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Sample records for genes affecting aortic

  1. Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve.

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    Rueda-Martínez, Carmen; Fernández, M Carmen; Soto-Navarrete, María Teresa; Jiménez-Navarro, Manuel; Durán, Ana Carmen; Fernández, Borja

    2016-01-01

    Bicuspid aortic valve (BAV) is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40%) incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR) assays. A total of 51 adult (180-240 days old) and 56 old (300-440 days old) animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30), or to the affected strain of hamsters with TAV (n = 45) or BAV (n = 32). The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta.

  2. Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve.

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    Carmen Rueda-Martínez

    Full Text Available Bicuspid aortic valve (BAV is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40% incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR assays. A total of 51 adult (180-240 days old and 56 old (300-440 days old animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30, or to the affected strain of hamsters with TAV (n = 45 or BAV (n = 32. The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta.

  3. Factors Affecting Optimal Aortic Remodeling After Thoracic Endovascular Aortic Repair of Type B (IIIb) Aortic Dissection

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    Chen, I-Ming; Chen, Po-Lin; Huang, Chun-Yang; Weng, Shih-Hsien; Chen, Wei-Yuan; Shih, Chun-Che

    2017-01-01

    PurposeThe purpose of this study was to determine factors associated with entire aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with type B dissection.Materials and MethodsThe patients with type B (IIIb) dissections who underwent TEVAR from 2006 to 2013 with minimum of 2 years of follow-up computed tomography data were retrospectively reviewed. Based on the status of false lumen remodeling of entire aorta, patients were divided into three groups: complete regression, total thrombosis, and inadequate regression with patent abdominal false lumen.ResultsA total of 90 patients (72 males, 18 females; mean age 56.6 ± 16.4 years) were included and divided into the complete regression (n = 22), total thrombosis (n = 18), and inadequate regression (n = 50) groups. Multivariate logistic regression analysis indicated that dissection extension to iliac arteries, increased preoperative number of dissection tear over abdominal aorta, and decreased preoperative abdominal aorta bifurcation true lumen ratio, as compared between the inadequate and complete regression groups, were associated with a persistent false lumen (odds ratio = 33.33, 2.304, and 0.021; all, p ≤ 0.012). Comparison of 6, 12, and 24 months postoperative data revealed no significant differences at any level, suggesting that the true lumen area ratio might not change after 6 months postoperatively.ConclusionsIncreased preoperative numbers of dissection tear around the abdominal visceral branches, dissection extension to the iliac arteries, and decreased preoperative true lumen area ratio of abdominal aorta are predictive of entire aortic remodeling after TEVAR in patients with type B dissection.Level of EvidenceIII.

  4. Factors Affecting Optimal Aortic Remodeling After Thoracic Endovascular Aortic Repair of Type B (IIIb) Aortic Dissection

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    Chen, I-Ming [National Yang Ming University, Institute of Clinical Medicine, School of Medicine (China); Chen, Po-Lin; Huang, Chun-Yang [National Yang Ming University, Department of Medicine, School of Medicine (China); Weng, Shih-Hsien; Chen, Wei-Yuan; Shih, Chun-Che, E-mail: ccshih@vghtpe.gov.tw [National Yang Ming University, Institute of Clinical Medicine, School of Medicine (China)

    2017-05-15

    PurposeThe purpose of this study was to determine factors associated with entire aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with type B dissection.Materials and MethodsThe patients with type B (IIIb) dissections who underwent TEVAR from 2006 to 2013 with minimum of 2 years of follow-up computed tomography data were retrospectively reviewed. Based on the status of false lumen remodeling of entire aorta, patients were divided into three groups: complete regression, total thrombosis, and inadequate regression with patent abdominal false lumen.ResultsA total of 90 patients (72 males, 18 females; mean age 56.6 ± 16.4 years) were included and divided into the complete regression (n = 22), total thrombosis (n = 18), and inadequate regression (n = 50) groups. Multivariate logistic regression analysis indicated that dissection extension to iliac arteries, increased preoperative number of dissection tear over abdominal aorta, and decreased preoperative abdominal aorta bifurcation true lumen ratio, as compared between the inadequate and complete regression groups, were associated with a persistent false lumen (odds ratio = 33.33, 2.304, and 0.021; all, p ≤ 0.012). Comparison of 6, 12, and 24 months postoperative data revealed no significant differences at any level, suggesting that the true lumen area ratio might not change after 6 months postoperatively.ConclusionsIncreased preoperative numbers of dissection tear around the abdominal visceral branches, dissection extension to the iliac arteries, and decreased preoperative true lumen area ratio of abdominal aorta are predictive of entire aortic remodeling after TEVAR in patients with type B dissection.Level of EvidenceIII.

  5. Polymorphisms of the MMP-9 gene and abdominal aortic aneurysm

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    Smallwood, Linda; Allcock, Richard; van Bockxmeer, Frank; Warrington, Nicole; Palmer, Lyle J; Iacopetta, Barry; Golledge, Jonathan; Norman, Paul E

    2008-01-01

    Background Increased matrix metalloproteinase-9 (MMP-9) activity has been implicated in the formation of abdominal aortic aneurysms (AAAs). The aim of the present study was to explore the association between potentially functional variants of the MMP-9 gene and AAA. Method The −1562C>T and −1811A>T variants of the MMP-9 gene were genotyped in 678 men with AAAs (>30mm in diameter) and 659 controls (aortic diameter 19−22mm) recruited from a population-based trial of screening for AAAs. The levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed using multivariate logistic regression. Results There was no association between the MMP-9 −1562C>T (OR 0.70 95%CI 0.27, 1.82) or −1811A>T (OR 0.71, 95%CI 0.28, 1.85) genotypes, or the most common haplotype (OR 0.81 95%CI 0.62, 1.05), and AAA. The serum MMP-9 concentration (ng/mL) was higher in cases than controls and in minor allele carriers in cases and controls although the differences were not statistically significant. Conclusion The results suggest that a genetic tendency to have higher levels of circulating MMP-9 is not associated with AAAs. PMID:18763261

  6. Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

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    Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

    2009-08-01

    To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

  7. Association of the C-Reactive Protein Gene (CRP rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis

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    Ewa Wypasek

    2015-10-01

    Full Text Available Elevation in C-reactive protein (CRP levels have been shown in patients with aortic valve stenosis (AS. Minor allele of the CRP gene (CRP rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51–3.96 vs. 1.68 (0.98–2.90 mg/L, p < 0.001 and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p = 0.01 compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.

  8. Screening key genes for abdominal aortic aneurysm based on gene expression omnibus dataset.

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    Wan, Li; Huang, Jingyong; Ni, Haizhen; Yu, Guanfeng

    2018-02-13

    Abdominal aortic aneurysm (AAA) is a common cardiovascular system disease with high mortality. The aim of this study was to identify potential genes for diagnosis and therapy in AAA. We searched and downloaded mRNA expression data from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) from AAA and normal individuals. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, transcriptional factors (TFs) network and protein-protein interaction (PPI) network were used to explore the function of genes. Additionally, immunohistochemical (IHC) staining was used to validate the expression of identified genes. Finally, the diagnostic value of identified genes was accessed by receiver operating characteristic (ROC) analysis in GEO database. A total of 1199 DEGs (188 up-regulated and 1011 down-regulated) were identified between AAA and normal individual. KEGG pathway analysis displayed that vascular smooth muscle contraction and pathways in cancer were significantly enriched signal pathway. The top 10 up-regulated and top 10 down-regulated DEGs were used to construct TFs and PPI networks. Some genes with high degrees such as NELL2, CCR7, MGAM, HBB, CSNK2A2, ZBTB16 and FOXO1 were identified to be related to AAA. The consequences of IHC staining showed that CCR7 and PDGFA were up-regulated in tissue samples of AAA. ROC analysis showed that NELL2, CCR7, MGAM, HBB, CSNK2A2, ZBTB16, FOXO1 and PDGFA had the potential diagnostic value for AAA. The identified genes including NELL2, CCR7, MGAM, HBB, CSNK2A2, ZBTB16, FOXO1 and PDGFA might be involved in the pathology of AAA.

  9. Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome

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    2014-01-01

    Background Bicuspid aortic valve (BAV) is the most frequent congenital heart disease with frequent involvement in thoracic aortic dilatation, aneurysm and dissection. Although BAV and Marfan syndrome (MFS) share some clinical features, and some MFS patients with BAV display mutations in FBN1, the gene encoding fibrillin-1, the genetic background of isolated BAV is poorly defined. Methods Ten consecutive BAV patients [8 men, age range 24–42 years] without MFS were clinically characterized. BAV phenotype and function, together with evaluation of aortic morphology, were comprehensively assessed by Doppler echocardiography. Direct sequencing of each FBN1 exon with flanking intron sequences was performed on eight patients. Results We detected three FBN1 mutations in two patients (aged 24 and 25 years) displaying aortic root aneurysm ≥50 mm and moderate aortic regurgitation. In particular, one patient had two mutations (p.Arg2726Trp and p.Arg636Gly) one of which has been previously associated with variable Marfanoid phenotypes. The other patient showed a pArg529Gln substitution reported to be associated with an incomplete MFS phenotype. Conclusions The present findings enlarge the clinical spectrum of isolated BAV to include patients with BAV without MFS who have involvement of FBN1 gene. These results underscore the importance of accurate phenotyping of BAV aortopathy and of clinical characterization of BAV patients, including investigation of systemic connective tissue manifestations and genetic testing. PMID:24564502

  10. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

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    Shin-ichiro Katsuda

    2014-01-01

    Full Text Available We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam. The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta.

  11. Analysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19

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    Ferrell Robert E

    2011-01-01

    Full Text Available Abstract Background Abdominal aortic aneurysm (AAA is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM database. Methods Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22 were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies. Results Several SNPs were nominally associated with AAA (p CEBPG, peptidase D (PEPD, and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples. Conclusions Association testing

  12. Aortic-Brachial Pulse Wave Velocity Ratio: A Measure of Arterial Stiffness Gradient Not Affected by Mean Arterial Pressure.

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    Fortier, Catherine; Desjardins, Marie-Pier; Agharazii, Mohsen

    2018-03-01

    Aortic stiffness, measured by carotid-femoral pulse wave velocity (cf-PWV), is used for the prediction of cardiovascular risk. This mini-review describes the nonlinear relationship between cf-PWV and operational blood pressure, presents the proposed methods to adjust for this relationship, and discusses a potential place for aortic-brachial PWV ratio (a measure of arterial stiffness gradient) as a blood pressure-independent measure of vascular aging. PWV is inherently dependent on the operational blood pressure. In cross-sectional studies, PWV adjustment for mean arterial pressure (MAP) is preferred, but still remains a nonoptimal approach, as the relationship between PWV and blood pressure is nonlinear and varies considerably among individuals due to heterogeneity in genetic background, vascular tone, and vascular remodeling. Extrapolations from the blood pressure-independent stiffness parameter β (β 0 ) have led to the creation of stiffness index β, which can be used for local stiffness. A similar approach has been used for cardio-ankle PWV to generate a blood pressure-independent cardio-ankle vascular index (CAVI). It was recently demonstrated that stiffness index β and CAVI remain slightly blood pressure-dependent, and a more appropriate formula has been proposed to make the proper adjustments. On the other hand, the negative impact of aortic stiffness on clinical outcomes is thought to be mediated through attenuation or reversal of the arterial stiffness gradient, which can also be influenced by a reduction in peripheral medium-sized muscular arteries in conditions that predispose to accelerate vascular aging. Arterial stiffness gradient, assessed by aortic-brachial PWV ratio, is emerging to be at least as good as cf-PWV for risk prediction, but has the advantage of not being affected by operating MAP. The negative impacts of aortic stiffness on clinical outcomes are proposed to be mediated through attenuation or reversal of arterial stiffness gradient

  13. Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene.

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    Backer, Julie De; Braverman, Alan C

    2018-05-01

    Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  14. Polymorphisms of the matrix metalloproteinase 9 gene and abdominal aortic aneurysm.

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    Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

    2008-10-01

    Increased matrix metalloproteinase (MMP) 9 activity has been implicated in the formation of abdominal aortic aneurysm (AAA). The aim was to explore the association between potentially functional variants of the MMP-9 gene and AAA. The -1562C > T and -1811A > T variants of the MMP-9 gene were genotyped in 678 men with an AAA (at least 30 mm in diameter) and 659 control subjects (aortic diameter 19-22 mm) recruited from a population-based trial of screening for AAA. Levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed by multivariable logistic regression. There was no association between the MMP-9-1562C > T (odds ratio (OR) 0.70 (95 per cent confidence interval (c.i.) 0.27 to 1.82)) or -1811A > T (OR 0.71 (95 per cent c.i. 0.28 to 1.85)) genotypes, or the most common haplotype (OR 0.81 (95 per cent c.i. 0.62 to 1.05)) and AAA. The serum MMP-9 concentration was higher in cases than controls, and in minor allele carriers in cases and controls, although the differences were not statistically significant. In this study, the genetic tendency to higher levels of circulating MMP-9 was not associated with AAA.

  15. Induced pluripotent stem cells with NOTCH1 gene mutation show impaired differentiation into smooth muscle and endothelial cells: Implications for bicuspid aortic valve-related aortopathy.

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    Jiao, Jiao; Tian, Weihua; Qiu, Ping; Norton, Elizabeth L; Wang, Michael M; Chen, Y Eugene; Yang, Bo

    2018-03-12

    The NOTCH1 gene mutation has been identified in bicuspid aortic valve patients. We developed an in vitro model with human induced pluripotent stem cells (iPSCs) to evaluate the role of NOTCH1 in smooth muscle and endothelial cell (EC) differentiation. The iPSCs were derived from a patient with a normal tricuspid aortic valve and aorta. The NOTCH1 gene was targeted in iPSCs with the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 nuclease (Cas9) system. The NOTCH1 -/- (NOTCH1 homozygous knockout) and isogenic control iPSCs (wild type) were differentiated into neural crest stem cells (NCSCs) and into cardiovascular progenitor cells (CVPCs). The NCSCs were differentiated into smooth muscle cells (SMCs). The CVPCs were differentiated into ECs. The differentiations of SMCs and ECs were compared between NOTCH1 -/- and wild type cells. The expression of NCSC markers (SRY-related HMG-box 10 and transcription factor AP-2 alpha) was significantly lower in NOTCH1 -/- NCSCs than in wild type NCSCs. The SMCs derived from NOTCH1 -/- NCSCs showed immature morphology with smaller size and decreased expression of all SMC-specific contractile proteins. In NOTCH1 -/- CVPCs, the expression of ISL1, NKX2.5, and MYOCD was significantly lower than that in isogenic control CVPCs, indicating impaired differentiation from iPSCs to CVPCs. The NOTCH1 -/- ECs derived from CVPCs showed significantly lower expression of cluster of differentiation 105 and cluster of differentiation 31 mRNA and protein, indicating a defective differentiation process. NOTCH1 is critical in SMC and EC differentiation of iPSCs through NCSCs and CVPCs, respectively. NOTCH1 gene mutations might potentially contribute to the development of thoracic aortic aneurysms by affecting SMC differentiation in some patients with bicuspid aortic valve. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  16. Iduronic Acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells

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    Bartolini, B.; Thelin, M.A.; Svensson, L.; Ghiselli, G.; Kuppevelt, T.H. van; Malmstrom, A.; Maccarana, M.

    2013-01-01

    Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS

  17. Elastic properties of the aorta and factors affecting aortic stiffness in patients with

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    Derya Tok

    2012-09-01

    Full Text Available Objectives: In this study, we evaluated aortic stiffnessand echocardiographic and laboratory factors affectingaortic stiffness in patients with metabolic syndrome(MetS.Materials and methods: Forty-six patients (25 male,mean age 47.3±6.5 years with the diagnosis of MetS accordingto the Adult Treatment Panel III Final Report criteriawere included. Forty-four age and gender matchedhealthy subjects (18 male, mean age 46.0±6.1 yearswere recruited as the control group. Aortic strain, distensibilityand stiffness index were calculated by M-modeechocardiography and diastolic parameters were measured.Results: Left ventricular mass index (LVMI, decelerationtime (DT, isovolumic relaxation time (IVRT wereincreased and mitral E/A ratio was decreased in patientswith MetS compared to controls. In the MetS patients,aortic distensibility was significantly decreased (10.4±3.5cm2.dyn-1.10-6 vs. 12.7±3.4 cm2.dyn-1.10-6, p=0.002,and ASI was significantly increased (6.5±2.0 vs. 3.2±0.8,p<0.001. ASI was positively correlated with triglycerides,fasting glucose, uric acid, hsCRP, LVMI, DT, IVRT andsystolic blood pressure level, and was negatively correlatedwith HDL-cholesterol and mitral E/A ratio. In regressionanalysis, hsCRP (p=0.05 and systolic blood pressurelevel (p<0.001 were independent predictors of ASI.Conclusions: ASI is increased in patients with MetS. Inthese patients; decrease in aortic elasticity properties wasassociated with left ventricular diastolic dysfunction. Highsystolic pressure and hsCRP levels were found to be independentpredictors of ASI.Key words: Metabolic syndrome, Echocardiography,elastic properties of aorta, hsCRP

  18. Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.

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    Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Norman, P E

    2008-01-01

    Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (AAAs). Although this implicates inflammation as a cause of AAAs, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and AAAs. An association study involving 677 men with screen-detected AAAs and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed: IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on AAA as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with AAAs. All analyses and haplotype estimation were performed under a generalized linear model framework. IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for AAA with an odds ratio (OR) of 6.00 (95%CI: 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for AAA (OR 1.56, 95%CI: 1.02, 2.39). The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with AAA, however it is too rare to be an important cause of most AAAs. This does not support the concept that the elevated level of IL-6 reported in patients with AAAs is a primary cause of the aneurysmal process.

  19. Survival affects decision making for fenestrated and branched endovascular aortic repair.

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    Beach, Jocelyn M; Rajeswaran, Jeevanantham; Parodi, F Ezequiel; Kuramochi, Yuki; Brier, Corey; Blackstone, Eugene; Eagleton, Matthew J

    2018-03-01

    Repair options for complex abdominal and thoracoabdominal aortic aneurysms (TAAAs) are evolving with increased experience and availability of less invasive endovascular techniques. Identifying risk factors for mortality after fenestrated and branched endovascular aortic repair (F/B-EVAR) could improve patient selection and facilitate decision making regarding who may benefit from prophylactic F/B-EVAR. We evaluated 1091 patients in a prospective investigational device exemption trial who underwent F/B-EVAR from August 2001 to June 2015 for complex aortic aneurysms (CAAs). Multivariable analysis of risk factors for death was performed using a nonproportional hazards model and a nonparametric analysis using random survival forest technology. Operative mortality after F/B-EVAR was low (3.7%), with high CAA-related survival at 30 day and 5 years (96.8% and 94.0%, respectively). All-cause 5-year survival, however, was 46.2% and older age, heart failure, chronic obstructive pulmonary disease, renal disease, anemia, and coagulation disorders were risk factors. Risk was highest for those undergoing type I/II TAAA repairs and those with larger aneurysms. Patients with multiple comorbidities and those undergoing type I or II TAAA repair are at greatest risk of mortality; however, in this high-risk population, F/B-EVAR offers greater survival compared with that reported for the natural history of untreated aneurysms. Operative and early mortality is lower than the best-reported open repair outcomes, even in this high-risk population, suggesting a potential benefit in extending the use of F/B-EVAR to low-to-average risk CAA patients. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  20. Assisted care as a baseline patient risk characteristic affecting the outcome of transcatheter aortic valve insertion.

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    Traynor, Megan M; Greason, Kevin L; Nkomo, Vuyisile T; Pochettino, Alberto; Holmes, David R; Rihal, Charanjit S; Reeder, Guy S; Bresnahan, John F; Mathew, Verghese

    2017-06-01

    Objective measures of frailty have not been well defined as risk factors for a poor outcome after transcatheter aortic valve insertion. We hypothesized that assisted care as a baseline patient characteristic was a simple objective measure of frailty. We reviewed our experience to assess for an association between assisted care and outcome of operation. We retrospectively reviewed the records of 597 patients operated with transcatheter aortic valve insertion from November 2008 through July 2015. The study cohort included patients with a dichotomous baseline characteristic of receiving assisted care (AC group, n = 60, 10.1%) or not receiving assisted care (NC group, n = 537, 89.9%). The endpoints of the study were operative stroke/death and 1-year survival. The age of the patients was 80.6 ± 9.0 years, male sex was present in 349 (58.5%), and STS predicted risk of mortality was 9.2 ± 6.2%. Alternate access was used in 26 (43.3%) patients in the AC care group and in 220 (41.0%) in the NC group (P = 0.724). Operative stroke/death occurred in 4 (6.7%) patients in the AC group and in 25 (4.7%) in the NC group (P = 0.492). Mortality at 1 year in the AC group was 14.8 ± 5.2% and in the NC group was 12.9 ± 1.7%; (P = 0. 250). Assisted care as a baseline patient characteristic does not result in increased operative stroke/death or 1-year mortality in patients following transcatheter aortic valve insertion. Assisted care should not by itself preclude operation. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Iduronic acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Barbara Bartolini

    Full Text Available Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA, catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK and phospho-FAK (pFAK was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis.

  2. Metformin treatment does not affect the risk of ruptured abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Kristensen, Katrine L.; Pottegård, Anton; Hallas, Jesper

    2017-01-01

    Objective: Diabetes counteracts formation and rupture of abdominal aortic aneurysms, possibly through arterial matrix accumulation. Use of metformin, on the other hand, reduces arterial accumulation of matrix molecules. Consequently, we hypothesized that metformin treatment may reverse...... the protective role of diabetes on the development and course of aneurysms, that is, that metformin would be associated with aneurysm rupture among individuals with diabetes. Methods: Using nationwide Danish registry data, we performed a nested case-control study on the association between long-term use....... In total, 22.4% of the case population were long-term metformin users compared with 28.8% of the controls. We found a statistically nonsignificant protective effect of long-term metformin use toward RAAA with crude odds ratio (OR) of 0.74 (confidence interval, 0.54-1.00). When adjusted for covariates...

  3. Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall.

    Science.gov (United States)

    Araos, Patricio; Mondaca, David; Jalil, Jorge E; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

    2016-12-01

    Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague-Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p diuretics alone or in combination with FAS. In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. © The Author(s), 2016.

  4. Patterns of prokaryotic lateral gene transfers affecting parasitic microbial eukaryotes

    DEFF Research Database (Denmark)

    Alsmark, Cecilia; Foster, Peter G; Sicheritz-Pontén, Thomas

    2013-01-01

    BACKGROUND: The influence of lateral gene transfer on gene origins and biology in eukaryotes is poorly understood compared with those of prokaryotes. A number of independent investigations focusing on specific genes, individual genomes, or specific functional categories from various eukaryotes have...... approach to systematically investigate lateral gene transfer affecting the proteomes of thirteen, mainly parasitic, microbial eukaryotes, representing four of the six eukaryotic super-groups. All of the genomes investigated have been significantly affected by prokaryote-to-eukaryote lateral gene transfers...... indicated that lateral gene transfer does indeed affect eukaryotic genomes. However, the lack of common methodology and criteria in these studies makes it difficult to assess the general importance and influence of lateral gene transfer on eukaryotic genome evolution. RESULTS: We used a phylogenomic...

  5. Aortic insufficiency

    Science.gov (United States)

    ... page, please enable JavaScript. Aortic insufficiency is a heart valve disease in which the aortic valve does not close ... aortic insufficiency Images Aortic insufficiency References Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman-Cecil ...

  6. Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells

    International Nuclear Information System (INIS)

    Wang, Yang; Zhao, Zhi-Min; Zhang, Guan-Xin; Yang, Fan; Yan, Yan; Liu, Su-Xuan; Li, Song-Hua; Wang, Guo-Kun; Xu, Zhi-Yun

    2016-01-01

    The aortic medial degeneration is the key histopathologic feature of Thoracic aortic dissection (TAD). The aim of this study was to identify the change of autophagic activity in the aortic wall during TAD development, and to explore the roles of autophagy on regulating functional properties of smooth muscle cells (SMCs). Firstly, compared with control group (n = 11), the increased expression of autophagic markers Beclin1 and LC3 was detected in the aortic wall from TAD group (n = 23) by immunochemistry and western blot. We found that more autophagic vacuoles were present in the aortic wall of TAD patients using Transmission electron microscopy. Next, autophagic activity was examined in AD mice model established by β-aminopropionitrile fumarate (BAPN) and angiotensin II. Immunochemistry proved that autophagic activity was dynamically changed during AD development. Beclin1 and LC3 were detected up-regulated in the aortic wall in the second week after BAPN feeding, earlier than the fragmentation or loss of elastic fibers. When AD occurred in the 4th week, the expression of Beclin1 and LC3 began to decrease, but still higher than the control. Furthermore, autophagy was found to inhibit starvation-induced apoptosis of SMCs. Meanwhile, blockage of autophagy could suppress PDGF-induced phenotypic switch of SMCs. Taken together, autophagic activity was dynamically changed in the aortic wall during TAD development. The abnormal autophagy could regulate the functional properties of aortic SMCs, which might be the potential pathogenesis of TAD. - Highlights: • Autophagy is up-regulated in aorta wall from thoracic aorta dissection (TAD) patient. • Autophagic activity is dynamically changed during TAD development. • Dynamically change of autophagy is associated with pathological process of TAD. • Autophagy participate in the development of TAD by regulating function of SMCs.

  7. Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts

    International Nuclear Information System (INIS)

    Wang Zhirong; Chen Yan; Labinskyy, Nazar; Hsieh Tzechen; Ungvari, Zoltan; Wu, Joseph M.

    2006-01-01

    Epidemiologic studies suggest that low to moderate consumption of red wine is inversely associated with the risk of coronary heart disease; the protection is in part attributed to grape-derived polyphenols, notably trans-resveratrol, present in red wine. It is not clear whether the cardioprotective effects of resveratrol can be reproduced by standardized grape extracts (SGE). In the present studies, we determined, using cultured human aortic smooth muscle cells (HASMC), growth and specific gene responses to resveratrol and SGE provided by the California Table Grape Commission. Suppression of HASMC proliferation by resveratrol was accompanied by a dose-dependent increase in the expression of tumor suppressor gene p53 and heat shock protein HSP27. Using resveratrol affinity chromatography and biochemical fractionation procedures, we showed by immunoblot analysis that treatment of HASMC with resveratrol increased the expression of quinone reductase I and II, and also altered their subcellular distribution. Growth of HASMC was significantly inhibited by 70% ethanolic SGE; however, gene expression patterns in various cellular compartments elicited in response to SGE were substantially different from those observed in resveratrol-treated cells. Further, SGE also differed from resveratrol in not being able to induce relaxation of rat carotid arterial rings. These results indicate that distinct mechanisms are involved in the regulation of HASMC growth and gene expression by SGE and resveratrol

  8. Thymol reduces oxidative stress, aortic intimal thickening, and inflammation-related gene expression in hyperlipidemic rabbits

    Directory of Open Access Journals (Sweden)

    Ya-Mei Yu

    2016-07-01

    Full Text Available Atherosclerosis plays a key role in the development of cardiovascular diseases, and is often associated with oxidative stress and local inflammation. Thymol, a major polyphenolic compound in thyme, exhibits antioxidant and anti-inflammatory properties. In this study, we measured the in vitro antioxidant activity of thymol, and investigated the effect of thymol on high-fat-diet-induced hyperlipidemia and atherosclerosis. New Zealand white rabbits were fed with regular chow, high-fat and high-cholesterol diet (HC, T3, or T6 (HC with thymol supplementation at 3 mg/kg/d or 6 mg/kg/d, respectively for 8 weeks. Aortic intimal thickening, serum lipid parameters, multiple inflammatory markers, proinflammatory cytokines, and atherosclerosis-associated indicators were significantly increased in the HC group but decreased upon thymol supplementation. In summary, thymol exhibits antioxidant activity, and may suppress the progression of high-fat-diet-induced hyperlipidemia and atherosclerosis by reducing aortic intimal lipid lesion, lowering serum lipids and oxidative stress, and alleviating inflammation-related responses.

  9. A parasitic selfish gene that affects host promiscuity.

    Science.gov (United States)

    Giraldo-Perez, Paulina; Goddard, Matthew R

    2013-11-07

    Selfish genes demonstrate transmission bias and invade sexual populations despite conferring no benefit to their hosts. While the molecular genetics and evolutionary dynamics of selfish genes are reasonably well characterized, their effects on hosts are not. Homing endonuclease genes (HEGs) are one well-studied family of selfish genes that are assumed to be benign. However, we show that carrying HEGs is costly for Saccharomyces cerevisiae, demonstrating that these genetic elements are not necessarily benign but maybe parasitic. We estimate a selective load of approximately 1-2% in 'natural' niches. The second aspect we examine is the ability of HEGs to affect hosts' sexual behaviour. As all selfish genes critically rely on sex for spread, then any selfish gene correlated with increased host sexuality will enjoy a transmission advantage. While classic parasites are known to manipulate host behaviour, we are not aware of any evidence showing a selfish gene is capable of affecting host promiscuity. The data presented here show a selfish element may increase the propensity of its eukaryote host to undergo sex and along with increased rates of non-Mendelian inheritance, this may counterbalance mitotic selective load and promote spread. Demonstration that selfish genes are correlated with increased promiscuity in eukaryotes connects with ideas suggesting that selfish genes promoted the evolution of sex initially.

  10. Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure.

    Science.gov (United States)

    Karimi, Ashkan; Milewicz, Dianna M

    2016-01-01

    The medial layer of the aorta confers elasticity and strength to the aortic wall and is composed of alternating layers of smooth muscle cells (SMCs) and elastic fibres. The SMC elastin-contractile unit is a structural unit that links the elastin fibres to the SMCs and is characterized by the following: (1) layers of elastin fibres that are surrounded by microfibrils; (2) microfibrils that bind to the integrin receptors in focal adhesions on the cell surface of the SMCs; and (3) SMC contractile filaments that are linked to the focal adhesions on the inner side of the membrane. The genes that are altered to cause thoracic aortic aneurysms and aortic dissections encode proteins involved in the structure or function of the SMC elastin-contractile unit. Included in this gene list are the genes encoding protein that are structural components of elastin fibres and microfibrils, FBN1, MFAP5, ELN, and FBLN4. Also included are genes that encode structural proteins in the SMC contractile unit, including ACTA2, which encodes SMC-specific α-actin and MYH11, which encodes SMC-specific myosin heavy chain, along with MYLK and PRKG1, which encode kinases that control SMC contraction. Finally, mutations in the gene encoding the protein linking integrin receptors to the contractile filaments, FLNA, also predispose to thoracic aortic disease. Thus, these data suggest that functional SMC elastin-contractile units are important for maintaining the structural integrity of the aorta. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  11. Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Majesky, M.W.; Benditt, E.P.; Schwartz, S.M.

    1988-01-01

    Cultured arterial smooth muscle cells (SMC) can produce platelet-derived growth factor (PDGF)-like molecules. This property raises the possibility that SMC-derived PDGFs function as autocrine/paracrine regulators in the formation and maintenance of the artery wall. In this study the authors have asked if levels of mRNAs directing synthesis of PDFG are modulated in aortic SMC during postnatal development. The authors report here that genes encoding PDGF A- and B-chain precursors are expressed at similar low levels in intact aortas from newborn and adult rats. Marked differences in regulation of transcript abundance of these genes were revealed when aortic SMC were grown in cell culture. PDGF B-chain transcripts accumulated in passaged newborn rat SMC but not adult rat SMC, whereas PDGF A-chain RNA was found in comparable amounts in SMC from both age groups. Similarly, SMC from newborn rats secreted at least 60-fold more PDGF-like activity into conditioned medium than did adult rat SMC. These results show that PDGF A- and B-chain genes are transcribed in the normal rat aorta and provide evidence for age-related change in the control of PDGF B-chain gene expression in aortic SMC. Independent regulation of transcript levels in cultured SMC leaves open the possibility that PDGFs of different composition (AA, AB, BB) play different roles in normal function of the artery wall

  12. Application of gene network analysis techniques identifies AXIN1/PDIA2 and endoglin haplotypes associated with bicuspid aortic valve.

    Directory of Open Access Journals (Sweden)

    Eric C Wooten

    2010-01-01

    Full Text Available Bicuspid Aortic Valve (BAV is a highly heritable congenital heart defect. The low frequency of BAV (1% of general population limits our ability to perform genome-wide association studies. We present the application of four a priori SNP selection techniques, reducing the multiple-testing penalty by restricting analysis to SNPs relevant to BAV in a genome-wide SNP dataset from a cohort of 68 BAV probands and 830 control subjects. Two knowledge-based approaches, CANDID and STRING, were used to systematically identify BAV genes, and their SNPs, from the published literature, microarray expression studies and a genome scan. We additionally tested Functionally Interpolating SNPs (fitSNPs present on the array; the fourth consisted of SNPs selected by Random Forests, a machine learning approach. These approaches reduced the multiple testing penalty by lowering the fraction of the genome probed to 0.19% of the total, while increasing the likelihood of studying SNPs within relevant BAV genes and pathways. Three loci were identified by CANDID, STRING, and fitSNPS. A haplotype within the AXIN1-PDIA2 locus (p-value of 2.926x10(-06 and a haplotype within the Endoglin gene (p-value of 5.881x10(-04 were found to be strongly associated with BAV. The Random Forests approach identified a SNP on chromosome 3 in association with BAV (p-value 5.061x10(-06. The results presented here support an important role for genetic variants in BAV and provide support for additional studies in well-powered cohorts. Further, these studies demonstrate that leveraging existing expression and genomic data in the context of GWAS studies can identify biologically relevant genes and pathways associated with a congenital heart defect.

  13. Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently

    NARCIS (Netherlands)

    de Waard, Vivian; Bot, Ilze; de Jager, Saskia C. A.; Talib, Sara; Egashira, Kensuke; de Vries, Margreet R.; Quax, Paul H. A.; Biessen, Erik A. L.; van Berkel, Theo J. C.

    2010-01-01

    Objective: CCR2, the receptor for monocyte chemoattractant protein 1 (MCP1), is involved in atherosclerosis and abdominal aortic aneurysms (AAAs). Here, we explored the potential beneficial blockade of the MCP1/CCR2 pathway. Methods: We applied an AAA model in aging apolipoprotein E deficient mice

  14. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.

    Science.gov (United States)

    Carrion, Katrina; Dyo, Jeffrey; Patel, Vishal; Sasik, Roman; Mohamed, Salah A; Hardiman, Gary; Nigam, Vishal

    2014-01-01

    Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-catenin is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-catenin signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification.

  15. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.

    Directory of Open Access Journals (Sweden)

    Katrina Carrion

    Full Text Available Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-catenin is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-catenin signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification.

  16. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  17. Huntingtin gene repeat size variations affect risk of lifetime depression

    DEFF Research Database (Denmark)

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.

    2017-01-01

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...

  18. Toxic Diatom Aldehydes Affect Defence Gene Networks in Sea Urchins.

    Directory of Open Access Journals (Sweden)

    Stefano Varrella

    Full Text Available Marine organisms possess a series of cellular strategies to counteract the negative effects of toxic compounds, including the massive reorganization of gene expression networks. Here we report the modulated dose-dependent response of activated genes by diatom polyunsaturated aldehydes (PUAs in the sea urchin Paracentrotus lividus. PUAs are secondary metabolites deriving from the oxidation of fatty acids, inducing deleterious effects on the reproduction and development of planktonic and benthic organisms that feed on these unicellular algae and with anti-cancer activity. Our previous results showed that PUAs target several genes, implicated in different functional processes in this sea urchin. Using interactomic Ingenuity Pathway Analysis we now show that the genes targeted by PUAs are correlated with four HUB genes, NF-κB, p53, δ-2-catenin and HIF1A, which have not been previously reported for P. lividus. We propose a working model describing hypothetical pathways potentially involved in toxic aldehyde stress response in sea urchins. This represents the first report on gene networks affected by PUAs, opening new perspectives in understanding the cellular mechanisms underlying the response of benthic organisms to diatom exposure.

  19. Overexpression of maize anthocyanin regulatory gene Lc affects rice fertility.

    Science.gov (United States)

    Li, Yuan; Zhang, Tao; Shen, Zhong-Wei; Xu, Yu; Li, Jian-Yue

    2013-01-01

    Seventeen independent transgenic rice plants with the maize anthocyanin regulatory gene Lc under control of the CaMV 35S promoter were obtained and verified by molecular identification. Ten plants showed red spikelets during early development of florets, and the degenerate florets were still red after heading. Additionally, these plants exhibited intense pigmentation on the surface of the anther and the bottom of the ovary. They were unable to properly bloom and were completely sterile. Following pollination with normal pollen, these plants yielded red caryopses but did not mature normally. QRT-PCR analysis indicated that mRNA accumulation of the CHS-like gene encoding a chalcone synthase-related protein was increased significantly in the sterile plant. This is the first report to suggest that upregulation of the CHS gene expression may result in rice sterility and affect the normal development of rice seeds.

  20. Evolutionary rate of a gene affected by chromosomal position.

    Science.gov (United States)

    Perry, J; Ashworth, A

    1999-09-09

    Genes evolve at different rates depending on the strength of selective pressure to maintain their function. Chromosomal position can also have an influence [1] [2]. The pseudoautosomal region (PAR) of mammalian sex chromosomes is a small region of sequence identity that is the site of an obligatory pairing and recombination event between the X and Y chromosomes during male meiosis [3] [4] [5] [6]. During female meiosis, X chromosomes can pair and recombine along their entire length. Recombination in the PAR is therefore approximately 10 times greater in male meiosis compared with female meiosis [4] [5] [6]. The gene Fxy (also known as MID1 [7]) spans the pseudoautosomal boundary (PAB) in the laboratory mouse (Mus musculus domesticus, C57BL/6) such that the 5' three exons of the gene are located on the X chromosome but the seven exons encoding the carboxy-terminal two-thirds of the protein are located within the PAR and are therefore present on both the X and Y chromosomes [8]. In humans [7] [9], the rat, and the wild mouse species Mus spretus, the gene is entirely X-unique. Here, we report that the rate of sequence divergence of the 3' end of the Fxy gene is much higher (estimated at 170-fold higher for synonymous sites) when pseudoautosomal (present on both the X and Y chromosomes) than when X-unique. Thus, chromosomal position can directly affect the rate of evolution of a gene. This finding also provides support for the suggestion that regions of the genome with a high recombination frequency, such as the PAR, may have an intrinsically elevated rate of sequence divergence.

  1. Alginate oligosaccharide indirectly affects toll-like receptor signaling via the inhibition of microRNA-29b in aneurysm patients after endovascular aortic repair

    Directory of Open Access Journals (Sweden)

    Yang Y

    2017-09-01

    Full Text Available Yong Yang,1–4,* Zhenhuan Ma,1–4,* Guokai Yang,1–4 Jia Wan,1–4 Guojian Li,1–4 Lingjuan Du,1–4 Ping Lu1–4 1Department of Vascular Surgery, The Second People’s Hospital of Yunnan Province, Kunming, China; 2Department of Vascular Surgery, The Fourth Affiliated Hospital of Kunming Medical University, Kunming, China; 3Department of Vascular Surgery, Vascular Surgery Centre in Yunnan Province, Kunming, China; 4Department of Vascular Surgery, Abdominal Surgery Centre in Yunnan Province, Kunming, China *These authors contributed equally to this work Abstract: Endovascular aortic repair (EVAR is often followed by aneurysm recurrence. Alginate oligosaccharide (AOS has potential antitumor properties as a natural product while the related mechanisms remain unclear. Toll-like receptor (TLR signaling is associated with inflammatory activity of aneurysm and may be affected by miR-29b. Thus, inhibitory function of AOS on aneurysms was explored by measuring the important molecules in TLR4 signaling. After EVAR, a total of 248 aortic aneurysm patients were recruited and randomly assigned into two groups: AOS group (AG, oral administration 10-mg AOS daily and control group (CG, placebo daily. The size of residual aneurysms, aneurysm recurrence, and side effects were investigated. Aneurysm recurrence was determined by Kaplan–Meier analysis. After 2 years, eight and two patients died in the CG and AG, respectively. The sizes of residual aneurysms were significantly larger in the CG than in the AG (P<0.05. The incidence of aneurysm recurrence was also significantly higher in the CG than in the AG (P<0.05. AOS treatment reduced the levels of miR-29b, TLR4, mitogen-activated protein kinase (MAPK, nuclear factor kappa B (NF-kappa B, interleukin 1 (IL-1 beta, and interleukin 6 (IL-6. Overexpression and silence of miR-29b increased and reduced the level of TLR4, phospho-p65 NF-kappa B, phospho-p38 MAPK, IL-1 beta, and IL-6. Spearman’s rank correlation

  2. Multiple controls affect arsenite oxidase gene expression in Herminiimonas arsenicoxydans

    Directory of Open Access Journals (Sweden)

    Coppée Jean-Yves

    2010-02-01

    Full Text Available Abstract Background Both the speciation and toxicity of arsenic are affected by bacterial transformations, i.e. oxidation, reduction or methylation. These transformations have a major impact on environmental contamination and more particularly on arsenic contamination of drinking water. Herminiimonas arsenicoxydans has been isolated from an arsenic- contaminated environment and has developed various mechanisms for coping with arsenic, including the oxidation of As(III to As(V as a detoxification mechanism. Results In the present study, a differential transcriptome analysis was used to identify genes, including arsenite oxidase encoding genes, involved in the response of H. arsenicoxydans to As(III. To get insight into the molecular mechanisms of this enzyme activity, a Tn5 transposon mutagenesis was performed. Transposon insertions resulting in a lack of arsenite oxidase activity disrupted aoxR and aoxS genes, showing that the aox operon transcription is regulated by the AoxRS two-component system. Remarkably, transposon insertions were also identified in rpoN coding for the alternative N sigma factor (σ54 of RNA polymerase and in dnaJ coding for the Hsp70 co-chaperone. Western blotting with anti-AoxB antibodies and quantitative RT-PCR experiments allowed us to demonstrate that the rpoN and dnaJ gene products are involved in the control of arsenite oxidase gene expression. Finally, the transcriptional start site of the aoxAB operon was determined using rapid amplification of cDNA ends (RACE and a putative -12/-24 σ54-dependent promoter motif was identified upstream of aoxAB coding sequences. Conclusion These results reveal the existence of novel molecular regulatory processes governing arsenite oxidase expression in H. arsenicoxydans. These data are summarized in a model that functionally integrates arsenite oxidation in the adaptive response to As(III in this microorganism.

  3. Aortic stenosis

    Science.gov (United States)

    ... Images Aortic stenosis Heart valves References Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman-Cecil ... ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/ ...

  4. Actin isoform and alpha 1B-adrenoceptor gene expression in aortic and coronary smooth muscle is influenced by cyclical stretch.

    Science.gov (United States)

    Lundberg, M S; Sadhu, D N; Grumman, V E; Chilian, W M; Ramos, K S

    1995-09-01

    The occurrence of vascular domains with specific biological and pharmacological characteristics suggests that smooth muscle cells in different arteries may respond differentially to a wide range of environmental stimuli. To determine if some of these vessel-specific differences may be attributable to mechano-sensitive gene regulation, the influence of cyclical stretch on the expression of actin isoform and alpha 1B-adrenoceptor genes was examined in aortic and coronary smooth muscle cells. Cells were seeded on an elastin substrate and subjected to maximal stretching (24% elongation) and relaxation cycles at a frequency of 120 cycles/min in a Flexercell strain unit for 72 h. Total RNA was extracted and hybridized to radiolabeled cDNA probes to assess gene expression. Stretch caused a greater reduction of actin isoform mRNA levels in aortic smooth muscle cells as compared to cells from the coronary artery. Steady-state mRNA levels of alpha 1B-adrenoceptor were also decreased by cyclical stretch in both cell types but the magnitude of the response was greater in coronary smooth muscle cells. No changes in alpha 1B-adrenoceptor or beta/gamma-actin steady-state mRNA levels were observed in H4IIE cells, a nonvascular, immortalized cell line. The relative gene expression of heat shock protein 70 was not influenced by the cyclic stretch regimen in any of these cell types. These results suggest that stretch may participate in the regulation of gene expression in vascular smooth muscle cells and that this response exhibits some degree of cell-specificity.

  5. A Gly1127Ser mutation in an EGF-like domain of the Fibrillin-I gene is a risk factor for ascending aortic aneurysm and dissection

    Energy Technology Data Exchange (ETDEWEB)

    Francke, U.; Berg, M.A.; Tynan, K. [Stanford Univ. Medical Center, CA (United States)] [and others

    1995-06-01

    Ascending aortic disease, ranging from mild aortic root enlargement to aneurysm and/or dissection, has been identified in 10 individuals of a kindred, none of whom had classical Marfan syndrome (MFS). Single-strand conformation analysis of the entire fibrillin-1 (FBN1) cDNA of an affected family member revealed a G-to-A transition at nucleotide 3379, predicting a Gly1127Ser substitution. The glycine in this position is highly conserved in EGF-like domains of FBN1 and other proteins. This mutation was present in 9 of 10 affected family members and in 1 young unaffected member but was not found in other unaffected members, in 168 chromsomes from normal controls, and in 188 chromosomes from other individuals with MFS or related phenotypes. FBN1 intragenic marker haplotypes ruled out the possibility that the other allele played a significant role in modulating the phenotype in this family. Pulse-chase studies revealed normal fibrillin synthesis but reduced fibrillin deposition into the extracellular matrix in cultured fibroblasts from a Gly1127Ser carrier. We postulate that the Gly1127Ser FBN1 mutation is responsible for reduced matrix deposition. We suggest that mutations such as this one may disrupt EFG-like domain folding less drastically than do substitutions of cysteine or of other amino acids important for calcium-binding that cause classical MFS. The Gly 1127Ser mutation, therefore, produces a mild form of autosomal dominantly inherited weakness of elastic tissue, which predisposes to ascending aortic aneurysm and dissection later in life. 33 refs., 6 figs.

  6. Serum Levels of Matrix Metalloproteinases 2 and 9 and TGFBR2 Gene Screening in Patients with Ascending Aortic Dilatation

    Czech Academy of Sciences Publication Activity Database

    Šímová, J.; Škvor, J.; Reissigová, Jindra; Dudra, J.; Lindner, J.; Čapek, P.; Zvárová, Jana

    2013-01-01

    Roč. 59, č. 4 (2013), s. 154-161 ISSN 0015-5500 R&D Projects: GA MŠk LN00B107; GA MŠk(CZ) 1M06014 Institutional support: RVO:67985807 Keywords : aortic dilatation * MMP-2 * MMP-9 * TGFBR2 Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 0.778, year: 2013 http://fb.cuni.cz/file/5695/FB2013A0021.pdf

  7. The FRIABLE1 gene product affects cell adhesion in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Lutz Neumetzler

    Full Text Available Cell adhesion in plants is mediated predominantly by pectins, a group of complex cell wall associated polysaccharides. An Arabidopsis mutant, friable1 (frb1, was identified through a screen of T-DNA insertion lines that exhibited defective cell adhesion. Interestingly, the frb1 plants displayed both cell and organ dissociations and also ectopic defects in organ separation. The FRB1 gene encodes a Golgi-localized, plant specific protein with only weak sequence similarities to known proteins (DUF246. Unlike other cell adhesion deficient mutants, frb1 mutants do not have reduced levels of adhesion related cell wall polymers, such as pectins. Instead, FRB1 affects the abundance of galactose- and arabinose-containing oligosaccharides in the Golgi. Furthermore, frb1 mutants displayed alteration in pectin methylesterification, cell wall associated extensins and xyloglucan microstructure. We propose that abnormal FRB1 action has pleiotropic consequences on wall architecture, affecting both the extensin and pectin matrices, with consequent changes to the biomechanical properties of the wall and middle lamella, thereby influencing cell-cell adhesion.

  8. Microarray analysis to identify the similarities and differences of pathogenesis between aortic occlusive disease and abdominal aortic aneurysm.

    Science.gov (United States)

    Wang, Guofu; Bi, Lechang; Wang, Gaofeng; Huang, Feilai; Lu, Mingjing; Zhu, Kai

    2018-06-01

    Objectives Expression profile of GSE57691 was analyzed to identify the similarities and differences between aortic occlusive disease and abdominal aortic aneurysm. Methods The expression profile of GSE57691 was downloaded from Gene Expression Omnibus database, including 20 small abdominal aortic aneurysm samples, 29 large abdominal aortic aneurysm samples, 9 aortic occlusive disease samples, and 10 control samples. Using the limma package in R, the differentially expressed genes were screened. Followed by enrichment analysis was performed for the differentially expressed genes using database for annotation, visualization, and integrated discovery online tool. Based on string online tool and Cytoscape software, protein-protein interaction network and module analyses were carried out. Moreover, integrated TF platform database and Cytoscape software were used for constructing transcriptional regulatory networks. Results As a result, 1757, 354, and 396 differentially expressed genes separately were identified in aortic occlusive disease, large abdominal aortic aneurysm, and small abdominal aortic aneurysm samples. UBB was significantly enriched in proteolysis related pathways with a high degree in three groups. SPARCL1 was another gene shared by these groups and regulated by NFIA, which had a high degree in transcriptional regulatory network. ACTB, a significant upregulated gene in abdominal aortic aneurysm samples, could be regulated by CLIC4, which was significantly enriched in cell motions. ACLY and NFIB were separately identified in aortic occlusive disease and small abdominal aortic aneurysm samples, and separately enriched in lipid metabolism and negative regulation of cell proliferation. Conclusions The downregulated UBB, NFIA, and SPARCL1 might play key roles in both aortic occlusive disease and abdominal aortic aneurysm, while the upregulated ACTB might only involve in abdominal aortic aneurysm. ACLY and NFIB were specifically involved in aortic occlusive

  9. Low-level overexpression of p53 promotes warfarin-induced calcification of porcine aortic valve interstitial cells by activating Slug gene transcription.

    Science.gov (United States)

    Gao, Li; Ji, Yue; Lu, Yan; Qiu, Ming; Shen, Yejiao; Wang, Yaqing; Kong, Xiangqing; Shao, Yongfeng; Sheng, Yanhui; Sun, Wei

    2018-03-09

    The most frequently used oral anti-coagulant warfarin has been implicated in inducing calcification of aortic valve interstitial cells (AVICs), whereas the mechanism is not fully understood. The low-level activation of p53 is found to be involved in osteogenic transdifferentiation and calcification of AVICs. Whether p53 participates in warfarin-induced AVIC calcification remains unknown. In this study, we investigated the role of low-level p53 overexpression in warfarin-induced porcine AVIC (pAVIC) calcification. Immunostaining, quantitative PCR, and Western blotting revealed that p53 was expressed in human and pAVICs and that p53 expression was slightly increased in calcific human aortic valves compared with non-calcific valves. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining indicated that apoptosis slightly increased in calcific aortic valves than in non-calcific valves. Warfarin treatment led to a low-level increase of p53 mRNA and protein in both pAVICs and mouse aortic valves. Low-level overexpression of p53 in pAVICs via an adenovirus vector did not affect pAVIC apoptosis but promoted warfarin-induced calcium deposition and expression of osteogenic markers. shRNA-mediated p53 knockdown attenuated the pAVIC calcium deposition and osteogenic marker expression. Moreover, ChIP and luciferase assays showed that p53 was recruited to the slug promoter and activated slug expression in calcific pAVICs. Of note, overexpression of Slug increased osteogenic marker Runx2 expression, but not pAVIC calcium deposition, and Slug knockdown attenuated pAVIC calcification and p53-mediated pAVIC calcium deposition and expression of osteogenic markers. In conclusion, we found that p53 plays an important role in warfarin induced pAVIC calcification, and increased slug transcription by p53 is required for p53-mediated pAVIC calcification. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Gene duplication and divergence affecting drug content in Cannabis sativa.

    Science.gov (United States)

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M David

    2015-12-01

    Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  11. A parasitic selfish gene that affects host promiscuity

    OpenAIRE

    Giraldo-Perez, Paulina; Goddard, Matthew R.

    2013-01-01

    Selfish genes demonstrate transmission bias and invade sexual populations despite conferring no benefit to their hosts. While the molecular genetics and evolutionary dynamics of selfish genes are reasonably well characterized, their effects on hosts are not. Homing endonuclease genes (HEGs) are one well-studied family of selfish genes that are assumed to be benign. However, we show that carrying HEGs is costly for Saccharomyces cerevisiae, demonstrating that these genetic elements are not nec...

  12. Transcatheter aortic valve replacement

    Science.gov (United States)

    ... gov/ency/article/007684.htm Transcatheter aortic valve replacement To use the sharing features on this page, please enable JavaScript. Transcatheter aortic valve replacement (TAVR) is surgery to replace the aortic valve. ...

  13. Huntingtin gene repeat size variations affect risk of lifetime depression.

    Science.gov (United States)

    Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

    2017-12-11

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

  14. Gene expression profiling of placentas affected by pre-eclampsia

    DEFF Research Database (Denmark)

    Hoegh, Anne Mette; Borup, Rehannah; Nielsen, Finn Cilius

    2010-01-01

    Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA...... expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000) were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia...... as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events...

  15. Fate of remnant sinuses of Valsalva in patients with bicuspid and trileaflet valves undergoing aortic valve, ascending aorta, and aortic arch replacement.

    Science.gov (United States)

    Milewski, Rita Karianna; Habertheuer, Andreas; Bavaria, Joseph E; Siki, Mary; Szeto, Wilson Y; Krause, Eric; Korutla, Varun; Desai, Nimesh D; Vallabhajosyula, Prashanth

    2017-08-01

    In patients presenting with aortic valvulopathy with concomitant ascending aortic aneurysm, surgical management of the sinus of Valsalva segment remains undefined, especially for moderately dilated aortic roots. In patients with this pathology undergoing aortic valve replacement with supracoronary ascending aorta replacement, we assessed the fate of the remnant preserved sinus of Valsalva segment stratified by aortic valve morphology and pathology. From 2002 to 2015, 428 patients underwent elective aortic valve replacement with supracoronary ascending aorta replacement. Patients were stratified on the basis of valvular morphology (bicuspid aortic valve [n = 254] and tricuspid aortic valve [n = 174]), valvular pathology (bicuspid aortic valve with aortic stenosis [n = 178], bicuspid aortic valve with aortic insufficiency [n = 76], tricuspid aortic valve with aortic stenosis [n = 61], tricuspid aortic valve with aortic insufficiency [n = 113]), and preoperative sinus of Valsalva dimensions (45 mm). Kaplan-Meier analysis revealed no significant difference in freedom from reoperation in tricuspid aortic valve versus bicuspid aortic valve (P = .576). Multivariable Cox regression model performed with sinus of Valsalva dimensions at baseline and follow-up as time-varying covariates did not adversely affect survival. A repeated-measure, mixed-effects model constructed to assess longitudinal sinus of Valsalva trends revealed that the retained sinus of Valsalva dimensions remain stable over long-term follow-up (discharge to ≥10 years), irrespective of valvular morphology/pathology (bicuspid aortic valve with aortic insufficiency, tricuspid aortic valve with aortic insufficiency, tricuspid aortic valve with aortic stenosis) and preoperative sinus of Valsalva groups (45 mm). In patients with nonaneurysmal sinuses of Valsalva undergoing aortic valve replacement with supracoronary ascending aorta replacement, the sinus segment can be preserved irrespective of

  16. The bicuspid aortic valve and its relation to aortic dilation

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2010-01-01

    Full Text Available BACKGROUND: A bicuspid aortic valve (BAV is a common congenital heart disease, which affects 1-2% of the population. However, the relationship between BAVs and aortic dilation has not been sufficiently elucidated. METHODS: A total of 241 BAV patients who were referred to this hospital for cardiac surgey over a 4.75-year period were included in this study. In addition to the clinical characteristics of the included patients, the morphological features of the aortic valve and aorta, the length of the left main coronary artery, and the laboratory findings (the coagulation and hematological parameters as well as the total cholesterol concentration were determined and compared with those of the tricuspid aortic valve (TAV patients. RESULTS: The BAV patients were younger than the TAV patients for a valve surgery in the last 3 months of the study period. The BAV patients were predominantly male. Most of the BAVs that were surgically treated were stenotic, regurgitant, or combined, and only 19 (7.88% were normally functioning valves. According to echocardiography or operative records, 148 (78.31% were type A, 31 (16.40% were type B, and 10 (5.29% were type C. The left main coronary artery was much shorter in the BAV patients than it was in the TAV patients. There was no significant difference between BAV and TAV patients in the total cholesterol concentrations; whereas differences were noted between patients receiving lipid-lowering therapy and those not receiving lipid-lowering therapy. The dimensions of the aortic root, sinotubular junction, and ascending aorta were beyond normal limits, while they were significantly smaller in the BAV patients than in the TAV patients. They were also much smaller in patients receiving statin therapy than those not receiving statin therapy in both groups. Moreover, the aortic dilation in the BAV group was found to be significantly associated with patient age. CONCLUSIONS: The BAV patients developed aortic wall and

  17. Directed mutagenesis affects recombination in Azospirillum brasilense nif genes

    Directory of Open Access Journals (Sweden)

    C.P. Nunes

    2000-12-01

    Full Text Available In order to improve the gene transfer/mutagenesis system for Azospirillum brasilense, gene-cartridge mutagenesis was used to replace the nifD gene with the Tn5 kanamycin resistance gene. The construct was transferred to A. brasilense by electrotransformation. Of the 12 colonies isolated using the suicide plasmid pSUP202 as vector, only four did not show vector integration into the chromosome. Nevertheless, all 12 colonies were deficient in acetylene reduction, indicating an Nif- phenotype. Four Nif- mutants were analyzed by Southern blot, using six different probes spanning the nif and Km r genes and the plasmid vector. Apparently, several recombination events occurred in the mutant genomes, probably caused mainly by gene disruption owing to the mutagenesis technique used: resistance gene-cartridge mutagenesis combined with electrotransformation.Com o objetivo de melhorar os sistemas de transferência gênica e mutagênese para Azospirillum brasilense, a técnica de mutagênese através do uso de um gene marcador ("gene-cartridge mutagenesis" foi utilizada para substituir a região genômica de A. brasilense correspondente ao gene nifD por um segmento de DNA do transposon Tn5 contendo o gene que confere resistência ao antibiótico canamicina. A construção foi transferida para a linhagem de A. brasilense por eletrotransformação. Doze colônias transformantes foram isoladas com o plasmídeo suicida pSUP202 servindo como vetor. Dessas, somente quatro não possuíam o vetor integrado no cromossomo da bactéria. Independentemente da integração ou não do vetor, as 12 colônias foram deficientes na redução do gás acetileno, evidenciando o fenótipo Nif -. Quatro mutantes Nif - foram analisados através da técnica de Southern blot, utilizando-se seis diferentes fragmentos contendo genes nif, de resistência à canamicina e do vetor como sondas. Os resultados sugerem a ocorrência de eventos recombinacionais variados no genoma dos mutantes. A

  18. Microarray analysis of genes affected by salt stress in tomato

    African Journals Online (AJOL)

    LANDA

    isoforms of cytochrome P450, genes for polyamine biosynthesis (putrescine and proline) ..... CAB97048 mitochondrial half-ABC transporter [Arabidopsis thaliana] up .... AAC72194 pyruvate dehydrogenase E1 beta subunit isoform 3 [Zea mays].

  19. Diaphanous gene mutation affects spiral cleavage and chirality in snails

    Science.gov (United States)

    Kuroda, Reiko; Fujikura, Kohei; Abe, Masanori; Hosoiri, Yuji; Asakawa, Shuichi; Shimizu, Miho; Umeda, Shin; Ichikawa, Futaba; Takahashi, Hiromi

    2016-01-01

    L-R (left and right) symmetry breaking during embryogenesis and the establishment of asymmetric body plan are key issues in developmental biology, but the onset including the handedness-determining gene locus still remains unknown. Using pure dextral (DD) and sinistral (dd) strains of the pond snail Lymnaea stagnalis as well as its F2 through to F10 backcrossed lines, the single handedness-determining-gene locus was mapped by genetic linkage analysis, BAC cloning and chromosome walking. We have identified the actin-related diaphanous gene Lsdia1 as the strongest candidate. Although the cDNA and derived amino acid sequences of the tandemly duplicated Lsdia1 and Lsdia2 genes are very similar, we could discriminate the two genes/proteins in our molecular biology experiments. The Lsdia1 gene of the sinistral strain carries a frameshift mutation that abrogates full-length LsDia1 protein expression. In the dextral strain, it is already translated prior to oviposition. Expression of Lsdia1 (only in the dextral strain) and Lsdia2 (in both chirality) decreases after the 1-cell stage, with no asymmetric localization throughout. The evolutionary relationships among body handedness, SD/SI (spiral deformation/spindle inclination) at the third cleavage, and expression of diaphanous proteins are discussed in comparison with three other pond snails (L. peregra, Physa acuta and Indoplanorbis exustus). PMID:27708420

  20. Oxygen and tissue culture affect placental gene expression.

    Science.gov (United States)

    Brew, O; Sullivan, M H F

    2017-07-01

    Placental explant culture is an important model for studying placental development and functions. We investigated the differences in placental gene expression in response to tissue culture, atmospheric and physiologic oxygen concentrations. Placental explants were collected from normal term (38-39 weeks of gestation) placentae with no previous uterine contractile activity. Placental transcriptomic expressions were evaluated with GeneChip ® Human Genome U133 Plus 2.0 arrays (Affymetrix). We uncovered sub-sets of genes that regulate response to stress, induction of apoptosis programmed cell death, mis-regulation of cell growth, proliferation, cell morphogenesis, tissue viability, and protection from apoptosis in cultured placental explants. We also identified a sub-set of genes with highly unstable pattern of expression after exposure to tissue culture. Tissue culture irrespective of oxygen concentration induced dichotomous increase in significant gene expression and increased enrichment of significant pathways and transcription factor targets (TFTs) including HIF1A. The effect was exacerbated by culture at atmospheric oxygen concentration, where further up-regulation of TFTs including PPARA, CEBPD, HOXA9 and down-regulated TFTs such as JUND/FOS suggest intrinsic heightened key biological and metabolic mechanisms such as glucose use, lipid biosynthesis, protein metabolism; apoptosis, inflammatory responses; and diminished trophoblast proliferation, differentiation, invasion, regeneration, and viability. These findings demonstrate that gene expression patterns differ between pre-culture and cultured explants, and the gene expression of explants cultured at atmospheric oxygen concentration favours stressed, pro-inflammatory and increased apoptotic transcriptomic response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Aortic valve bypass

    DEFF Research Database (Denmark)

    Lund, Jens T; Jensen, Maiken Brit; Arendrup, Henrik

    2013-01-01

    In aortic valve bypass (AVB) a valve-containing conduit is connecting the apex of the left ventricle to the descending aorta. Candidates are patients with symptomatic aortic valve stenosis rejected for conventional aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI). ...

  2. HFE gene variants affect iron in the brain.

    Science.gov (United States)

    Nandar, Wint; Connor, James R

    2011-04-01

    Iron accumulation in the brain and increased oxidative stress are consistent observations in many neurodegenerative diseases. Thus, we have begun examination into gene mutations or allelic variants that could be associated with loss of iron homeostasis. One of the mechanisms leading to iron overload is a mutation in the HFE gene, which is involved in iron metabolism. The 2 most common HFE gene variants are C282Y (1.9%) and H63D (8.9%). The C282Y HFE variant is more commonly associated with hereditary hemochromatosis, which is an autosomal recessive disorder, characterized by iron overload in a number of systemic organs. The H63D HFE variant appears less frequently associated with hemochromatosis, but its role in the neurodegenerative diseases has received more attention. At the cellular level, the HFE mutant protein resulting from the H63D HFE gene variant is associated with iron dyshomeostasis, increased oxidative stress, glutamate release, tau phosphorylation, and alteration in inflammatory response, each of which is under investigation as a contributing factor to neurodegenerative diseases. Therefore, the HFE gene variants are proposed to be genetic modifiers or a risk factor for neurodegenerative diseases by establishing an enabling milieu for pathogenic agents. This review will discuss the current knowledge of the association of the HFE gene variants with neurodegenerative diseases: amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and ischemic stroke. Importantly, the data herein also begin to dispel the long-held view that the brain is protected from iron accumulation associated with the HFE mutations.

  3. Correction of aortic insufficiency with an external adjustable prosthetic aortic ring.

    Science.gov (United States)

    Gogbashian, Andrew; Ghanta, Ravi K; Umakanthan, Ramanan; Rangaraj, Aravind T; Laurence, Rita G; Fox, John A; Cohn, Lawrence H; Chen, Frederick Y

    2007-09-01

    Less invasive, valve-sparing options are needed for patients with aortic insufficiency (AI). We sought to evaluate the feasibility of reducing AI with an external adjustable aortic ring in an ovine model. To create AI, five sheep underwent patch plasty enlargement of the aortic annulus and root by placement of a 10 x 15 mm pericardial patch between the right and noncoronary cusps. An adjustable external ring composed of a nylon band was fabricated and placed around the aortic root. Aortic flow, aortic pressure, and left ventricular pressures were measured with the ring loose (off) and tightened (on). Mean regurgitant orifice area decreased by 86%, from 0.07 +/- 0.03 cm2 (ring loose, off) to 0.01 +/- 0.00 cm2 (ring tightened, on) [p < 0.01]. The regurgitant fraction decreased from 18 +/- 4% to 2 +/- 1% [p < 0.01]. The ring did not significantly affect stroke volume and aortic pressure. An ovine model of aortic root dilatation resulting in acute AI has been developed. In this model, application of an external, adjustable constricting aortic ring eliminated AI. An aortic ring may be a useful adjunct in reducing AI secondary to annular dilatation.

  4. Land use type significantly affects microbial gene transcription in soil.

    Science.gov (United States)

    Nacke, Heiko; Fischer, Christiane; Thürmer, Andrea; Meinicke, Peter; Daniel, Rolf

    2014-05-01

    Soil microorganisms play an essential role in sustaining biogeochemical processes and cycling of nutrients across different land use types. To gain insights into microbial gene transcription in forest and grassland soil, we isolated mRNA from 32 sampling sites. After sequencing of generated complementary DNA (cDNA), a total of 5,824,229 sequences could be further analyzed. We were able to assign nonribosomal cDNA sequences to all three domains of life. A dominance of bacterial sequences, which were affiliated to 25 different phyla, was found. Bacterial groups capable of aromatic compound degradation such as Phenylobacterium and Burkholderia were detected in significantly higher relative abundance in forest soil than in grassland soil. Accordingly, KEGG pathway categories related to degradation of aromatic ring-containing molecules (e.g., benzoate degradation) were identified in high abundance within forest soil-derived metatranscriptomic datasets. The impact of land use type forest on community composition and activity is evidently to a high degree caused by the presence of wood breakdown products. Correspondingly, bacterial groups known to be involved in lignin degradation and containing ligninolytic genes such as Burkholderia, Bradyrhizobium, and Azospirillum exhibited increased transcriptional activity in forest soil. Higher solar radiation in grassland presumably induced increased transcription of photosynthesis-related genes within this land use type. This is in accordance with high abundance of photosynthetic organisms and plant-infecting viruses in grassland.

  5. Ionizing Radiation Affects Gene Expression in Mouse Skin and Bone

    Science.gov (United States)

    Terada, Masahiro; Tahimic, Candice; Sowa, Marianne B.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Alwood, Joshua; Globus, Ruth K.

    2017-01-01

    Future long-duration space exploration beyond low earth orbit will increase human exposure to space radiation and microgravity conditions as well as associated risks to skeletal health. In animal studies, radiation exposure (greater than 1 Gy) is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Definitive measurements and detection of bone loss typically require large and specialized equipment which can make their application to long duration space missions logistically challenging. Towards the goal of developing non-invasive and less complicated monitoring methods to predict astronauts' health during spaceflight, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (IR). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and IR (0.5 Gy 56Fe 600 MeV/n and 0.5 Gy 1H 150 MeV/n), euthanized at one and 11 days post-irradiation (IR). To determine the extent of bone loss, tibiae were harvested and cancellous microarchitecture in the proximal tibia quantified ex vivo using microcomputed tomography (microCT). Statistical analysis was performed using Student's t-test. At one day post-IR, expression of FGF18 in skin was significantly greater (3.8X) than sham-irradiated controls, but did not differ at 11 days post IR. Expression levels of other genes associated with antioxidant response (Nfe2l2, FoxO3 and Sod1) and the cell cycle (Trp53, Cdkn1a, Gadd45g) did not significantly differ between the control and IR groups

  6. Aortic Annular Enlargement during Aortic Valve Replacement

    Directory of Open Access Journals (Sweden)

    Selman Dumani

    2016-09-01

    Full Text Available In the surgery of aortic valve replacement is always attempted, as much as possible, to implant the larger prosthesis with the mains goals to enhance the potential benefits, to minimise transvalvular gradient, decrease left ventricular size and avoid the phenomenon of patient-prosthesis mismatch. Implantation of an ideal prosthesis often it is not possible, due to a small aortic annulus. A variety of aortic annulus enlargement techniques is reported to avoid patient-prosthesis mismatch. We present the case that has submitted four three times open heart surgery. We used Manouguian technique to enlarge aortic anulus with excellent results during the fourth time of surgery.

  7. Identification of nonviable genes affecting touch sensitivity in Caenorhabditis elegans using neuronally enhanced feeding RNA interference.

    Science.gov (United States)

    Chen, Xiaoyin; Cuadros, Margarete Diaz; Chalfie, Martin

    2015-01-09

    Caenorhabditis elegans senses gentle touch along the body via six touch receptor neurons. Although genetic screens and microarray analyses have identified several genes needed for touch sensitivity, these methods miss pleiotropic genes that are essential for the viability, movement, or fertility of the animals. We used neuronally enhanced feeding RNA interference to screen genes that cause lethality or paralysis when mutated, and we identified 61 such genes affecting touch sensitivity, including five positive controls. We confirmed 18 genes by using available alleles, and further studied one of them, tag-170, now renamed txdc-9. txdc-9 preferentially affects anterior touch response but is needed for tubulin acetylation and microtubule formation in both the anterior and posterior touch receptor neurons. Our results indicate that neuronally enhanced feeding RNA interference screens complement traditional mutageneses by identifying additional nonviable genes needed for specific neuronal functions. Copyright © 2015 Chen et al.

  8. Altered aortic shape in bicuspid aortic valve relatives influences blood flow patterns.

    Science.gov (United States)

    Schnell, Susanne; Smith, Danielle A; Barker, Alex J; Entezari, Pegah; Honarmand, Amir R; Carr, Maria L; Malaisrie, S Chris; McCarthy, Patrick M; Collins, Jeremy; Carr, James C; Markl, Michael

    2016-11-01

    Bicuspid aortic valve (BAV) is known to exhibit familial inheritance and is associated with aortopathy and altered aortic haemodynamics. However, it remains unclear whether BAV-related aortopathy can be inherited independently of valve morphology. Four-dimensional flow magnetic resonance imaging for the in vivo assessment of thoracic aortic 3D blood flow was performed in 24 BAV relatives with trileaflet aortic valves (age = 40 ± 14 years) and 15 healthy controls (age = 37 ± 10 years). Data analysis included aortic dimensions, shape (round/gothic/cubic), and 3D blood flow characteristics (semi-quantitative vortex/helix grading and peak velocities). Cubic and gothic aortic shapes were markedly more prevalent in BAV relatives compared with controls (38 vs. 7%). Ascending aorta (AAo) vortex flow in BAV relatives was significantly increased compared with controls (grading = 1.5 ± 1.0 vs. 0.6 ± 0.9, P = 0.015). Aortic haemodynamics were influenced by aortic shape: peak velocities were reduced for gothic aortas vs. round aortas (P = 0.003); vortex flow was increased for cubic aortas in the AAo (P gothic aortas in the AAo and descending aorta (P = 0.003, P = 0.029). Logistic regression demonstrated significant associations of shape with severity of vortex flow in AAo (P < 0.001) and aortic arch (P = 0.016) in BAV relatives. BAV relatives expressed altered aortic shape and increased vortex flow despite the absence of valvular disease or aortic dilatation. These data suggest a heritable component of BAV-related aortopathy affecting aortic shape and aberrant blood flow, independent of valve morphology. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  9. Identification of genes affecting vacuole membrane fragmentation in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Lydie Michaillat

    Full Text Available The equilibrium of membrane fusion and fission influences the volume and copy number of organelles. Fusion of yeast vacuoles has been well characterized but their fission and the mechanisms determining vacuole size and abundance remain poorly understood. We therefore attempted to systematically characterize factors necessary for vacuole fission. Here, we present results of an in vivo screening for deficiencies in vacuolar fragmentation activity of an ordered collection deletion mutants, representing 4881 non-essential genes of the yeast Saccharomyces cerevisiae. The screen identified 133 mutants with strong defects in vacuole fragmentation. These comprise numerous known fragmentation factors, such as the Fab1p complex, Tor1p, Sit4p and the V-ATPase, thus validating the approach. The screen identified many novel factors promoting vacuole fragmentation. Among those are 22 open reading frames of unknown function and three conspicuous clusters of proteins with known function. The clusters concern the ESCRT machinery, adaptins, and lipases, which influence the production of diacylglycerol and phosphatidic acid. A common feature of these factors of known function is their capacity to change membrane curvature, suggesting that they might promote vacuole fragmentation via this property.

  10. Aortic valve surgery - open

    Science.gov (United States)

    ... gov/ency/article/007408.htm Aortic valve surgery - open To use the sharing features on this page, ... separates the heart and aorta. The aortic valve opens so blood can flow out. It then closes ...

  11. Abdominal Aortic Aneurysm (AAA)

    Science.gov (United States)

    ... Professions Site Index A-Z Abdominal Aortic Aneurysm (AAA) Abdominal aortic aneurysm (AAA) occurs when atherosclerosis or plaque buildup causes the ... weak and bulge outward like a balloon. An AAA develops slowly over time and has few noticeable ...

  12. Inhibitory role of Notch1 in calcific aortic valve disease.

    Directory of Open Access Journals (Sweden)

    Asha Acharya

    Full Text Available Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs. We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

  13. Unstable Expression of Commonly Used Reference Genes in Rat Pancreatic Islets Early after Isolation Affects Results of Gene Expression Studies.

    Directory of Open Access Journals (Sweden)

    Lucie Kosinová

    Full Text Available The use of RT-qPCR provides a powerful tool for gene expression studies; however, the proper interpretation of the obtained data is crucially dependent on accurate normalization based on stable reference genes. Recently, strong evidence has been shown indicating that the expression of many commonly used reference genes may vary significantly due to diverse experimental conditions. The isolation of pancreatic islets is a complicated procedure which creates severe mechanical and metabolic stress leading possibly to cellular damage and alteration of gene expression. Despite of this, freshly isolated islets frequently serve as a control in various gene expression and intervention studies. The aim of our study was to determine expression of 16 candidate reference genes and one gene of interest (F3 in isolated rat pancreatic islets during short-term cultivation in order to find a suitable endogenous control for gene expression studies. We compared the expression stability of the most commonly used reference genes and evaluated the reliability of relative and absolute quantification using RT-qPCR during 0-120 hrs after isolation. In freshly isolated islets, the expression of all tested genes was markedly depressed and it increased several times throughout the first 48 hrs of cultivation. We observed significant variability among samples at 0 and 24 hrs but substantial stabilization from 48 hrs onwards. During the first 48 hrs, relative quantification failed to reflect the real changes in respective mRNA concentrations while in the interval 48-120 hrs, the relative expression generally paralleled the results determined by absolute quantification. Thus, our data call into question the suitability of relative quantification for gene expression analysis in pancreatic islets during the first 48 hrs of cultivation, as the results may be significantly affected by unstable expression of reference genes. However, this method could provide reliable information

  14. Strategy to avoid patient-prosthesis mismatch: aortic root enlargement.

    Science.gov (United States)

    Srivastava, Dharmendra Kumar; Sanki, Prokash; Bhattacharya, Subhankar; Siddique, Javed Veqar

    2014-02-01

    The choice of a valve with an effective orifice area matching the body surface area and providing efficient hemodynamics is an important factor affecting mortality and morbidity in patients undergoing aortic valve replacement. Our preventative strategy was to implant a larger prosthetic valve by aortic root enlargement using the Nunez procedure in 17 patients between February 2010 and January 2011. The decision to enlarge the aortic root was taken when the 19-mm sizer could not be negotiated easily through the aortic root, or on the basis of body surface area of the patient or type of prosthesis available. Postoperative reductions in peak and mean pressure gradients across aortic valve of 12.8-16.5 and 10.2-12.6 mm Hg, respectively, were observed. Postoperative effective orifice areas of the aortic valves were 1.1-1.5 cm(2). By upsizing the aortic valve, we were able to eliminate patient-prosthesis mismatch in 5 patients, and reduce severe patient-prosthesis mismatch to moderate in 11. Aortic root enlargement is a safe procedure. Therefore, cardiac surgeons should not be reluctant to enlarge the aortic root with an autologous pericardial patch to permit implantation of an adequate size of aortic valve prosthesis, with minimal additional aortic crossclamp time and no added cost.

  15. The use of transcatheter aortic valve replacement vs surgical aortic valve replacement for the treatment of aortic stenosis

    Directory of Open Access Journals (Sweden)

    Jensen HA

    2015-08-01

    Full Text Available Hanna A Jensen, Lillian L Tsai, Vinod H Thourani Division of Cardiothoracic Surgery, Joseph B Whitehead Department of Surgery, Structural Heart and Valve Center, Emory University School of Medicine, Atlanta, GA, USA Abstract: Severe aortic stenosis (AS is associated with considerable morbidity and mortality and is increasing in prevalence as the global population increases. Since AS primarily affects the elderly, many of these patients have comorbidities that make them poor candidates for the gold standard treatment for AS, surgical aortic valve replacement. Transcatheter aortic valve replacement has emerged as a novel technology for the management of AS in higher risk patients over the past decade. Randomized trials have established the safety and efficacy of transcatheter aortic valve replacement, and the medical community has rallied to identify the patients who are most suitable for this transformative treatment. This review focuses on outlining the key procedural differences, describing the unique challenges of both operations, and finally assessing and comparing outcomes both on a general level and in challenging patient subgroups. Keywords: aortic valve replacement, transcatheter aortic valve replacement, surgical aortic valve replacement 

  16. Systematic identification of novel, essential host genes affecting bromovirus RNA replication.

    Directory of Open Access Journals (Sweden)

    Brandi L Gancarz

    Full Text Available Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2a(Pol levels were significantly increased in strains depleted for a heat shock protein (HSF1 or proteasome components (PRE1 and RPT6, suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2a(Pol localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control.

  17. Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits.

    Science.gov (United States)

    Watson, Emma; MacNeil, Lesley T; Ritter, Ashlyn D; Yilmaz, L Safak; Rosebrock, Adam P; Caudy, Amy A; Walhout, Albertha J M

    2014-02-13

    Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits

    Science.gov (United States)

    Watson, Emma; MacNeil, Lesley T.; Ritter, Ashlyn D.; Yilmaz, L. Safak; Rosebrock, Adam P.; Caudy, Amy A.; Walhout, Albertha J. M.

    2014-01-01

    SUMMARY Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here we used an interspecies systems biology approach with Caenorhabditis elegans and two if its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal’s gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development and reduces fertility, but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. PMID:24529378

  19. Over-expression of KdSOC1 gene affected plantlet morphogenesis in Kalanchoe daigremontiana.

    Science.gov (United States)

    Zhu, Chen; Wang, Li; Chen, Jinhua; Liu, Chenglan; Zeng, Huiming; Wang, Huafang

    2017-07-17

    Kalanchoe daigremontiana reproduces asexually by producing plantlets along the leaf margin. The aim of this study was to identify the function of the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 gene in Kalanchoe daigremontiana (KdSOC1) during plantlet morphogenesis. In this study, KdSOC1 gene expression was detected at stem cell niche during in vitro somatic embryogenesis and plantlet morphogenesis. Disrupting endogenous auxin transportation suppressed the KdSOC1 gene response. Knockdown of the KdSOC1 gene caused a defect in cotyledon formation during the early heart stage of somatic embryogenesis. Over-expression (OE) of the KdSOC1 gene resulted in asymmetric plantlet distribution, a reduced number of plantlets, thicker leaves, and thicker vascular fibers. Higher KdPIN1 gene expression and auxin content were found in OE plant compared to those of wild-type plant leaves, which indicated possible KdSOC1 gene role in affecting auxin distribution and accumulation. KdSOC1 gene OE in DR5-GUS Arabidopsis reporting lines resulted in an abnormal auxin response pattern during different stages of somatic embryogenesis. In summary, the KdSOC1 gene OE might alter auxin distribution and accumulation along leaf margin to initiate plantlet formation and distribution, which is crucial for plasticity during plantlet formation under various environmental conditions.

  20. Activation and clustering of a Plasmodium falciparum var gene are affected by subtelomeric sequences.

    Science.gov (United States)

    Duffy, Michael F; Tang, Jingyi; Sumardy, Fransisca; Nguyen, Hanh H T; Selvarajah, Shamista A; Josling, Gabrielle A; Day, Karen P; Petter, Michaela; Brown, Graham V

    2017-01-01

    The Plasmodium falciparum var multigene family encodes the cytoadhesive, variant antigen PfEMP1. P. falciparum antigenic variation and cytoadhesion specificity are controlled by epigenetic switching between the single, or few, simultaneously expressed var genes. Most var genes are maintained in perinuclear clusters of heterochromatic telomeres. The active var gene(s) occupy a single, perinuclear var expression site. It is unresolved whether the var expression site forms in situ at a telomeric cluster or whether it is an extant compartment to which single chromosomes travel, thus controlling var switching. Here we show that transcription of a var gene did not require decreased colocalisation with clusters of telomeres, supporting var expression site formation in situ. However following recombination within adjacent subtelomeric sequences, the same var gene was persistently activated and did colocalise less with telomeric clusters. Thus, participation in stable, heterochromatic, telomere clusters and var switching are independent but are both affected by subtelomeric sequences. The var expression site colocalised with the euchromatic mark H3K27ac to a greater extent than it did with heterochromatic H3K9me3. H3K27ac was enriched within the active var gene promoter even when the var gene was transiently repressed in mature parasites and thus H3K27ac may contribute to var gene epigenetic memory. © 2016 Federation of European Biochemical Societies.

  1. Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

    Directory of Open Access Journals (Sweden)

    Marcelo Cury

    2013-01-01

    Full Text Available There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS, Ehlers-Danlos syndrome (EDS, Loeys-Dietz syndrome (LDS, familial thoracic aortic aneurysms and dissections (TAAD, bicuspid aortic valve disease (BAV, and autosomal dominant polycystic kidney disease (ADPKD. In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

  2. Identification of susceptibility genes for bipolar affective disorder and schizophrenia on chromosome 22q13

    DEFF Research Database (Denmark)

    Severinsen, Jacob Eg

    2006-01-01

    Linkage analyses suggest that chromosome 22q12-13 may harbor one or more shared susceptibility loci for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of distantly related cases and control individuals from the Faeroe Islands our group has previously reported that chromosome 22...... samples (total of 1,751 individuals), and by bioinformatic and expression analyses of a subset of disease associated genes and gene variants. In total 67 single nucleotide polymorphisms (SNPs) located in 18 positional candidate genes, and 4 microsattelite markers were investigated, using a Scottish case...

  3. Cloning of Bacteroides fragilis plasmid genes affecting metronidazole resistance and ultraviolet survival in Escherichia coli

    International Nuclear Information System (INIS)

    Wehnert, G.U.; Abratt, V.R.; Goodman, H.J.; Woods, D.R.

    1990-01-01

    Since reduced metronidazole causes DNA damage, resistance to metronidazole was used as a selection method for the cloning of Bacteroides fragilis genes affecting DNA repair mechanisms in Escherichia coli. Genes from B. fragilis Bf-2 were cloned on a recombinant plasmid pMT100 which made E. coli AB1157 and uvrA, B, and C mutant strains more resistant to metronidazole, but more sensitive to far uv irradiation under aerobic conditions. The loci affecting metronidazole resistance and uv sensitivity were linked and located on a 5-kb DNA fragment which originated from the small 6-kb cryptic plasmid pBFC1 present in B. fragilis Bf-2 cells

  4. Tumor SHB gene expression affects disease characteristics in human acute myeloid leukemia.

    Science.gov (United States)

    Jamalpour, Maria; Li, Xiujuan; Cavelier, Lucia; Gustafsson, Karin; Mostoslavsky, Gustavo; Höglund, Martin; Welsh, Michael

    2017-10-01

    The mouse Shb gene coding for the Src Homology 2-domain containing adapter protein B has recently been placed in context of BCRABL1-induced myeloid leukemia in mice and the current study was performed in order to relate SHB to human acute myeloid leukemia (AML). Publicly available AML databases were mined for SHB gene expression and patient survival. SHB gene expression was determined in the Uppsala cohort of AML patients by qPCR. Cell proliferation was determined after SHB gene knockdown in leukemic cell lines. Despite a low frequency of SHB gene mutations, many tumors overexpressed SHB mRNA compared with normal myeloid blood cells. AML patients with tumors expressing low SHB mRNA displayed longer survival times. A subgroup of AML exhibiting a favorable prognosis, acute promyelocytic leukemia (APL) with a PMLRARA translocation, expressed less SHB mRNA than AML tumors in general. When examining genes co-expressed with SHB in AML tumors, four other genes ( PAX5, HDAC7, BCORL1, TET1) related to leukemia were identified. A network consisting of these genes plus SHB was identified that relates to certain phenotypic characteristics, such as immune cell, vascular and apoptotic features. SHB knockdown in the APL PMLRARA cell line NB4 and the monocyte/macrophage cell line MM6 adversely affected proliferation, linking SHB gene expression to tumor cell expansion and consequently to patient survival. It is concluded that tumor SHB gene expression relates to AML survival and its subgroup APL. Moreover, this gene is included in a network of genes that plays a role for an AML phenotype exhibiting certain immune cell, vascular and apoptotic characteristics.

  5. Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm

    NARCIS (Netherlands)

    Gretarsdottir, Solveig; Baas, Annette F.; Thorleifsson, Gudmar; Holm, Hilma; den Heijer, Martin; de Vries, Jean-Paul P. M.; Kranendonk, Steef E.; Zeebregts, Clark J. A. M.; van Sterkenburg, Steven M.; Geelkerken, Robert H.; van Rij, Andre M.; Williams, Michael J. A.; Boll, Albert P. M.; Kostic, Jelena P.; Jonasdottir, Adalbjorg; Jonasdottir, Aslaug; Walters, G. Bragi; Masson, Gisli; Sulem, Patrick; Saemundsdottir, Jona; Mouy, Magali; Magnusson, Kristinn P.; Tromp, Gerard; Elmore, James R.; Sakalihasan, Natzi; Limet, Raymond; Defraigne, Jean-Olivier; Ferrell, Robert E.; Ronkainen, Antti; Ruigrok, Ynte M.; Wijmenga, Cisca; Grobbee, Diederick E.; Shah, Svati H.; Granger, Christopher B.; Quyyumi, Arshed A.; Vaccarino, Viola; Patel, Riyaz S.; Zafari, A. Maziar; Levey, Allan I.; Austin, Harland; Girelli, Domenico; Pignatti, Pier Franco; Olivieri, Oliviero; Martinelli, Nicola; Malerba, Giovanni; Trabetti, Elisabetta; Becker, Lewis C.; Becker, Diane M.; Reilly, Muredach P.; Rader, Daniel J.; Mueller, Thomas; Dieplinger, Benjamin; Haltmayer, Meinhard; Urbonavicius, Sigitas; Lindblad, Bengt; Gottsater, Anders; Gaetani, Eleonora; Pola, Roberto; Wells, Philip; Rodger, Marc; Forgie, Melissa; Langlois, Nicole; Corral, Javier; Vicente, Vicente; Fontcuberta, Jordi; Espana, Francisco; Grarup, Niels; Jorgensen, Torben; Witte, Daniel R.; Hansen, Torben; Pedersen, Oluf; Aben, Katja K.; de Graaf, Jacqueline; Holewijn, Suzanne; Folkersen, Lasse; Franco-Cereceda, Anders; Eriksson, Per; Collier, David A.; Stefansson, Hreinn; Steinthorsdottir, Valgerdur; Rafnar, Thorunn; Valdimarsson, Einar M.; Magnadottir, Hulda B.; Sveinbjornsdottir, Sigurlaug; Olafsson, Isleifur; Magnusson, Magnus Karl; Palmason, Robert; Haraldsdottir, Vilhelmina; Andersen, Karl; Onundarson, Pall T.; Thorgeirsson, Gudmundur; Kiemeney, Lambertus A.; Powell, Janet T.; Carey, David J.; Kuivaniemi, Helena; Lindholt, Jes S.; Jones, Gregory T.; Kong, Augustine; Blankensteijn, Jan D.; Matthiasson, Stefan E.; Thorsteinsdottir, Unnur; Stefansson, Kari

    We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to

  6. Refractory pulmonary edema secondary to severe aortic valvular stenosis - aortic valvuloplasty as bridge therapy to surgery

    International Nuclear Information System (INIS)

    Santiago, Salazar; Hanna, Franklin; Capasso, Aminta

    2009-01-01

    Aortic valve stenosis is a progressive disease; when it is severe and symptomatic has a bleak prognosis that affects adversely the patient survival. In these cases, the treatment of choice is valve replacement surgery that under certain circumstances can bear a huge risk that forces the physician to consider less aggressive management alternatives to solve the problem. The case of a 65 years old male with severe aortic valve stenosis is reported. He developed pulmonary edema refractory to medical treatment that was solved by aortic valvuloplasty as bridge therapy to surgery.

  7. Autosomal dominant Marfan-like connective-tissue disorder with aortic dilation and skeletal anomaslies not linked to the Fibrillin genes

    Energy Technology Data Exchange (ETDEWEB)

    Boileau, C.; Coulon, M.; Alexandre, J.-A.; Junien, C. (Laboratorie Central de Biochimie et de Genetique Moleculaire (France)); Jondeau, G.; Delorme, G.; Dubourg, O.; Bourdarias, J.-P. (CHU Ambroise Pare, Boulogne (France)); Babron, M.-C.; Bonaieti-Pellie, C. (INSERM, Chateau de Longchamp, Paris (France)); Sakai, L. (Shriners' Hospital for Crippled Children, Portland, OR (United States)); Melki, J. (Hopital Necker-Enfants Malades, Paris (France))

    1993-07-01

    The authors describe a large family with a connective-tissue disorder that exhibits some of the skeletal and cardiovascular features seen in Marfan syndrome. However, none of the 19 affected individuals displayed ocular abnormalities and therefore did not comply with recognized criteria for this disease. These patients could alternatively be diagnosed as MASS (mitral valve, aorta, skeleton, and skin) phenotype patients or represent a distinct clinical entity, i.e., a new autosomal dominant connective-tissue disorder. The fibrillin genes located on chromosomes 15 and 5 are clearly involved in the classic form of Marfan syndrome and a clinically related disorder (congenital contractural arachnodactyly), respectively. To test whether one of these genes was also implicated in this French family, the authors performed genetic analyses. Blood samples were obtained for 56 family members, and four polymorphic fibrillin gene markers, located on chromosomes 15 (Fib15) and 5 (Fib5), respectively, were tested. Linkage between the disease allele and the markers of these two genes was excluded with lod scores of [minus]11.39 (for Fib15) and [minus]13.34 (for Fib5), at 0 = .001, indicating that the mutation is at a different locus. This phenotype thus represents a new connective-tissue disorder, overlapping but different from classic Marfan syndrome. 33 refs., 1 fig. 2 tabs.

  8. Aortic aneurysm disease vs. aortic occlusive disease - differences in outcome and intensive care resource utilisation after elective surgery

    DEFF Research Database (Denmark)

    Bisgaard, Jannie; Gilsaa, Torben; Rønholm, Ebbe

    2013-01-01

    clamping is more pronounced in patients with aortic aneurysm disease, which may affect outcome. OBJECTIVES: The aim of this observational cohort study was to evaluate outcome after open elective abdominal aortic surgery, hypothesising a higher 30-day mortality, a higher incidence of postoperative organ...... dysfunction and a longer length of stay in patients with aortic aneurysm compared with aortic occlusive disease. DESIGN: Cohort observational study based on prospective registrations from national databases. SETTING: Eight Danish hospitals, including four university and four non-university centres, from 1...... or inotropes, ICU stay more than 24 h, hospital length of stay and mortality. RESULTS: Compared with aortic occlusive disease, more patients with aortic aneurysm disease had ICU stays more than 24 h (62 vs. 45%, P ...

  9. [Analysis of SOX10 gene mutation in a family affected with Waardenburg syndrome type II].

    Science.gov (United States)

    Zheng, Lei; Yan, Yousheng; Chen, Xue; Zhang, Chuan; Zhang, Qinghua; Feng, Xuan; Hao, Shen

    2018-02-10

    OBJECTIVE To detect potential mutation of SOX10 gene in a pedigree affected with Warrdenburg syndrome type II. METHODS Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Exons and flanking sequences of MITF, PAX3, SOX10, SNAI2, END3 and ENDRB genes were analyzed by chip capturing and high throughput sequencing. Suspected mutations were verified with Sanger sequencing. RESULTS A c.127C>T (p.R43X) mutation of the SOX10 gene was detected in the proband, for which both parents showed a wild-type genotype. CONCLUSION The c.127C>T (p.R43X) mutation of SOX10 gene probably underlies the ocular symptoms and hearing loss of the proband.

  10. Vitrification affects nuclear maturation and gene expression of immature human oocytes

    Directory of Open Access Journals (Sweden)

    Abbas Shahedi

    2017-02-01

    Full Text Available Background: Vitrification of oocytes is a fast-freezing technique, which may affect the quality of the human oocyte, and consequently affects the embryo development, pregnancy and birth. The aim of the current study was to investigate the consequence of in-vitro vitrification on maturation status of immature human oocytes, additionally, expression levels of stress, and apoptosis related genes. Materials and Methods: The total of 213 human immature oocytes which routinely discarded from assisted reproduction clinics were collected and divided into two groups including: (I fresh germinal vesicle (GV oocytes (n=106 (matured in-vitro  (fIVM , and  (II GV oocytes (n=107 that initially vitrified, then matured in  in-vitro (vIVM. After 36 hours of incubation, the oocytes were evaluated for nuclear maturation and expression level of DNA methyltransferase (DNMT1, stress related genes (Sod1 and Hsp70, and apoptotic related genes (Bax and Bcl-2 by quantitative Real-Time PCR. Results: Oocyte maturation rates were reduced in vIVM compared to fIVM oocytes (P=0.001. The expression of stress (Sod1 and Hsp70, and apoptotic-related genes (Bax and Bcl-2 in vIVM were significantly higher compared to the fIVM group. Additionally, pro-apoptotic gene up-regulated 4.3 times more than anti-apoptotic gene in vIVM oocyte. However, DNMT1 gene expression was reduced in vIVM oocyte (P = 0.047. Conclusions: The low survival rate of vitrified In-vitro matured GV oocytes could definitely be explained by the alterations of their gene expression profile. 

  11. Aortic Dissection Type A in Alpine Skiers

    Directory of Open Access Journals (Sweden)

    Thomas Schachner

    2013-01-01

    Full Text Available Patients and Methods. 140 patients with aortic dissection type A were admitted for cardiac surgery. Seventy-seven patients experienced their dissection in the winter season (from November to April. We analyzed cases of ascending aortic dissection associated with alpine skiing. Results. In 17 patients we found skiing-related aortic dissections. Skiers were taller (180 (172–200 cm versus 175 (157–191 cm, and heavier (90 (68–125 kg versus 80 (45–110 kg, than nonskiers. An extension of aortic dissection into the aortic arch, the descending thoracic aorta, and the abdominal aorta was found in 91%, 74%, and 69%, respectively, with no significant difference between skiers and nonskiers. Skiers experienced RCA ostium dissection requiring CABG in 17.6% while this was true for 5% of nonskiers (. Hospital mortality of skiers was 6% versus 13% in nonskiers (. The skiers live at an altitude of 170 (0–853 m.a.s.l. and experience their dissection at 1602 (1185–3105; m.a.s.l. In 82% symptom start was during recreational skiing without any trauma. Conclusion. Skiing associated aortic dissection type A is usually nontraumatic. The persons affected live at low altitudes and practice an outdoor sport at unusual high altitude at cold temperatures. Postoperative outcome is good.

  12. Aortic Dissection Type A in Alpine Skiers

    Science.gov (United States)

    Schachner, Thomas; Fischler, Nikolaus; Dumfarth, Julia; Bonaros, Nikolaos; Krapf, Christoph; Schobersberger, Wolfgang; Grimm, Michael

    2013-01-01

    Patients and Methods. 140 patients with aortic dissection type A were admitted for cardiac surgery. Seventy-seven patients experienced their dissection in the winter season (from November to April). We analyzed cases of ascending aortic dissection associated with alpine skiing. Results. In 17 patients we found skiing-related aortic dissections. Skiers were taller (180 (172–200) cm versus 175 (157–191) cm, P = 0.008) and heavier (90 (68–125) kg versus 80 (45–110) kg, P = 0.002) than nonskiers. An extension of aortic dissection into the aortic arch, the descending thoracic aorta, and the abdominal aorta was found in 91%, 74%, and 69%, respectively, with no significant difference between skiers and nonskiers. Skiers experienced RCA ostium dissection requiring CABG in 17.6% while this was true for 5% of nonskiers (P = 0.086). Hospital mortality of skiers was 6% versus 13% in nonskiers (P = 0.399). The skiers live at an altitude of 170 (0–853) m.a.s.l. and experience their dissection at 1602 (1185–3105; P < 0.001) m.a.s.l. In 82% symptom start was during recreational skiing without any trauma. Conclusion. Skiing associated aortic dissection type A is usually nontraumatic. The persons affected live at low altitudes and practice an outdoor sport at unusual high altitude at cold temperatures. Postoperative outcome is good. PMID:23971024

  13. Quantification of abdominal aortic deformation after EVAR

    Science.gov (United States)

    Demirci, Stefanie; Manstad-Hulaas, Frode; Navab, Nassir

    2009-02-01

    Quantification of abdominal aortic deformation is an important requirement for the evaluation of endovascular stenting procedures and the further refinement of stent graft design. During endovascular aortic repair (EVAR) treatment, the aortic shape is subject to severe deformation that is imposed by medical instruments such as guide wires, catheters, and, the stent graft. This deformation can affect the flow characteristics and morphology of the aorta which have been shown to be elicitors for stent graft failures and be reason for reappearance of aneurysms. We present a method for quantifying the deformation of an aneurysmatic aorta imposed by an inserted stent graft device. The outline of the procedure includes initial rigid alignment of the two abdominal scans, segmentation of abdominal vessel trees, and automatic reduction of their centerline structures to one specified region of interest around the aorta. This is accomplished by preprocessing and remodeling of the pre- and postoperative aortic shapes before performing a non-rigid registration. We further narrow the resulting displacement fields to only include local non-rigid deformation and therefore, eliminate all remaining global rigid transformations. Finally, deformations for specified locations can be calculated from the resulting displacement fields. In order to evaluate our method, experiments for the extraction of aortic deformation fields are conducted on 15 patient datasets from endovascular aortic repair (EVAR) treatment. A visual assessment of the registration results and evaluation of the usage of deformation quantification were performed by two vascular surgeons and one interventional radiologist who are all experts in EVAR procedures.

  14. Aortic arch malformations

    Energy Technology Data Exchange (ETDEWEB)

    Kellenberger, Christian J. [University Children' s Hospital, Department of Diagnostic Imaging, Zuerich (Switzerland)

    2010-06-15

    Although anomalies of the aortic arch and its branches are relatively uncommon malformations, they are often associated with congenital heart disease. Isolated lesions may be clinically significant when the airways are compromised by a vascular ring. In this article, the development and imaging appearance of the aortic arch system and its various malformations are reviewed. (orig.)

  15. Imaging in aortic dissection

    International Nuclear Information System (INIS)

    Yu-Qing Liu, M.D.

    1995-01-01

    Aortic dissection (AD) is a catastrophic aortic disease. Imaging techniques play an invaluable role in the diagnostic evaluation and management of patients with AD. Major signs of AD with different imaging modalities are described in this article with a pertinent discussion on guidelines for the optimized approach of imaging study (13 refs.)

  16. Aortic arch malformations

    International Nuclear Information System (INIS)

    Kellenberger, Christian J.

    2010-01-01

    Although anomalies of the aortic arch and its branches are relatively uncommon malformations, they are often associated with congenital heart disease. Isolated lesions may be clinically significant when the airways are compromised by a vascular ring. In this article, the development and imaging appearance of the aortic arch system and its various malformations are reviewed. (orig.)

  17. Imaging in aortic dissection

    Energy Technology Data Exchange (ETDEWEB)

    Yu-Qing Liu, M D [Chinese Academy of Medical Sciences, Beijing, BJ (China). Dept. of Radiology, Fu Wai Hospital and Cardiovascular Inst.

    1996-12-31

    Aortic dissection (AD) is a catastrophic aortic disease. Imaging techniques play an invaluable role in the diagnostic evaluation and management of patients with AD. Major signs of AD with different imaging modalities are described in this article with a pertinent discussion on guidelines for the optimized approach of imaging study (13 refs.).

  18. Functional Gene Discovery and Characterization of Genes and Alleles Affecting Wood Biomass Yield and Quality in Populus

    Energy Technology Data Exchange (ETDEWEB)

    Busov, Victor [Michigan Technological Univ., Houghton, MI (United States)

    2017-02-12

    Adoption of biofuels as economically and environmentally viable alternative to fossil fuels would require development of specialized bioenergy varieties. A major goal in the breeding of such varieties is the improvement of lignocellulosic biomass yield and quality. These are complex traits and understanding the underpinning molecular mechanism can assist and accelerate their improvement. This is particularly important for tree bioenergy crops like poplars (species and hybrids from the genus Populus), for which breeding progress is extremely slow due to long generation cycles. A variety of approaches have been already undertaken to better understand the molecular bases of biomass yield and quality in poplar. An obvious void in these undertakings has been the application of mutagenesis. Mutagenesis has been instrumental in the discovery and characterization of many plant traits including such that affect biomass yield and quality. In this proposal we use activation tagging to discover genes that can significantly affect biomass associated traits directly in poplar, a premier bioenergy crop. We screened a population of 5,000 independent poplar activation tagging lines under greenhouse conditions for a battery of biomass yield traits. These same plants were then analyzed for changes in wood chemistry using pyMBMS. As a result of these screens we have identified nearly 800 mutants, which are significantly (P<0.05) different when compared to wild type. Of these majority (~700) are affected in one of ten different biomass yield traits and 100 in biomass quality traits (e.g., lignin, S/G ration and C6/C5 sugars). We successfully recovered the position of the tag in approximately 130 lines, showed activation in nearly half of them and performed recapitulation experiments with 20 genes prioritized by the significance of the phenotype. Recapitulation experiments are still ongoing for many of the genes but the results are encouraging. For example, we have shown successful

  19. Linkage of the VNTR/insulin-gene and type I diabetes mellitus: Increased gene sharing in affected sibling pairs

    Energy Technology Data Exchange (ETDEWEB)

    Owerbach, D.; Gabbay, K.H. (Baylor College of Medicine, Houston, TX (United States))

    1994-05-01

    Ninety-six multiplex type I diabetic families were typed at the 5' flanking region of the insulin gene by using a PCR assay that better resolves the VNTR into multiple alleles. Affected sibling pairs shared 2, 1, and 0 VNTR alleles - identical by descent - at a frequency of .47, .45, and .08, respectively, a ratio that deviated from the expected 1:2:1 ratio (P<.001). These results confirm linkage of the chromosome 11p15.5 region with type I diabetes mellitus susceptibility. 20 refs., 2 tabs.

  20. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Directory of Open Access Journals (Sweden)

    Anastasia V. Ponasenko

    2017-01-01

    Full Text Available Infective endocarditis (IE is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

  1. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Science.gov (United States)

    Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

    2017-01-01

    Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

  2. Bovine aortic arch with supravalvular aortic stenosis.

    Science.gov (United States)

    Idhrees, Mohammed; Cherian, Vijay Thomas; Menon, Sabarinath; Mathew, Thomas; Dharan, Baiju S; Jayakumar, K

    2016-09-01

    A 5-year-old boy was diagnosed to have supravalvular aortic stenosis (SVAS). On evaluation of CT angiogram, there was associated bovine aortic arch (BAA). Association of BAA with SVAS has not been previously reported in literature, and to best of our knowledge, this is the first case report of SVAS with BAA. Recent studies show BAA as a marker for aortopathy. SVAS is also an arteriopathy. In light of this, SVAS can also possibly be a manifestation of aortopathy associated with BAA. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  3. Bovine aortic arch with supravalvular aortic stenosis

    Directory of Open Access Journals (Sweden)

    Mohammed Idhrees

    2016-09-01

    Full Text Available A 5-year-old boy was diagnosed to have supravalvular aortic stenosis (SVAS. On evaluation of CT angiogram, there was associated bovine aortic arch (BAA. Association of BAA with SVAS has not been previously reported in literature, and to best of our knowledge, this is the first case report of SVAS with BAA. Recent studies show BAA as a marker for aortopathy. SVAS is also an arteriopathy. In light of this, SVAS can also possibly be a manifestation of aortopathy associated with BAA.

  4. Association between osteopontin and human abdominal aortic aneurysm.

    Science.gov (United States)

    Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

    2007-03-01

    In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

  5. Ultrasonic delineation of aortic microstructure: The relative contribution of elastin and collagen to aortic elasticity

    Science.gov (United States)

    Marsh, Jon N.; Takiuchi, Shin; Lin, Shiow Jiuan; Lanza, Gregory M.; Wickline, Samuel A.

    2004-05-01

    Aortic elasticity is an important factor in hemodynamic health, and compromised aortic compliance affects not only arterial dynamics but also myocardial function. A variety of pathologic processes (e.g., diabetes, Marfan's syndrome, hypertension) can affect aortic elasticity by altering the microstructure and composition of the elastin and collagen fiber networks within the tunica media. Ultrasound tissue characterization techniques can be used to obtain direct measurements of the stiffness coefficients of aorta by measurement of the speed of sound in specific directions. In this study we sought to define the contributions of elastin and collagen to the mechanical properties of aortic media by measuring the magnitude and directional dependence of the speed of sound before and after selective isolation of either the collagen or elastin fiber matrix. Formalin-fixed porcine aortas were sectioned for insonification in the circumferential, longitudinal, or radial direction and examined using high-frequency (50 MHz) ultrasound microscopy. Isolation of the collagen or elastin fiber matrices was accomplished through treatment with NaOH or formic acid, respectively. The results suggest that elastin is the primary contributor to aortic medial stiffness in the unloaded state, and that there is relatively little anisotropy in the speed of sound or stiffness in the aortic wall.

  6. Aortic annulus eccentricity before and after transcatheter aortic valve implantation: Comparison of balloon-expandable and self-expanding prostheses

    International Nuclear Information System (INIS)

    Schuhbaeck, Annika; Weingartner, Christina; Arnold, Martin; Schmid, Jasmin; Pflederer, Tobias; Marwan, Mohamed; Rixe, Johannes; Nef, Holger; Schneider, Christian; Lell, Michael; Uder, Michael; Ensminger, Stephan; Feyrer, Richard; Weyand, Michael; Achenbach, Stephan

    2015-01-01

    Highlights: • Post-implant geometry of catheter-based aortic valve prostheses is influenced by aortic valve calcification. • Balloon-expandable prostheses are more circular as compared to self-expanding prostheses. • The impact of post-implant geometry on valve function needs to be investigated. - Abstract: Introduction: The geometry of the aortic annulus and implanted transcatheter aortic valve prosthesis might influence valve function. We investigated the influence of valve type and aortic valve calcification on post-implant geometry of catheter-based aortic valve prostheses. Methods: Eighty consecutive patients with severe aortic valve stenosis (mean age 82 ± 6 years) underwent computed tomography before and after TAVI. Aortic annulus diameters were determined. Influence of prosthesis type and degree of aortic valve calcification on post-implant eccentricity were analysed. Results: Aortic annulus eccentricity was reduced in patients after TAVI (0.21 ± 0.06 vs. 0.08 ± 0.06, p < 0.0001). Post-TAVI eccentricity was significantly lower in 65 patients following implantation of a balloon-expandable prosthesis as compared to 15 patients who received a self-expanding prosthesis (0.06 ± 0.05 vs. 0.15 ± 0.07, p < 0.0001), even though the extent of aortic valve calcification was not different. After TAVI, patients with a higher calcium amount retained a significantly higher eccentricity compared to patients with lower amounts of calcium. Conclusions: Patients undergoing TAVI with a balloon-expandable prosthesis show a more circular shape of the implanted prosthesis as compared to patients with a self-expanding prosthesis. Eccentricity of the deployed prosthesis is affected by the extent of aortic valve calcification

  7. Candidate genes affecting fat deposition, carcass composition and meat quality traits in pigs

    OpenAIRE

    Gandolfi, Greta

    2011-01-01

    Pig meat quality is determined by several parameters, such as lipid content, tenderness, water-holding capacity, pH, color and flavor, that affect consumers’ acceptance and technological properties of meat. Carcass quality parameters are important for the production of fresh and dry-cure high-quality products, in particular the fat deposition and the lean cut yield. The identification of genes and markers associated with meat and carcass quality traits is of prime interest, for the possibilit...

  8. A Key Gene, PLIN1, Can Affect Porcine Intramuscular Fat Content Based on Transcriptome Analysis

    Directory of Open Access Journals (Sweden)

    Bojiang Li

    2018-04-01

    Full Text Available Intramuscular fat (IMF content is an important indicator for meat quality evaluation. However, the key genes and molecular regulatory mechanisms affecting IMF deposition remain unclear. In the present study, we identified 75 differentially expressed genes (DEGs between the higher (H and lower (L IMF content of pigs using transcriptome analysis, of which 27 were upregulated and 48 were downregulated. Notably, Kyoto Encyclopedia of Genes and Genomes (KEGG enrichment analysis indicated that the DEG perilipin-1 (PLIN1 was significantly enriched in the fat metabolism-related peroxisome proliferator-activated receptor (PPAR signaling pathway. Furthermore, we determined the expression patterns and functional role of porcine PLIN1. Our results indicate that PLIN1 was highly expressed in porcine adipose tissue, and its expression level was significantly higher in the H IMF content group when compared with the L IMF content group, and expression was increased during adipocyte differentiation. Additionally, our results confirm that PLIN1 knockdown decreases the triglyceride (TG level and lipid droplet (LD size in porcine adipocytes. Overall, our data identify novel candidate genes affecting IMF content and provide new insight into PLIN1 in porcine IMF deposition and adipocyte differentiation.

  9. A Key Gene, PLIN1, Can Affect Porcine Intramuscular Fat Content Based on Transcriptome Analysis.

    Science.gov (United States)

    Li, Bojiang; Weng, Qiannan; Dong, Chao; Zhang, Zengkai; Li, Rongyang; Liu, Jingge; Jiang, Aiwen; Li, Qifa; Jia, Chao; Wu, Wangjun; Liu, Honglin

    2018-04-04

    Intramuscular fat (IMF) content is an important indicator for meat quality evaluation. However, the key genes and molecular regulatory mechanisms affecting IMF deposition remain unclear. In the present study, we identified 75 differentially expressed genes (DEGs) between the higher (H) and lower (L) IMF content of pigs using transcriptome analysis, of which 27 were upregulated and 48 were downregulated. Notably, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the DEG perilipin-1 ( PLIN1 ) was significantly enriched in the fat metabolism-related peroxisome proliferator-activated receptor (PPAR) signaling pathway. Furthermore, we determined the expression patterns and functional role of porcine PLIN1. Our results indicate that PLIN1 was highly expressed in porcine adipose tissue, and its expression level was significantly higher in the H IMF content group when compared with the L IMF content group, and expression was increased during adipocyte differentiation. Additionally, our results confirm that PLIN1 knockdown decreases the triglyceride (TG) level and lipid droplet (LD) size in porcine adipocytes. Overall, our data identify novel candidate genes affecting IMF content and provide new insight into PLIN1 in porcine IMF deposition and adipocyte differentiation.

  10. Changes in gravitational force affect gene expression in developing organ systems at different developmental times

    Directory of Open Access Journals (Sweden)

    Moorman Stephen J

    2005-05-01

    Full Text Available Abstract Background Little is known about the affect of microgravity on gene expression, particularly in vivo during embryonic development. Using transgenic zebrafish that express the gfp gene under the influence of a β-actin promoter, we examined the affect of simulated-microgravity on GFP expression in the heart, notochord, eye, somites, and rohon beard neurons. We exposed transgenic zebrafish to simulated-microgravity for different durations at a variety of developmental times in an attempt to determine periods of susceptibility for the different developing organ systems. Results The developing heart had a period of maximum susceptibility between 32 and 56 hours after fertilization when there was an approximately 30% increase in gene expression. The notochord, eye, somites, and rohon beard neurons all showed periods of susceptibility occurring between 24 and 72 hours after fertilization. In addition, the notochord showed a second period of susceptibility between 8 and 32 hours after fertilization. Interestingly, all organs appeared to be recovering by 80 hours after fertilization despite continued exposure to simulated-microgravity. Conclusion These results support the idea that exposure to microgravity can cause changes in gene expression in a variety of developing organ systems in live embryos and that there are periods of maximum susceptibility to the effects.

  11. [Analysis of USH2A gene mutation in a Chinese family affected with Usher syndrome].

    Science.gov (United States)

    Li, Pengcheng; Liu, Fei; Zhang, Mingchang; Wang, Qiufen; Liu, Mugen

    2015-08-01

    To investigate the disease-causing mutation in a Chinese family affected with Usher syndrome type II. All of the 11 members from the family underwent comprehensive ophthalmologic examination and hearing test, and their genomic DNA were isolated from venous leukocytes. PCR and direct sequencing of USH2A gene were performed for the proband. Wild type and mutant type minigene vectors containing exon 42, intron 42 and exon 43 of the USH2A gene were constructed and transfected into Hela cells by lipofectamine reagent. Reverse transcription (RT)-PCR was carried out to verify the splicing of the minigenes. Pedigree analysis and clinical diagnosis indicated that the patients have suffered from autosomal recessive Usher syndrome type II. DNA sequencing has detected a homozygous c.8559-2A>G mutation of the USH2A gene in the proband, which has co-segregated with the disease in the family. The mutation has affected a conserved splice site in intron 42, which has led to inactivation of the splice site. Minigene experiment has confirmed the retaining of intron 42 in mature mRNA. The c.8559-2A>G mutation in the USH2A gene probably underlies the Usher syndrome type II in this family. The splice site mutation has resulted in abnormal splicing of USH2A pre-mRNA.

  12. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions.

    Directory of Open Access Journals (Sweden)

    Nisha Puthiyedth

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation.The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD from the Entorhinal Cortex (EC, Hippocampus (HIP, Middle temporal gyrus (MTG, Posterior cingulate cortex (PC, Superior frontal gyrus (SFG and visual cortex (VCX brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets.We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we

  13. Single Nucleotide Polymorphisms in the HIRA Gene Affect Litter Size in Small Tail Han Sheep

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    Mei Zhou

    2018-05-01

    Full Text Available Maintenance of appropriate levels of fecundity is critical for efficient sheep production. Opportunities to increase sheep litter size include identifying single gene mutations with major effects on ovulation rate and litter size. Whole-genome sequencing (WGS data of 89 Chinese domestic sheep from nine different geographical locations and ten Australian sheep were analyzed to detect new polymorphisms affecting litter size. Comparative genomic analysis of sheep with contrasting litter size detected a novel set of candidate genes. Two SNPs, g.71874104G>A and g.71833755T>C, were genotyped in 760 Small Tail Han sheep and analyzed for association with litter size. The two SNPs were significantly associated with litter size, being in strong linkage disequilibrium in the region 71.80–71.87 Mb. This haplotype block contains one gene that may affect litter size, Histone Cell Cycle Regulator (HIRA. HIRA mRNA levels in sheep with different lambing ability were significantly higher in ovaries of Small Tail Han sheep (high fecundity than in Sunite sheep (low fecundity. Moreover, the expression levels of HIRA in eight tissues of uniparous Small Tail Han sheep were significantly higher than in multiparous Small Tail Han sheep (p < 0.05. HIRA SNPs significantly affect litter size in sheep and are useful as genetic markers for litter size.

  14. Abundance and genetic diversity of nifH gene sequences in anthropogenically affected Brazilian mangrove sediments.

    Science.gov (United States)

    Dias, Armando Cavalcante Franco; Pereira e Silva, Michele de Cassia; Cotta, Simone Raposo; Dini-Andreote, Francisco; Soares, Fábio Lino; Salles, Joana Falcão; Azevedo, João Lúcio; van Elsas, Jan Dirk; Andreote, Fernando Dini

    2012-11-01

    Although mangroves represent ecosystems of global importance, the genetic diversity and abundance of functional genes that are key to their functioning scarcely have been explored. Here, we present a survey based on the nifH gene across transects of sediments of two mangrove systems located along the coast line of São Paulo state (Brazil) which differed by degree of disturbance, i.e., an oil-spill-affected and an unaffected mangrove. The diazotrophic communities were assessed by denaturing gradient gel electrophoresis (DGGE), quantitative PCR (qPCR), and clone libraries. The nifH gene abundance was similar across the two mangrove sediment systems, as evidenced by qPCR. However, the nifH-based PCR-DGGE profiles revealed clear differences between the mangroves. Moreover, shifts in the nifH gene diversities were noted along the land-sea transect within the previously oiled mangrove. The nifH gene diversity depicted the presence of nitrogen-fixing bacteria affiliated with a wide range of taxa, encompassing members of the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Firmicutes, and also a group of anaerobic sulfate-reducing bacteria. We also detected a unique mangrove-specific cluster of sequences denoted Mgv-nifH. Our results indicate that nitrogen-fixing bacterial guilds can be partially endemic to mangroves, and these communities are modulated by oil contamination, which has important implications for conservation strategies.

  15. Abundance and Genetic Diversity of nifH Gene Sequences in Anthropogenically Affected Brazilian Mangrove Sediments

    Science.gov (United States)

    Dias, Armando Cavalcante Franco; Pereira e Silva, Michele de Cassia; Cotta, Simone Raposo; Dini-Andreote, Francisco; Soares, Fábio Lino; Salles, Joana Falcão; Azevedo, João Lúcio; van Elsas, Jan Dirk

    2012-01-01

    Although mangroves represent ecosystems of global importance, the genetic diversity and abundance of functional genes that are key to their functioning scarcely have been explored. Here, we present a survey based on the nifH gene across transects of sediments of two mangrove systems located along the coast line of São Paulo state (Brazil) which differed by degree of disturbance, i.e., an oil-spill-affected and an unaffected mangrove. The diazotrophic communities were assessed by denaturing gradient gel electrophoresis (DGGE), quantitative PCR (qPCR), and clone libraries. The nifH gene abundance was similar across the two mangrove sediment systems, as evidenced by qPCR. However, the nifH-based PCR-DGGE profiles revealed clear differences between the mangroves. Moreover, shifts in the nifH gene diversities were noted along the land-sea transect within the previously oiled mangrove. The nifH gene diversity depicted the presence of nitrogen-fixing bacteria affiliated with a wide range of taxa, encompassing members of the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Firmicutes, and also a group of anaerobic sulfate-reducing bacteria. We also detected a unique mangrove-specific cluster of sequences denoted Mgv-nifH. Our results indicate that nitrogen-fixing bacterial guilds can be partially endemic to mangroves, and these communities are modulated by oil contamination, which has important implications for conservation strategies. PMID:22941088

  16. Pleiotropic Genes Affecting Carcass Traits in Bos indicus (Nellore Cattle Are Modulators of Growth.

    Directory of Open Access Journals (Sweden)

    Anirene G T Pereira

    Full Text Available Two complementary methods, namely Multi-Trait Meta-Analysis and Versatile Gene-Based Test for Genome-wide Association Studies (VEGAS, were used to identify putative pleiotropic genes affecting carcass traits in Bos indicus (Nellore cattle. The genotypic data comprised over 777,000 single-nucleotide polymorphism markers scored in 995 bulls, and the phenotypic data included deregressed breeding values (dEBV for weight measurements at birth, weaning and yearling, as well visual scores taken at weaning and yearling for carcass finishing precocity, conformation and muscling. Both analyses pointed to the pleomorphic adenoma gene 1 (PLAG1 as a major pleiotropic gene. VEGAS analysis revealed 224 additional candidates. From these, 57 participated, together with PLAG1, in a network involved in the modulation of the function and expression of IGF1 (insulin like growth factor 1, IGF2 (insulin like growth factor 2, GH1 (growth hormone 1, IGF1R (insulin like growth factor 1 receptor and GHR (growth hormone receptor, suggesting that those pleiotropic genes operate as satellite regulators of the growth pathway.

  17. Methods for interpreting lists of affected genes obtained in a DNA microarray experiment

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    Hedegaard Jakob

    2009-07-01

    Full Text Available Abstract Background The aim of this paper was to describe and compare the methods used and the results obtained by the participants in a joint EADGENE (European Animal Disease Genomic Network of Excellence and SABRE (Cutting Edge Genomics for Sustainable Animal Breeding workshop focusing on post analysis of microarray data. The participating groups were provided with identical lists of microarray probes, including test statistics for three different contrasts, and the normalised log-ratios for each array, to be used as the starting point for interpreting the affected probes. The data originated from a microarray experiment conducted to study the host reactions in broilers occurring shortly after a secondary challenge with either a homologous or heterologous species of Eimeria. Results Several conceptually different analytical approaches, using both commercial and public available software, were applied by the participating groups. The following tools were used: Ingenuity Pathway Analysis, MAPPFinder, LIMMA, GOstats, GOEAST, GOTM, Globaltest, TopGO, ArrayUnlock, Pathway Studio, GIST and AnnotationDbi. The main focus of the approaches was to utilise the relation between probes/genes and their gene ontology and pathways to interpret the affected probes/genes. The lack of a well-annotated chicken genome did though limit the possibilities to fully explore the tools. The main results from these analyses showed that the biological interpretation is highly dependent on the statistical method used but that some common biological conclusions could be reached. Conclusion It is highly recommended to test different analytical methods on the same data set and compare the results to obtain a reliable biological interpretation of the affected genes in a DNA microarray experiment.

  18. Progranulin gene variation affects serum progranulin levels differently in Danish bipolar individuals compared with healthy controls.

    Science.gov (United States)

    Buttenschøn, Henriette N; Nielsen, Marit N; Thotakura, Gangadaar; Lee, Chris W; Nykjær, Anders; Mors, Ole; Glerup, Simon

    2017-06-01

    The identification of peripheral biomarkers for bipolar disorder is of great importance and has the potential to improve diagnosis, treatment and prognosis. Recent studies have reported lower plasma progranulin levels in bipolar individuals compared with controls and association with single nucleotide polymorphisms (SNPs) within the progranulin gene (GRN). In the present study, we investigated the effect of GRN and sortilin (SORT1) gene variation on serum progranulin levels in bipolar individuals and controls. In a Danish cohort of individuals with bipolar disorder and controls, we analysed the serum progranulin level (nbipolar=80, ncontrols=76) and five SNPs located within GRN and two SNPs near the SORT1 gene encoding sortilin, a progranulin scavenger receptor known to affect circulating progranulin levels (nbipolar=166, ncontrols=186). We observed no significant difference in the serum progranulin level between cases and controls and none of the analysed SNPs located within GRN or close to SORT1 were associated with bipolar disorder. Crude and adjusted (adjusted for case-control status, sex and age) linear regression analyses showed no effect of any SNPs on the serum progranulin level. However, we observed that the mean serum progranulin level in cases and controls is affected differently depending on the genotypes of two SNPs within GRN (rs2879096 and rs4792938). The sample size is relatively small and detailed information on medication and polarity of the disorder is not available. No correction for multiple testing was performed. Our study suggests that the potential of progranulin as a biomarker for bipolar disorder is genotype dependent.

  19. Factors affecting expression of the recF gene of Escherichia coli K-12.

    Science.gov (United States)

    Sandler, S J; Clark, A J

    1990-01-31

    This report describes four factors which affect expression of the recF gene from strong upstream lambda promoters under temperature-sensitive cIAt2-encoded repressor control. The first factor was the long mRNA leader sequence consisting of the Escherichia coli dnaN gene and 95% of the dnaA gene and lambda bet, N (double amber) and 40% of the exo gene. When most of this DNA was deleted, RecF became detectable in maxicells. The second factor was the vector, pBEU28, a runaway replication plasmid. When we substituted pUC118 for pBEU28, RecF became detectable in whole cells by the Coomassie blue staining technique. The third factor was the efficiency of initiation of translation. We used site-directed mutagenesis to change the mRNA leader, ribosome-binding site and the 3 bp before and after the translational start codon. Monitoring the effect of these mutational changes by translational fusion to lacZ, we discovered that the efficiency of initiation of translation was increased 30-fold. Only an estimated two- or threefold increase in accumulated levels of RecF occurred, however. This led us to discover the fourth factor, namely sequences in the recF gene itself. These sequences reduce expression of the recF-lacZ fusion genes 100-fold. The sequences responsible for this decrease in expression occur in four regions in the N-terminal half of recF. Expression is reduced by some sequences at the transcriptional level and by others at the translational level.

  20. Traumatic Aortic Injury

    Directory of Open Access Journals (Sweden)

    Brianna Miner

    2016-09-01

    Full Text Available History of present illness: A 48-year-old male with unknown past medical history presents as a trauma after being hit by a car traveling approximately 25 miles per hour. On initial presentation, the patient is confused, combative, and not answering questions appropriately. The patient is hypotensive with a blood pressure of 68/40 and a heart rate of 50 beats per minute, with oxygen saturation at 96% on room air. FAST scan is positive for fluid in Morrison’s pouch, splenorenal space, and pericardial space. Significant findings: The initial chest x-ray showed an abnormal superior mediastinal contour (blue line, suggestive of a possible aortic injury. The CT angiogram showed extensive circumferential irregularity and outpouching of the distal aortic arch (red arrows compatible with aortic transection. In addition, there was a circumferential intramural hematoma, which extended through the descending aorta to the proximal infrarenal abdominal aorta (green arrow. There was also an extensive surrounding mediastinal hematoma extending around the descending aorta and supraaortic branches (purple arrows. Discussion: Traumatic aortic injury is a life-threatening event. The incidence of blunt thoracic aortic injury is low, between 1 to 2 percent of those patients with blunt thoracic trauma.1 However, approximately 80% of patients with traumatic aortic injury die at the scene.2 Therefore it is imperative to diagnose traumatic aortic injury in a timely fashion. The diagnosis can be difficult due to the non-specific signs and symptoms and other distracting injuries. Clinical suspicion should be based on the mechanism of the injury and the hemodynamic status of the patient. In any patient with blunt or penetrating trauma to the chest that is hemodynamically unstable, traumatic aortic injury should be on the differential. Chest x-ray can be used as a screening tool. A normal chest x-ray has a negative predictive value of approximately 97%. CTA chest is the

  1. Biased perception about gene technology: How perceived naturalness and affect distort benefit perception.

    Science.gov (United States)

    Siegrist, Michael; Hartmann, Christina; Sütterlin, Bernadette

    2016-01-01

    In two experiments, the participants showed biased responses when asked to evaluate the benefits of gene technology. They evaluated the importance of additional yields in corn fields due to a newly introduced variety, which would increase a farmer's revenues. In one condition, the newly introduced variety was described as a product of traditional breeding; in the other, it was identified as genetically modified (GM). The two experiments' findings showed that the same benefits were perceived as less important for a farmer when these were the result of GM crops compared with traditionally bred crops. Mediation analyses suggest that perceived naturalness and the affect associated with the technology per se influence the interpretation of the new information. The lack of perceived naturalness of gene technology seems to be the reason for the participants' perceived lower benefits of a new corn variety in the gene technology condition compared with the perceptions of the participants assigned to the traditional breeding condition. The strategy to increase the acceptance of gene technology by introducing plant varieties that better address consumer and producer needs may not work because people discount its associated benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Association between the dopamine D3 receptor gene locus (DRD3) and unipolar affective disorder.

    Science.gov (United States)

    Dikeos, D G; Papadimitriou, G N; Avramopoulos, D; Karadima, G; Daskalopoulou, E G; Souery, D; Mendlewicz, J; Vassilopoulos, D; Stefanis, C N

    1999-12-01

    Dopamine neurotransmission has been implicated in the pathophysiology of schizophrenia and, more recently, affective disorders. Among the dopamine receptors, D3 can be considered as particularly related to affective disorders due to its neuroanatomical localization in the limbic region of the brain and its relation to the serotoninergic activity of the CNS. The possible involvement of dopamine receptor D3 in unipolar (UP) major depression was investigated by a genetic association study of the D3 receptor gene locus (DRD3) on 36 UP patients and 38 ethnically matched controls. An allelic association of DRD3 (Bal I polymorphism) and UP illness was observed, with the Gly-9 allele (allele '2', 206/98 base-pairs long) being more frequent in patients than in controls (49% vs 29%, P < 0.02). The genotypes containing this allele (1-2 and 2-2) were found in 75% of patients vs 50% of controls (P < 0.03, odds ratio = 3.00, 95% CI = 1.12-8.05). The effect of the genotype remained significant (P < 0.02) after sex and family history were controlled by a multiple linear regression analysis. These results further support the hypothesis that dopaminergic mechanisms may be implicated in the pathogenesis of affective disorder. More specifically, the '2' allele of the dopamine receptor D3 gene seems to be associated with unipolar depression and can be considered as a 'phenotypic modifier' for major psychiatric disorders.

  3. Left ventricular hypertrophy in valvular aortic stenosis: mechanisms and clinical implications.

    Science.gov (United States)

    Rader, Florian; Sachdev, Esha; Arsanjani, Reza; Siegel, Robert J

    2015-04-01

    Valvular aortic stenosis is the second most prevalent adult valve disease in the United States and causes progressive pressure overload, invariably leading to life-threatening complications. Surgical aortic valve replacement and, more recently, transcatheter aortic valve replacement effectively relieve the hemodynamic burden and improve the symptoms and survival of affected individuals. However, according to current American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, the indications for aortic valve replacement, including transcatheter aortic valve replacement, are based primarily on the development of clinical symptoms, because their presence indicates a dismal prognosis. Left ventricular hypertrophy develops in a sizeable proportion of patients before the onset of symptoms, and a growing body of literature demonstrates that regression of left ventricular hypertrophy resulting from aortic stenosis is incomplete after aortic valve replacement and associated with adverse early postoperative outcomes and worse long-term outcomes. Thus, reliance on the development of symptoms alone without consideration of structural abnormalities of the myocardium for optimal timing of aortic valve replacement potentially constitutes a missed opportunity to prevent postoperative morbidity and mortality from severe aortic stenosis, especially in the face of the quickly expanding indications of lower-risk transcatheter aortic valve replacement. The purpose of this review is to discuss the mechanisms and clinical implications of left ventricular hypertrophy in severe valvular aortic stenosis, which may eventually move to center stage as an indication for aortic valve replacement in the asymptomatic patient. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Affect

    NARCIS (Netherlands)

    Cetinic, M.; Diamanti, J.; Szeman, I.; Blacker, S.; Sully, J.

    2017-01-01

    This chapter historicizes four divergent but historically contemporaneous genres of affect theory – romantic, realist, speculative, and materialist. While critics credited with the turn to affect in the 1990s wrote largely in the wake of poststructuralism from the perspective of gender and queer

  5. Selective Aortic Arch and Root Replacement in Repair of Acute Type A Aortic Dissection.

    Science.gov (United States)

    Fleischman, Fernando; Elsayed, Ramsey S; Cohen, Robbin G; Tatum, James M; Kumar, S Ram; Kazerouni, Kayvan; Mack, Wendy J; Barr, Mark L; Cunningham, Mark J; Hackmann, Amy E; Baker, Craig J; Starnes, Vaughn A; Bowdish, Michael E

    2018-02-01

    Controversy exists regarding the optimal extent of repair for type A aortic dissection. Our approach is to replace the ascending aorta, and only replace the aortic root or arch when intimal tears are present in those areas. We examined intermediate outcomes with this approach to acute type A aortic dissection repair. Between March 2005 and October 2016, 195 patients underwent repair of acute type A aortic dissection. Repair was categorized by site of proximal and distal anastomosis and extent of repair. Mean follow-up was 31.0 ± 30.9 months. Kaplan-Meier analysis was used to assess survival. Multiple variable Cox proportional hazards modeling was utilized to identify factors associated with overall mortality. Overall survival was 85.1%, 83.9%, 79.1%, and 74.4% at 6, 12, 36, and 60 months, respectively. Eight patients required reintervention. The cumulative incidence of aortic reintervention at 1 year with death as a competing outcome was 3.95%. Multiple variable regression analysis identified factors such as age, preoperative renal failure, concomitant thoracic endograft, postoperative myocardial infarction and sepsis, and need for extracorporeal membrane oxygenation as predictive of overall mortality. Neither proximal or distal extent of repair, nor need for reintervention affected overall survival (proximal: hazard ratio 1.63, 95% confidence interval: 0.75 to 3.51, p = 0.22; distal: hazard ratio 1.12, 95% confidence interval: 0.43 to 2.97, p = 0.81; reintervention: hazard ratio 0.03, 95% confidence interval: 0.002 to 0.490, p < 0.01). A selective approach to root and arch repair in acute type A aortic dissection is safe. If aortic reintervention is needed, survival does not appear to be affected. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Aortic valve replacement for aortic stenosis caused by alkaptonuria.

    Science.gov (United States)

    Hiroyoshi, Junko; Saito, Aya; Panthee, Nirmal; Imai, Yasushi; Kawashima, Dai; Motomura, Noboru; Ono, Minoru

    2013-03-01

    We report a case of aortic stenosis associated with ochronosis in a 70-year-old man who underwent biologic aortic valve replacement. Intraoperative findings included ochronosis of a severely calcified pigmented aortic valve along with pigmentation of the intima of the aorta. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Vanillin Differentially Affects Azoxymethane-Injected Rat Colon Carcinogenesis and Gene Expression

    Science.gov (United States)

    Ho, Ket Li; Chong, Pei Pei; Yazan, Latifah Saiful

    2012-01-01

    Abstract Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rats were treated with vanillin orally and intraperitoneally at low and high concentrations and ACF density, multiplicity, and distribution were observed. The gene expression of 14 colorectal cancer-related genes was also studied. Results showed that vanillin consumed orally had no effect on ACF. However, high concentrations (300 mg/kg body weight) of vanillin administered through intraperitoneal injection could increase ACF density and ACF multiplicity. ACF were mainly found in the distal colon rather than in the mid-section and proximal colon. The expression of colorectal cancer biomarkers, protooncogenes, recombinational repair, mismatch repair, and cell cycle arrest, and tumor suppressor gene expression were also affected by vanillin. Vanillin was not cocarcinogenic when consumed orally. However, it was cocarcinogenic when being administered intraperitoneally at high concentration. Hence, the use of vanillin in food should be safe but might have cocarcinogenic potential when it is used in high concentration for therapeutic purposes. PMID:23216109

  8. Downregulation of RWA genes in hybrid aspen affects xylan acetylation and wood saccharification.

    Science.gov (United States)

    Pawar, Prashant Mohan-Anupama; Ratke, Christine; Balasubramanian, Vimal K; Chong, Sun-Li; Gandla, Madhavi Latha; Adriasola, Mathilda; Sparrman, Tobias; Hedenström, Mattias; Szwaj, Klaudia; Derba-Maceluch, Marta; Gaertner, Cyril; Mouille, Gregory; Ezcurra, Ines; Tenkanen, Maija; Jönsson, Leif J; Mellerowicz, Ewa J

    2017-06-01

    High acetylation of angiosperm wood hinders its conversion to sugars by glycoside hydrolases, subsequent ethanol fermentation and (hence) its use for biofuel production. We studied the REDUCED WALL ACETYLATION (RWA) gene family of the hardwood model Populus to evaluate its potential for improving saccharification. The family has two clades, AB and CD, containing two genes each. All four genes are expressed in developing wood but only RWA-A and -B are activated by master switches of the secondary cell wall PtNST1 and PtMYB21. Histochemical analysis of promoter::GUS lines in hybrid aspen (Populus tremula × tremuloides) showed activation of RWA-A and -B promoters in the secondary wall formation zone, while RWA-C and -D promoter activity was diffuse. Ectopic downregulation of either clade reduced wood xylan and xyloglucan acetylation. Suppressing both clades simultaneously using the wood-specific promoter reduced wood acetylation by 25% and decreased acetylation at position 2 of Xylp in the dimethyl sulfoxide-extracted xylan. This did not affect plant growth but decreased xylose and increased glucose contents in the noncellulosic monosaccharide fraction, and increased glucose and xylose yields of wood enzymatic hydrolysis without pretreatment. Both RWA clades regulate wood xylan acetylation in aspen and are promising targets to improve wood saccharification. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  9. Reprogramming Methods Do Not Affect Gene Expression Profile of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Trevisan, Marta; Desole, Giovanna; Costanzi, Giulia; Lavezzo, Enrico; Palù, Giorgio; Barzon, Luisa

    2017-01-20

    Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts. The reprogramming efficiency of the methods based on episomal and Sendai virus vectors was higher than that of the retroviral vector-based approach. All human iPSC clones derived with the different methods showed the typical features of pluripotent stem cells, including the expression of alkaline phosphatase and stemness maker genes, and could give rise to the three germ layer derivatives upon embryoid bodies assay. Microarray analysis confirmed the presence of typical stem cell gene expression profiles in all iPSC clones and did not identify any significant difference among reprogramming methods. In conclusion, the use of different reprogramming methods is equivalent and does not affect gene expression profile of the derived human iPSCs.

  10. Reprogramming Methods Do Not Affect Gene Expression Profile of Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Marta Trevisan

    2017-01-01

    Full Text Available Induced pluripotent stem cells (iPSCs are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts. The reprogramming efficiency of the methods based on episomal and Sendai virus vectors was higher than that of the retroviral vector-based approach. All human iPSC clones derived with the different methods showed the typical features of pluripotent stem cells, including the expression of alkaline phosphatase and stemness maker genes, and could give rise to the three germ layer derivatives upon embryoid bodies assay. Microarray analysis confirmed the presence of typical stem cell gene expression profiles in all iPSC clones and did not identify any significant difference among reprogramming methods. In conclusion, the use of different reprogramming methods is equivalent and does not affect gene expression profile of the derived human iPSCs.

  11. Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, I.L.; Sudhalter, V.; Nolin, S.L. [New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)

    1996-08-09

    Fragile X syndrome is one of the most common forms of inherited mental retardation, and the first of a new class of genetic disorders associated with expanded trinucleotide repeats. Previously, we found that about 41% of affected males are mosaic for this mutation in that some of their blood cells have an active fragile X gene and others do not. It has been hypothesized that these mosaic cases should show higher levels of functioning than those who have only the inactive full mutation gene, but previous studies have provided negative or equivocal results. In the present study, the cross-sectional development of communication, self-care, socialization, and motor skills was studied in 46 males with fragile X syndrome under age 20 years as a function of two variables: age and the presence or absence of mosaicism. The rate of adaptive skills development was 2-4 times as great in mosaic cases as in full mutation cases. There was also a trend for cases with autism to be more prevalent in the full-mutation group. These results have implications for prognosis, for the utility of gene or protein replacement therapies for this disorder, and for understanding the association between mental retardation, developmental disorders, and fragile X syndrome. 21 refs., 3 figs.

  12. Gain-of-function screen for genes that affect Drosophila muscle pattern formation.

    Directory of Open Access Journals (Sweden)

    Nicole Staudt

    2005-10-01

    Full Text Available This article reports the production of an EP-element insertion library with more than 3,700 unique target sites within the Drosophila melanogaster genome and its use to systematically identify genes that affect embryonic muscle pattern formation. We designed a UAS/GAL4 system to drive GAL4-responsive expression of the EP-targeted genes in developing apodeme cells to which migrating myotubes finally attach and in an intrasegmental pattern of cells that serve myotubes as a migration substrate on their way towards the apodemes. The results suggest that misexpression of more than 1.5% of the Drosophila genes can interfere with proper myotube guidance and/or muscle attachment. In addition to factors already known to participate in these processes, we identified a number of enzymes that participate in the synthesis or modification of protein carbohydrate side chains and in Ubiquitin modifications and/or the Ubiquitin-dependent degradation of proteins, suggesting that these processes are relevant for muscle pattern formation.

  13. Diversity of the Genes Implicated in Algerian Patients Affected by Usher Syndrome.

    Science.gov (United States)

    Abdi, Samia; Bahloul, Amel; Behlouli, Asma; Hardelin, Jean-Pierre; Makrelouf, Mohamed; Boudjelida, Kamel; Louha, Malek; Cheknene, Ahmed; Belouni, Rachid; Rous, Yahia; Merad, Zahida; Selmane, Djamel; Hasbelaoui, Mokhtar; Bonnet, Crystel; Zenati, Akila; Petit, Christine

    2016-01-01

    Usher syndrome (USH) is an autosomal recessive disorder characterized by a dual sensory impairment affecting hearing and vision. USH is clinically and genetically heterogeneous. Ten different causal genes have been reported. We studied the molecular bases of the disease in 18 unrelated Algerian patients by targeted-exome sequencing, and identified the causal biallelic mutations in all of them: 16 patients carried the mutations at the homozygous state and 2 at the compound heterozygous state. Nine of the 17 different mutations detected in MYO7A (1 of 5 mutations), CDH23 (4 of 7 mutations), PCDH15 (1 mutation), USH1C (1 mutation), USH1G (1 mutation), and USH2A (1 of 2 mutations), had not been previously reported. The deleterious consequences of a missense mutation of CDH23 (p.Asp1501Asn) and the in-frame single codon deletion in USH1G (p.Ala397del) on the corresponding proteins were predicted from the solved 3D-structures of extracellular cadherin (EC) domains of cadherin-23 and the sterile alpha motif (SAM) domain of USH1G/sans, respectively. In addition, we were able to show that the USH1G mutation is likely to affect the binding interface between the SAM domain and USH1C/harmonin. This should spur the use of 3D-structures, not only of isolated protein domains, but also of protein-protein interaction interfaces, to predict the functional impact of mutations detected in the USH genes.

  14. Nonsense mutations in the human β-globin gene affect mRNA metabolism

    International Nuclear Information System (INIS)

    Baserga, S.J.; Benz, E.J. Jr.

    1988-01-01

    A number of premature translation termination mutations (nonsense mutations) have been described in the human α- and β-globin genes. Studies on mRNA isolated from patients with β 0 -thalassemia have shown that for both the β-17 and the β-39 mutations less than normal levels of β-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human β-globin mRNA). In vitro studies using the cloned β-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. The authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human β-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation

  15. Pathogenetic Basis of Aortopathy and Aortic Valve Disease

    Science.gov (United States)

    2018-02-19

    Aortopathies; Thoracic Aortic Aneurysm; Aortic Valve Disease; Thoracic Aortic Disease; Thoracic Aortic Dissection; Thoracic Aortic Rupture; Ascending Aortic Disease; Descending Aortic Disease; Ascending Aortic Aneurysm; Descending Aortic Aneurysm; Marfan Syndrome; Loeys-Dietz Syndrome; Ehlers-Danlos Syndrome; Shprintzen-Goldberg Syndrome; Turner Syndrome; PHACE Syndrome; Autosomal Recessive Cutis Laxa; Congenital Contractural Arachnodactyly; Arterial Tortuosity Syndrome

  16. Bioaerosols from a food waste composting plant affect human airway epithelial cell remodeling genes.

    Science.gov (United States)

    Chang, Min-Wei; Lee, Chung-Ru; Hung, Hsueh-Fen; Teng, Kuo-Sheng; Huang, Hsin; Chuang, Chun-Yu

    2013-12-24

    The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 10(2) conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5-10 μm) having higher endotoxin levels than did fine particles (0.5-2.5 μm). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1 (p21 WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers.

  17. Bioaerosols from a Food Waste Composting Plant Affect Human Airway Epithelial Cell Remodeling Genes

    Science.gov (United States)

    Chang, Ming-Wei; Lee, Chung-Ru; Hung, Hsueh-Fen; Teng, Kuo-Sheng; Huang, Hsin; Chuang, Chun-Yu

    2013-01-01

    The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 102 conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5–10 μm) having higher endotoxin levels than did fine particles (0.5–2.5 μm). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers. PMID:24368426

  18. Myocardial gene expression of microRNA-133a and myosin heavy and light chains, in conjunction with clinical parameters, predict regression of left ventricular hypertrophy after valve replacement in patients with aortic stenosis.

    Science.gov (United States)

    Villar, Ana V; Merino, David; Wenner, Mareike; Llano, Miguel; Cobo, Manuel; Montalvo, Cecilia; García, Raquel; Martín-Durán, Rafael; Hurlé, Juan M; Hurlé, María A; Nistal, J Francisco

    2011-07-01

    Left ventricular (LV) reverse remodelling after valve replacement in aortic stenosis (AS) has been classically linked to the hydraulic performance of the replacement device, but myocardial status at the time of surgery has received little attention. To establish predictors of LV mass (LVM) regression 1 year after valve replacement in a surgical cohort of patients with AS based on preoperative clinical and echocardiographic parameters and the myocardial gene expression profile at surgery. Transcript levels of remodelling-related proteins and regulators were determined in LV intraoperative biopsies from 46 patients with AS by RT-PCR. Using multiple linear regression analysis, an equation was developed (adjusted R²=0.73; pregression analysis identified microRNA-133a as a significant positive predictor of LVM normalisation, whereas β-myosin heavy chain and BMI constituted negative predictors. Hypertrophy regression 1 year after pressure overload release is related to the preoperative myocardial expression of remodelling-related genes, in conjunction with the patient's clinical background. In this scenario, miR-133 emerges as a key element of the reverse remodelling process. Postoperative improvement of valve haemodynamics does not predict the degree of hypertrophy regression or LVM normalisation. These results led us to reconsider the current reverse remodelling paradigm and (1) to include criteria of hypertrophy reversibility in the decision algorithm used to decide timing for the operation; and (2) to modify other prevailing factors (overweight, diabetes, etc) known to maintain LV hypertrophy.

  19. Robotic aortic surgery.

    Science.gov (United States)

    Duran, Cassidy; Kashef, Elika; El-Sayed, Hosam F; Bismuth, Jean

    2011-01-01

    Surgical robotics was first utilized to facilitate neurosurgical biopsies in 1985, and it has since found application in orthopedics, urology, gynecology, and cardiothoracic, general, and vascular surgery. Surgical assistance systems provide intelligent, versatile tools that augment the physician's ability to treat patients by eliminating hand tremor and enabling dexterous operation inside the patient's body. Surgical robotics systems have enabled surgeons to treat otherwise untreatable conditions while also reducing morbidity and error rates, shortening operative times, reducing radiation exposure, and improving overall workflow. These capabilities have begun to be realized in two important realms of aortic vascular surgery, namely, flexible robotics for exclusion of complex aortic aneurysms using branched endografts, and robot-assisted laparoscopic aortic surgery for occlusive and aneurysmal disease.

  20. Subinhibitory concentrations of antibiotics affect stress and virulence gene expression in Listeria monocytogenes and cause enhanced stress sensitivity but do not affect Caco‐2 cell invasion

    DEFF Research Database (Denmark)

    Knudsen, Gitte Maegaard; Holch, Anne; Gram, Lone

    2012-01-01

    with promoter fusions, 14 of 16 antibiotics induced or repressed expression of one or more stress and/or virulence genes. Despite ampicillin‐induced up‐regulation of PinlA‐lacZ expression, Caco‐2 cell invasion was not affected. Subinhibitory concentrations of ampicillin and tetracycline caused up‐ and down...

  1. Aortic valve replacement

    DEFF Research Database (Denmark)

    Kapetanakis, Emmanouil I; Athanasiou, Thanos; Mestres, Carlos A

    2008-01-01

    mortality were collected. Group analysis by patient geographic distribution and by annular diameter of the prosthesis utilized was conducted. Patients with a manufacturer's labeled prosthesis size > or = 21 mm were assigned to the 'large' aortic size subset, while those with a prosthesis size ... differences in the distribution of either gender or BSA. In the multivariable model, south European patients were seven times more likely to receive a smaller-sized aortic valve (OR = 6.5, 95% CI = 4.82-8.83, p

  2. Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in Senescence-Accelerated Mice P1.

    Science.gov (United States)

    Chen, Jianglei; Fan, Jun; Wang, Shirley; Sun, Zhongjie

    2018-05-01

    Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by shortened lifespan and early signs of senescence. Klotho is an aging-suppressor gene. The purpose of this study is to investigate whether in vivo expression of secreted klotho ( Skl ) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1 mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80, and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation. An increase in expression of α-smooth muscle actin (myofibroblast marker), transforming growth factorβ-1, and scleraxis (a transcription factor of collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting that accelerated aging is associated with myofibroblast transition and collagen gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA for in vivo expression of Skl. Skl gene delivery effectively increased serum Skl of SAMP1 mice to the control level. Skl gene delivery inhibited inflammation and myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves. Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl cDNA effectively suppresses inflammation and myofibroblastic transition and attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for fibrotic aortic valve disease. © 2018 American Heart Association, Inc.

  3. DISC1 gene and affective psychopathology: a combined structural and functional MRI study.

    Science.gov (United States)

    Opmeer, Esther M; van Tol, Marie-José; Kortekaas, Rudie; van der Wee, Nic J A; Woudstra, Saskia; van Buchem, Mark A; Penninx, Brenda W; Veltman, Dick J; Aleman, André

    2015-02-01

    The gene Disrupted-In-Schizophrenia-1 (DISC1) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISC1 differentially modulates brain function during executive and memory processing, and morphology in regions relevant for depression and anxiety disorders (affective disorders). 128 participants, with (n = 103) and without (controls; n = 25) affective disorders underwent genotyping for Ser704Cys (with Cys-allele considered as risk-allele) and structural and functional (f) Magnetic Resonance Imaging (MRI) during visuospatial planning and emotional episodic memory tasks. For both voxel-based morphometry and fMRI analyses, we investigated the effect of genotype in controls and explored genotypeXdiagnosis interactions. Results are reported at p < 0.05 FWE small volume corrected. In controls, Cys-carriers showed smaller bilateral (para)hippocampal volumes compared with Ser-homozygotes, and lower activation in the anterior cingulate cortex (ACC) and dorsolateral PFC during visuospatial planning. In anxiety patients, Cys-carriers showed larger (para)hippocampal volumes and more ACC activation during visuospatial planning. In depressive patients, no effect of genotype was observed and overall, no effect of genotype on episodic memory processing was detected. We demonstrated that Ser704Cys-genotype influences (para)hippocampal structure and functioning the dorsal PFC during executive planning, most prominently in unaffected controls. Results suggest that presence of psychopathology moderates Ser704Cys effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Silver nanoparticles administered to chicken affect VEGFA and FGF2 gene expression in breast muscle and heart

    DEFF Research Database (Denmark)

    Hotowy, Anna Malgorzata; Sawosz, Ewa; Pineda, Lane Manalili

    2012-01-01

    Nanoparticles of colloidal silver (AgNano) can influence gene expression. Concerning trials of AgNano application in poultry as antimicrobial and metabolic agents, it is useful to reveal whether they affect the expression of genes crucial for bird development. AgNano were administered to broiler...... chickens as a water solution in two concentrations (10 and 20 ppm). After dissection of the birds, breast muscles and hearts were collected. Gene expression of FGF2 and VEGF on the mRNA and protein levels were evaluated using qPCR and ELISA methods. The results for gene expression in breast muscle revealed...

  5. Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

    International Nuclear Information System (INIS)

    Puddu, A.; Storace, D.; Odetti, P.; Viviani, G.L.

    2010-01-01

    Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic β-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

  6. C282Y-HFE gene variant affects cholesterol metabolism in human neuroblastoma cells.

    Science.gov (United States)

    Ali-Rahmani, Fatima; Huang, Michael A; Schengrund, C-L; Connor, James R; Lee, Sang Y

    2014-01-01

    Although disruptions in the maintenance of iron and cholesterol metabolism have been implicated in several cancers, the association between variants in the HFE gene that is associated with cellular iron uptake and cholesterol metabolism has not been studied. The C282Y-HFE variant is a risk factor for different cancers, is known to affect sphingolipid metabolism, and to result in increased cellular iron uptake. The effect of this variant on cholesterol metabolism and its possible relevance to cancer phenotype was investigated using wild type (WT) and C282Y-HFE transfected human neuroblastoma SH-SY5Y cells. Expression of C282Y-HFE in SH-SY5Y cells resulted in a significant increase in total cholesterol as well as increased transcription of a number of genes involved in its metabolism compared to cells expressing WT-HFE. The marked increase in expression of NPC1L1 relative to that of most other genes, was accompanied by a significant increase in expression of NPC1, a protein that functions in cholesterol uptake by cells. Because inhibitors of cholesterol metabolism have been proposed to be beneficial for treating certain cancers, their effect on the viability of C282Y-HFE neuroblastoma cells was ascertained. C282Y-HFE cells were significantly more sensitive than WT-HFE cells to U18666A, an inhibitor of desmosterol Δ24-reductase the enzyme catalyzing the last step in cholesterol biosynthesis. This was not seen for simvastatin, ezetimibe, or a sphingosine kinase inhibitor. These studies indicate that cancers presenting in carriers of the C282Y-HFE allele might be responsive to treatment designed to selectively reduce cholesterol content in their tumor cells.

  7. The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells.

    Science.gov (United States)

    Rimmerman, Neta; Juknat, Ana; Kozela, Ewa; Levy, Rivka; Bradshaw, Heather B; Vogel, Zvi

    2011-08-01

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ(9)-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD's anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed.

  8. Arabidopsis flower specific defense gene expression patterns affect resistance to pathogens

    KAUST Repository

    Ederli, Luisa

    2015-02-20

    We investigated whether the Arabidopsis flower evolved protective measures to increase reproductive success. Firstly, analyses of available transcriptome data show that the most highly expressed transcripts in the closed sepal (stage 12) are enriched in genes with roles in responses to chemical stimuli and cellular metabolic processes. At stage 15, there is enrichment in transcripts with a role in responses to biotic stimuli. Comparative analyses between the sepal and petal in the open flower mark an over-representation of transcripts with a role in responses to stress and catalytic activity. Secondly, the content of the biotic defense-associated phytohormone salicylic acid (SA) in sepals and petals is significantly higher than in leaves. To understand whether the high levels of stress responsive transcripts and the higher SA content affect defense, wild-type plants (Col-0) and transgenic plants defective in SA accumulation (nahG) were challenged with the biotrophic fungus Golovinomyces cichoracearum, the causal agent of powdery mildew, and the necrotrophic fungus Botrytis cinerea. NahG leaves were more sensitive than those of Col-0, suggesting that in leaves SA has a role in the defense against biotrophs. In contrast, sepals and petals of both genotypes were resistant to G. cichoracearum, indicating that in the flower, resistance to the biotrophic pathogen is not critically dependent on SA, but likely dependent on the up-regulation of stress-responsive genes. Since sepals and petals of both genotypes are equally susceptible to B. cinerea, we conclude that neither stress-response genes nor increased SA accumulation offers protection against the necrotrophic pathogen. These results are interpreted in the light of the distinctive role of the flower and we propose that in the early stages, the sepal may act as a chemical defense barrier of the developing reproductive structures against biotrophic pathogens.

  9. Characterization of three Agrobacterium tumefaciens avirulent mutants with chromosomal mutations that affect induction of vir genes.

    Science.gov (United States)

    Metts, J; West, J; Doares, S H; Matthysse, A G

    1991-02-01

    Three Agrobacterium tumefaciens mutants with chromosomal mutations that affect bacterial virulence were isolated by transposon mutagenesis. Two of the mutants were avirulent on all hosts tested. The third mutant, Ivr-211, was a host range mutant which was avirulent on Bryophyllum diagremontiana, Nicotiana tabacum, N. debneyi, N. glauca, and Daucus carota but was virulent on Zinnia elegans and Lycopersicon esculentum (tomato). That the mutant phenotype was due to the transposon insertion was determined by cloning the DNA containing the transposon insertion and using the cloned DNA to replace the wild-type DNA in the parent bacterial strain by marker exchange. The transposon insertions in the three mutants mapped at three widely separated locations on the bacterial chromosome. The effects of the mutations on various steps in tumor formation were examined. All three mutants showed no alteration in binding to carrot cells. However, none of the mutants showed any induction of vir genes by acetosyringone under conditions in which the parent strain showed vir gene induction. When the mutant bacteria were examined for changes in surface components, it was found that all three of the mutants showed a similar alteration in lipopolysaccharide (LPS). LPS from the mutants was larger in size and more heavily saccharide substituted than LPS from the parent strain. Two of the mutants showed no detectable alteration in outer membrane and periplasmic space proteins. The third mutant, Ivr-225, was missing a 79-kDa surface peptide. The reason(s) for the failure of vir gene induction in these mutants and its relationship, if any, to the observed alteration in LPS are unknown.

  10. Variable gene dispersal conditions and spatial deforestation patterns can interact to affect tropical tree conservation outcomes.

    Directory of Open Access Journals (Sweden)

    Yamini Kashimshetty

    Full Text Available Tropical lowland rain forest (TLRF biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG, which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively than spatial logging pattern (0.2% and 4.7% respectively, with 'Near' distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene

  11. Diversity of the Genes Implicated in Algerian Patients Affected by Usher Syndrome.

    Directory of Open Access Journals (Sweden)

    Samia Abdi

    Full Text Available Usher syndrome (USH is an autosomal recessive disorder characterized by a dual sensory impairment affecting hearing and vision. USH is clinically and genetically heterogeneous. Ten different causal genes have been reported. We studied the molecular bases of the disease in 18 unrelated Algerian patients by targeted-exome sequencing, and identified the causal biallelic mutations in all of them: 16 patients carried the mutations at the homozygous state and 2 at the compound heterozygous state. Nine of the 17 different mutations detected in MYO7A (1 of 5 mutations, CDH23 (4 of 7 mutations, PCDH15 (1 mutation, USH1C (1 mutation, USH1G (1 mutation, and USH2A (1 of 2 mutations, had not been previously reported. The deleterious consequences of a missense mutation of CDH23 (p.Asp1501Asn and the in-frame single codon deletion in USH1G (p.Ala397del on the corresponding proteins were predicted from the solved 3D-structures of extracellular cadherin (EC domains of cadherin-23 and the sterile alpha motif (SAM domain of USH1G/sans, respectively. In addition, we were able to show that the USH1G mutation is likely to affect the binding interface between the SAM domain and USH1C/harmonin. This should spur the use of 3D-structures, not only of isolated protein domains, but also of protein-protein interaction interfaces, to predict the functional impact of mutations detected in the USH genes.

  12. Variable gene dispersal conditions and spatial deforestation patterns can interact to affect tropical tree conservation outcomes.

    Science.gov (United States)

    Kashimshetty, Yamini; Pelikan, Stephan; Rogstad, Steven H

    2015-01-01

    Tropical lowland rain forest (TLRF) biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG), which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring) had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively) than spatial logging pattern (0.2% and 4.7% respectively), with 'Near' distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene dispersal

  13. Yeast genes involved in regulating cysteine uptake affect production of hydrogen sulfide from cysteine during fermentation.

    Science.gov (United States)

    Huang, Chien-Wei; Walker, Michelle E; Fedrizzi, Bruno; Gardner, Richard C; Jiranek, Vladimir

    2017-08-01

    An early burst of hydrogen sulfide (H2S) produced by Saccharomyces cerevisiae during fermentation could increase varietal thiols and therefore enhance desirable tropical aromas in varieties such as Sauvignon Blanc. Here we attempted to identify genes affecting H2S formation from cysteine by screening yeast deletion libraries via a colony colour assay on media resembling grape juice. Both Δlst4 and Δlst7 formed lighter coloured colonies and produced significantly less H2S than the wild type on high concentrations of cysteine, likely because they are unable to take up cysteine efficiently. We then examined the nine known cysteine permeases and found that deletion of AGP1, GNP1 and MUP1 led to reduced production of H2S from cysteine. We further showed that deleting genes involved in the SPS-sensing pathway such as STP1 and DAL81 also reduced H2S from cysteine. Together, this study indirectly confirms that Agp1p, Gnp1p and Mup1p are the major cysteine permeases and that they are regulated by the SPS-sensing and target of rapamycin pathways under the grape juice-like, cysteine-supplemented, fermentation conditions. The findings highlight that cysteine transportation could be a limiting factor for yeast to generate H2S from cysteine, and therefore selecting wine yeasts without defects in cysteine uptake could maximise thiol production potential. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Do circadian genes and ambient temperature affect substrate-borne signalling during Drosophila courtship?

    Directory of Open Access Journals (Sweden)

    Izarne Medina

    2015-11-01

    Full Text Available Courtship vibratory signals can be air-borne or substrate-borne. They convey distinct and species-specific information from one individual to its prospective partner. Here, we study the substrate-borne vibratory signals generated by the abdominal quivers of the Drosophila male during courtship; these vibrations travel through the ground towards courted females and coincide with female immobility. It is not known which physical parameters of the vibrations encode the information that is received by the females and induces them to pause. We examined the intervals between each vibratory pulse, a feature that was reported to carry information for animal communication. We were unable to find evidence of periodic variations in the lengths of these intervals, as has been reported for fly acoustical signals. Because it was suggested that the genes involved in the circadian clock may also regulate shorter rhythms, we search for effects of period on the interval lengths. Males that are mutant for the period gene produced vibrations with significantly altered interpulse intervals; also, treating wild type males with constant light results in similar alterations to the interpulse intervals. Our results suggest that both the clock and light/dark cycles have input into the interpulse intervals of these vibrations. We wondered if we could alter the interpulse intervals by other means, and found that ambient temperature also had a strong effect. However, behavioural analysis suggests that only extreme ambient temperatures can affect the strong correlation between female immobility and substrate-borne vibrations.

  15. Gene Expression Profiles in Paired Gingival Biopsies from Periodontitis-Affected and Healthy Tissues Revealed by Massively Parallel Sequencing

    Science.gov (United States)

    Båge, Tove; Lagervall, Maria; Jansson, Leif; Lundeberg, Joakim; Yucel-Lindberg, Tülay

    2012-01-01

    Periodontitis is a chronic inflammatory disease affecting the soft tissue and bone that surrounds the teeth. Despite extensive research, distinctive genes responsible for the disease have not been identified. The objective of this study was to elucidate transcriptome changes in periodontitis, by investigating gene expression profiles in gingival tissue obtained from periodontitis-affected and healthy gingiva from the same patient, using RNA-sequencing. Gingival biopsies were obtained from a disease-affected and a healthy site from each of 10 individuals diagnosed with periodontitis. Enrichment analysis performed among uniquely expressed genes for the periodontitis-affected and healthy tissues revealed several regulated pathways indicative of inflammation for the periodontitis-affected condition. Hierarchical clustering of the sequenced biopsies demonstrated clustering according to the degree of inflammation, as observed histologically in the biopsies, rather than clustering at the individual level. Among the top 50 upregulated genes in periodontitis-affected tissues, we investigated two genes which have not previously been demonstrated to be involved in periodontitis. These included interferon regulatory factor 4 and chemokine (C-C motif) ligand 18, which were also expressed at the protein level in gingival biopsies from patients with periodontitis. In conclusion, this study provides a first step towards a quantitative comprehensive insight into the transcriptome changes in periodontitis. We demonstrate for the first time site-specific local variation in gene expression profiles of periodontitis-affected and healthy tissues obtained from patients with periodontitis, using RNA-seq. Further, we have identified novel genes expressed in periodontitis tissues, which may constitute potential therapeutic targets for future treatment strategies of periodontitis. PMID:23029519

  16. Double aortic arch

    Science.gov (United States)

    Surgery can be done to fix double aortic arch. The surgeon ties off the smaller branch and separates it from the larger branch. Then the surgeon closes the ends of the aorta with stitches. This relieves pressure on the esophagus and windpipe.

  17. Bicuspid aortic valve

    Science.gov (United States)

    ... aortic disease. In: Otto CM, Bonow RO, eds. Valvular Heart Disease: A Companion to Braunwald’s Heart Disease . 4th ed. ... PA: Elsevier Saunders; 2014:chap 13. Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman’s Cecil ...

  18. Aortic Valve Stenosis

    Science.gov (United States)

    ... most cases, doctors don't know why a heart valve fails to develop properly, so it isn't something you could have prevented. Calcium buildup on the valve. With age, heart valves may accumulate deposits of calcium (aortic valve ...

  19. Mastication markedly affects mandibular condylar cartilage growth, gene expression, and morphology.

    Science.gov (United States)

    Enomoto, Akiko; Watahiki, Junichi; Nampo, Tomoki; Irie, Tarou; Ichikawa, Yuuta; Tachikawa, Tetsuhiko; Maki, Koutaro

    2014-09-01

    Mandibular growth is believed to be strongly related to mastication. Furthermore, mandibular condylar cartilage is known to be derived from neural crest cells. We examined whether the degree of chewing affects condylar cartilage growth of the mandible. Mice were fed diets with varying hardness. Genes specific to neural crest-derived cells were measured by real-time polymerase chain reaction to compare the expression changes between the mandibular and tibia cartilages. The mandibular condylar cartilage was then evaluated histologically, and proliferation was evaluated using proliferating cell nuclear antigen. Immunostaining was conducted for osteopontin, type X collagen, and Musashi1, and real-time polymerase chain reaction was used to assess the expression levels of osteopontin and type X collagen. Markers including P75, Wnt-1, Musashi1, and Nestin were upregulated in the mandibular condylar cartilage as compared with the tibial cartilage. Histologic assessment of the mandibular cartilage showed that the hypertrophic chondrocyte zone was statistically significantly thicker in mice fed a hard diet. Chondrocyte proliferation and Musashi1 expression were lower in mice fed a hard diet. After 4 weeks, numerous osteopontin and type X collagen-positive cells were observed in mice fed a mixed diet. Mastication affects the balance between differentiation and proliferation in the mandibular condylar cartilage. This phenomenon might be attributed to the presence of neural crest-derived cells. Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  20. System-level analysis of genes and functions affecting survival during nutrient starvation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Gresham, David; Boer, Viktor M; Caudy, Amy; Ziv, Naomi; Brandt, Nathan J; Storey, John D; Botstein, David

    2011-01-01

    An essential property of all cells is the ability to exit from active cell division and persist in a quiescent state. For single-celled microbes this primarily occurs in response to nutrient deprivation. We studied the genetic requirements for survival of Saccharomyces cerevisiae when starved for either of two nutrients: phosphate or leucine. We measured the survival of nearly all nonessential haploid null yeast mutants in mixed populations using a quantitative sequencing method that estimates the abundance of each mutant on the basis of frequency of unique molecular barcodes. Starvation for phosphate results in a population half-life of 337 hr whereas starvation for leucine results in a half-life of 27.7 hr. To measure survival of individual mutants in each population we developed a statistical framework that accounts for the multiple sources of experimental variation. From the identities of the genes in which mutations strongly affect survival, we identify genetic evidence for several cellular processes affecting survival during nutrient starvation, including autophagy, chromatin remodeling, mRNA processing, and cytoskeleton function. In addition, we found evidence that mitochondrial and peroxisome function is required for survival. Our experimental and analytical methods represent an efficient and quantitative approach to characterizing genetic functions and networks with unprecedented resolution and identified genotype-by-environment interactions that have important implications for interpretation of studies of aging and quiescence in yeast.

  1. Psoriatic T cells reduce epidermal turnover time and affect cell proliferation contributed from differential gene expression.

    Science.gov (United States)

    Li, Junqin; Li, Xinhua; Hou, Ruixia; Liu, Ruifeng; Zhao, Xincheng; Dong, Feng; Wang, Chunfang; Yin, Guohua; Zhang, Kaiming

    2015-09-01

    Psoriasis is mediated primarily by T cells, which reduce epidermal turnover time and affect keratinocyte proliferation. We aimed to identify differentially expressed genes (DEG) in T cells from normal, five pairs of monozygotic twins concordant or discordant for psoriasis, to determine whether these DEG may account for the influence to epidermal turnover time and keratinocyte proliferation. The impact of T cells on keratinocyte proliferation and epidermal turnover time were investigated separately by immunohistochemistry and cultured with (3) H-TdR. mRNA expression patterns were investigated by RNA sequencing and verified by real-time reverse transcription polymerase chain reaction. After co-culture with psoriatic T cells, the expression of Ki-67, c-Myc and p53 increased, while expression of Bcl-2 and epidermal turnover time decreased. There were 14 DEG which were found to participate in the regulation of cell proliferation or differentiation. Psoriatic T cells exhibited the ability to decrease epidermal turnover time and affect keratinocyte proliferation because of the differential expression of PPIL1, HSPH1, SENP3, NUP54, FABP5, PLEKHG3, SLC9A9 and CHCHD4. © 2015 Japanese Dermatological Association.

  2. Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G/+ Marfan Mouse Model

    NARCIS (Netherlands)

    Hibender, Stijntje; Franken, Romy; van Roomen, Cindy; ter Braake, Anique; van der Made, Ingeborg; Schermer, Edith E.; Gunst, Quinn; van den Hoff, Maurice J.; Lutgens, Esther; Pinto, Yigal M.; Groenink, Maarten; Zwinderman, Aeilko H.; Mulder, Barbara J. M.; de Vries, Carlie J. M.; de Waard, Vivian

    2016-01-01

    Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure-lowering drugs are used to reduce aortic events; however, this is not sufficient for most patients. In

  3. Genes of the most conserved WOX clade in plants affect root and flower development in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Moreau Hervé

    2008-10-01

    Full Text Available Abstract Background The Wuschel related homeobox (WOX family proteins are key regulators implicated in the determination of cell fate in plants by preventing cell differentiation. A recent WOX phylogeny, based on WOX homeodomains, showed that all of the Physcomitrella patens and Selaginella moellendorffii WOX proteins clustered into a single orthologous group. We hypothesized that members of this group might preferentially share a significant part of their function in phylogenetically distant organisms. Hence, we first validated the limits of the WOX13 orthologous group (WOX13 OG using the occurrence of other clade specific signatures and conserved intron insertion sites. Secondly, a functional analysis using expression data and mutants was undertaken. Results The WOX13 OG contained the most conserved plant WOX proteins including the only WOX detected in the highly proliferating basal unicellular and photosynthetic organism Ostreococcus tauri. A large expansion of the WOX family was observed after the separation of mosses from other land plants and before monocots and dicots have arisen. In Arabidopsis thaliana, AtWOX13 was dynamically expressed during primary and lateral root initiation and development, in gynoecium and during embryo development. AtWOX13 appeared to affect the floral transition. An intriguing clade, represented by the functional AtWOX14 gene inside the WOX13 OG, was only found in the Brassicaceae. Compared to AtWOX13, the gene expression profile of AtWOX14 was restricted to the early stages of lateral root formation and specific to developing anthers. A mutational insertion upstream of the AtWOX14 homeodomain sequence led to abnormal root development, a delay in the floral transition and premature anther differentiation. Conclusion Our data provide evidence in favor of the WOX13 OG as the clade containing the most conserved WOX genes and established a functional link to organ initiation and development in Arabidopsis, most

  4. Sequencing and transcriptional analysis of the Streptococcus thermophilus histamine biosynthesis gene cluster: factors that affect differential hdcA expression

    DEFF Research Database (Denmark)

    Calles-Enríquez, Marina; Hjort, Benjamin Benn; Andersen, Pia Skov

    2010-01-01

    to produce histamine. The hdc clusters of S. thermophilus CHCC1524 and CHCC6483 were sequenced, and the factors that affect histamine biosynthesis and histidine-decarboxylating gene (hdcA) expression were studied. The hdc cluster began with the hdcA gene, was followed by a transporter (hdcP), and ended...... with the hdcB gene, which is of unknown function. The three genes were orientated in the same direction. The genetic organization of the hdc cluster showed a unique organization among the lactic acid bacterial group and resembled those of Staphylococcus and Clostridium species, thus indicating possible...... acquisition through a horizontal transfer mechanism. Transcriptional analysis of the hdc cluster revealed the existence of a polycistronic mRNA covering the three genes. The histidine-decarboxylating gene (hdcA) of S. thermophilus demonstrated maximum expression during the stationary growth phase, with high...

  5. Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum

    Energy Technology Data Exchange (ETDEWEB)

    Tsukue, Naomi [Tokyo University of Science, Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Noda, Chiba (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); Japan Automobile Research Institute, Health Effects Research Group, Energy and Environment Research Division, Tsukuba, Ibaraki (Japan); Watanabe, Manabu; Kumamoto, Takayuki; Takeda, Ken [Tokyo University of Science, Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Noda, Chiba (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); Takano, Hirohisa [Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); National Institute for Environmental Studies, Pathophysiology Research Team, Tsukuba, Ibaraki (Japan)

    2009-11-15

    Many environmental toxins alter reproductive function and affect the central nervous system (CNS). Gonadal steroid hormones cause differentiation of neurons and affect brain function and behavior during the perinatal period, and the CNS is thought to be particularly susceptible to toxic insult during this period. It was, therefore, hypothesized that inhalation of diesel exhaust (DE) during the fetal or suckling period would disrupt the sexual differentiation of brain function in mice, and the effects of exposure to DE during the perinatal period on sexual differentiation related gene expression of the brain were investigated. In the fetal period exposure group, pregnant ICR mice were exposed to DE from 1.5 days post-coitum (dpc) until 16 dpc. In the neonatal period exposure group, dams and their offspring were exposed to DE from the day of birth [postnatal day (PND)-0] until PND-16. Then, the cerebrums of males and females at PND-2, -5, and -16 from both groups were analyzed for expression level of mRNA encoding stress-related proteins [cytochrome P450 1A1 (CYP1A1), heme oxygenase-1 (HO-1)] and steroid hormone receptors [estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR)]. Expression levels of ER alpha and ER beta mRNA were increased in the cerebrum of newborns in the DE exposure groups as well as mRNA for CYP1A1 and HO-1. Results indicate that perinatal exposure to DE during the critical period of sexual differentiation of the brain may affect endocrine function. (orig.)

  6. Rapid pannus formation after few months of obstructing aortic mechanical prosthesis.

    Science.gov (United States)

    Al-Alao, Bassel; Simoniuk, Urszula; Heron, Brian; Parissis, Haralabos

    2015-11-01

    We report a rare case of a prosthetic aortic valve obstruction due to pannus formation only 3 months following aortic and mitral valve replacement. Fragments of asymmetrical pannus formation affected one of the leaflets of the bi-leaflet mechanical valve; the leaflet appeared immobile due to pannus ingrowth into the mechanical skeleton resulting in encroachment of the leaflet, which in turn became immobile. The patient successfully underwent emergency redo-aortic valve replacement.

  7. Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study.

    Science.gov (United States)

    Papadimitriou, George N; Dikeos, Dimitris G; Souery, Daniel; Del-Favero, Jurgen; Massat, Isabelle; Avramopoulos, Dimitrios; Blairy, Sylvie; Cichon, Sven; Ivezic, Sladjana; Kaneva, Radka; Karadima, Georgia; Lilli, Roberta; Milanova, Vihra; Nöthen, Markus; Oruc, Lilijana; Rietschel, Marcella; Serretti, Alessandro; Van Broeckhoven, Christine; Stefanis, Costas N; Mendlewicz, Julien

    2003-12-01

    The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.

  8. Impact of Aortic Insufficiency on Ascending Aortic Dilatation and Adverse Aortic Events After Isolated Aortic Valve Replacement in Patients With a Bicuspid Aortic Valve.

    Science.gov (United States)

    Wang, Yongshi; Wu, Boting; Li, Jun; Dong, Lili; Wang, Chunsheng; Shu, Xianhong

    2016-05-01

    Aberrant flow pattern and congenital fragility bestows bicuspid aortic valve (BAV) with a propensity toward ascending aorta dilatation, aneurysm, and dissection. Whether isolated aortic valve replacement (AVR) can prevent further dilatation in BAV ascending aorta and what indicates concurrent aortic intervention in the case of valve operation remain controversial. From June 2006 to January 2009, patients with a BAV who underwent isolated AVR were consecutively included and categorized into aortic insufficiency (BAV-AI, n = 84) and aortic stenosis (n = 112) groups, and another population of patients with a tricuspid aortic valve with aortic insufficiency (n = 149) was also recruited during the same period for comparison of annual aortic dilatation rate and adverse aortic events after isolated AVR. With a median follow-up period of 72 months (interquartile range, 66 to 78 months), ascending aorta dilatation rates were faster in the BAV-AI group than the BAV plus aortic stenosis and tricuspid aortic valve with aortic insufficiency groups (both p regression analysis identified aortic insufficiency (hazard ratio, 3.7; 95% confidence interval, 1.2 to 11.1; p = 0.019) as an independent risk factor for adverse aortic events among patients with BAV in general, whereas preoperative ascending aortic diameter larger than 45 mm (hazard ratio, 13.8; 95% confidence interval, 3.0 to 63.3; p = 0.001) served as a prognostic indicator in the BAV-AI group. An aggressive policy of preventive aortic interventions seemed appropriate in patients with BAV-AI during AVR, and BAV phenotype presenting as either insufficiency or stenosis should be taken into consideration when contemplating optimal surgical strategies for BAV aortopathy. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Light quality affects flavonoid production and related gene expression in Cyclocarya paliurus.

    Science.gov (United States)

    Liu, Yang; Fang, Shengzuo; Yang, Wanxia; Shang, Xulan; Fu, Xiangxiang

    2018-02-01

    Understanding the responses of plant growth and secondary metabolites to differential light conditions is very important to optimize cultivation conditions of medicinal woody plants. As a highly valued and multiple function tree species, Cyclocarya paliurus is planted and managed for timber production and medical use. In this study, LED-based light including white light (WL), blue light (BL), red light (RL), and green light (GL) were used to affect leaf biomass production, flavonoid accumulation and related gene expression of one-year C. paliurus seedlings in controlled environments. After the treatments of 60 days, the highest leaf biomass appeared in the treatment of WL, while the lowest leaf biomass was found under GL. Compared to WL, the total flavonoid contents of C. paliurus leaves were significantly higher in BL, RL, and GL, but the highest values of selected flavonoids (kaempferol, isoquercitrin and quercetin) were observed under BL. Furthermore, the greatest yields of total and selected flavonoids in C. paliurus leaves per seedling were also achieved under BL, indicating that blue light was effective for inducing the production of flavonoids in C. paliurus leaves. Pearson's correlation analysis showed that there were significantly positive correlations between leaf flavonoid content and relative gene expression of key enzymes (phenylalanine ammonia lyase, PAL; 4-coumaroyl CoA-ligase, 4CL; and chalcone synthase, CHS) in the upstream, which converting phenylalanine into the flavonoid skeleton of tetrahydroxy chalcone. It is concluded that manipulating light quality may be potential mean to achieve the highest yields of flavonoids in C. paliurus cultivation, however this needs to be further verified by more field trials. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    International Nuclear Information System (INIS)

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J. Jr; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M.

    2013-01-01

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g -1 ·min -1 ) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g -1 ·min -1 ) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring

  11. A new self-expandable aortic valved stent deployed above native leaflets for aortic insufficiency: an in vitro study.

    Science.gov (United States)

    Huang, H; Zhou, Y; Shao, J; Cai, J; Mei, Y; Wang, Y

    2012-12-01

    The aim of this paper was to develop a new self-expandable aortic valved stent following the shape of the sinus of Valsalva, which can be deployed above native leaflets for aortic regurgitation, and study it's effect on coronary artery flow when orthotopic implantation in and above native leaflets. New self-expandable aortic valved stent consist of nitinol stent and bovine pericardium, and was designed following the shape of the sinus of Valsalva, the bovine pericardium was tailed as native leaflet. Thirty-six swine hearts were divided into three equal groups of twelve. In Group A (N.=12), the new self-expandable aortic valved stents deployed in native leaflets. In Group B (N.=12), the new self-expandable aortic valved stents deployed above native leaflets. In Group C (N.=12), the cylinder-like valved stents deployed only in native leaflets. The measurements of each coronary flow rate and endoscopic inspections were repeated post-implantation. In Group A and C, valve implantation in native leaflets resulted in a significant decrease in both left and right coronary flows. In Group B, no significant change in either right or left coronary flow was found after new self-expandable aortic valved stent placement. Endoscopic inspections showed that in group A and C the native leaflets sandwiched between valved stent and aortic wall, whereas, in group B the native leaflets were under the artificial leaflets. Two kinds of stents deployed in native leaflets affect left and right coronary flows significantly. No significant effect was found when the new self-expandable aortic valved stent deployed above native leaflets. This new self-expandable aortic valved stent can be deployed above the native leaflets, which avoids the obstruction of native leaflets on coronary flow.

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

    Science.gov (United States)

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

    2015-02-01

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

  13. Fluoride at non-toxic dose affects odontoblast gene expression in vitro

    International Nuclear Information System (INIS)

    Wurtz, Tilmann; Houari, Sophia; Mauro, Nicole; MacDougall, Mary; Peters, Heiko; Berdal, Ariane

    2008-01-01

    Elevated fluoride intake may lead to local tissue disturbances, known as fluorosis. Towards an understanding of this effect, fluoride-induced molecular responses were analyzed in MO6-G3 cultured odontoblasts cells. NaF at 1 mM changed expression of genes implicated in tissue formation and growth, without affecting cell proliferation or inducing stress factor RNAs. Up to 1 mM NaF, DNA accumulation was not inhibited, whereas at 3 mM, cells detached from their support and did not proliferate. Intracellular structures, characterized by EM, were normal up to 1 mM, but at 3 mM, necrotic features were evident. No sign of apoptotic transformation appeared at any NaF concentration. Fluoride-sensitive genes were identified by microarray analysis; expression levels of selected RNAs were determined by conventional and real-time RT-PCR. At 1 mM fluoride, RNAs encoding the extracellular matrix proteins asporin and fibromodulin, and the cell membrane associated proteins periostin and IMT2A were 10-fold reduced. RNA coding for signaling factor TNF-receptor 9 was diminished to one-third, whereas that for the chemokine Scya-5 was enhanced 2.5-fold. These RNAs are present in vivo in tooth forming cells. This was demonstrated by in situ hybridization and RT-PCR on RNA from dissected tissue samples; for the presence and functioning of fibromodulin in dentin matrix, a more comprehensive study has earlier been performed by others [Goldberg, M., Septier, D., Oldberg, A., Young, M.F., Ameye, L.G., 2006. Fibromodulin deficient mice display impaired collagen fibrillogenesis in predentin as well as altered dentin mineralization and enamel formation. J. Histochem. Cytochem. 54, 525-537]. Expression of most other RNA species, in particular of stress factor coding RNAs, was not altered. It was concluded that fluoride could influence the transcription pattern without inducing cell stress or apoptosis. In odontoblasts in vivo, aberrant expression of these fluoride-sensitive genes may impair the

  14. Missense mutation in GRN gene affecting RNA splicing and plasma progranulin level in a family affected by frontotemporal lobar degeneration.

    Science.gov (United States)

    Luzzi, Simona; Colleoni, Lara; Corbetta, Paola; Baldinelli, Sara; Fiori, Chiara; Girelli, Francesca; Silvestrini, Mauro; Caroppo, Paola; Giaccone, Giorgio; Tagliavini, Fabrizio; Rossi, Giacomina

    2017-06-01

    Gene coding for progranulin, GRN, is a major gene linked to frontotemporal lobar degeneration. While most of pathogenic GRN mutations are null mutations leading to haploinsufficiency, GRN missense mutations do not have an obvious pathogenicity, and only a few have been revealed to act through different pathogenetic mechanisms, such as cytoplasmic missorting, protein degradation, and abnormal cleavage by elastase. The aim of this study was to disclose the pathogenetic mechanisms of the GRN A199V missense mutation, which was previously reported not to alter physiological progranulin features but was associated with a reduced plasma progranulin level. After investigating the family pedigree, we performed genetic and biochemical analysis on its members and performed RNA expression studies. We found that the mutation segregates with the disease and discovered that its pathogenic feature is the alteration of GRN mRNA splicing, actually leading to haploinsufficiency. Thus, when facing with a missense GRN mutation, its pathogenetic effects should be investigated, especially if associated with low plasma progranulin levels, to determine its nature of either benign polymorphism or pathogenic mutation. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Effect of aging on the configurational change of the aortic arch

    Directory of Open Access Journals (Sweden)

    Atsuhiro Kojima

    2016-04-01

    Full Text Available We explored the relationship between aging and the configuration of the aortic arch using computed tomography angiography (CTA. We retrospectively reviewed CTA obtained in 140 cases. The configuration of the aortic arch was categorized into three types based on the criteria mentioned by Madhwal et al., and the relationships between each configuration and patient characteristics were analyzed. Anomalies of the aortic arch were also explored. Twenty patients had a type-1 aortic arch (mean age, 56.1 years, 30 patients had a type-2 aortic arch (mean age, 66.3 years, and 89 patients had a type-3 aortic arch (mean age, 71.7 years. The mean age of patients with a type-3 aortic arch was significantly higher than that of patients with a type-1 aortic arch. No significant correlations between the type of aortic arch and other factors, such as smoking habit, were seen. The configuration of the aortic arch in our study appears to be significantly affected by the age of the patients.

  16. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    Science.gov (United States)

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. I219V polymorphism in hMLH1 gene in patients affected with ulcerative colitis.

    Science.gov (United States)

    Vietri, Maria Teresa; Riegler, Gabriele; De Paola, Marialaura; Simeone, Serena; Boggia, Maria; Improta, Alessia; Parisi, Mariarita; Molinari, Anna Maria; Cioffi, Michele

    2009-04-01

    hMLH1 gene, lying on chromosome 3p21-23, is a key factor of the mismatch repair (MMR) complex, which amends DNA replication errors. MMR alterations are involved in the development of both hereditary and sporadic forms of colorectal carcinoma related to ulcerative colitis (UC). I219V Polymorphism is located on exon 8 of hMLH1 and provides an aminoacidic substitution of isoleucine to valine, on the protein codon 219. This may affect the speed and fidelity of protein synthesis because of a tRNA paucity or changes in the mRNA secondary structure. Most of the hereditary nonpolyposis colon cancer-associated missense mutations of hMLH1 cause structural changes of the amino- or carboxy-terminal regions, involving the domains that interact with ATP and hPMS2. In this study, we analyzed the hMLH1 I219V polymorphism frequency in colectomized patients with UC. Venous blood from 100 ulcerative patients and 97 apparently healthy subjects has been collected. Out of 100 patients affected with UC, 75 noncolectomized showed an alternating course of disease, while 25 did not respond to the common drugs, and underwent colectomy. Genotyping was performed by polymerase chain reaction and following enzymatic digestion by BccI. No significant differences were found between patients with UC and controls both for genotype and allele frequencies. However, our data show a significant association when colectomized and noncolectomized patients are compared. The frequencies of G homozygosity were 28% in colectomized and 10.7% in noncolectomized patients (p < 0.05, chi(2) = 4.4, Odds ratio = 3.3). The allele frequencies of allele A were 52% in colectomized and 68% in noncolectomized patients; while those of allele G were 48% and 32%, respectively. I219V polymorphism in hMLH1 could influence the clinical course of the disease and lead to resistance to therapy.

  18. Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex

    International Nuclear Information System (INIS)

    Golubovskaya, Vita M.; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Wang, Dan; Cance, William G.

    2014-01-01

    Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53 +/+ and p53 −/− cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53 +/+ cells but not in p53 −/− cells. Among up-regulated genes in HCT p53 +/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53 +/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach

  19. Acute Aortic Arch Perforation During Transcatheter Aortic Valve Replacement in Bicuspid Aortic Stenosis and a Gothic Aortic Arch.

    Science.gov (United States)

    Millan-Iturbe, Oscar; Sawaya, Fadi J; Bieliauskas, Gintautas; Chow, Danny H F; De Backer, Ole; Søndergaard, Lars

    2017-09-01

    Transcatheter aortic valve replacement (TAVR) has evolved from a novel technology to an established therapy for high/intermediate-risk patients with severe symptomatic aortic stenosis (AS). Although TAVR is used to treat bicuspid severe AS, the large randomized trials typically excluded bicuspid AS because of its unique anatomic features. This case report describes an acute aortic perforation during delivery of a transcatheter heart valve to treat a severe bicuspid AS with a "gothic aortic arch"; more careful evaluation of the preprocedural multislice computed tomographic scan would have unveiled a sharply angulated aortic arch. This life-threatening complication was successfully treated by thoracic endovascular aortic repair. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  20. A mutation in the aroE gene affects pigment production, virulence, and chemotaxis in Xanthomonas oryzae pv. oryzae.

    Science.gov (United States)

    Kim, Hong-Il; Noh, Tae-Hwan; Lee, Chang-Soo; Park, Young-Jin

    2015-01-01

    Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight (BB) in rice. To study its function, a random insertion mutation library of Xoo was constructed using the Tn5 transposon. A mutant strain with decreased virulence against the susceptible rice cultivar IR24 was isolated from the library (aroE mutant), which also had extremely low pigment production. Thermal asymmetric interlaced-polymerase chain reaction (TAIL-PCR) and sequence analysis of the mutant revealed that the transposon was inserted into the aroE gene (encoding shikimate dehydrogenase). To investigate gene expression changes in the pigment- and virulence-deficient mutant, DNA microarray analysis was performed, which showed downregulation of 20 genes involved in the chemotaxis of Xoo. Our findings reveal that mutation of the aroE gene affects virulence and pigment production, as well as expression of genes involved in Xoo chemotaxis. Copyright © 2014 Elsevier GmbH. All rights reserved.

  1. Transcription factor organic cation transporter 1 (OCT-1 affects the expression of porcine Klotho (KL gene

    Directory of Open Access Journals (Sweden)

    Yan Li

    2016-07-01

    Full Text Available Klotho (KL, originally discovered as an aging suppressor, is a membrane protein that shares sequence similarity with the β-glucosidase enzymes. Recent reports showed Klotho might play a role in adipocyte maturation and systemic glucose metabolism. However, little is known about the transcription factors involved in regulating the expression of porcine KL gene. Deletion fragment analysis identified KL-D2 (−418 bp to −3 bp as the porcine KL core promoter. MARC0022311SNP (A or G in KL intron 1 was detected in Landrace × DIV pigs using the Porcine SNP60 BeadChip. The pGL-D2-A and pGL-D2-G were constructed with KL-D2 and the intron fragment of different alleles and relative luciferase activity of pGL3-D2-G was significantly higher than that of pGL3-D2-A in the PK cells and ST cells. This was possibly the result of a change in KL binding ability with transcription factor organic cation transporter 1 (OCT-1, which was confirmed using electrophoretic mobility shift assays (EMSA and chromatin immune-precipitation (ChIP. Moreover, OCT-1 regulated endogenous KL expression by RNA interference experiments. Our study indicates SNP MARC0022311 affects porcine KL expression by regulating its promoter activity via OCT-1.

  2. Serotonin transporter gene-linked polymorphism affects detection of facial expressions.

    Directory of Open Access Journals (Sweden)

    Ai Koizumi

    Full Text Available Previous studies have demonstrated that the serotonin transporter gene-linked polymorphic region (5-HTTLPR affects the recognition of facial expressions and attention to them. However, the relationship between 5-HTTLPR and the perceptual detection of others' facial expressions, the process which takes place prior to emotional labeling (i.e., recognition, is not clear. To examine whether the perceptual detection of emotional facial expressions is influenced by the allelic variation (short/long of 5-HTTLPR, happy and sad facial expressions were presented at weak and mid intensities (25% and 50%. Ninety-eight participants, genotyped for 5-HTTLPR, judged whether emotion in images of faces was present. Participants with short alleles showed higher sensitivity (d' to happy than to sad expressions, while participants with long allele(s showed no such positivity advantage. This effect of 5-HTTLPR was found at different facial expression intensities among males and females. The results suggest that at the perceptual stage, a short allele enhances the processing of positive facial expressions rather than that of negative facial expressions.

  3. Association of aortic and main left coronary aneurysms with severe aortic insufficiency in Takayasu’s arteritis

    Directory of Open Access Journals (Sweden)

    Marcelo Ferraz de Freitas

    2011-04-01

    Full Text Available Takayasu’s arteritis is a granulomatous vasculitis of unknown etiology that affects mainly the aorta and its branches. As a result of intimal fibroproliferation, segmental stenosis, occlusion, dilatation, and aneurysmal formation of the involved vessels may develop. It is an uncommon disease and usually affects young Asian female patients during the second and third decades of life. Coronary arteries are exceptionally affected and coronary aneurysm formation is a very rare finding. We describe a case of a previously healthy 26-year-old Caucasian female whose Takayasu’s arteritis presented as a previously undescribed association of aortic and main left coronary aneurysms with severe aortic insufficiency.

  4. Association of aortic and main left coronary aneurysms with severe aortic insufficiency in Takayasu’s arteritis

    Science.gov (United States)

    Schafranski, Marcelo Derbli; Ferraz de Freitas, Marcelo; Valladão de Carvalho, Marcelo

    2011-01-01

    Takayasu’s arteritis is a granulomatous vasculitis of unknown etiology that affects mainly the aorta and its branches. As a result of intimal fibroproliferation, segmental stenosis, occlusion, dilatation, and aneurysmal formation of the involved vessels may develop. It is an uncommon disease and usually affects young Asian female patients during the second and third decades of life. Coronary arteries are exceptionally affected and coronary aneurysm formation is a very rare finding. We describe a case of a previously healthy 26-year-old Caucasian female whose Takayasu’s arteritis presented as a previously undescribed association of aortic and main left coronary aneurysms with severe aortic insufficiency. PMID:24765288

  5. Neonatal aortic stenosis.

    Science.gov (United States)

    Drury, Nigel E; Veldtman, Gruschen R; Benson, Lee N

    2005-09-01

    Neonatal aortic stenosis is a complex and heterogeneous condition, defined as left ventricular outflow tract obstruction at valvular level, presenting and often requiring treatment in the first month of life. Initial presentation may be catastrophic, necessitating hemodynamic, respiratory and metabolic resuscitation. Subsequent management is focused on maintaining systemic blood flow, either via a univentricular Norwood palliation or a biventricular route, in which the effective aortic valve area is increased by balloon dilation or surgical valvotomy. In infants with aortic annular hypoplasia but adequately sized left ventricle, the Ross-Konno procedure is also an attractive option. Outcomes after biventricular management have improved in recent years as a consequence of better patient selection, perioperative management and advances in catheter technology. Exciting new developments are likely to significantly modify the natural history of this disorder, including fetal intervention for the salvage of the hypoplastic left ventricle; 3D echocardiography providing better definition of valve morphology and aiding patient selection for a surgical or catheter-based intervention; and new transcutaneous approaches, such as duel beam echo, to perforate the valve.

  6. Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia.

    Science.gov (United States)

    Balan, Shabeesh; Yamada, Kazuo; Iwayama, Yoshimi; Hashimoto, Takanori; Toyota, Tomoko; Shimamoto, Chie; Maekawa, Motoko; Takagai, Shu; Wakuda, Tomoyasu; Kameno, Yosuke; Kurita, Daisuke; Yamada, Kohei; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Yoshikawa, Takeo

    2017-07-01

    Involvement of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia pathogenesis through disrupted neurodevelopment has been highlighted in numerous studies. However, the function of common genetic variants of this system in determining schizophrenia risk is unknown. We therefore tested the association of 375 tagged SNPs in genes derived from the GABAergic system, such as GABA A receptor subunit genes, and GABA related genes (glutamate decarboxylase genes, GABAergic-marker gene, genes involved in GABA receptor trafficking and scaffolding) in Japanese schizophrenia case-control samples (n=2926; 1415 cases and 1511 controls). We observed nominal association of SNPs in nine GABA A receptor subunit genes and the GPHN gene with schizophrenia, although none survived correction for study-wide multiple testing. Two SNPs located in the GABRA1 gene, rs4263535 (P allele =0.002; uncorrected) and rs1157122 (P allele =0.006; uncorrected) showed top hits, followed by rs723432 (P allele =0.007; uncorrected) in the GPHN gene. All three were significantly associated with schizophrenia and survived gene-wide multiple testing. Haplotypes containing associated variants in GABRA1 but not GPHN were significantly associated with schizophrenia. To conclude, we provided substantiating genetic evidence for the involvement of the GABAergic system in schizophrenia susceptibility. These results warrant further investigations to replicate the association of GABRA1 and GPHN with schizophrenia and to discern the precise mechanisms of disease pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Detection of differentially expressed genes in broiler pectoralis major muscle affected by White Striping - Wooden Breast myopathies.

    Science.gov (United States)

    Zambonelli, Paolo; Zappaterra, Martina; Soglia, Francesca; Petracci, Massimiliano; Sirri, Federico; Cavani, Claudio; Davoli, Roberta

    2016-12-01

    White Striping and Wooden Breast (WS/WB) are abnormalities increasingly occurring in the fillets of high breast yield and growth rate chicken hybrids. These defects lead to consistent economic losses for poultry meat industry, as affected broiler fillets present an impaired visual appearance that negatively affects consumers' acceptability. Previous studies have highlighted in affected fillets a severely damaged muscle, showing profound inflammation, fibrosis, and lipidosis. The present study investigated the differentially expressed genes and pathways linked to the compositional changes observed in WS/WB breast muscles, in order to outline a more complete framework of the gene networks related to the occurrence of this complex pathological picture. The biochemical composition was performed on 20 pectoralis major samples obtained from high breast yield and growth rate broilers (10 affected vs. 10 normal) and 12 out of the 20 samples were used for the microarray gene expression profiling (6 affected vs. 6 normal). The obtained results indicate strong changes in muscle mineral composition, coupled to an increased deposition of fat. In addition, 204 differentially expressed genes (DEG) were found: 102 up-regulated and 102 down-regulated in affected breasts. The gene expression pathways found more altered in WS/WB muscles are those related to muscle development, polysaccharide metabolic processes, proteoglycans synthesis, inflammation, and calcium signaling pathway. On the whole, the findings suggest that a multifactorial and complex etiology is associated with the occurrence of WS/WB muscle abnormalities, contributing to further defining the transcription patterns associated with these myopathies. © 2016 Poultry Science Association Inc.

  8. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    Energy Technology Data Exchange (ETDEWEB)

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J. Jr; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M. [Departamento de Fisiologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP (Brazil)

    2013-03-15

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g{sup -1}·min{sup -1}) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g{sup -1}·min{sup -1}) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.

  9. Preconceptional paternal glycidamide exposure affects embryonic gene expression: Single embryo gene expression study following in vitro fertilization

    Czech Academy of Sciences Publication Activity Database

    Brevik, A.; Rusňáková, Vendula; Duale, N.; Slagsvold, H.H.; Olsen, A.-K.; Storeng, R.; Kubista, Mikael; Brunborg, G.; Lindeman, B.

    2011-01-01

    Roč. 32, č. 4 (2011), s. 463-471 ISSN 0890-6238 R&D Projects: GA AV ČR(CZ) IAA500520809 Institutional research plan: CEZ:AV0Z50520701 Keywords : Single-cell gene expression * Glycidamide * Acrylamide Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.226, year: 2011

  10. Disruption of plant carotenoid biosynthesis through virus-induced gene silencing affects oviposition behaviour of the butterfly Pieris rapae

    NARCIS (Netherlands)

    Zheng, S.J.; Snoeren, T.A.L.; Hogewoning, S.W.; Loon, van J.J.A.; Dicke, M.

    2010-01-01

    Optical plant characteristics are important cues to plant-feeding insects. In this article, we demonstrate for the first time that silencing the phytoene desaturase (PDS) gene, encoding a key enzyme in plant carotenoid biosynthesis, affects insect oviposition site selection behaviour. Virus-induced

  11. When silence is noise: infantile-onset Barth syndrome caused by a synonymous substitution affecting TAZ gene transcription

    NARCIS (Netherlands)

    Ferri, L.; Dionisi-Vici, C.; Taurisano, R.; Vaz, F. M.; Guerrini, R.; Morrone, A.

    2016-01-01

    Barth syndrome (BTHS) is an X-linked inborn error of metabolism which affects males. The main manifestations are cardiomyopathy, myopathy, hypotonia, growth delay, intermittent neutropenia and 3-methylglutaconic aciduria. Diagnosis is confirmed by mutational analysis of the TAZ gene and biochemical

  12. Calling genotypes from public RNA-sequencing data enables identification of genetic variants that affect gene-expression levels

    NARCIS (Netherlands)

    Deelen, Patrick; Zhernakova, Daria V.; de Haan, Mark; van der Sijde, Marijke; Bonder, Marc Jan; Karjalainen, Juha; van der Velde, K. Joeri; Abbott, Kristin M.; Fu, Jingyuan; Wijmenga, Cisca; Sinke, Richard J.; Swertz, Morris A.; Franke, Lude

    2015-01-01

    Background: RNA-sequencing (RNA-seq) is a powerful technique for the identification of genetic variants that affect gene-expression levels, either through expression quantitative trait locus (eQTL) mapping or through allele-specific expression (ASE) analysis. Given increasing numbers of RNA-seq

  13. Social context-induced song variation affects female behavior and gene expression.

    Directory of Open Access Journals (Sweden)

    Sarah C Woolley

    2008-03-01

    Full Text Available Social cues modulate the performance of communicative behaviors in a range of species, including humans, and such changes can make the communication signal more salient. In songbirds, males use song to attract females, and song organization can differ depending on the audience to which a male sings. For example, male zebra finches (Taeniopygia guttata change their songs in subtle ways when singing to a female (directed song compared with when they sing in isolation (undirected song, and some of these changes depend on altered neural activity from a specialized forebrain-basal ganglia circuit, the anterior forebrain pathway (AFP. In particular, variable activity in the AFP during undirected song is thought to actively enable syllable variability, whereas the lower and less-variable AFP firing during directed singing is associated with more stereotyped song. Consequently, directed song has been suggested to reflect a "performance" state, and undirected song a form of vocal motor "exploration." However, this hypothesis predicts that directed-undirected song differences, despite their subtlety, should matter to female zebra finches, which is a question that has not been investigated. We tested female preferences for this natural variation in song in a behavioral approach assay, and we found that both mated and socially naive females could discriminate between directed and undirected song-and strongly preferred directed song. These preferences, which appeared to reflect attention especially to aspects of song variability controlled by the AFP, were enhanced by experience, as they were strongest for mated females responding to their mate's directed songs. We then measured neural activity using expression of the immediate early gene product ZENK, and found that social context and song familiarity differentially modulated the number of ZENK-expressing cells in telencephalic auditory areas. Specifically, the number of ZENK-expressing cells in the

  14. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    DEFF Research Database (Denmark)

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

  15. Thioridazine affects transcription of genes involved in cell wall biosynthesis in methicillin-resistant Staphylococcus aureus

    DEFF Research Database (Denmark)

    Bonde, Mette; Højland, Dorte Heidi; Kolmos, Hans Jørn

    2011-01-01

    have previously shown that the expression of some resistance genes is abolished after treatment with thioridazine and oxacillin. To further understand the mechanism underlying the reversal of resistance, we tested the expression of genes involved in antibiotic resistance and cell wall biosynthesis...... in response to thioridazine in combination with oxacillin. We observed that the oxacillin-induced expression of genes belonging to the VraSR regulon is reduced by the addition of thioridazine. The exclusion of such key factors involved in cell wall biosynthesis will most likely lead to a weakened cell wall...... reversal of resistance by thioridazine relies on decreased expression of specific genes involved in cell wall biosynthesis....

  16. Aortic Volumetry at Contrast-Enhanced Magnetic Resonance Angiography: Feasibility as a Sensitive Method for Monitoring Bicuspid Aortic Valve Aortopathy.

    Science.gov (United States)

    Trinh, Brian; Dubin, Iram; Rahman, Ozair; Ferreira Botelho, Marcos P; Naro, Nicholas; Carr, James C; Collins, Jeremy D; Barker, Alex J

    2017-04-01

    Bicuspid aortic valve patients can develop thoracic aortic aneurysms and therefore require serial imaging to monitor aortic growth. This study investigates the reliability of contrast-enhanced magnetic resonance angiography (CEMRA) volumetry compared with 2-dimensional diameter measurements to identify thoracic aortic aneurysm growth. A retrospective, institutional review board-approved, and Health Insurance Portability and Accountability Act-compliant study was conducted on 20 bicuspid aortic valve patients (45 ± 8.9 years, 20% women) who underwent serial CEMRA with a minimum imaging follow-up of 11 months. Magnetic resonance imaging was performed at 1.5 T with electrocardiogram-gated, time-resolved CEMRA. Independent observers measured the diameter at the sinuses of Valsalva (SOVs) and mid ascending aorta (MAA) as well as ascending aorta volume between the aortic valve annulus and innominate branch. Intraobserver/interobserver coefficient of variation (COV) and intraclass correlation coefficient (ICC) were computed to assess reliability. Growth rates were calculated and assessed by Student t test (P volumetry. Three-dimensional CEMRA volumetry exhibited a larger effect when examining percentage growth, a better ICC, and a marginally lower COV. Volumetry may be more sensitive to growth and possibly less affected by error than diameter measurements.

  17. Aortic obstruction: anatomy and echocardiography

    Directory of Open Access Journals (Sweden)

    Keirns Candace

    2006-09-01

    Full Text Available Abstract Echocardiography is a valuable non-invasive technique for identifying the site and type of aortic obstruction. Knowledge of the morphological details of each type of obstruction is the basis for correct interpretation of the diagnostic images and clinical decisions. This study was undertaken to correlate the echocardiographic images with anatomic specimens of equivalent valvular and supravalvular aortic obstruction. Specimens were part of the collection of the Department of Embryology. Fifty six patients were studied, and forty specimens with aortic obstruction were analyzed. Echocardiographic characteristics: Thirty one (55.3% patients were women and twenty five (44.7% men. Valvular aortic obstruction was found in Thirty six patients (64.3 % and supravalvular aortic obstruction in twenty (35.7%. Anatomic characteristics: Of the forty specimens examined, twenty one (52.5% had valvular aortic obstruction and nineteen (47.5% supravalvular aortic obstruction. The anatomoechocardiographic correlation clearly showed that the anatomic findings of the specimen hearts and aortas corresponded to echocardiographic images of valvular and supravalvular aortic obstruction and provided solid corroboration of echocardiographic diagnoses.

  18. Acute Aortic Arch Perforation During Transcatheter Aortic Valve Replacement in Bicuspid Aortic Stenosis and a Gothic Aortic Arch

    DEFF Research Database (Denmark)

    Millan-Iturbe, Oscar; Sawaya, Fadi J.; Bieliauskas, Gintautas

    2017-01-01

    AS because of its unique anatomic features. This case report describes an acute aortic perforation during delivery of a transcatheter heart valve to treat a severe bicuspid AS with a “gothic aortic arch”; more careful evaluation of the preprocedural multislice computed tomographic scan would have unveiled...

  19. Comparative symbiotic plasmid analysis indicates that symbiosis gene ancestor type affects plasmid genetic evolution.

    Science.gov (United States)

    Wang, X; Zhao, L; Zhang, L; Wu, Y; Chou, M; Wei, G

    2018-07-01

    Rhizobial symbiotic plasmids play vital roles in mutualistic symbiosis with legume plants by executing the functions of nodulation and nitrogen fixation. To explore the gene composition and genetic constitution of rhizobial symbiotic plasmids, comparison analyses of 24 rhizobial symbiotic plasmids derived from four rhizobial genera was carried out. Results illustrated that rhizobial symbiotic plasmids had higher proportion of functional genes participating in amino acid transport and metabolism, replication; recombination and repair; carbohydrate transport and metabolism; energy production and conversion and transcription. Mesorhizobium amorphae CCNWGS0123 symbiotic plasmid - pM0123d had similar gene composition with pR899b and pSNGR234a. All symbiotic plasmids shared 13 orthologous genes, including five nod and eight nif/fix genes which participate in the rhizobia-legume symbiosis process. These plasmids contained nod genes from four ancestors and fix genes from six ancestors. The ancestral type of pM0123d nod genes was similar with that of Rhizobium etli plasmids, while the ancestral type of pM0123d fix genes was same as that of pM7653Rb. The phylogenetic trees constructed based on nodCIJ and fixABC displayed different topological structures mainly due to nodCIJ and fixABC ancestral type discordance. The study presents valuable insights into mosaic structures and the evolution of rhizobial symbiotic plasmids. This study compared 24 rhizobial symbiotic plasmids that included four genera and 11 species, illuminating the functional gene composition and symbiosis gene ancestor types of symbiotic plasmids from higher taxonomy. It provides valuable insights into mosaic structures and the evolution of symbiotic plasmids. © 2018 The Society for Applied Microbiology.

  20. Minimally invasive aortic valve replacement

    DEFF Research Database (Denmark)

    Foghsgaard, Signe; Schmidt, Thomas Andersen; Kjaergard, Henrik K

    2009-01-01

    In this descriptive prospective study, we evaluate the outcomes of surgery in 98 patients who were scheduled to undergo minimally invasive aortic valve replacement. These patients were compared with a group of 50 patients who underwent scheduled aortic valve replacement through a full sternotomy...... operations were completed as mini-sternotomies, 4 died later of noncardiac causes. The aortic cross-clamp and perfusion times were significantly different across all groups (P replacement...... is an excellent operation in selected patients, but its true advantages over conventional aortic valve replacement (other than a smaller scar) await evaluation by means of randomized clinical trial. The "extended mini-aortic valve replacement" operation, on the other hand, is a risky procedure that should...

  1. Choroideremia gene product affects trophoblast development and vascularization in mouse extra-embryonic tissues.

    NARCIS (Netherlands)

    Shi, W.; Hurk, J.A.J.M. van den; Alamo-Bethencourt, V.; Mayer, W.; Winkens, H.J.; Ropers, H.H.; Cremers, F.P.M.; Fundele, R.

    2004-01-01

    Choroideremia (CHM) is a hereditary eye disease caused by mutations in the X-linked CHM gene. Disruption of the Chm gene in mice resulted in prenatal death of Chm-/Y males and Chm-/Chm+ females that had inherited the mutation from their mothers. Male chimeras and Chm+/Chm- females with paternal

  2. Abundance and genetic diversity of nifH gene sequences in anthropogenically affected Brazilian mangrove sediments

    NARCIS (Netherlands)

    Franco Dias, Armando Cavalcante; Pereira e Silva, Michele de Cassia; Cotta, Simone Raposo; Dini Andreote, Francisco; Soares, Fabio Lino; Salles, Joana Falcao; Azevedo, Joao Lucio; van Elsas, Jan Dirk; Andreote, Fernando Dini

    Although mangroves represent ecosystems of global importance, the genetic diversity and abundance of functional genes that are key to their functioning scarcely have been explored. Here, we present a survey based on the nifH gene across transects of sediments of two mangrove systems located along

  3. Gene expression in gut symbiotic organ of stinkbug affected by extracellular bacterial symbiont.

    Science.gov (United States)

    Futahashi, Ryo; Tanaka, Kohjiro; Tanahashi, Masahiko; Nikoh, Naruo; Kikuchi, Yoshitomo; Lee, Bok Luel; Fukatsu, Takema

    2013-01-01

    The bean bug Riptortus pedestris possesses a specialized symbiotic organ in a posterior region of the midgut, where numerous crypts harbor extracellular betaproteobacterial symbionts of the genus Burkholderia. Second instar nymphs orally acquire the symbiont from the environment, and the symbiont infection benefits the host by facilitating growth and by occasionally conferring insecticide resistance. Here we performed comparative transcriptomic analyses of insect genes expressed in symbiotic and non-symbiotic regions of the midgut dissected from Burkholderia-infected and uninfected R. pedestris. Expression sequence tag analysis of cDNA libraries and quantitative reverse transcription PCR identified a number of insect genes expressed in symbiosis- or aposymbiosis-associated patterns. For example, genes up-regulated in symbiotic relative to aposymbiotic individuals, including many cysteine-rich secreted protein genes and many cathepsin protease genes, are likely to play a role in regulating the symbiosis. Conversely, genes up-regulated in aposymbiotic relative to symbiotic individuals, including a chicken-type lysozyme gene and a defensin-like protein gene, are possibly involved in regulation of non-symbiotic bacterial infections. Our study presents the first transcriptomic data on gut symbiotic organ of a stinkbug, which provides initial clues to understanding of molecular mechanisms underlying the insect-bacterium gut symbiosis and sheds light on several intriguing commonalities between endocellular and extracellular symbiotic associations.

  4. Full-root aortic valve replacement with stentless xenograft achieves superior regression of left ventricular hypertrophy compared to pericardial stented aortic valves.

    Science.gov (United States)

    Tavakoli, Reza; Auf der Maur, Christoph; Mueller, Xavier; Schläpfer, Reinhard; Jamshidi, Peiman; Daubeuf, François; Frossard, Nelly

    2015-02-03

    Full-root aortic valve replacement with stentless xenografts has potentially superior hemodynamic performance compared to stented valves. However, a number of cardiac surgeons are reluctant to transform a classical stented aortic valve replacement into a technically more demanding full-root stentless aortic valve replacement. Here we describe our technique of full-root stentless aortic xenograft implantation and compare the early clinical and midterm hemodynamic outcomes to those after aortic valve replacement with stented valves. We retrospectively compared the pre-operative characteristics of 180 consecutive patients who underwent full-root replacement with stentless aortic xenografts with those of 80 patients undergoing aortic valve replacement with stented valves. In subgroups presenting with aortic stenosis, we further analyzed the intra-operative data, early postoperative outcomes and mid-term regression of left ventricular mass index. Patients in the stentless group were younger (62.6 ± 13 vs. 70.3 ± 11.8 years, p regression of the left ventricular mass index in the stentless (p replacement can be performed without adversely affecting the early morbidity or mortality in patients operated on for aortic valve stenosis provided that the coronary ostia are not heavily calcified. The additional time necessary for the full-root stentless compared to the classical stented aortic valve replacement is therefore not detrimental to the early clinical outcomes and is largely rewarded in patients with aortic stenosis by lower transvalvular gradients at mid-term and a better regression of their left ventricular mass index.

  5. Beta-blockers for preventing aortic dissection in Marfan syndrome.

    Science.gov (United States)

    Koo, Hyun-Kyoung; Lawrence, Kendra Ak; Musini, Vijaya M

    2017-11-07

    Marfan syndrome is a hereditary disorder affecting the connective tissue and is caused by a mutation of the fibrillin-1 (FBN1) gene. It affects multiple systems of the body, most notably the cardiovascular, ocular, skeletal, dural and pulmonary systems. Aortic root dilatation is the most frequent cardiovascular manifestation and its complications, including aortic regurgitation, dissection and rupture are the main cause of morbidity and mortality. To assess the long-term efficacy and safety of beta-blocker therapy as compared to placebo, no treatment or surveillance only in people with Marfan syndrome. We searched the following databases on 28 June 2017; CENTRAL, MEDLINE, Embase, Science Citation Index Expanded and the Conference Proceeding Citation Index - Science in the Web of Science Core Collection. We also searched the Online Metabolic and Molecular Bases of Inherited Disease (OMMBID), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 June 2017. We did not impose any restriction on language of publication. All randomised controlled trials (RCTs) of at least one year in duration assessing the effects of beta-blocker monotherapy compared with placebo, no treatment or surveillance only, in people of all ages with a confirmed diagnosis of Marfan syndrome were eligible for inclusion. Two review authors independently screened titles and abstracts for inclusion, extracted data and assessed trial quality. Trial authors were contacted to obtain missing data. Dichotomous outcomes will be reported as relative risk and continuous outcomes as mean differences with 95% confidence intervals. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. One open-label, randomised, single-centre trial including 70 participants with Marfan syndrome (aged 12 to 50 years old) met the inclusion criteria. Participants were randomly assigned to

  6. Acute Type II Aortic Dissection with Severe Aortic Regurgitation and Chronic Descending Aortic Dissection in Pregnant Patient with Marfan Syndrome.

    Science.gov (United States)

    Lee, Seok-Soo; Jung, Tae-Eun; Lee, Dong Hyup

    2012-12-01

    Aortic dilatation and dissection are severe complications during pregnancy that can be fatal to both the mother and the fetus. The risks of these complications are especially high in pregnant patients with Marfan syndrome; however, incidents of descending aortic dissection are very rare. This case report involves a successful Bentall procedure for and recovery from a rare aortic dissection in a pregnant Marfan patient who developed acute type II aortic dissection with severe aortic regurgitation and chronic descending aortic dissection immediately after Cesarean section. Regular follow-up will be needed to monitor the descending aortic dissection.

  7. Suppression of PCD-related genes affects salt tolerance in Arabidopsis.

    Science.gov (United States)

    Bahieldin, Ahmed; Alqarni, Dhafer A M; Atef, Ahmed; Gadalla, Nour O; Al-matary, Mohammed; Edris, Sherif; Al-Kordy, Magdy A; Makki, Rania M; Al-Doss, Abdullah A; Sabir, Jamal S M; Mutwakil, Mohammed H Z; El-Domyati, Fotouh M

    2016-01-01

    This work aims at examining a natural exciting phenomenon suggesting that suppression of genes inducing programmed cell death (PCD) might confer tolerance against abiotic stresses in plants. PCD-related genes were induced in tobacco under oxalic acid (OA) treatment (20 mM), and plant cells were characterized to confirm the incidence of PCD. The results indicated that PCD was triggered 24 h after the exposure to OA. Then, RNAs were extracted from tobacco cells 0, 2, 6, 12 and 24 h after treatment for deep sequencing. RNA-Seq analyses were done with a special emphasis to clusters whose PCD-related genes were upregulated after 2 h of OA exposure. Accordingly, 23 tobacco PCD-related genes were knocked down via virus-induced gene silencing (VIGS), whereas our results indicated the influence of five of them on inducing or suppressing PCD. Knockout T-DNA insertion mutants of these five genes in Arabidopsis were tested under salt stress (0, 100, 150, and 200 mM NaCl), and the results indicated that a mutant of an antiapoptotic gene, namely Bax Inhibitor-1 (BI-1), whose VIGS induced PCD in tobacco, was salt sensitive, while a mutant of an apoptotic gene, namely mildew resistance locus O (Mlo), whose VIGS suppressed PCD, was salt tolerant as compared to the WT (Col) control. These data support our hypothesis that retarding PCD-inducing genes can result in higher levels of salt tolerance, while retarding PCD-suppressing genes can result in lower levels of salt tolerance in plants. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  8. Abdominal Aortic Emergencies.

    Science.gov (United States)

    Lech, Christie; Swaminathan, Anand

    2017-11-01

    This article discusses abdominal aortic emergencies. There is a common thread of risk factors and causes of these diseases, including age, male gender, hypertension, dyslipidemia, and connective tissue disorders. The most common presenting symptom of these disorders is pain, usually in the chest, flank, abdomen, or back. Computed tomography scan is the gold standard for diagnosis of pathologic conditions of the aorta in the hemodynamically stable patient. Treatment consists of a combination of blood pressure and heart rate control and, in many cases, emergent surgical intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?

    Directory of Open Access Journals (Sweden)

    Carmela R. Balistreri

    2018-01-01

    Full Text Available Bicuspid valve disease is associated with the development of thoracic aortic aneurysm. The molecular mechanisms underlying this association still need to be clarified. Here, we evaluated the circulating levels of T and B lymphocyte subsets associated with the development of vascular diseases in patients with bicuspid aortic valve or tricuspid aortic valve with and without thoracic aortic aneurysm. We unveiled that the circulating levels of the MAIT, CD4+IL−17A+, and NKT T cell subsets were significantly reduced in bicuspid valve disease cases, when compared to tricuspid aortic valve cases in either the presence or the absence of thoracic aortic aneurysm. Among patients with tricuspid aortic valve, these cells were higher in those also affected by thoracic aortic aneurysm. Similar data were obtained by examining CD19+ B cells, naïve B cells (IgD+CD27−, memory unswitched B cells (IgD+CD27+, memory switched B cells (IgD−CD27+, and double-negative B cells (DN (IgD−CD27−. These cells resulted to be lower in subjects with bicuspid valve disease with respect to patients with tricuspid aortic valve. In whole, our data indicate that patients with bicuspid valve disease show a quantitative reduction of T and B lymphocyte cell subsets. Future studies are encouraged to understand the molecular mechanisms underlying this observation and its pathophysiological significance.

  10. Imaging of aortic valve dynamics in 4D OCT

    Directory of Open Access Journals (Sweden)

    Schnabel Christian

    2015-09-01

    Full Text Available The mechanical components of the heart, especially the valves and leaflets, are enormous stressed during lifetime. Therefore, those structures undergo different pathophysiological tissue transformations which affect cardiac output and in consequence living comfort of affected patients. These changes may lead to calcific aortic valve stenosis (AVS, the major heart valve disease in humans. The knowledge about changes of the dynamic behaviour during the course of this disease and the possibility of early stage diagnosis is of particular interest and could lead to the development of new treatment strategies and drug based options of prevention or therapy. 4D optical coherence tomography (OCT in combination with high-speed video microscopy were applied to characterize dynamic behaviour of the murine aortic valve and to characterize dynamic properties during artificial stimulation. We present a promising tool to investigate the aortic valve dynamics in an ex vivo disease model with a high spatial and temporal resolution using a multimodal imaging setup.

  11. Acute Type II Aortic Dissection with Severe Aortic Regurgitation and Chronic Descending Aortic Dissection in Pregnant Patient with Marfan Syndrome

    OpenAIRE

    Lee, Seok-Soo; Jung, Tae-Eun; Lee, Dong Hyup

    2012-01-01

    Aortic dilatation and dissection are severe complications during pregnancy that can be fatal to both the mother and the fetus. The risks of these complications are especially high in pregnant patients with Marfan syndrome; however, incidents of descending aortic dissection are very rare. This case report involves a successful Bentall procedure for and recovery from a rare aortic dissection in a pregnant Marfan patient who developed acute type II aortic dissection with severe aortic regurgitat...

  12. Valve-sparing aortic root replacement and aortic valve repair in a patient with acromegaly and aortic root dilatation

    Directory of Open Access Journals (Sweden)

    Karel Van Praet

    2015-07-01

    Full Text Available Aortic regurgitation and dilatation of the aortic root and ascending aorta are severe complications of acromegaly. The current trend for management of an aortic root aneurysm is valve-sparing root replacement as well as restoring the diameter of the aortic sinotubular junction (STJ and annulus. Our case report supports the recommendation that in patients with acromegaly, severe aortic root involvement may indicate the need for surgery.

  13. Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders

    Directory of Open Access Journals (Sweden)

    Baohu Ji

    2015-08-01

    Research in context: Due to lack of biological markers, diagnosis and treatment of psychiatric disorders are subjective. There is utmost urgency to identify biomarkers for clinics, research, and drug development. We found that XIST and KDM5C gene expression may be used as a biological marker for diagnosis of major affective disorders in a significantly large subset of female patients from the general population. Our studies show that over-expression of XIST and some X-linked escapee genes may be a common mechanism for development of psychiatric disorders between the patients with rare genetic diseases (XXY or XXX and the general population of female psychiatric patients.

  14. HLA non-class II genes may confer type I diabetes susceptibility in a Mapuche (Amerindian) affected family.

    Science.gov (United States)

    Pérez-Bravo, Francisco; Martinez-Laso, Jorge; Martin-Villa, Jose M; Moscoso, Juan; Moreno, Almudena; Serrano-Vela, Juan I; Zamora, Jorge; Asenjo, Silvia; Gleisner, Andrea; Arnaiz-Villena, Antonio

    2006-01-01

    A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.

  15. Agrobacterium rhizogenes rolB gene affects photosynthesis and chlorophyll content in transgenic tomato (Solanum lycopersicum L.) plants.

    Science.gov (United States)

    Bettini, Priscilla P; Marvasi, Massimiliano; Fani, Fabiola; Lazzara, Luigi; Cosi, Elena; Melani, Lorenzo; Mauro, Maria Luisa

    2016-10-01

    Insertion of Agrobacterium rhizogenes rolB gene into plant genome affects plant development, hormone balance and defence. However, beside the current research, the overall transcriptional response and gene expression of rolB as a modulator in plant is unknown. Transformed rolB tomato plant (Solanum lycopersicum L.) cultivar Tondino has been used to investigate the differential expression profile. Tomato is a well-known model organism both at the genetic and molecular level, and one of the most important commercial food crops in the world. Through the construction and characterization of a cDNA subtracted library, we have investigated the differential gene expression between transgenic clones of rolB and control tomato and have evaluated genes specifically transcribed in transgenic rolB plants. Among the selected genes, five genes encoding for chlorophyll a/b binding protein, carbonic anhydrase, cytochrome b 6 /f complex Fe-S subunit, potassium efflux antiporter 3, and chloroplast small heat-shock protein, all involved in chloroplast function, were identified. Measurement of photosynthesis efficiency by the level of three different photosynthetic parameters (F v /F m , rETR, NPQ) showed rolB significant increase in non-photochemical quenching and a, b chlorophyll content. Our results point to highlight the role of rolB on plant fitness by improving photosynthesis. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. RNA-Seq reveals seven promising candidate genes affecting the proportion of thick egg albumen in layer-type chickens.

    Science.gov (United States)

    Wan, Yi; Jin, Sihua; Ma, Chendong; Wang, Zhicheng; Fang, Qi; Jiang, Runshen

    2017-12-22

    Eggs with a much higher proportion of thick albumen are preferred in the layer industry, as they are favoured by consumers. However, the genetic factors affecting the thick egg albumen trait have not been elucidated. Using RNA sequencing, we explored the magnum transcriptome in 9 Rhode Island white layers: four layers with phenotypes of extremely high ratios of thick to thin albumen (high thick albumen, HTA) and five with extremely low ratios (low thick albumen, LTA). A total of 220 genes were differentially expressed, among which 150 genes were up-regulated and 70 were down-regulated in the HTA group compared with the LTA group. Gene Ontology (GO) analysis revealed that the up-regulated genes in HTA were mainly involved in a wide range of regulatory functions. In addition, a large number of these genes were related to glycosphingolipid biosynthesis, focal adhesion, ECM-receptor interactions and cytokine-cytokine receptor interactions. Based on functional analysis, ST3GAL4, FUT4, ITGA2, SDC3, PRLR, CDH4 and GALNT9 were identified as promising candidate genes for thick albumen synthesis and metabolism during egg formation. These results provide new insights into the molecular mechanisms of egg albumen traits and may contribute to future breeding strategies that optimise the proportion of thick egg albumen.

  17. Unusual Case of Overt Aortic Dissection Mimicking Aortic Intramural Hematoma

    Directory of Open Access Journals (Sweden)

    Kushtrim Disha

    2016-04-01

    Full Text Available We report an interesting case in which overt aortic dissection mimicked two episodes of aortic intramural hematoma (IMH (Stanford A, DeBakey I. This took place over the course of four days and had a major influence on the surgical treatment strategy. The first episode of IMH regressed completely within 15 hours after it was clinically diagnosed and verified using imaging techniques. The recurrence of IMH was detected three days thereafter, resulting in an urgent surgical intervention. Overt aortic dissection with evidence of an intimal tear was diagnosed intraoperatively.

  18. Factors affecting the gene expression of in vitro cultured human preimplantation embryos

    NARCIS (Netherlands)

    Mantikou, E.; Jonker, M.J.; Wong, K.M.; van Montfoort, A.P.A.; de Jong, M.; Breit, T.M.; Repping, S.; Mastenbroek, S.

    2016-01-01

    STUDY QUESTION: What is the relative effect of common environmental and biological factors on transcriptome changes during human preimplantation development? SUMMARY ANSWER: Developmental stage and maternal age had a larger effect on the global gene expression profile of human preimplantation

  19. Aortic root replacement after previous surgical intervention on the aortic valve, aortic root, or ascending aorta.

    Science.gov (United States)

    Kirsch, E W Matthias; Radu, N Costin; Mekontso-Dessap, Armand; Hillion, Marie-Line; Loisance, Daniel

    2006-03-01

    Aortic root replacement after a previous operation on the aortic valve, aortic root, or ascending aorta remains a major challenge. Records of 56 consecutive patients (44 men; mean age, 56.4 +/- 13.6 years) undergoing reoperative aortic root replacement between June 1994 and June 2005 were reviewed retrospectively. Reoperation was performed 9.4 +/- 6.7 years after the last cardiac operation. Indications for reoperation were true aneurysm (n = 14 [25%]), false aneurysm (n = 10 [18%]), dissection or redissection (n = 9 [16%]), structural or nonstructural valve dysfunction (n = 10 [18%]), prosthetic valve-graft infection (n = 12 [21%]), and miscellaneous (n = 1 [2%]). Procedures performed were aortic root replacement (n = 47 [84%]), aortic root replacement plus mitral valve procedure (n = 5 [9%]), and aortic root replacement plus arch replacement (n = 4 [7%]). In 14 (25%) patients coronary artery bypass grafting had to be performed unexpectedly during the same procedure or immediately after the procedure to re-establish coronary perfusion. Hospital mortality reached 17.9% (n = 10). Multivariate logistic regression analysis revealed the need for unplanned perioperative coronary artery bypass grafting as the sole independent risk factor for hospital death (P = .005). Actuarial survival was 83.8% +/- 4.9% at 1 month, 73.0% +/- 6.3% at 1 year, and 65.7% +/- 9.0% at 5 years after the operation. One patient had recurrence of endocarditis 6.7 months after the operation and required repeated homograft aortic root replacement. Reoperative aortic root replacement remains associated with a high postoperative mortality. The need to perform unplanned coronary artery bypass grafting during reoperative aortic root replacement is a major risk factor for hospital death. The optimal technique for coronary reconstruction in this setting remains to be debated.

  20. Reinforced aortic root reconstruction for acute type A aortic dissection involving the aortic root

    Directory of Open Access Journals (Sweden)

    Han Qing-qi

    2013-06-01

    Full Text Available OBJECTIVE: There are debates regarding the optimal approach for AAAD involving the aortic root. We described a modified reinforced aortic root reconstruction approach for treating AAAD involving the aortic root. METHODS: A total of 161 patients with AAAD involving the aortic root were treated by our modified reinforced aortic root reconstruction approach from January 1998 to December 2008. Key features of our modified approach were placement of an autologous pericardial patch in the false lumen, lining of the sinotubular junction lumen with a polyester vascular ring, and wrapping of the vessel with Teflon strips. Outcome measures included post-operative mortality, survival, complications, and level of aortic regurgitation. RESULTS: A total of 161 patients were included in the study (mean age: 43.3 1 15.5 years. The mean duration of follow-up was 5.1 1 2.96 years (2-12 years. A total of 10 (6.2% and 11 (6.8% patients died during hospitalization and during follow-up, respectively. Thirty-one (19.3% patients experienced postoperative complications. The 1-, 3-, 5-, and 10-year survival rates were 99.3%, 98%, 93.8%, and 75.5%, respectively. There were no instances of recurrent aortic dissection, aortic aneurysm, or pseudoaneurysm during the entire study period. The severity of aortic regurgitation dramatically decreased immediately after surgery (from 28.6% to 0% grade 3-4 and thereafter slightly increased (from 0% to 7.2% at 5 years and 9.1% at 10 years. CONCLUSION: This modified reinforced aortic root reconstruction was feasible, safe and durable/effective, as indicated by its low mortality, low postoperative complications and high survival rate.

  1. Mild aerobic exercise blocks elastin fiber fragmentation and aortic dilatation in a mouse model of Marfan syndrome associated aortic aneurysm.

    Science.gov (United States)

    Gibson, Christine; Nielsen, Cory; Alex, Ramona; Cooper, Kimbal; Farney, Michael; Gaufin, Douglas; Cui, Jason Z; van Breemen, Cornelis; Broderick, Tom L; Vallejo-Elias, Johana; Esfandiarei, Mitra

    2017-07-01

    Regular low-impact physical activity is generally allowed in patients with Marfan syndrome, a connective tissue disorder caused by heterozygous mutations in the fibrillin-1 gene. However, being above average in height encourages young adults with this syndrome to engage in high-intensity contact sports, which unfortunately increases the risk for aortic aneurysm and rupture, the leading cause of death in Marfan syndrome. In this study, we investigated the effects of voluntary (cage-wheel) or forced (treadmill) aerobic exercise at different intensities on aortic function and structure in a mouse model of Marfan syndrome. Four-week-old Marfan and wild-type mice were subjected to voluntary and forced exercise regimens or sedentary lifestyle for 5 mo. Thoracic aortic tissue was isolated and subjected to structural and functional studies. Our data showed that exercise improved aortic wall structure and function in Marfan mice and that the beneficial effect was biphasic, with an optimum at low intensity exercise (55-65% V̇o 2max ) and tapering off at a higher intensity of exercise (85% V̇o 2max ). The mechanism underlying the reduced elastin fragmentation in Marfan mice involved reduction of the expression of matrix metalloproteinases 2 and 9 within the aortic wall. These findings present the first evidence of potential beneficial effects of mild exercise on the structural integrity of the aortic wall in Marfan syndrome associated aneurysm. Our finding that moderate, but not strenuous, exercise protects aortic structure and function in a mouse model of Marfan syndrome could have important implications for the medical care of young Marfan patients. NEW & NOTEWORTHY The present study provides conclusive scientific evidence that daily exercise can improve aortic health in a mouse model of Marfan syndrome associated aortic aneurysm, and it establishes the threshold for the exercise intensity beyond which exercise may not be as protective. These findings establish a platform

  2. [Identification of new genes that affect [PSI^(+)] prion toxicity in Saccharomyces cerevisiae yeast].

    Science.gov (United States)

    Matveenko, A G; Belousov, M V; Bondarev, S A; Moskalenko, S E; Zhouravleva, G A

    2016-01-01

    Translation termination is an important step in gene expression. Its correct processing is governed by eRF1 (Sup45) and eRF3 (Sup35) proteins. In Saccharomyces cerevisiae, mutations in the corresponding genes, as well as Sup35 aggregation in [PSI^(+)] cells that propagate the prion form of Sup35 lead to inaccurate stop codon recognition and, consequently, nonsense suppression. The presence of stronger prion variants results in the more efficient suppression of nonsense mutations. Previously, we proposed a synthetic lethality test that enables the identification of genes that may influence either translation termination factors or [PSI^(+)] manifestation. This is based on the fact that the combination of sup45 mutations with the strong [PSI^(+)] prion variant in diploids is lethal. In this work, a set of genes that were previously shown to enhance nonsense suppression was analyzed. It was found that ABF1, FKH2, and REB1 overexpression decreased the growth of strains in a prion-dependent manner and, thus, might influence [PSI^(+)] prion toxicity. It was also shown that the synthetic lethality of [PSI^(+)] and sup45 mutations increased with the overexpression of GLN3 and MOT3 that encode Q/N-rich transcription factors. An analysis of the effects of their expression on the transcription of the release factors genes revealed an increase in SUP35 transcription in both cases. Since SUP35 overexpression is known to be toxic in [PSI^(+)] strains, these genes apparently enhance [PSI^(+)] toxicity via the regulation of SUP35 transcription.

  3. Current indications for stentless aortic bioprostheses.

    Science.gov (United States)

    Hegazy, Yasser Y; Rayan, Amr; Bauer, Stefan; Keshk, Noha; Bauer, Kerstin; Ennker, Ina; Ennker, Jürgen

    2018-01-01

    The best aortic prostheses have been debated for decades. The introduction of stentless aortic bioprostheses was aimed at improving hemodynamics and potentially the durability of aortic bioprostheses. Despite the good short- and long-term outcomes after implantation of stentless aortic bioprostheses, their use remains limited owing to the technically demanding implantation techniques. Nevertheless, stentless aortic bioprostheses might be of special benefit in certain indications, where they could be a valuable addition to the surgical armamentarium.

  4. Tribbles 3: A potential player in diabetic aortic remodelling.

    Science.gov (United States)

    Ti, Yun; Xie, Guo-lu; Wang, Zhi-hao; Ding, Wen-yuan; Zhang, Yun; Zhong, Ming; Zhang, Wei

    2016-01-01

    Tribbles 3, whose expression is up-regulated by insulin resistance, was confirmed to be involved in diabetic cardiomyopathy in our previous study. However, it is not known whether Tribbles 3 has a role on conduit arteries such as the aorta in diabetes. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of diabetic rats by serial ultrasonography and histopathologic analyses of aortic wall architecture. Diabetic rats displayed increased aortic medial thickness, excessive collagen deposition, diminished elastic fibres and reduced vascular compliance together with Tribbles 3 overexpression. To further investigate the role of Tribbles 3 in aortic remodelling, we used Tribbles 3 gene silencing in vivo 12 weeks after onset of diabetes. Silence of Tribbles 3 significantly reversed pathological aortic remodelling without blood pressure modification. In Tribbles 3-small interfering RNA group, medial thickness and perivascular fibrosis were markedly decreased; moreover, there were prominent reductions in collagen content and collagen/elastin ratio, resulting in an improved arterial compliance. Additionally, with Tribbles 3 silencing, the diminished phosphorylation of PI3K/Akt was restored, and increased activation of MKK4/JNK was decreased. Silence of Tribbles 3 is potent in mediating reversal of aortic remodelling, implicating that Tribbles 3 is proposed to be a potential therapeutic target for vascular complication in diabetes. © The Author(s) 2015.

  5. Uremia modulates the phenotype of aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Madsen, Marie; Pedersen, Annemarie Aarup; Albinsson, Sebastian

    2017-01-01

    the phenotype of aortic SMCs in vivo. METHODS: Moderate uremia was induced by 5/6 nephrectomy in apolipoprotein E knockout (ApoE(-/-)) and wildtype C57Bl/6 mice. Plasma analysis, gene expression, histology, and myography were used to determine uremia-mediated changes in the arterial wall. RESULTS: Induction...... of moderate uremia in ApoE(-/-) mice increased atherosclerosis in the aortic arch en face 1.6 fold (p = 0.04) and induced systemic inflammation. Based on histological analyses of aortic root sections, uremia increased the medial area, while there was no difference in the content of elastic fibers or collagen...... in the aortic media. In the aortic arch, mRNA and miRNA expression patterns were consistent with a uremia-mediated phenotypic modulation of SMCs; e.g. downregulation of myocardin, α-smooth muscle actin, and transgelin; and upregulation of miR146a. Notably, these expression patterns were observed after acute (2...

  6. SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism

    DEFF Research Database (Denmark)

    Christensen, Lise-Lotte; True, Kirsten; Hamilton, Mark P.

    2016-01-01

    It is well established that lncRNAs are aberrantly expressed in cancer where they have been shown to act as oncogenes or tumor suppressors. RNA profiling of 314 colorectal adenomas/adenocarcinomas and 292 adjacent normal colon mucosa samples using RNA-sequencing demonstrated that the snoRNA host...... gene 16 (SNHG16) is significantly up-regulated in adenomas and all stages of CRC. SNHG16 expression was positively correlated to the expression of Wnt-regulated transcription factors, including ASCL2, ETS2, and c-Myc. In vitro abrogation of Wnt signaling in CRC cells reduced the expression of SNHG16...... indicating that SNHG16 is regulated by the Wnt pathway. Silencing of SNHG16 resulted in reduced viability, increased apoptotic cell death and impaired cell migration. The SNHG16 silencing particularly affected expression of genes involved in lipid metabolism. A connection between SNHG16 and genes involved...

  7. Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Kim, Dae Seong; Lee, Myoung Woo; Lee, Tae-Hee; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2017-03-01

    The results of clinical trials using mesenchymal stem cells (MSCs) are controversial due to the heterogeneity of human MSCs and differences in culture conditions. In this regard, it is important to identify gene expression patterns according to culture conditions, and to determine how the cells are expanded and when they should be clinically used. In the current study, stemness gene expression was investigated in adipose tissue-derived MSCs (AT-MSCs) harvested following culture at different densities. AT-MSCs were plated at a density of 200 or 5,000 cells/cm 2 . After 7 days of culture, stemness gene expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The proliferation rate of AT-MSCs harvested at a low density (~50% confluent) was higher than that of AT-MSCs harvested at a high density (~90% confluent). Although there were differences in the expression levels of stemness gene, such as octamer-binding transcription factor 4, nanog homeobox ( Nanog ), SRY-box 2, Kruppel like factor 4, v-myc avian myelocytomatosis viral oncogene homolog ( c-Myc ), and lin-28 homolog A, in the AT-MSCs obtained from different donors, RT-qPCR analysis demonstrated differential gene expression patterns according to the cell culture density. Expression levels of stemness genes, particularly Nanog and c-Myc , were upregulated in AT-MSCs harvested at a low density (~50% confluent) in comparison to AT-MSCs from the same donor harvested at a high density (~90% confluent). These results imply that culture conditions, such as the cell density at harvesting, modulate the stemness gene expression and proliferation of MSCs.

  8. Acid environments affect biofilm formation and gene expression in isolates of Salmonella enterica Typhimurium DT104.

    Science.gov (United States)

    O'Leary, Denis; McCabe, Evonne M; McCusker, Matthew P; Martins, Marta; Fanning, Séamus; Duffy, Geraldine

    2015-08-03

    The aim of this study was to examine the survival and potential virulence of biofilm-forming Salmonella Typhimurium DT104 under mild acid conditions. Salmonella Typhimurium DT104 employs an acid tolerance response (ATR) allowing it to adapt to acidic environments. The threat that these acid adapted cells pose to food safety could be enhanced if they also produce biofilms in acidic conditions. The cells were acid-adapted by culturing them in 1% glucose and their ability to form biofilms on stainless steel and on the surface of Luria Bertani (LB) broth at pH7 and pH5 was examined. Plate counts were performed to examine cell survival. RNA was isolated from cells to examine changes in the expression of genes associated with virulence, invasion, biofilm formation and global gene regulation in response to acid stress. Of the 4 isolates that were examined only one (1481) that produced a rigid biofilm in LB broth at pH7 also formed this same structure at pH5. This indicated that the lactic acid severely impeded the biofilm producing capabilities of the other isolates examined under these conditions. Isolate 1481 also had higher expression of genes associated with virulence (hilA) and invasion (invA) with a 24.34-fold and 13.68-fold increase in relative gene expression respectively at pH5 compared to pH7. Although genes associated with biofilm formation had increased expression in response to acid stress for all the isolates this only resulted in the formation of a biofilm by isolate 1481. This suggests that in addition to the range of genes associated with biofilm production at neutral pH, there are genes whose protein products specifically aid in biofilm production in acidic environments. Furthermore, it highlights the potential for the use of lactic acid for the inhibition of Salmonella biofilms. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Novel Genes Affecting the Interaction between the Cabbage Whitefly and Arabidopsis Uncovered by Genome-Wide Association Mapping.

    Directory of Open Access Journals (Sweden)

    Colette Broekgaarden

    Full Text Available Plants have evolved a variety of ways to defend themselves against biotic attackers. This has resulted in the presence of substantial variation in defense mechanisms among plants, even within a species. Genome-wide association (GWA mapping is a useful tool to study the genetic architecture of traits, but has so far only had limited exploitation in studies of plant defense. Here, we study the genetic architecture of defense against the phloem-feeding insect cabbage whitefly (Aleyrodes proletella in Arabidopsis thaliana. We determined whitefly performance, i.e. the survival and reproduction of whitefly females, on 360 worldwide selected natural accessions and subsequently performed GWA mapping using 214,051 SNPs. Substantial variation for whitefly adult survival and oviposition rate (number of eggs laid per female per day was observed between the accessions. We identified 39 candidate SNPs for either whitefly adult survival or oviposition rate, all with relatively small effects, underpinning the complex architecture of defense traits. Among the corresponding candidate genes, i.e. genes in linkage disequilibrium (LD with candidate SNPs, none have previously been identified as a gene playing a role in the interaction between plants and phloem-feeding insects. Whitefly performance on knock-out mutants of a number of candidate genes was significantly affected, validating the potential of GWA mapping for novel gene discovery in plant-insect interactions. Our results show that GWA analysis is a very useful tool to gain insight into the genetic architecture of plant defense against herbivorous insects, i.e. we identified and validated several genes affecting whitefly performance that have not previously been related to plant defense against herbivorous insects.

  10. Association between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) and bipolar affective disorder.

    Science.gov (United States)

    Papadimitriou, G N; Dikeos, D G; Karadima, G; Avramopoulos, D; Daskalopoulou, E G; Vassilopoulos, D; Stefanis, C N

    1998-02-07

    Genetic factors seem to play an important role in the pathogenesis of affective disorder. The candidate gene strategies are being used, among others, to identify the genes conferring vulnerability to the disease. The genes coding for the receptors of gamma-aminobutyric acid (GABA) have been proposed as candidates for affective disorder, since the GABA neurotransmitter system has been implicated in the pathogenesis of the illness. We examined the possible genetic association between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) on chromosome 15 and affective disorder, in 48 bipolar patients (BP), 40 unipolar patients (UP), and 50 healthy individuals, age- and sex-matched to the patients. All patients and controls were unrelated Greeks. Diagnoses were made after direct interviews according to the DSM-IV and ICD-10 criteria. For the genotyping, a dinucleotide (CA) repeat marker was used. The polymerase chain reaction (PCR) products found were nine alleles with lengths between 272 and 290 base pairs (bp). The distribution of allelic frequencies of the GABRA5 locus differed significantly between BP patients and controls with the 282-bp allele found to be associated with BP affective disorder, while no such difference was observed between the groups of UP patients and controls nor between the two patient groups. The presence or absence of the 282-bp allele in the genotype of BP patients was not shown to influence the age of onset and the overall clinical severity, but was found to be associated with a preponderance of manic over depressive episodes in the course of the illness.

  11. A Simple Network to Remove Interference in Surface EMG Signal from Single Gene Affected Phenylketonuria Patients for Proper Diagnosis

    Science.gov (United States)

    Mohanty, Madhusmita; Basu, Mousumi; Pattanayak, Deba Narayan; Mohapatra, Sumant Kumar

    2018-04-01

    Recently Autosomal Recessive Single Gene (ARSG) diseases are highly effective to the children within the age of 5-10 years. One of the most ARSG disease is a Phenylketonuria (PKU). This single gene disease is associated with mutations in the gene that encodes the enzyme phenylalanine hydroxylase (PAH, Gene 612349). Through this mutation process, PAH of the gene affected patient can not properly manufacture PAH as a result the patients suffer from decreased muscle tone which shows abnormality in EMG signal. Here the extraction of the quality of the PKU affected EMG (PKU-EMG) signal is a keen interest, so it is highly necessary to remove the added ECG signal as well as the biological and instrumental noises. In the Present paper we proposed a method for detection and classification of the PKU affected EMG signal. Here Discrete Wavelet Transformation is implemented for extraction of the features of the PKU affected EMG signal. Adaptive Neuro-Fuzzy Inference System (ANFIS) network is used for the classification of the signal. Modified Particle Swarm Optimization (MPSO) and Modified Genetic Algorithm (MGA) are used to train the ANFIS network. Simulation result shows that the proposed method gives better performance as compared to existing approaches. Also it gives better accuracy of 98.02% for the detection of PKU-EMG signal. The advantages of the proposed model is to use MGA and MPSO to train the parameters of ANFIS network for classification of ECG and EMG signal of PKU affected patients. The proposed method obtained the high SNR (18.13 ± 0.36 dB), SNR (0.52 ± 1.62 dB), RE (0.02 ± 0.32), MSE (0.64 ± 2.01), CC (0.99 ± 0.02), RMSE (0.75 ± 0.35) and MFRE (0.01 ± 0.02), RMSE (0.75 ± 0.35) and MFRE (0.01 ± 0.02). From authors knowledge, this is the first time a composite method is used for diagnosis of PKU affected patients. The accuracy (98.02%), sensitivity (100%) and specificity (98.59%) helps for proper clinical treatment. It can help for readers

  12. Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice.

    Science.gov (United States)

    Horii, Yasuyuki; Nagasawa, Tatsuhiro; Sakakibara, Hiroyuki; Takahashi, Aki; Tanave, Akira; Matsumoto, Yuki; Nagayama, Hiromichi; Yoshimi, Kazuto; Yasuda, Michiko T; Shimoi, Kayoko; Koide, Tsuyoshi

    2017-08-01

    Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.

  13. Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner.

    Science.gov (United States)

    de Jong, Simone; Chepelev, Iouri; Janson, Esther; Strengman, Eric; van den Berg, Leonard H; Veldink, Jan H; Ophoff, Roel A

    2012-09-06

    Chromosome 17q21.31 contains a common inversion polymorphism of approximately 900 kb in populations with European ancestry. Two divergent MAPT haplotypes, H1 and H2 are described with distinct linkage disequilibrium patterns across the region reflecting the inversion status at this locus. The MAPT H1 haplotype has been associated with progressive supranuclear palsy, corticobasal degeneration, Parkinson's disease and Alzheimer's disease, while the H2 is linked to recurrent deletion events associated with the 17q21.31 microdeletion syndrome, a disease characterized by developmental delay and learning disability. In this study, we investigate the effect of the inversion on the expression of genes in the 17q21.31 region. We find the expression of several genes in and at the borders of the inversion to be affected; specific either to whole blood or different regions of the human brain. The H1 haplotype was found to be associated with an increased expression of LRRC37A4, PLEKH1M and MAPT. In contrast, a decreased expression of MGC57346, LRRC37A and CRHR1 was associated with H1. Studies thus far have focused on the expression of MAPT in the inversion region. However, our results show that the inversion status affects expression of other genes in the 17q21.31 region as well. Given the link between the inversion status and different neurological diseases, these genes may also be involved in disease pathology, possibly in a tissue-specific manner.

  14. A deletion affecting an LRR-RLK gene co-segregates with the fruit flat shape trait in peach.

    Science.gov (United States)

    López-Girona, Elena; Zhang, Yu; Eduardo, Iban; Mora, José Ramón Hernández; Alexiou, Konstantinos G; Arús, Pere; Aranzana, María José

    2017-07-27

    In peach, the flat phenotype is caused by a partially dominant allele in heterozygosis (Ss), fruits from homozygous trees (SS) abort a few weeks after fruit setting. Previous research has identified a SSR marker (UDP98-412) highly associated with the trait, found suitable for marker assisted selection (MAS). Here we report a ∼10 Kb deletion affecting the gene PRUPE.6G281100, 400 Kb upstream of UDP98-412, co-segregating with the trait. This gene is a leucine-rich repeat receptor-like kinase (LRR-RLK) orthologous to the Brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) group. PCR markers suitable for MAS confirmed its strong association with the trait in a collection of 246 cultivars. They were used to evaluate the DNA from a round fruit derived from a somatic mutation of the flat variety 'UFO-4', revealing that the mutation affected the flat associated allele (S). Protein BLAST alignment identified significant hits with genes involved in different biological processes. Best protein hit occurred with AtRLP12, which may functionally complement CLAVATA2, a key regulator that controls the stem cell population size. RT-PCR analysis revealed the absence of transcription of the partially deleted allele. The data support PRUPE.6G281100 as a candidate gene for flat shape in peach.

  15. Tobacco smoking and aortic aneurysm

    DEFF Research Database (Denmark)

    Sode, Birgitte F; Nordestgaard, Børge; Grønbæk, Morten

    2013-01-01

    BACKGROUND: We determined the predictive power of tobacco smoking on aortic aneurysm as opposed to other risk factors in the general population. METHODS: We recorded tobacco smoking and other risk factors at baseline, and assessed hospitalization and death from aortic aneurysm in 15,072 individuals...... aneurysm in males and females consuming above 20g tobacco daily was 3.5% and 1.3%, among those >60years with plasma cholesterol >5mmol/L and a systolic blood pressure >140mmHg. CONCLUSIONS: Tobacco smoking is the most important predictor of future aortic aneurysm outcomes in the general population...

  16. Nuclear orphan receptor TLX affects gene expression, proliferation and cell apoptosis in beta cells

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Xiaoli; Xiong, Xiaokan; Dai, Zhe; Deng, Haohua; Sun, Li; Hu, Xuemei; Zhou, Feng; Xu, Yancheng, E-mail: oxyccc@163.com

    2015-12-04

    Nuclear orphan receptor TLX is an essential regulator of the growth of neural stem cells. However, its exact function in pancreatic islet cells is still unknown. In the present study, gene expression profiling analysis revealed that overexpression of TLX in beta cell line MIN6 causes suppression of 176 genes and upregulation of 49 genes, including a cadre of cell cycle, cell proliferation and cell death control genes, such as Btg2, Ddit3 and Gadd45a. We next examined the effects of TLX overexpression on proliferation, apoptosis and insulin secretion in MIN6 cells. Proliferation analysis using EdU assay showed that overexpression of TLX increased percentage of EdU-positive cells. Cell cycle and apoptosis analysis revealed that overexpression of TLX in MIN6 cells resulted in higher percentage of cells exiting G1 into S-phase, and a 58.8% decrease of cell apoptosis induced by 0.5 mM palmitate. Moreover, TLX overexpression did not cause impairment of insulin secretion. Together, we conclude that TLX is among factors capable of controlling beta cell proliferation and survival, which may serve as a target for the development of novel therapies for diabetes. - Highlights: • TLX overexpression in MIN6 cell causes significant expression changes of 225 genes. • TLX overexpression promotes MIN6 cell proliferation and decreases cell apoptosis. • TLX overexpression does not cause impairment of insulin secretion.

  17. Iron Content Affects Lipogenic Gene Expression in the Muscle of Nelore Beef Cattle.

    Directory of Open Access Journals (Sweden)

    Wellison Jarles da Silva Diniz

    Full Text Available Iron (Fe is an essential mineral for metabolism and plays a central role in a range of biochemical processes. Therefore, this study aimed to identify differentially expressed (DE genes and metabolic pathways in Longissimus dorsi (LD muscle from cattle with divergent iron content, as well as to investigate the likely role of these DE genes in biological processes underlying beef quality parameters. Samples for RNA extraction for sequencing and iron, copper, manganese, and zinc determination were collected from LD muscles at slaughter. Eight Nelore steers, with extreme genomic estimated breeding values for iron content (Fe-GEBV, were selected from a reference population of 373 animals. From the 49 annotated DE genes (FDR<0.05 found between the two groups, 18 were up-regulated and 31 down-regulated for the animals in the low Fe-GEBV group. The functional enrichment analyses identified several biological processes, such as lipid transport and metabolism, and cell growth. Lipid metabolism was the main pathway observed in the analysis of metabolic and canonical signaling pathways for the genes identified as DE, including the genes FASN, FABP4, and THRSP, which are functional candidates for beef quality, suggesting reduced lipogenic activities with lower iron content. Our results indicate metabolic pathways that are partially influenced by iron, contributing to a better understanding of its participation in skeletal muscle physiology.

  18. Nuclear orphan receptor TLX affects gene expression, proliferation and cell apoptosis in beta cells

    International Nuclear Information System (INIS)

    Shi, Xiaoli; Xiong, Xiaokan; Dai, Zhe; Deng, Haohua; Sun, Li; Hu, Xuemei; Zhou, Feng; Xu, Yancheng

    2015-01-01

    Nuclear orphan receptor TLX is an essential regulator of the growth of neural stem cells. However, its exact function in pancreatic islet cells is still unknown. In the present study, gene expression profiling analysis revealed that overexpression of TLX in beta cell line MIN6 causes suppression of 176 genes and upregulation of 49 genes, including a cadre of cell cycle, cell proliferation and cell death control genes, such as Btg2, Ddit3 and Gadd45a. We next examined the effects of TLX overexpression on proliferation, apoptosis and insulin secretion in MIN6 cells. Proliferation analysis using EdU assay showed that overexpression of TLX increased percentage of EdU-positive cells. Cell cycle and apoptosis analysis revealed that overexpression of TLX in MIN6 cells resulted in higher percentage of cells exiting G1 into S-phase, and a 58.8% decrease of cell apoptosis induced by 0.5 mM palmitate. Moreover, TLX overexpression did not cause impairment of insulin secretion. Together, we conclude that TLX is among factors capable of controlling beta cell proliferation and survival, which may serve as a target for the development of novel therapies for diabetes. - Highlights: • TLX overexpression in MIN6 cell causes significant expression changes of 225 genes. • TLX overexpression promotes MIN6 cell proliferation and decreases cell apoptosis. • TLX overexpression does not cause impairment of insulin secretion.

  19. Heat Stress Affects Pi-related Genes Expression and Inorganic Phosphate Deposition/Accumulation in Barley

    DEFF Research Database (Denmark)

    Pacak, Andrzej; Barciszewska-Pacak, Maria; Swida-Barteczka, Aleksandra

    2016-01-01

    Phosphorus (P) in plants is taken from soil as an inorganic phosphate (Pi) and is one of the most important macroelements in growth and development. Plants actively react to Pi starvation by the induced expression of Pi transporters, MIR399, MIR827, and miR399 molecular sponge - IPS1 genes...... and by the decreased expression of the ubiquitin-conjugating enzyme E2 (PHOSPHATE2 - PHO2) and Pi sensing and transport SPX-MFS genes. The PHO2 protein is involved in the degradation of Pi transporters PHT1;1 (from soil to roots) and PHO1 (from roots to shoots). The decreased expression of PHO2 leads to Pi....... In shoots, the PHO2 mRNA level is decreased, leading to an increased Pi level. We concluded that Pi homeostasis in barley during heat stress is maintained by dynamic changes in Pi-related genes expression....

  20. Mutations in sit B and sit D genes affect manganese-growth requirements in Sinorhizobium meliloti.

    Science.gov (United States)

    Platero, Raúl A; Jaureguy, Melina; Battistoni, Federico J; Fabiano, Elena R

    2003-01-21

    Two transposon-induced mutants of Sinorhizobium meliloti 242 were isolated based on their inability to grow on rich medium supplemented with the metal chelator ethylenediamine di-o-hydroxyphenylacetic acid (EDDHA) and either heme-compounds or siderophores as iron sources. Tagged loci of these mutants were identified as sit B and sit D genes. These genes encode components of an ABC (ATP-binding cassette) metal-type permease in several Gram-negative bacteria. In this work, the phenotypes of these two mutants were compared with those of two siderophore-mediated iron transport mutants. The results strongly implicate a role of the sit genes in manganese acquisition when this metal is limiting in S. meliloti.

  1. Inoculum pretreatment affects bacterial survival, activity and catabolic gene expression during phytoremediation of diesel contaminated soil.

    Science.gov (United States)

    Khan, Sumia; Afzal, Muhammad; Iqbal, Samina; Mirza, Muhammad Sajjad; Khan, Qaiser M

    2013-04-01

    Plant-bacteria partnership is a promising approach for remediating soil contaminated with organic pollutants. The colonization and metabolic activity of an inoculated microorganism depend not only on environmental conditions but also on the physiological condition of the applied microorganisms. This study assessed the influence of different inoculum pretreatments on survival, gene abundance and catabolic gene expression of an applied strain (Pantoea sp. strain BTRH79) in the rhizosphere of ryegrass vegetated in diesel contaminated soil. Maximum bacterium survival, gene abundance and expression were observed in the soil inoculated with bacterial cells that had been pregrown on complex medium, and hydrocarbon degradation and genotoxicity reduction were also high in this soil. These findings propose that use of complex media for growing plant inocula may enhance bacterial survival and colonization and subsequently the efficiency of pollutant degradation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Monoterpenoid-based preparations in beehives affect learning, memory, and gene expression in the bee brain.

    Science.gov (United States)

    Bonnafé, Elsa; Alayrangues, Julie; Hotier, Lucie; Massou, Isabelle; Renom, Allan; Souesme, Guillaume; Marty, Pierre; Allaoua, Marion; Treilhou, Michel; Armengaud, Catherine

    2017-02-01

    Bees are exposed in their environment to contaminants that can weaken the colony and contribute to bee declines. Monoterpenoid-based preparations can be introduced into hives to control the parasitic mite Varroa destructor. The long-term effects of monoterpenoids are poorly investigated. Olfactory conditioning of the proboscis extension reflex (PER) has been used to evaluate the impact of stressors on cognitive functions of the honeybee such as learning and memory. The authors tested the PER to odorants on bees after exposure to monoterpenoids in hives. Octopamine receptors, transient receptor potential-like (TRPL), and γ-aminobutyric acid channels are thought to play a critical role in the memory of food experience. Gene expression levels of Amoa1, Rdl, and trpl were evaluated in parallel in the bee brain because these genes code for the cellular targets of monoterpenoids and some pesticides and neural circuits of memory require their expression. The miticide impaired the PER to odors in the 3 wk following treatment. Short-term and long-term olfactory memories were improved months after introduction of the monoterpenoids into the beehives. Chronic exposure to the miticide had significant effects on Amoa1, Rdl, and trpl gene expressions and modified seasonal changes in the expression of these genes in the brain. The decrease of expression of these genes in winter could partly explain the improvement of memory. The present study has led to new insights into alternative treatments, especially on their effects on memory and expression of selected genes involved in this cognitive function. Environ Toxicol Chem 2017;36:337-345. © 2016 SETAC. © 2016 SETAC.

  3. Transgene-induced gene silencing is not affected by a change in ploidy level.

    Directory of Open Access Journals (Sweden)

    Daniela Pignatta

    Full Text Available BACKGROUND: Whole genome duplication, which results in polyploidy, is a common feature of plant populations and a recurring event in the evolution of flowering plants. Polyploidy can result in changes to gene expression and epigenetic instability. Several epigenetic phenomena, occurring at the transcriptional or post-transcriptional level, have been documented in allopolyploids (polyploids derived from species hybrids of Arabidopsis thaliana, yet findings in autopolyploids (polyploids derived from the duplication of the genome of a single species are limited. Here, we tested the hypothesis that an increase in ploidy enhances transgene-induced post-transcriptional gene silencing using autopolyploids of A. thaliana. METHODOLOGY/PRINCIPAL FINDINGS: Diploid and tetraploid individuals of four independent homozygous transgenic lines of A. thaliana transformed with chalcone synthase (CHS inverted repeat (hairpin constructs were generated. For each line diploids and tetraploids were compared for efficiency in post-transcriptional silencing of the endogenous CHS gene. The four lines differed substantially in their silencing efficiency. Yet, diploid and tetraploid plants derived from these plants and containing therefore identical transgene insertions showed no difference in the efficiency silencing CHS as assayed by visual scoring, anthocyanin assays and quantification of CHS mRNA. CONCLUSIONS/SIGNIFICANCE: Our results in A. thaliana indicated that there is no effect of ploidy level on transgene-induced post-transcriptional gene silencing. Our findings that post-transcriptional mechanisms were equally effective in diploids and tetraploids supports the use of transgene-driven post-transcriptional gene silencing as a useful mechanism to modify gene expression in polyploid species.

  4. Feeding-Related Traits Are Affected by Dosage of the foraging Gene in Drosophila melanogaster.

    Science.gov (United States)

    Allen, Aaron M; Anreiter, Ina; Neville, Megan C; Sokolowski, Marla B

    2017-02-01

    Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging's functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for 0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {for BAC } rescue allele. We show that a total loss of foraging expression in larvae results in reduced larval path length and food intake behavior, while conversely showing an increase in triglyceride levels. Furthermore, varying foraging gene dosage demonstrates a linear dose-response on these phenotypes in relation to foraging gene expression levels. These experiments have unequivocally proven a causal, dose-dependent relationship between the foraging gene and its pleiotropic influence on these feeding-related traits. Our analysis of foraging's transcription start sites, termination sites, and splicing patterns using rapid amplification of cDNA ends (RACE) and full-length cDNA sequencing, revealed four independent promoters, pr1-4, that produce 21 transcripts with nine distinct open reading frames (ORFs). The use of alternative promoters and alternative splicing at the foraging locus creates diversity and flexibility in the regulation of gene expression, and ultimately function. Future studies will exploit these genetic tools to precisely dissect the isoform- and tissue-specific requirements of foraging's functions and shed light on the genetic control of feeding-related traits involved in energy homeostasis. Copyright © 2017 by the Genetics Society of America.

  5. Peripartal alterations of calcitonin gene-related peptide and minerals in dairy cows affected by milk fever.

    Science.gov (United States)

    Zebeli, Qendrim; Beitz, Donald C; Bradford, Barry J; Dunn, Suzanna M; Ametaj, Burim N

    2013-03-01

    Milk fever, a metabolic disease of dairy cattle, is associated with perturbations of calcium homeostasis, the pathogenesis of which is not yet completely understood. The aim of this study was to investigate plasma concentrations of calcitonin gene-related peptide and selected minerals and metabolites in periparturient cows with and without milk fever. Plasma concentrations of calcitonin gene-related peptide, as well as calcium, phosphate, magnesium, iron, glucose, lactate, and cortisol, were determined in multiple plasma samples from Jersey cows with and without spontaneous milk fever. Cows affected by milk fever (n = 5) had lower concentrations of calcitonin gene-related peptide (P = .038) and inorganic phosphate (P cows tended to have lower calcium concentrations (P = .071). Magnesium, iron, lactate, glucose, and cortisol concentrations were comparable between both groups of cows (P > .10). Around the day of calving, plasma concentrations of lactate, glucose, and cortisol increased and the concentration of iron decreased in all cows (P ≤ .01). Despite the limited number of cows evaluated, this report is the first to indicate lowered concentrations of calcitonin gene-related peptide as part of the metabolic changes during milk fever in cows. Further work with a larger cohort of animals is warranted to understand the precise role of calcitonin gene-related peptide and the potential associations with disturbances in plasma minerals typically observed during milk fever. © 2013 American Society for Veterinary Clinical Pathology.

  6. Immunohistochemical loss of 5-hydroxymethylcytosine expression in acute myeloid leukaemia: relationship to somatic gene mutations affecting epigenetic pathways.

    Science.gov (United States)

    Magotra, Minoti; Sakhdari, Ali; Lee, Paul J; Tomaszewicz, Keith; Dresser, Karen; Hutchinson, Lloyd M; Woda, Bruce A; Chen, Benjamin J

    2016-12-01

    Genes affecting epigenetic pathways are frequently mutated in myeloid malignancies, including acute myeloid leukaemia (AML). The genes encoding TET2, IDH1 and IDH2 are among the most commonly mutated genes, and cause defective conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), impairing demethylation of DNA, and presumably serving as driver mutations in leukaemogenesis. The aim of this study was to correlate 5hmC immunohistochemical loss with the mutation status of genes involved in epigenetic pathways in AML. Immunohistochemical staining with an anti-5hmC antibody was performed on 41 decalcified, formalin-fixed paraffin-embedded (FFPE) bone marrow biopsies from patients with AML. Archived DNA was subjected to next-generation sequencing for analysis of a panel of genes, including TET2, IDH1, IDH2, WT1 and DNMT3A. TET2, IDH1, IDH2, WT1 and DNMT3A mutations were found in 46% (19/41) of the cases. Ten of 15 cases (67%) with TET2, IDH1, IDH2 or WT1 mutations showed deficient 5hmC staining, whereas nine of 26 cases (35%) without a mutation in these genes showed loss of 5hmC. It is of note that all four cases with TET2 mutations showed deficient 5hmC staining. Overall, somatic mutations in TET2, IDH1, IDH2, WT1 and DNMT3A were common in our cohort of AML cases. Immunohistochemical staining for 5hmC was lost in the majority of cases harbouring mutations in these genes, reflecting the proposed relationship between dysfunctional epigenetic pathways and leukaemogenesis. © 2016 John Wiley & Sons Ltd.

  7. Reoperative Aortic Root Replacement in Patients with Previous Aortic Root or Aortic Valve Procedures

    Directory of Open Access Journals (Sweden)

    Byung Kwon Chong

    2016-08-01

    Full Text Available Background: Generalization of standardized surgical techniques to treat aortic valve (AV and aortic root diseases has benefited large numbers of patients. As a consequence of the proliferation of patients receiving aortic root surgeries, surgeons are more frequently challenged by reoperative aortic root procedures. The aim of this study was to evaluate the outcomes of redo-aortic root replacement (ARR. Methods: We retrospectively reviewed 66 patients (36 male; mean age, 44.5±9.5 years who underwent redo-ARR following AV or aortic root procedures between April 1995 and June 2015. Results: Emergency surgeries comprised 43.9% (n=29. Indications for the redo-ARR were aneurysm (n=12, pseudoaneurysm (n=1, or dissection (n=6 of the residual native aortic sinus in 19 patients (28.8%, native AV dysfunction in 8 patients (12.1%, structural dysfunction of an implanted bioprosthetic AV in 19 patients (28.8%, and infection of previously replaced AV or proximal aortic grafts in 30 patients (45.5%. There were 3 early deaths (4.5%. During follow- up (median, 54.65 months; quartile 1–3, 17.93 to 95.71 months, there were 14 late deaths (21.2%, and 9 valve-related complications including reoperation of the aortic root in 1 patient, infective endocarditis in 3 patients, and hemorrhagic events in 5 patients. Overall survival and event-free survival rates at 5 years were 81.5%±5.1% and 76.4%±5.4%, respectively. Conclusion: Despite technical challenges and a high rate of emergency conditions in patients requiring redo-ARR, early and late outcomes were acceptable in these patients.

  8. Integration of transcriptome and whole genomic resequencing data to identify key genes affecting swine fat deposition.

    Directory of Open Access Journals (Sweden)

    Kai Xing

    Full Text Available Fat deposition is highly correlated with the growth, meat quality, reproductive performance and immunity of pigs. Fatty acid synthesis takes place mainly in the adipose tissue of pigs; therefore, in this study, a high-throughput massively parallel sequencing approach was used to generate adipose tissue transcriptomes from two groups of Songliao black pigs that had opposite backfat thickness phenotypes. The total number of paired-end reads produced for each sample was in the range of 39.29-49.36 millions. Approximately 188 genes were differentially expressed in adipose tissue and were enriched for metabolic processes, such as fatty acid biosynthesis, lipid synthesis, metabolism of fatty acids, etinol, caffeine and arachidonic acid and immunity. Additionally, many genetic variations were detected between the two groups through pooled whole-genome resequencing. Integration of transcriptome and whole-genome resequencing data revealed important genomic variations among the differentially expressed genes for fat deposition, for example, the lipogenic genes. Further studies are required to investigate the roles of candidate genes in fat deposition to improve pig breeding programs.

  9. Identification of genes affecting the response of tomato and Arabidopsis upon powdery mildew infection

    NARCIS (Netherlands)

    Gao, D.

    2014-01-01

    Many plant species are hosts of powdery mildew fungi, including Arabidopsis and economically important crops such as wheat, barley and tomato. Resistance has been explored using induced mutagenesis and natural variation in the plant species. The isolated genes encompass loss-of-function

  10. Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

    KAUST Repository

    Zhang, Xiaomei; Bocca, Silvina Maria; Franchi, Anahí ; Anderson, Sandra; Kaur, Mandeep; Bajic, Vladimir B.; Oehninger, Sergio Carlos

    2010-01-01

    were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues

  11. Transcriptomic analysis to uncover genes affecting cold resistance in the Chinese honey bee (Apis cerana cerana).

    Science.gov (United States)

    Xu, Kai; Niu, Qingsheng; Zhao, Huiting; Du, Yali; Jiang, Yusuo

    2017-01-01

    The biological activity and geographical distribution of honey bees is strongly temperature-dependent, due to their ectothermic physiology. In China, the endemic Apis cerana cerana exhibits stronger cold hardiness than Western honey bees, making the former species important pollinators of winter-flowering plants. Although studies have examined behavioral and physiological mechanisms underlying cold resistance in bees, data are scarce regarding the exact molecular mechanisms. Here, we investigated gene expression in A. c. cerana under two temperature treatments, using transcriptomic analysis to identify differentially expressed genes (DEGs) and relevant biological processes, respectively. Across the temperature treatments, 501 DEGs were identified. A gene ontology analysis showed that DEGs were enriched in pathways related to sugar and amino acid biosynthesis and metabolism, as well as calcium ion channel activity. Additionally, heat shock proteins, zinc finger proteins, and serine/threonine-protein kinases were differentially expressed between the two treatments. The results of this study provide a general digital expression profile of thermoregulation genes responding to cold hardiness in A. c. cerana. Our data should prove valuable for future research on cold tolerance mechanisms in insects, and may be beneficial in breeding efforts to improve bee hardiness.

  12. Transcriptomic analysis to uncover genes affecting cold resistance in the Chinese honey bee (Apis cerana cerana.

    Directory of Open Access Journals (Sweden)

    Kai Xu

    Full Text Available The biological activity and geographical distribution of honey bees is strongly temperature-dependent, due to their ectothermic physiology. In China, the endemic Apis cerana cerana exhibits stronger cold hardiness than Western honey bees, making the former species important pollinators of winter-flowering plants. Although studies have examined behavioral and physiological mechanisms underlying cold resistance in bees, data are scarce regarding the exact molecular mechanisms. Here, we investigated gene expression in A. c. cerana under two temperature treatments, using transcriptomic analysis to identify differentially expressed genes (DEGs and relevant biological processes, respectively. Across the temperature treatments, 501 DEGs were identified. A gene ontology analysis showed that DEGs were enriched in pathways related to sugar and amino acid biosynthesis and metabolism, as well as calcium ion channel activity. Additionally, heat shock proteins, zinc finger proteins, and serine/threonine-protein kinases were differentially expressed between the two treatments. The results of this study provide a general digital expression profile of thermoregulation genes responding to cold hardiness in A. c. cerana. Our data should prove valuable for future research on cold tolerance mechanisms in insects, and may be beneficial in breeding efforts to improve bee hardiness.

  13. Nuclear orphan receptor TLX affects gene expression, proliferation and cell apoptosis in beta cells.

    Science.gov (United States)

    Shi, Xiaoli; Xiong, Xiaokan; Dai, Zhe; Deng, Haohua; Sun, Li; Hu, Xuemei; Zhou, Feng; Xu, Yancheng

    Nuclear orphan receptor TLX is an essential regulator of the growth of neural stem cells. However, its exact function in pancreatic islet cells is still unknown. In the present study, gene expression profiling analysis revealed that overexpression of TLX in beta cell line MIN6 causes suppression of 176 genes and upregulation of 49 genes, including a cadre of cell cycle, cell proliferation and cell death control genes, such as Btg2, Ddit3 and Gadd45a. We next examined the effects of TLX overexpression on proliferation, apoptosis and insulin secretion in MIN6 cells. Proliferation analysis using EdU assay showed that overexpression of TLX increased percentage of EdU-positive cells. Cell cycle and apoptosis analysis revealed that overexpression of TLX in MIN6 cells resulted in higher percentage of cells exiting G1 into S-phase, and a 58.8% decrease of cell apoptosis induced by 0.5 mM palmitate. Moreover, TLX overexpression did not cause impairment of insulin secretion. Together, we conclude that TLX is among factors capable of controlling beta cell proliferation and survival, which may serve as a target for the development of novel therapies for diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Synthetic lethality between gene defects affecting a single non-essential molecular pathway with reversible steps.

    Directory of Open Access Journals (Sweden)

    Andrei Zinovyev

    2013-04-01

    Full Text Available Systematic analysis of synthetic lethality (SL constitutes a critical tool for systems biology to decipher molecular pathways. The most accepted mechanistic explanation of SL is that the two genes function in parallel, mutually compensatory pathways, known as between-pathway SL. However, recent genome-wide analyses in yeast identified a significant number of within-pathway negative genetic interactions. The molecular mechanisms leading to within-pathway SL are not fully understood. Here, we propose a novel mechanism leading to within-pathway SL involving two genes functioning in a single non-essential pathway. This type of SL termed within-reversible-pathway SL involves reversible pathway steps, catalyzed by different enzymes in the forward and backward directions, and kinetic trapping of a potentially toxic intermediate. Experimental data with recombinational DNA repair genes validate the concept. Mathematical modeling recapitulates the possibility of kinetic trapping and revealed the potential contributions of synthetic, dosage-lethal interactions in such a genetic system as well as the possibility of within-pathway positive masking interactions. Analysis of yeast gene interaction and pathway data suggests broad applicability of this novel concept. These observations extend the canonical interpretation of synthetic-lethal or synthetic-sick interactions with direct implications to reconstruct molecular pathways and improve therapeutic approaches to diseases such as cancer.

  15. Factors affecting the gene expression of in vitro cultured human preimplantation embryos

    NARCIS (Netherlands)

    Mantikou, E.; Jonker, M. J.; Wong, K. M.; van Montfoort, A. P. A.; de Jong, M.; Breit, T. M.; Repping, S.; Mastenbroek, S.

    2016-01-01

    What is the relative effect of common environmental and biological factors on transcriptome changes during human preimplantation development? Developmental stage and maternal age had a larger effect on the global gene expression profile of human preimplantation embryos than the culture medium or

  16. Detection of the Helicobacter pylori dupA gene is strongly affected by the PCR design

    NARCIS (Netherlands)

    Abadi, Amin Talebi Bezmin; Loffeld, Ruud J L F; Constancia, Ashandra C; Wagenaar, Jaap A; Kusters, Johannes G

    2014-01-01

    The Helicobacter pylori virulence gene dupA is usually detected by PCR, but the primer binding sites used are highly variable. Our newly designed qPCR against a conserved region of dupA was positive in 64.2% of 394 clinical isolates while the positivity rate of the commonly used PCRs ranged from

  17. Altered Expression of Genes Implicated in Xylan Biosynthesis Affects Penetration Resistance against Powdery Mildew.

    Science.gov (United States)

    Chowdhury, Jamil; Lück, Stefanie; Rajaraman, Jeyaraman; Douchkov, Dimitar; Shirley, Neil J; Schwerdt, Julian G; Schweizer, Patrick; Fincher, Geoffrey B; Burton, Rachel A; Little, Alan

    2017-01-01

    Heteroxylan has recently been identified as an important component of papillae, which are formed during powdery mildew infection of barley leaves. Deposition of heteroxylan near the sites of attempted fungal penetration in the epidermal cell wall is believed to enhance the physical resistance to the fungal penetration peg and hence to improve pre-invasion resistance. Several glycosyltransferase (GT) families are implicated in the assembly of heteroxylan in the plant cell wall, and are likely to work together in a multi-enzyme complex. Members of key GT families reported to be involved in heteroxylan biosynthesis are up-regulated in the epidermal layer of barley leaves during powdery mildew infection. Modulation of their expression leads to altered susceptibility levels, suggesting that these genes are important for penetration resistance. The highest level of resistance was achieved when a GT43 gene was co-expressed with a GT47 candidate gene, both of which have been predicted to be involved in xylan backbone biosynthesis. Altering the expression level of several candidate heteroxylan synthesis genes can significantly alter disease susceptibility. This is predicted to occur through changes in the amount and structure of heteroxylan in barley papillae.

  18. How Gene-Environment Interaction Affects Children's Anxious and Fearful Behavior. Science Briefs

    Science.gov (United States)

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Evidence for a Gene-Environment Interaction in Predicting Behavioral Inhibition in Middle Childhood" (N. A. Fox, K E. Nichols, H. A. Henderson, K. Rubin, L. Schmidt, D. Hamer, M. Ernst, and D. S.…

  19. Microarray analysis of genes affected by salt stress in tomato | Zhou ...

    African Journals Online (AJOL)

    This study has provided a set of candidate genes, especially those in the regulatory machinery that can be further investigated to define salt stress in tomato and other plant species. Keywords: Antioxidants, cellular metabolism, cell wall, chaperonine, ethylene, protein kinase, tomato, transcription regulator, translation ...

  20. Targeted mutation of the SC3 hydrophobin gene of Schizophyllum commune affects formation of aerial hyphae

    NARCIS (Netherlands)

    vanWetter, MA; Schuren, FHJ; Schuurs, TA; Wessels, JGH

    1996-01-01

    The SC3 hydrophobin gene of Schizophyllum commune was disrupted by homologous integration of an SC3 genomic fragment interrupted by a phleomycin resistance cassette. The phenotype of the mutant was particularly clear in sealed plates in which formation of aerial hyphae was blocked. In non-sealed

  1. An indication of major genes affecting hip and elbow dysplasia in four Finnish dog populations

    NARCIS (Netherlands)

    Maki, K.; Janss, L.L.G.; Groen, A.F.; Liinamo, A.E.; Ojala, M.

    2004-01-01

    The aim of the study was to assess the possible existence of major genes influencing hip and elbow dysplasia in four dog populations. A Bayesian segregation analysis was performed separately on each population. In total, 34 140 dogs were included in the data set. Data were analysed with both a

  2. Tumor-specific mutations in low-frequency genes affect their functional properties

    NARCIS (Netherlands)

    L. Erdem-Eraslan (Lale); D. Heijsman (Daphne); M. De Wit (Maurice); A.E. Kremer (Andreas); A. Sacchetti (Andrea); P.J. van der Spek (Peter); P.A.E. Sillevis Smitt (Peter); P.J. French (Pim)

    2015-01-01

    textabstractCausal genetic changes in oligodendrogliomas (OD) with 1p/19q co-deletion include mutations in IDH1, IDH2, CIC, FUBP1, TERT promoter and NOTCH1. However, it is generally assumed that more somatic mutations are required for tumorigenesis. This study aimed to establish whether genes

  3. Infrarenal Abdominal Aortic Pseudoaneurysm: Is It a Real Emergency?

    Science.gov (United States)

    Massara, Mafalda; Prunella, Roberto; Gerardi, Pasquale; Lillo, Antonio; De Caridi, Giovanni; Serra, Raffaele; Notarstefano, Stefano; Impedovo, Giovanni

    2017-01-01

    Abdominal aortic pseudoaneurysm is a rare but life-threatening condition that occurs due to penetrating or blunt trauma. Clinical manifestations are variable, and the time interval from the initial trauma to diagnosis is variable. A prompt diagnosis and an aggressive management approach are required to avoid catastrophic complications. Possible treatment options are open surgical repair, endovascular repair, pseudoanerysmal sac thrombosis induction through direct thrombin injection, and coil embolization. Here, we present the case of a 75-year-old man affected by an infrarenal abdominal aortic pseudoaneurysm presenting with abdominal and lumbar pain for 3 days, who was successfully treated with an endograft. PMID:29515707

  4. Abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes S.

    2010-01-01

    Although the number of elective operations for abdominal aortic aneurysms (AAA) is increasing, the sex- and age-standardised mortality rate of AAAs continues to rise, especially among men aged 65 years or more. The lethality of ruptured AAA continues to be 80-95%, compared with 5-7% by elective...... surgery of symptomfree AAA. In order to fulfil all WHO, European, and Danish criteria for screening, a randomised hospitalbased screening trial of 12,639 65-73 year old men in Viborg County (Denmark) was initiated in 1994. It seemed that US screening is a valid, suitable and acceptable method of screening...... patients without previous hospital discharge diagnoses due to cardiovascular disease than among similar men without AAA. The absolute risk difference after 5 years was 16%. So, they will benefit from general cardiovascular preventive action as smoking cessation, statins and low-dose aspirin, which could...

  5. Abdominal aortic aneurysm surgery

    DEFF Research Database (Denmark)

    Gefke, K; Schroeder, T V; Thisted, B

    1994-01-01

    The goal of this study was to identify patients who need longer care in the ICU (more than 48 hours) following abdominal aortic aneurysm (AAA) surgery and to evaluate the influence of perioperative complications on short- and long-term survival and quality of life. AAA surgery was performed in 553...... patients, 51 (9%) of whom died within the first 48 hours. Of the 502 patients who survived for more than 48 hours, 109 required ICU therapy for more than 48 hours, whereas 393 patients were in the ICU for less than 48 hours. The incidence of preoperative risk factors was similar for the two groups...... combined failed to permit identification of patients in whom the perioperative survival rate was 0%. Even 20% of patients with multiorgan failure survived for 6 months. Of those patients who needed ICU therapy for more than 48 hours, 41 (38%) were alive at the end of 1988. In response to a questionnaire...

  6. Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

    KAUST Repository

    Zhang, Xiaomei

    2010-03-04

    We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

  7. Evaluation of the aortic anulus

    International Nuclear Information System (INIS)

    Link, K.M.; Margosian, P.

    1991-01-01

    This paper evaluates the efficacy of echocardiography and MR imaging for measuring the aortic anulus in patients who are candidates for aortic valve replacement. The MR imaging study was performed on a 1.5-T system, and the results were compared with echocardiography results obtained with use of a Toshiba system with a 2.5-mHz transducer. The aortic valve anulus was evaluated in the coronal, long-axis, and short-axis views with the MR imaging technique and in the right parasternal suprasternal, and apical projections with the echocardiographic technique. Twenty-four patients studied with MR imaging and echocardiography went on to have aortic valve replacement. When compared with surgical results, MR imaging had an r value of .95 while echocardiography had an r value of .70

  8. Cloning and characterization of chicken fat mass and obesity associated (Fto) gene: fasting affects Fto expression.

    Science.gov (United States)

    Tiwari, A; Krzysik-Walker, S M; Ramachandran, R

    2012-01-01

    Fat mass and obesity associated gene (Fto), also known as Fatso, is a member of the Fe-II and 2-oxoglutarate-dependent dioxygenase superfamily. Recent studies in humans and rodents suggest that Fto is involved in food intake regulation and lipid metabolism, whereas single nucleotide mutations in the Fto gene are associated with obesity and type 2 diabetes. The Fto gene is highly conserved from green algae to humans, but little is known about the avian Fto gene or protein. The objectives of the current study were to clone full-length chicken Fto cDNA and to determine the effect of age or feeding status on Fto expression. With the use of rapid amplification of cDNA ends, the full-length chicken Fto cDNA was cloned and found to share 63% to 66% homology with the mammalian Fto nucleotide sequence. Several regions of the chicken Fto protein, including the substrate (2-oxoglutarate) binding domains, were found to be identical to mammalian Fto protein. Western blotting with anti-human Fto antibody and reverse transcription PCR studies showed that Fto protein and gene were ubiquitously expressed in various tissues of the chicken. With the use of quantitative PCR, Fto mRNA levels were found to be higher in liver and skeletal muscle of 8-wk-old chickens than in 4-wk-old chickens. In addition, alterations in feeding status resulted in significant changes in Fto mRNA and Fto protein expression in the liver but not in skeletal muscle and adipose tissue of broiler chickens. Taken together, our data suggest that Fto probably plays a significant role in liver function and energy metabolism in the chicken. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Network Analysis Reveals Putative Genes Affecting Meat Quality in Angus Cattle.

    Science.gov (United States)

    Mateescu, Raluca G; Garrick, Dorian J; Reecy, James M

    2017-01-01

    Improvements in eating satisfaction will benefit consumers and should increase beef demand which is of interest to the beef industry. Tenderness, juiciness, and flavor are major determinants of the palatability of beef and are often used to reflect eating satisfaction. Carcass qualities are used as indicator traits for meat quality, with higher quality grade carcasses expected to relate to more tender and palatable meat. However, meat quality is a complex concept determined by many component traits making interpretation of genome-wide association studies (GWAS) on any one component challenging to interpret. Recent approaches combining traditional GWAS with gene network interactions theory could be more efficient in dissecting the genetic architecture of complex traits. Phenotypic measures of 23 traits reflecting carcass characteristics, components of meat quality, along with mineral and peptide concentrations were used along with Illumina 54k bovine SNP genotypes to derive an annotated gene network associated with meat quality in 2,110 Angus beef cattle. The efficient mixed model association (EMMAX) approach in combination with a genomic relationship matrix was used to directly estimate the associations between 54k SNP genotypes and each of the 23 component traits. Genomic correlated regions were identified by partial correlations which were further used along with an information theory algorithm to derive gene network clusters. Correlated SNP across 23 component traits were subjected to network scoring and visualization software to identify significant SNP. Significant pathways implicated in the meat quality complex through GO term enrichment analysis included angiogenesis, inflammation, transmembrane transporter activity, and receptor activity. These results suggest that network analysis using partial correlations and annotation of significant SNP can reveal the genetic architecture of complex traits and provide novel information regarding biological mechanisms

  10. Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures.

    Directory of Open Access Journals (Sweden)

    Purificación Gómez-Abellán

    Full Text Available to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V and subcutaneous (S adipose tissue (AT in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX on positive and negative clock genes expression.VAT and SAT biopsies were obtained from morbid obese women (body mass index ≥ 40 kg/m(2 (n = 6. In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX and AT explants treated with DEX (2 hours were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR.CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements in the SAT (situation not present in VAT. A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues.24 h patterns in CLOCK and BMAL1 (positive clock elements and PER2 (negative element mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure.

  11. Imaging techniques in transcatheter aortic valve replacement

    Directory of Open Access Journals (Sweden)

    Quaife RA

    2013-11-01

    Full Text Available Robert A Quaife, Jennifer Dorosz, John C Messenger, Ernesto E Salcedo Division of Cardiology, University of Colorado, Aurora, CO, USA Abstract: Calcific aortic stenosis is now understood as a complex valvular degenerative process sharing many risk factors with atherosclerosis. Once patients develop symptomatic calcific aortic stenosis, the only effective treatment is aortic valve replacement. In the past decade, transcatheter aortic valve replacement (TAVR has been developed as an alternative to surgery to treat severe calcific aortic stenosis. Cardiac imaging plays a pivotal role in the contemporary management of patients with calcific aortic stenosis, and particularly in patients being considered for TAVR, who demand detailed imaging of the aortic valve apparatus. In this review, we highlight the role of cardiac imaging for patient selection, procedural guidance, and evaluation of results of TAVR. Keywords: aortic stenosis, cardiovascular imaging, transcutaneous aortic valve replacement

  12. A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

    Directory of Open Access Journals (Sweden)

    Emond Mary

    2007-09-01

    Full Text Available Abstract Background Marfan syndrome (MFS is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms. Results We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR. Conclusion Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value -6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status. An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.

  13. SNPs at exonic region of aquaporin-7 (AQP7) gene may affect ...

    Indian Academy of Sciences (India)

    improvement in sire herd and quality parameters of bull semen have tremendous ... A total of 96 mature Frieswal bulls were included in this study. Semen was ..... management, and genetic factors affecting semen production in. Holstein bulls.

  14. Alkaptonuria-associated aortic stenosis.

    Science.gov (United States)

    Lok, Zoe S Y; Goldstein, Jacob; Smith, Julian A

    2013-07-01

    Alkaptonuria is an autosomal recessive disorder of tyrosine metabolism, which results in accumulation of unmetabolized homogentisic acid and its oxidized product in various tissues, including the heart. Cardiovascular involvement is a rare but serious complication of the disease. We present two patients who have undergone successful aortic valve replacement for alkaptonuria-associated aortic stenosis along with a review of the literature. © 2013 Wiley Periodicals, Inc.

  15. Aortic Involvement in Pediatric Marfan syndrome: A Review.

    Science.gov (United States)

    Ekhomu, Omonigho; Naheed, Zahra J

    2015-06-01

    Outlining specific protocols for the management of pediatric patients with Marfan syndrome has been challenging. This is mostly due to a dearth of clinical studies performed in pediatric patients. In Marfan syndrome, the major sources of morbidity and mortality relate to the cardiovascular system. In this review, we focus on aortic involvement seen in pediatric patients with Marfan syndrome, ranging from aortic dilatation to aortic rupture and heart failure. We discuss the histological, morphological, and pathogenetic basis of the cardiac manifestations seen in pediatric Marfan syndrome and use a specific case to depict our experienced range of cardiovascular manifestations. The survival for patients with Marfan syndrome may approach the expected survival for non-affected patients, with optimal management. With this potentiality in mind, we explore possible and actual management considerations for pediatric Marfan syndrome, examining both medical and surgical therapy modalities that can make the possibility of improved survival a reality.

  16. Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms

    NARCIS (Netherlands)

    T. Treasure (Tom); J.J.M. Takkenberg (Hanneke); J. Pepper (John)

    2016-01-01

    textabstractElective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a

  17. Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms

    NARCIS (Netherlands)

    T. Treasure (Tom); J.J.M. Takkenberg (Hanneke); J. Pepper (John)

    2014-01-01

    textabstractElective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a

  18. Activation tagging of the two closely linked genes LEP and VAS independently affects vascular cell number

    DEFF Research Database (Denmark)

    van der Graaff, Eric; Hooykaas, Paul J J; Keller, Beat

    2002-01-01

    report that in addition to this leafy petiole phenotype, the size of the vascular bundles is increased in all aerial organs in let as a result of an increase in the number of xylem, phloem (pro)cambial and pericycle cells. This vascular phenotype is caused by activation tagging of the two genes VASCULAR......-promoting factor. The activation tagging of VAS only resulted in a specific increase in phloem (pro)cambial and pericycle cells. We conclude that activation tagging of LEP and VAS results in additive phenotypes. Insertional mutants for LEP and VAS display wild-type vascular development, indicating the relevance...... of activation tagging for functional analysis of novel genes involved in plant development....

  19. Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission

    OpenAIRE

    Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J.

    2016-01-01

    Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discriminatio...

  20. Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Yang, Lihua; Zha, Jinmiao; Li, Wei; Li, Zhaoli; Wang, Zijian

    2010-05-05

    Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333microg/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na(+),K(+)-ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10microg/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10microg/l. The expressions of Na(+),K(+)-ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100microg/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

  1. Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus)

    Energy Technology Data Exchange (ETDEWEB)

    Yang Lihua; Zha Jinmiao; Li Wei; Li Zhaoli [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing Road 18, P.O. Box 2871, Beijing 100085 (China); Wang Zijian, E-mail: wangzj@rcees.ac.cn [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing Road 18, P.O. Box 2871, Beijing 100085 (China)

    2010-05-05

    Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333 {mu}g/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na{sup +},K{sup +}-ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10 {mu}g/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10 {mu}g/l. The expressions of Na{sup +},K{sup +}-ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100 {mu}g/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

  2. Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus)

    International Nuclear Information System (INIS)

    Yang Lihua; Zha Jinmiao; Li Wei; Li Zhaoli; Wang Zijian

    2010-01-01

    Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333 μg/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na + ,K + -ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10 μg/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10 μg/l. The expressions of Na + ,K + -ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100 μg/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

  3. Detection of the Helicobacter pylori dupA gene is strongly affected by the PCR design.

    Science.gov (United States)

    Abadi, Amin Talebi Bezmin; Loffeld, Ruud J L F; Constancia, Ashandra C; Wagenaar, Jaap A; Kusters, Johannes G

    2014-11-01

    The Helicobacter pylori virulence gene dupA is usually detected by PCR, but the primer binding sites used are highly variable. Our newly designed qPCR against a conserved region of dupA was positive in 64.2% of 394 clinical isolates while the positivity rate of the commonly used PCRs ranged from 29.9% to 37.8%. Copyright © 2014. Published by Elsevier B.V.

  4. Does fragmentation of wetlands affect gene flow in sympatric Acrocephalus warblers with different migration strategies?

    OpenAIRE

    Ceresa, Francesco; Belda, E.J.; Kvist, Laura; Rguibi-Idrissi, Hamid; Monrós González, Juan Salvador

    2015-01-01

    Wetlands are naturally patchy habitats, but patchiness has been accentuated by the extensive wetlands loss due to human activities. In such a fragmented habitat, dispersal ability is especially important to maintain gene flow between populations. Here we studied population structure, genetic diversity and demographic history of Iberian and North African populations of two wetland passerines, the Eurasian reed warbler Acrocephalus scirpaceus and the moustached warbler Acrocephalus melanopogon....

  5. Dietary Resveratrol Does Not Affect Life Span, Body Composition, Stress Response, and Longevity-Related Gene Expression in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Stefanie Staats

    2018-01-01

    Full Text Available In this study, we tested the effect of the stilbene resveratrol on life span, body composition, locomotor activity, stress response, and the expression of genes encoding proteins centrally involved in ageing pathways in the model organism Drosophila melanogaster. Male and female w1118 D. melanogaster were fed diets based on sucrose, corn meal, and yeast. Flies either received a control diet or a diet supplemented with 500 µmol/L resveratrol. Dietary resveratrol did not affect mean, median, and maximal life span of male and female flies. Furthermore, body composition remained largely unchanged following the resveratrol supplementation. Locomotor activity, as determined by the climbing index, was not significantly different between control and resveratrol-supplemented flies. Resveratrol-fed flies did not exhibit an improved stress response towards hydrogen peroxide as compared to controls. Resveratrol did not change mRNA steady levels of antioxidant (catalase, glutathione-S-transferase, NADH dehydrogenase, glutathione peroxidase, superoxide dismutase 2 and longevity-related genes, including sirtuin 2, spargel, and I’m Not Dead Yet. Collectively, present data suggest that resveratrol does not affect life span, body composition, locomotor activity, stress response, and longevity-associated gene expression in w1118 D. melanogaster.

  6. Dietary Resveratrol Does Not Affect Life Span, Body Composition, Stress Response, and Longevity-Related Gene Expression in Drosophila melanogaster.

    Science.gov (United States)

    Staats, Stefanie; Wagner, Anika E; Kowalewski, Bianca; Rieck, Florian T; Soukup, Sebastian T; Kulling, Sabine E; Rimbach, Gerald

    2018-01-11

    In this study, we tested the effect of the stilbene resveratrol on life span, body composition, locomotor activity, stress response, and the expression of genes encoding proteins centrally involved in ageing pathways in the model organism Drosophila melanogaster . Male and female w 1118 D. melanogaster were fed diets based on sucrose, corn meal, and yeast. Flies either received a control diet or a diet supplemented with 500 µmol/L resveratrol. Dietary resveratrol did not affect mean, median, and maximal life span of male and female flies. Furthermore, body composition remained largely unchanged following the resveratrol supplementation. Locomotor activity, as determined by the climbing index, was not significantly different between control and resveratrol-supplemented flies. Resveratrol-fed flies did not exhibit an improved stress response towards hydrogen peroxide as compared to controls. Resveratrol did not change mRNA steady levels of antioxidant ( catalase , glutathione-S-transferase , NADH dehydrogenase , glutathione peroxidase , superoxide dismutase 2 ) and longevity-related genes, including sirtuin 2 , spargel , and I'm Not Dead Yet . Collectively, present data suggest that resveratrol does not affect life span, body composition, locomotor activity, stress response, and longevity-associated gene expression in w 1118 D. melanogaster .

  7. Methyl jasmonate affects phenolic metabolism and gene expression in blueberry (Vaccinium corymbosum).

    Science.gov (United States)

    Cocetta, Giacomo; Rossoni, Mara; Gardana, Claudio; Mignani, Ilaria; Ferrante, Antonio; Spinardi, Anna

    2015-02-01

    Blueberry (Vaccinium corymbosum) is a fruit very much appreciated by consumers for its antioxidant potential and health-promoting traits. Its beneficial potential properties are mainly due to a high content of anthocyanins and their amount can change after elicitation with methyl jasmonate. The aim of this work is to evaluate the changes in expression of several genes, accumulation of phenolic compounds and alterations in antioxidant potential in two different blueberry cultivars ('Duke' and 'Blueray') in response to methyl jasmonate (0.1 mM). Results showed that 9 h after treatment, the expression of phenylalanine ammonium lyase, chalcone synthase and anthocyanidin synthase genes was stimulated more in the 'Blueray' variety. Among the phenols measured an increase was recorded also for epicatechin and anthocyanin concentrations. 'Duke' is a richer sourche of anthocyanins compared to 'Blueray', treatment with methyl jasmonate promoted in 'Blueray' an increase in pigments as well as in the antioxidant potential, especially in fully ripe berries, but treated 'Duke' berries had greater levels, which were not induced by methyl jasmonate treatment. In conclusion, methyl jasmonate was, in some cases, an effective elicitor of phenolic metabolism and gene expression in blueberry, though with different intensity between cultivars. © 2014 Scandinavian Plant Physiology Society.

  8. Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

    International Nuclear Information System (INIS)

    Canuto, K S; Sergio, L P S; Mencalha, A L; Fonseca, A S; Paoli, F

    2016-01-01

    Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases. (paper)

  9. Natural variation in the VELVET gene bcvel1 affects virulence and light-dependent differentiation in Botrytis cinerea.

    Science.gov (United States)

    Schumacher, Julia; Pradier, Jean-Marc; Simon, Adeline; Traeger, Stefanie; Moraga, Javier; Collado, Isidro González; Viaud, Muriel; Tudzynski, Bettina

    2012-01-01

    Botrytis cinerea is an aggressive plant pathogen causing gray mold disease on various plant species. In this study, we identified the genetic origin for significantly differing phenotypes of the two sequenced B. cinerea isolates, B05.10 and T4, with regard to light-dependent differentiation, oxalic acid (OA) formation and virulence. By conducting a map-based cloning approach we identified a single nucleotide polymorphism (SNP) in an open reading frame encoding a VELVET gene (bcvel1). The SNP in isolate T4 results in a truncated protein that is predominantly found in the cytosol in contrast to the full-length protein of isolate B05.10 that accumulates in the nuclei. Deletion of the full-length gene in B05.10 resulted in the T4 phenotype, namely light-independent conidiation, loss of sclerotial development and oxalic acid production, and reduced virulence on several host plants. These findings indicate that the identified SNP represents a loss-of-function mutation of bcvel1. In accordance, the expression of the B05.10 copy in T4 rescued the wild-type/B05.10 phenotype. BcVEL1 is crucial for full virulence as deletion mutants are significantly hampered in killing and decomposing plant tissues. However, the production of the two best known secondary metabolites, the phytotoxins botcinic acid and botrydial, are not affected by the deletion of bcvel1 indicating that other factors are responsible for reduced virulence. Genome-wide expression analyses of B05.10- and Δbcvel1-infected plant material revealed a number of genes differentially expressed in the mutant: while several protease- encoding genes are under-expressed in Δbcvel1 compared to the wild type, the group of over-expressed genes is enriched for genes encoding sugar, amino acid and ammonium transporters and glycoside hydrolases reflecting the response of Δbcvel1 mutants to nutrient starvation conditions.

  10. Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms.

    Science.gov (United States)

    Treasure, Tom; Takkenberg, J J M; Pepper, John

    2014-10-01

    Elective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long-term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered.

  11. Results of aortic root reimplantation in patients with ascending aortic aneurysm and concomitant aortic insufficiency

    Directory of Open Access Journals (Sweden)

    А. М. Чернявский

    2016-01-01

    Full Text Available Objective. The research was designed to evaluate the results of valve-sparing operations: aortic root reimplantation versus aortic valve reimplantation when repairing an ascending aortic aneurysm with concomitant aortic insufficiency.Methods. Within a blind prospective randomized study conducted over a period from 2011 to 2015, 64 patients underwent aortic valve-sparing surgery. The inclusion criteria were the presence of an aortic aneurysm of the ascending aorta exceeding 4.5 cm and concomitant aortic insufficiency. All patients were divided into two groups: FS-group, aortic root reimplantation (modified Florida Sleeve technique (n = 32 and D-group, aortic valve reimplantation (David procedure (n = 32. The average age of patients was 57±13 (23–73 years in the FS-group and 55±11 (15–72 years in the D-group (p = 0.54. Both groups had 78% of males (p>0.99. A Marfan syndrome was identified in 6% and 9% in the FS-group and D-group respectively (p>0.99. Mean diameter of the sinuses of Valsalva was 51±7 mm and 56±10 mm (p = 0.09, aortic insufficiency 2.6±0.7 and 2.8±0.8 (p = 0.15 in the FS-group and D-group respectively. In the FS-group and D-group LVEDD amounted to 5.5±0.7 mm and 5.9±1.0 mm (p = 0.09 respectively. All patients took echocardiography in the preoperative, postoperative and follow-up periods.Results. In the long-term period, the degree of aortic regurgitation was 1.2±0.1 in the FS-group and 1.3±0.6 in the D-group (p = 0.72. LVEDD was 123±23 mm in the FS-group and 139.6±80 mm in the D-group at follow-up (p = 0.77. There were no statistically significant differences in the analysis of complications. Overall 30-day in-hospital mortality was 7.8%. There were 2 (6.3% deaths in the FS-group and 3 (9.4% in the D-group (p = 0.5.Late mortality was 6.3% in the FS-group and 3.1% in the D-group (p>0.99. Cumulative survival at 4 years was 84.3% and 84.8% in the FS-group and the D-group respectively (p = 0.94. Cumulative freedom from

  12. Current role of endovascular therapy in Marfan patients with previous aortic surgery

    Directory of Open Access Journals (Sweden)

    Ibrahim Akin

    2008-02-01

    Full Text Available Ibrahim Akin, Stephan Kische, Tim C Rehders, Tushar Chatterjee, Henrik Schneider, Thomas Körber, Christoph A Nienaber, Hüseyin InceDepartment of Medicine, Division of Cardiology at the University Hospital Rostock, Rostock School of Medicine, Ernst-Heydemann-Str. 6, 18057 Rostock, GermanyAbstract: The Marfan syndrome is a heritable disorder of the connective tissue which affects the cardiovascular, ocular, and skeletal system. The cardiovascular manifestation with aortic root dilatation, aortic valve regurgitation, and aortic dissection has a prevalence of 60% to 90% and determines the premature death of these patients. Thirty-four percent of the patients with Marfan syndrome will have serious cardiovascular complications requiring surgery in the first 10 years after diagnosis. Before aortic surgery became available, the majority of the patients died by the age of 32 years. Introduction in the aortic surgery techniques caused an increase of the 10 year survival rate up to 97%. The purpose of this article is to give an overview about the feasibility and outcome of stent-graft placement in the descending thoracic aorta in Marfan patients with previous aortic surgery.Keywords: Marfan syndrome, aortic dissection, root replacement, stent-graft, previous aortic surgery

  13. Adaptive evolution of a key gene affecting queen and worker traits in the honey bee, Apis mellifera.

    Science.gov (United States)

    Kent, Clement F; Issa, Amer; Bunting, Alexandra C; Zayed, Amro

    2011-12-01

    The vitellogenin egg yolk precursor protein represents a well-studied case of social pleiotropy in the model organism Apis mellifera. Vitellogenin is associated with fecundity in queens and plays a major role in controlling division of labour in workers, thereby affecting both individual and colony-level fitness. We studied the molecular evolution of vitellogenin and seven other genes sequenced in a large population panel of Apis mellifera and several closely related species to investigate the role of social pleiotropy on adaptive protein evolution. We found a significant excess of nonsynonymous fixed differences between A. mellifera, A. cerana and A. florea relative to synonymous sites indicating high rates of adaptive evolution at vitellogenin. Indeed, 88% of amino acid changes were fixed by selection in some portions of the gene. Further, vitellogenin exhibited hallmark signatures of selective sweeps in A. mellifera, including a significant skew in the allele frequency spectrum, extreme levels of genetic differentiation and linkage disequilibrium. Finally, replacement polymorphisms in vitellogenin were significantly enriched in parts of the protein involved in binding lipid, establishing a link between the gene's structure, function and effects on fitness. Our case study provides unequivocal evidence of historical and ongoing bouts of adaptive evolution acting on a key socially pleiotropic gene in the honey bee. © 2011 Blackwell Publishing Ltd.

  14. Two distinct genomic regions, harbouring the period and fruitless genes, affect male courtship song in Drosophila montana.

    Science.gov (United States)

    Lagisz, M; Wen, S-Y; Routtu, J; Klappert, K; Mazzi, D; Morales-Hojas, R; Schäfer, M A; Vieira, J; Hoikkala, A; Ritchie, M G; Butlin, R K

    2012-06-01

    Acoustic signals often have a significant role in pair formation and in species recognition. Determining the genetic basis of signal divergence will help to understand signal evolution by sexual selection and its role in the speciation process. An earlier study investigated quantitative trait locus for male courtship song carrier frequency (FRE) in Drosophila montana using microsatellite markers. We refined this study by adding to the linkage map markers for 10 candidate genes known to affect song production in Drosophila melanogaster. We also extended the analyses to additional song characters (pulse train length (PTL), pulse number (PN), interpulse interval, pulse length (PL) and cycle number (CN)). Our results indicate that loci in two different regions of the genome control distinct features of the courtship song. Pulse train traits (PTL and PN) mapped to the X chromosome, showing significant linkage with the period gene. In contrast, characters related to song pulse properties (PL, CN and carrier FRE) mapped to the region of chromosome 2 near the candidate gene fruitless, identifying these genes as suitable loci for further investigations. In previous studies, the pulse train traits have been found to vary substantially between Drosophila species, and so are potential species recognition signals, while the pulse traits may be more important in intra-specific mate choice.

  15. Renal Infarction from Type B Aortic Dissection

    Directory of Open Access Journals (Sweden)

    Marit Tweet

    2017-07-01

    ascending aorta and is usually managed surgically. A Stanford Type B dissection begins distal to the left subclavian artery and is often managed medically with specific focus on blood pressure reduction. Aortic dissection can involve various branching vessels which will affect both how the patient presents and the complexity of their medical course. Patients can present with limb ischemia, syncope, stroke, acute renal failure, mesenteric ischemia, myocardial infarction, or, such as the above patient, back and abdominal pain.1 While pain is often a presenting complaint, aortic dissections should be considered in the absence of pain.2 Painless limb paralysis can occur secondary to dissection involving vessels supplying the spinal cord.3 Diagnosis is typically made by CTA, which has a sensitivity of 98%-100%, although an initial chest x-ray can detect findings concerning for aortic dissection in 60%-90% of cases.4 Early and aggressive blood pressure control is essential to prevent worsening of the dissection by decreasing afterload and shearing forces. The preferred anti-hypertensive would be a titratable beta blocker such as esmolol or labetalol. Vascular surgery consultation can help determine the effects of branching vessel compromise or the treatment course for the patient. For management of the above patient, vascular surgery was emergently consulted. Repeat vital signs included blood pressure 182/97, heart rate 77, respiratory rate 16, and oxygen saturation 100% on 2L nasal cannula. Labetalol infusion was initiated to control her elevated blood pressure with a goal of less than 120/80, intermittent fentanyl addressed pain and intravenous hydration was begun to protect her renal function. Additionally, she was started on a heparin drip to prevent thrombosis in the false lumen. This is not generally the standard of care for aortic dissections, but can be appropriate to avoid thrombosis-related complications in some patients.6

  16. Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with tricuspid aortic valve.

    Science.gov (United States)

    Xuan, Yue; Wang, Zhongjie; Liu, Raymond; Haraldsson, Henrik; Hope, Michael D; Saloner, David A; Guccione, Julius M; Ge, Liang; Tseng, Elaine

    2018-03-08

    Guidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts. Patients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress. Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid

  17. AAV-mediated gene transfer of the obesity-associated gene Etv5 in rat midbrain does not affect energy balance or motivated behavior.

    Directory of Open Access Journals (Sweden)

    Arjen J Boender

    Full Text Available Several genome-wide association studies have implicated the transcription factor E-twenty- six version 5 (Etv5 in the regulation of body mass index. Further substantiating the role of Etv5 in feeding behavior are the findings that targeted disruption of Etv5 in mice leads to decreased body weight gain and that expression of Etv5 is decreased in the ventral tegmental area and substantia nigra pars compacta (VTA/SNpc after food restriction. As Etv5 has been suggested to influence dopaminergic neurotransmission by driving the expression of genes that are responsible for the synthesis and release of dopamine, we investigated if expression levels of Etv5 are dependent on nutritional state and subsequently influence the expression levels of tyrosine hydroxylase. While it was shown that Etv5 expression in the VTA/SNpc increases after central administration of leptin and that Etv5 was able to drive expression of tyrosine hydroxylase in vitro, AAV-mediated gene transfer of Etv5 into the VTA/SNpc of rats did not alter expression of tyrosine hydroxylase in vivo. Moreover, AAV-mediated gene transfer of Etv5 in the VTA/SNpc did not affect measures of energy balance or performances in a progressive ratio schedule. Thus, these data do not support a role for increased expression of Etv5 in the VTA/SNpc in the regulation of feeding behavior.

  18. Evidence of major genes affecting stress response in rainbow trout using Bayesian methods of complex segregation analysis

    DEFF Research Database (Denmark)

    Vallejo, R L; Rexroad III, C E; Silverstein, J T

    2009-01-01

    As a first step toward the genetic mapping of QTL affecting stress response variation in rainbow trout, we performed complex segregation analyses (CSA) fitting mixed inheritance models of plasma cortisol by using Bayesian methods in large full-sib families of rainbow trout. To date, no studies have...... been conducted to determine the mode of inheritance of stress response as measured by plasma cortisol response when using a crowding stress paradigm and CSA in rainbow trout. The main objective of this study was to determine the mode of inheritance of plasma cortisol after a crowding stress....... The results from fitting mixed inheritance models with Bayesian CSA suggest that 1 or more major genes with dominant cortisol-decreasing alleles and small additive genetic effects of a large number of independent genes likely underlie the genetic variation of plasma cortisol in the rainbow trout families...

  19. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells

    NARCIS (Netherlands)

    M.J. Crop (Meindert); C.C. Baan (Carla); S.S. Korevaar (Sander); J.N.M. IJzermans (Jan); M. Pescatori (Mario); A. Stubbs (Andrew); W.F.J. van IJcken (Wilfred); M.H. Dahlke (Marc); E. Eggenhofer (Elke); W. Weimar (Willem); M.J. Hoogduijn (Martin)

    2010-01-01

    textabstractThere is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose

  20. Agaricus brasiliensis (sun mushroom) affects the expression of genes related to cholesterol homeostasis.

    Science.gov (United States)

    de Miranda, Aline Mayrink; Rossoni Júnior, Joamyr Victor; Souza E Silva, Lorena; Dos Santos, Rinaldo Cardoso; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia

    2017-06-01

    The sun mushroom (Agaricus brasiliensis) is considered a major source of bioactive compounds with potential health benefits. Mushrooms typically act as lipid-lowering agents; however, little is known about the mechanisms of action of A. brasiliensis in biological systems. This study aimed to determine the underlying mechanism involved in the cholesterol-lowering effect of A. brasiliensis through the assessment of fecal and serum lipid profiles in addition to gene expression analysis of specific transcription factors, enzymes, and transporters involved in cholesterol homeostasis. Twenty-four albino Fischer rats approximately 90 days old, with an average weight of 205 g, were divided into four groups of 6 each and fed a standard AIN-93 M diet (C), hypercholesterolemic diet (H), hypercholesterolemic diet +1 % A. brasiliensis (HAb), or hypercholesterolemic diet +0.008 % simvastatin (HS) for 6 weeks. Simvastatin was used as a positive control, as it is a typical drug prescribed for lipid disorders. Subsequently, blood, liver, and feces samples were collected for lipid profile and quantitative real-time polymerase chain reaction gene expression analyses. Diet supplementation with A. brasiliensis significantly improved serum lipid profiles, comparable to the effect observed for simvastatin. In addition, A. brasiliensis dietary supplementation markedly promoted fecal cholesterol excretion. Increased expression of 7α-hydroxylase (CYP7A1), ATP-binding cassette subfamily G-transporters (ABCG5/G8), and low-density lipoprotein receptor (LDLR) was observed following A. brasiliensis administration. Our results suggest that consumption of A. brasiliensis improves the serum lipid profile in hypercholesterolemic rats by modulating the expression of key genes involved in hepatic cholesterol metabolism.

  1. Manipulation of MKS1 gene expression affects Kalanchoë blossfeldiana and Petunia hybrida phenotypes.

    Science.gov (United States)

    Gargul, Joanna Maria; Mibus, Heiko; Serek, Margrethe

    2015-01-01

    The establishment of alternative methods to chemical treatments for growth retardation and pathogen protection in ornamental plant production has become a major goal in recent breeding programmes. This study evaluates the effect of manipulating MAP kinase 4 nuclear substrate 1 (MKS1) expression in Kalanchoë blossfeldiana and Petunia hybrida. The Arabidopsis thaliana MKS1 gene was overexpressed in both species via Agrobacterium-mediated transformation, resulting in dwarfed phenotypes and delayed flowering in both species and increased tolerance to Pseudomonas syringae pv. tomato in transgenic Petunia plants. The lengths of the stems and internodes were decreased, while the number of nodes in the transgenic plants was similar to that of the control plants in both species. The transgenic Kalanchoë flowers had an increased anthocyanin concentration, and the length of the inflorescence stem was decreased. The morphology of transgenic Petunia flowers was not altered. The results of the Pseudomonas syringae tolerance test showed that Petunia plants with one copy of the transgene reacted similarly to the nontransgenic control plants; however, plants with four copies of the transgene exhibited considerably higher tolerance to bacterial attack. Transgene integration and expression was determined by Southern blot hybridization and RT-PCR analyses. MKS1 in wild-type Petunia plants was down-regulated through a virus-induced gene silencing (VIGS) method using tobacco rattle virus vectors. There were no significant phenotypic differences between the plants with silenced MKS1 genes and the controls. The relative concentration of the MKS1 transcript in VIGS-treated plants was estimated by quantitative RT-PCR. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  2. Identification of Chloride Intracellular Channel Protein 3 as a Novel Gene Affecting Human Bone Formation

    DEFF Research Database (Denmark)

    Brum, A M; Leije, M; J, Schreuders-Koedam

    2017-01-01

    is diminished and more adipocytes are seen in the bone marrow, suggesting a shift in MSC lineage commitment. Identification of specific factors that stimulate osteoblast differentiation from human MSCs may deliver therapeutic targets to treat osteoporosis. The aim of this study was to identify novel genes...... an in vivo human bone formation model in which hMSCs lentivirally transduced with the CLIC3 overexpression construct were loaded onto a scaffold (hydroxyapatite-tricalcium-phosphate), implanted under the skin of NOD-SCID mice, and analyzed for bone formation 8 weeks later. CLIC3 overexpression led to a 15...

  3. Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants.

    Science.gov (United States)

    Pauwels, Sara; Ghosh, Manosij; Duca, Radu Corneliu; Bekaert, Bram; Freson, Kathleen; Huybrechts, Inge; Langie, Sabine A S; Koppen, Gudrun; Devlieger, Roland; Godderis, Lode

    2017-01-01

    Maternal nutrition during pregnancy and infant nutrition in the early postnatal period (lactation) are critically involved in the development and health of the newborn infant. The Maternal Nutrition and Offspring's Epigenome (MANOE) study was set up to assess the effect of maternal methyl-group donor intake (choline, betaine, folate, methionine) on infant DNA methylation. Maternal intake of dietary methyl-group donors was assessed using a food-frequency questionnaire (FFQ). Before and during pregnancy, we evaluated maternal methyl-group donor intake through diet and supplementation (folic acid) in relation to gene-specific ( IGF2 DMR, DNMT1 , LEP , RXRA ) buccal epithelial cell DNA methylation in 6 months old infants ( n  = 114) via pyrosequencing. In the early postnatal period, we determined the effect of maternal choline intake during lactation (in mothers who breast-fed for at least 3 months) on gene-specific buccal DNA methylation ( n  = 65). Maternal dietary and supplemental intake of methyl-group donors (folate, betaine, folic acid), only in the periconception period, was associated with buccal cell DNA methylation in genes related to growth ( IGF2 DMR), metabolism ( RXRA ), and appetite control ( LEP ). A negative association was found between maternal folate and folic acid intake before pregnancy and infant LEP (slope = -1.233, 95% CI -2.342; -0.125, p  = 0.0298) and IGF2 DMR methylation (slope = -0.706, 95% CI -1.242; -0.107, p  = 0.0101), respectively. Positive associations were observed for maternal betaine (slope = 0.875, 95% CI 0.118; 1.633, p  = 0.0241) and folate (slope = 0.685, 95% CI 0.245; 1.125, p  = 0.0027) intake before pregnancy and RXRA methylation. Buccal DNMT1 methylation in the infant was negatively associated with maternal methyl-group donor intake in the first and second trimester of pregnancy and negatively in the third trimester. We found no clear association between maternal choline intake

  4. When silence is noise: infantile-onset Barth syndrome caused by a synonymous substitution affecting TAZ gene transcription.

    Science.gov (United States)

    Ferri, L; Dionisi-Vici, C; Taurisano, R; Vaz, F M; Guerrini, R; Morrone, A

    2016-11-01

    Barth syndrome (BTHS) is an X-linked inborn error of metabolism which affects males. The main manifestations are cardiomyopathy, myopathy, hypotonia, growth delay, intermittent neutropenia and 3-methylglutaconic aciduria. Diagnosis is confirmed by mutational analysis of the TAZ gene and biochemical dosage of the monolysocardiolipin/tetralinoleoyl cardiolipin (MLCL:L4-CL) ratio. We report a 6-year-old boy who presented with severe hypoglycemia, lactic acidosis and severe dilated cardiomyopathy soon after birth. The MLCL:L4-CL ratio confirmed BTHS (3.90 on patient's fibroblast, normal: 0-0.3). Subsequent sequencing of the TAZ gene revealed only the new synonymous variant NM_000116.3 (TAZ):c.348C>T p.(Gly116Gly), which did not appear to affect the protein sequence. In silico prediction analysis suggested the new c.348C>T nucleotide change could alter the TAZ mRNA splicing processing. We analyzed TAZ mRNAs in the patient's fibroblasts and found an abnormal skipping of 24 bases (NM_000116.3:c.346_371), with the consequent ablation of 8 amino acid residues in the tafazzin protein (NP_000107.1:p.Lys117_Gly124del). Molecular analysis of at risk female family members identified the patient's sister and mother as heterozygous carriers. Apparently harmless synonymous variants in the TAZ gene can damage gene expression. Such findings widen our knowledge of molecular heterogeneity in BTHS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Das, Amitabh, E-mail: amitabhdas.kn@gmail.com [Department of Bionanotechnology, Hanyang University, Seoul 133-791 (Korea, Republic of); Chai, Jin Choul, E-mail: jincchai@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Jung, Kyoung Hwa, E-mail: khjung2@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Das, Nando Dulal, E-mail: nando.hu@gmail.com [Clinical Research Centre, Inha University School of Medicine, Incheon 400-711 (Korea, Republic of); Kang, Sung Chul, E-mail: gujiju11@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Lee, Young Seek, E-mail: yslee@hanyang.ac.kr [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Seo, Hyemyung, E-mail: hseo@hanyang.ac.kr [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Chai, Young Gyu, E-mail: ygchai@hanyang.ac.kr [Department of Bionanotechnology, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of)

    2014-11-01

    JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53-null neuroectodermal stem cells (p53{sup −/−} NE-4Cs). We determined the effect of LPS as a model of inflammation in p53{sup −/−} NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53{sup −/−} NE-4Cs and in LPS-stimulated JMJD2A-kd p53{sup −/−} NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6rα, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-α (PFT-α). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. - Highlights: • Significant up-regulation of epigenetic modifier JMJD2A mRNA upon LPS treatment. • Inhibition of JMJD2A attenuated key inflammatory and tumourigenic genes. • Establishing IPA based functional genomics in JMJD2A-attenuated p53{sup

  6. Polymorphism screening and haplotype analysis of the tryptophan hydroxylase gene (TPH1 and association with bipolar affective disorder in Taiwan

    Directory of Open Access Journals (Sweden)

    Lin Yi-Mei J

    2005-03-01

    Full Text Available Abstract Background Disturbances in serotonin neurotransmission are implicated in the etiology of many psychiatric disorders, including bipolar affective disorder (BPD. The tryptophan hydroxylase gene (TPH, which codes for the enzyme catalyzing the rate-limiting step in serotonin biosynthetic pathway, is one of the leading candidate genes for psychiatric and behavioral disorders. In a preliminary study, we found that TPH1 intron7 A218C polymorphism was associated with BPD. This study was designed to investigate sequence variants of the TPH1 gene in Taiwanese and to test whether the TPH1 gene is a susceptibility factor for the BPD. Methods Using a systematic approach, we have searched the exons and promoter region of the TPH1 gene for sequence variants in Taiwanese Han and have identified five variants, A-1067G, G-347T, T3804A, C27224T, and A27237G. These five variants plus another five taken from the literature and a public database were examined for an association in 108 BPD patients and 103 controls; no association was detected for any of the 10 variants. Results Haplotype constructions using these 10 SNPs showed that the 3 most common haplotypes in both patients and controls were identical. One of the fourth common haplotype in the patient group (i.e. GGGAGACCCA was unique and showed a trend of significance with the disease (P = 0.028. However, the significance was abolished after Bonferroni correction thus suggesting the association is weak. In addition, three haplotype-tagged SNPs (htSNPs were selected to represent all haplotypes with frequencies larger than 2% in the Taiwanese Han population. The defined TPH1 htSNPs significantly reduce the marker number for haplotype analysis thus provides useful information for future association studies in our population. Conclusion Results of this study did not support the role of TPH1 gene in BPD etiology. As the current studies found the TPH1 gene under investigation belongs to the peripheral

  7. Bovine aortic arch: A novel association with thoracic aortic dilation

    International Nuclear Information System (INIS)

    Malone, C.D.; Urbania, T.H.; Crook, S.E.S.; Hope, M.D.

    2012-01-01

    Aim: To investigate whether there is a link between bovine arch and thoracic aortic aneurysm. Materials and methods: Computed tomography (CT) and magnetic resonance imaging (MRI) images of the thorax of 191 patients with dilated thoracic aortas and 391 consecutive, unselected patients as controls were retrospectively reviewed. Bovine arch was considered present if either a shared origin of the left common carotid and innominate arteries or an origin of the left common carotid from the innominate artery was identified. A chi-square test was used to evaluate the significance of differences between subgroups. Results: A trend towards increased prevalence of bovine arch was seen in patients with dilated aortas (26.2%) compared to controls (20.5%, p = 0.12). The association was statistically significant in patients over 70 years old (31.9%, p = 0.019) and when dilation involved the aortic arch (47.6%, p = 0.003). Conclusions: An association between bovine arch and aortic dilation is seen in older patients, and when dilation involves the aortic arch. Bovine arch should be considered a potential risk factor for thoracic aortic aneurysm.

  8. The garlic allelochemical diallyl disulfide affects tomato root growth by influencing cell division, phytohormone balance and expansin gene expression

    Directory of Open Access Journals (Sweden)

    Fang Cheng

    2016-08-01

    Full Text Available Diallyl disulfide (DADS is a volatile organosulfur compound derived from garlic (Allium sativum L., and it is known as an allelochemical responsible for the strong allelopathic potential of garlic. The anticancer properties of DADS have been studied in experimental animals and various types of cancer cells, but to date, little is known about its mode of action as an allelochemical at the cytological level. The current research presents further studies on the effects of DADS on tomato (Solanum lycopersicum L. seed germination, root growth, mitotic index and cell size in root meristem, as well as the phytohormone levels and expression profile of auxin biosynthesis genes (FZYs, auxin transport genes (SlPINs and expansin genes (EXPs in tomato root. The results showed a biphasic, dose-dependent effect on tomato seed germination and root growth under different DADS concentrations. Lower concentrations (0.01-0.62 mM of DADS significantly promoted root growth, whereas higher levels (6.20-20.67 mM showed inhibitory effects. Cytological observations showed that the cell length of root meristem was increased and that the mitotic activity of meristematic cells in seedling root tips was enhanced at lower concentrations of DADS. In contrast, DADS at higher concentrations inhibited root growth by affecting both the length and division activity of meristematic cells. However, the cell width of the root meristem was not affected. Additionally, DADS increased the IAA and ZR contents of seedling roots in a dose-dependent manner. The influence on IAA content may be mediated by the up-regulation of FZYs and PINs. Further investigation into the underlying mechanism revealed that the expression levels of tomato EXPs were significantly affected by DADS. The expression levels of EXPB2 and beta-expansin precursor were increased after 3 d, and those of EXP1, EXPB3 and EXLB1 were increased after 5 d of DADS treatment (0.41 mM. This result suggests that tomato root growth

  9. Endoluminal treatment of aortic dissection

    Energy Technology Data Exchange (ETDEWEB)

    Chavan, Ajay; Lotz, Joachim; Galanski, Michael [Department of Diagnostic Radiology, Hannover Medical School, Carl Neuberg Strasse 1, 30625, Hannover (Germany); Oelert, Frank; Haverich, Axel; Karck, Matthias [Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl Neuberg Strasse 1, 30625, Hannover (Germany)

    2003-11-01

    Aortic dissection is most often a catastrophic medical emergency which, if untreated, can be potentially fatal. The intention of therapy in patients with aortic dissection is to prevent aortic rupture or aneurysm formation as well as to relieve branch vessel ischaemia. Patients with aortic dissection are often poor candidates for anaesthesia and surgery and the surgical procedure itself is challenging requiring thoracotomy, aortic cross clamping, blood transfusion as well as prolonged hospital stay in some cases. Operative mortality is especially high in patients with critical mesenteric or renal ischaemia. The past decade has experienced the emergence of a number of interventional radiological or minimally invasive techniques which have significantly improved the management of patients with aortic dissection. These include stent grafting for entry site closure to prevent aneurysmatic widening of the false lumen as well as percutaneous techniques such as balloon fenestration of the intimal flap and aortic true lumen stenting to alleviate branch vessel ischaemia. False lumen thrombosis following entry closure with stent grafts has been observed in 86-100% of patients, whereas percutaneous interventions are able to effectively relieve organ ischaemia in approximately 90% of the cases. In the years to come, it is to be expected that these endoluminal techniques will become the method of choice for treating most type-B dissections and will assist in significantly reducing the number of open surgical procedures required for type-A dissections. The intention of this article is to provide an overview of the current status of these endoluminal techniques based on our own experience as well as on a review of the relevant literature. (orig.)

  10. Endoluminal treatment of aortic dissection

    International Nuclear Information System (INIS)

    Chavan, Ajay; Lotz, Joachim; Galanski, Michael; Oelert, Frank; Haverich, Axel; Karck, Matthias

    2003-01-01

    Aortic dissection is most often a catastrophic medical emergency which, if untreated, can be potentially fatal. The intention of therapy in patients with aortic dissection is to prevent aortic rupture or aneurysm formation as well as to relieve branch vessel ischaemia. Patients with aortic dissection are often poor candidates for anaesthesia and surgery and the surgical procedure itself is challenging requiring thoracotomy, aortic cross clamping, blood transfusion as well as prolonged hospital stay in some cases. Operative mortality is especially high in patients with critical mesenteric or renal ischaemia. The past decade has experienced the emergence of a number of interventional radiological or minimally invasive techniques which have significantly improved the management of patients with aortic dissection. These include stent grafting for entry site closure to prevent aneurysmatic widening of the false lumen as well as percutaneous techniques such as balloon fenestration of the intimal flap and aortic true lumen stenting to alleviate branch vessel ischaemia. False lumen thrombosis following entry closure with stent grafts has been observed in 86-100% of patients, whereas percutaneous interventions are able to effectively relieve organ ischaemia in approximately 90% of the cases. In the years to come, it is to be expected that these endoluminal techniques will become the method of choice for treating most type-B dissections and will assist in significantly reducing the number of open surgical procedures required for type-A dissections. The intention of this article is to provide an overview of the current status of these endoluminal techniques based on our own experience as well as on a review of the relevant literature. (orig.)

  11. Interplay of Gene Expression Noise and Ultrasensitive Dynamics Affects Bacterial Operon Organization

    Science.gov (United States)

    Ray, J. Christian J; Igoshin, Oleg A.

    2012-01-01

    Bacterial chromosomes are organized into polycistronic cotranscribed operons, but the evolutionary pressures maintaining them are unclear. We hypothesized that operons alter gene expression noise characteristics, resulting in selection for or against maintaining operons depending on network architecture. Mathematical models for 6 functional classes of network modules showed that three classes exhibited decreased noise and 3 exhibited increased noise with same-operon cotranscription of interacting proteins. Noise reduction was often associated with a decreased chance of reaching an ultrasensitive threshold. Stochastic simulations of the lac operon demonstrated that the predicted effects of transcriptional coupling hold for a complex network module. We employed bioinformatic analysis to find overrepresentation of noise-minimizing operon organization compared with randomized controls. Among constitutively expressed physically interacting protein pairs, higher coupling frequencies appeared at lower expression levels, where noise effects are expected to be dominant. Our results thereby suggest an important role for gene expression noise, in many cases interacting with an ultrasensitive switch, in maintaining or selecting for operons in bacterial chromosomes. PMID:22956903

  12. Left Ventricular Assist Device Implantation with Concomitant Aortic Valve and Ascending Aortic Replacement.

    Science.gov (United States)

    Huenges, Katharina; Panholzer, Bernd; Cremer, Jochen; Haneya, Assad

    2018-01-01

    Left ventricular assist device (LVAD) is nowadays a routine therapy for patients with advanced heart failure. We present the case of a 74-year-old male patient who was admitted to our center with terminal heart failure in dilated cardiomyopathy and ascending aortic aneurysm with aortic valve regurgitation. The LVAD implantation with simultaneous aortic valve and supracoronary ascending aortic replacement was successfully performed.

  13. Dynamics of the aortic annulus in 4D CT angiography for transcatheter aortic valve implantation patients

    NARCIS (Netherlands)

    Elattar, Mustafa A.; Vink, Leon W.; van Mourik, Martijn S.; Baan, Jan; Vanbavel, Ed T.; Planken, R. Nils; Marquering, Henk A.

    2017-01-01

    Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic valve stenosis. This procedure requires pre-operative planning by assessment of aortic dimensions on CT Angiography (CTA). It is well-known that the aortic root dimensions vary over the

  14. The expression of the clock gene cycle has rhythmic pattern and is affected by photoperiod in the moth Sesamia nonagrioides.

    Science.gov (United States)

    Kontogiannatos, Dimitrios; Gkouvitsas, Theodoros; Kourti, Anna

    2017-06-01

    To obtain clues to the link between the molecular mechanism of circadian and photoperiod clocks, we have cloned the circadian clock gene cycle (Sncyc) in the corn stalk borer, Sesamia nonagrioides, which undergoes facultative diapause controlled by photoperiod. Sequence analysis revealed a high degree of conservation among insects for this gene. SnCYC consists of 667 amino acids and structural analysis showed that it contains a BCTR domain in its C-terminal in addition to the common domains found in Drosophila CYC, i.e. bHLH, PAS-A, PAS-B domains. The results revealed that the sequence of Sncyc showed a similarity to that of its mammalian orthologue, Bmal1. We also investigated the expression patterns of Sncyc in the brain of larvae growing under long-day 16L: 8D (LD), constant darkness (DD) and short-day 10L: 14D (SD) conditions using qRT-PCR assays. The mRNAs of Sncyc expression was rhythmic in LD, DD and SD cycles. Also, it is remarkable that the photoperiodic conditions affect the expression patterns and/or amplitudes of circadian clock gene Sncyc. This gene is associated with diapause in S. nonagrioides, because under SD (diapause conditions) the photoperiodic signal altered mRNA accumulation. Sequence and expression analysis of cyc in S. nonagrioides shows interesting differences compared to Drosophila where this gene does not oscillate or change in expression patterns in response to photoperiod, suggesting that this species is an interesting new model to study the molecular control of insect circadian and photoperiodic clocks. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Are languages really independent from genes? If not, what would a genetic bias affecting language diversity look like?

    Science.gov (United States)

    Dediu, Dan

    2011-04-01

    It is generally accepted that the relationship between human genes and language is very complex and multifaceted. This has its roots in the “regular” complexity governing the interplay among genes and between genes and environment for most phenotypes, but with the added layer of supraontogenetic and supra-individual processes defining culture. At the coarsest level, focusing on the species, it is clear that human-specific--but not necessarily faculty-specific--genetic factors subtend our capacity for language and a currently very productive research program is aiming at uncovering them. At the other end of the spectrum, it is uncontroversial that individual-level variations in different aspects related to speech and language have an important genetic component and their discovery and detailed characterization have already started to revolutionize the way we think about human nature. However, at the intermediate, glossogenetic/population level, the relationship becomes controversial, partly due to deeply ingrained beliefs about language acquisition and universality and partly because of confusions with a different type of gene-languages correlation due to shared history. Nevertheless, conceptual, mathematical and computational models--and, recently, experimental evidence from artificial languages and songbirds--have repeatedly shown that genetic biases affecting the acquisition or processing of aspects of language and speech can be amplified by population-level intergenerational cultural processes and made manifest either as fixed “universal” properties of language or as structured linguistic diversity. Here, I review several such models as well as the recently proposed case of a causal relationship between the distribution of tone languages and two genes related to brain growth and development, ASPM and Microcephalin, and I discuss the relevance of such genetic biasing for language evolution, change, and diversity.

  16. Characterization of three Agrobacterium tumefaciens avirulent mutants with chromosomal mutations that affect induction of vir genes.

    OpenAIRE

    Metts, J; West, J; Doares, S H; Matthysse, A G

    1991-01-01

    Three Agrobacterium tumefaciens mutants with chromosomal mutations that affect bacterial virulence were isolated by transposon mutagenesis. Two of the mutants were avirulent on all hosts tested. The third mutant, Ivr-211, was a host range mutant which was avirulent on Bryophyllum diagremontiana, Nicotiana tabacum, N. debneyi, N. glauca, and Daucus carota but was virulent on Zinnia elegans and Lycopersicon esculentum (tomato). That the mutant phenotype was due to the transposon insertion was d...

  17. Bicuspid Aortic Valve Disease: A Comprehensive Review

    OpenAIRE

    Mordi, Ify; Tzemos, Nikolaos

    2012-01-01

    Bicuspid aortic valve is the commonest congenital cardiac abnormality in the general population. This paper article will discuss our current knowledge of the anatomy, pathophysiology, genetics, and clinical aspects of bicuspid aortic valve disease.

  18. Mutational analysis of the Wolfram syndrome gene in two families with chromosome 4p-linked bipolar affective disorder.

    Science.gov (United States)

    Evans, K L; Lawson, D; Meitinger, T; Blackwood, D H; Porteous, D J

    2000-04-03

    Bipolar affective disorder (BPAD) is a complex disease with a significant genetic component. Heterozygous carriers of Wolfram syndrome (WFS) are at increased risk of psychiatric illness. A gene for WFS (WFS1) has recently been cloned and mapped to chromosome 4p, in the general region we previously reported as showing linkage to BPAD. Here we present sequence analysis of the WFS1 coding sequence in five affected individuals from two chromosome 4p-linked families. This resulted in the identification of six polymorphisms, two of which are predicted to change the amino acid sequence of the WFS1 protein, however none of the changes segregated with disease status. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:158-160, 2000. Copyright 2000 Wiley-Liss, Inc.

  19. Identification of novel mutations in HEXA gene in children affected with Tay Sachs disease from India.

    Directory of Open Access Journals (Sweden)

    Mehul Mistri

    Full Text Available Tay Sachs disease (TSD is a neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients. Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Mutations were confirmed in parents and looked up in public databases. In silico analysis for mutations was carried out using SIFT, Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen families were included in the study. We identified six novel missense mutations, c.340 G>A (p.E114K, c.964 G>A (p.D322N, c.964 G>T (p.D322Y, c.1178C>G (p.R393P and c.1385A>T (p.E462V, c.1432 G>A (p.G478R and two previously reported mutations. c.1277_1278insTATC and c.508C>T (p.R170W. The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. Mutations could not be identified in one family. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V.

  20. Identification of novel mutations in HEXA gene in children affected with Tay Sachs disease from India.

    Science.gov (United States)

    Mistri, Mehul; Tamhankar, Parag M; Sheth, Frenny; Sanghavi, Daksha; Kondurkar, Pratima; Patil, Swapnil; Idicula-Thomas, Susan; Gupta, Sarita; Sheth, Jayesh

    2012-01-01

    Tay Sachs disease (TSD) is a neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients). Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Mutations were confirmed in parents and looked up in public databases. In silico analysis for mutations was carried out using SIFT, Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen families were included in the study. We identified six novel missense mutations, c.340 G>A (p.E114K), c.964 G>A (p.D322N), c.964 G>T (p.D322Y), c.1178C>G (p.R393P) and c.1385A>T (p.E462V), c.1432 G>A (p.G478R) and two previously reported mutations. c.1277_1278insTATC and c.508C>T (p.R170W). The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. Mutations could not be identified in one family. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V.

  1. Aortic compliance in patients with aortic regurgitation. Evaluation with magnetic resonance imaging

    International Nuclear Information System (INIS)

    Murai, Sachiko; Hamada, Seiki; Ueguchi, Takashi

    2005-01-01

    The purpose of this study was to assess by means of cine magnetic resonance imaging (MRI) aortic compliance before and after aortic valve replacement (AVR with SJM (St. Jude Medical, St paul, MN) valve) in patients with aortic regurgitation (AR). Two groups (healthy controls and patients with severe isolated AR) of 10 subjects each were included in this study. Cine MRI was performed at three locations of the aorta, and aortic compliance was calculated by dividing the maximum change in the aortic area by pulse pressure. Cine MRI is useful to assess abnormalities of aortic compliance in patients with AR. Compared with the control group, aortic compliance in the AR group was significantly less in the ascending aorta (p<0.05), decreasing in order of aortic location. After AVR, aortic compliance improved for all locations. Cine MRI enables assessment of aortic biophysical properties such as a compliance for evaluating the progression of AR and the efficacy of treatment. (author)

  2. Abdominal aortic feminism.

    Science.gov (United States)

    Mortimer, Alice Emily

    2014-11-14

    A 79-year-old woman presented to a private medical practice 2 years previously for an elective ultrasound screening scan. This imaging provided the evidence for a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a number of recognised risk factors for an AAA, her general practitioner at the time did not follow the guidance set out by the private medical professional, that is, to refer the patient to a vascular specialist to be entered into a surveillance programme and surgically evaluated. The patient became symptomatic with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6 cm leaking AAA. She consented for an emergency open AAA repair within a few hours of being admitted to hospital, despite the 50% perioperative mortality risk. The patient spent 4 days in intensive care where she recovered well. She was discharged after a 12 day hospital stay but unfortunately passed away shortly after her discharge from a previously undiagnosed gastric cancer. 2014 BMJ Publishing Group Ltd.

  3. Analysis of the VP2 protein gene of canine parvovirus strains from affected dogs in Japan.

    Science.gov (United States)

    Soma, Takehisa; Taharaguchi, Satoshi; Ohinata, Tsuyoshi; Ishii, Hiroshi; Hara, Motonobu

    2013-04-01

    To clarify the evolution of canine parvovirus 2 (CPV-2) that has recently been epidemic in Japan, VP2 gene sequences at positions 3556-4166 were analyzed in 107 CPV-2 strains obtained from rectal swabs of diarrheic dogs from 2009 to 2011. CPV-2b (95 strains) was more frequently detected than CPV-2a (nine strains), while CPV-2c was not detected. Remaining three strains were identified as the original type CPV-2, which should be derived from vaccines. These findings are similar to the previous results involving Japanese strains, suggesting there has been no great change in the recent CPV-2 epidemic in Japan. This epidemic is the same as that in Taiwan. Furthermore, a 324-lle mutant, which has been reported in Korean and Chinese strains, was detected in 66.7% of CPV-2a strains. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia

    DEFF Research Database (Denmark)

    Tørring, Pernille M; Kjeldsen, A.D.; Ousager, L.B.

    2012-01-01

    Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817......-3T>G in ENG) initially seemed to be homozygous for the mutation. Aim: To explore the possibility of allelic dropout causing a false result in this patient. Methods: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal...... the presence of a possible sequence variant, which could explain the presumed allelic dropout. Results: Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. Conclusion: Sequence variants outside of the primer regions...

  5. Exogenous wild type p53 gene affects radiosensitivity of human lung adenocarcinoma cell line under hypoxia

    International Nuclear Information System (INIS)

    Wang Jianhua; Wang Feng; Liu Yongping; Zhang Yaping; Ni Yan; Li Shirong

    2008-01-01

    Objective: To evaluate the effect of exogenous wild type p53 (wtp53) gene on radiosensitivity of human lung adenocarcinoma cell line under hypoxia. Methods: Human lung adenocarcinoma cell line A549 was transfected with adenovirus carrying recombinant exogenous wtp53. Four irradiation groups were studied: normal cell (Group A), wtp53 transfected cell (Group B), normal cell under hypoxia (Group C) and wtp53 transfected cell under hypoxia(Group D). Cells were irradiated with 9 MeV electron beams. Cellular survival fraction was analyzed. Multi-target single-hit model was used to plot the survival curve. D 0 , D q , oxygen enhancement ratio (OER), sensitizing enhancement ratio (SER) and other parameters were used to evaluate the effects of wtp53 gene on radiosensitivity of A549. The cell apoptotic rate of each group was examined by flow cytometry. Results: OER was 1.75 and 0.81 before and after wtp53 transfection. SER was 1.77 in oxic circumstance and 3.84 under hypoxia. The cell apoptotic rate of Group A and B was lower than Group C and D (F=7.92, P=0.048), with Group A lower than B and Group C lower than D (F=82.50, P=0.001). But Group B and D were similar(t=2.04, P=0.111). Conclusions: Hypoxia can increase the radiation resistance of lung adenocarcinoma cell line A549. The wtp53 can promote apoptosis and improve tumor radiosensitivity, especially under hypoxia. (authors)

  6. Aortic atresia with normal sized left ventricle

    OpenAIRE

    Priya Jagia; Arun Sharma; Saurabh K Gupta; Munish Guleria

    2016-01-01

    Aortic atresia with an associated ventricular septal defect and adequate sized left ventricle is extremely rare. We present two cases in which an alternate diagnosis was suggested on echocardiography because the hypoplastic aortic trunk was missed due to its small caliber. The final diagnosis was, however, clinched on dual source computed tomography, which not only showed the thin aortic trunk but also clearly depicted the coronary artery origins from the hypoplastic aortic root. To the best ...

  7. A History of Thoracic Aortic Surgery.

    Science.gov (United States)

    McFadden, Paul Michael; Wiggins, Luke M; Boys, Joshua A

    2017-08-01

    Ancient historical texts describe the presence of aortic pathology conditions, although the surgical treatment of thoracic aortic disease remained insurmountable until the 19th century. Surgical treatment of thoracic aortic disease then progressed along with advances in surgical technique, conduit production, cardiopulmonary bypass, and endovascular technology. Despite radical advances in aortic surgery, principles established by surgical pioneers of the 19th century hold firm to this day. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Early life stress affects mortality rate more than social behavior, gene expression or oxidative damage in honey bee workers.

    Science.gov (United States)

    Rueppell, Olav; Yousefi, Babak; Collazo, Juan; Smith, Daniel

    2017-04-01

    Early life stressors can affect aging and life expectancy in positive or negative ways. Individuals can adjust their behavior and molecular physiology based on early life experiences but relatively few studies have connected such mechanisms to demographic patterns in social organisms. Sociality buffers individuals from environmental influences and it is unclear how much early life stress affects later life history. Workers of the honey bee (Apis mellifera L.) were exposed to two stressors, Varroa parasitism and Paraquat exposure, early in life. Consequences were measured at the molecular, behavioral, and demographic level. While treatments did not significantly affect levels of oxidative damage, expression of select genes, and titers of the common deformed wing virus, most of these measures were affected by age. Some of the age effects, such as declining levels of deformed wing virus and oxidative damage, were opposite to our predictions but may be explained by demographic selection. Further analyses suggested some influences of worker behavior on mortality and indicated weak treatment effects on behavior. The latter effects were inconsistent among the two experiments. However, mortality rate was consistently reduced by Varroa mite stress during development. Thus, mortality was more responsive to early life stress than our other response variables. The lack of treatment effects on these measures may be due to the social organization of honey bees that buffers the individual from the impact of stressful developmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Aortic or Mitral Valve Replacement With the Biocor and Biocor Supra

    Science.gov (United States)

    2017-04-26

    Aortic Valve Insufficiency; Aortic Valve Regurgitation; Aortic Valve Stenosis; Aortic Valve Incompetence; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Stenosis; Mitral Valve Incompetence

  10. Thoracic Endovascular Aortic Repair (TEVAR) in Proximal (Type A) Aortic Dissection: Ready for a Broader Application?

    OpenAIRE

    Nienaber, Christoph A.; Sakalihasan, Natzi; Clough, Rachel E.; Aboukoura, Mohamed; Mancuso, Enrico; Yeh, James S.M.; Defraigne, Jean-Olivier; Cheshire, Nick; Rosendahl, Ulrich Peter; Quarto, Cesare; Pepper, John

    2016-01-01

    ObjectiveThoracic endovascular aortic repair (TEVAR) has demonstrated encouraging results and is gaining increasing acceptance as a treatment option for aortic aneurysms and dissections. Yet, its role in managing proximal aortic pathologies is unknown - this is important because in proximal (Stanford type A) aortic dissections, 10-30% are not accepted for surgery, and 30-50% are technically amenable for TEVAR. We describe our case series of type A aortic dissections treated using TEVAR.Method...

  11. Grapevine rootstocks differentially affect the rate of ripening and modulate auxin-related genes in Cabernet Sauvignon berries

    Directory of Open Access Journals (Sweden)

    Massimiliano eCorso

    2016-02-01

    Full Text Available In modern viticulture, grafting commercial grapevine varieties on interspecific rootstocks is a common practice required for conferring resistance to many biotic and abiotic stresses. Nevertheless, the use of rootstocks to gain these essential traits is also known to impact grape berry development and quality, although the underlying mechanisms are still poorly understood. In grape berries, the onset of ripening (véraison is regulated by a complex network of mobile signals including hormones such as auxins, ethylene, abscisic acid and brassinosteroids. Recently, a new rootstock, designated M4, was selected based on its enhanced tolerance to water stress and medium vigour. This study investigates the effect of M4 on Cabernet Sauvignon (CS berry development in comparison to the commercial 1103P rootstock. Physical and biochemical parameters showed that the ripening rate of CS berries is faster when grafted onto M4. A multifactorial analysis performed on mRNA-Seq data obtained from skin and pulp of berries grown in both graft combinations revealed that genes controlling auxin action (ARF and Aux/IAA represent one of main categories affected by the rootstock genotype. Considering that the level of auxin tightly regulates the transcription of these genes, we investigated the behaviour of the main gene families involved in auxin biosynthesis and conjugation. Molecular and biochemical analyses confirmed a link between the rate of berry development and the modulation of auxin metabolism. Moreover the data indicate that this phenomenon appears to be particularly pronounced in skin tissue in comparison to the flesh.

  12. Grapevine Rootstocks Differentially Affect the Rate of Ripening and Modulate Auxin-Related Genes in Cabernet Sauvignon Berries.

    Science.gov (United States)

    Corso, Massimiliano; Vannozzi, Alessandro; Ziliotto, Fiorenza; Zouine, Mohamed; Maza, Elie; Nicolato, Tommaso; Vitulo, Nicola; Meggio, Franco; Valle, Giorgio; Bouzayen, Mondher; Müller, Maren; Munné-Bosch, Sergi; Lucchin, Margherita; Bonghi, Claudio

    2016-01-01

    In modern viticulture, grafting commercial grapevine varieties on interspecific rootstocks is a common practice required for conferring resistance to many biotic and abiotic stresses. Nevertheless, the use of rootstocks to gain these essential traits is also known to impact grape berry development and quality, although the underlying mechanisms are still poorly understood. In grape berries, the onset of ripening (véraison) is regulated by a complex network of mobile signals including hormones such as auxins, ethylene, abscisic acid, and brassinosteroids. Recently, a new rootstock, designated M4, was selected based on its enhanced tolerance to water stress and medium vigor. This study investigates the effect of M4 on Cabernet Sauvignon (CS) berry development in comparison to the commercial 1103P rootstock. Physical and biochemical parameters showed that the ripening rate of CS berries is faster when grafted onto M4. A multifactorial analysis performed on mRNA-Seq data obtained from skin and pulp of berries grown in both graft combinations revealed that genes controlling auxin action (ARF and Aux/IAA) represent one of main categories affected by the rootstock genotype. Considering that the level of auxin tightly regulates the transcription of these genes, we investigated the behavior of the main gene families involved in auxin biosynthesis and conjugation. Molecular and biochemical analyses confirmed a link between the rate of berry development and the modulation of auxin metabolism. Moreover, the data indicate that this phenomenon appears to be particularly pronounced in skin tissue in comparison to the flesh.

  13. Single Nucleotide Polymorphisms Can Create Alternative Polyadenylation Signals and Affect Gene Expression through Loss of MicroRNA-Regulation

    Science.gov (United States)

    Thomas, Laurent F.; Sætrom, Pål

    2012-01-01

    Alternative polyadenylation (APA) can for example occur when a protein-coding gene has several polyadenylation (polyA) signals in its last exon, resulting in messenger RNAs (mRNAs) with different 3′ untranslated region (UTR) lengths. Different 3′UTR lengths can give different microRNA (miRNA) regulation such that shortened transcripts have increased expression. The APA process is part of human cells' natural regulatory processes, but APA also seems to play an important role in many human diseases. Although altered APA in disease can have many causes, we reasoned that mutations in DNA elements that are important for the polyA process, such as the polyA signal and the downstream GU-rich region, can be one important mechanism. To test this hypothesis, we identified single nucleotide polymorphisms (SNPs) that can create or disrupt APA signals (APA-SNPs). By using a data-integrative approach, we show that APA-SNPs can affect 3′UTR length, miRNA regulation, and mRNA expression—both between homozygote individuals and within heterozygote individuals. Furthermore, we show that a significant fraction of the alleles that cause APA are strongly and positively linked with alleles found by genome-wide studies to be associated with disease. Our results confirm that APA-SNPs can give altered gene regulation and that APA alleles that give shortened transcripts and increased gene expression can be important hereditary causes for disease. PMID:22915998

  14. The ADRA2B gene in the production of false memories for affective information in healthy female volunteers.

    Science.gov (United States)

    Fairfield, Beth; Mammarella, Nicola; Di Domenico, Alberto; D'Aurora, Marco; Stuppia, Liborio; Gatta, Valentina

    2017-08-30

    False memories are common memory distortions in everyday life and seem to increase with affectively connoted complex information. In line with recent studies showing a significant interaction between the noradrenergic system and emotional memory, we investigated whether healthy volunteer carriers of the deletion variant of the ADRA2B gene that codes for the α2b-adrenergic receptor are more prone to false memories than non-carriers. In this study, we collected genotype data from 212 healthy female volunteers; 91 ADRA2B carriers and 121 non-carriers. To assess gene effects on false memories for affective information, factorial mixed model analysis of variances (ANOVAs) were conducted with genotype as the between-subjects factor and type of memory error as the within-subjects factor. We found that although carriers and non-carriers made comparable numbers of false memory errors, they showed differences in the direction of valence biases, especially for inferential causal errors. Specifically, carriers produced fewer causal false memory errors for scripts with a negative outcome, whereas non-carriers showed a more general emotional effect and made fewer causal errors with both positive and negative outcomes. These findings suggest that putatively higher levels of noradrenaline in deletion carriers may enhance short-term consolidation of negative information and lead to fewer memory distortions when facing negative events. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Letrozole induced low estrogen levels affected the expressions of duodenal and renal calcium-processing gene in laying hens.

    Science.gov (United States)

    Li, Qiao; Zhao, Xingkai; Wang, Shujie; Zhou, Zhenlei

    2018-01-01

    Estrogen regulates the calcium homeostasis in hens, but the mechanisms involved are still unclear fully. In this study, we investigated whether letrozole (LZ) induced low estrogen levels affected the calcium absorption and transport in layers. In the duodenum, we observed a significant decrease of mRNA expressions of Calbindin-28k (CaBP-28k) and plasma membrane Ca 2+ -ATPase (PMCA 1b) while CaBP-28k protein expression was declined in birds with LZ treatment, and the mRNA levels of duodenal transient receptor potential vanilloid 6 (TRPV6) and Na + /Ca 2+ exchanger 1 (NCX1) were not affected. Interestingly, we observed the different changes in the kidney. The renal mRNA expressions of TRPV6 and NCX1 were unregulated while the PMCA1b was down-regulated in low estrogen layers, however, the CaBP-28k gene and protein expressions were no changed in the kidney. Furthermore, it showed that the duodenal estradiol receptor 2 (ESR2) transcripts rather than parathyroid hormone 1 receptor (PTH1R) and calcitonin receptor (CALCR) played key roles to down-regulate calcium transport in LZ-treated birds. In conclusion, CaBP-28k, PMCA 1b and ESR2 genes in the duodenum may be primary targets for estrogen regulation in order to control calcium homeostasis in hens. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection.

    Science.gov (United States)

    Cikach, Frank S; Koch, Christopher D; Mead, Timothy J; Galatioto, Josephine; Willard, Belinda B; Emerton, Kelly B; Eagleton, Matthew J; Blackstone, Eugene H; Ramirez, Francesco; Roselli, Eric E; Apte, Suneel S

    2018-03-08

    Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.

  17. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles.

    Science.gov (United States)

    Zaya, Renee M; Amini, Zakariya; Whitaker, Ashley S; Ide, Charles F

    2011-08-01

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 μg/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 μg/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 μg/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 μg/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p=0.07) increases in peroxisome proliferator-activated receptor β (PPAR-β) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid β-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-β, an energy homeostasis regulatory molecule, also

  18. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    International Nuclear Information System (INIS)

    Zaya, Renee M.; Amini, Zakariya; Whitaker, Ashley S.; Ide, Charles F.

    2011-01-01

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 μg/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 μg/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 μg/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 μg/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor β (PPAR-β) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid β-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-β, an energy homeostasis regulatory molecule

  19. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    Energy Technology Data Exchange (ETDEWEB)

    Zaya, Renee M., E-mail: renee.zaya@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Amini, Zakariya, E-mail: zakariya.amini@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Whitaker, Ashley S., E-mail: ashley.s.whitaker@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Ide, Charles F., E-mail: charles.ide@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States)

    2011-08-15

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 {mu}g/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 {mu}g/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 {mu}g/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 {mu}g/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor {beta} (PPAR-{beta}) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid {beta}-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-{beta}, an energy

  20. A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.

    Directory of Open Access Journals (Sweden)

    Michael Oster

    Full Text Available In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. The underlying programming of fetal development was shown to be associated with an increased risk of degenerative diseases in adulthood, including the metabolic syndrome. There are clues that diet-dependent modifications of the metabolism during fetal life can persist until adulthood. This leads to the hypothesis that the offspring's transcriptomes show short-term and long-term changes depending on the maternal diet. To this end pregnant German landrace gilts were fed either a high protein diet (HP, 30% CP or an adequate protein diet (AP, 12% CP throughout pregnancy. Hepatic transcriptome profiles of the offspring were analyzed at prenatal (94 dpc and postnatal stages (1, 28, 188 dpn. Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner. Gene expression profiles at fetal stage 94 dpc were almost unchanged between the diets. The gestational HP diet affected the hepatic expression profiles at prenatal and postnatal stages. The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways. Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages.

  1. SHI/STY Genes Affect Pre- and Post-meiotic Anther Processes in Auxin Sensing Domains in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Leandro H. Estornell

    2018-02-01

    Full Text Available In flowering plants, mature sperm cells are enclosed in pollen grains formed in structures called anthers. Several cell layers surrounding the central sporogenous cells of the anther are essential for directing the developmental processes that lead to meiosis, pollen formation, and the subsequent pollen release. The specification and function of these tissues are regulated by a large number of genetic factors. Additionally, the plant hormone auxin has previously been shown to play important roles in the later phases of anther development. Using the R2D2 auxin sensor system we here show that auxin is sensed also in the early phases of anther cell layer development, suggesting that spatiotemporal regulation of auxin levels is important for early anther morphogenesis. Members of the SHI/STY transcription factor family acting as direct regulators of YUC auxin biosynthesis genes have previously been demonstrated to affect early anther patterning. Using reporter constructs we show that SHI/STY genes are dynamically active throughout anther development and their expression overlaps with those of three additional downstream targets, PAO5, EOD3 and PGL1. Characterization of anthers carrying mutations in five SHI/STY genes clearly suggests that SHI/STY transcription factors affect anther organ identity. In addition, their activity is important to repress periclinal cell divisions as well as premature entrance into programmed cell death and cell wall lignification, which directly influences the timing of anther dehiscence and the pollen viability. The SHI/STY proteins also prevent premature pollen germination suggesting that they may play a role in the induction or maintenance of pollen dormancy.

  2. CNVs affecting cancer predisposing genes (CPGs) detected as incidental findings in routine germline diagnostic chromosomal microarray (CMA) testing.

    Science.gov (United States)

    Innes, Josie; Reali, Lisa; Clayton-Smith, Jill; Hall, Georgina; Lim, Derek Hk; Burghel, George J; French, Kim; Khan, Unzela; Walker, Daniel; Lalloo, Fiona; Evans, D Gareth R; McMullan, Dominic; Maher, Eamonn R; Woodward, Emma R

    2018-02-01

    Identification of CNVs through chromosomal microarray (CMA) testing is the first-line investigation in individuals with learning difficulties/congenital abnormalities. Although recognised that CMA testing may identify CNVs encompassing a cancer predisposition gene (CPG), limited information is available on the frequency and nature of such results. We investigated CNV gains and losses affecting 39 CPGs in 3366 pilot index case individuals undergoing CMA testing, and then studied an extended cohort (n=10 454) for CNV losses at 105 CPGs and CNV gains at 9 proto-oncogenes implicated in inherited cancer susceptibility. In the pilot cohort, 31/3366 (0.92%) individuals had a CNV involving one or more of 16/39 CPGs. 30/31 CNVs involved a tumour suppressor gene (TSG), and 1/30 a proto-oncogene (gain of MET ). BMPR1A , TSC2 and TMEM127 were affected in multiple cases. In the second stage analysis, 49/10 454 (0.47%) individuals in the extended cohort had 50 CNVs involving 24/105 CPGs. 43/50 CNVs involved a TSG and 7/50 a proto-oncogene (4 gains, 3 deletions). The most frequently involved genes, FLCN (n=10) and SDHA (n=7), map to the Smith-Magenis and cri-du-chat regions, respectively. Incidental identification of a CNV involving a CPG is not rare and poses challenges for future cancer risk estimation. Prospective data collection from CPG-CNV cohorts ascertained incidentally and through syndromic presentations is required to determine the risks posed by specific CNVs. In particular, ascertainment and investigation of adults with CPG-CNVs and adults with learning disability and cancer, could provide important information to guide clinical management and surveillance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. 5B.05: MARFAN SYNDROME: ASSESSMENT OF AORTIC DISSECTION RISK BY ANALYSIS OF AORTIC VISCOELASTIC PROPERTIES.

    Science.gov (United States)

    Grillo, A; Pini, A; Marelli, S; Gan, L; Giuliano, A; Trifirò, G; Santini, F; Salvi, L; Salvi, P; Viecca, F; Carretta, R; Parati, G

    2015-06-01

    Marfan syndrome is an autosomal dominant genetic disorder characterized by an abnormal fibrillin-1 synthesis. Aortic root dilation and dissection are the main problems affecting patients prognosis in these patients. Their pharmacological prophylaxis with losartan or with a beta-blocker counteracts the aortic root dilation, but a close follow-up is required to assess therapeutic response rate and to identify non-responders. Unfortunately genotype-phenotype studies do not allow to determine the exact risk profile in these patients and there is no reliable method to accurately predict their risk of aortic dissection. Aim of this study was to evaluate non-invasive markers for identification of Marfan patients at higher risk of aortic complications. We studied 187 Marfan patients (identified according to 2010 Revised Ghent Criteria and positive genetic analysis), age 32.3 ± 16.5 yrs (mean ± SD). 52 patients (27.8%) had undergone surgical ascending aorta replacement (David or Bentall procedure). Central pressure curves were recorded by PulsePen tonometer, and the aortic viscoelastic aortic properties were studied by determination of carotid-femoral pulse wave velocity (PWV). With reference to the age related distribution of PWV values in a normal population, defined according to Arterial-Stiffness-Collaboration, PWV mean values in Marfan patients corresponded to 60th percentile in non- operated patients and to the 67th percentile in those operated. Adult Marfan patients (n = 146) generally displayed a low blood pressure, because of the pharmacological prophylaxis, and were compared with a population of 189 adult healthy subjects (81 males), matched by age (38 ± 13 vs 38 ± 16 yrs.), heart rate (64 ± 9 bpm vs 64 ± 11 bpm) and blood pressure (mean BP = 78 ± 9 mmHg vs 79 ± 4 mmHg) values. Average PWV value was higher than in healthy controls (PWV = 7.0 ± 1.7) both in not operated (PWV = 7.6 ± 1.6; p = 0

  4. Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission.

    Science.gov (United States)

    Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J

    2016-07-01

    Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood. © The Author 2016. Published by Oxford University Press.

  5. Interfacial stress affects rat alveolar type II cell signaling and gene expression.

    Science.gov (United States)

    Hobi, Nina; Ravasio, Andrea; Haller, Thomas

    2012-07-01

    Previous work from our group (Ravasio A, Hobi N, Bertocchi C, Jesacher A, Dietl P, Haller T. Am J Physiol Cell Physiol 300: C1456-C1465, 2011.) showed that contact of alveolar epithelial type II cells with an air-liquid interface (I(AL)) leads to a paradoxical situation. It is a potential threat that can cause cell injury, but also a Ca(2+)-dependent stimulus for surfactant secretion. Both events can be explained by the impact of interfacial tensile forces on cellular structures. Here, the strength of this mechanical stimulus became also apparent in microarray studies by a rapid and significant change on the transcriptional level. Cells challenged with an I(AL) in two different ways showed activation/inactivation of cellular pathways involved in stress response and defense, and a detailed Pubmatrix search identified genes associated with several lung diseases and injuries. Altogether, they suggest a close relationship of interfacial stress sensation with current models in alveolar micromechanics. Further similarities between I(AL) and cell stretch were found with respect to the underlying signaling events. The source of Ca(2+) was extracellular, and the transmembrane Ca(2+) entry pathway suggests the involvement of a mechanosensitive channel. We conclude that alveolar type II cells, due to their location and morphology, are specific sensors of the I(AL), but largely protected from interfacial stress by surfactant release.

  6. A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning.

    Directory of Open Access Journals (Sweden)

    Mikhail eVotinov

    2015-07-01

    Full Text Available Whether the opioid system plays a role in the ability to flexibly adapt behavior is still unclear. We used fMRI to investigate the effect of a nucleotide tandem repeat (68-bp VNTR functional polymorphism of the prodynorphin gene on cerebral activation during a reversal learning task in which participants had to flexibly adapt stimulus-response associations. Past studies suggested that alleles with 3 or 4 repeats (HH genotype of this polymorphism are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype. On the behavioral level, the HH group made more perseverative errors than the LL group. On the neural level, the HH group demonstrated less engagement of left orbitofrontal cortex (lOFC and cortico-striatal circuitry, and lower effective connectivity of lOFC with anterior midcingulate cortex and anterior insula/ventrolateral prefrontal cortex during reversal learning and processing negative feedback. This points to a lower ability of the HH genotype to monitor or adapt to changes in reward contingencies. These findings provide first evidence that dynorphins may contribute to individual differences in reversal learning, and that considering the opioid system may shed new light on the neurochemical correlates of decision-making and behavioral regulation.

  7. The callipyge mutation and other genes that affect muscle hypertrophy in sheep

    Directory of Open Access Journals (Sweden)

    Cockett Noelle E

    2005-12-01

    Full Text Available Abstract Genetic strategies to improve the profitability of sheep operations have generally focused on traits for reproduction. However, natural mutations exist in sheep that affect muscle growth and development, and the exploitation of these mutations in breeding strategies has the potential to significantly improve lamb-meat quality. The best-documented mutation for muscle development in sheep is callipyge (CLPG, which causes a postnatal muscle hypertrophy that is localized to the pelvic limbs and loin. Enhanced skeletal muscle growth is also observed in animals with the Carwell (or rib-eye muscling mutation, and a double-muscling phenotype has been documented for animals of the Texel sheep breed. However, the actual mutations responsible for these muscular hypertrophy phenotypes in sheep have yet to be identified, and further characterization of the genetic basis for these phenotypes will provide insight into the biological control of muscle growth and body composition.

  8. Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Nikitidou, Litsa; Ledri, Marco

    2009-01-01

    (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY...... is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected...... injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP...

  9. Natural variation in the VELVET gene bcvel1 affects virulence and light-dependent differentiation in Botrytis cinerea.

    Directory of Open Access Journals (Sweden)

    Julia Schumacher

    Full Text Available Botrytis cinerea is an aggressive plant pathogen causing gray mold disease on various plant species. In this study, we identified the genetic origin for significantly differing phenotypes of the two sequenced B. cinerea isolates, B05.10 and T4, with regard to light-dependent differentiation, oxalic acid (OA formation and virulence. By conducting a map-based cloning approach we identified a single nucleotide polymorphism (SNP in an open reading frame encoding a VELVET gene (bcvel1. The SNP in isolate T4 results in a truncated protein that is predominantly found in the cytosol in contrast to the full-length protein of isolate B05.10 that accumulates in the nuclei. Deletion of the full-length gene in B05.10 resulted in the T4 phenotype, namely light-independent conidiation, loss of sclerotial development and oxalic acid production, and reduced virulence on several host plants. These findings indicate that the identified SNP represents a loss-of-function mutation of bcvel1. In accordance, the expression of the B05.10 copy in T4 rescued the wild-type/B05.10 phenotype. BcVEL1 is crucial for full virulence as deletion mutants are significantly hampered in killing and decomposing plant tissues. However, the production of the two best known secondary metabolites, the phytotoxins botcinic acid and botrydial, are not affected by the deletion of bcvel1 indicating that other factors are responsible for reduced virulence. Genome-wide expression analyses of B05.10- and Δbcvel1-infected plant material revealed a number of genes differentially expressed in the mutant: while several protease- encoding genes are under-expressed in Δbcvel1 compared to the wild type, the group of over-expressed genes is enriched for genes encoding sugar, amino acid and ammonium transporters and glycoside hydrolases reflecting the response of Δbcvel1 mutants to nutrient starvation conditions.

  10. Aortic atresia with normal sized left ventricle

    Directory of Open Access Journals (Sweden)

    Priya Jagia

    2016-01-01

    Full Text Available Aortic atresia with an associated ventricular septal defect and adequate sized left ventricle is extremely rare. We present two cases in which an alternate diagnosis was suggested on echocardiography because the hypoplastic aortic trunk was missed due to its small caliber. The final diagnosis was, however, clinched on dual source computed tomography, which not only showed the thin aortic trunk but also clearly depicted the coronary artery origins from the hypoplastic aortic root. To the best of our knowledge, use of multi-detector computed tomography in aortic atresia with well developed left ventricle has not been reported in literature till date.

  11. RNA editing differently affects protein-coding genes in D. melanogaster and H. sapiens.

    Science.gov (United States)

    Grassi, Luigi; Leoni, Guido; Tramontano, Anna

    2015-07-14

    When an RNA editing event occurs within a coding sequence it can lead to a different encoded amino acid. The biological significance of these events remains an open question: they can modulate protein functionality, increase the complexity of transcriptomes or arise from a loose specificity of the involved enzymes. We analysed the editing events in coding regions that produce or not a change in the encoded amino acid (nonsynonymous and synonymous events, respectively) in D. melanogaster and in H. sapiens and compared them with the appropriate random models. Interestingly, our results show that the phenomenon has rather different characteristics in the two organisms. For example, we confirm the observation that editing events occur more frequently in non-coding than in coding regions, and report that this effect is much more evident in H. sapiens. Additionally, in this latter organism, editing events tend to affect less conserved residues. The less frequently occurring editing events in Drosophila tend to avoid drastic amino acid changes. Interestingly, we find that, in Drosophila, changes from less frequently used codons to more frequently used ones are favoured, while this is not the case in H. sapiens.

  12. MSCs with ACE II gene affect apoptosis pathway of acute lung injury induced by bleomycin.

    Science.gov (United States)

    Zhang, Xiaomiao; Gao, Fengying; Li, Qian; Dong, Zhixia; Sun, Bo; Hou, Lili; Li, Zhuozhe; Liu, Zhenwei

    2015-02-01

    The aim of this study was to evaluate the effect and related mechanisms of Mesenchymal stem cells (MSCs) and Angiotensin converting enzyme II (ACE II) on acute lung injury (ALI). MSCs were separated from umbilical cord cells, and the changes of phenotype before and after ACE II silence were observed using Flow Cytometer. ALI model was induced by 10 mg/mL bleomycin in 60 Balb/c mice, and the rest 8 mice were regarded as the baseline group. The mice were randomly divided into four groups (n = 15): control, ACE II, stem, and stem + ACE II. The apoptotic index (AI) was calculated using TUNEL, and the detection of protein and mRNA of Bax, Bak and p53, Bcl-2, Grp78, CHOP and Caspase 12 were used by western-blot and RT-PCR, respectively. The umbilical cord cells differentiated into stable MSCs about 14 days, and ACE II transfection reached a peak at the 5th day after transfection. ACE II silence did not affect the phenotype of MSCs. All the proteins and mRNAs expression except Bcl-2 in the stem and stem + ACE II were significantly lower than those in control from 8 h (p ACE II performed a better effect than single stem in most indexes, including AI (p ACE II can significantly suppress apoptosis in ALI mice, and may be an effective clinical treatment for ALI.

  13. MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms

    Science.gov (United States)

    Tscheuschler, Anke; Meffert, Philipp; Beyersdorf, Friedhelm; Heilmann, Claudia; Kocher, Nadja; Uffelmann, Xenia; Discher, Philipp; Siepe, Matthias; Kari, Fabian A.

    2016-01-01

    Objective The need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress. Methods Serum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography. 24 patients had ascending aortic aneurysms, 10 of them also had aortic root aneurysms. Three patients had normally functioning valves, 12 had regurgitation alone, eight had regurgitation and stenosis and one had only stenosis. Patients had bicuspid and tricuspid aortic valves (9/15). Serum samples were taken preoperatively, and the aortic wall specimen collected during surgical aortic repair. Results Pro-MMP-2 was identified in all serum and tissue samples. Pro-MMP-2 was detected in all tissue and serum samples from patients with ascending aortic/aortic root aneurysms, irrespective of valve morphology or other clinical parameters and in serum from healthy controls. We also identified active MMP-2 in all tissue samples from patients with ascending aortic/aortic root aneurysms. None of the analyzed serum samples revealed signals relatable to active MMP-2. No correlation between aortic tissue total MMP-2 or tissue pro-MMP-2 or tissue active MMP-2 and serum MMP-2 was found and tissue MMP-2/pro-MMP-2/active MMP-2 did not correlate with aortic diameter. This evidence shows that pro-MMP-2 is the predominant MMP-2 species in serum of patients and healthy individuals and in aneurysmatic aortic tissue, irrespective of aortic valve configuration. Active MMP-2 species are either not released into systemic circulation or not detectable in serum. There is no reliable connection between aortic tissue—and serum MMP-2

  14. Dopamine D1 receptor gene variation modulates opioid dependence risk by affecting transition to addiction.

    Directory of Open Access Journals (Sweden)

    Feng Zhu

    Full Text Available Dopamine D1 receptor (DRD1 modulates opioid reinforcement, reward, and opioid-induced neuroadaptation. We propose that DRD1 polymorphism affects susceptibility to opioid dependence (OD, the efficiency of transition to OD, and opioid-induced pleasure response. We analyzed potential association between seven DRD1 polymorphisms with the following traits: duration of transition from the first use to dependence (DTFUD, subjective pleasure responses to opioid on first use and post-dependence use, and OD risk in 425 Chinese with OD and 514 healthy controls. DTFUD and level of pleasure responses were examined using a semi-structured interview. The DTFUD of opioid addicts ranged from 5 days to 11 years. Most addicts (64.0% reported non-comfortable response upon first opioid use, while after dependence, most addicts (53.0% felt strong opioid-induced pleasure. Survival analysis revealed a correlation of prolonged DTFUD with the minor allele-carrying genotypes of DRD1 rs4532 (hazard ratios (HR = 0.694; p = 0.001 and rs686 (HR = 0.681, p = 0.0003. Binary logistic regression indicated that rs10063995 GT genotype (vs. GG+TT, OR = 0.261 could predict decreased pleasure response to first-time use and the minor alleles of rs686 (OR = 0.535 and rs4532 (OR = 0.537 could predict decreased post-dependence pleasure. Moreover, rs686 minor allele was associated with a decreased risk for rapid transition from initial use to dependence (DTFUD≤30 days; OR = 0.603 or post-dependence euphoria (OR = 0.603 relative to major allele. In conclusion, DRD1 rs686 minor allele decreases the OD risk by prolonging the transition to dependence and attenuating opioid-induced pleasure in Chinese.

  15. Subinhibitory concentrations of perilla oil affect the expression of secreted virulence factor genes in Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Jiazhang Qiu

    Full Text Available BACKGROUND: The pathogenicity of staphylococcus aureus is dependent largely upon its ability to secrete a number of virulence factors, therefore, anti-virulence strategy to combat S. aureus-mediated infections is now gaining great interest. It is widely recognized that some plant essential oils could affect the production of staphylococcal exotoxins when used at subinhibitory concentrations. Perilla [Perilla frutescens (L. Britton], a natural medicine found in eastern Asia, is primarily used as both a medicinal and culinary herb. Its essential oil (perilla oil has been previously demonstrated to be active against S. aureus. However, there are no data on the influence of perilla oil on the production of S. aureus exotoxins. METHODOLOGY/PRINCIPAL FINDINGS: A broth microdilution method was used to determine the minimum inhibitory concentrations (MICs of perilla oil against S. aureus strains. Hemolysis, tumour necrosis factor (TNF release, Western blot, and real-time RT-PCR assays were performed to evaluate the effects of subinhibitory concentrations of perilla oil on exotoxins production in S. aureus. The data presented here show that perilla oil dose-dependently decreased the production of α-toxin, enterotoxins A and B (the major staphylococcal enterotoxins, and toxic shock syndrome toxin 1 (TSST-1 in both methicillin-sensitive S. aureus (MSSA and methicillin-resistant S. aureus (MRSA. CONCLUSIONS/SIGNIFICANCE: The production of α-toxin, SEA, SEB, and TSST-1 in S. aureus was decreased by perilla oil. These data suggest that perilla oil may be useful for the treatment of S. aureus infections when used in combination with β-lactam antibiotics, which can increase exotoxins production by S. aureus at subinhibitory concentrations. Furthermore, perilla oil could be rationally applied in food systems as a novel food preservative both to inhibit the growth of S. aureus and to repress the production of exotoxins, particularly staphylococcal enterotoxins.

  16. Mutations in the human adenosine deaminase gene that affect protein structure and RNA splicing

    International Nuclear Information System (INIS)

    Akeson, A.L.; Wiginton, D.A.; States, C.J.; Perme, C.M.; Dusing, M.R.; Hutton, J.J.

    1987-01-01

    Adenosine deaminase deficiency is one cause of the genetic disease severe combined immunodeficiency. To identify mutations responsible for ADA deficiency, the authors synthesized cDNAs to ADA mRNAs from two cell lines, GM2756 and GM2825A, derived from ADA-deficient immunodeficient patients. Sequence analysis of GM2756 cDNA clones revealed a different point mutation in each allele that causes amino acid changes of alanine to valine and arginine to histidine. One allele of GM2825A also has a point mutation that causes an alanine to valine substitution. The other allele of GM2825A was found to produce an mRNA in which exon 4 had been spliced out but had no other detrimental mutations. S1 nuclease mapping of GM2825A mRNA showed equal abundance of the full-length ADA mRNA and the ADA mRNA that was missing exon 4. Several of the ADA cDNA clones extended 5' of the major initiation start site, indicating multiple start sites for ADA transcription. The point mutations in GM2756 and GM2825A and the absence of exon 4 in GM2825A appear to be directly responsible for the ADA deficiency. Comparison of a number of normal and mutant ADA cDNA sequences showed a number of changes in the third base of codons. These change do not affect the amino acid sequence. Analyses of ADA cDNAs from different cell lines detected aberrant RNA species that either included intron 7 or excluded exon 7. Their presence is a result of aberrant splicing of pre-mRNAs and is not related to mutations that cause ADA deficiency

  17. Aortic Root Enlargement or Sutureless Valve Implantation?

    Directory of Open Access Journals (Sweden)

    Nikolaos G. Baikoussis

    2016-11-01

    Full Text Available Aortic valve replacement (AVR in patients with a small aortic annulus is a challenging issue. The importance of prosthesis–patient mismatch (PPM post aortic valve replacement (AVR is controversial but has to be avoided. Many studies support the fact that PPM has a negative impact on short and long term survival. In order to avoid PPM, aortic root enlargement may be performed. Alternatively and keeping in mind that often some comorbidities are present in old patients with small aortic root, the Perceval S suturelles valve implantation could be a perfect solution. The Perceval sutureless bioprosthesis provides reasonable hemodynamic performance avoiding the PPM and providing the maximum of aortic orifice area. We would like to see in the near future the role of the aortic root enlargement techniques in the era of surgical implantation of the sutureless valve (SAVR and the transcatheter valve implantation (TAVI.

  18. Aortic valve function after bicuspidization of the unicuspid aortic valve.

    Science.gov (United States)

    Aicher, Diana; Bewarder, Moritz; Kindermann, Michael; Abdul-Khalique, Hashim; Schäfers, Hans-Joachim

    2013-05-01

    Unicuspid aortic valve (UAV) anatomy leads to dysfunction of the valve in young individuals. We introduced a reconstructive technique of bicuspidizing the UAV. Initially we copied the typical asymmetry of a normal bicuspid aortic valve (BAV) (I), later we created a symmetric BAV (II). This study compared the hemodynamic function of the two designs of a bicuspidized UAV. Aortic valve function was studied at rest and during exercise in 28 patients after repair of UAV (group I, n = 8; group II, n = 20). There were no differences among the groups I and II with respect to gender, age, body size, or weight. All patients were in New York Heart Association class I. Six healthy adults served as control individuals. All patients were studied with transthoracic echocardiography between 4 and 65 months postoperatively. Systolic gradients were assessed by continuous wave Doppler while patients were at rest and exercising on a bicycle ergometer. Aortic regurgitation was grade I or less in all patients. Resting gradients were significantly elevated in group I compared with group II and control individuals (group I, peak 33.8 ± 7.8 mm Hg; mean 19.1 ± 5.4 mm Hg; group II, peak 15.8 ± 5.4, mean 8.2 ± 2.8 mm Hg; control individuals, peak 6.0 ± 1.6, mean 3.2 ± 0.8 mm Hg; p competence. A symmetric repair design leads to improved systolic aortic valve function at rest and during exercise. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Denitrification nitrogen gas formation and gene expression in alpine grassland soil as affected by climate change conditions

    Science.gov (United States)

    Chen, Zhe; Wang, Changhui; Gschwendtner, Silvia; Schloter, Michael; Butterbach-Bahl, Klaus; Dannenmann, Michael

    2013-04-01

    Due to methodological problems, reliable data on soil dinitrogen (N2) emission by denitrification are extremely scarce, and the impacts of climate change on nitrogen (N) gas formation by denitrification and N gas product ratios as well as the underlying microbial drivers remain unclear. We combined the helium-gas-flow-soil-core technique for simultaneously quantification of nitrous oxide (N2O) and N2 emission with the reverse transcript qPCR technology. Our goals were to characterize denitrification dynamics and N gas product ratios in alpine grassland soil as affected by climate change conditions and to evaluate relationships between denitrification gene expression and N gas emission. We used soils from the pre-alpine grassland Terrestrial Environmental Observatory (TERENO), exposed to ambient temperature and precipitation (control treatment), or three years of simulated climate change conditions (increased temperature, reduction of summer precipitation and reduced snow cover). Soils were amended with glucose and nitrate and incubated subsequently at 1) 5°C and 20% oxygen; 2) 5°C and 0% oxygen; 3) 20°C and 0% oxygen until stabilization of N gas emissions in each incubation step. After switching incubation conditions to 0% oxygen and 20°C, N2O emission peaked immediately and declined again, followed by a delayed peak in N2 emission. The dynamics of cnorB gene expression, encoding the reduction of nitric oxide (NO) to N2O, followed the N2O emission pattern, while nosZ gene expression, encoding N2O reduction to N2 followed the course of N2 emission. The mean N2O:N2 ratios were 1.31 + 0.10 and 1.56 + 0.16 for control and climate change treatment respectively, but the denitrification potential was overall lower in climate change treatment. Hence, simulated climate change promoted N2O but lessened N2 emission. This stimulation of N2O was in accordance with increased cnorB gene expression in soil of the climate change treatment. N mass balance calculations revealed

  20. The intraventricular filling vortex under heightened aortic blood pressure

    Science.gov (United States)

    Nelsen, Nicholas; Gaddam, Manikantam; Santhanakrishnan, Arvind

    2017-11-01

    Hypertension, or high aortic blood pressure, can induce structural changes in the left ventricle (LV) such as concentric hypertrophy. Previous studies have identified that the intraventricular filling vortex serves as an effective means of blood transport during diastolic filling. However, a fundamental understanding of how hypertension affects this vortex is unavailable. This knowledge can be useful for improving diagnosis and treatment of related heart disease conditions, including hypertensive heart failure. In this experimental study, we hypothesized that the circulation of the filling vortex would diminish with increased aortic pressure. Using a LV physical model within a left heart simulator, we performed hemodynamic measurements to acquire pressure and volumetric inflow profiles and 2D particle image velocimetry to visualize the intraventricular flow fields. Peak aortic pressures of 120 mm Hg, 140 mm Hg, and 160 mm Hg were each tested at heart rates of 70, 100, and 110 beats per minute, under: 1) reduced ejection fraction (EF), and 2) constant EF. Our results indicate that peak vortex circulation is reduced under elevated aortic pressures. Hemodynamics and characteristics of the intraventricular filling vortex in all examined experimental cases will be presented.

  1. Gene expression signatures affected by ethanol and/or nicotine in normal human normal oral keratinocytes (NHOKs

    Directory of Open Access Journals (Sweden)

    Jeffrey J. Kim

    2014-12-01

    Full Text Available It has been reported that nicotine/alcohol alters epigenetic control and leads to abrogated DNA methylation and histone modifications, which could subsequently perturb transcriptional regulation critically important in cellular transformation. The aim of this study is to determine the molecular mechanisms of nicotine/alcohol-induced epigenetic alterations and their mechanistic roles in transcriptional regulation in human adult stem cells. We hypothesized that nicotine/alcohol induces deregulation of epigenetic machinery and leads to epigenetic alterations, which subsequently affect transcriptional regulation in oral epithelial stem cells. As an initiating step we have profiled transcriptomic alterations induced by the combinatory administration of EtOH and nicotine in primary normal human oral keratinocytes. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO under GSE57634. Our data provide comprehensive transcriptomic map describing molecular changes induced by EtOH and nicotine on normal human oral keratinocytes.

  2. Identification of a mutation in the CHAT gene of Old Danish Pointing Dogs affected with congenital myasthenic syndrome

    DEFF Research Database (Denmark)

    Proschowsky, Helle Friis; Flagstad, Annette; Cirera, Susanna

    2007-01-01

    The presence of a recessive inherited muscle disease in Old Danish Pointing Dogs has been well known for years. Comparisons of this disease with myasthenic diseases of other dog breeds and humans have pointed toward a defect in the synthesis of the neurotransmitter acetylcholine possibly due...... to decreased activity of the enzyme choline acetyltransferase. We sequenced exons 5-18 of the gene encoding choline acetyltransferase (CHAT) in 2 affected and 2 unaffected dogs and identified a G to A missense mutation in exon 6. The mutation causes a valine to methionine substitution and segregates...... in agreement with the inheritance of the disease. The mutation was not detected in 50 dogs representing 25 other dog breeds. A DNA test has been developed and is now available to the breeders of Old Danish Pointing Dogs....

  3. Variation in the Williams syndrome GTF2I gene and anxiety proneness interactively affect prefrontal cortical response to aversive stimuli.

    Science.gov (United States)

    Jabbi, M; Chen, Q; Turner, N; Kohn, P; White, M; Kippenhan, J S; Dickinson, D; Kolachana, B; Mattay, V; Weinberger, D R; Berman, K F

    2015-08-18

    Characterizing the molecular mechanisms underlying the heritability of complex behavioral traits such as human anxiety remains a challenging endeavor for behavioral neuroscience. Copy-number variation (CNV) in the general transcription factor gene, GTF2I, located in the 7q11.23 chromosomal region that is hemideleted in Williams syndrome and duplicated in the 7q11.23 duplication syndrome (Dup7), is associated with gene-dose-dependent anxiety in mouse models and in both Williams syndrome and Dup7. Because of this recent preclinical and clinical identification of a genetic influence on anxiety, we examined whether sequence variation in GTF2I, specifically the single-nucleotide polymorphism rs2527367, interacts with trait and state anxiety to collectively impact neural response to anxiety-laden social stimuli. Two hundred and sixty healthy adults completed the Tridimensional Personality Questionnaire Harm Avoidance (HA) subscale, a trait measure of anxiety proneness, and underwent functional magnetic resonance imaging (fMRI) while matching aversive (fearful or angry) facial identity. We found an interaction between GTF2I allelic variations and HA that affects brain response: in individuals homozygous for the major allele, there was no correlation between HA and whole-brain response to aversive cues, whereas in heterozygotes and individuals homozygous for the minor allele, there was a positive correlation between HA sub-scores and a selective dorsolateral prefrontal cortex (DLPFC) responsivity during the processing of aversive stimuli. These results demonstrate that sequence variation in the GTF2I gene influences the relationship between trait anxiety and brain response to aversive social cues in healthy individuals, supporting a role for this neurogenetic mechanism in anxiety.

  4. Dynamics of floret initiation/death determining spike fertility in wheat as affected by Ppd genes under field conditions.

    Science.gov (United States)

    Prieto, Paula; Ochagavía, Helga; Savin, Roxana; Griffiths, Simon; Slafer, Gustavo A

    2018-04-27

    As wheat yield is linearly related to grain number, understanding the physiological determinants of the number of fertile florets based on floret development dynamics due to the role of the particular genes is relevant. The effects of photoperiod genes on dynamics of floret development are largely ignored. Field experiments were carried out to (i) characterize the dynamics of floret primordia initiation and degeneration and (ii) to determine which are the most critical traits of such dynamics in establishing genotypic differences in the number of fertile florets at anthesis in near isogenic lines (NILs) carrying photoperiod-insensitive alleles. Results varied in magnitude between the two growing seasons, but in general introgression of Ppd-1a alleles reduced the number of fertile florets. The actual effect was affected not only by the genome and the doses but also by the source of the alleles. Differences in the number of fertile florets were mainly explained by differences in the floret generation/degeneration dynamics, and in most cases associated with floret survival. Manipulating photoperiod insensitivity, unquestionably useful for changing flowering time, may reduce spike fertility but much less than proportionally to the change in duration of development, as the insensitivity alleles did increase the rate of floret development.

  5. Culture temperature affects gene expression and metabolic pathways in the 2-methylisoborneol-producing cyanobacterium Pseudanabaena galeata.

    Science.gov (United States)

    Kakimoto, Masayuki; Ishikawa, Toshiki; Miyagi, Atsuko; Saito, Kazuaki; Miyazaki, Motonobu; Asaeda, Takashi; Yamaguchi, Masatoshi; Uchimiya, Hirofumi; Kawai-Yamada, Maki

    2014-02-15

    A volatile metabolite, 2-methylisoborneol (2-MIB), causes an unpleasant taste and odor in tap water. Some filamentous cyanobacteria produce 2-MIB via a two-step biosynthetic pathway: methylation of geranyl diphosphate (GPP) by methyl transferase (GPPMT), followed by the cyclization of methyl-GPP by monoterpene cyclase (MIBS). We isolated the genes encoding GPPMT and MIBS from Pseudanabaena galeata, a filamentous cyanobacterium known to be a major causal organism of 2-MIB production in Japanese lakes. The predicted amino acid sequence showed high similarity with that of Pseudanabaena limnetica (96% identity in GPPMT and 97% identity in MIBS). P. galeata was cultured at different temperatures to examine the effect of growth conditions on the production of 2-MIB and major metabolites. Gas chromatograph-mass spectrometry (GC-MS) measurements showed higher accumulation of 2-MIB at 30 °C than at 4 °C or 20 °C after 24 h of culture. Real-time-RT PCR analysis showed that the expression levels of the genes encoding GPPMT and MIBS decreased at 4 °C and increased at 30 °C, compared with at 20 °C. Furthermore, metabolite analysis showed dramatic changes in primary metabolite concentrations in cyanobacteria grown at different temperatures. The data indicate that changes in carbon flow in the TCA cycle affect 2-MIB biosynthesis at higher temperatures. Copyright © 2013 Elsevier GmbH. All rights reserved.

  6. Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome

    Science.gov (United States)

    Bertelsen, Birgitte; Melchior, Linea; Jensen, Lars R; Groth, Camilla; Glenthøj, Birte; Rizzo, Renata; Debes, Nanette Mol; Skov, Liselotte; Brøndum-Nielsen, Karen; Paschou, Peristera; Silahtaroglu, Asli; Tümer, Zeynep

    2014-01-01

    Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor and vocal tics, and the disorder is often accompanied by comorbidities such as attention-deficit hyperactivity-disorder and obsessive compulsive disorder. Tourette syndrome has a complex etiology, but the underlying environmental and genetic factors are largely unknown. IMMP2L (inner mitochondrial membrane peptidase, subunit 2) located on chromosome 7q31 is one of the genes suggested as a susceptibility factor in disease pathogenesis. Through screening of a Danish cohort comprising 188 unrelated Tourette syndrome patients for copy number variations, we identified seven patients with intragenic IMMP2L deletions (3.7%), and this frequency was significantly higher (P=0.0447) compared with a Danish control cohort (0.9%). Four of the seven deletions identified did not include any known exons of IMMP2L, but were within intron 3. These deletions were found to affect a shorter IMMP2L mRNA species with two alternative 5′-exons (one including the ATG start codon). We showed that both transcripts (long and short) were expressed in several brain regions, with a particularly high expression in cerebellum and hippocampus. The current findings give further evidence for the role of IMMP2L as a susceptibility factor in Tourette syndrome and suggest that intronic changes in disease susceptibility genes should be investigated further for presence of alternatively spliced exons. PMID:24549057

  7. Low intensity infrared laser affects expression of oxidative DNA repair genes in mitochondria and nucleus

    International Nuclear Information System (INIS)

    Fonseca, A S; Magalhães, L A G; Mencalha, A L; Geller, M; Paoli, F

    2014-01-01

    Practical properties and physical characteristics of low intensity lasers have made possible their application to treat soft tissue diseases. Excitation of intracellular chromophores by red and infrared radiation at low energy fluences with increase of mitochondrial metabolism is the basis of the biostimulation effect but free radicals can be produced. DNA lesions induced by free radicals are repaired by the base excision repair pathway. In this work, we evaluate the expression of POLγ and APEX2 genes related to repair of mitochondrial and nuclear DNA, respectively. Skin and muscle tissue of Wistar rats were exposed to low intensity infrared laser at different fluences. One hour and 24 hours after laser exposure, tissue samples were withdrawn for total RNA extraction, cDNA synthesis, and evaluation of POLγ and APEX2 mRNA expression by real time quantitative polymerase chain reaction. Skin and muscle tissue of Wistar rats exposed to laser radiation show different expression of POLγ and APEX2 mRNA depending of the fluence and time after exposure. Our study suggests that a low intensity infrared laser affects expression of genes involved in repair of oxidative lesions in mitochondrial and nuclear DNA. (paper)

  8. Transcatheter valve-in-valve implantation due to severe aortic regurgitation in a degenerated aortic homograft

    DEFF Research Database (Denmark)

    Olsen, Lene Kjaer; Engstrøm, Thomas; Søndergaard, Lars

    2009-01-01

    Transcatheter aortic valve implantation (TAVI) in severe aortic stenosis has proven to be a feasible and effective treatment modality for inoperable patients. Until now, neither aortic regurgitation nor degenerated bioprostheses has been an indication for TAVI. However, this article reports...... a successful valve-in-valve implantation of a CoreValve aortic valve prosthesis through the right subclavian artery in a case of severe aortic regurgitation within a degenerated aortic homograft. The case exemplifies the possibilities of expanding the indications for TAVI, as well as other vascular access...

  9. Statins for aortic valve stenosis

    Directory of Open Access Journals (Sweden)

    Luciana Thiago

    Full Text Available ABSTRACT BACKGROUND: Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. OBJECTIVES: To evaluate the effectiveness and safety of statins in aortic valve stenosis. METHODS: Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions. Selection criteria: Randomized controlled clinical trials (RCTs comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. Data collection and analysis: Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity, freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalization for any reason, overall mortality, adverse events and patient quality of life. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. MAIN RESULTS: We included four RCTs with 2360 participants comparing statins (1185 participants with placebo (1175 participants. We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD -0.54, 95% confidence interval (CI -1.88 to 0.80; participants = 1935; studies = 2, valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2

  10. Statins for aortic valve stenosis.

    Science.gov (United States)

    Thiago, Luciana; Tsuji, Selma Rumiko; Nyong, Jonathan; Puga, Maria Eduarda Dos Santos; Góis, Aécio Flávio Teixeira de; Macedo, Cristiane Rufino; Valente, Orsine; Atallah, Álvaro Nagib

    2016-01-01

    Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. To evaluate the effectiveness and safety of statins in aortic valve stenosis. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions.Selection criteria: Randomized controlled clinical trials (RCTs) comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. Data collection and analysis: Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity), freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalization for any reason, overall mortality, adverse events and patient quality of life.Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO) was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. We included four RCTs with 2360 participants comparing statins (1185 participants) with placebo (1175 participants). We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD) -0.54, 95% confidence interval (CI) -1.88 to 0.80; participants = 1935; studies = 2), valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2), and aortic jet velocity (MD -0.06, 95% CI -0.26 to 0

  11. Contemporary Management of Type B Aortic Dissection in the Endovascular Era.

    Science.gov (United States)

    Bannazadeh, Mohsen; Tadros, Rami O; McKinsey, James; Chander, Rajiv; Marin, Michael L; Faries, Peter L

    2016-04-01

    Aortic dissection (AD) is one of the most common catastrophic pathologies affecting the aorta. Anatomic classification is based on the origin of entry tear and its extension. Type A dissections originate in the ascending aorta, whereas the entry tear in Type B dissections starts distal to the left subclavian artery. The patients with aortic dissection who manifest complications such as rupture, malperfusion, aneurysmal degeneration, and intractable pain are classified as complicated AD. Risk factors for developing aortic dissection include age, male gender, and aortic wall structural abnormalities. The most common presenting symptom of acute aortic dissection is pain. Malperfusion occurs as a result of end-organ ischemia due to involvement of aortic branches from the dissecting process. This can happen in various locations causing mesenteric ischemia (mesenteric vessels), stroke (aortic arch vessels), renal failure (renal arteries), spinal ischemia, and limb ischemia (iliac or subclavian arteries). Aneurysmal degeneration is the most common complication of patients with chronic Type B dissection who are managed with medical therapy. Management of Type B aortic dissection (TBAD) remains controversial. Many groups recommend conservative therapy for newly diagnosed TBAD and reserve surgical management for patients who develop complications such as rupture, malperfusion, aneurysmal dilatation, and refractory pain. The mainstay of medical therapy includes antihypertensive medication to reduced ΔP/ ΔT by lowering blood pressure and heart rate. With the continued success of thoracic endovascular aortic repair (TEVAR), this procedure has been extended to treat TBAD in selected patients. The outcomes of TEVAR are promising, with early mortality rates from 10% to 20%. With promising results from these series, some groups recommend early TEVAR in uncomplicated TBAD to prevent future adverse events. The goals of endovascular treatment of TBAD are to cover the entry tear

  12. Aortic intramural hematoma : assessment of clinical and radiological features in comparison to acute aortic dissection

    International Nuclear Information System (INIS)

    Yoon, Kwon Ha; Hwang, Jae Cheol; Lee, Jin Seong; Kang, Duk Hyun; Song, Jae Kwan; Song, Koun Sik; Lim, Tae Hwan

    1996-01-01

    To compare the clinical and radiological features of aortic intramural hematoma(IMH) to those of acute aortic dissection(AD). We analyzed the clinical and radiological features of 12 patients with aortic IMH and 43 patients with acute AD. In aortic IMH, the diagnoses were made by means of both CT and transesophageal echocardiography(TEE) and included two surgically proven cases. In acute AD, the diagnoses were made by means of CT and TEE and included 21 surgically proven cases. We compared patients ages, etiologies, the extent of the disease, the presence or absence of aortic branch involvement, complications, and outcomes. Aortic IMH tended to develop in older patients (67.8±7.9 vs. 50.4±13.4, P .05). In aortic IMH, there was no involvement of aortic branches, whereas in acute AD, 14(33%) patients showed involvement of one or more aortic branches. Complications of aortic IMH included pericardial effusion (n=2) and pleural effusion (n=4);in acute AD, pericardial effusion (n=7), pleural effusion (n=4), aortic insufficiency (n=8), cerebral infarction (n=3), renal infarction (n=4) and spinal infarction (n=1) were seen. There was one (8%) death due to aortic IMH and ten (23%) deaths due to acute AD (p<.01). Aortic IMH is characterized by its occurrence in older patients with hypertension, a less frequent incidence of complications, and a more favorable outcome than acute AD

  13. Decreased expression of fibulin-4 in aortic wall of aortic dissection.

    Science.gov (United States)

    Huawei, P; Qian, C; Chuan, T; Lei, L; Laing, W; Wenlong, X; Wenzhi, L

    2014-02-01

    In this research, we will examine the expression of Fibulin-4 in aortic wall to find out its role in aortic dissection development. The samples of aortic wall were obtained from 10 patients operated for acute ascending aortic dissection and five patients for chronic ascending aortic dissection. Another 15 pieces of samples from patients who had coronary artery bypass were as controls. The aortic samples were stained with aldehyde magenta dyeing to evaluate the arrangement of elastic fibers. The Fibulin-4 protein and mRNA expression were both determined by Western blot and realtime quantitative polymerase chain reaction. Compared with the control group, both in acute and chronic ascending aortic dissection, elastic fiber fragments increased and the expression of fibulin-4 protein significantly decreased (P= 0.045 < 0.05). The level of fibulin-4 mRNA decreased in acute ascending aortic dissection (P= 0.034 < 0.05), while it increased in chronic ascending aortic dissection (P=0.004 < 0.05). The increased amounts of elastic fiber fragments were negatively correlated with the expression of fibulin-4 mRNA in acute ascending aortic dissection. In conclusion, in aortic wall of ascending aortic dissection, the expression of fibulin-4 protein decreased and the expression of fibulin-4 mRNA was abnormal. Fibulin-4 may play an important role in the pathogenesis of aortic dissection.

  14. Molecular and cellular mechanisms of aortic stenosis.

    Science.gov (United States)

    Yetkin, Ertan; Waltenberger, Johannes

    2009-06-12

    Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

  15. Precursor Amino Acids Inhibit Polymyxin E Biosynthesis in Paenibacillus polymyxa, Probably by Affecting the Expression of Polymyxin E Biosynthesis-Associated Genes

    Directory of Open Access Journals (Sweden)

    Zhiliang Yu

    2015-01-01

    Full Text Available Polymyxin E belongs to cationic polypeptide antibiotic bearing four types of direct precursor amino acids including L-2,4-diaminobutyric acid (L-Dab, L-Leu, D-Leu, and L-Thr. The objective of this study is to evaluate the effect of addition of precursor amino acids during fermentation on polymyxin E biosynthesis in Paenibacillus polymyxa. The results showed that, after 35 h fermentation, addition of direct precursor amino acids to certain concentration significantly inhibited polymyxin E production and affected the expression of genes involved in its biosynthesis. L-Dab repressed the expression of polymyxin synthetase genes pmxA and pmxE, as well as 2,4-diaminobutyrate aminotransferase gene ectB; both L-Leu and D-Leu repressed the pmxA expression. In addition, L-Thr affected the expression of not only pmxA, but also regulatory genes spo0A and abrB. As L-Dab precursor, L-Asp repressed the expression of ectB, pmxA, and pmxE. Moreover, it affected the expression of spo0A and abrB. In contrast, L-Phe, a nonprecursor amino acid, had no obvious effect on polymyxin E biosynthesis and those biosynthesis-related genes expression. Taken together, our data demonstrated that addition of precursor amino acids during fermentation will inhibit polymyxin E production probably by affecting the expression of its biosynthesis-related genes.

  16. Aorto-aortic intrathoracic bypass in surgical treatment of aortic

    International Nuclear Information System (INIS)

    Gutierrez Perez, F.; Duran Reyes, A.; Bigalli, D.; Filgueira Berobide, J.

    1998-01-01

    The prevalence of coarctation of the aorta is 6.5 percent of all congenital heart defects, according to national and international data. There is a restenosis rate of patients after surgery. Factors that influence this evolution depends on the age at which patients underwent surgery for the first time the anatomy of the aortic arch and type of surgical technique. Several procedures can be used to correct the coarctation, which include surgery and balloon catheter dilation. We present here a case of a patient of 22 years old, with a recurrent coarctation of the aorta studied by echocardiography and magnetic resonance imaging. The patient underwent surgery a third time. We used an anterior approach (median sternotomy) and performed an aortic bypass graft, intrathoracic, under cardiopulmonary bypass. Evolved favorably and was discharged on the sixth day of post operative day (Author) [es

  17. Aortic root geometry in aortic stenosis patients (a SEAS substudy)

    DEFF Research Database (Denmark)

    Bahlmann, Edda; Nienaber, Christoph A; Cramariuc, Dana

    2011-01-01

    -specified requirements for the aortic root geometry for current available prostheses, CoreValve and Edwards-Sapien. The ratio of sinus of Valsalva height to sinus width was 1:2. In multivariate linear regression analysis, larger sinus of Valsalva height was associated with older age, larger sinus of Valsalva diameter......, lower ejection fraction and smaller supracoronary diameter (multiple R(2) = 0.19, PSapien prosthesis in 66.9%. Overall, annular dimension feasible for TAVI using any available prosthesis was found...

  18. The cardiovascular effects of aortic clamping and unclamping

    African Journals Online (AJOL)

    aortic clamping is that afterload and blood pressure increase, and ... individually, albeit they interact with each other. The degree of ... position of the aortic clamp, the greater the increase ... the increase in preload in response to aortic clamping.

  19. Indexing aortic valve area by body surface area increases the prevalence of severe aortic stenosis

    DEFF Research Database (Denmark)

    Jander, Nikolaus; Gohlke-Bärwolf, Christa; Bahlmann, Edda

    2014-01-01

    To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are......To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are...

  20. Republished review: Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms.

    Science.gov (United States)

    Treasure, Tom; Takkenberg, J J M; Pepper, John

    2016-02-01

    Elective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long-term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Personal resources and satisfaction with life in Marfan syndrome patients with aortic pathology and in abdominal aortic aneurysm patients.

    Science.gov (United States)

    Stanišić, Michał-Goran; Rzepa, Teresa; Gawrońska, Alicja; Kubaszewski, Przemysław; Putowski, Maciej; Stefaniak, Sebastian; Perek, Bartłomiej

    2018-03-01

    Whether or not the source of aortic pathology is Marfan syndrome (MFS) or other processes leading to development of abdominal aorta aneurysms (AAA), the awareness of pathology may lead to an emotional upset and low assessment of satisfaction with life. To assess, in regard to MFS patients with aortic pathology and to abdominal aortic aneurysm patients: 1) whether or not self-efficacy (SE) and health locus of control (HLoC) affect the patients' satisfaction with life; 2) whether the two groups of patients differ in terms of mental dispositions. The study population consisted of 16 MFS patients with aortic pathology and 16 AAA patients, 9 men and 7 women in each group. The mean age of the MFS patients was 28.5 ±8.214, and of the AAA patients 64.25 ±7.019. The following scales were applied: Generalized Self-Efficacy Scale, Satisfaction With Life Scale, Multidimensional Health Locus of Control Scale. Abdominal aorta aneurysms patients compared to MFS patients gave a higher rating for SE ( MD = 33.94 and MD = 29.56), internal health locus of control ( MD = 25.00 and MD = 21.13), external personal HL o C ( MD = 24.50 and MD = 19.25), external impersonal HLoC ( MD = 23.06 and MD = 18.25), and satisfaction with life ( M = 22.06 and M = 20.13). Internal and external HL o C were significantly lower in MFS patients compared to AAA patients. In patients with aortic diseases, special attention must be paid to the state of personal resources (PR). Interactions made by medical professionals should focus on enhancing PR supporting the patients' self-knowledge on their SE. This will help to improve their satisfaction with life and form a positive attitude to the illness.

  2. Aortic valvuloplasty of calcific aortic stenosis with monofoil and trefoil balloon catheters: practical considerations

    NARCIS (Netherlands)

    S. Plante (Sylvain); M.J.B.M. van den Brand (Marcel); L.C.P. van Veen; C. di Mario (Carlo); C.E. Essed; K.J. Beatt (Kevin); P.W.J.C. Serruys (Patrick)

    1990-01-01

    textabstractIn order to evaluate the relation between balloon design (monofoil, trefoil) and valvular configuration, experimental aortic valvuloplasty was performed in four post-mortem hearts with calcific aortic stenosis of various morphology. The degree of obstruction of the aortic orifice was

  3. Association Between Gout and Aortic Stenosis.

    Science.gov (United States)

    Chang, Kevin; Yokose, Chio; Tenner, Craig; Oh, Cheongeun; Donnino, Robert; Choy-Shan, Alana; Pike, Virginia C; Shah, Binita D; Lorin, Jeffrey D; Krasnokutsky, Svetlana; Sedlis, Steven P; Pillinger, Michael H

    2017-02-01

    An independent association between gout and coronary artery disease is well established. The relationship between gout and valvular heart disease, however, is unclear. The aim of this study was to assess the association between gout and aortic stenosis. We performed a retrospective case-control study. Aortic stenosis cases were identified through a review of outpatient transthoracic echocardiography (TTE) reports. Age-matched controls were randomly selected from patients who had undergone TTE and did not have aortic stenosis. Charts were reviewed to identify diagnoses of gout and the earliest dates of gout and aortic stenosis diagnosis. Among 1085 patients who underwent TTE, 112 aortic stenosis cases were identified. Cases and nonaortic stenosis controls (n = 224) were similar in age and cardiovascular comorbidities. A history of gout was present in 21.4% (n = 24) of aortic stenosis subjects compared with 12.5% (n = 28) of controls (unadjusted odds ratio 1.90, 95% confidence interval 1.05-3.48, P = .038). Multivariate analysis retained significance only for gout (adjusted odds ratio 2.08, 95% confidence interval 1.00-4.32, P = .049). Among subjects with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis by 5.8 ± 1.6 years. The age at onset of aortic stenosis was similar among patients with and without gout (78.7 ± 1.8 vs 75.8 ± 1.0 years old, P = .16). Aortic stenosis patients had a markedly higher prevalence of precedent gout than age-matched controls. Whether gout is a marker of, or a risk factor for, the development of aortic stenosis remains uncertain. Studies investigating the potential role of gout in the pathophysiology of aortic stenosis are warranted and could have therapeutic implications. Published by Elsevier Inc.

  4. Low-gradient aortic stenosis.

    Science.gov (United States)

    Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

    2016-09-07

    An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA gradient (gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  5. Distinct mutations in yeast TAF(II)25 differentially affect the composition of TFIID and SAGA complexes as well as global gene expression patterns.

    Science.gov (United States)

    Kirschner, Doris B; vom Baur, Elmar; Thibault, Christelle; Sanders, Steven L; Gangloff, Yann-Gaël; Davidson, Irwin; Weil, P Anthony; Tora, Làszlò

    2002-05-01

    The RNA polymerase II transcription factor TFIID, composed of the TATA-binding protein (TBP) and TBP-associated factors (TAF(II)s), nucleates preinitiation complex formation at protein-coding gene promoters. SAGA, a second TAF(II)-containing multiprotein complex, is involved in transcription regulation in Saccharomyces cerevisiae. One of the essential protein components common to SAGA and TFIID is yTAF(II)25. We define a minimal evolutionarily conserved 91-amino-acid region of TAF(II)25 containing a histone fold domain that is necessary and sufficient for growth in vivo. Different temperature-sensitive mutations of yTAF(II)25 or chimeras with the human homologue TAF(II)30 arrested cell growth at either the G(1) or G(2)/M cell cycle phase and displayed distinct phenotypic changes and gene expression patterns. Immunoprecipitation studies revealed that TAF(II)25 mutation-dependent gene expression and phenotypic changes correlated at least partially with the integrity of SAGA and TFIID. Genome-wide expression analysis revealed that the five TAF(II)25 temperature-sensitive mutant alleles individually affect the expression of between 18 and 33% of genes, whereas taken together they affect 64% of all class II genes. Thus, different yTAF(II)25 mutations induce distinct phenotypes and affect the regulation of different subsets of genes, demonstrating that no individual TAF(II) mutant allele reflects the full range of its normal functions.

  6. Thoracic aortic aneurysms and dissections: endovascular treatment.

    Science.gov (United States)

    Baril, Donald T; Cho, Jae S; Chaer, Rabih A; Makaroun, Michel S

    2010-01-01

    The treatment of thoracic aortic disease has changed radically with the advances made in endovascular therapy since the concept of thoracic endovascular aortic repair was first described 15 years ago. Currently, there is a diverse array of endografts that are commercially available to treat the thoracic aorta. Multiple studies, including industry-sponsored and single-institution reports, have demonstrated excellent outcomes of thoracic endovascular aortic repair for the treatment of thoracic aortic aneurysms, with less reported perioperative morbidity and mortality in comparison with conventional open repair. Additionally, similar outcomes have been demonstrated for the treatment of type B dissections. However, the technology remains relatively novel, and larger studies with longer term outcomes are necessary to more fully evaluate the role of endovascular therapy for the treatment of thoracic aortic disease. This review examines the currently available thoracic endografts, preoperative planning for thoracic endovascular aortic repair, and outcomes of thoracic endovascular aortic repair for the treatment of both thoracic aortic aneurysms and type B aortic dissections. Mt Sinai J Med 77:256-269, 2010. (c) 2010 Mount Sinai School of Medicine.

  7. Hybrid treatment of penetrating aortic ulcer

    International Nuclear Information System (INIS)

    Lara, Juan Antonio Herrero; Martins-Romeo, Daniela de Araujo; Escudero, Carlos Caparros; Falcon, Maria del Carmen Prieto; Batista, Vinicius Bianchi; Vazquez, Rosa Maria Lepe

    2015-01-01

    Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease. (author)

  8. Hybrid treatment of penetrating aortic ulcer

    Energy Technology Data Exchange (ETDEWEB)

    Lara, Juan Antonio Herrero; Martins-Romeo, Daniela de Araujo; Escudero, Carlos Caparros; Falcon, Maria del Carmen Prieto; Batista, Vinicius Bianchi, E-mail: jaherrero5@hotmail.com [Unidade de Gestao Clinica (UGC) de Diagnostico por Imagem - Hosppital Universitario Virgen Macarena, Sevilha (Spain); Vazquez, Rosa Maria Lepe [Unit of Radiodiagnosis - Hospital Nuestra Senora de la Merced, Osuna, Sevilha (Spain)

    2015-05-15

    Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease. (author)

  9. Surgery for acute Type I aortic dissection without resection of supra-aortic entry sites leads to unfavourable aortic remodelling.

    Science.gov (United States)

    Heo, Woon; Song, Suk-Won; Lee, Kwang-Hun; Lee, Shin-Young; Kim, Tae-Hoon; Baek, Min-Young; Yoo, Kyung-Jong

    2018-01-29

    This study aimed to evaluate the impact of remnant re-entries in arch branches on postoperative change in the aortic arch and descending aortic diameters and the rate of major adverse aortic events. Between January 2010 and December 2016, 249 patients underwent surgery for acute Type I aortic dissection. Patients who underwent total arch replacement, had Marfan syndrome or had intramural haematoma were excluded. Seventy-two patients with predischarge and follow-up computed tomography scans were enrolled. Patients with and without re-entries in the arch branches after surgery were assigned to the supra-aortic entry (SAE, n = 21) and no supra-aortic entry (n = 51) groups, respectively. Diameters were measured at 7 levels: the innominate artery, left common carotid artery, left subclavian artery, 20 mm distal to the left subclavian artery, pulmonary artery bifurcation, coeliac axis and maximal diameter of the descending thoracic aorta. Growth rates at the levels of the pulmonary artery bifurcation and 20 mm distal to the left subclavian artery were significantly higher in the SAE group than in the no supra-aortic entry group. The rate of freedom from major adverse aortic events (annual growth >5 mm or maximal diameter of the descending thoracic aorta >50 mm) at 5 years was significantly higher in the no supra-aortic entry group than in the SAE group. Remnant SAE leads to unfavourable aortic remodelling after acute Type I aortic dissection repair. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  10. The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484.

    Science.gov (United States)

    Bradshaw, Nicholas J; Ukkola-Vuoti, Liisa; Pankakoski, Maiju; Zheutlin, Amanda B; Ortega-Alonso, Alfredo; Torniainen-Holm, Minna; Sinha, Vishal; Therman, Sebastian; Paunio, Tiina; Suvisaari, Jaana; Lönnqvist, Jouko; Cannon, Tyrone D; Haukka, Jari; Hennah, William

    2017-11-01

    Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1 , NDE1 , NDEL1 , PDE4B and PDE4D , the 'DISC1 network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 ( p = 3.0 × 10 -8 ), located on a non-coding exon of NDE1 Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment. © 2017 The Authors.

  11. Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women.

    Science.gov (United States)

    Martinelli, F; Signorelli, M; Bogani, G; Ditto, A; Chiappa, V; Perotto, S; Scaffa, C; Lorusso, D; Raspagliesi, F

    2016-10-01

    The aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. Retrospective evaluation of consecutive 261 patients affected by LACC (stage IB2-IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. Stage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. Our data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  12. Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine.

    Science.gov (United States)

    Kim, Ha Won; Blomkalns, Andra L; Ogbi, Mourad; Thomas, Manesh; Gavrila, Daniel; Neltner, Bonnie S; Cassis, Lisa A; Thompson, Robert W; Weiss, Robert M; Lindower, Paul D; Blanco, Victor M; McCormick, Michael L; Daugherty, Alan; Fu, Xiaoming; Hazen, Stanley L; Stansfield, Brian K; Huo, Yuqing; Fulton, David J; Chatterjee, Tapan; Weintraub, Neal L

    2017-12-01

    Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl 2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration. NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation

  13. Removal of antibiotic-resistant bacteria and antibiotic resistance genes affected by varying degrees of fouling on anaerobic microfiltration membranes

    KAUST Repository

    Cheng, Hong; Hong, Pei-Ying

    2017-01-01

    An anaerobic membrane bioreactor was retrofitted with polyvinylidene fluoride (PVDF) microfiltration membrane units, each of which was fouled to a different extent. The membranes with different degrees of fouling were evaluated for their efficiencies in removing three antibiotic-resistant bacteria (ARB), namely, blaNDM-1-positive Escherichia coli PI-7, blaCTX-M-15-positive Klebsiella pneumoniae L7, and blaOXA-48-positive E. coli UPEC-RIY-4, as well as their associated plasmid-borne antibiotic resistance genes (ARGs). The results showed that the log removal values (LRVs) of ARGs correlated positively with the extent of membrane fouling and ranged from 1.9 to 3.9. New membranes with a minimal foulant layer could remove more than 5 log units of ARB. However, as the membranes progressed to subcritical fouling, the LRVs of ARB decreased at increasing operating transmembrane pressures (TMPs). The LRV recovered back to 5 when the membrane was critically fouled, and the achieved LRV remained stable at different operating TMPs. Furthermore, characterization of the surface attributed the removal of both the ARB and ARGs to adsorption, which was facilitated by an increasing hydrophobicity and a decreasing surface ζ potential as the membranes fouled. Our results indicate that both the TMP and the foulant layer synergistically affected ARB removal, but the foulant layer was the main factor that contributed to ARG removal.

  14. Removal of antibiotic-resistant bacteria and antibiotic resistance genes affected by varying degrees of fouling on anaerobic microfiltration membranes

    KAUST Repository

    Cheng, Hong

    2017-09-28

    An anaerobic membrane bioreactor was retrofitted with polyvinylidene fluoride (PVDF) microfiltration membrane units, each of which was fouled to a different extent. The membranes with different degrees of fouling were evaluated for their efficiencies in removing three antibiotic-resistant bacteria (ARB), namely, blaNDM-1-positive Escherichia coli PI-7, blaCTX-M-15-positive Klebsiella pneumoniae L7, and blaOXA-48-positive E. coli UPEC-RIY-4, as well as their associated plasmid-borne antibiotic resistance genes (ARGs). The results showed that the log removal values (LRVs) of ARGs correlated positively with the extent of membrane fouling and ranged from 1.9 to 3.9. New membranes with a minimal foulant layer could remove more than 5 log units of ARB. However, as the membranes progressed to subcritical fouling, the LRVs of ARB decreased at increasing operating transmembrane pressures (TMPs). The LRV recovered back to 5 when the membrane was critically fouled, and the achieved LRV remained stable at different operating TMPs. Furthermore, characterization of the surface attributed the removal of both the ARB and ARGs to adsorption, which was facilitated by an increasing hydrophobicity and a decreasing surface ζ potential as the membranes fouled. Our results indicate that both the TMP and the foulant layer synergistically affected ARB removal, but the foulant layer was the main factor that contributed to ARG removal.

  15. Removal of Antibiotic-Resistant Bacteria and Antibiotic Resistance Genes Affected by Varying Degrees of Fouling on Anaerobic Microfiltration Membranes.

    Science.gov (United States)

    Cheng, Hong; Hong, Pei-Ying

    2017-11-07

    An anaerobic membrane bioreactor was retrofitted with polyvinylidene fluoride (PVDF) microfiltration membrane units, each of which was fouled to a different extent. The membranes with different degrees of fouling were evaluated for their efficiencies in removing three antibiotic-resistant bacteria (ARB), namely, bla NDM-1 -positive Escherichia coli PI-7, bla CTX-M-15 -positive Klebsiella pneumoniae L7, and bla OXA-48 -positive E. coli UPEC-RIY-4, as well as their associated plasmid-borne antibiotic resistance genes (ARGs). The results showed that the log removal values (LRVs) of ARGs correlated positively with the extent of membrane fouling and ranged from 1.9 to 3.9. New membranes with a minimal foulant layer could remove more than 5 log units of ARB. However, as the membranes progressed to subcritical fouling, the LRVs of ARB decreased at increasing operating transmembrane pressures (TMPs). The LRV recovered back to 5 when the membrane was critically fouled, and the achieved LRV remained stable at different operating TMPs. Furthermore, characterization of the surface attributed the removal of both the ARB and ARGs to adsorption, which was facilitated by an increasing hydrophobicity and a decreasing surface ζ potential as the membranes fouled. Our results indicate that both the TMP and the foulant layer synergistically affected ARB removal, but the foulant layer was the main factor that contributed to ARG removal.

  16. Failure to induce a DNA repair gene, RAD54, in Saccharomyces cerevisiae does not affect DNA repair or recombination phenotypes

    International Nuclear Information System (INIS)

    Cole, G.M.; Mortimer, R.K.

    1989-01-01

    The Saccharomyces cerevisiae RAD54 gene is transcriptionally regulated by a broad spectrum of DNA-damaging agents. Induction of RAD54 by DNA-damaging agents is under positive control. Sequences responsible for DNA damage induction (the DRS element) lie within a 29-base-pair region from -99 to -70 from the most proximal transcription start site. This inducible promoter element is functionally separable from a poly(dA-dT) region immediately downstream which is required for constitutive expression. Deletions which eliminate induction of RAD54 transcription by DNA damage but do not affect constitutive expression have no effect on growth or survival of noninducible strains relative to wild-type strains in the presence of DNA-damaging agents. The DRS element is also not required for homothallic mating type switching, transcriptional induction of RAD54 during meiosis, meiotic recombination, or spontaneous or X-ray-induced mitotic recombination. We find no phenotype for a lack of induction of RAD54 message via the damage-inducible DRS, which raises significant questions about the physiology of DNA damage induction in S. cerevisiae

  17. Mutational Biases and GC-Biased Gene Conversion Affect GC Content in the Plastomes of Dendrobium Genus

    Directory of Open Access Journals (Sweden)

    Zhitao Niu

    2017-11-01

    Full Text Available The variation of GC content is a key genome feature because it is associated with fundamental elements of genome organization. However, the reason for this variation is still an open question. Different kinds of hypotheses have been proposed to explain the variation of GC content during genome evolution. However, these hypotheses have not been explicitly investigated in whole plastome sequences. Dendrobium is one of the largest genera in the orchid species. Evolutionary studies of the plastomic organization and base composition are limited in this genus. In this study, we obtained the high-quality plastome sequences of D. loddigesii and D. devonianum. The comparison results showed a nearly identical organization in Dendrobium plastomes, indicating that the plastomic organization is highly conserved in Dendrobium genus. Furthermore, the impact of three evolutionary forces—selection, mutational biases, and GC-biased gene conversion (gBGC—on the variation of GC content in Dendrobium plastomes was evaluated. Our results revealed: (1 consistent GC content evolution trends and mutational biases in single-copy (SC and inverted repeats (IRs regions; and (2 that gBGC has influenced the plastome-wide GC content evolution. These results suggest that both mutational biases and gBGC affect GC content in the plastomes of Dendrobium genus.

  18. Mutational Biases and GC-Biased Gene Conversion Affect GC Content in the Plastomes of Dendrobium Genus

    Science.gov (United States)

    Niu, Zhitao; Xue, Qingyun; Wang, Hui; Xie, Xuezhu; Zhu, Shuying; Liu, Wei; Ding, Xiaoyu

    2017-01-01

    The variation of GC content is a key genome feature because it is associated with fundamental elements of genome organization. However, the reason for this variation is still an open question. Different kinds of hypotheses have been proposed to explain the variation of GC content during genome evolution. However, these hypotheses have not been explicitly investigated in whole plastome sequences. Dendrobium is one of the largest genera in the orchid species. Evolutionary studies of the plastomic organization and base composition are limited in this genus. In this study, we obtained the high-quality plastome sequences of D. loddigesii and D. devonianum. The comparison results showed a nearly identical organization in Dendrobium plastomes, indicating that the plastomic organization is highly conserved in Dendrobium genus. Furthermore, the impact of three evolutionary forces—selection, mutational biases, and GC-biased gene conversion (gBGC)—on the variation of GC content in Dendrobium plastomes was evaluated. Our results revealed: (1) consistent GC content evolution trends and mutational biases in single-copy (SC) and inverted repeats (IRs) regions; and (2) that gBGC has influenced the plastome-wide GC content evolution. These results suggest that both mutational biases and gBGC affect GC content in the plastomes of Dendrobium genus. PMID:29099062

  19. Early results of valve-sparing ascending aortic replacement in type A aortic dissection and aortic insufficiency

    Directory of Open Access Journals (Sweden)

    М. Л. Гордеев

    2016-08-01

    Full Text Available Aim: The study was designed to investigate predictors of effective valve-sparing ascending aortic replacement in patients with Stanford type A aortic dissection combined with aortic insufficiency and to analyze efficacy and safety of this kind of surgery.Methods: From January 2010 to December 2015, 49 patients with Stanford type A aortic dissection combined with aortic insufficiency underwent ascending aortic replacement. All patients were divided into 3 groups: valve-sparing procedures (group 1, n = 11, combined aortic valve and supracoronary ascending aortic replacement (group 2, n = 12, and Bentall procedure (group 3, n = 26. We assessed the initial status of patients, incidence of complications and efficacy of valve-sparing ascending aortic replacement.Results: The hospital mortality rate was 8.2% (4/49 patients. The amount of surgical correction correlated with the initial diameter of the aorta at the level of the sinuses of Valsalva. During the hospital period, none of patients from group 1 developed aortic insufficiency exceeding Grade 2 and the vast majority of patients had trivial aortic regurgitation. The parameters of cardiopulmonary bypass, cross-clamp time and circulatory arrest time did not correlate with the initial size of the ascending aorta and aortic valve blood flow impairment, neither did they influence significantly the incidence and severity of neurological complications. The baseline size of the ascending aorta and degree of aortic regurgitation did not impact the course of the early hospital period.Conclusions: Supracoronary ascending aortic replacement combined with aortic valve repair in ascending aortic dissection and aortic regurgitation is effective and safe. The initial size of the ascending aorta and aortic arch do not influence immediate results. The diameter of the aorta at the level of the sinuses of Valsalva and the condition of aortic valve leaflets could be considered as the limiting factors. Further long

  20. A systems biology approach using transcriptomic data reveals genes and pathways in porcine skeletal muscle affected by dietary lysine

    Science.gov (United States)

    Meeting the increasing market demands for pork products requires improvement of the feed efficiency of growing pigs. The use of Affymetrix Porcine Gene 1.0 ST array containing 19,211 genes in this study provides a comprehensive gene expression profile of skeletal muscle of finishing pigs in response...

  1. [Metabolic syndrome and aortic stiffness].

    Science.gov (United States)

    Simková, A; Bulas, J; Murín, J; Kozlíková, K; Janiga, I

    2010-09-01

    The metabolic syndrome (MS) is a cluster of risk factors that move the patient into higher level of risk category of cardiovascular disease and the probability of type 2 diabetes mellitus manifestation. Definition of MS is s based on the presence of selected risk factors as: abdominal obesity (lager waist circumpherence), atherogenic dyslipidemia (low value of HDL-cholesterol and increased level of triglycerides), increased fasting blood glucose (or type 2 DM diagnosis), higher blood pressure or antihypertensive therapy. In 2009 there were created harmonizing criteria for MS definition; the condition for assignment of MS is the presence of any 3 criteria of 5 mentioned above. The underlying disorder of MS is an insulin resistance or prediabetes. The patients with MS more frequently have subclinical (preclinical) target organ disease (TOD) which is the early sings of atherosclerosis. Increased aortic stiffness is one of the preclinical diseases and is defined by pathologically increased carotidofemoral pulse wave velocity in aorta (PWV Ao). With the aim to assess the influence of MS on aortic stiffness we examined the group of women with arterial hypertension and MS and compare them with the group of women without MS. The aortic stiffness was examined by Arteriograph--Tensiomed, the equipment working on the oscillometric principle in detection of pulsations of brachial artery. This method determines the global aortic stiffness based on the analysis of the shape of pulse curve of brachial artery. From the cohort of 49 pts 31 had MS, the subgroups did not differ in age or blood pressure level. The mean number of risk factors per person in MS was 3.7 comparing with 1.7 in those without MS. In the MS group there was more frequently abdominal obesity present (87% vs 44%), increased fasting blood glucose (81% vs 22%) and low HDL-cholesterol level. The pulse wave velocity in aorta, PWV Ao, was significantly higher in patients with MS (mean value 10,19 m/s vs 8,96 m

  2. Aortic elongation in aortic aneurysm and dissection: the Tübingen Aortic Pathoanatomy (TAIPAN) project.

    Science.gov (United States)

    Krüger, Tobias; Sandoval Boburg, Rodrigo; Lescan, Mario; Oikonomou, Alexandre; Schneider, Wilke; Vöhringer, Luise; Lausberg, Henning; Bamberg, Fabian; Blumenstock, Gunnar; Schlensak, Christian

    2018-01-24

    To study the lengths and diameters of aortic segments in healthy and diseased aortas and to assess the role of aortic elongation in Type A aortic dissection (TAD) prediction. Ectasia and aneurysm were defined by ascending aorta diameters of 45-54 mm and ≥55 mm, respectively. Computed tomography angiography studies of 256 healthy, 102 ectasia, 38 aneurysm, 17 pre-TAD and 166 TAD aortas were analysed using curved multiplanar reformats. The study groups were structurally equal. The diameter of the ascending aorta was 35 mm in the control group and was larger (P TAD (43 mm) and TAD (56 mm) groups. The length of the ascending aorta from the aortic annulus to the brachiocephalic trunk was 92 mm in the control group, 113 mm in the ectasia group, 120 mm in the aneurysm group and 111 mm and 118 mm in the pre-TAD and TAD groups (all P TAD group and 48% of the TAD group. The correlation between the diameter and the length of the ascending aorta was r = 0.752; therefore, both parameters must be examined separately. A score considering both parameters identified 23.5% of pre-TAD patients, significantly more than the diameter alone, and 31.4% of ectasia aortas were elongated. Patients with ectatic (45-54 mm diameter) and elongated (≥120 mm) ascending aortas represent a high-risk subpopulation for TAD. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  3. Epidemiology of aortic disease - aneurysm, dissection, occlusion

    International Nuclear Information System (INIS)

    Steckmeier, B.

    2001-01-01

    The physiological infrarenal aortic diameter varies between 12.4 mm in women an 27.6 mm in men. As defined, an aneurysmatic dilatation begins with 29 mm. According to that, 9% of all people above the age of 65 are affected by an abdominal aortic aneurysm (AAA). Compared with the female sex, the male sex predominates at a rate of about 5:1. The disease is predominant in men of the white race. In black men, black and white women the incidence of AAA is identical. 38 to 50 percent of the AAA patients (patients) suffer from hypertension, 33 to 60% from coronary, 28% from cerebrovascular and 25% from peripheral occlusive disease. The AAA expansion rate varies between 0.2 and 0.8 cm per year and is exponential from a diameter of 5 cm on. In autopsy studies, the rupture rates with AAA diameters of 7 cm were below 5%, 39% and 65%, respecitvely. 70% of the AAA patients do not die of a rupture, but of a cardiac disease. Serum markers, such as metalloproteinases and procollagen peptides are significantly increased in AAA patients. Thoraco-abdominal aneurysms (TAA) make up only 2 to 5% of all degenerative aneurysms. 20 to 30% of the TAA patients are also affected by an AAA. 80% of the TAA are degenerative, 15 to 20% are a consequence of the chronic dissection - including 5% of Marfan patients -, 2% occur in case of infections and 1 to 2% in case of aortitis. The TAA incidence in 100,000 person-years is 5.9% during a monitoring period of 30 years. In case of TAA, an operation is indicated with a maximum diameter of 5.5 to 6 cm and more and, in case of a Marfan's syndrome (incidence of 1:10,000), with a maximum diameter of 5.5 cm and more. With regard to aorto-iliac occlusive diseases, there are defined 3 types of distribution. Type I refers to the region of the bifurcation itself. Type II defines the diffuse aortoiliac spread of the disease. Type III designates multiple-level occlusions also beyond the inguinal ligament. Type I patients in most cases are female and more

  4. Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome.

    Science.gov (United States)

    García-Herrera, Claudio M; Celentano, Diego J; Herrera, Emilio A

    2017-03-01

    Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention.

  5. Infected aortic aneurysm and inflammatory aortic aneurysm. In search of an optimal differential diagnosis

    International Nuclear Information System (INIS)

    Ishizaka, Nobukazu; Sohmiya, Koichi; Miyamura, Masatoshi; Umeda, Tatsuya; Tsuji, Motomu; Katsumata, Takahiro; Miyata, Tetsuro

    2012-01-01

    Infected aortic aneurysm and inflammatory aortic aneurysm each account for a minor fraction of the total incidence of aortic aneurysm and are associated with periaortic inflammation. Despite the similarity, infected aortic aneurysm generally shows a more rapid change in clinical condition, leading to a fatal outcome; in addition, delayed diagnosis and misuse of corticosteroid or immunosuppressing drugs may lead to uncontrolled growth of microorganisms. Therefore, it is mandatory that detection of aortic aneurysm is followed by accurate differential diagnosis. In general, infected aortic aneurysm appears usually as a saccular form aneurysm with nodularity, irregular configuration; however, the differential diagnosis may not be easy sometimes for the following reasons: symptoms, such as abdominal and/or back pain and fever, and blood test abnormalities, such as elevated C-reactive protein and enhanced erythrocyte sedimentation rate, are common in infected aortic aneurysm, but they are not found infrequently in inflammatory aortic aneurysm; some inflammatory aortic aneurysms are immunoglobulin (Ig) G4-related, but not all of them; the prevalence of IgG4 positivity in infected aortic aneurysm has not been well investigated; enhanced uptake of 18F-fluorodeoxyglucose (FDG) by 18F-FDG-positron emission tomography may not distinguish between inflammation mediated by autoimmunity and that mediated by microorganism infection. Here we discuss the characteristics of these two forms of aortic aneurysm and the points of which we have to be aware before reaching a final diagnosis. (author)

  6. A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

    Directory of Open Access Journals (Sweden)

    Cigudosa Juan C

    2011-05-01

    Full Text Available Abstract Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs, will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents. With the extension of this analysis to an Array-CGH dataset (glioblastomas from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.

  7. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain

    NARCIS (Netherlands)

    Doelen, R.H.A. van der; Arnoldussen, I.A.C.; Ghareh, H.; Och, L. van; Homberg, J.R.; Kozicz, L.T.

    2015-01-01

    The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene x Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid

  8. Effect of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the Placement of Aortic Transcatheter Valves II inoperable cohort.

    Science.gov (United States)

    Lindman, Brian R; Maniar, Hersh S; Jaber, Wael A; Lerakis, Stamatios; Mack, Michael J; Suri, Rakesh M; Thourani, Vinod H; Babaliaros, Vasilis; Kereiakes, Dean J; Whisenant, Brian; Miller, D Craig; Tuzcu, E Murat; Svensson, Lars G; Xu, Ke; Doshi, Darshan; Leon, Martin B; Zajarias, Alan

    2015-04-01

    Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized. Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively (Pright atrial and RV enlargement were also associated with increased mortality (Pright atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity (P=0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation. In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01314313. © 2015 American Heart Association, Inc.

  9. Delayed Presentation of a Giant Ascending Aortic Aneurysm following Aortic Valve Replacement

    Directory of Open Access Journals (Sweden)

    Tugrul Göncü

    2009-01-01

    Full Text Available Giant ascending aortic aneurysm formation following aortic valve replacement is rare. A 28-year-old man who underwent aortic valve replacement with a prosthetic valve for aortic regurgitation secondary to congenital bicuspid aortic valve about 10 years ago was diagnosed with a giant ascending aortic aneurysm about 16 cm in diameter in follow-up. The aneurysm was resected leaving the functional old mechanical prosthesis in place and implanted a 34-mm Hemashield woven graft, associated with the left and right coronary artery button implantation. Histological findings of the aortic aneurysm wall showed cystic medial necrosis. The postoperative course was uneventful and postoperative examination demonstrated good surgical results.

  10. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  11. Surgical treatment and thoracic endovascular aortic repair in type A aortic dissection in a pregnant patient with Marfan syndrome.

    Science.gov (United States)

    Sterner, Doerthe; Probst, Chris; Mellert, Friedrich; Schiller, Wolfgang

    2014-07-01

    We report an acute aortic dissection type Stanford A extending down to both iliac arteries affecting a 32-year-old woman suspected to have Marfan syndrome during week 37 of pregnancy. In a multidisciplinary approach, and emergency Cesarean section was performed followed by an abdominal hysterectomy and a valve-sparing aortic root replacement using a reimplantation technique. The aorta was replaced up to the hemi arch. Because of the high suspicion of visceral ischemia as confirmed ex juvantibus, an endovascular stent graft was implanted. Molecular testing revealed a frameshift mutation and confirmed the diagnosis of Marfan syndrome. Both the patient and her healthy child underwent an uneventful recovery. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Dyslipidemia rather than Type 2 Diabetes Mellitus or Chronic Periodontitis Affects the Systemic Expression of Pro- and Anti-Inflammatory Genes.

    Science.gov (United States)

    Nepomuceno, Rafael; Villela, Bárbara Scoralick; Corbi, Sâmia Cruz Tfaile; Bastos, Alliny De Souza; Dos Santos, Raquel Alves; Takahashi, Catarina Satie; Orrico, Silvana Regina Perez; Scarel-Caminaga, Raquel Mantuaneli

    2017-01-01

    A high percentage of type 2 diabetes mellitus (T2D) patients are also affected by dyslipidemia and chronic periodontitis (CP), but no studies have determined the gene expression in patients that are simultaneously affected by all three diseases. We investigated the systemic expression of immune-related genes in T2D, dyslipidemia, and CP patients. One hundred and fifty patients were separated into five groups containing 30 individuals each: (G1) poorly controlled T2D with dyslipidemia and CP; (G2) well-controlled T2D with dyslipidemia and CP; (G3) normoglycemic individuals with dyslipidemia and CP; (G4) healthy individuals with CP; (G5) systemic and periodontally healthy individuals. Blood analyses of lipid and glycemic profiles were carried out. The expression of genes, including IL10, JAK1, STAT3, SOCS3, IP10, ICAM1, IFNA, IFNG, STAT1, and IRF1, was investigated by RT-qPCR. Patients with dyslipidemia demonstrated statistically higher expression of the IL10 and IFNA genes, while IFNG, IP10, IRF1, JAK1, and STAT3 were lower in comparison with nondyslipidemic patients. Anti-inflammatory genes, such as IL10 , positively correlated with parameters of glucose, lipid, and periodontal profiles, while proinflammatory genes, such as IFNG , were negatively correlated with these parameters. We conclude that dyslipidemia appears to be the primary disease that is associated with gene expression of immune-related genes, while parameters of T2D and CP were correlated with the expression of these important immune genes.

  13. Light regimes differentially affect baseline transcript abundance of stress-axis and (neurodevelopment-related genes in zebrafish (Danio rerio, Hamilton 1822 AB and TL larvae

    Directory of Open Access Journals (Sweden)

    Ruud van den Bos

    2017-11-01

    Full Text Available Many strains of zebrafish (Danio rerio are readily available. Earlier we observed differences between AB and Tupfel long-fin (TL larvae regarding baseline hypothalamus-pituitary-interrenal (HPI axis activity and (neurodevelopment. Light regimes, i.e. 14 h light:10 h dark and 24 h continuous dark or light, affect hatching rate and larval growth. Here, we assessed baseline transcript abundance of HPI-axis-related genes and (neurodevelopment-related genes of AB and TL larvae (5 days post fertilisation using these light regimes. A principal component analysis revealed that in AB larvae the baseline expression of HPI-axis-related genes was higher the more hours of light, while the expression of (neurodevelopment-related genes was higher under 14 h light:10 h dark than under both continuous light or dark. In TL larvae, a complex pattern emerged regarding baseline expression of HPI-axis-related and (neurodevelopment-related genes. These data extend data of earlier studies by showing that light regimes affect gene-expression in larvae, and more importantly so, strengthen the notion of differences between larvae of the AB and TL strain. The latter finding adds to the growing database of phenotypical differences between zebrafish of the AB and TL strain.

  14. The Arabidopsis DELAY OF GERMINATION 1 gene affects ABSCISIC ACID INSENSITIVE 5 (ABI5) expression and genetically interacts with ABI3 during Arabidopsis seed development

    NARCIS (Netherlands)

    Dekkers, B.J.W.; Hanson, S.J.|info:eu-repo/dai/nl/304822299; Willems, L.A.J.; Jamar, D.C.L.; Cueff, Gwendal; Raijou, G.; Hilhorst, H.W.M.; Bentsink, L.|info:eu-repo/dai/nl/241338735

    2016-01-01

    The seed expressed gene DELAY OF GERMINATION (DOG) 1 is absolutely required for the induction of dormancy. Next to a non-dormant phenotype, the dog1-1 mutant is also characterized by a reduced seed longevity suggesting that DOG1 may affect additional seed processes as well. This aspect however, has

  15. The Arabidopsis DELAY OF GERMINATION 1 gene affects ABSCISIC ACID INSENSITIVE 5 (ABI5) expression and genetically interacts with ABI3 during Arabidopsis seed development

    NARCIS (Netherlands)

    Dekkers, B.J.W.; He, Hanzi; Hanson, Johannes; Willems, L.A.J.; Jamar, D.C.L.; Cueff, Gwendal; Rajjou, Loïc; Hilhorst, H.W.M.; Bentsink, Leónie

    2016-01-01

    The seed expressed gene DELAY OF GERMINATION (DOG) 1 is absolutely required for the induction of dormancy. Next to a non-dormant phenotype, the dog1-1 mutant is also characterized by a reduced seed longevity suggesting that DOG1 may affect additional seed processes as well. This aspect however,

  16. Transcatheter Aortic Valve Replacement in Europe

    DEFF Research Database (Denmark)

    Mylotte, Darren; Osnabrugge, Ruben L J; Windecker, Stephan

    2013-01-01

    The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy.......The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy....

  17. Graft infections after surgical aortic reconstructions

    NARCIS (Netherlands)

    Berger, P.

    2015-01-01

    Prosthetic vascular grafts are frequently used to reconstruct (part) of the aorta. Every surgical procedure caries a certain risk for infection and when a prosthetic aortic graft is implanted, this may lead to an aortic graft infection (AGI). Endovascular techniques have gradually replaced open

  18. Severe aortic stenosis: diagnosis, treatment and prognosis

    NARCIS (Netherlands)

    M.W.A. van Geldorp (Martijn)

    2013-01-01

    textabstractDegenerative aortic stenosis is the most common valvular heart disease in developed countries. The prevalence of severe aortic stenosis increases with age from 1% in people below 65 years of age to nearly 6% in people over the age of 85. Since the population life expectancy continues to

  19. Valve-sparing aortic root replacement†

    NARCIS (Netherlands)

    Koolbergen, David R.; Manshanden, Johan S. J.; Bouma, Berto J.; Blom, Nico A.; Mulder, Barbara J. M.; de Mol, Bas A. J. M.; Hazekamp, Mark G.

    2015-01-01

    To evaluate our results of valve-sparing aortic root replacement and associated (multiple) valve repair. From September 2003 to September 2013, 97 patients had valve-sparing aortic root replacement procedures. Patient records and preoperative, postoperative and recent echocardiograms were reviewed.

  20. Do dopaminergic gene polymorphisms affect mesolimbic reward activation of music listening response? Therapeutic impact on Reward Deficiency Syndrome (RDS).

    Science.gov (United States)

    Blum, Kenneth; Chen, Thomas J H; Chen, Amanda L H; Madigan, Margaret; Downs, B William; Waite, Roger L; Braverman, Eric R; Kerner, Mallory; Bowirrat, Abdalla; Giordano, John; Henshaw, Harry; Gold, Mark S

    2010-03-01

    Using fMRI, Menon and Levitin [9] clearly found for the first time that listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the nucleus accumbens (NAc) and the ventral tegmental area (VTA), as well as the hypothalamus, and insula, which are thought to be involved in regulating autonomic and physiological responses to rewarding and emotional stimuli. Importantly, responses in the NAc and VTA were strongly correlated pointing to an association between dopamine release and NAc response to music. Listing to pleasant music induced a strong response and significant activation of the VTA-mediated interaction of the NAc with the hypothalamus, insula, and orbitofrontal cortex. Blum et al. [10] provided the first evidence that the dopamine D2 receptor gene (DRD2) Taq 1 A1 allele significantly associated with severe alcoholism whereby the author's suggested that they found the first "reward gene" located in the mesolimbic system. The enhanced functional and effective connectivity between brain regions mediating reward, autonomic, and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. However, little is known about why some people have a more or less powerful mesolimbic experience when they are listening to music. It is well-known that music may induce an endorphinergic response that is blocked by naloxone, a known opioid antagonist (Goldstein [19]). Opioid transmission in the NAc is associated with dopamine release in the VTA. Moreover, dopamine release in the VTA is linked to polymorphisms of the DRD2 gene and even attention-deficit hyperactivity disorder (ADHD), whereby carriers of the DRD2 A1 allele show a reduced NAc release of dopamine (DA). Thus it is conjectured that similar mechanisms in terms of adequate dopamine release and subsequent activation of reward circuitry by listening to music might also be

  1. Transcriptome and Gene Ontology (GO) Enrichment Analysis Reveals Genes Involved in Biotin Metabolism That Affect L-Lysine Production in Corynebacterium glutamicum.

    Science.gov (United States)

    Kim, Hong-Il; Kim, Jong-Hyeon; Park, Young-Jin

    2016-03-09

    Corynebacterium glutamicum is widely used for amino acid production. In the present study, 543 genes showed a significant change in their mRNA expression levels in L-lysine-producing C. glutamicum ATCC21300 than that in the wild-type C. glutamicum ATCC13032. Among these 543 differentially expressed genes (DEGs), 28 genes were up- or downregulated. In addition, 454 DEGs were functionally enriched and categorized based on BLAST sequence homologies and gene ontology (GO) annotations using the Blast2GO software. Interestingly, NCgl0071 (bioB, encoding biotin synthase) was expressed at levels ~20-fold higher in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain. Five other genes involved in biotin metabolism or transport--NCgl2515 (bioA, encoding adenosylmethionine-8-amino-7-oxononanoate aminotransferase), NCgl2516 (bioD, encoding dithiobiotin synthetase), NCgl1883, NCgl1884, and NCgl1885--were also expressed at significantly higher levels in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain, which we determined using both next-generation RNA sequencing and quantitative real-time PCR analysis. When we disrupted the bioB gene in C. glutamicum ATCC21300, L-lysine production decreased by approximately 76%, and the three genes involved in biotin transport (NCgl1883, NCgl1884, and NCgl1885) were significantly downregulated. These results will be helpful to improve our understanding of C. glutamicum for industrial amino acid production.

  2. Ascophyllum nodosum Seaweed Extract Alleviates Drought Stress in Arabidopsis by Affecting Photosynthetic Performance and Related Gene Expression

    Directory of Open Access Journals (Sweden)

    Antonietta Santaniello

    2017-08-01

    Full Text Available Drought represents one of the most relevant abiotic stress affecting growth and yield of crop plants. In order to improve the agricultural productivity within the limited water and land resources, it is mandatory to increase crop yields in presence of unfavorable environmental stresses. The use of biostimulants, often containing seaweed extracts, represents one of the options for farmers willing to alleviate abiotic stress consequences on crops. In this work, we investigated the responses of Arabidopsis plants treated with an extract from the brown alga Ascophyllum nodosum (ANE, under drought stress conditions, demonstrating that ANE positively influences Arabidopsis survival. Pre-treatment with ANE induced a partial stomatal closure, associated with changes in the expression levels of genes involved in ABA-responsive and antioxidant system pathways. The pre-activation of these pathways results in a stronger ability of ANE-treated plants to maintain a better photosynthetic performance compared to untreated plants throughout the dehydration period, combined with a higher capacity to dissipate the excess of energy as heat in the reaction centers of photosystem II. Our results suggest that drought stressed plants treated with ANE are able to maintain a strong stomatal control and relatively higher values of both water use efficiency (WUE and mesophyll conductance during the last phase of dehydration. Simultaneously, the activation of a pre-induced antioxidant defense system, in combination with a more efficient energy dissipation mechanism, prevents irreversible damages to the photosynthetic apparatus. In conclusion, pre-treatment with ANE is effective to acclimate plants to the incoming stress, promoting an increased WUE and dehydration tolerance.

  3. MRI evaluation of the aortic disease

    International Nuclear Information System (INIS)

    Kapuscinski, O.; Polkowski, J.; Zaleska, T.; Walecki, J.; Biesiadko, M.

    1994-01-01

    The goal of our study was to establish the value of MRI in diagnosing aortic disease. During 3 years period 46 patients were examined (12 women aged from 6 to 62 years and 34 men aged from 8 to 72 years). In 28 cases the thoracic aorta was examined, in 6 cases the abdominal aorta and in 12 - both the thoracic and the abdominal aorta. MR images were performed on MRT 50 A Toshiba unit 0.5 T. MR images demonstrated aortic aneurysm (caused by atherosclerosis or trauma), aortic dissections, aortic anomalies (i.e. in Turner syndrome) and non-specific aortitis and vasculitis. We regard MRI as preferable noninvasive imaging technique in diagnosing aortic disease. (author)

  4. The rumen microbiome as a reservoir of antimicrobial resistance and pathogenicity genes is directly affected by diet in beef cattle.

    Science.gov (United States)

    Auffret, Marc D; Dewhurst, Richard J; Duthie, Carol-Anne; Rooke, John A; John Wallace, R; Freeman, Tom C; Stewart, Robert; Watson, Mick; Roehe, Rainer

    2017-12-11

    The emergence and spread of antimicrobial resistance is the most urgent current threat to human and animal health. An improved understanding of the abundance of antimicrobial resistance genes and genes associated with microbial colonisation and pathogenicity in the animal gut will have a major role in reducing the contribution of animal production to this problem. Here, the influence of diet on the ruminal resistome and abundance of pathogenicity genes was assessed in ruminal digesta samples taken from 50 antibiotic-free beef cattle, comprising four cattle breeds receiving two diets containing different proportions of concentrate. Two hundred and four genes associated with antimicrobial resistance (AMR), colonisation, communication or pathogenicity functions were identified from 4966 metagenomic genes using KEGG identification. Both the diversity and abundance of these genes were higher in concentrate-fed animals. Chloramphenicol and microcin resistance genes were dominant in samples from forage-fed animals (P resistances were enriched in concentrate-fed animals. The concentrate-based diet also increased the relative abundance of Proteobacteria, which includes many animal and zoonotic pathogens. A high ratio of Proteobacteria to (Firmicutes + Bacteroidetes) was confirmed as a good indicator for rumen dysbiosis, with eight cases all from concentrate-fed animals. Finally, network analysis demonstrated that the resistance/pathogenicity genes are potentially useful as biomarkers for health risk assessment of the ruminal microbiome. Diet has important effects on the complement of AMR genes in the rumen microbial community, with potential implications for human and animal health.

  5. The Varicella-Zoster Virus Immediate-Early 63 protein affects chromatin controlled gene transcription in a cell-type dependent manner

    Directory of Open Access Journals (Sweden)

    Bontems Sébastien

    2007-10-01

    Full Text Available Abstract Background Varicella Zoster Virus Immediate Early 63 protein (IE63 has been shown to be essential for VZV replication, and critical for latency establishment. The activity of the protein as a transcriptional regulator is not fully clear yet. Using transient transfection assays, IE63 has been shown to repress viral and cellular promoters containing typical TATA boxes by interacting with general transcription factors. Results In this paper, IE63 regulation properties on endogenous gene expression were evaluated using an oligonucleotide-based micro-array approach. We found that IE63 modulates the transcription of only a few genes in HeLa cells including genes implicated in transcription or immunity. Furthermore, we showed that this effect is mediated by a modification of RNA POL II binding on the promoters tested and that IE63 phosphorylation was essential for these effects. In MeWo cells, the number of genes whose transcription was modified by IE63 was somewhat higher, including genes implicated in signal transduction, transcription, immunity, and heat-shock signalling. While IE63 did not modify the basal expression of several NF-κB dependent genes such as IL-8, ICAM-1, and IκBα, it modulates transcription of these genes upon TNFα induction. This effect was obviously correlated with the amount of p65 binding to the promoter of these genes and with histone H3 acetylation and HDAC-3 removal. Conclusion While IE63 only affected transcription of a small number of cellular genes, it interfered with the TNF-inducibility of several NF-κB dependent genes by the accelerated resynthesis of the inhibitor IκBα.

  6. Treatment strategy for ruptured abdominal aortic aneurysms.

    Science.gov (United States)

    Davidovic, L

    2014-07-01

    Rupture is the most serious and lethal complication of the abdominal aortic aneurysm. Despite all improvements during the past 50 years, ruptured abdominal aortic aneurysms are still associated with very high mortality. Namely, including patients who die before reaching the hospital, the mortality rate due to abdominal aortic aneurysm rupture is 90%. On the other hand, during the last twenty years, the number of abdominal aortic aneurysms significantly increased. One of the reasons is the fact that in majority of countries the general population is older nowadays. Due to this, the number of degenerative AAA is increasing. This is also the case for patients with abdominal aortic aneurysm rupture. Age must not be the reason of a treatment refusal. Optimal therapeutic option ought to be found. The following article is based on literature analysis including current guidelines but also on my Clinics significant experience. Furthermore, this article show cases options for vascular medicine in undeveloped countries that can not apply endovascular procedures at a sufficient level and to a sufficient extent. At this moment the following is evident. Thirty-day-mortality after repair of ruptured abdominal aortic aneurysms is significantly lower in high-volume hospitals. Due to different reasons all ruptured abdominal aortic aneurysms are not suitable for EVAR. Open repair of ruptured abdominal aortic aneurysm should be performed by experienced open vascular surgeons. This could also be said for the treatment of endovascular complications that require open surgical conversion. There is no ideal procedure for the treatment of AAA. Each has its own advantages and disadvantages, its own limits and complications, as well as indications and contraindications. Future reductions in mortality of ruptured abdominal aortic aneurysms will depend on implementation of population-based screening; on strategies to prevent postoperative organ injury and also on new medical technology

  7. [Modern aortic surgery in Marfan syndrome--2011].

    Science.gov (United States)

    Kallenbach, K; Schwill, S; Karck, M

    2011-09-01

    Marfan syndrome is a hereditary disease with a prevalence of 2-3 in 10,000 births, leading to a fibrillin connective tissue disorder with manifestations in the skeleton, eye, skin, dura mater and in particular the cardiovascular system. Since other syndromes demonstrate similar vascular manifestations, but therapy may differ significantly, diagnosis should be established using the revised Ghent nosology in combination with genotypic analysis in specialized Marfan centres. The formation of aortic root aneurysms with the subsequent risk of acute aortic dissection type A (AADA) or aortic rupture limits life expectancy in patients with Marfan syndrome. Therefore, prophylactic replacement of the aortic root needs to be performed before the catastrophic event of AADA can occur. The goal of surgery is the complete resection of pathological aortic tissue. This can be achieved with excellent results by using a (mechanically) valved conduit that replaces both the aortic valve and the aortic root (Bentall operation). However, the need for lifelong anticoagulation with Coumadin can be avoided using the aortic valve sparing reimplantation technique according to David. The long-term durability of the reconstructed valve is favourable, and further technical improvements may improve longevity. Although results of prospective randomised long-term studies comparing surgical techniques are lacking, the David operation has become the surgical method of choice for aortic root aneurysms, not only at the Heidelberg Marfan Centre. Replacement of the aneurysmal dilated aortic arch is performed under moderate hypothermic circulatory arrest combined with antegrade cerebral perfusion using a heart-lung machine, which we also use in thoracic or thoracoabdominal aneurysms. Close post-operative follow-up in a Marfan centre is pivotal for the early detection of pathological changes on the diseased aorta.

  8. Impairment of flow-mediated dilation correlates with aortic dilation in patients with Marfan syndrome.

    Science.gov (United States)

    Takata, Munenori; Amiya, Eisuke; Watanabe, Masafumi; Omori, Kazuko; Imai, Yasushi; Fujita, Daishi; Nishimura, Hiroshi; Kato, Masayoshi; Morota, Tetsuro; Nawata, Kan; Ozeki, Atsuko; Watanabe, Aya; Kawarasaki, Shuichi; Hosoya, Yumiko; Nakao, Tomoko; Maemura, Koji; Nagai, Ryozo; Hirata, Yasunobu; Komuro, Issei

    2014-07-01

    Marfan syndrome is an inherited disorder characterized by genetic abnormality of microfibrillar connective tissue proteins. Endothelial dysfunction is thought to cause aortic dilation in subjects with a bicuspid aortic valve; however, the role of endothelial dysfunction and endothelial damaging factors has not been elucidated in Marfan syndrome. Flow-mediated dilation, a noninvasive measurement of endothelial function, was evaluated in 39 patients with Marfan syndrome. Aortic diameter was measured at the aortic annulus, aortic root at the sinus of Valsalva, sinotubular junction and ascending aorta by echocardiography, and adjusted for body surface area (BSA). The mean value of flow-mediated dilation was 6.5 ± 2.4 %. Flow-mediated dilation had a negative correlation with the diameter of the ascending thoracic aorta (AscAd)/BSA (R = -0.39, p = 0.020) and multivariate analysis revealed that flow-mediated dilation was an independent factor predicting AscAd/BSA, whereas other segments of the aorta had no association. Furthermore, Brinkman index had a somewhat greater influence on flow-mediated dilation (R = -0.42, p = 0.008). Although subjects who smoked tended to have a larger AscAd compared with non-smokers (AscA/BSA: 17.3 ± 1.8 versus 15.2 ± 3.0 mm/m(2), p = 0.013), there was no significant change in flow-mediated dilation, suggesting that smoking might affect aortic dilation via an independent pathway. Common atherogenic risks, such as impairment of flow-mediated dilation and smoking status, affected aortic dilation in subjects with Marfan syndrome.

  9. MR imaging of aortic coarctation

    International Nuclear Information System (INIS)

    Beslic, S.

    2004-01-01

    Purpose. The purpose of this paper is to analyse the contribution of MRI as diagnostic procedure in the preoperative diagnosis of aortic coarctation (CoA), in patients with clinical and echocardiographic suspicion for this disease. Patients and methods. During the period of three years, eight patients were examined, 5 (62.5%) male and 3 (37.5%) female patients with clinical echocardiographic suspicion of CoA. The ratio between male and female patients was 1.7 : 1. The youngest patient was 3 and the oldest 46 years (median age was 15 years). Without administration of contrast media and using body coil the examinations were performed with MR machine Magnetom 1.0 Tesla ( S iemens ) , with the slice thickness of 6 mm, Fast spin-echo (FSE) T1W sequences, Cine gradient echo (GRE) sequence with slab 7 mm and time of flight (TOF) sequence with MIP reconstructions were applied. During the examinations the patients underwent also ECG gating. Examinations were done in axial, coronal and oblique sagittal projections with measuring of the dimensions of cardiovascular structures. Results. CoA was found in 8 (100%) patients. In 7 (87.5%) cases, coarctation developed at isthmus and in one case, coarctation was detected at the horizontal part of aortic arch, between the truncus arteriosus of the left carotid communis artery. Aortal insufficiency was found in 7 (87.5%) patients; in four of them (50%), bicuspidia was confirmed (bicuspid aortic valve), 7 (87.5%) patients had slightly expressed hypertrophy of the left ventricle. Two (25%) patients had dilatation of the ascendant aorta, six (75%) wider outgoing vessels of the aortic arch, four (50%) had well developed arterial collaterals and 2 (25%) patients rib notching. In 2 (25%) patients as side finding thymus persistent was found. Average diameter of coarctation was 10 mm. In one patient, CoA was accompanied with stenosis of pulmonary artery, in one with ventricular septal defect, and one with tricuspid insufficiency. The results

  10. Imaging techniques in aortic valve and root surgery

    NARCIS (Netherlands)

    Regeer, M.V.

    2017-01-01

    Aortic valve sparing surgery for aortic regurgitation and/or aortopathy serves as an alternative to aortic valve and root replacement. One of the advantages of aortic valve sparing surgery over conventional replacement is that there is no need for life-long anticoagulation, which is particularly

  11. An Interaction of the Pre- and Post-Weaning Diets Rich in Omega-6 Polyunsaturated Fats Alters Plasma Lipids, Hepatic Gene Expression and Aortic Vascular Reactivity in Adult 057Bl/6 Mice

    Directory of Open Access Journals (Sweden)

    Kanta Chechi

    2010-01-01

    Full Text Available Aim To investigate the effects of diets rich in n-6 polyunsaturated fats (PUFA fed during pre- and post-weaning time periods on the lipid metabolism and vascular reactivity in adult C57Bl/6 mice, in order to assess the impact of maternal nutrition and its interaction with the offspring diet on the metabolism of adult offspring. Methods Female C57Bl/6 mice were fed a high-fat diet enriched with n-6 PUFA (P or control diet (C for 2-weeks before, during mating, gestation and lactation, while their pups received either P or C for 8-weeks post-weaning. Results A significant interaction between the maternal and post-weaning diets was observed for the offspring body weight, food-, caloric-intake, plasma lipids, hepatic mRNA expression of lecithin cholesterol acyltransferase, aortic contractile and relaxation responses ( P < 0.05. Conclusion The overall metabolic and physiological outcome in the offspring is dependent upon the interaction between the pre- and post-weaning dietary environments.

  12. Valve-sparing aortic root replacement in Marfan syndrome.

    Science.gov (United States)

    Cameron, Duke E; Vricella, Luca A

    2005-01-01

    Marfan syndrome is the most common inherited connective tissue disorder, affecting approximately 1 in 10,000 live births. The cardinal features of Marfan syndrome are the abnormalities of the skeleton (tall stature, arachnodactyly, and joint hyperelasticity), eye (lens subluxation), and aorta (root aneurysm with proclivity toward rupture and dissection). Aortic catastrophe accounts for most of the premature mortality among Marfan patients, a risk that climbs steeply during adolescence and results in death of half of Marfan patients by the age of 40 years. Most of the improvement in life expectancy that has been achieved in Marfan syndrome is attributable to early recognition of aortic root aneurysms and prophylactic replacement with composite grafts (mechanical valve prostheses within Dacron conduits) before rupture or dissection occurs. Despite the excellent early and late results with composite grafts, there has been growing interest in operative procedures that replace the sinuses but preserve the aortic valve leaflets, to avoid anticoagulation and minimize the risk of prosthesis-related endocarditis. These procedures are still in evolution and late results are not yet known, but as with mitral repair in the setting of myxomatous disease, valve-sparing procedures in Marfan syndrome have weathered a storm of initial criticism and skepticism and are steadily gaining acceptance.

  13. Aortic root surgery in Marfan syndrome: Comparison of aortic valve-sparing reimplantation versus composite grafting.

    Science.gov (United States)

    Karck, Matthias; Kallenbach, Klaus; Hagl, Christian; Rhein, Christine; Leyh, Rainer; Haverich, Axel

    2004-02-01

    The objective of this study was to compare the results of aortic valve-sparing reimplantation and aortic root replacement with mechanical valve conduits in patients with Marfan syndrome undergoing operation for aortic root aneurysms. Patients and methods Between March 1979 and April 2002, 119 patients with clinical evidence of Marfan syndrome underwent composite graft replacement with mechanical valve conduits (n = 74) or aortic valve-sparing reimplantation according to David (n = 45). The underlying causes were aortic dissection type A (43 patients) and aneurysms (76 patients). Patients undergoing aortic valve reimplantation were younger compared with patients undergoing composite grafting (28 vs 35 years, P =.002) and had longer intraoperative aortic crossclamp times (125 vs 78 minutes, P valve reimplantation (P =.15). Mean follow-up was 30 months for patients undergoing aortic valve reimplantation and 114 months for patients undergoing composite grafting. Freedom from reoperation and death after 5 years postoperatively was 92% and 89% in patients undergoing composite grafting and 84% and 96% in patients undergoing aortic valve reimplantation (P =.31; P =.54), respectively. Thromboembolic complications or late postoperative bleeding occurred in 17 patients undergoing composite grafting, and an early postoperative event occurred in 1 patient undergoing aortic valve reimplantation. The results of aortic valve reimplantation and composite grafting of the aortic valve and ascending aorta with mechanical valve conduits are similar with regard to early and mid-term postoperative mortality and to the incidence of late reoperations in patients with Marfan syndrome. The low risk of thromboembolic or bleeding complications favors aortic valve reimplantation in these patients.

  14. Transcriptome reprogramming due to the introduction of a barley telosome into bread wheat affects more barley genes than wheat.

    Science.gov (United States)

    Rey, Elodie; Abrouk, Michael; Keeble-Gagnère, Gabriel; Karafiátová, Miroslava; Vrána, Jan; Balzergue, Sandrine; Soubigou-Taconnat, Ludivine; Brunaud, Véronique; Martin-Magniette, Marie-Laure; Endo, Takashi R; Bartoš, Jan; Appels, Rudi; Doležel, Jaroslav

    2018-03-06

    Despite a long history, the production of useful alien introgression lines in wheat remains difficult mainly due to linkage drag and incomplete genetic compensation. In addition, little is known about the molecular mechanisms underlying the impact of foreign chromatin on plant phenotype. Here, a comparison of the transcriptomes of barley, wheat and a wheat-barley 7HL addition line allowed the transcriptional impact both on 7HL genes of a non-native genetic background and on the wheat gene complement as a result of the presence of 7HL to be assessed. Some 42% (389/923) of the 7HL genes assayed were differentially transcribed, which was the case for only 3% (960/35 301) of the wheat gene complement. The absence of any transcript in the addition line of a suite of chromosome 7A genes implied the presence of a 36 Mbp deletion at the distal end of the 7AL arm; this deletion was found to be in common across the full set of Chinese Spring/Betzes barley addition lines. The remaining differentially transcribed wheat genes were distributed across the whole genome. The up-regulated barley genes were mostly located in the proximal part of the 7HL arm, while the down-regulated ones were concentrated in the distal part; as a result, genes encoding basal cellular functions tended to be transcribed, while those encoding specific functions were suppressed. An insight has been gained into gene transcription in an alien introgression line, thereby providing a basis for understanding the interactions between wheat and exotic genes in introgression materials. © 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  15. Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4.

    Science.gov (United States)

    Tóth, Lola; Fábos, Beáta; Farkas, Katalin; Sulák, Adrienn; Tripolszki, Kornélia; Széll, Márta; Nagy, Nikoletta

    2017-03-15

    Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities. OCA type IV (OCA4, OMIM 606574) develops due to homozygous or compound heterozygous mutations in the solute carrier family 45, member 2 (SLC45A2) gene. This gene encodes a membrane-associated transport protein, which regulates tyrosinase activity and, thus, melanin content by changing melanosomal pH and disrupting the incorporation of copper into tyrosinase. Here we report two Hungarian siblings affected by an unusual OCA4 phenotype. After genomic DNA was isolated from peripheral blood of the patients, the coding regions of the SLC45A2 gene were sequenced. In silico tools were applied to identify the functional impact of the newly detected mutations. Direct sequencing of the SLC45A2 gene revealed two novel, heterozygous mutations, one missense (c.1226G > A, p.Gly409Asp) and one nonsense (c.1459C > T, p.Gln437*), which were present in both patients, suggesting the mutations were compound heterozygous. In silico tools suggest that these variations are disease causing mutations. The newly identified mutations may affect the transmembrane domains of the protein, and could impair transport function, resulting in decreases in both melanosomal pH and tyrosinase activity. Our study provides expands on the mutation spectrum of the SLC45A2 gene and the genetic background of OCA4.

  16. Overexpression of an Arabidopsis heterogeneous nuclear ribonucleoprotein gene, AtRNP1, affects plant growth and reduces plant tolerance to drought and salt stresses

    International Nuclear Information System (INIS)

    Wang, Zhenyu; Zhao, Xiuyang; Wang, Bing; Liu, Erlong; Chen, Ni; Zhang, Wei; Liu, Heng

    2016-01-01

    Heterogeneous nuclear ribonucleoproteins (hnRNPs) participate in diverse regulations of plant growth and environmental stress responses. In this work, an Arabidopsis hnRNP of unknown function, AtRNP1, was investigated. We found that AtRNP1 gene is highly expressed in rosette and cauline leaves, and slightly induced under drought, salt, osmotic and ABA stresses. AtRNP1 protein is localized to both the nucleus and cytoplasm. We performed homologous overexpression of AtRNP1 and found that the transgenic plants showed shortened root length and plant height, and accelerated flowering. In addition, the transgenic plants also showed reduced tolerance to drought, salt, osmotic and ABA stresses. Further studies revealed that under both normal and stress conditions, the proline contents in the transgenic plants are markedly decreased, associated with reduced expression levels of a proline synthase gene and several stress-responsive genes. These results suggested that the overexpression of AtRNP1 negatively affects plant growth and abiotic stress tolerance. - Highlights: • AtRNP1 is a widely expressed gene and its expression is slightly induced under abiotic stresses. • AtRNP1 protein is localized to both the nucleus and cytoplasm. • Overexpression of AtRNP1 affects plant growth. • Overexpression of AtRNP1 reduces plant tolerance to drought and salt stresses. • AtRNP1 overexpression plants show decreased proline accumulation and stress-responsive gene expressions.

  17. Overexpression of an Arabidopsis heterogeneous nuclear ribonucleoprotein gene, AtRNP1, affects plant growth and reduces plant tolerance to drought and salt stresses

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhenyu, E-mail: wzy72609@163.com [Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730030 (China); Zhao, Xiuyang, E-mail: xiuzh@psb.vib-ugent.be [Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730030 (China); Wang, Bing, E-mail: wangbing@ibcas.ac.cn [Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730030 (China); Liu, Erlong, E-mail: liuel14@lzu.edu.cn [Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730030 (China); Chen, Ni, E-mail: 63710156@qq.com [Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730030 (China); Zhang, Wei, E-mail: wzhang1216@yahoo.com [Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444 (China); Liu, Heng, E-mail: hengliu@lzu.edu.cn [Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730030 (China)

    2016-04-01

    Heterogeneous nuclear ribonucleoproteins (hnRNPs) participate in diverse regulations of plant growth and environmental stress responses. In this work, an Arabidopsis hnRNP of unknown function, AtRNP1, was investigated. We found that AtRNP1 gene is highly expressed in rosette and cauline leaves, and slightly induced under drought, salt, osmotic and ABA stresses. AtRNP1 protein is localized to both the nucleus and cytoplasm. We performed homologous overexpression of AtRNP1 and found that the transgenic plants showed shortened root length and plant height, and accelerated flowering. In addition, the transgenic plants also showed reduced tolerance to drought, salt, osmotic and ABA stresses. Further studies revealed that under both normal and stress conditions, the proline contents in the transgenic plants are markedly decreased, associated with reduced expression levels of a proline synthase gene and several stress-responsive genes. These results suggested that the overexpression of AtRNP1 negatively affects plant growth and abiotic stress tolerance. - Highlights: • AtRNP1 is a widely expressed gene and its expression is slightly induced under abiotic stresses. • AtRNP1 protein is localized to both the nucleus and cytoplasm. • Overexpression of AtRNP1 affects plant growth. • Overexpression of AtRNP1 reduces plant tolerance to drought and salt stresses. • AtRNP1 overexpression plants show decreased proline accumulation and stress-responsive gene expressions.

  18. Exposure of Lactating Dairy Cows to Acute Pre-Ovulatory Heat Stress Affects Granulosa Cell-Specific Gene Expression Profiles in Dominant Follicles

    Science.gov (United States)

    Vanselow, Jens; Vernunft, Andreas; Koczan, Dirk; Spitschak, Marion; Kuhla, Björn

    2016-01-01

    High environmental temperatures induce detrimental effects on various reproductive processes in cattle. According to the predicted global warming the number of days with unfavorable ambient temperatures will further increase. The objective of this study was to investigate effects of acute heat stress during the late pre-ovulatory phase on morphological, physiological and molecular parameters of dominant follicles in cycling cows during lactation. Eight German Holstein cows in established lactation were exposed to heat stress (28°C) or thermoneutral conditions (15°C) with pair-feeding for four days. After hormonal heat induction growth of the respective dominant follicles was monitored by ultrasonography for two days, then an ovulatory GnRH dose was given and follicular steroid hormones and granulosa cell-specific gene expression profiles were determined 23 hrs thereafter. The data showed that the pre-ovulatory growth of dominant follicles and the estradiol, but not the progesterone concentrations tended to be slightly affected. mRNA microarray and hierarchical cluster analysis revealed distinct expression profiles in granulosa cells derived from heat stressed compared to pair-fed animals. Among the 255 affected genes heatstress-, stress- or apoptosis associated genes were not present. But instead, we found up-regulation of genes essentially involved in G-protein coupled signaling pathways, extracellular matrix composition, and several members of the solute carrier family as well as up-regulation of FST encoding follistatin. In summary, the data of the present study show that acute pre-ovulatory heat stress can specifically alter gene expression profiles in granulosa cells, however without inducing stress related genes and pathways and suggestively can impair follicular growth due to affecting the activin-inhibin-follistatin system. PMID:27532452

  19. Abscisic acid affects transcription of chloroplast genes via protein phosphatase 2C-dependent activation of nuclear genes: repression by guanosine-3'-5'-bisdiphosphate and activation by sigma factor 5.

    Science.gov (United States)

    Yamburenko, Maria V; Zubo, Yan O; Börner, Thomas

    2015-06-01

    Abscisic acid (ABA) represses the transcriptional activity of chloroplast genes (determined by run-on assays), with the exception of psbD and a few other genes in wild-type Arabidopsis seedlings and mature rosette leaves. Abscisic acid does not influence chloroplast transcription in the mutant lines abi1-1 and abi2-1 with constitutive protein phosphatase 2C (PP2C) activity, suggesting that ABA affects chloroplast gene activity by binding to the pyrabactin resistance (PYR)/PYR1-like or regulatory component of ABA receptor protein family (PYR/PYL/RCAR) and signaling via PP2Cs and sucrose non-fermenting protein-related kinases 2 (SnRK2s). Further we show by quantitative PCR that ABA enhances the transcript levels of RSH2, RSH3, PTF1 and SIG5. RelA/SpoT homolog 2 (RSH2) and RSH3 are known to synthesize guanosine-3'-5'-bisdiphosphate (ppGpp), an inhibitor of the plastid-gene-encoded chloroplast RNA polymerase. We propose, therefore, that ABA leads to an inhibition of chloroplast gene expression via stimulation of ppGpp synthesis. On the other hand, sigma factor 5 (SIG5) and plastid transcription factor 1 (PTF1) are known to be necessary for the transcription of psbD from a specific light- and stress-induced promoter (the blue light responsive promoter, BLRP). We demonstrate that ABA activates the psbD gene by stimulation of transcription initiation at BLRP. Taken together, our data suggest that ABA affects the transcription of chloroplast genes by a PP2C-dependent activation of nuclear genes encoding proteins involved in chloroplast transcription. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  20. Aortography following subdiaphragmal aortic biopsy

    International Nuclear Information System (INIS)

    Schimmler, J.

    1982-01-01

    A juxtaposition of the subdiaphragmal and infrarenal translumbar aortic biopsy sites showed decisive advantages in favour of the higher site: a more stable position because of better anatomic fixation and rarer incidence of vascular alterations, a wider vascular lumen. Disadvantages lie in the fact that the large visceral arteries (especially Tr. coeliacus) branch off nearly and in the close anatomic relationship to large abdominal organs and the thoracal region. Evaluation of the radiographical image of the vascular tree after subdiaphragmal aortic biopsy showed an average 82% of the vessels to the area of the Knees to be assessable (renal arteries approximately 93%, popliteal arteries approximately 70%). Beyong, the method proved unsatisfactory: 52% of the vessels could not, or not safety, be evaluated. A relatively broad spectrum of indications by comparison with transfemoral catheter aortography had no influence on the rate of complications with reference to either method. A comparison of the topographic conditions shows the need for even more scrupulons observation of the technique in subdiaphragmal biopsy than in the infrarenal one. To sum up the results obtained, subdiaphregmal translumbar aortography is to be preferred to the infrarenal one where transfemoral catheter aortography is contra-indicated, within the limits mentioned. (orig.) [de

  1. Imaging of thoracic aortic dissection

    International Nuclear Information System (INIS)

    Vu, F.H.; Young, N.; Soo, Y.S.

    1994-01-01

    Acute thoracic aortic dissection has a high mortality rate if untreated, so the diagnosis must be rapidly made. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause of death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 out of 12 patients studied and correctly classified the type in only five. Aortography was preformed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were preformed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention. 17 refs., 4 tabs., 4 figs

  2. Diabetes Mellitus Impairs Left Ventricular Mass Regression after Surgical or Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis.

    Science.gov (United States)

    Nakamura, Teruya; Toda, Koichi; Kuratani, Toru; Miyagawa, Shigeru; Yoshikawa, Yasushi; Fukushima, Satsuki; Saito, Shunsuke; Yoshioka, Daisuke; Kashiyama, Noriyuki; Daimon, Takashi; Sawa, Yoshiki

    2016-01-01

    It is well-documented that persistent myocardial hypertrophy in patients with aortic stenosis is related to suboptimal postoperative outcomes after aortic valve replacement. Although diabetes is known to potentially exacerbate myocardial hypertrophy, it has yet to be examined if it affects postoperative left ventricular mass regression (LVMR). A single-centre, retrospective analysis was performed on 183 consecutive patients who underwent either surgical or transcatheter aortic valve replacement between 2010 and May 2013. Patient demographics, postoperative outcomes and echocardiographic data were obtained preoperatively and a year after surgery. There were 42 diabetic and 141 non-diabetic patients. Preoperative characteristics of diabetic patients were statistically similar to those of non-diabetic patients, except for higher prevalence of hyperlipidaemia (p regression analysis demonstrated that diabetes (standardised partial regression coefficient (SPRC)=-0.187, p=0.018), female gender (SPRC=0.245, p=0.026) and age (SPRC=0.203, p=0.018) were associated with poor postoperative LVMR. Patients with diabetes showed suboptimal postoperative LVMR, and the disease was a prognostic factor that was associated with poor LVMR. These findings suggest that diabetes may predispose the particular group of patients to worse postoperative outcomes. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  3. Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves.

    Science.gov (United States)

    Saikrishnan, Neelakantan; Mirabella, Lucia; Yoganathan, Ajit P

    2015-06-01

    Congenital bicuspid aortic valves (BAVs) are associated with accelerated disease progression, such as leaflet calcification and ascending aorta dilatation. Although common underlying genetic factors have been implicated in accelerated disease in BAV patients, several studies have suggested that altered hemodynamics also play a role in this disease process. The present study compares turbulence and wall shear stress (WSS) measurements between various BAV and trileaflet aortic valve (TAV) models to provide information for mechanobiological models of BAV disease. BAV and TAV models were constructed from excised porcine aortic valves to simulate parametric variations in BAV stenosis, hemodynamics and geometry. Particle image velocimetry experiments were conducted at physiological pressure conditions to characterize velocity fields in the ascending aorta. The velocity fields were post-processed to calculate turbulence, viscous and wall shear stresses in the ascending aorta. Stenosed BAV models showed the presence of eccentric systolic jets, causing increased WSS. Lower cardiac output resulted in a narrower jet, lower turbulence and lower viscous shear stress (VSS). The specific severe stenosis BAV model studied here showed reduced WSS due to reduction in non-fused leaflet mobility. Dilation of the aorta did not affect any turbulence or VSS, but reduced the WSS. In comparison with BAVs, TAVs have similar VSS values, but much smaller WSS and turbulence levels. These increased turbulence  and WSS levels in BAVs may play a key role in amplifying the biological responses of the ascending aorta wall and valvular leaflets, and support the hemodynamic underpinnings of BAV disease processes.

  4. Genetic analysis identifies DDR2 as a novel gene affecting bone mineral density and osteoporotic fractures in Chinese population.

    Directory of Open Access Journals (Sweden)

    Yan Guo

    Full Text Available DDR2 gene, playing an essential role in regulating osteoblast differentiation and chondrocyte maturation, may influence bone mineral density (BMD and osteoporosis, but the genetic variations actually leading to the association remain to be elucidated. Therefore, the aim of this study was to investigate whether the genetic variants in DDR2 are associated with BMD and fracture risk. This study was performed in three samples from two ethnicities, including 1,300 Chinese Han subjects, 700 Chinese Han subjects (350 with osteoporotic hip fractures and 350 healthy controls and 2,286 US white subjects. Twenty-eight SNPs in DDR2 were genotyped and tested for associations with hip BMD and fractures. We identified 3 SNPs in DDR2 significantly associated with hip BMD in the Chinese population after multiple testing adjustments, which were rs7521233 (P = 1.06×10-4, β: -0.018 for allele C, rs7553831 (P = 1.30×10-4, β: -0.018 for allele T, and rs6697469 (P = 1.59×10-3, β: -0.015 for allele C, separately. These three SNPs were in high linkage disequilibrium. Haplotype analyses detected two significantly associated haplotypes, including one haplotype in block 2 (P = 9.54×10-4, β: -0.016 where these three SNPs located. SNP rs6697469 was also associated with hip fractures (P = 0.043, OR: 1.42 in the Chinese population. The effect on fracture risk was consistent with its association with lower BMD. However, in the white population, we didn't observe significant associations with hip BMD. eQTL analyses revealed that SNPs associated with BMD also affected DDR2 mRNA expression levels in Chinese. Our findings, together with the prior biological evidence, suggest that DDR2 could be a new candidate for osteoporosis in Chinese population. Our results also reveal an ethnic difference, which highlights the need for further genetic studies in each ethnic group.

  5. Hypoxia and bicarbonate could limit the expression of iron acquisition genes in Strategy I plants by affecting ethylene synthesis and signaling in different ways.

    Science.gov (United States)

    García, María J; García-Mateo, María J; Lucena, Carlos; Romera, Francisco J; Rojas, Carmen L; Alcántara, Esteban; Pérez-Vicente, Rafael

    2014-01-01

    In a previous work, it was shown that bicarbonate (one of the most important factors causing Fe chlorosis in Strategy I plants) can limit the expression of several genes involved in Fe acquisition. Hypoxia is considered another important factor causing Fe chlorosis, mainly on calcareous soils. However, to date it is not known whether hypoxia aggravates Fe chlorosis by affecting bicarbonate concentration or by specific negative effects on Fe acquisition. Results found in this work show that hypoxia, generated by eliminating the aeration of the nutrient solution, can limit the expression of several Fe acquisition genes in Fe-deficient Arabidopsis, cucumber and pea plants, like the genes for ferric reductases AtFRO2, PsFRO1 and CsFRO1; iron transporters AtIRT1, PsRIT1 and CsIRT1; H(+) -ATPase CsHA1; and transcription factors AtFIT, AtbHLH38, and AtbHLH39. Interestingly, the limitation of the expression of Fe-acquisition genes by hypoxia did not occur in the Arabidopsis ethylene constitutive mutant ctr1, which suggests that the negative effect of hypoxia is related to ethylene, an hormone involved in the upregulation of Fe acquisition genes. As for hypoxia, results obtained by applying bicarbonate to the nutrient solution suggests that ethylene is also involved in its negative effect, since ACC (1-aminocyclopropane-1-carboxylic acid; ethylene precursor) partially reversed the negative effect of bicarbonate on the expression of Fe acquisition genes. Taken together, the results obtained show that hypoxia and bicarbonate could induce Fe chlorosis by limiting the expression of Fe acquisition genes, probably because each factor negatively affects different steps of ethylene synthesis and/or signaling. © 2013 Scandinavian Plant Physiology Society.

  6. Ascending aortic injuries following blunt trauma.

    Science.gov (United States)

    Sun, Xiumei; Hong, Jenny; Lowery, Robert; Goldstein, Steven; Wang, Zuyue; Lindsay, Joseph; Hill, Peter C; Corso, Paul J

    2013-11-01

    The diagnosis and the management of traumatic thoracic aortic injuries have undergone significant changes due to new technology and improved prehospital care. Most of the discussions have focused on descending aortic injuries. In this review, we discuss the recent management of ascending aortic injuries. We found 5 cohort studies on traumatic aortic injuries and 11 case reports describing ascending aortic injuries between 1998 to the present through Medline research. Among case reports, 78.9% of cases were caused by motor vehicle accidents (MVA). 42.1% of patients underwent emergent open repair and the operative mortality was 12.5%. 36.8% underwent delayed repair. Associated injuries occurred in 84.2% of patients. Aortic valve injury was concurrent in 26.3% of patients. The incidence of ascending aortic injury ranged 1.9-20% in cohort studies. Traumatic injuries to the ascending aorta are relatively uncommon among survivors following blunt trauma. Aortography has been replaced by computed tomography and echocardiography as a diagnostic tool. Open repair, either emergent or delayed, remains the treatment of choice. © 2013 Wiley Periodicals, Inc.

  7. Aortic stenosis and vascular calcifications in alkaptonuria.

    Science.gov (United States)

    Hannoush, Hwaida; Introne, Wendy J; Chen, Marcus Y; Lee, Sook-Jin; O'Brien, Kevin; Suwannarat, Pim; Kayser, Michael A; Gahl, William A; Sachdev, Vandana

    2012-02-01

    Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports. We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications. Published by Elsevier Inc.

  8. Aortic reconstruction with bovine pericardial grafts

    Directory of Open Access Journals (Sweden)

    Silveira Lindemberg Mota

    2003-01-01

    Full Text Available INTRODUCTION: Glutaraldehyde-treated crimped bovine pericardial grafts are currently used in aortic graft surgery. These conduits have become good options for these operations, available in different sizes and shapes and at a low cost. OBJECTIVE:To evaluate the results obtained with bovine pericardial grafts for aortic reconstruction, specially concerning late complications. METHOD: Between January 1995 and January 2002, 57 patients underwent different types of aortic reconstruction operations using bovine pericardial grafts. A total of 29 (50.8% were operated on an urgent basis (mostly acute Stanford A dissection and 28 electively. Thoracotomy was performed in three patients for descending aortic replacement (two patients and aortoplasty with a patch in one. All remaining 54 underwent sternotomy, cardiopulmonary bypass and aortic resection. Deep hypothermia and total circulatory arrest was used in acute dissections and arch operations. RESULTS: Hospital mortality was 17.5%. Follow-up was 24.09 months (18.5 to 29.8 months confidence interval and complication-free actuarial survival curve was 92.3% (standard deviation ± 10.6. Two patients lately developed thoracoabdominal aneurysms following previous DeBakey II dissection and one died from endocarditis. One "patch" aortoplasty patient developed local descending aortic pseudoaneurysm 42 months after surgery. All other patients are asymptomatic and currently clinically evaluated with echocardiography and CT scans, showing no complications. CONCLUSION: Use of bovine pericardial grafts in aortic reconstruction surgery is adequate and safe, with few complications related to the conduits.

  9. Aortic stenosis: From diagnosis to optimal treatment

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    Tavčiovski Dragan

    2008-01-01

    Full Text Available Aortic stenosis is the most frequent valvular heart disease. Aortic sclerosis is the first characteristic lesion of the cusps, which is considered today as the process similar to atherosclerosis. Progression of the disease is an active process leading to forming of bone matrix and heavily calcified stiff cusps by inflammatory cells and osteopontin. It is a chronic, progressive disease which can remain asymptomatic for a long time even in the presence of severe aortic stenosis. Proper physical examination remains an essential diagnostic tool in aortic stenosis. Recognition of characteristic systolic murmur draws attention and guides further diagnosis in the right direction. Doppler echocardiography is an ideal tool to confirm diagnosis. It is well known that exercise tests help in stratification risk of asymptomatic aortic stenosis. Serial measurements of brain natriuretic peptide during a follow-up period may help to identify the optimal time for surgery. Heart catheterization is mostly restricted to preoperative evaluation of coronary arteries rather than to evaluation of the valve lesion itself. Currently, there is no ideal medical treatment for slowing down the disease progression. The first results about the effect of ACE inhibitors and statins in aortic sclerosis and stenosis are encouraging, but there is still not enough evidence. Onset symptoms based on current ACC/AHA/ESC recommendations are I class indication for aortic valve replacement. Aortic valve can be replaced with a biological or prosthetic valve. There is a possibility of percutaneous aortic valve implantation and transapical operation for patients that are contraindicated for standard cardiac surgery.

  10. Histone Acetylation Modifications Affect Tissue-Dependent Expression of Poplar Homologs of C4 Photosynthetic Enzyme Genes

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    Yuan Li

    2017-06-01

    Full Text Available Histone modifications play important roles in regulating the expression of C4 photosynthetic genes. Given that all enzymes required for the C4 photosynthesis pathway are present in C3 plants, it has been hypothesized that this expression regulatory mechanism has been conserved. However, the relationship between histone modification and the expression of homologs of C4 photosynthetic enzyme genes has not been well determined in C3 plants. In the present study, we cloned nine hybrid poplar (Populus simonii × Populus nigra homologs of maize (Zea mays C4 photosynthetic enzyme genes, carbonic anhydrase (CA, pyruvate orthophosphate dikinase (PPDK, phosphoenolpyruvate carboxykinase (PCK, and phosphoenolpyruvate carboxylase (PEPC, and investigated the correlation between the expression levels of these genes and the levels of promoter histone acetylation modifications in four vegetative tissues. We found that poplar homologs of C4 homologous genes had tissue-dependent expression patterns that were mostly well-correlated with the level of histone acetylation modification (H3K9ac and H4K5ac determined by chromatin immunoprecipitation assays. Treatment with the histone deacetylase inhibitor trichostatin A further confirmed the role of histone acetylation in the regulation of the nine target genes. Collectively, these results suggest that both H3K9ac and H4K5ac positively regulate the tissue-dependent expression pattern of the PsnCAs, PsnPPDKs, PsnPCKs, and PsnPEPCs genes and that this regulatory mechanism seems to be conserved among the C3 and C4 species. Our findings provide new insight that will aid efforts to modify the expression pattern of these homologs of C4 genes to engineer C4 plants from C3 plants.

  11. Cloning of affecting pyruvate decarboxylase gene in the production bioethanol of agricultural waste in the E.coli bacteria

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    Masome Zeinali

    2016-09-01

    Full Text Available Introduction: Ethanol made by a biomass is one of the useful strategies in terms of economic and environmental and as a clean and safe energy to replace fossil fuels considered and examined. Materials and methods: In this study, key enzyme in the production of ethanol (Pyruvate decarboxylase from Zymomonas mobilis bacteria was isolated and cloned at E. coli bacteria by freeze and thaw method. For gene cloning, we used specific primers of pdc and PCR reaction and then pdc gene isolated and pET 28a plasmid double digested with (Sal I and Xho I enzymes. Digestion Products were ligated by T4 DNA ligase in 16 °C for 16 hours. Results: Results of bacteria culture showed that a few colonies containing pET 28a plasmid could grow. Result of colony pcr of pdc gene with specific primers revealed 1700 bp bands in 1% agarose gel electrophoresis. The results of PCR with T7 promotor forward primer and pdc revers primer have proved the accurate direction of integration of pdc gene into plasmid and revealed 1885 bp band. Double digestion of recombinant plasmid with SalI and XhoI enzymes revealed same bands. Finally, RT showed the expected band of 1700 bp that implies the desired gene expression in the samples. Discussion and conclusion: Due to the increased production of ethanol via pyruvate decarboxylase gene cloning in expression plasmids with a strong promoter upstream of the cloning site can conclude that, pyruvate decarboxylase cloning as a key gene would be useful and according to beneficial properties of E. coli bacteria, transfering the gene to bacteria appears to be reasonable.

  12. Differentially expressed genes in embryonic cardiac tissues of mice lacking Folr1 gene activity

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    Schwartz Robert J

    2007-11-01

    Full Text Available Abstract Background Heart anomalies are the most frequently observed among all human congenital defects. As with the situation for neural tube defects (NTDs, it has been demonstrated that women who use multivitamins containing folic acid peri-conceptionally have a reduced risk for delivering offspring with conotruncal heart defects 123. Cellular folate transport is mediated by a receptor or binding protein and by an anionic transporter protein system. Defective function of the Folr1 (also known as Folbp1; homologue of human FRα gene in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. Results We have observed cardiovascular abnormalities including outflow tract and aortic arch arterial defects in genetically compromised Folr1 knockout mice. In order to investigate the molecular mechanisms underlying the failure to complete development of outflow tract and aortic arch arteries in the Folr1 knockout mouse model, we examined tissue-specific gene expression difference between Folr1 nullizygous embryos and morphologically normal heterozygous embryos during early cardiac development (14-somite stage, heart tube looping (28-somite stage, and outflow track septation (38-somite stage. Microarray analysis was performed as a primary screening, followed by investigation using quantitative real-time PCR assays. Gene ontology analysis highlighted the following ontology groups: cell migration, cell motility and localization of cells, structural constituent of cytoskeleton, cell-cell adhesion, oxidoreductase, protein folding and mRNA processing. This study provided preliminary data and suggested potential candidate genes for further description and investigation. Conclusion The results suggested that Folr1 gene ablation and abnormal folate homeostasis altered gene expression in developing heart and conotruncal tissues. These changes affected normal cytoskeleton structures, cell migration and

  13. Expression conservation within the circadian clock of a monocot: natural variation at barley Ppd-H1 affects circadian expression of flowering time genes, but not clock orthologs.

    Science.gov (United States)

    Campoli, Chiara; Shtaya, Munqez; Davis, Seth J; von Korff, Maria

    2012-06-21

    The circadian clock is an endogenous mechanism that coordinates biological processes with daily changes in the environment. In plants, circadian rhythms contribute to both agricultural productivity and evolutionary fitness. In barley, the photoperiod response regulator and flowering-time gene Ppd-H1 is orthologous to the Arabidopsis core-clock gene PRR7. However, relatively little is known about the role of Ppd-H1 and other components of the circadian clock in temperate crop species. In this study, we identified barley clock orthologs and tested the effects of natural genetic variation at Ppd-H1 on diurnal and circadian expression of clock and output genes from the photoperiod-response pathway. Barley clock orthologs HvCCA1, HvGI, HvPRR1, HvPRR37 (Ppd-H1), HvPRR73, HvPRR59 and HvPRR95 showed a high level of sequence similarity and conservation of diurnal and circadian expression patterns, when compared to Arabidopsis. The natural mutation at Ppd-H1 did not affect diurnal or circadian cycling of barley clock genes. However, the Ppd-H1 mutant was found to be arrhythmic under free-running conditions for the photoperiod-response genes HvCO1, HvCO2, and the MADS-box transcription factor and vernalization responsive gene Vrn-H1. We suggest that the described eudicot clock is largely conserved in the monocot barley. However, genetic differentiation within gene families and differences in the function of Ppd-H1 suggest evolutionary modification in the angiosperm clock. Our data indicates that natural variation at Ppd-H1 does not affect the expression level of clock genes, but controls photoperiodic output genes. Circadian control of Vrn-H1 in barley suggests that this vernalization responsive gene is also controlled by the photoperiod-response pathway. Structural and functional characterization of the barley circadian clock will set the basis for future studies of the adaptive significance of the circadian clock in Triticeae species.

  14. Combined Repair of Ascending Aortic Pseudoaneurysm and Abdominal Aortic Aneurysm in a Patient with Marfan Syndrome

    OpenAIRE

    Kokotsakis, John N.; Lioulias, Achilleas G.; Foroulis, Christophoros N.; Skouteli, Eleni Anna T.; Milonakis, Michael K.; Bastounis, Elias A.; Boulafendis, Dimitrios G.

    2003-01-01

    Pseudoaneurysms of the ascending aorta after the original inclusion/wrap technique of the Bentall procedure present a difficult surgical management problem and are associated with substantial morbidity and mortality. Patients with Marfan syndrome frequently develop aneurysms and dissections that involve multiple aortic segments. We present the case of a Marfan patient who successfully underwent repair of a giant ascending aortic pseudoaneurysm and concomitant repair of an abdominal aortic ane...

  15. The future of aortic surgery in Europe

    DEFF Research Database (Denmark)

    Czerny, Martin; Bachet, Jean; Bavaria, Joseph

    2012-01-01

    the interested reader with an overview of how aortic surgery and (perhaps more accurately) aortic medicine has evolved in Europe, and its present standing; also to provide a glimpse into the future, trying to disseminate the thoughts of a group of people actively involved in the development of aortic medicine......At least every ten years, each specialty should reflect upon its past, its present and its future, in order to be able to reconfirm the direction in which it is headed, to adopt suggestions from inside and outside and, consequently, to improve. As such, the aim of this manuscript is to provide...

  16. Mycotic Aneurysm of the Aortic Arch

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    Ji Hye Seo

    2014-08-01

    Full Text Available A mycotic aneurysm of the thoracic aorta is rare. We report a case of mycotic aneurysm that developed in the aortic arch. An 86-year-old man was admitted with fever and general weakness. Blood culture yielded methicillin-resistant Staphylococcus aureus. Chest X-ray showed an enlarged aortic arch, and computed tomography scan revealed an aneurysm in the aortic arch. The patient was treated only with antibiotics and not surgically. The size of the aneurysm increased rapidly, resulting in bronchial obstruction and superimposed pneumonia. The patient died of respiratory failure.

  17. Genomic Imbalances in Rhabdomyosarcoma Cell Lines Affect Expression of Genes Frequently Altered in Primary Tumors: An Approach to Identify Candidate Genes Involved in Tumor Development

    NARCIS (Netherlands)

    Missiaglia, Edoardo; Selfe, Joanna; Hamdi, Mohamed; Williamson, Daniel; Schaaf, Gerben; Fang, Cheng; Koster, Jan; Summersgill, Brenda; Messahel, Boo; Versteeg, Rogier; Pritchard-Jones, Kathy; Kool, Marcel; Shipley, Janet

    2009-01-01

    Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. They resemble developing skeletal muscle and are histologically divided into two main subtypes; alveolar and embryonal RMS. Characteristic genomic aberrations, including the PAX3- and PAX7-FOXO1 fusion genes in alveolar

  18. Reverse extra-anatomic aortic arch debranching procedure allowing thoracic endovascular aortic repair of a chronic ascending aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Ludovic Canaud, MD, PhD

    2018-06-01

    Full Text Available A 79-year-old woman was admitted with a large chronic dissecting ascending aortic aneurysm starting 5 mm distal to the ostia of the left coronary artery and ending immediately proximal to the innominate artery. A reverse extra-anatomic aortic arch debranching procedure was performed. During the same operative time, through a transapical approach, a thoracic stent graft was deployed with the proximal landing zone just distal to the coronary ostia and the distal landing zone excluding the origin of the left common carotid artery. The postoperative course was uneventful. Computed tomography at 12 months documented patent extra-anatomic aortic arch debranching and no evidence of endoleak. Keywords: Ascending aorta, Thoracic aorta, Aortic dissection, Stent graft

  19. The role of aortic wall CT attenuation measurements for the diagnosis of acute aortic syndromes

    International Nuclear Information System (INIS)

    Knollmann, Friedrich D.; Lacomis, Joan M.; Ocak, Iclal; Gleason, Thomas

    2013-01-01

    Objectives: To determine if measurements of aortic wall attenuation can improve the CT diagnosis of acute aortic syndromes. Methods: CT reports from a ten year period were searched for acute aortic syndromes (AAS). Studies with both an unenhanced and a contrast enhanced (CTA) series that had resulted in the diagnosis of intramural hematoma (IMH) were reviewed. Diagnoses were confirmed by medical records. The attenuation of aortic wall abnormalities was measured. The observed attenuation threshold was validated using studies from 39 new subjects with a variety of aortic conditions. Results: The term “aortic dissection” was identified in 1206, and IMH in 124 patients’ reports. IMH was confirmed in 31 patients, 21 of whom had both unenhanced and contrast enhanced images. All 21 had pathologic CTA findings, and no CTA with IMH was normal. Attenuation of the aortic wall was greater than 45 HUs on the CTA images in all patients with IMH. When this threshold was applied to the new group, sensitivity for diagnosing AAS was 100% (19/19), and specificity 94% (16/17). Addition of unenhanced images did not improve accuracy. Conclusions: Measurements of aortic wall attenuation in CTA have a high negative predictive value for the diagnosis of acute aortic syndromes

  20. Stroke Volume estimation using aortic pressure measurements and aortic cross sectional area: Proof of concept.

    Science.gov (United States)

    Kamoi, S; Pretty, C G; Chiew, Y S; Pironet, A; Davidson, S; Desaive, T; Shaw, G M; Chase, J G

    2015-08-01

    Accurate Stroke Volume (SV) monitoring is essential for patient with cardiovascular dysfunction patients. However, direct SV measurements are not clinically feasible due to the highly invasive nature of measurement devices. Current devices for indirect monitoring of SV are shown to be inaccurate during sudden hemodynamic changes. This paper presents a novel SV estimation using readily available aortic pressure measurements and aortic cross sectional area, using data from a porcine experiment where medical interventions such as fluid replacement, dobutamine infusions, and recruitment maneuvers induced SV changes in a pig with circulatory shock. Measurement of left ventricular volume, proximal aortic pressure, and descending aortic pressure waveforms were made simultaneously during the experiment. From measured data, proximal aortic pressure was separated into reservoir and excess pressures. Beat-to-beat aortic characteristic impedance values were calculated using both aortic pressure measurements and an estimate of the aortic cross sectional area. SV was estimated using the calculated aortic characteristic impedance and excess component of the proximal aorta. The median difference between directly measured SV and estimated SV was -1.4ml with 95% limit of agreement +/- 6.6ml. This method demonstrates that SV can be accurately captured beat-to-beat during sudden changes in hemodynamic state. This novel SV estimation could enable improved cardiac and circulatory treatment in the critical care environment by titrating treatment to the effect on SV.

  1. The role of aortic wall CT attenuation measurements for the diagnosis of acute aortic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Knollmann, Friedrich D., E-mail: friedrich.knollmann@ucdmc.ucdavis.edu [Department of Radiology, University of California, Davis, 4860 Y Street, Sacramento, CA 95817 (United States); Departments of Radiology and Cardiothoracic Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213 (United States); Lacomis, Joan M.; Ocak, Iclal; Gleason, Thomas [Department of Radiology, University of California, Davis, 4860 Y Street, Sacramento, CA 95817 (United States); Departments of Radiology and Cardiothoracic Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213 (United States)

    2013-12-01

    Objectives: To determine if measurements of aortic wall attenuation can improve the CT diagnosis of acute aortic syndromes. Methods: CT reports from a ten year period were searched for acute aortic syndromes (AAS). Studies with both an unenhanced and a contrast enhanced (CTA) series that had resulted in the diagnosis of intramural hematoma (IMH) were reviewed. Diagnoses were confirmed by medical records. The attenuation of aortic wall abnormalities was measured. The observed attenuation threshold was validated using studies from 39 new subjects with a variety of aortic conditions. Results: The term “aortic dissection” was identified in 1206, and IMH in 124 patients’ reports. IMH was confirmed in 31 patients, 21 of whom had both unenhanced and contrast enhanced images. All 21 had pathologic CTA findings, and no CTA with IMH was normal. Attenuation of the aortic wall was greater than 45 HUs on the CTA images in all patients with IMH. When this threshold was applied to the new group, sensitivity for diagnosing AAS was 100% (19/19), and specificity 94% (16/17). Addition of unenhanced images did not improve accuracy. Conclusions: Measurements of aortic wall attenuation in CTA have a high negative predictive value for the diagnosis of acute aortic syndromes.

  2. Aortic root reimplantation procedure: a new milestone in aortic valve-sparing operations

    Directory of Open Access Journals (Sweden)

    А. М. Чернявский

    2016-08-01

    Full Text Available Aim: Emphasis in this study was placed on clinical and functional assessment of a modified "Florida Sleeve" procedure during surgical correction of ascending aorta aneurysms with concomitant aortic insufficiency.Methods: 32 patients with an aneurysm of the ascending aorta and aortic insufficiency underwent a modified "Florida Sleeve" procedure. The average follow-up was 17 (0-60 months. The average age of patients was 57±13 (23-73 years 56±13 years.Results: The expected 4-year cumulative survival rate was 84.3%. Overall freedom from aortic insufficiency in the late period was 88.9%. Median aortic regurgitation was 1+ (1; 2. Long-term follow-up revealed no valve-associated complications.Conclusion: The aortic root reimplantation procedure enables optimal correction of the existing lesions of the aortic root without performing aortic valve replacement and demonstrates stable clinical and functional outcomes in the long-term period.Key words: aortic aneurysm; aortic valve; valve-sparing operations.FundingThe study had no sponsorship.Conflict of interestThe authors declare no conflict of interest.

  3. Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep.

    Science.gov (United States)

    Nuruddin, Syed; Krogenæs, Anette; Brynildsrud, Ola Brønstad; Verhaegen, Steven; Evans, Neil P; Robinson, Jane E; Haraldsen, Ira Ronit Hebold; Ropstad, Erik

    2013-12-01

    The nature of hormonal involvement in pubertal brain development has attracted wide interest. Structural changes within the brain that occur during pubertal development appear mainly in regions closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors, results in exaggerated sex-differences in cognitive executive function and emotional control, as well as sex and hemisphere specific patterns of expression of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explored effects of this treatment regime on the gene expression profile of the ovine amygdala. The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until approximately 50 weeks of age. Gene expression profiles of the left and right amygdala were measured using 8×15 K Agilent ovine microarrays. Differential expression of selected genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for Annotation, Visualization and integrated Discovery) version 6.7 software packages, respectively. GnRHa treatment was associated with significant sex- and hemisphere-specific differential patterns of gene expression. GnRHa treatment was associated with differential expression of 432 (|logFC|>0.3, adj. p value expressed as a result of GnRHa treatment in the male animals. The results indicated that GnRH may, directly and/or indirectly, be involved in the regulation of sex- and hemisphere-specific differential expression of genes in the amygdala. This finding should be considered when long-term peri-pubertal GnRHa treatment is used in children. Copyright

  4. Culture medium composition affects the gene expression pattern and in vitro development potential of bovine somatic cell nuclear transfer (SCNT) embryos.

    Science.gov (United States)

    Arias, María E; Ross, Pablo J; Felmer, Ricardo N

    2013-01-01

    Different culture systems have been studied that support development of somatic cell nuclear transfer (SCNT) embryos up to the blastocyst stage. However, the use of sequential and two-step culture systems has been less studied. The objective of the present study was to examine the developmental potential and quality of bovine SCNT embryos cultured in different two-step culture media based on KSOM, SOF and the macromolecules FBS and BSA (K-K/FBS, K-S/BSA and K-K/BSA, respectively). No differences were observed in the cleavage rate for any of the culture systems. However, there was a significant difference (Pculture system yielding a higher rate of blastocysts (28%) compared to other treatments (18 and 15%, for K-S/BSA and K-K/BSA, respectively). Although quality of embryos, as assessed by the total number of cells, was not different, the apoptosis index was significantly affected in the sequential culture system (K-S/BSA). Gene expression analysis showed alterations of DNMT1, IGF2, LIF, and PRDX6 genes in embryos cultured in K-S/FBS and of SOD2 in embryos cultured in K-K/BSA. In conclusion, we demonstrated that culture medium may affect not only the developmental potential of SCNT embryos but also, more importantly, the gene expression pattern and apoptotic index, presenting the possibility to manipulate the culture medium composition to modulate global gene expression and improve the overall efficiency of this technique.

  5. Antifungal genes expressed in transgenic pea (Pisum sativum L.) do not affect root colonization of arbuscular mycorrhizae fungi.

    Science.gov (United States)

    Kahlon, Jagroop Gill; Jacobsen, Hans-Jörg; Cahill, James F; Hall, Linda M

    2017-10-01

    Genetically modified crops have raised concerns about unintended consequences on non-target organisms including beneficial soil associates. Pea transformed with four antifungal genes 1-3 β glucanase, endochitinase, polygalacturonase-inhibiting proteins, and stilbene synthase is currently under field-testing for efficacy against fungal diseases in Canada. Transgenes had lower expression in the roots than leaves in greenhouse experiment. To determine the impact of disease-tolerant pea or gene products on colonization by non-target arbuscular mycorrhizae and nodulation by rhizobium, a field trial was established. Transgene insertion, as single gene or stacked genes, did not alter root colonization by arbuscular mycorrhiza fungus (AMF) or root nodulation by rhizobium inoculation in the field. We found no effect of transgenes on the plant growth and performance although, having a dual inoculant with both AMF and rhizobium yielded higher fresh weight shoot-to-root ratio in all the lines tested. This initial risk assessment of transgenic peas expressing antifungal genes showed no deleterious effect on non-target organisms.

  6. Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle.

    Science.gov (United States)

    Mota, R R; Guimarães, S E F; Fortes, M R S; Hayes, B; Silva, F F; Verardo, L L; Kelly, M J; de Campos, C F; Guimarães, J D; Wenceslau, R R; Penitente-Filho, J M; Garcia, J F; Moore, S

    2017-12-01

    We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., PAPPA, PREP, FER1L6, TPR, NMNAT1, ACAD10, PCMTD1, CRH, OPKR1, NPBWR1 and NCOA2) and transcription factors (TF) (STAT1, STAT3, RELA, E2F1 and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing h