthodontic treatment in a different way from their control teeth with vital pulps in subjects homozygous for allele 2 [2/2(TT)]. © 2012 International Endodontic Journal.

  15. Synchronization, TIGoRS, and Information Flow in Complex Systems: Dispositional Cellular Automata.

    Science.gov (United States)

    Sulis, William H

    2016-04-01

    Synchronization has a long history in physics where it refers to the phase matching of two identical oscillators. This notion has been extensively studied in physics as well as in biology, where it has been applied to such widely varying phenomena as the flashing of fireflies and firing of neurons in the brain. Human behavior, however, may be recurrent but it is not oscillatory even though many physiological systems do exhibit oscillatory tendencies. Moreover, much of human behaviour is collaborative and cooperative, where the individual behaviours may be distinct yet contemporaneous (if not simultaneous) and taken collectively express some functionality. In the context of behaviour, the important aspect is the repeated co-occurrence in time of behaviours that facilitate the propagation of information or of functionality, regardless of whether or not these behaviours are similar or identical. An example of this weaker notion of synchronization is transient induced global response synchronization (TIGoRS). Previous work has shown that TIGoRS is a ubiquitous phenomenon among complex systems, enabling them to stably parse environmental transients into salient units to which they stably respond. This leads to the notion of Sulis machines, which emergently generate a primitive linguistic structure through their dynamics. This article reviews the notion of TIGoRS and its expression in several complex systems models including tempered neural networks, driven cellular automata and cocktail party automata. The emergent linguistics of Sulis machines are discussed. A new class of complex systems model, the dispositional cellular automaton is introduced. A new metric for TIGoRS, the excess synchronization, is introduced and applied to the study of TIGoRS in dispositional cellular automata. It is shown that these automata exhibit a nonlinear synchronization response to certain perturbing transients.

  16. THREE-DIMENSIONAL DOPPLER TOMOGRAPHY OF THE RS VULPECULAE INTERACTING BINARY

    International Nuclear Information System (INIS)

    Richards, Mercedes T.; Sharova, Olga I.; Agafonov, Michail I.

    2010-01-01

    Three-dimensional Doppler tomography has been used to study the Hα emission sources in the RS Vulpeculae (RS Vul) interacting binary. The two-dimensional tomogram of this binary suggested that most of the emission arises from the cool mass losing star with additional evidence of a gas stream flowing close to its predicted trajectory. However, the three-dimensional tomogram revealed surprising evidence that the gas stream has an average velocity of -85 km s -1 relative to the central velocity plane at V z = 0 km s -1 , unlike U CrB in which the stream was prominent along this central plane. These unexpected V z motions may result from the interaction between magnetic activity on the cool star and the gravitationally induced Roche lobe overflow from that star. Evidence of a loop prominence on the cool star close to the L1 point has been found in the three-dimensional tomogram of RS Vul; hence, the magnetic field lines may have deflected the gas stream relative to the central plane. This result is consistent with earlier detections of RS Vul as both an X-ray and a radio source, and represents the first detection of a loop prominence in an interacting binary based on tomography. Moreover, recent radio images of β Per, the prototype of the Algols, show that the magnetic field of the mass losing star is asymmetric and extends well beyond the orbital plane of the binary, so it is now plausible that the gas flow between the stars in RS Vul could be deflected in an asymmetric way by the magnetic field.

  17. Expanding the three Rs to meet new challenges in humane animal experimentation.

    Science.gov (United States)

    Schuppli, Catherine A; Fraser, David; McDonald, Michael

    2004-11-01

    The Three Rs are the main principles used by Animal Ethics Committees in the governance of animal experimentation, but they appear not to cover some ethical issues that arise today. These include: a) claims that certain species should be exempted on principle from harmful research; b) increased emphasis on enhancing quality of life of research animals; c) research involving genetically modified (GM) animals; and d) animals bred as models of disease. In some cases, the Three Rs can be extended to cover these developments. The burgeoning use of GM animals in science calls for new forms of reduction through improved genetic modification technology, plus continued attention to alternative approaches and cost-benefit analyses that include the large numbers of animals involved indirectly. The adoption of more expanded definitions of refinement that go beyond minimising distress will capture concerns for enhancing the quality of life of animals through improved husbandry and handling. Targeting refinement to the unpredictable effects of gene modification may be difficult; in these cases, careful attention to monitoring and endpoints are the obvious options. Refinement can also include sharing data about the welfare impacts of gene modifications, and modelling earlier stages of disease, in order to reduce the potential suffering caused to disease models. Other issues may require a move beyond the Three Rs. Certain levels of harm, or numbers and use of certain species, may be unacceptable, regardless of potential benefits. This can be addressed by supplementing the utilitarian basis of the Three Rs with principles based on deontological and relational ethics. The Three Rs remain very useful, but they require thoughtful interpretation and expansion in order for Animal Ethics Committees to address the full range of issues in animal-based research.

  18. LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese population.

    Science.gov (United States)

    Zhang, Zhuorong; Chang, Yitian; Jia, Wei; Zhang, Jiao; Zhang, Ruizhong; Zhu, Jinhong; Yang, Tianyou; Xia, Huimin; Zou, Yan; He, Jing

    2018-02-28

    Neuroblastoma, which accounts for approximately 10% of all pediatric cancer-related deaths, has become a therapeutic challenge and global burden attributed to poor outcomes and mortality rates of its high-risk form. Previous genome-wide association studies (GWASs) identified the LINC00673 rs11655237 C>T polymorphism to be associated with the susceptibility of several malignant tumors. However, the association between this polymorphism and neuroblastoma susceptibility is not clear. We genotyped LINC00673 rs11655237 C>T in 393 neuroblastoma patients in comparison with 812 age-, gender-, and ethnicity-matched healthy controls. We found a significant association between the LINC00673 rs11655237 C>T polymorphism and neuroblastoma risk (TT compared with CC: adjusted odds ratio (OR) =1.80, 95% confidence interval (CI) =1.06-3.06, P =0.029; TT/CT compared with CC: adjusted OR =1.31, 95% CI =1.02-1.67, P =0.033; and T compared with C: adjusted OR =1.29, 95% CI =1.06-1.58, P =0.013). Furthermore, stratified analysis indicated that the rs11655237 T allele carriers were associated with increased neuroblastoma risk for patients with tumor originating from the adrenal gland (adjusted OR =1.51, 95% CI =1.06-2.14, P =0.021) and International Neuroblastoma Staging System (INSS) stage IV disease (adjusted OR =1.60, 95% CI =1.12-2.30, P =0.011). In conclusion, we verified that the LINC00673 rs11655237 C>T polymorphism might be associated with neuroblastoma susceptibility. Prospective studies with a large sample size and different ethnicities are needed to validate our findings. © 2018 The Author(s).

  19. Effect of Bcl-2 rs956572 polymorphism on age-related gray matter volume changes.

    Directory of Open Access Journals (Sweden)

    Mu-En Liu

    Full Text Available The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2 gene is a major regulator of neural plasticity and cellular resilience. Recently, the Bcl-2 rs956572 single nucleotide polymorphism was proposed to be a functional allelic variant that modulates cellular vulnerability to apoptosis. Our cross-sectional study investigated the genetic effect of this Bcl-2 polymorphism on age-related decreases in gray matter (GM volume across the adult lifespan. Our sample comprised 330 healthy volunteers (191 male, 139 female with a mean age of 56.2±22.0 years (range: 21-92. Magnetic resonance imaging and genotyping of the Bcl-2 rs956572 were performed for each participant. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. The association between the Bcl-2 rs956572 polymorphism and age was a predictor of regional GM volumes in the right cerebellum, bilateral lingual gyrus, right middle temporal gyrus, and right parahippocampal gyrus. We found that the volume of these five regions decreased with increasing age (all P<.001. Moreover, the downward slope was steeper among the Bcl-2 rs956572 A-allele carriers than in the G-homozygous participants. Our data provide convergent evidence for the genetic effect of the Bcl-2 functional allelic variant in brain aging. The rs956572 G-allele, which is associated with significantly higher Bcl-2 protein expression and diminished cellular sensitivity to stress-induced apoptosis, conferred a protective effect against age-related changes in brain GM volume, particularly in the cerebellum.

  20. Studies of physicochemical properties of graphite oxide and thermally exfoliated/reduced graphene oxide

    Directory of Open Access Journals (Sweden)

    Drewniak Sabina Elżbieta

    2015-12-01

    Full Text Available The aim of the experimental research studies was to determine some electrical properties of graphite oxide and thermally exfoliated/reduced graphene oxide. The authors tried to interpret the obtained physicochemical results. For that purpose, both resistance measurements and investigation studies were carried out in order to characterize the samples. The resistance was measured at various temperatures in the course of composition changes of gas atmospheres (which surround the samples. The studies were also supported by such methods as: scanning electron microscopy (SEM, Raman spectroscopy (RS, atomic force microscopy (AFM and thermogravimetry (TG. Moreover, during the experiments also the elemental analyses (EA of the tested samples (graphite oxide and thermally exfoliated/reduced graphene oxide were performed.

  1. Studies of Reduced Graphene Oxide and Graphite Oxide in the Aspect of Their Possible Application in Gas Sensors

    Science.gov (United States)

    Drewniak, Sabina; Muzyka, Roksana; Stolarczyk, Agnieszka; Pustelny, Tadeusz; Kotyczka-Morańska, Michalina; Setkiewicz, Maciej

    2016-01-01

    The paper presents the results of investigations on resistance structures based on graphite oxide (GRO) and graphene oxide (rGO). The subject matter of the investigations was thaw the sensitivity of the tested structures was affected by hydrogen, nitrogen dioxide and carbon dioxide. The experiments were performed at a temperature range from 30 °C to 150 °C in two carrier gases: nitrogen and synthetic air. The measurements were also aimed at characterization of the graphite oxide and graphene oxide. In our measurements we used (among others) techniques such as: Atomic Force Microscopy (AFM); Scanning Electron Microscopy (SEM); Raman Spectroscopy (RS); Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Photoelectron Microscopy (XPS). The data resulting from the characterizations of graphite oxide and graphene oxide have made it possible to interpret the obtained results from the point of view of physicochemical changes occurring in these structures. PMID:26784198

  2. Studies of Reduced Graphene Oxide and Graphite Oxide in the Aspect of Their Possible Application in Gas Sensors.

    Science.gov (United States)

    Drewniak, Sabina; Muzyka, Roksana; Stolarczyk, Agnieszka; Pustelny, Tadeusz; Kotyczka-Morańska, Michalina; Setkiewicz, Maciej

    2016-01-15

    The paper presents the results of investigations on resistance structures based on graphite oxide (GRO) and graphene oxide (rGO). The subject matter of the investigations was thaw the sensitivity of the tested structures was affected by hydrogen, nitrogen dioxide and carbon dioxide. The experiments were performed at a temperature range from 30 °C to 150 °C in two carrier gases: nitrogen and synthetic air. The measurements were also aimed at characterization of the graphite oxide and graphene oxide. In our measurements we used (among others) techniques such as: Atomic Force Microscopy (AFM); Scanning Electron Microscopy (SEM); Raman Spectroscopy (RS); Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Photoelectron Microscopy (XPS). The data resulting from the characterizations of graphite oxide and graphene oxide have made it possible to interpret the obtained results from the point of view of physicochemical changes occurring in these structures.

  3. Research status in ultra-precision machining of silicon carbide parts by oxidation-assisted polishing

    Directory of Open Access Journals (Sweden)

    Xinmin SHEN

    2016-10-01

    Full Text Available Oxidation-assisted polishing is an important machining method for obtaining SiC parts with high precision. Through plasma oxidation, thermal oxidation, and anodic oxidation, soft oxide can be obtained on the RS-SiC substrate. With the assistance of abrasive polishing to remove the oxide rapidly, the material removal rate can be increased and the surface quality can be improved. The research results indicate that the surface roughness root-mean-square (RMS and roughness-average (Ra can reach 0.626 nm and 0.480 nm by plasma oxidation-assisted polishing; in thermal oxidation-assisted polishing, the RMS and Ra can be 0.920 nm and 0.726 nm; in anodic oxidation, the calculated oxidation rate is 5.3 nm/s based on Deal-Grove model, and the RMS and Ra are 4.428 nm and 3.453 nm respectively in anodic oxidation-assisted polishing. The oxidation-assisted polishing can be propitious to improve the process level in machining RS-SiC, which would promote the application of SiC parts in optics and ceramics fields.

  4. Vascular endothelial growth factor (VEGF-related single nucleotide polymorphisms rs10738760 and rs6921438 are not associated with diabetic retinopathy (DR in Slovenian patients with type 2 diabetes mellitus (T2DM

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    Rifet Terzić

    2017-11-01

    Full Text Available Diabetic retinopathy (DR is a complication of diabetes characterized by vascular permeability, increased tissue ischemia, and angiogenesis. One of the most important proteins involved in angiogenesis is vascular endothelial growth factor (VEGF, also known as VEGFA. A previous study demonstrated that two single nucleotide polymorphisms (SNPs, rs6921438 and rs10738760, account for nearly half the variation in circulating VEGF levels. The aim of our study was to assess the association between rs6921438 and rs10738760 and DR in Slovenian patients with type 2 diabetes mellitus (T2DM. This case-control study enrolled 1037 unrelated Slovenian individuals (Caucasians with T2DM. DR group included 415 T2DM patients with DR, while control group included 622 T2DM patients with no clinical signs of DR. The clinical and laboratory data were obtained from the medical records of the patients. The genotyping of rs6921438 and rs10738760 SNPs was carried out with real-time PCR assays. Significant differences were observed between patients with DR and controls in the duration of diabetes (p < 0.001, insulin therapy (p < 0.001, glycated hemoglobin (p = 0.001, body mass index (p = 0.002, total cholesterol (p = 0.002, and low-density lipoprotein cholesterol (p < 0.001. However, we did not observe significant differences in the genotype and allele distribution of the two SNPs, between DR and control group (p < 0.05. Logistic regression analysis showed that rs6921438 and rs10738760 were not independent genetic risk factors for DR in the co-dominant model adjusted for the above-mentioned clinical and laboratory data. In conclusion, VEGF-related SNPs