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Sample records for assembly factor chd1

  1. Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster.

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    Johanna Sebald

    Full Text Available The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has indicated that intestinal bacterial load can be affected by chromatin-targeted regulatory mechanisms. Here we studied a potential role of the conserved chromatin assembly and remodeling factor CHD1 in the shaping of the gut microbiome in Drosophila melanogaster. Using high-throughput sequencing of 16S rRNA gene amplicons, we found that Chd1 deletion mutant flies exhibit significantly reduced microbial diversity compared to rescued control strains. Specifically, although Acetobacteraceae dominated the microbiota of both Chd1 wild-type and mutant guts, Chd1 mutants were virtually monoassociated with this bacterial family, whereas in control flies other bacterial taxa constituted ~20% of the microbiome. We further show age-linked differences in microbial load and microbiota composition between Chd1 mutant and control flies. Finally, diet supplementation experiments with Lactobacillus plantarum revealed that, in contrast to wild-type flies, Chd1 mutant flies were unable to maintain higher L. plantarum titres over time. Collectively, these data provide evidence that loss of the chromatin remodeler CHD1 has a major impact on the gut microbiome of Drosophila melanogaster.

  2. The Drosophila melanogaster CHD1 chromatin remodeling factor modulates global chromosome structure and counteracts HP1a and H3K9me2.

    Science.gov (United States)

    Bugga, Lakshmi; McDaniel, Ivy E; Engie, Liana; Armstrong, Jennifer A

    2013-01-01

    CHD1 is a conserved chromatin remodeling factor that localizes to active genes and functions in nucleosome assembly and positioning as well as histone turnover. Mouse CHD1 is required for the maintenance of stem cell pluripotency while human CHD1 may function as a tumor suppressor. To investigate the action of CHD1 on higher order chromatin structure in differentiated cells, we examined the consequences of loss of CHD1 and over-expression of CHD1 on polytene chromosomes from salivary glands of third instar Drosophila melanogaster larvae. We observed that chromosome structure is sensitive to the amount of this remodeler. Loss of CHD1 resulted in alterations of chromosome structure and an increase in the heterochromatin protein HP1a, while over-expression of CHD1 disrupted higher order chromatin structure and caused a decrease in levels of HP1a. Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.

  3. The Drosophila melanogaster CHD1 chromatin remodeling factor modulates global chromosome structure and counteracts HP1a and H3K9me2.

    Directory of Open Access Journals (Sweden)

    Lakshmi Bugga

    Full Text Available CHD1 is a conserved chromatin remodeling factor that localizes to active genes and functions in nucleosome assembly and positioning as well as histone turnover. Mouse CHD1 is required for the maintenance of stem cell pluripotency while human CHD1 may function as a tumor suppressor. To investigate the action of CHD1 on higher order chromatin structure in differentiated cells, we examined the consequences of loss of CHD1 and over-expression of CHD1 on polytene chromosomes from salivary glands of third instar Drosophila melanogaster larvae. We observed that chromosome structure is sensitive to the amount of this remodeler. Loss of CHD1 resulted in alterations of chromosome structure and an increase in the heterochromatin protein HP1a, while over-expression of CHD1 disrupted higher order chromatin structure and caused a decrease in levels of HP1a. Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.

  4. Type 1 diabetes mellitus and associated risk factors in patients with or without CHD: a case-control study.

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    Björk, Anna; Svensson, Ann-Marie; Fard, Mir Nabi Pirouzi; Eriksson, Peter; Dellborg, Mikael

    2017-05-29

    Approximately 1% of children are born with CHD, and 90-95% reach adulthood. Increased exposure to infections and stress-strain can contribute to an increased risk of developing type 1 diabetes mellitus. CHD may increase the risk of more serious infections, stress-strain, and increased risk of developing type 1 diabetes mellitus. We analysed the onset of and the risk of mortality and morbidity associated with concurrent CHD in patients with type 1 diabetes mellitus compared with patients with type 1 diabetes mellitus without CHD. The study combined data from the National Diabetes Register and the National Patient Register. A total of 104 patients with CHD and type 1 diabetes mellitus were matched with 520 controls. Patients with CHD and type 1 diabetes mellitus had an earlier onset of diabetes (13.9 versus 17.4 years, p1), longer duration of diabetes (22.4 versus 18.1 years, p1), higher prevalence of retinopathy (64.0 versus 43.0%, p=0.003), higher creatinine levels (83.5 versus 74.1 µmol/L, p=0.03), higher mortality (16 versus 5%, p=0.002), and after onset of type 1 diabetes mellitus higher rates of co-morbidity (5.28 versus 3.18, p⩽0.01), heart failure (9 versus 2%, p=0.02), and stroke (6 versus 2%, p=0.048) compared with controls. From a nationwide register of patients with type 1 diabetes mellitus, the coexistence of CHD and type 1 diabetes mellitus was associated with an earlier onset, a higher frequency of microvascular complications, co-morbidity, and mortality.

  5. The Chd1 Chromatin Remodeler Shifts Nucleosomal DNA Bidirectionally as a Monomer

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    Qiu, Yupeng; Levendosky, Robert F.; Chakravarthy, Srinivas; Patel, Ashok; Bowman, Gregory D.; Myong, Sua

    2017-10-01

    Chromatin remodelers catalyze dynamic packaging of the genome by carrying out nucleosome assembly/disassembly, histone exchange, and nucleosome repositioning. Remodeling results in evenly spaced nucleosomes, which requires probing both sides of the nucleosome, yet the way remodelers organize sliding activity to achieve this task is not understood. Here, we show that the monomeric Chd1 remodeler shifts DNA back and forth by dynamically alternating between different segments of the nucleosome. During sliding, Chd1 generates unstable remodeling intermediates that spontaneously relax to a pre-remodeled position. We demonstrate that nucleosome sliding is tightly controlled by two regulatory domains: the DNA-binding domain, which interferes with sliding when its range is limited by a truncated linking segment, and the chromodomains, which play a key role in substrate discrimination. We propose that active interplay of the ATPase motor with the regulatory domains may promote dynamic nucleosome structures uniquely suited for histone exchange and chromatin reorganization during transcription.

  6. CHD1 regulates cell fate determination by activation of differentiation-induced genes

    DEFF Research Database (Denmark)

    Baumgart, Simon J; Najafova, Zeynab; Hossan, Tareq

    2017-01-01

    The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start...... site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes....... Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close...

  7. CHD1 regulates cell fate determination by activation of differentiation-induced genes.

    Science.gov (United States)

    Baumgart, Simon J; Najafova, Zeynab; Hossan, Tareq; Xie, Wanhua; Nagarajan, Sankari; Kari, Vijayalakshmi; Ditzel, Nicholas; Kassem, Moustapha; Johnsen, Steven A

    2017-07-27

    The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma

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    Sara Badodi

    2017-12-01

    Full Text Available Summary: We describe molecular convergence between BMI1 and CHD7 in the initiation of medulloblastoma. Identified in a functional genomic screen in mouse models, a BMI1High;CHD7Low expression signature within medulloblastoma characterizes patients with poor overall survival. We show that BMI1-mediated repression of the ERK1/2 pathway leads to increased proliferation and tumor burden in primary human MB cells and in a xenograft model, respectively. We provide evidence that repression of the ERK inhibitor DUSP4 by BMI1 is dependent on a more accessible chromatin configuration in G4 MB cells with low CHD7 expression. These findings extend current knowledge of the role of BMI1 and CHD7 in medulloblastoma pathogenesis, and they raise the possibility that pharmacological targeting of BMI1 or ERK may be particularly indicated in a subgroup of MB with low expression levels of CHD7. : Badodi et al. find convergence of the chromatin modifiers BMI1 and CHD7 in medulloblastoma pathogenesis, and they show that this pathway regulates tumor proliferation and growth via ERK signaling. Keywords: BMI1, CHD7, DUSP4, ERK, medulloblastoma, PcG genes, mouse models, epigenetics, chromatin

  9. Loss of CHD1 causes DNA repair defects and enhances prostate cancer therapeutic responsiveness

    DEFF Research Database (Denmark)

    Kari, Vijayalakshmi; Mansour, Wael Yassin; Raul, Sanjay Kumar

    2016-01-01

    The CHD1 gene, encoding the chromo-domain helicase DNA-binding protein-1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of Ct......-homologous end joining. Together, we provide evidence for a previously unknown role of CHD1 in DNA DSB repair via HR and show that CHD1 depletion sensitizes cells to PARP inhibitors, which has potential therapeutic relevance. Our findings suggest that CHD1 deletion, like BRCA1/2 mutation in ovarian cancer, may...... serve as a marker for prostate cancer patient stratification and the utilization of targeted therapies such as PARP inhibitors, which specifically target tumors with HR defects....

  10. Do family history of CHD, education, paternal social class, number of siblings and height explain the association between psychosocial factors at work and coronary heart disease? The Whitehall II study

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    Hintsa, T; Shipley, M; Gimeno, D; Elovainio, M; Chandola, T; Jokela, M; Keltikangas-Järvinen, L; Vahtera, J; Marmot, MG; Kivimäki, M

    2011-01-01

    Objectives To examine whether the association between psychosocial factors at work and incident coronary heart disease (CHD) is explained by pre-employment factors such as family history of CHD, education, paternal social class, number of siblings and height. Methods A prospective cohort study of 6435 of British men aged 35–55 years at phase 1 (1985–1988) and free from prevalent CHD at phase 2 (1989–1990) was conducted. Psychosocial factors at work were assessed at phases 1 and 2 and mean scores across the two phases were used to determine long-term exposure. Selected pre-employment factors were assessed at phase 1. Follow-up for coronary death, first non-fatal myocardial infarction or definite angina between phase 2 and 1999 was based on clinical records (250 events, follow-up 8.7 years). Results Pre-employment factors were associated with risk for CHD: hazard ratio, HRs (95% CI) were 1.33 (1.03 to 1.73) for family history of CHD, 1.18 (1.05–1.32) for each quartile decrease in height, and marginally 1.16 (0.99–1.35) for each category increase in number of siblings. Psychosocial work factors predicted CHD: 1.72 (1.08–2.74) for low job control and 1.72 (1.10–2.67) for low organisational justice. Adjustment for pre-employment factors changed these associations by 4.1% or less. Conclusions In this well-characterised occupational cohort of British men, the association between psychosocial factors at work and CHD was largely independent of family history of CHD, education, paternal education and social class, number of siblings and height. PMID:19819857

  11. Analysis list: Chd8 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Chd8 Blood,Embryo + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Chd8.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Chd8.5.tsv http://dbarchive.biosciencedbc.jp/kyu...shu-u/mm9/target/Chd8.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Chd8.Blood.tsv,http://dbarc...hive.biosciencedbc.jp/kyushu-u/mm9/colo/Chd8.Embryo.tsv http://dbarchive.bioscien...cedbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Embryo.gml ...

  12. Identification of CHD1L as an Important Regulator for Spermatogonial Stem Cell Survival and Self-Renewal

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    Shan-Shan Liu

    2016-01-01

    Full Text Available Chromodomain helicase/ATPase DNA binding protein 1-like gene (Chd1l participates in chromatin-dependent processes, including transcriptional activation and DNA repair. In this study, we have found for the first time that Chd1l is mainly expressed in the testicular tissues of prepubertal and adult mice and colocalized with PLZF, OCT4, and GFRα1 in the neonatal mouse testis and THY1+ undifferentiated spermatogonia or spermatogonial stem cells (SSCs. Knockdown of endogenous Chd1l in cultured mouse undifferentiated SSCs inhibited the expression levels of Oct4, Plzf, Gfrα1, and Pcna genes, suppressed SSC colony formation, and reduced BrdU incorporation, while increasing SSC apoptosis. Moreover, the Chd1l gene expression is activated by GDNF in the cultured mouse SSCs, and the GDNF signaling pathway was modulated by endogenous levels of Chd1l; as demonstrated by the gene expression levels of GDNF, inducible transcripts Etv5, Bcl6b, Pou3f, and Lhx1, but not that of GDNF-independent gene, Taf4b, were significantly downregulated by Chd1l knockdown in mouse SSCs. Taken together, this study provides the first evidence to support the notion that Chd1l is an intrinsic and novel regulator for SSC survival and self-renewal, and it exerts such regulation at least partially through a GDNF signaling pathway.

  13. Dicty_cDB: CHD753 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHD753 (Link to dictyBase) - - - Contig-U15579-1 - (Link to Or...iginal site) - - CHD753Z 650 - - - - Show CHD753 Library CH (Link to library) Clone ID CHD753 (Link to dicty...Base) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15579-1 Original site URL http://dictycdb.b...---IQACGPDNNYQCEFVDKICNTTNDKCLVESCEIGFGCLAIPKNCNDNDPCTTDHCDP AIGCYYDKFDNCDACNAVDTCITNDLCFPRECNPRGNPPCLINPINCTSTDPCIFSYCEN GVCIPTYICT...NPRGNPPCLINPINCTSTDPCIFSYCEN GVCIPTYICTPTPSVTPTVTPTVTPTVTPTVTPTVTPTVTPTPTTTPTPSPTTVPPRPTP TPLPADPPPYDLEEGCLV

  14. Hypoxia-inducible factor-1α, vascular endothelial growth factor, inducible nitric oxide synthase, and endothelin-1 expression correlates with angiogenesis in congenital heart disease

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    Hsin-Ling Yin

    2016-07-01

    Full Text Available In Taiwan, the average prevalence of congenital heart disease (CHD is 13.08/1000 live births. Most children with CHD die before the age of 5 years; therefore, identifying treatment methods to extend the life of CHD patients is an important issue in clinical practice. The objective of this study is to evaluate the roles of hypoxia-inducible factor-1α (HIF-1α, vascular endothelial growth factor (VEGF, inducible nitric oxide synthase (iNOS, endothelin-1 (ET-1, and CD34 in CHD autopsy cases in comparison with autopsy cases without CHD. The study included 19 autopsy cases, which were divided into the following four groups: acyanotic CHD (n = 11, cyanotic CHD (n = 3, CHD associated with chromosomal abnormalities (n = 3, and complex CHD (n = 2. Heart specimens obtained from 10 autopsy cases without CHD were included as controls. Our results indicated that high percentages of HIF-1α (100%, VEGF (89.5%, iNOS (78.9%, and ET-1 (84.2% expressions were observed in CHD autopsy cases and this was found to be significant. HIF-1α induced by hypoxia could play a potential role in relating downstream gene expressions in CHD patients. Upregulation of VEGF by HIF-1α could play an important role in triggering angiogenesis to protect myocardial cell survival in a hypoxic microenvironment. Therefore, HIF-1α could be a significant prognosis marker in CHD and be a prospective candidate in the development of target therapy in cardiovascular diseases.

  15. Dicty_cDB: CHD152 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHD152 (Link to dictyBase) - - - - - (Link to Original site) C...HD152F 603 - - - - - - Show CHD152 Library CH (Link to library) Clone ID CHD152 (Link to dictyBase) Atlas ID - NBRP ID - dict...yBase ID - Link to Contig - Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/CH/CHD...Score E Sequences producing significant alignments: (bits) Value N U36937 |U36937.1 Dictyostelium discoideum...UF_IpTrk_27_j08 Trunk kidney cDNA library Ictalurus punctatus cDNA 5' similar to

  16. Dicty_cDB: CHD492 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHD492 (Link to dictyBase) - - - - CHD492P (Link to Original site) CHD492F 531 CHD492...Z 728 CHD492P 1239 - - Show CHD492 Library CH (Link to library) Clone ID CHD492 (Link...sukuba.ac.jp/CSM/CH/CHD4-D/CHD492Q.Seq.d/ Representative seq. ID CHD492P (Link to... Original site) Representative DNA sequence >CHD492 (CHD492Q) /CSM/CH/CHD4-D/CHD492Q.Seq.d/ ATATACAATTTAATTT...A Score E Sequences producing significant alignments: (bits) Value CHD492 (CHD492Q) /CSM/CH/CHD4-D/CHD492

  17. CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors

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    Sugathan, Aarathi; Biagioli, Marta; Golzio, Christelle; Erdin, Serkan; Blumenthal, Ian; Manavalan, Poornima; Ragavendran, Ashok; Brand, Harrison; Lucente, Diane; Miles, Judith; Sheridan, Steven D.; Stortchevoi, Alexei; Kellis, Manolis; Haggarty, Stephen J.; Katsanis, Nicholas; Gusella, James F.; Talkowski, Michael E.

    2014-01-01

    Truncating mutations of chromodomain helicase DNA-binding protein 8 (CHD8), and of many other genes with diverse functions, are strong-effect risk factors for autism spectrum disorder (ASD), suggesting multiple mechanisms of pathogenesis. We explored the transcriptional networks that CHD8 regulates in neural progenitor cells (NPCs) by reducing its expression and then integrating transcriptome sequencing (RNA sequencing) with genome-wide CHD8 binding (ChIP sequencing). Suppressing CHD8 to levels comparable with the loss of a single allele caused altered expression of 1,756 genes, 64.9% of which were up-regulated. CHD8 showed widespread binding to chromatin, with 7,324 replicated sites that marked 5,658 genes. Integration of these data suggests that a limited array of direct regulatory effects of CHD8 produced a much larger network of secondary expression changes. Genes indirectly down-regulated (i.e., without CHD8-binding sites) reflect pathways involved in brain development, including synapse formation, neuron differentiation, cell adhesion, and axon guidance, whereas CHD8-bound genes are strongly associated with chromatin modification and transcriptional regulation. Genes associated with ASD were strongly enriched among indirectly down-regulated loci (P neurodevelopmental pathways in which many ASD-associated genes may converge on shared mechanisms of pathogenesis. PMID:25294932

  18. Influence of Comprehensive Life Style Intervention in Patients of CHD.

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    Dehghani, Ali; Kumar Bhasin, Sanjiv; Dwivedi, Shridhar; Kumar Malhotra, Rajeev

    2015-03-26

    Over the past 30 years, the CHD rates have doubled in India whereas CHD rates have declined by 15% in most developed countries due to lifestyle interventions during the same period. So, the present study was conducted to find out the effectiveness of lifestyle intervention in reducing major risk factors in CHD patients in an Indian setting. We conducted this randomized controlled trial on 640 eligible subjects who were randomly assigned to two groups. The study group was given an interventional package at baseline and at three months, detailing the aspects of a healthy lifestyle in relation to CHD risk factors whereas no intervention was provided for the control group. The study subjects were followed at three and six months and the risk factors were assessed to find out reduction, if any, in the prevalence of the risk factors amongst them. There was a significant reduction in hypertension, tobacco, and lack of physical activity at three and at six months (plifestyle intervention was successful in increasing physical activity, improving the hypertension control, and decreasing lipid profile disorders, obesity, and tobacco use in the study group.

  19. Dicty_cDB: CHD534 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHD534 (Link to dictyBase) - - - Contig-U15540-1 CHD534E (Link...) Clone ID CHD534 (Link to dictyBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15540-1 Ori...nts: (bits) Value N AC114263 |AC114263.2 Dictyostelium discoideum chromosome 2 ma...p 215673-367476 strain AX4, complete sequence. 40 1e-05 6 AC117081 |AC117081.2 Dictyostelium discoideum chro...mosome 2 map 5862124-6045772 strain AX4, complete sequence. 40 2e-05 5 AJ277590 |AJ277590.1 Dictyostelium di

  20. Chromatin Remodeling Proteins in Epilepsy: Lessons From CHD2-Associated Epilepsy

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    Kay-Marie J. Lamar

    2018-06-01

    Full Text Available The chromodomain helicase DNA-binding (CHD family of proteins are ATP-dependent chromatin remodelers that contribute to the reorganization of chromatin structure and deposition of histone variants necessary to regulate gene expression. CHD proteins play an important role in neurodevelopment, as pathogenic variants in CHD1, CHD2, CHD4, CHD7 and CHD8 have been associated with a range of neurological phenotypes, including autism spectrum disorder (ASD, intellectual disability (ID and epilepsy. Pathogenic variants in CHD2 are associated with developmental epileptic encephalopathy (DEE in humans, however little is known about how these variants contribute to this disorder. Of the nine CHD family members, CHD2 is the only one that leads to a brain-restricted phenotype when disrupted in humans. This suggests that despite being expressed ubiquitously, CHD2 has a unique role in human brain development and function. In this review, we will discuss the phenotypic spectrum of patients with pathogenic variants in CHD2, current animal models of CHD2 deficiency, and the role of CHD2 in proliferation, neurogenesis, neuronal differentiation, chromatin remodeling and DNA-repair. We also consider how CHD2 depletion can affect each of these biological mechanisms and how these defects may underpin neurodevelopmental disorders including epilepsy.

  1. Hearing loss is associated with increased CHD risk and unfavorable CHD-related biomarkers in the Dongfeng-Tongji cohort.

    Science.gov (United States)

    Fang, Qin; Wang, Zhichao; Zhan, Yue; Li, Dan; Zhang, Kun; Zhou, Tao; Yang, Handong; Zhang, Ce; Li, Xiulou; Min, Xinwen; Chen, Weihong; Guo, Huan; He, Mei-An; Kong, Weijia; Wu, Tangchun; Zhang, Xiaomin

    2018-04-01

    The association between hearing loss and coronary heart disease (CHD) is inconsistent. We aimed to investigate the association of hearing loss with prevalent CHD and CHD-related biomarkers among a middle aged and elderly Chinese population. We included 14,755 Chinese aged 64.6 years from the Dongfeng-Tongji Cohort in 2013. Hearing loss was classified into normal, mild, moderate or greater levels by the pure tone average (PTA) at low frequency and high frequency, respectively. Logistic regression models were used to estimate the odds ratios (ORs) of CHD risk in relation to hearing loss. Linear regression models were used to evaluate the effect of hearing loss on CHD-related biomarkers. The adjusted ORs for prevalent CHD increased gradually with the increasing hearing loss levels. Compared with normal hearing, individuals having mild- and moderate or greater-hearing loss had a higher CHD risk of 19% and 20% at low frequency, and 33% and 41% at high frequency, respectively (all p for trend occupational noise and with hyperglycemia, hypertension or dyslipidemia at low frequency, and those with hyperglycemia at high frequency. Meanwhile, moderate or greater hearing loss combined with overweight, hyperglycemia, hypertension or dyslipidemia had joint effects on CHD. In addition, the majority of CHD-related biomarkers worsened with increasing hearing loss levels. There may be a dose-response relationship between hearing loss and CHD prevalence, and the association could partially be explained by intermediate CHD-related biomarkers. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Effect of CH stretching excitation on the reaction dynamics of F + CHD{sub 3} → DF + CHD{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jiayue; Zhang, Dong; Chen, Zhen; Jiang, Bo [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, 457 Zhongshan Road, Dalian, Liaoning 116023 (China); Blauert, Florian [Dynamics at Surfaces, Faculty of Chemistry, Georg-August-Universität Göttingen, 37077 Göttingen (Germany); Dai, Dongxu; Wu, Guorong, E-mail: wugr@dicp.ac.cn, E-mail: xmyang@dicp.ac.cn; Zhang, Donghui; Yang, Xueming, E-mail: wugr@dicp.ac.cn, E-mail: xmyang@dicp.ac.cn [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, 457 Zhongshan Road, Dalian, Liaoning 116023 (China); Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China)

    2015-07-28

    The vibrationally excited reaction of F + CHD{sub 3}(ν{sub 1} = 1) → DF + CHD{sub 2} at a collision energy of 9.0 kcal/mol is investigated using the crossed-beams and time-sliced velocity map imaging techniques. Detailed and quantitative information of the CH stretching excitation effects on the reactivity and dynamics of the title reaction is extracted with the help of an accurate determination of the fraction of the excited CHD{sub 3} reagent in the crossed-beam region. It is found that all vibrational states of the CHD{sub 2} products observed in the ground-state reaction, which mainly involve the excitation of the umbrella mode of the CHD{sub 2} products, are severely suppressed by the CH stretching excitation. However, there are four additional vibrational states of the CHD{sub 2} products appearing in the excited-state reaction which are not presented in the ground-state reaction. These vibrational states either have the CH stretching excitation retained or involve one quantum excitation in the CH stretching and the excitation of the umbrella mode. Including all observed vibrational states, the overall cross section of the excited-state reaction is estimated to be 66.6% of that of the ground-state one. Experimental results also show that when the energy of CH stretching excitation is released during the reaction, it is deposited almost exclusively as the rovibrational energy of the DF products, with little portion in the translational degree of freedom. For vibrational states of the CHD{sub 2} products observed in both ground- and excited-state reactions, the CH stretching excitation greatly suppresses the forward scattered products, causing a noticeable change in the product angular distributions.

  3. Prevalence and risk factors associated with non-attendance in neurodevelopmental follow-up clinic among infants with CHD.

    Science.gov (United States)

    Loccoh, Eméfah C; Yu, Sunkyung; Donohue, Janet; Lowery, Ray; Butcher, Jennifer; Pasquali, Sara K; Goldberg, Caren S; Uzark, Karen

    2018-04-01

    Neurodevelopmental impairment is increasingly recognised as a potentially disabling outcome of CHD and formal evaluation is recommended for high-risk patients. However, data are lacking regarding the proportion of eligible children who actually receive neurodevelopmental evaluation, and barriers to follow-up are unclear. We examined the prevalence and risk factors associated with failure to attend neurodevelopmental follow-up clinic after infant cardiac surgery. Survivors of infant (neurodevelopmental clinic attendees and non-attendees in univariate and multivariable analyses. A total of 552 patients were included; median age at surgery was 2.4 months, 15% were premature, and 80% had moderate-severe CHD. Only 17% returned for neurodevelopmental evaluation, with a median age of 12.4 months. In univariate analysis, non-attendees were older at surgery, had lower surgical complexity, fewer non-cardiac anomalies, shorter hospital stay, and lived farther from the surgical center. Non-attendee families had lower income, and fewer were college graduates or had private insurance. In multivariable analysis, lack of private insurance remained independently associated with non-attendance (adjusted odds ratio 1.85, p=0.01), with a trend towards significance for distance from surgical center (adjusted odds ratio 2.86, p=0.054 for ⩾200 miles). The majority of infants with CHD at high risk for neurodevelopmental dysfunction evaluated in this study are not receiving important neurodevelopmental evaluation. Efforts to remove financial/insurance barriers, increase access to neurodevelopmental clinics, and better delineate other barriers to receipt of neurodevelopmental evaluation are needed.

  4. Dicty_cDB: CHD405 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHD405 (Link to dictyBase) - - - Contig-U15984-1 CHD405E (Link... Clone ID CHD405 (Link to dictyBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15984-1 Original site URL http://dict...ts) Value N AC115599 |AC115599.2 Dictyostelium discoideum chromosome 2 map 422909...8-4354721 strain AX4, complete sequence. 42 3e-11 9 AC115598 |AC115598.2 Dictyostelium discoideum chromosome... 2 map 581427-735498 strain AX4, complete sequence. 50 4e-11 11 CK417372 |CK417372.1 AUF_IpInt_56_d19 Intestine cDNA library Ict

  5. The metabolic syndrome: prevalence, CHD risk, and treatment.

    Science.gov (United States)

    Sarti, Cinzia; Gallagher, John

    2006-01-01

    An increased risk of coronary heart disease (CHD) morbidity and mortality is associated with the metabolic syndrome, a condition characterized by the concomitant presence of several abnormalities, including abdominal obesity, dyslipidemia, hypertension, insulin resistance (with or without glucose intolerance or diabetes), microalbuminuria, prothrombotic, and proinflammatory states. Estimates of the prevalence of the metabolic syndrome indicate that this condition is now common and likely to increase dramatically over the coming decades, in parallel with greater rates of obesity and Type 2 diabetes. Risk factors for the metabolic syndrome are already present in obese children and adolescents. Thus, identifying and treating all affected individuals promptly and optimally are critical to ensure that this potentially challenging healthcare burden is minimized. Here, we review the prevalence of the metabolic syndrome, dyslipidemias, and CHD risk. Although changes in lifestyle are fundamental to reducing many of the CHD risk factors associated with the metabolic syndrome, pharmacologic interventions also play an important role. Retrospective subanalyses of the effects of statins on coronary event rates and lipid levels in patients with the metabolic syndrome included in clinical trials indicate that these agents are beneficial in correcting the extensive lipid abnormalities that are frequently present in these individuals. However, the optimal management of metabolic syndrome dyslipidemia will depend on the outcomes of future prospective clinical trials. This review examines the underlying causes and prevalence of the metabolic syndrome and its impact on CHD morbidity and mortality and discusses the role of statins in optimizing its management.

  6. 21 CFR 101.83 - Health claims: plant sterol/stanol esters and risk of coronary heart disease (CHD).

    Science.gov (United States)

    2010-04-01

    ... factors for CHD is a major public health goal that can assist in reducing risk of CHD. High blood total... LDL cholesterol levels. (c) Requirements—(1) General. All requirements set forth in § 101.14 shall be... benefits of exercise and management of body weight to help lower the risk of heart disease. (2) The claim...

  7. Managing Metabolic Syndrome and CHD Risk Factors: Evidence based re-examination of macro nutrients from the Malaysian Population Prospective Study

    Directory of Open Access Journals (Sweden)

    Kalyana Sundram

    2014-11-01

    Full Text Available Our understanding of dietary factors and habits associated with coronary heart disease (CHD risk are undergoing dramatic rethinking in light of fast emerging new scientific data. Multiple risk assessments, especially in understanding Metabolic Syndrome triggers in the population have further confounded understanding and management of traditional risk factors. By far the largest change-impact is being made with regard to fat consumption, especially saturated fats. Emerging evidence, largely through meta-analysis and population studies have regularly challenged the association of saturated fats with increased CHD risk. Indeed there is a growing appreciation that saturates no longer glove-fit risk assessment especially when newer biochemical factors such as lipoprotein particle sizes have emerged to partially explain observed anomalies. The fats we eat may not necessarily be associated with making us fat (obese and obesity is a major health challenge globally. This has redirected dietary assessments more towards excess carbohydrate consumption and their possible adverse outcomes.Drawing on an ongoing population prospective study in Malaysia, such observations are similarly amplified in an urban Malaysian population. Significant carbohydrate associated negative impacts on CHD risk is seen emerging, especially when evaluated against more advanced biochemical markers. Differences in the ethnic groups of the population, modulated through cultural dietary preferences are similarly apparent. In this model, a surprisingly lower risk contributor is the prevailing fat consumption trends in the country. These observations are explained in this presentation aimed at creating better awareness of food factors impacting disease outcomes in an urban Malaysian environment whose make-up includes a substantive South Indian population as well.

  8. Managing Metabolic Syndrome and CHD Risk Factors: Evidence based re-examination of macro nutrients from the Malaysian Population Prospective Study

    Directory of Open Access Journals (Sweden)

    Kalyana Sundram

    2014-12-01

    Full Text Available Our understanding of dietary factors and habits associated with coronary heart disease (CHD risk are undergoing dramatic rethinking in light of fast emerging new scientific data. Multiple risk assessments, especially in understanding Metabolic Syndrome triggers in the population have further confounded understanding and management of traditional risk factors. By far the largest change-impact is being made with regard to fat consumption, especially saturated fats. Emerging evidence, largely through meta-analysis and population studies have regularly challenged the association of saturated fats with increased CHD risk. Indeed there is a growing appreciation that saturates no longer glove-fit risk assessment especially when newer biochemical factors such as lipoprotein particle sizes have emerged to partially explain observed anomalies. The fats we eat may not necessarily be associated with making us fat (obese and obesity is a major health challenge globally. This has redirected dietary assessments more towards excess carbohydrate consumption and their possible adverse outcomes. Drawing on an ongoing population prospective study in Malaysia, such observations are similarly amplified in an urban Malaysian population. Significant carbohydrate associated negative impacts on CHD risk is seen emerging, especially when evaluated against more advanced biochemical markers. Differences in the ethnic groups of the population, modulated through cultural dietary preferences are similarly apparent. In this model, a surprisingly lower risk contributor is the prevailing fat consumption trends in the country. These observations are explained in this presentation aimed at creating better awareness of food factors impacting disease outcomes in an urban Malaysian environment whose make-up includes a substantive South Indian population as well.

  9. CHD2 variants are a risk factor for photosensitivity in epilepsy

    DEFF Research Database (Denmark)

    Galizia, Elizabeth C.; Myers, Candace T.; Leu, Costin

    2015-01-01

    Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic e...

  10. [The role of remodeling complexes CHD1 and ISWI in spontaneous and UV-induced mutagenesis control in yeast Saccharomyces cerevisiae].

    Science.gov (United States)

    Evstiukhina, T A; Alekseeva, E A; Fedorov, D V; Peshekhonov, V T; Korolev, V G

    2017-02-01

    Chromatin remodulators are special multiprotein machines capable of transforming the structure, constitution, and positioning of nucleosomes on DNA. Biochemical activities of remodeling complexes CHD1 and ISWI from the SWI2/SNF2 family are well established. They ensure correct positioning of nucleosomes along the genome, which is probably critical for genome stability, in particular, after action of polymerases, repair enzymes, and transcription. In this paper, we show that single mutations in genes ISW1, ISW2, and CHD1 weakly affect repair and mutagenic processes in yeast cells. At the same time, there are differences in the effect of these mutations on spontaneous mutation levels, which indicates certain specificity of action of protein complexes ISW1, ISW2, and CHD1 on expression of different genes that control repair and mutation processes in yeast.

  11. Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Persson, Jenna [Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet (Sweden); Ekwall, Karl, E-mail: karl.ekwall@ki.se [Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet (Sweden); School of Life Sciences, University College Sodertorn, NOVUM, Huddinge (Sweden)

    2010-05-01

    Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that can arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.

  12. Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation

    International Nuclear Information System (INIS)

    Persson, Jenna; Ekwall, Karl

    2010-01-01

    Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that can arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.

  13. Cardiovascular malformations caused by NOTCH1 mutations do not keep left : data on 428 probands with left-sided CHD and their families

    NARCIS (Netherlands)

    Kerstjens-Frederikse, Wilhelmina S.; van de Laar, Ingrid M. B. H.; Vos, Yvonne J.; Verhagen, Judith M. A.; Berger, Rolf M. F.; Lichtenbelt, Klaske D.; Wassink-Ruiter, Jolien S. Klein; van der Zwaag, Paul A.; Sarvaas, Gideon J. du Marchie; Bergman, Klasien A.; Bilardo, Catia M.; Roos-Hesselink, Jolien W.; Janssen, Johan H. P.; Frohn-Mulder, Ingrid M.; van Spaendonck-Zwarts, Karin Y.; Melle, van Joost P.; Hofstra, Robert M. W.; Wessels, M. W.

    Purpose: We aimed to determine the prevalence and phenotypic spectrum of NOTCH1 mutations in left-sided congenital heart disease (LS-CHD). LS-CHD includes aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, and hypoplastic left heart syndrome. Methods: NOTCH1 was screened for

  14. New Face for Chromatin-Related Mesenchymal Modulator: n-CHD9 Localizes to Nucleoli and Interacts With Ribosomal Genes.

    Science.gov (United States)

    Salomon-Kent, Ronit; Marom, Ronit; John, Sam; Dundr, Miroslav; Schiltz, Louis R; Gutierrez, Jose; Workman, Jerry; Benayahu, Dafna; Hager, Gordon L

    2015-09-01

    Mesenchymal stem cells' differentiation into several lineages is coordinated by a complex of transcription factors and co-regulators which bind to specific gene promoters. The Chromatin-Related Mesenchymal Modulator, CHD9 demonstrated in vitro its ability for remodeling activity to reposition nucleosomes in an ATP-dependent manner. Epigenetically, CHD9 binds with modified H3-(K9me2/3 and K27me3). Previously, we presented a role for CHD9 with RNA Polymerase II (Pol II)-dependent transcription of tissue specific genes. Far less is known about CHD9 function in RNA Polymerase I (Pol I) related transcription of the ribosomal locus that also drives specific cell fate. We here describe a new form, the nucleolar CHD9 (n-CHD9) that is dynamically associated with Pol I, fibrillarin, and upstream binding factor (UBF) in the nucleoli, as shown by imaging and molecular approaches. Inhibitors of transcription disorganized the nucleolar compartment of transcription sites where rDNA is actively transcribed. Collectively, these findings link n-CHD9 with RNA pol I transcription in fibrillar centers. Using chromatin immunoprecipitation (ChIP) and tilling arrays (ChIP- chip), we find an association of n-CHD9 with Pol I related to rRNA biogenesis. Our new findings support the role for CHD9 in chromatin regulation and association with rDNA genes, in addition to its already known function in transcription control of tissue specific genes. © 2015 Wiley Periodicals, Inc.

  15. Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations

    Science.gov (United States)

    Laitinen, Eeva-Maria; Tommiska, Johanna; Sane, Timo; Vaaralahti, Kirsi; Toppari, Jorma; Raivio, Taneli

    2012-01-01

    Background Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features. Methods and Findings Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18–61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHβ were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21–39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q), which was accompanied by another GNRHR mutation (R139H or del309F). In addition, both of the KS patients had a mutation in CHD7 (p.Q51X) or FGFR1 (c.91+2T>A). Conclusions Considerable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal. PMID:22724017

  16. Reversible congenital hypogonadotropic hypogonadism in patients with CHD7, FGFR1 or GNRHR mutations.

    Directory of Open Access Journals (Sweden)

    Eeva-Maria Laitinen

    Full Text Available BACKGROUND: Congenital hypogonadotropic hypogonadism (HH is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH have common phenotypic or genotypic features. METHODS AND FINDINGS: Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26 or normal sense of smell (nHH; n = 6 were enrolled (age range, 18-61 yrs. The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHβ were screened for mutations. Six HH patients (2 KS, 4 nHH were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21-39 yrs. All had spontaneous testicular growth while on testosterone replacement therapy (TRT. One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q, which was accompanied by another GNRHR mutation (R139H or del309F. In addition, both of the KS patients had a mutation in CHD7 (p.Q51X or FGFR1 (c.91+2T>A. CONCLUSIONS: Considerable proportion of patients with HH (8% of KS probands may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal.

  17. Quality of life of Malaysian children with CHD.

    Science.gov (United States)

    Ong, Lai C; Teh, Ching S; Darshinee, Joyce; Omar, Asma; Ang, Hak L

    2017-09-01

    The objectives of this study were to compare the quality-of-life scores of Malaysian children with CHD and their healthy siblings, to determine the level of agreement between proxy-reports and child self-reports, and to examine variables that have an impact on quality of life in those with CHD. Parental-proxy scores of the Pediatric Quality of Life Inventory 4.0 core scales were obtained for 179 children with CHD and 172 siblings. Intra-class coefficients were derived to determine the levels of proxy-child agreement in 66 children aged 8-18 years. Multiple regression analysis was used to determine factors that impacted Pediatric Quality of Life Inventory scores. Proxy scores were lower in children with CHD than siblings for all scales except physical health. Maximum differences were noted in children aged 5-7 years, whereas there were no significant differences in the 2-4 and 13-18 years age groups. Good levels of proxy-child agreement were found in children aged 8-12 years for total, psychosocial health, social, and school functioning scales (correlation coefficients 0.7-0.8). In children aged 13-18 years, the level of agreement was poor to fair for emotional and social functioning. The need for future surgery and severity of symptoms were associated with lower scores. Differences in proxy perception of quality of life appear to be age related. The level of proxy-child agreement was higher compared with other reported studies, with lower levels of agreement in teenagers. Facilitating access to surgery and optimising control of symptoms may improve quality of life in this group of children.

  18. Role of Chromatin assembly factor 1 in DNA replication of Plasmodium falciparum.

    Science.gov (United States)

    Gupta, Mohit Kumar; Agarawal, Meetu; Banu, Khadija; Reddy, K Sony; Gaur, Deepak; Dhar, Suman Kumar

    2018-01-01

    Nucleosome assembly in P. falciparum could be the key process in maintaining its genomic integrity as DNA replicates more than once per cell cycle during several stages of its life cycle. Here, we report the functional characterization of P. falciparum chromatin assembly factor 1 (CAF1), which interacts with several proteins namely PfCAF2, Histones, PfHP1 and others. Consistent with the above findings, we demonstrate the presence of PfCAF1 at the telomeric repeat regions, central and subtelomeric var genes of multiple var gene family along with PfHP1. Further, we report the upregulation of PfCAF1 after treatment with genotoxic agents like MMS and HU. Together, these findings establish role of PfCAF1 in heterochromatin maintenance and as histone chaperone in nucleosome assembly and DNA damage repair. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Pregnancy in complex CHD: focus on patients with Fontan circulation and patients with a systemic right ventricle.

    Science.gov (United States)

    Khan, Abigail; Kim, Yuli Y

    2015-12-01

    The majority of children with congenital heart disease (CHD) now survive into adulthood, and many women with CHD want to pursue pregnancy. Pregnancy represents a complex issue for the CHD care provider. It requires balancing the interests of the woman against the risk to her health during pregnancy, while also factoring in the long-term risks to her health and the risk to her fetus. Our knowledge about this subject has been historically limited by lack of data regarding the outcome of pregnancy in CHD; however, in recent years, more data have begun to emerge. In this review, we will summarise what is known about risk assessment in pregnant CHD patients. We provide a framework for healthcare providers managing pregnancy in this population, with focus on the systemic right ventricle and the Fontan operation.

  20. A Single Nucleotide Polymorphism in the Stromal Cell-Derived Factor 1 Gene Is Associated with Coronary Heart Disease in Chinese Patients

    Directory of Open Access Journals (Sweden)

    Lei Feng

    2014-06-01

    Full Text Available Coronary heart disease (CHD is highly prevalent globally and a major cause of mortality. Genetic predisposition is a non-modifiable risk factor associated with CHD. Eighty-four Chinese patients with CHD and 253 healthy Chinese controls without CHD were recruited. Major clinical data were collected, and a single nucleotide polymorphism (SNP in the stromal cell-derived factor 1 (SDF-1 gene at position 801 (G to A, rs1801157 in the 3'-untranslated region was identified. The correlation between rs1801157 genotypes and CHD was evaluated by a multivariate logistic regression analysis. The allele frequency in the CHD and control groups was in Hardy-Weinberg equilibrium (HWE (p > 0.05. The frequency of the GG genotype in the CHD group (59.5% was significantly higher than that in the control group (49.8% (p = 0.036. A number of variables, including male sex, age, presence of hypertension, and the levels of low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, triglycerides (TG, uric acid, and total bilirubin, were associated with CHD in a primary univariate analysis. In a multivariable logistic regression analysis, the GG genotype (GG:AA, odds ratio (OR = 2.31, 95% confidence interval (CI = 1.21–5.23, male sex, advanced age (≥60 years, presence of hypertension, LDL-C level ≥ 3.33 mg/dL, HDL-C level < 1.03 mg/dL, and TG level ≥ 1.7 mg/dL were independent risk factors for CHD.

  1. Assembly factors of F1FO-ATP synthase across genomes

    Czech Academy of Sciences Publication Activity Database

    Pícková, Andrea; Potocký, Martin; Houštěk, Josef

    2005-01-01

    Roč. 59, č. 3 (2005), s. 393-402 ISSN 0887-3585 R&D Projects: GA MŠk(CZ) 1M0520; GA MZd(CZ) NR7790 Grant - others:GA UK(CZ) 12/2002; GA UK(CZ) 11/2004; EC Framework Programme(XE) LSHM-CT-2004-503116 Institutional research plan: CEZ:AV0Z50110509 Keywords : assembly * ATP synthase * phylogenetic and sequence analysis Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.684, year: 2005

  2. Mutations and modeling of the chromatin remodeler CHD8 define an emerging autism etiology

    Directory of Open Access Journals (Sweden)

    Rebecca A Barnard

    2015-12-01

    Full Text Available Autism Spectrum Disorder (ASD is a common neurodevelopmental disorder with a strong but complex genetic component. Recent family based exome-sequencing strategies have identified recurrent de novo mutations at specific genes, providing strong evidence for ASD risk, but also highlighting the extreme genetic heterogeneity of the disorder. However, disruptions in these genes converge on key molecular pathways early in development. In particular, functional enrichment analyses have found that there is a bias towards genes involved in transcriptional regulation, such as chromatin regulators. Here we review recent genetic, animal model, co-expression network, and functional genomics studies relating to the high confidence ASD risk gene, CHD8. CHD8 a chromatin remodeling factor, may serve as a master regulator of a common ASD etiology. Individuals with a CHD8 mutation show an ASD subtype that includes similar physical characteristics, such as macrocephaly and prolonged GI problems including recurrent constipation. Similarly, animal models of CHD8 disruption exhibit enlarged head circumference and reduced gut motility phenotypes. Systems biology approaches suggest CHD8 and other candidate ASD risk genes are enriched during mid-fetal development, which may represent a critical time window in ASD etiology. Transcription profiles from cell and primary tissue models of early development indicate that CHD8 may also positively regulate other candidate ASD risk genes through both direct and indirect means. However continued study is needed to elucidate the mechanism of regulation as well as identify which CHD8 targets are most relevant to ASD risk. Overall, these initial studies suggest the potential for common ASD etiologies and the development of personalized treatments in the future.

  3. Development of a Coronary Heart Disease Risk Prediction Model for Type 1 Diabetes: The Pittsburgh CHD in Type 1 Diabetes Risk Mode

    NARCIS (Netherlands)

    Zgibor, J.C.; Ruppert, K.; Orchard, T.J.; Soedamah-Muthu, S.S.; Fuller, J.H.; Chaturvedi, N.; Roberts, M.S.

    2010-01-01

    Aim - To create a coronary heart disease (CHD) risk prediction model specific to type 1 diabetes. Methods - Development of the model used data from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC). EDC subjects had type 1 diabetes diagnosed between 1950 and 1980, received their

  4. Olive oil intake and CHD in the European Prospective Investigation into Cancer and Nutrition Spanish cohort.

    Science.gov (United States)

    Buckland, Genevieve; Travier, Noemie; Barricarte, Aurelio; Ardanaz, Eva; Moreno-Iribas, Conchi; Sánchez, María-José; Molina-Montes, Esther; Chirlaque, María Dolores; Huerta, José María; Navarro, Carmen; Redondo, Maria Luisa; Amiano, Pilar; Dorronsoro, Miren; Larrañaga, Nerea; Gonzalez, Carlos A

    2012-12-14

    Olive oil is well known for its cardioprotective properties; however, epidemiological data showing that olive oil consumption reduces incident CHD events are still limited. Therefore, we studied the association between olive oil and CHD in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort study. The analysis included 40 142 participants (38 % male), free of CHD events at baseline, recruited from five EPIC-Spain centres from 1992 to 1996 and followed up until 2004. Baseline dietary and lifestyle information was collected using interview-administered questionnaires. Cox proportional regression models were used to assess the relationship between validated incident CHD events and olive oil intake (energy-adjusted quartiles and each 10 g/d per 8368 kJ (2000 kcal) increment), while adjusting for potential confounders. During a 10·4-year follow-up, 587 (79 % male) CHD events were recorded. Olive oil intake was negatively associated with CHD risk after excluding dietary mis-reporters (hazard ratio (HR) 0·93; 95 % CI 0·87, 1·00 for each 10 g/d per 8368 kJ (2000 kcal) and HR 0·78; 95 % CI 0·59, 1·03 for upper v. lower quartile). The inverse association between olive oil intake (per 10 g/d per 8368 kJ (2000 kcal)) and CHD was more pronounced in never smokers (11 % reduced CHD risk (P = 0·048)), in never/low alcohol drinkers (25 % reduced CHD risk (P culinary use of olive oil within the Mediterranean diet to reduce the CHD burden.

  5. The cardiac phenotype in patients with a CHD7 mutation

    DEFF Research Database (Denmark)

    Corsten-Janssen, Nicole; Kerstjens-Frederikse, Wilhelmina S; du Marchie Sarvaas, Gideon J

    2013-01-01

    Loss-of-function mutations in CHD7 cause Coloboma, Heart Disease, Atresia of Choanae, Retardation of Growth and/or Development, Genital Hypoplasia, and Ear Abnormalities With or Without Deafness (CHARGE) syndrome, a variable combination of multiple congenital malformations including heart defects....... Heart defects are reported in 70% to 92% of patients with a CHD7 mutation, but most studies are small and do not provide a detailed classification of the defects. We present the first, detailed, descriptive study on the cardiac phenotype of 299 patients with a CHD7 mutation and discuss the role of CHD7...

  6. Comparison of risk factors of CHD in the men and women with MI.

    Science.gov (United States)

    Ilali, E; Taraghi, Z

    2010-04-01

    The purpose of this study is comparison of risk factors of MI in hospitalized men and women patients in CCU. The CHD is the most important cause of mortality in the industry countries. Different environmental and race in each location can affect on frequency of risk factors of MI. In this cross sectional study, comparison was done between men and women who have involved in MI. The random sampling method was used Blood sugar, cholesterol and homocystein, LPa, BMI, family history, skin color, smoking and the amount of activity were assessed with variables such as age. The data was collected via questionnaire from September until March 2004-2005. Finally the data were analyzed with using t-test, Chi square and pearson correlation. In this research 169 patients who involved in MI (114 men and 55 women) have participated. The mean of age in the men was 55.4 and in the women was 61.02. All patients had risk factors. In the men, smoking (52.6%) and family history (41.1%) were the most common risk factors of MI. In the women, hyperlipidemia (66.4%), diabetes (62%) and hypertension (58.2%) were the most common risk factors of MI. The mean of BMI in the men was 25.9 +/- 4.25 and in the women was 27.6 +/- 4.71. The mean of LPa in the men was 59.2 +/- 4.21 and in the women was 50.9 +/- 4.25. the mean of homocystein in the men was 10.7 +/- 7.67 and in the women was 8.9 +/- 14.45. Diabetes, hyperlipidemia, hypertension and smoking had significant relationship with age and sex (p homocystein, LPa, job, personality type and mobility didn't have significant relationship with age and sex. In this study the most common risk factors of MI in the men were smoking and positive family history and in the women were known hyperlipidemia and diabetes.

  7. Impact of cigarette smoking on the relationship between body mass index and coronary heart disease: a pooled analysis of 3264 stroke and 2706 CHD events in 378579 individuals in the Asia Pacific region

    Directory of Open Access Journals (Sweden)

    2009-08-01

    Full Text Available Abstract Background Elevated levels of body mass index (BMI and smoking are well established lifestyle risk factors for coronary heart disease (CHD and stroke. If these two risk factors have a synergistic relationship, rigorous lifestyle modification may contribute to greater reduction in cardiovascular burden than previously expected. Methods A pooled analysis of individual participant data from 38 cohorts, involving 378,579 participants. Hazards ratios (HRs and 95% confidence intervals (CIs for BMI by cigarette smoking status were estimated using Cox proportional hazard models. Results During a mean follow-up of 3.8 years, 2706 CHD and 3264 strokes were recorded. There was a log-linear, positive relationship of BMI with CHD and stroke in both smokers and non-smokers with evidence of a synergistic effect of smoking on the association between BMI and CHD only: HRs (95% CIs associated with a 2 kg/m2 higher BMI were 1.13 (1.10 – 1.17 in current smokers and 1.09 (1.06 – 1.11 in non-smokers (p-value for interaction = 0.04. Conclusion Smoking amplifies the positive association between BMI and CHD but not stroke. If confirmed, these results suggest that effective strategies that target smoking cessation and weight loss are likely to have a greater impact than anticipated on reducing the burden of CHD.

  8. Association between previously identified loci affecting telomere length and coronary heart disease (CHD in Han Chinese population

    Directory of Open Access Journals (Sweden)

    Ding H

    2014-05-01

    Full Text Available Hui Ding,1 Fen Yan,1 Lin-Lin Zhou,2 Xiu-Hai Ji,3 Xin-Nan Gu,1 Zhi-Wei Tang,1 Ru-Hua Chen11Department of Pulmonary Medicine, The Affiliated Yixing People's Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, 2Department of Cardiology, Affiliated Cixi Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, 3Department of Oncology, Affiliated Taicang Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu Province, People's Republic of ChinaPurpose: To replicate previously confirmed telomere-length loci in a Chinese Han population with coronary heart disease (CHD, and investigate these loci and the possibility of and age at onset of CHD.Patients and methods: 1514 CHD patients and 2470 normal controls were recruited. Medical data including age, sex, body mass index, lipid profiles, history of hypertension, type 2 diabetes mellitus, and dyslipidemia were collected from all the participants. Seven previously identified single-nucleotide polymorphisms (SNPs related to leucocyte telomere length were genotyped, including rs10936599 in TERC, rs2736100 in TERT, rs7675998 in NAF1, rs9420907 in OBFC1, rs8105767 in ZNF208, rs755017 in RTEL1, and rs11125529 in ACYP2.Results: No significant difference in genotype frequencies from the Hardy–Weinberg equilibrium test was noted for all tested SNPs both in the CHD patients and the normal controls. No polymorphism was observed for rs9420907, and AA genotype was noted in both the CHD patients and the controls. Neither the genotype nor the allele frequencies of rs2736100, rs8105767, rs11125529, and rs2967374 were significantly different between the CHD patients and the normal controls. For rs10936599 and rs755017, statistical difference was found for the allele frequency but not genotype. Distributions of genotype and allele were significantly different between the two groups for rs7675998. The odds ratio for carriers of CHD was 2.127 (95% confidence interval: 1.909–2.370 for the A allele of rs

  9. CHR729 Is a CHD3 Protein That Controls Seedling Development in Rice.

    Science.gov (United States)

    Ma, Xiaoding; Ma, Jian; Zhai, Honghong; Xin, Peiyong; Chu, Jinfang; Qiao, Yongli; Han, Longzhi

    2015-01-01

    CHD3 is one of the chromatin-remodeling factors that contribute to controlling the expression of genes associated with plant development. Loss-of-function mutants display morphological and growth defects. However, the molecular mechanisms underlying CHD3 regulation of plant development remain unclear. In this study, a rice CHD3 protein, CHR729, was identified. The corresponding mutant line (t483) exhibited late seed germination, low germination rate, dwarfism, low tiller number, root growth inhibition, adaxial albino leaves, and short and narrow leaves. CHR729 encoded a nuclear protein and was expressed in almost all organs. RNA-sequencing analysis showed that several plant hormone-related genes were up- or down-regulated in t483 compared to wild type. In particular, expression of the gibberellin synthetase gibberellin 20 oxidase 4 gene was elevated in the mutant. Endogenous gibberellin assays demonstrated that the content of bioactive GA3 was reduced in t483 compared to wild type. Moreover, the seedling dwarfism, late seed germination, and short root length phenotypes of t483 were partially rescued by treatment with exogenous GA3. These results suggest that the rice CHD3 protein CHR729 plays an important role in many aspects of seedling development and controls this development via the gibberellin pathway.

  10. CHR729 Is a CHD3 Protein That Controls Seedling Development in Rice.

    Directory of Open Access Journals (Sweden)

    Xiaoding Ma

    Full Text Available CHD3 is one of the chromatin-remodeling factors that contribute to controlling the expression of genes associated with plant development. Loss-of-function mutants display morphological and growth defects. However, the molecular mechanisms underlying CHD3 regulation of plant development remain unclear. In this study, a rice CHD3 protein, CHR729, was identified. The corresponding mutant line (t483 exhibited late seed germination, low germination rate, dwarfism, low tiller number, root growth inhibition, adaxial albino leaves, and short and narrow leaves. CHR729 encoded a nuclear protein and was expressed in almost all organs. RNA-sequencing analysis showed that several plant hormone-related genes were up- or down-regulated in t483 compared to wild type. In particular, expression of the gibberellin synthetase gibberellin 20 oxidase 4 gene was elevated in the mutant. Endogenous gibberellin assays demonstrated that the content of bioactive GA3 was reduced in t483 compared to wild type. Moreover, the seedling dwarfism, late seed germination, and short root length phenotypes of t483 were partially rescued by treatment with exogenous GA3. These results suggest that the rice CHD3 protein CHR729 plays an important role in many aspects of seedling development and controls this development via the gibberellin pathway.

  11. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1

    DEFF Research Database (Denmark)

    Carvill, Gemma L; Heavin, Sinéad B; Yendle, Simone C

    2013-01-01

    Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify...... CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies...

  12. Covalent Modifications of Histone H3K9 Promote Binding of CHD3

    Directory of Open Access Journals (Sweden)

    Adam H. Tencer

    2017-10-01

    Full Text Available Chromatin remodeling is required for genome function and is facilitated by ATP-dependent complexes, such as nucleosome remodeling and deacetylase (NuRD. Among its core components is the chromodomain helicase DNA binding protein 3 (CHD3 whose functional significance is not well established. Here, we show that CHD3 co-localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched promoters of the NuRD target genes. The tandem PHD fingers of CHD3 bind histone H3 tails and posttranslational modifications that increase hydrophobicity of H3K9—methylation or acetylation (H3K9me3 or H3K9ac—enhance this interaction. Binding of CHD3 PHDs promotes H3K9Cme3-nucleosome unwrapping in vitro and perturbs the pericentric heterochromatin structure in vivo. Methylation or acetylation of H3K9 uniquely alleviates the intra-nucleosomal interaction of histone H3 tails, increasing H3K9 accessibility. Collectively, our data suggest that the targeting of covalently modified H3K9 by CHD3 might be essential in diverse functions of NuRD.

  13. Mutation update on the CHD7 gene involved in CHARGE syndrome

    DEFF Research Database (Denmark)

    Janssen, Nicole; Bergman, Jorieke E H; Swertz, Morris A

    2012-01-01

    , for example, the central nervous system, eye, ear, nose, and mediastinal organs, are variably involved. In this article, we review all the currently described CHD7 variants, including 183 new pathogenic mutations found by our laboratories. In total, we compiled 528 different pathogenic CHD7 alterations from......, predominantly arginine to stop codon mutations. We built a locus-specific database listing all the variants that is easily accessible at www.CHD7.org. In addition, we summarize the latest data on CHD7 expression studies, animal models, and functional studies, and we discuss the latest clinical insights...

  14. Risk factors predisposing to congenital heart defects

    International Nuclear Information System (INIS)

    Ul Haq, Faheem; Jalil, Fatima; Hashmi, Saman; Jumani, Maliha Iqbal; Imdad, Aamer; Jabeen, Mehnaz; Hashmi, Javad Tauseef; Irfan, Furqan Bin; Imran, Muhammad; Atiq, Mehnaz

    2011-01-01

    Congenital heart disease (CHD) is associated with multiple risk factors, consanguinity may be one such significant factor. The role of consanguinity in the etiology of CHD is supported by inbreeding studies, which demonstrate an autosomal recessive pattern of inheritance of some congenital heart defects. This study was done to find out the risk factors for CHD. A case-control study was done on pediatric patients at a tertiary care hospital, Aga Khan University Hospital, located in Karachi, Pakistan. A total of 500 patients, 250 cases and 250 controls were included in the study. Amongst the 250 cases (i.e. those diagnosed with CHD), 122 patients (48.8%) were born of consanguineous marriages while in the controls (i.e. non-CHD) only 72 patients (28.9%) showed a consanguinity amongst parents. On multivariate analysis, consanguinity emerged as an independent risk factor for CHD; adjusted odds ratio 2.59 (95% C. I. 1.73 - 3.87). Other risk factors included low birth weight, maternal co-morbidities, family history of CHD and first born child. On the other hand, medications used by the mother during the index pregnancy, maternal age and gender of the child did not significantly increase the risk of developing CHD. Analyses of our results show that parental consanguinity, family history of CHD, maternal co-morbidities, first born child and low birth weight are independent risk factors for CHD

  15. ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state.

    Science.gov (United States)

    Chudnovsky, Yakov; Kim, Dohoon; Zheng, Siyuan; Whyte, Warren A; Bansal, Mukesh; Bray, Mark-Anthony; Gopal, Shuba; Theisen, Matthew A; Bilodeau, Steve; Thiru, Prathapan; Muffat, Julien; Yilmaz, Omer H; Mitalipova, Maya; Woolard, Kevin; Lee, Jeongwu; Nishimura, Riko; Sakata, Nobuo; Fine, Howard A; Carpenter, Anne E; Silver, Serena J; Verhaak, Roel G W; Califano, Andrea; Young, Richard A; Ligon, Keith L; Mellinghoff, Ingo K; Root, David E; Sabatini, David M; Hahn, William C; Chheda, Milan G

    2014-01-30

    Glioblastoma (GBM) harbors subpopulations of therapy-resistant tumor-initiating cells (TICs) that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC maintenance and identified ZFHX4, a 397 kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its suppression increases glioma-free survival in intracranial xenografts. ZFHX4 interacts with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD) complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and control similar gene expression programs. Using expression data derived from GBM patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression perturbations, which defines ZFHX4 as a master regulator of CHD4. These observations define ZFHX4 as a regulatory factor that links the chromatin-remodeling NuRD complex and the GBM TIC state. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor initiating cell state

    Science.gov (United States)

    Chudnovsky, Yakov; Kim, Dohoon; Zheng, Siyuan; Whyte, Warren A.; Bansal, Mukesh; Bray, Mark-Anthony; Gopal, Shuba; Theisen, Matthew A.; Bilodeau, Steve; Thiru, Prathapan; Muffat, Julien; Yilmaz, Omer H.; Mitalipova, Maya; Woolard, Kevin; Lee, Jeongwu; Nishimura, Riko; Sakata, Nobuo; Fine, Howard A.; Carpenter, Anne E.; Silver, Serena J.; Verhaak, Roel G. W.; Califano, Andrea; Young, Richard A.; Ligon, Keith L.; Mellinghoff, Ingo K.; Root, David E.; Sabatini, David M.; Hahn, William C.; Chheda, Milan G.

    2014-01-01

    Summary Glioblastomas (GBM) harbor subpopulations of therapy-resistant tumor initiating cells (TICs) that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC maintenance and identified ZFHX4, a 397-kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its suppression increases glioma-free survival in intracranial xenografts. ZFHX4 interacts with CHD4, a core member of the NuRD (nucleosome remodeling and deacetylase) complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and control similar gene expression programs. Using expression data derived from GBM patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression perturbations, which defines ZFHX4 as a master regulator of CHD4. These observations define ZFHX4 as a regulatory factor that links the chromatin remodeling NuRD complex and the GBM TIC state. PMID:24440720

  17. ZFHX4 Interacts with the NuRD Core Member CHD4 and Regulates the Glioblastoma Tumor-Initiating Cell State

    Directory of Open Access Journals (Sweden)

    Yakov Chudnovsky

    2014-01-01

    Full Text Available Glioblastoma (GBM harbors subpopulations of therapy-resistant tumor-initiating cells (TICs that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC maintenance and identified ZFHX4, a 397 kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its suppression increases glioma-free survival in intracranial xenografts. ZFHX4 interacts with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and control similar gene expression programs. Using expression data derived from GBM patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression perturbations, which defines ZFHX4 as a master regulator of CHD4. These observations define ZFHX4 as a regulatory factor that links the chromatin-remodeling NuRD complex and the GBM TIC state.

  18. CHD chromatin remodelers and the transcription cycle

    Science.gov (United States)

    Murawska, Magdalena

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by “opening” or “closing” chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but also are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts. PMID:22223048

  19. Midlife moderation-quantified healthy diet and 40-year mortality risk from CHD: the prospective National Heart, Lung, and Blood Institute Twin Study.

    Science.gov (United States)

    Dai, Jun; Krasnow, Ruth E; Reed, Terry

    2016-07-01

    It is unknown whether influences of midlife whole diet on the long-term CHD mortality risk are independent of genetic and common environmental factors or familial predisposition. We addressed this question prospectively using data from the National Heart, Lung, and Blood Institute Twin Study. We included 910 male twins who were middle-aged and had usual diet assessed with nutritionist-administered, cross-checked dietary history interview at baseline (1969-1973). Moderation-quantified healthy diet (MQHD), a dietary pattern, was created to evaluate a whole diet. Primary outcome was time-to-CHD death. Hazard ratios (HR) were estimated using frailty survival model. Known CHD risk factors were controlled. During the follow-up of 40 years through 31 December 2009, 113 CHD deaths, 198 total cardiovascular deaths and 610 all-cause deaths occurred. In the entire cohort, the multivariable-adjusted HR for the overall association (equivalent to a general population association) was 0·76 (95 % CI 0·66, 0·88) per 10-unit increment in the MQHD score for CHD, and the multivariable-adjusted HR for a twin with a MQHD score ten units higher than his co-twin brother was 0·79 (95 % CI 0·64, 0·96, P=0·02) for CHD independent of familial predisposition. Similar results were found for a slightly more food-specified alternative moderation-quantified healthy diet (aMQHD). The between-pair association (reflecting familial influence) was significant for CHD for both MQHD and aMQHD. It is concluded that associations of MQHD and aMQHD with a lower long-term CHD mortality risk are both nutritionally and familially affected, supporting their use for dietary planning to prevent CHD mortality.

  20. Midlife moderation-quantified healthy diet and 40-year mortality risk from CHD: the prospective National Heart, Lung, and Blood Institute Twin Study

    Science.gov (United States)

    Dai, Jun; Krasnow, Ruth E.; Reed, Terry

    2018-01-01

    It is unknown whether influences of midlife whole diet on the long-term CHD mortality risk are independent of genetic and common environmental factors or familial predisposition. We addressed this question prospectively using data from the National Heart, Lung, and Blood Institute Twin Study. We included 910 male twins who were middle-aged and had usual diet assessed with nutritionist-administered, crosschecked dietary history interview at baseline (1969–1973). Moderation-quantified healthy diet (MQHD), a dietary pattern, was created to evaluate a whole diet. Primary outcome was time-to-CHD death. Hazard ratios (HR) were estimated using frailty survival model. Known CHD risk factors were controlled. During the follow-up of 40 years through 31 December 2009, 113 CHD deaths, 198 total cardiovascular deaths and 610 all-cause deaths occurred. In the entire cohort, the multivariable-adjusted HR for the overall association (equivalent to a general population association) was 0·76 (95 % CI 0·66, 0·88) per 10-unit increment in the MQHD score for CHD, and the multivariable-adjusted HR for a twin with a MQHD score ten units higher than his co-twin brother was 0·79 (95 % CI 0·64, 0·96, P = 0·02) for CHD independent of familial predisposition. Similar results were found for a slightly more food-specified alternative moderation-quantified healthy diet (aMQHD). The between-pair association (reflecting familial influence) was significant for CHD for both MQHD and aMQHD. It is concluded that associations of MQHD and aMQHD with a lower long-term CHD mortality risk are both nutritionally and familially affected, supporting their use for dietary planning to prevent CHD mortality. PMID:27188259

  1. Identification and validation of quantitative trait loci (QTL for canine hip dysplasia (CHD in German Shepherd Dogs.

    Directory of Open Access Journals (Sweden)

    Lena Fels

    Full Text Available Canine hip dysplasia (CHD is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we genotyped 96 German Shepherd Dogs affected by mild, moderate and severe CHD and 96 breed, sex, age and birth year matched controls using the Affymetrix canine high density SNP chip. A mixed linear model analysis identified five SNPs associated with CHD scores on dog chromosomes (CFA 19, 24, 26 and 34. These five SNPs were validated in a by sex, age, birth year and coancestry stratified sample of 843 German Shepherd Dogs including 277 unaffected dogs and 566 CHD-affected dogs. Mean coancestry coefficients among and within cases and controls were <0.1%. Genotype effects of these SNPs explained 20-32% of the phenotypic variance of CHD in German Shepherd Dogs employed for validation. Genome-wide significance in the validation data set could be shown for each one CHD-associated SNP on CFA24, 26 and 34. These SNPs are located within or in close proximity of genes involved in bone formation and related through a joint network. The present study validated positional candidate genes within two previously known quantitative trait loci (QTL and a novel QTL for CHD in German Shepherd Dogs.

  2. Single nucleotide polymorphism rs3774261 in the AdipoQ gene is associated with the risk of coronary heart disease (CHD) in Northeast Han Chinese population: a case-control study.

    Science.gov (United States)

    Kanu, Joseph Sam; Gu, Yulu; Zhi, Sun; Yu, Mingxi; Lu, Yuping; Cong, Yetong; Liu, Yunkai; Li, Yong; Yu, Yaqin; Cheng, Yi; Liu, Yawen

    2016-01-12

    Coronary Heart Disease (CHD) is one of the leading causes of death in the world with a projected global 82 million DALYs by 2020. Genetic and environmental factors contribute to CHD development. Here, the authors investigate the association between CHD risk and three Single Nucleotide Polymorphisms (SNPs) in the AdipoQ gene (rs3774261, rs1063537 and rs2082940); and the interaction of this association with environmental factors, in Northeast Han Chinese population. Using a case-control study design, 1514 participants (754 cases and 760 controls) were investigated. Three variants in the AdipoQ gene (rs3774261, rs1063537 and rs2082940) were selected and genotyped. The online SNPstats program and SPSS 21.0 software were used for data analyses. The authors found that the rs3774261G allele is associated with the risk of CHD but that the rs2082940T allele protects against CHD. No significant association was found between rs1063537 and CHD risk. The study also found significant interactions between triglyceride levels and the SNPs studied (P Variations in AdipoQ gene can protect against CHD (as with rs2082940T) or associated with CHD risk (as with rs3774261G) in Northeast Han Chinese - findings that will help shed light on the reported conflicting roles of AdipoQ in cardiovascular diseases. Serum triglycerides levels also interact in the AdipoQ - CHD association, thus further highlighting the roles environmental factors play in the genetic aspect of diseases.

  3. hs-CRP is strongly associated with coronary heart disease (CHD): A data mining approach using decision tree algorithm.

    Science.gov (United States)

    Tayefi, Maryam; Tajfard, Mohammad; Saffar, Sara; Hanachi, Parichehr; Amirabadizadeh, Ali Reza; Esmaeily, Habibollah; Taghipour, Ali; Ferns, Gordon A; Moohebati, Mohsen; Ghayour-Mobarhan, Majid

    2017-04-01

    Coronary heart disease (CHD) is an important public health problem globally. Algorithms incorporating the assessment of clinical biomarkers together with several established traditional risk factors can help clinicians to predict CHD and support clinical decision making with respect to interventions. Decision tree (DT) is a data mining model for extracting hidden knowledge from large databases. We aimed to establish a predictive model for coronary heart disease using a decision tree algorithm. Here we used a dataset of 2346 individuals including 1159 healthy participants and 1187 participant who had undergone coronary angiography (405 participants with negative angiography and 782 participants with positive angiography). We entered 10 variables of a total 12 variables into the DT algorithm (including age, sex, FBG, TG, hs-CRP, TC, HDL, LDL, SBP and DBP). Our model could identify the associated risk factors of CHD with sensitivity, specificity, accuracy of 96%, 87%, 94% and respectively. Serum hs-CRP levels was at top of the tree in our model, following by FBG, gender and age. Our model appears to be an accurate, specific and sensitive model for identifying the presence of CHD, but will require validation in prospective studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Assembly factors for the membrane arm of human complex I.

    Science.gov (United States)

    Andrews, Byron; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2013-11-19

    Mitochondrial respiratory complex I is a product of both the nuclear and mitochondrial genomes. The integration of seven subunits encoded in mitochondrial DNA into the inner membrane, their association with 14 nuclear-encoded membrane subunits, the construction of the extrinsic arm from 23 additional nuclear-encoded proteins, iron-sulfur clusters, and flavin mononucleotide cofactor require the participation of assembly factors. Some are intrinsic to the complex, whereas others participate transiently. The suppression of the expression of the NDUFA11 subunit of complex I disrupted the assembly of the complex, and subcomplexes with masses of 550 and 815 kDa accumulated. Eight of the known extrinsic assembly factors plus a hydrophobic protein, C3orf1, were associated with the subcomplexes. The characteristics of C3orf1, of another assembly factor, TMEM126B, and of NDUFA11 suggest that they all participate in constructing the membrane arm of complex I.

  5. Characteristic Comparison of CHD for Active Smoker by Smoking Characteristic

    OpenAIRE

    Diastutik, Desy

    2016-01-01

    Coronary Heart Disease (CHD) is a type of cardiovascular disease that has highest level of morbidity and mortality among non communicable disease group. One of the factor that contribute for coronary heart disease is smoking characteristic. The research was aimed to analyze characteristic comparison of coronary heart disease for active smoker by smoking characteristic. The research was observational study using cross sectional design. Thirty eight active smokers were involved as research samp...

  6. Control of trichome branching by Chromatin Assembly Factor-1

    Directory of Open Access Journals (Sweden)

    Hennig Lars

    2008-05-01

    Full Text Available Abstract Background Chromatin dynamics and stability are both required to control normal development of multicellular organisms. Chromatin assembly factor CAF-1 is a histone chaperone that facilitates chromatin formation and the maintenance of specific chromatin states. In plants and animals CAF-1 is essential for normal development, but it is poorly understood which developmental pathways require CAF-1 function. Results Mutations in all three CAF-1 subunits affect Arabidopsis trichome morphology and lack of CAF-1 function results in formation of trichomes with supernumerary branches. This phenotype can be partially alleviated by external sucrose. In contrast, other aspects of the CAF-1 mutant phenotype, such as defective meristem function and organ formation, are aggravated by external sucrose. Double mutant analyses revealed epistatic interactions between CAF-1 mutants and stichel, but non-epistatic interactions between CAF-1 mutants and glabra3 and kaktus. In addition, mutations in CAF-1 could partly suppress the strong overbranching and polyploidization phenotype of kaktus mutants. Conclusion CAF-1 is required for cell differentiation and regulates trichome development together with STICHEL in an endoreduplication-independent pathway. This function of CAF-1 can be partially substituted by application of exogenous sucrose. Finally, CAF-1 is also needed for the high degree of endoreduplication in kaktus mutants and thus for the realization of kaktus' extreme overbranching phenotype.

  7. Is having a job a protective factor? Employment status and state of medical care as subjectively perceived by adults with CHD in Germany.

    Science.gov (United States)

    Helm, Paul C; Sticker, Elisabeth J; Keuchen, Roland; Koerten, Marc-André; Diller, Gerhard-Paul; Tutarel, Oktay; Bauer, Ulrike M M

    2017-08-01

    Most patients born with CHD nowadays reach adulthood, and thus quality of life, life situation, and state of medical care aspects are gaining importance in the current era. The present study aimed to investigate whether patients' assessment depends on their means of occupation. The findings are expected to be helpful in optimising care and for developing individual treatment plans. The present study was based on an online survey conducted in cooperation with patient organisations. Participants were recruited from the database of the German National Register for Congenital Heart Defects. In total, 1828 individuals (777 males, 1051 females) took part. Participants were asked to rate aspects such their state of health on a six-tier scale (1=worst specification). Response behaviour was measured against the background of occupational details. Training for or pursuing a profession was found to be significantly associated with participants' rating of five of the six examined aspects (pemployment status. To work out such an optimal and individual treatment plan for each adult CHD patient, an objective tool to measure patients' actual CHD-specific knowledge precluding socially accepted response bias would be very useful.

  8. Prevalence of coronary heart disease risk factors and screening for high cholesterol levels among young adults, United States, 1999-2006.

    Science.gov (United States)

    Kuklina, Elena V; Yoon, Paula W; Keenan, Nora L

    2010-01-01

    Previous studies have reported low rates of screening for high cholesterol levels among young adults in the United States. Although recommendations for screening young adults without risk factors for coronary heart disease (CHD) differ, all guidelines recommend screening adults with CHD, CHD equivalents, or 1 or more CHD risk factors. This study examined national prevalence of CHD risk factors and compliance with the cholesterol screening guidelines among young adults. National estimates were obtained using results for 2,587 young adults (men aged 20 to 35 years; women aged 20 to 45 years) from the 1999-2006 National Health and Nutrition Examination Surveys. We defined high low-density lipoprotein cholesterol (LDL-C) as levels higher than the goal specific for each CHD risk category outlined in the National Cholesterol Education Program Adult Treatment Panel III guidelines. About 59% of young adults had CHD or CHD equivalents, or 1 or more of the following CHD risk factors: family history of early CHD, smoking, hypertension, or obesity. In our study, the overall screening rate in this population was less than 50%. Moreover, no significant difference in screening rates between young adults with no risk factors and their counterparts with 1 or more risk factors was found even after adjustment for sociodemographic and health care factors. Approximately 65% of young adults with CHD or CHD equivalents, 26% of young adults with 2 or more risk factors, 12% of young adults with 1 risk factor, and 7% with no risk factor had a high level of LDL-C. CHD risk factors are common in young adults but do not appear to alter screening rates. Improvement of risk assessment and management for cardiovascular disease among young adults is warranted.

  9. Assessment of congenital heart disease (CHD): Is there a role for fetal magnetic resonance imaging (MRI)?

    Energy Technology Data Exchange (ETDEWEB)

    Manganaro, L. [Department of Radiological Sciences, UMBERTO I Hospital, SAPIENZA University of Rome, Viale del Policlinico 155, 00161 Rome (Italy); Savelli, S. [Department of Radiological Sciences, UMBERTO I Hospital, SAPIENZA University of Rome, Viale del Policlinico 155, 00161 Rome (Italy)], E-mail: sarasavelli@hotmail.it; Di Maurizio, M.; Perrone, A.; Francioso, A.; La Barbera, L.; Totaro, P.; Fierro, F.; Tomei, A.; Coratella, F. [Department of Radiological Sciences, UMBERTO I Hospital, SAPIENZA University of Rome, Viale del Policlinico 155, 00161 Rome (Italy); Giancotti, A. [Department of Gynaecological Sciences, UMBERTO I Hospital, SAPIENZA University of Rome, Viale del Policlinico 155, 00161 Rome (Italy); Ballesio, L. [Department of Radiological Sciences, UMBERTO I Hospital, SAPIENZA University of Rome, Viale del Policlinico 155, 00161 Rome (Italy); Ventriglia, F. [Department of Pediatric Cardiology, UMBERTO I Hospital, SAPIENZA University of Rome, Viale del Policlinico 155, 00161 Rome (Italy)

    2009-10-15

    Purpose: To review our experience with fetal magnetic resonance imaging (MRI) to evaluate congenital heart disease (CHD). Methods: We performed fetal MRI in 32 fetuses with an echocardiographically assessed CHD. Both direct and indirect signs of CHD were investigated. Direct signs considered were: morpho-volumetric abnormalities of the heart; malrotations; ventricular and atrial septal defects; anomalies of the origin, size and course of the great arteries. Indirect signs considered were: difficulty to recognize a 'normal' anatomical structures in the reference projections; increase of the vascular size before a stenosis; hypertrophy of the papillary muscles; cardiomegaly and pericardial effusion. All MRI findings were compared with postnatal or autoptic findings. Results: MRI allowed the CHD to be visualised by direct signs in 17 fetuses, indirect signs in 5 and both direct and indirect signs in 9 fetuses, excluding the prenatal echocardiographic suspect of hypoplastic left heart syndrome in 1 fetus. Postnatal echocardiograms or autoptic findings confirmed a normal heart in 1 fetus and CHD in 31 fetuses including a single cardiac anomaly or syndrome in 19 fetuses, 2 associated cardiac abnormalities in 11 and 3 cardiac anomalies in 1 fetus. However, in 2 fetuses MRI detected a ventricular septal defect successively disclosed by gold standard. Conclusions: MRI is a promising method for further assessment of the cardiovascular pathologies diagnosed by echocardiography, and may be a valuable tool in assessing associated extracardiac anomalies.

  10. Adult CHD patients under clinical follow-up have a similar quality of life to the general population in Malta.

    Science.gov (United States)

    Caruana, Maryanne; Grech, Victor

    2017-08-01

    The improved survival of patients born with CHD has led to increasing interest in research on quality of life of adult survivors. We report the findings of the first study in Malta carried out to investigate quality of life in adults with CHD under follow-up. A self-reporting questionnaire modelled on the basis of the European Health Interview Survey 2008, including questions on mental health and vitality, was administered to consecutive adult CHD outpatients, aged 16 years and over, between May, 2013 and May, 2014. Foreigners and patients with learning difficulties or cognitive impairment were excluded. Quality-of-life data were compared with that from 371 age- and sex-matched 2008 survey responders - general population cohort. The impact of congenital lesion complexity, hospitalisation in the preceding 12 months, arrhythmias, co-morbidities, and cardiac medication use on quality of life of the CHD cohort was also investigated. There were a total of 120 patient responders (63 males; mean age 30.53, SD 12.77 years). Overall, there were no significant differences in mental health and vitality between patient and general population cohorts, although older patients had better mental health scores compared with age-matched controls. Within the adult CHD cohort, hospitalisation in the preceding 12 months was the only factor associated with a poorer quality of life. Overall, CHD has no negative impact on mental health and vitality in Maltese adult patients under follow-up. Patients needing frequent hospitalisations might warrant closer attention by clinical psychologists.

  11. Congenital Heart Disease (CHD) and Environmental Physical Activity, Kaunas, 1995-2005.

    Science.gov (United States)

    Stoupel, E.; Dulskiene, V.; Kuciene, R.; Abramson, E.; Israelevich, P.; Sulkes, J.

    2009-12-01

    Recent studies described a number of fetal development sides related to the environmental physical activity. The aim of this study was to check the possible links between congenital heart disease (CHD) born in a non-selected medical network and indices of environmental physical activity. Children born with CHD in Kaunas, Lithuania, in years 1995-2005 were analyzed at the end of the first year of life (including also those died after birth from this condition). Monthly distribution of CHD (total - 371, both gender (178 boys and 193 girls), 41435 births) were compared with parameters of solar (SA), geomagnetic (GMA) and cosmic ray (CRA) activity, as well as the year, at the month of birth, 9 months before and at year of birth and one year before. CRA was represented by neutron activity on the Earth's surface. Heliogeophysical data were obtained from space research centers in the USA, Russia and Finland. There was found a significant correlation between yearly number of births (r = - 0.9, p = 0.00012). Monthly number of CHD was correlated with SA and CRA often highly at the beginning of pregnancy both in monthly and yearly (r = - 0.7, p = 0.025 for SA, r = 0.8, p = 0.005 for CRA) comparison. For boys the correlation was stronger, but also it was significant for girls. GMA has not shown significant effects. It is concluded that the number of yearly and monthly CHD is connected with SA and CRA in pregnancy. Boys show high levels in these correlations. The mechanism of the cosmophysical effects on human development and temporal distribution of CHD deserve special studies.

  12. Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

    Science.gov (United States)

    Al-Wakeel, Nadya; O h-Ici, Darach; Schmitt, Katharina R; Messroghli, Daniel R; Riesenkampff, Eugénie; Berger, Felix; Kuehne, Titus; Peters, Bjoern

    2016-02-01

    In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

  13. Do pre-employment influences explain the association between psychosocial factors at work and coronary heart disease? The Whitehall II study.

    Science.gov (United States)

    Hintsa, Taina; Shipley, Martin J; Gimeno, David; Elovainio, Marko; Chandola, Tarani; Jokela, Markus; Keltikangas-Järvinen, Liisa; Vahtera, Jussi; Marmot, Michael G; Kivimäki, Mika

    2010-05-01

    To examine whether the association between psychosocial factors at work and incident coronary heart disease (CHD) is explained by pre-employment factors, such as family history of CHD, education, paternal education and social class, number of siblings and height. A prospective cohort study of 6435 British men aged 35-55 years at phase 1 (1985-1988) and free from prevalent CHD at phase 2 (1989-1990) was conducted. Psychosocial factors at work were assessed at phases 1 and 2 and mean scores across the two phases were used to determine long-term exposure. Selected pre-employment factors were assessed at phase 1. Follow-up for coronary death, first non-fatal myocardial infarction or definite angina between phase 2 and 1999 was based on clinical records (250 events, follow-up 8.7 years). The selected pre-employment factors were associated with risk for CHD: HRs (95% CI) were 1.33 (1.03 to 1.73) for family history of CHD, 1.18 (1.05 to 1.32) for each quartile decrease in height and 1.16 (0.99 to 1.35) for each category increase in number of siblings. Psychosocial work factors also predicted CHD: 1.72 (1.08 to 2.74) for low job control and 1.72 (1.10 to 2.67) for low organisational justice. Adjustment for pre-employment factors changed these associations by 4.1% or less. In this occupational cohort of British men, the association between psychosocial factors at work and CHD was largely independent of family history of CHD, education, paternal educational attainment and social class, number of siblings and height.

  14. Genetics Home Reference: CHD2 myoclonic encephalopathy

    Science.gov (United States)

    ... Møller RS, Linnankivi T, Dimova P, Striano P, Zara F, Marini C, Guerrini R, Depienne C, Baulac S, ... M, Accorsi P, Cappelletti S, Claps DJ, Vigevano F, Zara F, Specchio N. CHD2 mutations are a rare ...

  15. Prevalence of CHD-related metabolic comorbidity of diabetes mellitus in Northern Chinese adults: the REACTION study.

    Science.gov (United States)

    Gao, Nannan; Yuan, Zhongshang; Tang, Xulei; Zhou, Xiaoming; Zhao, Meng; Liu, Lu; Ji, Jiadong; Xue, Fuzhong; Ning, Guang; Zhao, Jiajun; Zhang, Haiqing; Gao, Ling

    2016-03-01

    To gain more precise understanding of the epidemiology of comorbidities with diabetes and to clarify the correlation with coronary heart disease (CHD) in Chinese population. Based on REACTION study, 18,696 participants aged over 40 years were included in the cross-sectional analysis. Prevalence and patterns of comorbid diseases were demonstrated, and their impact on CHD was also analyzed by logistic regression. Diabetes was more prevalent in patients with older age and lower education level, with relatively low awareness (36.3%), treatment (27.9%) and control (34.7%) rate. The proportion of diabetics with additional condition was 88.8%; 53.2% had more than two comorbidities. Compared with patients with comorbidities, diabetics only had the highest controlled HbA1c rate (37.9%). Dyslipidemia (71.97%) was the most common comorbidity, followed by hypertension (58.19%), and hypothyroidism (21.24%). A strong gradient existed between the number of comorbidities and CHD versus "diabetes only" group; the odds ratio was 1.38, 2.48 and 3.01 for diabetics with one, two and three additional diseases, respectively. Low glycemic control and high prevalence of diabetes comorbidities are common in China, which increases the risk of CHD. Full-scale and individualized guidelines for diabetics should be planned. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Infective endocarditis: call for education of adults with CHD: review of the evidence.

    Science.gov (United States)

    Hays, Laura H

    2016-03-01

    Advanced surgical repair procedures have resulted in the increased survival rate to adulthood of patients with CHD. The resulting new chronic conditions population is greater than one million in the United States of America and >1.2 million in Europe. This review describes the risks and effects of infective endocarditis - a systemic infectious process with high morbidity and mortality - on this population and examines the evidence to determine whether greater patient education on recognition of symptoms and preventative measures is warranted. The literature search included the terms "infective endocarditis" and "adult congenital heart disease". Search refinement, the addition of articles cited by included articles, as well as addition of supporting articles, resulted in utilisation of 24 articles. Infective endocarditis, defined by the modified Duke Criteria, occurs at a significantly higher rate in the CHD population due to congenitally or surgically altered cardiac anatomies and placement of prosthetic valves. This literature review returned no studies in the past five years assessing knowledge of the definition, recognition of symptoms, and preventative measures of infective endocarditis in the adult CHD population. Existing data are more than 15 years old and show significant knowledge deficits. Studies have consistently shown the need for improved CHD patient knowledge with regard to infective endocarditis, and there is no recent evidence that these knowledge deficits have decreased. It is important to address and decrease knowledge deficits in order to improve patient outcomes and decrease healthcare utilisation and costs.

  17. The association of 83 plasma proteins with CHD mortality, BMI, HDL-, and total-cholesterol in men: applying multivariate statistics to identify proteins with prognostic value and biological relevance.

    Science.gov (United States)

    Heidema, A Geert; Thissen, Uwe; Boer, Jolanda M A; Bouwman, Freek G; Feskens, Edith J M; Mariman, Edwin C M

    2009-06-01

    In this study, we applied the multivariate statistical tool Partial Least Squares (PLS) to analyze the relative importance of 83 plasma proteins in relation to coronary heart disease (CHD) mortality and the intermediate end points body mass index, HDL-cholesterol and total cholesterol. From a Dutch monitoring project for cardiovascular disease risk factors, men who died of CHD between initial participation (1987-1991) and end of follow-up (January 1, 2000) (N = 44) and matched controls (N = 44) were selected. Baseline plasma concentrations of proteins were measured by a multiplex immunoassay. With the use of PLS, we identified 15 proteins with prognostic value for CHD mortality and sets of proteins associated with the intermediate end points. Subsequently, sets of proteins and intermediate end points were analyzed together by Principal Components Analysis, indicating that proteins involved in inflammation explained most of the variance, followed by proteins involved in metabolism and proteins associated with total-C. This study is one of the first in which the association of a large number of plasma proteins with CHD mortality and intermediate end points is investigated by applying multivariate statistics, providing insight in the relationships among proteins, intermediate end points and CHD mortality, and a set of proteins with prognostic value.

  18. A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome.

    Science.gov (United States)

    Kohmoto, Tomohiro; Shono, Miki; Naruto, Takuya; Watanabe, Miki; Suga, Ken-Ichi; Nakagawa, Ryuji; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

    2016-01-01

    CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)].

  19. CT coronary angiography vs. invasive coronary angiography in CHD

    Directory of Open Access Journals (Sweden)

    Anja Hagen

    2012-04-01

    Full Text Available Scientific background: Various diagnostic tests including conventional invasive coronary angiography and non-invasive computed tomography (CT coronary angiography are used in the diagnosis of coronary heart disease (CHD. Research questions: The present report aims to evaluate the clinical efficacy, diagnostic accuracy, prognostic value cost-effectiveness as well as the ethical, social and legal implications of CT coronary angiography versus invasive coronary angiography in the diagnosis of CHD. Methods: A systematic literature search was conducted in electronic data bases (MEDLINE, EMBASE etc. in October 2010 and was completed with a manual search. The literature search was restricted to articles published from 2006 in German or English. Two independent reviewers were involved in the selection of the relevant publications. The medical evaluation was based on systematic reviews of diagnostic studies with invasive coronary angiography as the reference standard and on diagnostic studies with intracoronary pressure measurement as the reference standard. Study results were combined in a meta-analysis with 95 % confidence intervals (CI. Additionally, data on radiation doses from current non-systematic reviews were taken into account. A health economic evaluation was performed by modelling from the social perspective with clinical assumptions derived from the meta-analysis and economic assumptions derived from contemporary German sources. Data on special indications (bypass or in-stent-restenosis were not included in the evaluation. Only data obtained using CT scanners with at least 64 slices were considered. Results: No studies were found regarding the clinical efficacy or prognostic value of CT coronary angiography versus conventional invasive coronary angiography in the diagnosis of CHD. Overall, 15 systematic reviews with data from 44 diagnostic studies using invasive coronary angiography as the reference standard (identification of obstructive

  20. The Influencing Factor Analysis on the Performance Evaluation of Assembly Line Balancing Problem Level 1 (SALBP-1) Based on ANOVA Method

    Science.gov (United States)

    Chen, Jie; Hu, Jiangnan

    2017-06-01

    Industry 4.0 and lean production has become the focus of manufacturing. A current issue is to analyse the performance of the assembly line balancing. This study focus on distinguishing the factors influencing the assembly line balancing. The one-way ANOVA method is applied to explore the significant degree of distinguished factors. And regression model is built to find key points. The maximal task time (tmax ), the quantity of tasks (n), and degree of convergence of precedence graph (conv) are critical for the performance of assembly line balancing. The conclusion will do a favor to the lean production in the manufacturing.

  1. Communication: Reactivity borrowing in the mode selective chemistry of H + CHD3 → H2 + CD3

    Science.gov (United States)

    Ellerbrock, Roman; Manthe, Uwe

    2017-12-01

    Quantum state-resolved reaction probabilities for the H + CHD3 → H2 + CD3 reaction are calculated by accurate full-dimensional quantum dynamics calculations using the multi-layer multi-configurational time-dependent Hartree approach and the quantum transition state concept. Reaction probabilities of various ro-vibrational states of the CHD3 reactant are investigated for vanishing total angular momentum. While the reactivity of the different vibrational states of CHD3 mostly follows intuitive patterns, an unusually large reaction probability is found for CHD3 molecules triply excited in the CD3 umbrella-bending vibration. This surprising reactivity can be explained by a Fermi resonance-type mixing of the single CH-stretch excited and the triple CD3 umbrella-bend excited vibrational states of CHD3. These findings show that resonant energy transfer can significantly affect the mode-selective chemistry of CHD3 and result in counter-intuitive reactivity patterns.

  2. Effects of insulin-like growth factor-1 on the assembly and secretion of very low-density lipoproteins in cow hepatocytes in vitro.

    Science.gov (United States)

    Li, Xinwei; Guan, Yuan; Li, Ying; Wu, Dianjun; Liu, Lei; Deng, Qinghua; Li, Xiaobing; Wang, Zhe; Liu, Guowen

    2016-01-15

    Fatty liver is a major metabolic disorder of dairy cows. One important reason is that hepatic very low-density lipoproteins (VLDL) assembly was significant decreased in dairy cows with fatty liver. In addition, the impairment of insulin-like growth factor (IGF)-1 synthesis was involved in the development of fatty liver. Therefore, the objective of this study was to investigate the effects of IGF-1 on the VLDL assembly in cow hepatocytes. In this study, cow hepatocytes were cultured and then transfected with Ad-GFP-IGF-1 (inhibited the IGF-1 expression) and Ad-GFP (negative control), and treated with different concentrations of IGF-1, respectively. The results showed that IGF-1 increased the mRNA abundance of apolipoprotein B100 (ApoB100), apolipoprotein E (ApoE), microsomal triglyceride transfer protein (MTTP), and low-density lipoprotein receptor (LDLR) and then increased the VLDL assembly in cow hepatocytes. Nevertheless, impairment of IGF-1 expression by Ad-GFP-IGF-1 could inhibit above genes expression and VLDL assembly in hepatocytes. Taken together, these results indicate that IGF-1 increases the VLDL assembly and impairment of IGF-1 expression decreases the VLDL assembly in cow hepatocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The single-nucleotide polymorphisms in CHD5 affect the prognosis of patients with hepatocellular carcinoma

    Science.gov (United States)

    Zhu, Xiao; Kong, Qingming; Xie, Liwei; Chen, Zhihong; Li, Hongmei; Zhu, Zhu; Huang, Yongmei; Lan, Feifei; Luo, Haiqing; Zhan, Jingting; Ding, Hongrong; Lei, Jinli; Xiao, Qin; Fu, Weiming; Fan, Wenguo; Zhang, Jinfang; Luo, Hui

    2018-01-01

    Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether CHD5 single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a rare haplotype AG in CHD5 (SNPs: rs12564469-rs9434711) was markedly associated with HCC prognosis. The univariate and multivariate regression analyses revealed the patients with worse overall survival time were those with tumor metastasis and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage. Based on the available public databases, we discovered the significant association between haplotype AG and CHD5 mRNA expressions only existed in Chinese. These data proposed that the potentially genetic haplotype might functionally contribute to HCC prognosis and CHD5 mRNA expressions. PMID:29568352

  4. Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis.

    Science.gov (United States)

    Ma, Lu; Rebane, Aleksander A; Yang, Guangcan; Xi, Zhiqun; Kang, Yuhao; Gao, Ying; Zhang, Yongli

    2015-12-23

    Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins couple their stage-wise folding/assembly to rapid exocytosis of neurotransmitters in a Munc18-1-dependent manner. The functions of the different assembly stages in exocytosis and the role of Munc18-1 in SNARE assembly are not well understood. Using optical tweezers, we observed four distinct stages of assembly in SNARE N-terminal, middle, C-terminal, and linker domains (or NTD, MD, CTD, and LD, respectively). We found that SNARE layer mutations differentially affect SNARE assembly. Comparison of their effects on SNARE assembly and on exocytosis reveals that NTD and CTD are responsible for vesicle docking and fusion, respectively, whereas MD regulates SNARE assembly and fusion. Munc18-1 initiates SNARE assembly and structures t-SNARE C-terminus independent of syntaxin N-terminal regulatory domain (NRD) and stabilizes the half-zippered SNARE complex dependent upon the NRD. Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1.

  5. Longer Sleep Duration and Midday Napping Are Associated with a Higher Risk of CHD Incidence in Middle-Aged and Older Chinese: the Dongfeng-Tongji Cohort Study.

    Science.gov (United States)

    Yang, Liangle; Yang, Handong; He, Meian; Pan, An; Li, Xiulou; Min, Xinwen; Zhang, Ce; Xu, Chengwei; Zhu, Xiaoyan; Yuan, Jing; Wei, Sheng; Miao, Xiaoping; Hu, Frank B; Wu, Tangchun; Zhang, Xiaomin

    2016-03-01

    To analyze the independent and combined relations of sleep duration and midday napping with coronary heart diseases (CHD) incidence along with the underlying changes of cardiovascular disease (CVD) risk factors among Chinese adults. We included 19,370 individuals aged 62.8 years at baseline from September 2008 to June 2010, and they were followed until October 2013. Cox proportional hazards models and general linear models were used for multivariate longitudinal analyses. Compared with sleeping 7- napping > 90 min compared with 1-30 min. When sleep duration and midday napping were combined, individuals having sleep duration ≥ 10 h and midday napping > 90 min were at a greater risk of CHD than those with sleeping 7- napping 1-30 min: the HR was 1.67 (95% CI = 1.04 to 2.66; P for trend = 0.017). In addition, longer sleep duration ≥ 10 h was significantly associated with increases in triglycerides and waist circumference, and a reduction in HDL-cholesterol; while longer midday napping > 90 min was related to increased waist circumference. Both longer sleep duration and midday napping were independently and jointly associated with a higher risk of CHD incidence, and altered lipid profile and waist circumference may partially explain the relationships. © 2016 Associated Professional Sleep Societies, LLC.

  6. Determinants of quality of life in adults with CHD: an Australian cohort.

    Science.gov (United States)

    Eaton, Sarah L; Wang, QiFeng; Menahem, Samuel

    2017-10-01

    Following improved survival rates in children with CHD, their quality of life and its determinants have become increasingly important. As part of a multicentre study entitled "Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart Disease - International Study", this article reviews the relationships among quality of life, anxiety and depression, sense of coherence, and severity of disease in an Australian cohort of adults with CHD. Methods and results Adults with CHD were recruited from a single, community-based cardiology practice. All patients completed a self-reported questionnaire. A total of 135 patients, 71 males and 64 females, were recruited with a mean age of 26 years. The median quality of life in this cohort was 90; one-fifth of the patients experienced symptoms of anxiety. There was a significant negative correlation between quality of life and symptoms of anxiety and depression and a positive correlation between quality of life and sense of coherence. The quality of life of this cohort was generally excellent; however, one-fifth of them experienced symptoms of anxiety. Those with less anxiety and depression symptoms appeared to have a better quality of life, as did those who reported a higher sense of coherence. Interestingly, there was no significant relationship between complexity of CHD and quality of life.

  7. Prominent scapulae mimicking an inherited myopathy expands the phenotype of CHD7-related disease

    NARCIS (Netherlands)

    O'Grady, Gina L.; Ma, Alan; Sival, Deborah; Wong, Monica T. Y.; Peduto, Tony; Menezes, Manoj P.; Young, Helen; Waddell, Leigh; Ghaoui, Roula; Needham, Merrilee; Lek, Monkol; North, Kathryn N.; MacArthur, Daniel G.; van Ravenswaaij-Arts, Conny M. A.; Clarke, Nigel F.

    CHD7 variants are a well-established cause of CHARGE syndrome, a disabling multi-system malformation disorder that is often associated with deafness, visual impairment and intellectual disability. Less severe forms of CHD7-related disease are known to exist, but the full spectrum of phenotypes

  8. Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors

    Science.gov (United States)

    Song, C; Chang, Z; Magnusson, P K E; Ingelsson, E; Pedersen, N L

    2014-01-01

    Astract Song C, Chang Z, Magnusson PKE, Ingelsson E, Pedersen NL (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; Sweden). Genetic factors may play a prominent role in the developmentofcoronary heart diseasedependenton important environmental factors. J InternMed2014; 275: 631–639. Objective The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD). Design The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene–environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors. Subjects In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded. Results Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women. Conclusions The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene–environment interactions will be important for a full understanding of the aetiology of CHD. PMID:24330166

  9. Evaluation of Carbohydrate-Derived Fulvic Acid (CHD-FA) as a Topical Broad-Spectrum Antimicrobial for Drug-Resistant Wound Infections

    Science.gov (United States)

    2016-10-01

    the newly formulated CHD-FA-Zn. Our initial results demonstrated that CHD-FA-Zn reduced microbial burdens of susceptible and drug- resistant planktonic...wound-associated drug resistant bacteria and fungi. Rat models of wound infection (open, and burn model) will be established with healthy animals ...Establish MIC90s for CHD-FA with clinical isolates of major drug resistant pathogens Assess CHD-FA in animal models of wound infection for major

  10. Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation.

    Science.gov (United States)

    Logue, Jennifer; Murray, Heather M; Welsh, Paul; Shepherd, James; Packard, Chris; Macfarlane, Peter; Cobbe, Stuart; Ford, Ian; Sattar, Naveed

    2011-04-01

    The effect of body mass index (BMI) on coronary heart disease (CHD) risk is attenuated when mediators of this risk (such as diabetes, hypertension and hyperlipidaemia) are accounted for. However, there is now evidence of a differential effect of risk factors on fatal and non-fatal CHD events, with markers of inflammation more strongly associated with fatal than non-fatal events. To describe the association with BMI separately for both fatal and non-fatal CHD risk after accounting for classical risk factors and to assess any independent effects of obesity on CHD risk. In the West of Scotland Coronary Prevention Study BMI in 6082 men (mean age 55 years) with hypercholesterolaemia, but no history of diabetes or CVD, was related to the risk of fatal and non-fatal CHD events. After excluding participants with any event in the first 2 years, 1027 non-fatal and 214 fatal CHD events occurred during 14.7 years of follow-up. A minimally adjusted model (age, sex, statin treatment) and a maximally adjusted model (including known CVD risk factors and deprivation) were compared, with BMI 25-27.4 kg/m² as referent. The risk of non-fatal events was similar across all BMI categories in both models. The risk of fatal CHD events was increased in men with BMI 30.0-39.9 kg/m² in both the minimally adjusted model (HR = 1.75 (95% CI 1.12 to 2.74)) and the maximally adjusted model (HR = 1.60 (95% CI 1.02 to 2.53)). These hypothesis generating data suggest that obesity is associated with fatal, but not non-fatal, CHD after accounting for known cardiovascular risk factors and deprivation. Clinical trial registration WOSCOPS was carried out and completed before the requirement for clinical trial registration.

  11. Preventable coronary heart disease events from control of cardiovascular risk factors in US adults with diabetes (projections from utilizing the UKPDS risk engine).

    Science.gov (United States)

    Wong, Nathan D; Patao, Christopher; Malik, Shaista; Iloeje, Uchenna

    2014-04-15

    Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Impacts of chronic kidney disease and albuminuria on associations between coronary heart disease and its traditional risk factors in type 2 diabetic patients – the Hong Kong diabetes registry

    Directory of Open Access Journals (Sweden)

    Cockram Clive S

    2007-12-01

    Full Text Available Abstract Background Glycated haemoglobin (HbA1c, blood pressure and body mass index (BMI are risk factors for albuminuria, the latter in turn can lead to hyperlipidaemia. We used novel statistical analyses to examine how albuminuria and chronic kidney disease (CKD may influence the effects of other risk factors on coronary heart disease (CHD. Methods A prospective cohort of 7067 Chinese type 2 diabetic patients without history of CHD enrolled since 1995 were censored on July 30th, 2005. Cox proportional hazard regression with restricted cubic spline was used to auto-select predictors. Hazard ratio plots were used to examine the risk of CHD. Based on these plots, non-linear risk factors were categorised and the categorised variables were refitted into various Cox models in a stepwise manner to confirm the findings. Results Age, male gender, duration of diabetes, spot urinary albumin: creatinine ratio, estimated glomerular filtration rate, total cholesterol (TC, high density lipoprotein cholesterol (HDL-C and current smoking status were risk factors of CHD. Linear association between TC and CHD was observed only in patients with albuminuria. Although in general, increased HDL-C was associated with decreased risk of CHD, full-range HDL-C was associated with CHD in an A-shaped manner with a zenith at 1.1 mmol/L. Albuminuria and CKD were the main contributors for the paradoxically positive association between HDL-C and CHD for HDL-C values less than 1.1 mmol/L. Conclusion In type 2 diabetes, albuminuria plays a linking role between conventional risk factors and CHD. The onset of CKD changes risk associations between lipids and CHD.

  13. Development and validation of the coronary heart disease scale under the system of quality of life instruments for chronic diseases QLICD-CHD: combinations of classical test theory and Generalizability Theory.

    Science.gov (United States)

    Wan, Chonghua; Li, Hezhan; Fan, Xuejin; Yang, Ruixue; Pan, Jiahua; Chen, Wenru; Zhao, Rong

    2014-06-04

    Quality of life (QOL) for patients with coronary heart disease (CHD) is now concerned worldwide with the specific instruments being seldom and no one developed by the modular approach. This paper is aimed to develop the CHD scale of the system of Quality of Life Instruments for Chronic Diseases (QLICD-CHD) by the modular approach and validate it by both classical test theory and Generalizability Theory. The QLICD-CHD was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, pre-testing and quantitative statistical procedures. 146 inpatients with CHD were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, t-tests and also G studies and D studies of Genralizability Theory analysis. Multi-trait scaling analysis, correlation and factor analyses confirmed good construct validity and criterion-related validity when using SF-36 as a criterion. The internal consistency α and test-retest reliability coefficients (Pearson r and Intra-class correlations ICC) for the overall instrument and all domains were higher than 0.70 and 0.80 respectively; The overall and all domains except for social domain had statistically significant changes after treatments with moderate effect size SRM (standardized response mea) ranging from 0.32 to 0.67. G-coefficients and index of dependability (Ф coefficients) confirmed the reliability of the scale further with more exact variance components. The QLICD-CHD has good validity, reliability, and moderate responsiveness and some highlights, and can be used as the quality of life instrument for patients with CHD. However, in order to obtain better reliability, the numbers of items for social domain should be increased or the items' quality, not quantity, should be

  14. Relationship between serum thyroid hormones levels and heart failure in patients with coronary heart disease (CHD)

    International Nuclear Information System (INIS)

    Du Fuman; Liu Tongmei; Wang Weimin

    2006-01-01

    Objective: To investigate the relationship between serum thyroid hormones levels and severity of heart failure in patients with coronary heart disease (CHD). Methods: Serum thyroid hormones (FT 3 , FT 4 , TSH) levels were measured with RIA in 38 patients with CHD but no cardiac failure, 40 CHD patients with heat failure and 37 controls. Results: The serum FT 3 levels in patients with heart failure were significantly lower than those in the other two groups (P 4 and TSH in all these three groups of subjects. Moreover, the serum FT 3 levels in the patients with heart fail- ure were significantly positively correlated with the ejection fractions (EF) in these patients. Conclusion: Serum FT 3 levels dropped markedly in CHD patients with heart failure and the magnitude of decrease was positively correlated with the severity of the disease. (authors)

  15. Prevalence and risk factors of coronary heart disease in a rural population of Bangladesh

    Directory of Open Access Journals (Sweden)

    M Abu Sayeed

    2010-07-01

    Full Text Available Coronary heart disease (CHD is a major global health problem with the majority of burden observed increasingly in the developing countries. There has been no estimate of CHD in Bangladesh. This study addresses the prevalence of CHD in a Bangladeshi rural population which also aimed to determine the risk factors related to CHD. Ten villages of Nandail sub-district under Mymensingh were selected purposively. All subjects of age ³20y were considered eligible and were interviewed about family income, family history of T2DM, CHD and HTN. The investigations included height, weight, waist-girth, hip-girth, systolic and diastolic blood pressure (SBP & DBP, fasting blood glucose (FBG, triglycerides (TG, cholesterol (Chol and high density lipoprotein (HDL. Hemoglobin A1c (HbA1c and albumin-creatinine ratio (ACR were also estimated. Finally, electrocardiography (ECG was undertaken in all participants who had family history of diabetes or hypertension or CHD. Diagnosis of CHD was based on history of angina or changes in ECG or diagnosed by a cardiologist. A total of 6235 subjects were enlisted as eligible (age ³20y participants. Of them, 4141 (m / f: 1749 / 2392 subjects volunteered for the study. The age-adjusted (20-69y prevalence of CHD was 1.85 with 95% CI, 1.42 – 2.28. There was no significant difference between men and women. The mean (SD values of age (p<0.001, SBP (p<0.01, DBP (p<0.05, HbA1c (p<0.05 and ACR (p<0.01 were significantly higher among subjects with CHD than those without; whereas, there were no significant differences in BMI and WHR, TG, Chol and HDL. Logistic regression analysis showed that adjusted for age, sex, social class and obesity, the subjects with higher age (³45y, higher 2hBG (³7.0mmol/l, higher ACR (³17.2 and family history of CHD had significant risk for CHD. The prevalence of CHD is comparable with other Asian population. Family history of CHD and age over 45 years, and who had hyperglycemia and higher ACR were

  16. CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression

    DEFF Research Database (Denmark)

    Egan, Chris M; Nyman, Ulrika; Skotte, Julie

    2013-01-01

    The chromatin remodeler CHD5 is expressed in neural tissue and is frequently deleted in aggressive neuroblastoma. Very little is known about the function of CHD5 in the nervous system or its mechanism of action. Here we report that depletion of Chd5 in the developing neocortex blocks neuronal...... of this candidate tumor suppressor might contribute to neuroblastoma....

  17. Accurate diagnosis of CHD by Paediatricians with Expertise in Cardiology.

    Science.gov (United States)

    Jacob, Hannah C; Massey, Hannah; Yates, Robert W M; Kelsall, A Wilfred

    2017-08-01

    Introduction Paediatricians with Expertise in Cardiology assess children with a full history, examination, and often perform an echocardiogram. A minority are then referred to an outreach clinic run jointly with a visiting paediatric cardiologist. The accuracy of the echocardiography diagnosis made by the Paediatrician with Expertise in Cardiology is unknown. Materials and methods We conducted a retrospective review of clinic letters for children seen in the outreach clinic for the first time between March, 2004 and March, 2011. Children with CHD diagnosed antenatally or elsewhere were excluded. We recorded the echocardiography diagnosis made by the paediatric cardiologist and previously by the Paediatrician with Expertise in Cardiology. The Paediatrician with Expertise in Cardiology referred 317/3145 (10%) children seen in the local cardiac clinics to the outreach clinic over this period, and among them 296 were eligible for inclusion. Their median age was 1.5 years (range 1 month-15.1 years). For 244 (82%) children, there was complete diagnostic agreement between the Paediatrician with Expertise in Cardiology and the paediatric cardiologist. For 29 (10%) children, the main diagnosis was identical with additional findings made by the paediatric cardiologist. The abnormality had resolved in 17 (6%) cases by the time of clinic attendance. In six (2%) patients, the paediatric cardiologist made a different diagnosis. In total, 138 (47%) patients underwent a surgical or catheter intervention. Discussion Paediatricians with Expertise in Cardiology can make accurate diagnoses of CHD in children referred to their clinics. This can allow effective triage of children attending the outreach clinic, making best use of limited specialist resources.

  18. LINE-1 Hypomethylation is Associated with the Risk of Coronary Heart Disease in Chinese Population

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Li [Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin (China); Liu, Shuchuan [Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin (China); Su, Zhendong; Cheng, Rongchao; Bai, Xiuping; Li, Xueqi, E-mail: xueqi-li@163.com [Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin (China)

    2014-05-15

    Global methylation level in blood leukocyte DNA has been associated with the risk of coronary heart disease (CHD), with inconsistent results in various populations. Similar data are lacking in Chinese population where different genetic, lifestyle and environmental factors may affect DNA methylation and its risk relationship with CHD. To examine whether global methylation is associated with the risk of CHD in Chinese population. A total of 334 cases with CHD and 788 healthy controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing LINE-1 repeats using bisulfite pyrosequencing. In an initial analysis restricted to control subjects, LINE-1 level reduced significantly with aging, elevated total cholesterol, and diagnosis of diabetes. In the case-control analysis, reduced LINE-1 methylation was associated with increased risk of CHD; analysis by quartile revealed odds ratios (95%CI) of 0.9 (0.6-1.4), 1.9 (1.3-2.9) and 2.3 (1.6-3.5) for the third, second and first (lowest) quartile (P{sub trend} < 0.001), respectively, compared to the fourth (highest) quartile. Lower (1 methylation was associated with a 2.2-fold (95%CI = 1.7-3.0) increased risk of CHD. The lower LINE-1-related CHD risk estimates tended to be stronger among subjects with the highest tertile of homocysteine (P{sub interaction} = 0.042) and those with diagnosis of hypertension (P{sub interaction} = 0.012). LINE-1 hypomethylation is associated with the risk of CHD in Chinese population. Potential CHD risk factors such as older age, elevated total cholesterol, and diagnosis of diabetes may have impact on global DNA methylation, whereby exerting their effect on CHD risk.

  19. LINE-1 Hypomethylation is Associated with the Risk of Coronary Heart Disease in Chinese Population

    International Nuclear Information System (INIS)

    Wei, Li; Liu, Shuchuan; Su, Zhendong; Cheng, Rongchao; Bai, Xiuping; Li, Xueqi

    2014-01-01

    Global methylation level in blood leukocyte DNA has been associated with the risk of coronary heart disease (CHD), with inconsistent results in various populations. Similar data are lacking in Chinese population where different genetic, lifestyle and environmental factors may affect DNA methylation and its risk relationship with CHD. To examine whether global methylation is associated with the risk of CHD in Chinese population. A total of 334 cases with CHD and 788 healthy controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing LINE-1 repeats using bisulfite pyrosequencing. In an initial analysis restricted to control subjects, LINE-1 level reduced significantly with aging, elevated total cholesterol, and diagnosis of diabetes. In the case-control analysis, reduced LINE-1 methylation was associated with increased risk of CHD; analysis by quartile revealed odds ratios (95%CI) of 0.9 (0.6-1.4), 1.9 (1.3-2.9) and 2.3 (1.6-3.5) for the third, second and first (lowest) quartile (P trend < 0.001), respectively, compared to the fourth (highest) quartile. Lower (1 methylation was associated with a 2.2-fold (95%CI = 1.7-3.0) increased risk of CHD. The lower LINE-1-related CHD risk estimates tended to be stronger among subjects with the highest tertile of homocysteine (P interaction = 0.042) and those with diagnosis of hypertension (P interaction = 0.012). LINE-1 hypomethylation is associated with the risk of CHD in Chinese population. Potential CHD risk factors such as older age, elevated total cholesterol, and diagnosis of diabetes may have impact on global DNA methylation, whereby exerting their effect on CHD risk

  20. Quality of life in adolescents and young adults with CHD is not reduced

    DEFF Research Database (Denmark)

    Schrøder, Morten; Boisen, Kirsten A.; Reimers, Jesper

    2016-01-01

    We performed a systematic review and meta-analysis of observational studies assessing quality of life in adolescents and young adults born with CHD compared with age-matched controls. We carried out a systematic search of the literature published in Medline, Embase, PsychINFO, and the Cochrane....... The studies were of acceptable-to-good quality. The meta-analysis of six studies on quality of life showed no significant difference – mean difference: −1.31; 95% confidence intervals: −6.51 to +3.89, I2=90.9% – between adolescents and young adults with CHD and controls. Similar results were found in 10...... studies not eligible for the meta-analysis. In subdomains, it seems that patients had reduced physical quality of life; however, social functioning was comparable or better compared with controls. For the first time in a meta-analysis, we have shown that quality of life in adolescents and young adults...

  1. Determination of mixing factors for VVER-440 fuel assembly head

    Energy Technology Data Exchange (ETDEWEB)

    Tóth, S., E-mail: toth@reak.bme.hu [Institute of Nuclear Techniques, Budapest University of Technology and Economics, Műegyetem rkp. 9, H-1111 Budapest (Hungary); Aszódi, A. [Institute of Nuclear Techniques, Budapest University of Technology and Economics, Műegyetem rkp. 9, H-1111 Budapest (Hungary)

    2013-11-15

    CFD models have been developed for the heads of the old, the present and the new type VVER-440 fuel assemblies using the experience of a former validation process. With these models temperature distributions are investigated in the heads of some typical assemblies and the in-core thermocouple signals are calculated. The analyses show that the coolant mixing is intensive but not-perfect in the assembly heads. The difference between the thermocouple signal and the cross-sectional average temperature at the measurement level depends on the assembly type. Using the results of these CFD calculations the weight factors of the rod bundle regions for the in-core thermocouple have been determined. With these factors the thermocouple signals are estimated and the results are statistically tested using the registered data of the Hungarian nuclear power plant. This test shows that the deviations between the measured and the calculated temperatures can be significantly decreased and consequently monitoring uncertainties can be reduced with using the weight factors.

  2. The M235T polymorphism in the AGT gene and CHD risk: evidence of a Hardy-Weinberg equilibrium violation and publication bias in a meta-analysis

    NARCIS (Netherlands)

    Zafarmand, Mohammad Hadi; van der Schouw, Yvonne T.; Grobbee, Diederick E.; de Leeuw, Peter W.; Bots, Michiel L.

    2008-01-01

    The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective

  3. DIABETES ASSOCIATED OXIDATIVE STRESS AND INFLAMMATION ALTERS THE PROTECTIVE EFFECT OF OBESITY ON SURVIVAL IN CHD PATIENTS

    Directory of Open Access Journals (Sweden)

    Serpil M. Deger

    2012-06-01

    Full Text Available In contrast to the adverse outcomes of obesity in general population, increased body mass index (BMI is associated with improved survival in hemodialysis (CHD patients. The aim of this retrospective study was to evaluate the association between obesity and mortality by diabetic status among 98 maintenance CHD patients. The median follow up was 33 (19, 56 months. Mean age was 49±13 years, 66% were male and 48 % had obesity. 45% of obese subjects were diabetic. Among the subgroups of study population, survival of diabetic obese patients was significantly lower compared to non-diabetic obese subjects (p=0.007 (Figure 1. The subgroup comparisons showed that diabetic obese patients tend to have higher truncal fat percentage (p<0.001 and lower lean body mass standardized by body surface area compared to nondiabetic counterparts although difference was not statistically significance. Diabetic obese patients had higher leptin (p=0.001 and high sensitivity C-reactive protein levels (0.005. Additionally, protein thiols (P-SH were significantly decreased in diabetic obese participants (p=0.03. Although, elevated body fatness appears to be protective for CHD population, presence of overt diabetes alters this advantage by increasing inflammation and oxidative stress.fx1

  4. A novel classification system to predict the pathogenic effects of CHD7 missense variants in CHARGE syndrome

    DEFF Research Database (Denmark)

    Bergman, Jorieke E H; Janssen, Nicole; van der Sloot, Almer M

    2012-01-01

    CHARGE syndrome is characterized by the variable occurrence of multisensory impairment, congenital anomalies, and developmental delay, and is caused by heterozygous mutations in the CHD7 gene. Correct interpretation of CHD7 variants is essential for genetic counseling. This is particularly diffic...

  5. Traditional Cardiovascular Risk Factors as Predictors of Cardiovascular Events in the U.S. Astronaut Corps

    Science.gov (United States)

    Halm, M. K.; Clark, A.; Wear, M. L.; Murray, J. D.; Polk, J. D.; Amirian, E.

    2009-01-01

    Risk prediction equations from the Framingham Heart Study are commonly used to predict the absolute risk of myocardial infarction (MI) and coronary heart disease (CHD) related death. Predicting CHD-related events in the U.S. astronaut corps presents a monumental challenge, both because astronauts tend to live healthier lifestyles and because of the unique cardiovascular stressors associated with being trained for and participating in space flight. Traditional risk factors may not hold enough predictive power to provide a useful indicator of CHD risk in this unique population. It is important to be able to identify individuals who are at higher risk for CHD-related events so that appropriate preventive care can be provided. This is of special importance when planning long duration missions since the ability to provide advanced cardiac care and perform medical evacuation is limited. The medical regimen of the astronauts follows a strict set of clinical practice guidelines in an effort to ensure the best care. The purpose of this study was to evaluate the utility of the Framingham risk score (FRS), low-density lipoprotein (LDL) and high-density lipoprotein levels, blood pressure, and resting pulse as predictors of CHD-related death and MI in the astronaut corps, using Cox regression. Of these factors, only two, LDL and pulse at selection, were predictive of CHD events (HR(95% CI)=1.12 (1.00-1.25) and HR(95% CI)=1.70 (1.05-2.75) for every 5-unit increase in LDL and pulse, respectively). Since traditional CHD risk factors may lack the specificity to predict such outcomes in astronauts, the development of a new predictive model, using additional measures such as electron-beam computed tomography and carotid intima-media thickness ultrasound, is planned for the future.

  6. Study on the rhythmic variation of plasma cortisol levels in patients with essential hypertension (EH) and coronary heart disease (CHD)

    International Nuclear Information System (INIS)

    Zhu Mei; Wu Guo; Li Ying

    2007-01-01

    Objective: To study the rhythmic fluctuation of plasma cortisol levels in patients with EH and CHD. Methods: Plasma cortisol levels were determined with RIA at 8Am, 4Pm and midnight in 61 patients with EH, 46 patients with CHD and 36 controls. Results: The normal rhythmic fluctuation pattern of plasma cortisol levels was retained in the EH and CHD patients. However, the levels were all significantly higher in the patients than those in the controls, especially in the midnight specimens. Conclusion: Marked elevated plasma cortisol levels were observed in patients with EH and CHD, with the normal rhythmic fluctuation pattern retained. (authors)

  7. Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis.

    Science.gov (United States)

    Zhao, Luqian; Zhu, Zhigang; Lou, Huiling; Zhu, Guodong; Huang, Weimin; Zhang, Shaogang; Liu, Feng

    2016-06-07

    Some studies reported a significant association between polycystic ovary syndrome (PCOS) and risk of cardiovascular disease (CVD). However, the results are controversial. A systematic search was conducted in the PubMed, Science Direct, EMBASE, and Cochrane Library databases. Five case-control studies and 5 cohort studies were selected, involving a total of 104392 subjects in this meta-analysis. PCOS was significantly associated with the increased risk of CVD (OR = 1.30; 95% CI 1.09 - 1.56; P = 0.004). In the subgroup analysis of study design, both case-control studies and prospective cohort studies showed significant results (OR = 1.79; 95% CI 1.16 - 2.77; P = 0.009; OR = 1.20; 95% CI 1.06 - 1.37; P = 0.005), while retrospective cohort studies did not show positive result (OR = 0.91; 95% CI 0.60 - 1.40; P = 0.68). In a further stratified analysis by type of CVD, a significant association was found between PCOS and coronary heart disease (CHD) (OR = 1.44; 95% CI 1.13 - 1.84; P = 0.004). However, no significant association was observed between PCOS and myocardial infarction (MI) (OR = 1.01; 95% CI 0.68 - 1.51; P = 0.95). In conclusion, this meta-analysis suggested that PCOS is significantly associated with increased CHD risk.

  8. Pulmonary hypertension in children with congenital heart disease (PAH-CHD, PPHVD-CHD). Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    Science.gov (United States)

    Kozlik-Feldmann, Rainer; Hansmann, Georg; Bonnet, Damien; Schranz, Dietmar; Apitz, Christian; Michel-Behnke, Ina

    2016-05-01

    Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a complex disease that presents with a broad spectrum of morphological and haemodynamic findings of varying severity. Recently, the aspect of paediatric pulmonary hypertensive vascular disease (PPHVD) has been introduced to expand the understanding of the full spectrum of pulmonary hypertension and increased pulmonary vascular resistance. Evaluation and treatment of PAH-CHD/PPHVD-CHD can be divided into in different topics. First, defining criteria for operability and initiation of advanced therapies preoperatively and postoperatively is an unresolved issue. Second, management of Eisenmenger syndrome is still an important question, with recent evidence on the severity of the disease and a more rapidly progressive course than previously described. Third, the Fontan circulation with no subpulmonary ventricle requires a distinct discussion, definition and classification since even a mild rise in pulmonary vascular resistance may lead to the so-called failing Fontan situation. Patients with CHD and single-ventricle physiology (Fontan/total cavopulmonary anastomosis) require a particularly stepwise and individualised approach. This consensus statement is on the current evidence for the most accurate evaluation and treatment of increased pulmonary artery pressure and resistance, as well as ventricular dysfunction, in children with congenital heart defects, and provides according practical recommendations. To optimise preoperative and postoperative management in patients with PAH-CHD, diagnostic and treatment algorithms are provided. 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/

  9. Risk factors of coronary heart disease among medical diagnostic X-ray workers

    International Nuclear Information System (INIS)

    Zhang Wei; Wang Jixian; Zhao Yongcheng; Li Benxiao; Fan Tiqiang; Zhao Zhigang; Lin Zhidong

    2002-01-01

    Objective: To investigate risk factors of coronary heart disease (CHD) in medical diagnostic X-ray workers in China, especially the relationship of CHD with occupational irradiation. Methods: A 1:2 matched case-control study was carried out. The study subjects consisted of 112 pair-matched cases and controls coming from different hospitals in China. Information about occupational and non-occupational risk factors obtained by interviewing every subjects personally. Individual doses were estimated by normalized work load method. SAS 6.12 software conditional Logistic regression method was applied to data analysis. Results: Variables such as family history of CHD (OR=17.298, P = 0.0001), history of hypertension (OR = 6.172, P = 0.0003), overweight (OR = 2.679, P = 0.0150), physical exercises (OR = 0.421, P0.0333), diabetes (OR = 7.823, P = 0.0200), radiation protection condition (OR = 3.992, P 0.0027), and accumulated radiation dose (OR = 1.612, P 0.0454) were included in the last model. Conclusions: For the medical diagnostic X-ray workers, family history of coronary heart disease, history of hypertension, diabetes, etc. are the main risk factors of CHD, and occupational exposure may be a potential risk factor. As for the mechanism, further studies are needed

  10. CTCF-KDM4A complex correlates with histone modifications that negatively regulate CHD5 gene expression in cancer cell lines

    Science.gov (United States)

    Guerra-Calderas, Lissania; González-Barrios, Rodrigo; Patiño, Carlos César; Alcaraz, Nicolás; Salgado-Albarrán, Marisol; de León, David Cantú; Hernández, Clementina Castro; Sánchez-Pérez, Yesennia; Maldonado-Martínez, Héctor Aquiles; De la Rosa-Velazquez, Inti A.; Vargas-Romero, Fernanda; Herrera, Luis A.; García-Carrancá, Alejandro; Soto-Reyes, Ernesto

    2018-01-01

    Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5, and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood. Here, we show that CTCF and KDM4A form a protein complex, which is recruited into the first intron of CHD5. This is related to a decrease in H3K36me3/2 histone marks and is associated with its transcriptional downregulation. Depletion of CTCF or KDM4A by siRNA, triggered the reactivation of CHD5 expression, suggesting that both proteins are involved in the negative regulation of this gene. Furthermore, the knockout of KDM4A restored the CHD5 expression and H3K36me3 and H3K36me2 histone marks. Such mechanism acts independently of CHD5 promoter DNA methylation. Our findings support a novel mechanism of epigenetic repression at the gene body that does not involve promoter silencing. PMID:29682202

  11. THE FREQUENCY AND ASSOCIATION OF RISK FACTORS IN DEVELOPMENT OF CORONARY HEART DISEASE IN DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Dušan Sokolović

    2003-01-01

    Full Text Available The coronary heart disease (CHD is a leading cause of lethality in both sexes. The risk for development of CHD is 2-4 times higher in non insulin dependent diabetes mellitus (NIDDM than in nondiabetics, and annual rate of fatal and non-fatal cardiovascular diseases in NIDDM is 2-5%. The etiology of CHD is still unknown until the risk factors connected to the development of CHD are well known.The purpose of this research was to establish the frequency and importance of the risk factors in development of CHD in NIDDM.The research included 60 patients with NIDDM who were by presence of CHD classified into two groups. We determined body mass index and waist hip ratio, total and HDL cholesterol, triglicerides, LDL cholesterols, uric acid and fibrinogen.Values of BMI were statistically higher in patients with CHD than in diabetics without CHD 29.67+3.31 vs. 27.87±3.17 kg/m2 (p<0.05. Raised risk levels of cholesterol had90% with CHD and 76% without CHD (Hi2=6.12, p<0.05. Larger percentage of patients in group with CHD had raised lipid risk levels of triglicerides 70% than in patients without CHD 56.5% (Hi2=4.36, p<0.05. The obesity was relatively rare in patients without CHD than in diabetics with CHD (13.6% vs. 76%, p<0.01.The frequency of risk factors was very high in NIDDM patients, which clearly points at their cumulative effect in development of CHD in diabetics.

  12. Effects of reagent rotational excitation on the H + CHD3 → H2 + CD3 reaction: A seven dimensional time-dependent wave packet study

    International Nuclear Information System (INIS)

    Zhang, Zhaojun; Zhang, Dong H.

    2014-01-01

    Seven-dimensional time-dependent wave packet calculations have been carried out for the title reaction to obtain reaction probabilities and cross sections for CHD 3 in J 0 = 1, 2 rotationally excited initial states with k 0 = 0 − J 0 (the projection of CHD 3 rotational angular momentum on its C 3 axis). Under the centrifugal sudden (CS) approximation, the initial states with the projection of the total angular momentum on the body fixed axis (K 0 ) equal to k 0 are found to be much more reactive, indicating strong dependence of reactivity on the orientation of the reagent CHD 3 with respect to the relative velocity between the reagents H and CHD 3 . However, at the coupled-channel (CC) level this dependence becomes much weak although in general the K 0 specified cross sections for the K 0 = k 0 initial states remain primary to the overall cross sections, implying the Coriolis coupling is important to the dynamics of the reaction. The calculated CS and CC integral cross sections obtained after K 0 averaging for the J 0 = 1, 2 initial states with all different k 0 are essentially identical to the corresponding CS and CC results for the J 0 = 0 initial state, meaning that the initial rotational excitation of CHD 3 up to J 0 = 2, regardless of its initial k 0 , does not have any effect on the total cross sections for the title reaction, and the errors introduced by the CS approximation on integral cross sections for the rotationally excited J 0 = 1, 2 initial states are the same as those for the J 0 = 0 initial state

  13. GIT1 enhances neurite outgrowth by stimulating microtubule assembly

    Directory of Open Access Journals (Sweden)

    Yi-sheng Li

    2016-01-01

    Full Text Available GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.

  14. [Correlation between polymorphisms in the coagulation factor VII gene hypervariable region 4 site and the risk of coronary heart disease in population with different ethnic backgrounds: a Meta-analysis].

    Science.gov (United States)

    Wang, Li-li; Ma, Bin; Qian, Dun; Pang, Jun; Yao, Ya-li

    2013-12-01

    To assess the correlation between polymorphisms in the coagulation factor VII (F VII)gene hypervariable region 4 (HVR4)site and risk related to coronary heart disease (CHD)in different ethnic populations, especially the Asian populations. Publications up to April 2013, from CBM, CNKI, Wanfang Database,VIP, PubMed, Cochrane Library and Embase were searched to collect data from case-control studies related to F VII gene HVR4 site and CHD in populations from different ethnicities. Quality of studies was evaluated, available data extracted and both RevMan 5.1 and Stata 11.0 softwares were used for Meta-analysis. Fifteen case-control studies were included, involving 3167 cases with CHD group and 3168 cases in the control group. on this Meta-analysis showed that:a)polymorphism of the F VII gene HVR4 site H7/H6+H5 and CHD, b)H7H7/H6H6 + H7H6 and CHD were both slightly correlated between people with different ethnic backgrounds. However, the H6 allele versus H7+H5 allele and CHD showed different results-a high correlation seen in different ethnic groups. H5 allele versus H6+H7 allele and CHD did not appear significant difference(OR = 1.20, 95%CI:0.76-1.90, P = 0.43). Both F VII gene HVR4 polymorphisms H7 allele and the H7H7 genotype might have served as protective factors for CHD in different ethnic groups, H6 allele might serve as a risk factor for CHD, but H5 allele was likely not to be associated with CHD in different ethnic groups.

  15. Cutaneous Uptake of 14C-HD Vapor by the Hairless Guinea Pig.

    Science.gov (United States)

    1996-10-01

    guinea pig (HGP) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD) exposure. We have determined the HD content in the skin of HOP after 7-minute exposures to vapors saturated with a mixture of HD and 14C-HD. Concentration/time (C1) values in the range of 2 mg/sq cm/min were determined by counting skin 14C disintegrations per minute (dpm) in animals euthanized immediately after exposure. These values are similar to human penetration rates obtained by other investigators. A direct relationship between C1 and relative humidity was

  16. eHealth literacy and preferences for eHealth resources in parents of children with complex CHD.

    Science.gov (United States)

    Kasparian, Nadine A; Lieu, Nathan; Winlaw, David S; Cole, Andrew; Kirk, Edwin; Sholler, Gary F

    2017-05-01

    Introduction This study aimed to (a) examine eHealth literacy, beliefs, and behaviours in parents of children with complex CHD, and (b) identify parents' preferences for the content, format, features, and functions of eHealth resources for CHD. Materials and methods Families (n=198) of children born between 2008 and 2011 and diagnosed with CHD requiring surgery were mailed a survey assessing a range of variables including eHealth literacy, beliefs, and behaviours as well as preferences for the format, functions, features, and content of eHealth resources for CHD. A total of 132 parents (83 mothers, 49 fathers) completed the survey (response rate: 50%). Mothers (96%) were more likely to access eHealth resources than fathers (83%, χ2=6.74, p=0.009). Despite high eHealth resource use, eHealth literacy was relatively low, with results demonstrating considerable and widespread gaps in awareness of, access to, and communication about eHealth resources. Over 50% of parents reported that decisions regarding their child's healthcare were influenced, to some extent, by web-based resources. Barriers to doctor-patient communication about eHealth included limited consultation time and concern about doctors' disapproval. Participants demonstrated a strong desire for "eHealth prescriptions" from their child's healthcare team, and perceived a wide range of eHealth topics as highly important, including treatment-related complications as well as physical, cognitive, and emotional development in children with CHD. Discussion Results suggest a need for stronger, more proactive partnerships between clinicians, researchers, educators, technologists, and patients and families to bring about meaningful innovations in the development and implementation of eHealth interventions in paediatric cardiology.

  17. Colours of fruit and vegetables and 10-year incidence of CHD

    NARCIS (Netherlands)

    Oude Griep, L.M.; Verschuren, W.M.M.; Kromhout, D.; Ocke, M.C.; Geleijnse, J.M.

    2011-01-01

    The colours of the edible part of fruit and vegetables indicate the presence of specific micronutrients and phytochemicals. The extent to which fruit and vegetable colour groups contribute to CHD protection is unknown. We therefore examined the associations between fruit and vegetables of different

  18. Communication: Mode specific quantum dynamics of the F + CHD{sub 3} → HF + CD{sub 3} reaction

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Ji; Song, Hongwei; Yang, Minghui, E-mail: yangmh@wipm.ac.cn, E-mail: juliana@unq.edu.ar, E-mail: uwe.manthe@uni-bielefeld.de [Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Palma, Juliana, E-mail: yangmh@wipm.ac.cn, E-mail: juliana@unq.edu.ar, E-mail: uwe.manthe@uni-bielefeld.de [Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, CONICET, Sáenz Peña 352, Bernal B1876BXD (Argentina); Manthe, Uwe, E-mail: yangmh@wipm.ac.cn, E-mail: juliana@unq.edu.ar, E-mail: uwe.manthe@uni-bielefeld.de [Theoretische Chemie, Fakultät für Chemie, Universität Bielefeld, Universitätsstr. 25, D-33615 Bielefeld (Germany); Guo, Hua [Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131 (United States)

    2016-05-07

    The mode specific reactivity of the F + CHD{sub 3} → HF + CD{sub 3} reaction is investigated using an eight-dimensional quantum dynamical model on a recently developed ab initio based full-dimensional potential energy surface. Our results indicate prominent resonance structures at low collision energies and absence of an energy threshold in reaction probabilities. It was also found that excitation of the C–D stretching or CD{sub 3} umbrella mode has a relatively small impact on reactivity. On the other hand, the excitation of the C–H vibration (v{sub 1}) in CHD{sub 3} is shown to significantly increase the reactivity, which, like several recent quasi-classical trajectory studies, is at odds with the available experimental data. Possible sources of the disagreement are discussed.

  19. Application of CHD1 Gene and EE0.6 Sequences to Identify Sexes of Several Protected Bird Species in Taiwan

    Directory of Open Access Journals (Sweden)

    E.-C. Lin

    2011-06-01

    Full Text Available Many bird species, for example: Crested Serpent Eagle (Spilornis cheela hoya, Collared Scops (Owl Otus bakkamoena, Tawny Fish Owl (Ketupa flavipes, Crested Goshawk (Accipiter trivirgatus, and Grass Owl (Tyto longimembris... etc, are monomorphic, which is difficult to identify their sex simply by their outward appearance. Especially for those monomorphic endangered species, finding an effective tool to identify their sex beside outward appearance is needed for further captive breeding programs or other conservation plans. In this study, we collected samples of Black Swan (Cygmus atratus and Nicobar Pigeon (Caloenas nicobarica, two aviaries introduced monomorphic species served as control group, and Crested Serpent Eagle, Collared Scops Owl, Tawny Fish Owl, Crested Goshawk, and Grass Owl, five protected monomorphic species in Taiwan. We used sex-specific primers of avian CHD1 (chromo-helicase-DNA-binding gene and EE0.6 (EcoRI 0.6-kb fragment sequences to identify the sex of these birds. The results showed that CHD1 gene primers could be used to correctly identify the sex of Black Swans, Nicobar Pigeons and Crested Serpent Eagles, but it could not be used to correctly identify sex in Collared Scops Owls, Tawny Fish Owls, and Crested Goshawks. In the sex identification using EE0.6 sequence fragment, A, C, D and E primer sets could be used for sexing Black Swans; A, B, C, and D primer sets could be used for sexing Crested Serpent Eagles; and E primer set could be used for sexing Nicobar Pigeons and the two owl species. Correct determination of sex is the first step if a captive breeding measure is required. We have demonstrated that several of the existing primer sets can be used for sex determination of several captive breeding and indigenous bird species.

  20. Genetic variants in loci 1p13 and 9p21 and fatal coronary heart disease in a Norwegian case-cohort study.

    Science.gov (United States)

    Jansen, Mona Dverdal; Knudsen, Gun Peggy; Myhre, Ronny; Høiseth, Gudrun; Mørland, Jørg; Næss, Øyvind; Tambs, Kristian; Magnus, Per

    2014-05-01

    Single nucleotide polymorphisms (SNPs) in loci 1p13 and 9p21 have previously been found to be associated with incident coronary heart disease (CHD). This study aimed to investigate whether these SNPs show associations with fatal CHD in a population-based cohort study after adjustment for socioeconomic- and lifestyle-related CHD risk factors not commonly included in genetic association studies. Using the population-based Cohort of Norway (CONOR), a nested case-cohort study was set up and DNA from 2,953 subjects (829 cases and 2,124 non-cases) were genotyped. The association with fatal CHD was estimated for four SNPs, three from locus 1p13 and one from locus 9p21. Multivariable Cox regression was used to estimate unstratified and gender-stratified hazard ratios while adjusting for major CHD risk factors. The associations between three SNPs from locus 1p13 and non-HDL cholesterol levels were also estimated. Men homozygous for the risk alleles on rs1333049 (9p21) and rs14000 (1p13) were found to have significantly increased hazard ratios in crude and adjusted models, and the hazard ratios remained statistically significant when both genders were analyzed together. Adjustment for additional socioeconomic- and lifestyle-related CHD risk factors influenced the association estimates only slightly. No significant associations were observed between the other two SNPs in loci 1p13 (rs599839 and rs646776) and CHD mortality in either gender. Both rs599839 and rs646776 showed significant, gradual increases in non-HDL cholesterol levels with increasing number of risk alleles. This study confirms the association between 9p21 (rs1333049) and fatal CHD in a Norwegian population-based cohort. The effect was not influenced by several socioeconomic- and lifestyle-related risk factors. Our results show that 1p13 (rs14000) may also be associated with fatal CHD. SNPs at 1p13 (rs599839 and rs646776) were associated with non-HDL cholesterol levels.

  1. Gender differences in risk factors for coronary heart disease.

    Science.gov (United States)

    Tan, Yen Y; Gast, Gerrie-Cor M; van der Schouw, Yvonne T

    2010-02-01

    Coronary heart disease (CHD), traditionally considered a male disease, is also a major threat to women. This review article addresses independent risk factors for CHD that are specific for women as well as non-gender-specific risk factors and how their effects differ between men and women. Although polycystic ovary syndrome (PCOS) in women is associated with an adverse metabolic risk profile, current evidence regarding future risk of CHD is conflicting. Preeclampsia is consistently associated with higher risk of CHD later in life. Menopause is associated with an increased risk of CHD, and the earlier the onset of menopause, the larger the risk. Existing data on postmenopausal hormone therapy (HT) was inconclusive with regard to possible protection when HT is initiated close to menopause in young peri- or postmenopausal women. Evidence on use of low-dose oral contraceptives strongly suggests no increased risk of CHD. Although levels of physical inactivity are similar for men and women, the higher prevalences of hypertension, diabetes, and obesity in older women portends a greater risk in women than in men. Additionally, risk factors like smoking, hypertriglyceridemia and low high-density lipoprotein cholesterol levels have greater impact in women than in men. This review indicates that acknowledgement of non-gender-specific risk factors in addition to those that are unique to women would help optimize diagnosis, treatment and earlier prevention of CHD in women. Further research is needed to ascertain if incorporating these gender-specific risks into a clinically used risk stratification model would change outcome in women. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  2. A comparison of the 12-year mortality and predictive factors of coronary heart disease among Japanese men in Japan and Hawaii

    International Nuclear Information System (INIS)

    Yano, Katsuhiko; Maclean, C.J.; Reed, D.M.; Shimizu, Yukiko; Sasaki, Hideo; Kodama, Kazunori; Kato, Hiroo; Kagan, A.

    1988-08-01

    The mortality and predictive factors of coronary heart disease (CHD) among men of Japanese ancestry in Japan and Hawaii were compared on the basis of 12 - year follow-up data using comparable methods of case ascertainment and risk factor measurements. Among 1,687 men (Japan) and 7,536 men (Hawaii) who were free of CHD and aged 45 - 69 at baseline examination, 20 (Japan) and 123 (Hawaii) cases of fatal CHD were identified. The age-adjusted mortality rate was 40 % higher in Hawaii than in Japan. The difference was not statistically significant, but consistent with earlier studies. More than half of this difference in mortality rate was attributed to different levels of known risk factors in the two cohorts. In multivariate analysis using the combined population, age, blood pressure, serum cholesterol, serum glucose, cigarette smoking, and alcohol intake (inversely) remained as significant predictors of CHD mortality. Although the associations of risk factors with CHD tended to be stronger in Hawaii than in Japan, there was no statistically significant difference in regression coefficient for any of the risk factors studied. These findings cannot be claimed definitive because of the small number of cases, especially in Japan. (author)

  3. Comparison of serum lipid management between elderly and non-elderly patients with and without coronary heart disease (CHD

    Directory of Open Access Journals (Sweden)

    Rumiko Shimizu

    2016-12-01

    In conclusion, in CHD, serum lipid goal attainment was comparable between the two age groups although the lipid-lowering drugs were less frequently prescribed in patients aged ≥75. Without CHD, it was significantly better in patients aged ≥75 than those aged <75 although the lipid-lowering drug subscription rates were comparable between the two age groups.

  4. Self-assembly behaviours of peptide-drug conjugates: influence of multiple factors on aggregate morphology and potential self-assembly mechanism

    Science.gov (United States)

    Fan, Qin; Ji, Yujie; Wang, Jingjing; Wu, Li; Li, Weidong; Chen, Rui; Chen, Zhipeng

    2018-04-01

    Peptide-drug conjugates (PDCs) as self-assembly prodrugs have the unique and specific features to build one-component nanomedicines. Supramolecular structure based on PDCs could form various morphologies ranging from nanotube, nanofibre, nanobelt to hydrogel. However, the assembly process of PDCs is too complex to predict or control. Herein, we investigated the effects of extrinsic factors on assembly morphology and the possible formation of nanostructures based on PDCs. To this end, we designed a PDC consisting of hydrophobic drug (S)-ketoprofen (Ket) and valine-glutamic acid dimeric repeats peptide (L-VEVE) to study their assembly behaviour. Our results showed that the critical assembly concentration of Ket-L-VEVE was 0.32 mM in water to form various nanostructures which experienced from micelle, nanorod, nanofibre to nanoribbon. The morphology was influenced by multiple factors including molecular design, assembly time, pH and hydrogen bond inhibitor. On the basis of experimental results, we speculated the possible assembly mechanism of Ket-L-VEVE. The π-π stacking interaction between Ket molecules could serve as an anchor, and hydrogen bonded-induced β-sheets and hydrophilic/hydrophobic balance between L-VEVE peptide play structure-directing role in forming filament-like or nanoribbon morphology. This work provides a new sight to rationally design and precisely control the nanostructure of PDCs based on aromatic fragment.

  5. Risk factors of coronary heart disease among medical students in King Abdulaziz University, Jeddah, Saudi Arabia.

    Science.gov (United States)

    Ibrahim, Nahla Khamis; Mahnashi, Morooj; Al-Dhaheri, Amal; Al-Zahrani, Borooj; Al-Wadie, Ebtihal; Aljabri, Mydaa; Al-Shanketi, Rajaa; Al-Shehri, Rawiah; Al-Sayes, Fatin M; Bashawri, Jamil

    2014-04-28

    Nowadays, Cardiovascular Diseases (CVDs) represents an escalating worldwide public health problem. Providing consistent data on the magnitude and risk factors of CVDs among young population will help in controlling the risks and avoiding their consequences. The objective was to estimate the prevalence of risk factors of Coronary Heart Disease (CHD) among medical students during their clinical clerkship (4th - 6th years). A cross-sectional study was done during the educational year 2012-2013 at King Abdulaziz University (KAU), Jeddah. Ethical standards were followed and a multistage stratified random sample method was used for selection of 214 medical students. Data was collected through an interviewing questionnaire, measurements and laboratory investigations. Both descriptive and analytical statistics were done by SPSS version 21. CHD risk percent in thirty years was calculated using Framingham algorithm for each student, then the risk among all students was determined. The commonest risk factors of CHDs were daily intake of high fat diet (73.4%), physical inactivity (57.9%), overweight/or obesity (31.2%) and daily consumption of fast food (13.1%). Hyper-cholesterolemia (17.2%) and hypertension (9.3%) were also prevalent risk factors. Smoking prevalence was low (2.8%). Males had significantly higher mean scores for most of CHD risk factors compared to females (p Students't test = 4.74, p students was 10.7%, 2.3% and 0.5% for mild, moderate and severe risk, respectively. An alarmingly high prevalence of CHD risk factors was prevailed among medical students, especially among males. However, a low prevalence of smoking may indicate the success of "Smoke-free Campus" program. Screening risk factors of CHD among medical students and implementation of intervention programs are recommended. Programs to raise awareness about CHD risk factors, encourage young adult students to adopt a healthy dietary behavior and promote physical exercise should be initiated.

  6. [Risk factors and coronary heart disease prevention in selected Lódź population--part II].

    Science.gov (United States)

    Kowalski, Jan; Kos, Małgorzata; Gburek, Jolanta; Wrocławski, Witold; Pawlicki, Lucjan

    2005-12-01

    Evaluation of the knowledge on CHD risk factors in selected Lódź population was made. Realization of primary and secondary CHD prevention principles was assessed. Over 20% of patients with CHD and over 38% of subjects without CHD did not realize the prevention principles. Hypolipemic therapy was effective only in 44.21% of patients with CHD and 35.9% of subjects without CHD. Antihypertensive therapy was successful in about 55% of patients with CHD and 35% of subjects without CHD. The results of our study have shown low effectiveness of both CHD prevention principles realization and hipolipemic and antihypertensive therapy in selected Lódź population.

  7. 13CHD2–CEST NMR spectroscopy provides an avenue for studies of conformational exchange in high molecular weight proteins

    International Nuclear Information System (INIS)

    Rennella, Enrico; Huang, Rui; Velyvis, Algirdas; Kay, Lewis E.

    2015-01-01

    An NMR experiment for quantifying slow (millisecond) time-scale exchange processes involving the interconversion between visible ground state and invisible, conformationally excited state conformers is presented. The approach exploits chemical exchange saturation transfer (CEST) and makes use of 13 CHD 2 methyl group probes that can be readily incorporated into otherwise highly deuterated proteins. The methodology is validated with an application to a G48A Fyn SH3 domain that exchanges between a folded conformation and a sparsely populated and transiently formed unfolded ensemble. Experiments on a number of different protein systems, including a 360 kDa half-proteasome, establish that the sensitivity of this 13 CHD 2 13 C–CEST technique can be upwards of a factor of 5 times higher than for a previously published 13 CH 3 13 C–CEST approach (Bouvignies and Kay in J Biomol NMR 53:303–310, 2012), suggesting that the methodology will be powerful for studies of conformational exchange in high molecular weight proteins

  8. Levels of interleukin-1β in gingival crevicular fluid in patients with coronary heart disease and its relationship to periodontal status

    Science.gov (United States)

    Lenggogeny, Putri; Masulili, Sri Lelyati C.; Tadjoedin, Fatimah M.; Radi, Basuni

    2017-02-01

    Periodontitis is a risk factor for coronary heart disease (CHD). Both diseases are an inflammatory diseases and have the same potential pathogenic mechanisms. Interleukin-1β as a pro-inflammatory main cytokine, can be found in this both diseases. Gingival crevicular fluid (GCF) derived from the serum of gingival sulcus, affected by inflammatory mechanism and the amount of this fluid will increase in that situation. Objective: To analyze the relationship of interleukin-1β levels in gingival crevicular fluid (GCF) of CHD and non-CHD patients with periodontal status. Methods: Oral clinical examination (plaque index, bleeding on probing, pocket depth and clinical attachment loss) for 35 subjects with CHD and 35 non CHD were checked, laboratory test to measure the levels of Interleukin-1β was checked with enzyme-linked immunosorbent assay (ELISA). Results: There was no significant differences between interleukin-1β levels in CHD and non-CHD patients (p>0.05); there was no significant difference between the level of Interleukin-1β with periodontal status in CHD and control (non CHD) patients (p>0.05). Conclusions: levels of Interleukin-1β in CHD patients do not have a relationships with plaque index, pocket depth and clinical attachment loss, but has a relationships with bleeding on probing.

  9. Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus.

    Directory of Open Access Journals (Sweden)

    Clint L Miller

    Full Text Available Coronary heart disease (CHD is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin is a member of the basic-helix-loop-helix (bHLH transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1 element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β and Wilms tumor 1 (WT1 pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.

  10. The Burden of Cardiovascular Disease Attributable to Major Modifiable Risk Factors in Indonesia

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    Mohammad Akhtar Hussain

    2016-10-01

    Full Text Available Background: In Indonesia, coronary heart disease (CHD and stroke are estimated to cause more than 470 000 deaths annually. In order to inform primary prevention policies, we estimated the sex- and age-specific burden of CHD and stroke attributable to five major and modifiable vascular risk factors: cigarette smoking, hypertension, diabetes, elevated total cholesterol, and excess body weight. Methods: Population attributable risks for CHD and stroke attributable to these risk factors individually were calculated using summary statistics obtained for prevalence of each risk factor specific to sex and to two age categories (<55 and ≥55 years from a national survey in Indonesia. Age- and sex-specific relative risks for CHD and stroke associated with each of the five risk factors were derived from prospective data from the Asia-Pacific region. Results: Hypertension was the leading vascular risk factor, explaining 20%–25% of all CHD and 36%–42% of all strokes in both sexes and approximately one-third of all CHD and half of all strokes across younger and older age groups alike. Smoking in men explained a substantial proportion of vascular events (25% of CHD and 17% of strokes. However, given that these risk factors are likely to be strongly correlated, these population attributable risk proportions are likely to be overestimates and require verification from future studies that are able to take into account correlation between risk factors. Conclusions: Implementation of effective population-based prevention strategies aimed at reducing levels of major cardiovascular risk factors, especially blood pressure, total cholesterol, and smoking prevalence among men, could reduce the growing burden of CVD in the Indonesian population.

  11. RhoA and RhoC are involved in stromal cell-derived factor-1-induced cell migration by regulating F-actin redistribution and assembly.

    Science.gov (United States)

    Luo, Jixian; Li, Dingyun; Wei, Dan; Wang, Xiaoguang; Wang, Lan; Zeng, Xianlu

    2017-12-01

    Stromal cell-derived factor-1 (SDF-1) signaling is important to the maintenance and progression of T-cell acute lymphoblastic leukemia by inducing chemotaxis migration. To identify the mechanism of SDF-1 signaling in the migration of T-ALL, Jurkat acute lymphoblastic leukemia cells were used. Results showed that SDF-1 induces Jurkat cell migration by F-actin redistribution and assembly, which is dependent on Rho activity. SDF-1 induced RhoA and RhoC activation, as well as reactive oxygen species (ROS) production, which was inhibited by Rho inhibitor. The Rho-dependent ROS production led to subsequent cytoskeleton redistribution and assembly in the process of migration. Additionally, RhoA and RhoC were involved in SDF-1-induced Jurkat cell migration. Taken together, we found a SDF-1/CXCR4-RhoA and RhoC-ROS-cytoskeleton pathway that regulates Jurkat cell migration in response to SDF-1. This work will contribute to a clearer insight into the migration mechanism of acute lymphoblastic leukemia.

  12. Heart Disease and Depression: Is Culture a Factor?

    Science.gov (United States)

    Gholizadeh, Leila; Davidson, Patricia M; Heydari, Mehrdad; Salamonson, Yenna

    2014-07-01

    This article seeks to review and discuss the evidence linking depression, coronary heart disease (CHD), and culture. PsychInfo, CINAHL, PubMed, and Google were searched for pertinent evidence linking depression, culture, and CHD, and retrieved articles were analyzed using thematic content analysis. Identified themes were the followings: depression is a factor in development and prognosis of CHD and affects the capacity to self-manage and adhere to treatment recommendations; culture mediates mental health/illness representations and treatment-seeking behaviors; screening and assessment of depression can be affected by cultural factors; and there is a need for culturally appropriate screening and therapeutic strategies. As depression is a predictor and moderating variable in the genesis and progression of CHD, understanding how factors such as culture affect screening and management of the disease is important to inform the development of culturally and linguistically competent strategies that ensure accurate screening, detection, and treatment of depression in cardiac patients in clinical practice. © The Author(s) 2014.

  13. Prognosis and Risk Factors for Congenital Airway Anomalies in Children with Congenital Heart Disease: A Nationwide Population-Based Study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Yu-Sheng Lee

    Full Text Available The mortality risk associated with congenital airway anomalies (CAA in children with congenital heart disease (CHD is unclear. This study aimed to investigate the factors associated with CAA, and the associated mortality risk, among children with CHD.This nationwide, population-based study evaluated 39,652 children with CHD aged 0-5 years between 2000 and 2011, using the Taiwan National Health Insurance Research Database (NHIRD. We performed descriptive, logistic regression, Kaplan-Meier, and Cox regression analyses of the data.Among the children with CHD, 1,591 (4.0% had concomitant CAA. Children with CHD had an increased likelihood of CAA if they were boys (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.33-1.64, infants (OR, 5.42; 95%CI, 4.06-7.24, or had a congenital musculoskeletal anomaly (OR, 3.19; 95%CI, 2.67-3.81, and were typically identified 0-3 years after CHD diagnosis (OR, 1.33; 95%CI 1.17-1.51. The mortality risk was increased in children with CHD and CAA (crude hazard ratio [HR], 2.05; 95%CI, 1.77-2.37, even after adjusting for confounders (adjusted HR, 1.76; 95%CI, 1.51-2.04. Mortality risk also changed by age and sex (adjusted HR and 95%CI are quoted: neonates, infants, and toddlers and preschool children, 1.67 (1.40-2.00, 1.93 (1.47-2.55, and 4.77 (1.39-16.44, respectively; and boys and girls, 1.62 (1.32-1.98 and 2.01 (1.61-2.50, respectively.The mortality risk is significantly increased among children with CHD and comorbid CAA. Clinicians should actively seek CAA during the follow-up of children with CHD.

  14. NT-proBNP is associated with coronary heart disease risk in healthy older women but fails to enhance prediction beyond established risk factors: results from the British Women's Heart and Health Study.

    Science.gov (United States)

    Sattar, Naveed; Welsh, Paul; Sarwar, Nadeem; Danesh, John; Di Angelantonio, Emanuele; Gudnason, Vilmundur; Davey Smith, George; Ebrahim, Shah; Lawlor, Debbie A

    2010-03-01

    Limited evidence suggests NT-proBNP improves prediction of coronary heart disease (CHD) events but further data are needed, especially in people without pre-existing CHD and in women. We measured NT-proBNP in serum from 162 women with incident CHD events and 1226 controls (60-79 years) in a case-control study nested within the prospective British Women's Heart and Health Study. All cases and controls were free from CHD at baseline. We related NT-proBNP to CHD event risk, and determined to what extent NT-proBNP enhanced CHD risk prediction beyond established risk factors. The odds ratio for CHD per 1 standard deviation increase in log(e)NT-proBNP was 1.37 (95% CI: 1.13-1.68) in analyses adjusted for established CHD risk factors, social class, CRP and insulin. However, addition of log(e)NT-proBNP did not improve the discrimination of a prediction model including age, social class, smoking, physical activity, lipids, fasting glucose, waist:hip ratio, hypertension, statin and aspirin use, nor a standard Framingham risk score model; area under the receiver operator curve for the former model increased from 0.676 to 0.687 on inclusion of NT-proBNP (p=0.3). Furthermore, adding NT-proBNP did not improve calibration of a prediction model containing established risk factors, nor did inclusion more appropriately re-classify participants in relation to their final outcome. Findings were similar (independent associations, but no prediction improvement) for fasting insulin and CRP. These results caution against use of NT-proBNP for CHD risk prediction in healthy women and suggest a need for larger studies in both genders to resolve outstanding uncertainties.

  15. Human Factors and Their Effects on Human-Centred Assembly Systems - A Literature Review-Based Study

    Science.gov (United States)

    Wang, Q.; Abubakar, M. I.

    2017-09-01

    If a product has more than one component, then it must be assembled. Assembly of products relies on assembly systems or lines in which assembly of each product is often carried out manually by human workers following assembly sequences in various forms. It is widely understood that efficiency of assembling a product by reducing assembly times (therefore costs) is vital particularly for small and medium-sized manufacturing companies to survive in an increasingly competitive market. Ideally, it is helpful for pre-determining efficiency or productivity of a human-centred assembly system at the early design stage. To date, most research on performance of an assembly system using modelling simulation methods is focused on its “operational functions”. The term used in a narrow sense always indicates the performance of the “operational system”, which does not incorporate the effect of human factors that may also affect the system performance. This paper presents a research outcome of findings through a literature review-based study by identifying possible human factors that mostly affect the performance on human-centred manufacturing systems as part of the research project incorporating parameters of human factors into a DES (discrete event simulation) tool.

  16. De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms

    NARCIS (Netherlands)

    Weiss, Karin; Terhal, Paulien A; Cohen, Lior; Bruccoleri, Michael; Irving, Melita; Martinez, Ariel F; Rosenfeld, Jill A; Machol, Keren; Yang, Yaping; Liu, Pengfei; Walkiewicz, Magdalena; Beuten, Joke; Gomez-Ospina, Natalia; Haude, Katrina; Fong, Chin-To; Enns, Gregory M; Bernstein, Jonathan A; Fan, Judith; Gotway, Garrett; Ghorbani, Mohammad; van Gassen, Koen; Monroe, Glen R; van Haaften, Gijs; Basel-Vanagaite, Lina; Yang, Xiang-Jiao; Campeau, Philippe M; Muenke, Maximilian

    2016-01-01

    Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2β, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we

  17. Still Heart Encodes a Structural HMT, SMYD1b, with Chaperone-Like Function during Fast Muscle Sarcomere Assembly.

    Directory of Open Access Journals (Sweden)

    Kendal Prill

    Full Text Available The vertebrate sarcomere is a complex and highly organized contractile structure whose assembly and function requires the coordination of hundreds of proteins. Proteins require proper folding and incorporation into the sarcomere by assembly factors, and they must also be maintained and replaced due to the constant physical stress of muscle contraction. Zebrafish mutants affecting muscle assembly and maintenance have proven to be an ideal tool for identification and analysis of factors necessary for these processes. The still heart mutant was identified due to motility defects and a nonfunctional heart. The cognate gene for the mutant was shown to be smyd1b and the still heart mutation results in an early nonsense codon. SMYD1 mutants show a lack of heart looping and chamber definition due to a lack of expression of heart morphogenesis factors gata4, gata5 and hand2. On a cellular level, fast muscle fibers in homozygous mutants do not form mature sarcomeres due to the lack of fast muscle myosin incorporation by SMYD1b when sarcomeres are first being assembled (19hpf, supporting SMYD1b as an assembly protein during sarcomere formation.

  18. Heat shock-induced accumulation of translation elongation and termination factors precedes assembly of stress granules in S. cerevisiae.

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    Tomas Grousl

    Full Text Available In response to severe environmental stresses eukaryotic cells shut down translation and accumulate components of the translational machinery in stress granules (SGs. Since they contain mainly mRNA, translation initiation factors and 40S ribosomal subunits, they have been referred to as dominant accumulations of stalled translation preinitiation complexes. Here we present evidence that the robust heat shock-induced SGs of S. cerevisiae also contain translation elongation factors eEF3 (Yef3p and eEF1Bγ2 (Tef4p as well as translation termination factors eRF1 (Sup45p and eRF3 (Sup35p. Despite the presence of the yeast prion protein Sup35 in heat shock-induced SGs, we found out that its prion-like domain is not involved in the SGs assembly. Factors eEF3, eEF1Bγ2 and eRF1 were accumulated and co-localized with Dcp2 foci even upon a milder heat shock at 42°C independently of P-bodies scaffolding proteins. We also show that eEF3 accumulations at 42°C determine sites of the genuine SGs assembly at 46°C. We suggest that identification of translation elongation and termination factors in SGs might help to understand the mechanism of the eIF2α factor phosphorylation-independent repression of translation and SGs assembly.

  19. Measuring method for effective neutron multiplication factor upon containing irradiated fuel assembly

    International Nuclear Information System (INIS)

    Ueda, Makoto; Mitsuhashi, Ishi; Sasaki, Tomoharu.

    1993-01-01

    A portion of irradiated fuel assemblies at a place where a reactivity effect is high, that is, at a place where neutron importance is high is replaced with standard fuel assemblies having a known composition to measure neutron fluxes at each of the places. An effective composition at the periphery of the standard fuel assemblies is determined by utilizing a calibration curve determined separately based on the composition and neutron flux values of the standard assemblies. By using the calibration curve determined separately based on this composition and the known composition of the standard fuel assemblies, an effective neutron multiplication factor for the fuel containing portion containing the irradiated fuel assemblies is recognized. Then, subcriticality is ensured and critical safety upon containing the fuel assemblies can be secured quantitatively. (N.H.)

  20. MUTATION ON WD DIPEPTIDE MOTIFS OF THE p48 SUBUNIT OF CHROMATIN ASSEMBLY FACTOR-1 CAUSING VIABILITY AND GROWTH OF DT40 CHICKEN B CELL LINE

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    Ahyar Ahmad

    2010-07-01

    Full Text Available Chromatin assembly factor-1 (CAF-1, a protein complex consisting of three subunits, p150, p60, and p48, is highly conserved from yeast to humans and facilitated nucleosome assembly of newly replicated DNA. The p48 subunit, CAF-1p48 (p48, with seven WD (Trp-Asp repeat motifs, is a member of the WD protein family. The immunoprecipitation experiment revealed that ß-propeller structure of p48 was less stringent for it's binding to HDAC-1, but more stringent for its binding to both histones H4 and CAF-1p60 but not to ASF-1, indicating that the proper ß-propeller structure of p48 is essential for the binding to these two proteins histone H4 and CAF-1p60. Complementation experiments, involving missense and truncated mutants of FLAG-tagged p48, revealed that mutations of every of seven WD dipeptide motifs, like both the N-terminal and C-terminal truncated mutations, could not rescue for the tet-induced lethality. These results indicate not only that p48 is essential for the viability of vertebrate cells, although the yeast p48 homolog is nonessential, but also that all the seven WD dipeptide motifs are necessary for the maintenance of the proper structure of p48 that is fundamentally important for cell viability.   Keywords: Chromatin assembly factor-1, complementation experiments, viability

  1. Variations of CITED2 are associated with congenital heart disease (CHD in Chinese population.

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    Yan Liu

    Full Text Available CITED2 was identified as a cardiac transcription factor which is essential to the heart development. Cited2-deficient mice showed cardiac malformations, adrenal agenesis and neural crest defects. To explore the potential impact of mutations in CITED2 on congenital heart disease (CHD in humans, we screened the coding region of CITED2 in a total of 700 Chinese people with congenital heart disease and 250 healthy individuals as controls. We found five potential disease-causing mutations, p.P140S, p.S183L, p.S196G, p.Ser161delAGC and p. Ser192_Gly193delAGCGGC. Two mammalian two-hybrid assays showed that the last four mutations significantly affected the interaction between p300CH1 and CITED2 or HIF1A. Further studies showed that four CITED2 mutations recovered the promoter activity of VEGF by decreasing its competitiveness with HIF1A for binding to p300CH1 and three mutations decreased the consociation of TFAP2C and CITED2 in the transactivation of PITX2C. Both VEGF and PITX2C play very important roles in cardiac development. In conclusion, we demonstrated that CITED2 has a potential causative impact on congenital heart disease.

  2. Formation of the embryonic organizer is restricted by the competitive influences of Fgf signaling and the SoxB1 transcription factors.

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    Cheng-Liang Kuo

    Full Text Available The organizer is one of the earliest structures to be established during vertebrate development and is crucial to subsequent patterning of the embryo. We have previously shown that the SoxB1 transcription factor, Sox3, plays a central role as a transcriptional repressor of zebrafish organizer gene expression. Recent data suggest that Fgf signaling has a positive influence on organizer formation, but its role remains to be fully elucidated. In order to better understand how Fgf signaling fits into the complex regulatory network that determines when and where the organizer forms, the relationship between the positive effects of Fgf signaling and the repressive effects of the SoxB1 factors must be resolved. This study demonstrates that both fgf3 and fgf8 are required for expression of the organizer genes, gsc and chd, and that SoxB1 factors (Sox3, and the zebrafish specific factors, Sox19a and Sox19b can repress the expression of both fgf3 and fgf8. However, we also find that these SoxB1 factors inhibit the expression of gsc and chd independently of their repression of fgf expression. We show that ectopic expression of organizer genes induced solely by the inhibition of SoxB1 function is dependent upon the activation of fgf expression. These data allow us to describe a comprehensive signaling network in which the SoxB1 factors restrict organizer formation by inhibiting Fgf, Nodal and Wnt signaling, as well as independently repressing the targets of that signaling. The organizer therefore forms only where Nodal-induced Fgf signaling overlaps with Wnt signaling and the SoxB1 proteins are absent.

  3. Trends in risk factors for coronary heart disease in the Netherlands

    NARCIS (Netherlands)

    Koopman, C.; Vaartjes, I.; Blokstra, A.; Verschuren, W. M M; Visser, M.; Deeg, D. J H; Bots, M. L.; Van Dis, I.

    2016-01-01

    Background: Favourable trends in risk factor levels in the general population may partly explain the decline in coronary heart disease (CHD) morbidity and mortality. Our aim was to present long-term national trends in established risk factors for CHD.  Methods: Data were obtained from five data

  4. Trends in risk factors for coronary heart disease in the Netherlands

    NARCIS (Netherlands)

    Koopman, C; Vaartjes, I; Blokstra, A; Verschuren, W M M; Visser, M; Deeg, D J H; Bots, M L; van Dis, I

    2016-01-01

    BACKGROUND: Favourable trends in risk factor levels in the general population may partly explain the decline in coronary heart disease (CHD) morbidity and mortality. Our aim was to present long-term national trends in established risk factors for CHD. METHODS: Data were obtained from five data

  5. Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Lee, Chi Ho; Woo, Yu Cho; Chow, Wing Sun; Cheung, Chloe Yu Yan; Fong, Carol Ho Yi; Yuen, Michele Mae Ann; Xu, Aimin; Tse, Hung Fat; Lam, Karen Siu Ling

    2017-06-06

    Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases. Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; P 1). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; P =0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors. We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  6. MR-1S Interacts with PET100 and PET117 in Module-Based Assembly of Human Cytochrome c Oxidase

    Directory of Open Access Journals (Sweden)

    Sara Vidoni

    2017-02-01

    Full Text Available The biogenesis of human cytochrome c oxidase (COX is an intricate process in which three mitochondrial DNA (mtDNA-encoded core subunits are assembled in a coordinated way with at least 11 nucleus-encoded subunits. Many chaperones shared between yeast and humans are involved in COX assembly. Here, we have used a MT-CO3 mutant cybrid cell line to define the composition of assembly intermediates and identify new human COX assembly factors. Quantitative mass spectrometry analysis led us to modify the assembly model from a sequential pathway to a module-based process. Each module contains one of the three core subunits, together with different ancillary components, including HIGD1A. By the same analysis, we identified the short isoform of the myofibrillogenesis regulator 1 (MR-1S as a new COX assembly factor, which works with the highly conserved PET100 and PET117 chaperones to assist COX biogenesis in higher eukaryotes.

  7. MR-1S Interacts with PET100 and PET117 in Module-Based Assembly of Human Cytochrome c Oxidase.

    Science.gov (United States)

    Vidoni, Sara; Harbour, Michael E; Guerrero-Castillo, Sergio; Signes, Alba; Ding, Shujing; Fearnley, Ian M; Taylor, Robert W; Tiranti, Valeria; Arnold, Susanne; Fernandez-Vizarra, Erika; Zeviani, Massimo

    2017-02-14

    The biogenesis of human cytochrome c oxidase (COX) is an intricate process in which three mitochondrial DNA (mtDNA)-encoded core subunits are assembled in a coordinated way with at least 11 nucleus-encoded subunits. Many chaperones shared between yeast and humans are involved in COX assembly. Here, we have used a MT-CO3 mutant cybrid cell line to define the composition of assembly intermediates and identify new human COX assembly factors. Quantitative mass spectrometry analysis led us to modify the assembly model from a sequential pathway to a module-based process. Each module contains one of the three core subunits, together with different ancillary components, including HIGD1A. By the same analysis, we identified the short isoform of the myofibrillogenesis regulator 1 (MR-1S) as a new COX assembly factor, which works with the highly conserved PET100 and PET117 chaperones to assist COX biogenesis in higher eukaryotes. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 21 CFR 101.81 - Health claims: Soluble fiber from certain foods and risk of coronary heart disease (CHD).

    Science.gov (United States)

    2010-04-01

    ... health goal that can assist in reducing risk of CHD. High blood total and LDL-cholesterol are major...-cholesterol levels. (c) Requirements. (1) All requirements set forth in § 101.14 shall be met. The label and... also provide additional information about the benefits of exercise and management of body weight to...

  9. Absence epilepsy and the CHD2 gene: an adolescent male with moderate intellectual disability, short-lasting psychoses, and an interstitial deletion in 15q26.1–q26.2

    Directory of Open Access Journals (Sweden)

    Verhoeven WMA

    2016-05-01

    Full Text Available Willem MA Verhoeven,1,2 Jos IM Egger,1,3,4 Alida C Knegt,5 José Zuydam,6 Tjitske Kleefstra7 1Centre of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry, Venray, 2Department of Psychiatry, Erasmus University Medical Center, Rotterdam, 3Donders Institute for Brain, Cognition and Behaviour, 4Behavioural Science Institute, Radboud University, Nijmegen, 5Department of Clinical Genetics, University of Amsterdam Medical Center, Amsterdam, 6Reigersdaal Institute for Intellectual Disabilities, Heerhugowaard, 7Department of Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands Abstract: Deletions of the 15q26 region encompassing the chromodomain helicase DNA binding domain 2 (CHD2 gene have been associated with intellectual disability, behavioral problems, and several types of epilepsy. Including the cases mentioned in ECARUCA (European cytogeneticists association register of unbalanced chromosome aberrations and DECIPHER (database of genomic variation and phenotype in humans using ensembl resources, so far, a total of 13 intellectually disabled patients with a genetically proven deletion of the CHD2 gene are described, of whom eleven had a history of severe forms of epilepsy starting from a young age. In this article, a moderately intellectually disabled 15-year-old male with a 15q26.1–q26.2 interstitial deletion is reported, who was referred for analysis of two recent short-lasting psychotic episodes that were nonresponsive to antipsychotic treatment and recurrent disinhibited behaviors since early infancy. Careful interdisciplinary assessment revealed that the psychotic phenomena originated from a previously unrecognized absence epilepsy. Treatment with valproic acid was started which resulted in full remission of psychotic symptoms, and consequently, substantial improvement of behavior. It was concluded that in case of (rare developmental disorders with genetically proven etiology, a detailed inventory of

  10. ECHOCARDIOGRAPHY BASED STUDY OF THE PREVALENCE AND PATTERN OF CONGENITAL HEART DISEASE (CHD IN 5-15 YEARS OLD SCHOOL GOING CHILDREN OF MANIPUR, A NORTH-EAST HILLY INDIAN STATE

    Directory of Open Access Journals (Sweden)

    Rajendra Singh Thangjam

    2017-12-01

    Full Text Available BACKGROUND CHD is the leading cause of morbidity and mortality in the developed world, while reports from India looking into the burden of the disease have been variable depending on the age group of subjects studied and the methodology involved. We were interested to find the prevalence and pattern of the disease in this north eastern Indian state of Manipur, which has a unique geographical and racial composition. MATERIALS AND METHODS This is a community based, prospective, cross sectional study where each and every child aged 5-15 years from randomly selected schools of Manipur were examined by 2D colour Doppler Echocardiography and physically as well, where the examiners were blinded, and the findings were noted independent of each other. The anthropometric parameters, clinical details and echocardiography findings were all recorded. RESULTS Of the 3600 children examined, 47 cases of CHD were detected, giving echocardiographic prevalence of 13 per 1000 where BAV (44% was found as the commonest lesion followed by VSD (17% and ASD (14%. Clinically detectable lesion was found in 21 subjects (VSD -8, ASD-7, PS-3, PDA -1, AVSD-1, BAV-1 with AR. Of the clinically detectable CHD, VSD was the commonest followed by ASD. In the subclinical CHD category, 20 cases of BAV, 4 cases of mild MVP without MR, 1 case of apical LV discompacta, 1 case of IASA were detected. CONCLUSION The echocardiography prevalence of congenital heart disease in school going children of Manipur is 13/1000. This highest ever reported prevalence of CHD in children is most probably related to the use of the highly sensitive investigative tool of Echocardiography in each subject of our study resulting in detection of clinically silent lesions.

  11. Psychosocial factors in the development of heart disease in women: current research and future directions.

    Science.gov (United States)

    Low, Carissa A; Thurston, Rebecca C; Matthews, Karen A

    2010-11-01

    To review the recent (1995-2009) literature on psychosocial risk and protective factors for coronary heart disease (CHD) among women, including negative emotions, stress, social relationships, and positive psychological factors. Articles for the review were identified using PubMed and bibliographies of relevant articles. Eligible studies included at least 100 women and either focused on a) exclusively female participants or b) both men and women, conducting either gender-stratified analyses or examining interactions with gender. Sixty-seven published reports were identified that examined prospective associations with incident or recurrent CHD. In general, evidence suggests that depression, anxiety disorders, anger suppression, and stress associated with relationships or family responsibilities are associated with elevated CHD risk among women, that supportive social relationships and positive psychological factors may be associated with reduced risk, and that general anxiety, hostility, and work-related stress are less consistently associated with CHD among women relative to men. A growing literature supports the significance of psychosocial factors for the development of CHD among women. Consideration of both traditional psychosocial factors (e.g., depression) and factors that may be especially important for women (e.g., stress associated with responsibilities at home or multiple roles) may improve identification of women at elevated risk as well as the development of effective psychological interventions for women with or at risk for CHD.

  12. De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms.

    Science.gov (United States)

    Weiss, Karin; Terhal, Paulien A; Cohen, Lior; Bruccoleri, Michael; Irving, Melita; Martinez, Ariel F; Rosenfeld, Jill A; Machol, Keren; Yang, Yaping; Liu, Pengfei; Walkiewicz, Magdalena; Beuten, Joke; Gomez-Ospina, Natalia; Haude, Katrina; Fong, Chin-To; Enns, Gregory M; Bernstein, Jonathan A; Fan, Judith; Gotway, Garrett; Ghorbani, Mohammad; van Gassen, Koen; Monroe, Glen R; van Haaften, Gijs; Basel-Vanagaite, Lina; Yang, Xiang-Jiao; Campeau, Philippe M; Muenke, Maximilian

    2016-10-06

    Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2β, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we report five individuals with de novo missense substitutions in CHD4 identified through whole-exome sequencing and web-based gene matching. These individuals have overlapping phenotypes including developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. The variants, c.3380G>A (p.Arg1127Gln), c.3443G>T (p.Trp1148Leu), c.3518G>T (p.Arg1173Leu), and c.3008G>A, (p.Gly1003Asp) (GenBank: NM_001273.3), affect evolutionarily highly conserved residues and are predicted to be deleterious. Previous studies in yeast showed the equivalent Arg1127 and Trp1148 residues to be crucial for SNF2 function. Furthermore, mutations in the same positions were reported in malignant tumors, and a de novo missense substitution in an equivalent arginine residue in the C-terminal helicase domain of SMARCA4 is associated with Coffin Siris syndrome. Cell-based studies of the p.Arg1127Gln and p.Arg1173Leu mutants demonstrate normal localization to the nucleus and HDAC1 interaction. Based on these findings, the mutations potentially alter the complex activity but not its formation. This report provides evidence for the role of CHD4 in human development and expands an increasingly recognized group of Mendelian disorders involving chromatin remodeling and modification. Published by Elsevier Inc.

  13. Upper extremities musculoskeletal disorders: Prevalence and associated ergonomic factors in an electronic assembly factory

    Directory of Open Access Journals (Sweden)

    Somthus Pullopdissakul

    2013-10-01

    Full Text Available Objectives:To determine the magnitude, distribution and associated ergonomic factors of upper extremities musculoskeletal disorders (UEMSD among workers of electronic assembly in Thailand. Material and Methods: This was a cross-sectional study. 591 of 853 workers in an electronic and electrical appliance assembly factory in Bangkok, Thailand, participated in this study. A self-administered questionnaire consisting of demographic data and ergonomic factors was collected from October 2010 to January 2011. Clinical examination of each worker was performed by an occupational physician. The criteria for diagnosis of UEMSD came as a result of a consensus reached by a group of orthopedists. The associated factors were analyzed using a multiple logistic regression. Results: The point prevalence of clinically diagnosed UEMSD was as follows: radial styloid tenosynovitis - 13.03% (95% CI: 10.31-15.75, trigger finger - 9.48% (95% CI: 7.11-11.84, carpal tunnel syndrome - 8.12% (95% CI: 5.91-10.33, lateral epicondylitis - 3.38% (95% CI: 1.92-4.85, and medial epicondylitis - 1.69% (95% CI: 0.65-2.73, respectively. The adjusted odds ratio with statistical significance associated with UEMSD was as follows: high force of wrist - 1.78 (95% CI: 1.06-2.99, awkward posture of wrist - 2.37 (95% CI: 1.28-4.37 and contact stress at wrists - 1.75 (95% CI: 1.02-3.00 to develop radial styloid tenosynovitis. For trigger finger, the ratios were awkward posture of fingers - 2.09 (95% CI: 1.12-3.90 and contact stress on finger - 1.86 (95% CI: 1.04-3.34. For medial epicondylitis, it was an awkward posture of using elbows - 3.14 (95% CI: 1.10-8.95. However, this study did not find any associations between repetitive motion and any UEMSD. Conclusions: UEMSD are most commonly found in electronic assembly workers. The relevant parties should provide comprehensive ergonomic resolution for these workers.

  14. Effects of a novel multimodal group intervention on myocardial perfusion in patients with coronary heart disease (CHD)

    International Nuclear Information System (INIS)

    Theissen, P.; Schicha, H.; Albus, C.; Koehle, K.; Griebenow, R.; Son, P.

    2002-01-01

    Full text: Recently, it could be shown that a multimodal intervention can promote health behavior in patients with CHD. Purpose of the actual study was to evaluate the effects on somatic endpoints, e.g. myocardial perfusion. We randomly assigned 77 patients (age 54 ± 6.9 y, male 87 %) with angiographically documented CHD to a multimodal group intervention plus standardized cardiological care (INT n=39) or standardized cardiological care only (CO n = 38). The intervention, for out-patients only, consisted of 77.5 hours of group-psychotherapy, relaxation and exercise training, and teaching lessons for one year. A Thallium myocardial perfusion scintigraphy (MyoSc) (after bicycle exercise test and at rest; 70 - 110 MBq Thallium-201, SPECT-technique, quantitative wash-out (w.-o.) analysis derived from polar maps) was performed at baseline, after 2 years, and 3 years, respectively: A w.-o. increase res. decrease by 5 % or more indicated an improved / a diminished myocardial perfusion within the affected coronary artery territory. Results were analyzed on an intention to treat basis. 70/77 patients (91 %) completed the study (drop-outs CO n=4, INT n=3). After 2 years (1st interval), there was no significant difference between groups. After 3 years (2nd interval) 36/39 patients (92.3 %) of INT showed a stable or improved myocardial perfusion, compared to 18/38 patients (47.4 %) of CO (p= 0.008). The recent data analysis demonstrates the extra benefit of a multimodal intervention, compared to standardized cardiological care alone, on myocardial perfusion in CHD patients. (author)

  15. C-reactive protein and serum creatinine, but not haemoglobin A1c, are independent predictors of coronary heart disease risk in non-diabetic Chinese.

    Science.gov (United States)

    Salim, Agus; Tai, E Shyong; Tan, Vincent Y; Welsh, Alan H; Liew, Reginald; Naidoo, Nasheen; Wu, Yi; Yuan, Jian-Min; Koh, Woon P; van Dam, Rob M

    2016-08-01

    In western populations, high-sensitivity C-reactive protein (hsCRP), and to a lesser degree serum creatinine and haemoglobin A1c, predict risk of coronary heart disease (CHD). However, data on Asian populations that are increasingly affected by CHD are sparse and it is not clear whether these biomarkers can be used to improve CHD risk classification. We conducted a nested case-control study within the Singapore Chinese Health Study cohort, with incident 'hard' CHD (myocardial infarction or CHD death) as an outcome. We used data from 965 men (298 cases, 667 controls) and 528 women (143 cases, 385 controls) to examine the utility of hsCRP, serum creatinine and haemoglobin A1c in improving the prediction of CHD risk over and above traditional risk factors for CHD included in the ATP III model. For each sex, the performance of models with only traditional risk factors used in the ATP III model was compared with models with the biomarkers added using weighted Cox proportional hazards analysis. The impact of adding these biomarkers was assessed using the net reclassification improvement index. For men, loge hsCRP (hazard ratio 1.25, 95% confidence interval: 1.05; 1.49) and loge serum creatinine (hazard ratio 4.82, 95% confidence interval: 2.10; 11.04) showed statistically significantly associations with CHD risk when added to the ATP III model. We did not observe a significant association between loge haemoglobin A1c and CHD risk (hazard ratio 1.83, 95% confidence interval: 0.21; 16.06). Adding hsCRP and serum creatinine to the ATP III model improved risk classification in men with a net gain of 6.3% of cases (p-value = 0.001) being reclassified to a higher risk category, while it did not significantly reduce the accuracy of classification for non-cases. For women, squared hsCRP was borderline significantly (hazard ratio 1.01, 95% confidence interval: 1.00; 1.03) and squared serum creatinine was significantly (hazard ratio 1.81, 95% confidence interval: 1.49; 2

  16. Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity.

    Science.gov (United States)

    Sojka, Stephen; Amin, Nirav M; Gibbs, Devin; Christine, Kathleen S; Charpentier, Marta S; Conlon, Frank L

    2014-08-01

    The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development. © 2014. Published by The Company of Biologists Ltd.

  17. Types of social supports predicting health-related quality of life among adult patients with CHD in the Institut Jantung Negara (National Heart Institute), Malaysia.

    Science.gov (United States)

    Tye, Sue K; Kandavello, Geetha; Gan, Kah L

    2017-01-01

    The objectives of this study were to examine which types of social supports - emotional/informational support, tangible support, affectionate support, and positive interactions - are the predictors of health-related quality of life (HRQoL) in adult patients with CHD and to assess the influence of demographic variables and clinical factors on these variables. In total, 205 adult patients with CHD from the National Heart Institute, Malaysia, were recruited. Patients were first screened by cardiology consultants to ensure they fit the inclusion criteria before filling in questionnaires, which were medical outcome studies - social support survey and AQoL-8D. Results/conclusions All social supports and their subscales were found to have mild-to-moderate significant relationships with physical dimension, psychological dimension, and overall HRQoL; however, only positive interaction, marital status, and types of diagnosis were reported as predictors of HRQoL. Surprisingly, with regard to the physical dimension of quality of life, social supports were not significant predictors, but educational level, marital status, and types of diagnosis were significant predictors. Positive interaction, affectionate support, marital status, and types of diagnosis were again found to be predictors in the aspects of the psychological dimension of quality of life. In conclusion, positive interaction and affectionate support, which include elements of fun, relaxation, love, and care, should be included in the care of adult patients with CHD.

  18. Inter-assembly gap deviations in VVER-1000: Accounting for effects on engineering margin factors

    Energy Technology Data Exchange (ETDEWEB)

    Shishkov, Lev; Gorodkov, Sergey; Mikailov, Eldar; Sukhino-Khomenko, Evgenia [Nuclear Research Centre ' ' Kurchatov Institute' ' , Moscow (Russian Federation)

    2015-09-15

    Jacketless fuel assemblies change their form in the course of operation. Often they bow lengthwise. Primarily, these fuel assembly (FA) bows threaten to reduce the control rods' fall rate, but at the same time they change (e.g. increase) the amount of moderator in inter-assembly gaps, thus producing additional power surges. Gap sizes vary randomly and their impact is accounted for with the help of engineering margin factors. For VVER-1000, this account of engineering margin factors increases the fuel component of electricity generation cost by 3 - 5 %, and a half of this increase is due to inter- assembly gap variations. This paper discusses the technique used to account for the impact produced by these gaps on fuel rod power; gives numerical values of sensitivity factors for power variations vs. gap sizes depending on the computational model assumed; and discusses the interference of gap effects and the account of power and coolant temperature feedbacks.

  19. MAS NMR of HIV-1 protein assemblies

    Science.gov (United States)

    Suiter, Christopher L.; Quinn, Caitlin M.; Lu, Manman; Hou, Guangjin; Zhang, Huilan; Polenova, Tatyana

    2015-04-01

    The negative global impact of the AIDS pandemic is well known. In this perspective article, the utility of magic angle spinning (MAS) NMR spectroscopy to answer pressing questions related to the structure and dynamics of HIV-1 protein assemblies is examined. In recent years, MAS NMR has undergone major technological developments enabling studies of large viral assemblies. We discuss some of these evolving methods and technologies and provide a perspective on the current state of MAS NMR as applied to the investigations into structure and dynamics of HIV-1 assemblies of CA capsid protein and of Gag maturation intermediates.

  20. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

    Science.gov (United States)

    Yiannakouris, Nikos; Katsoulis, Michail; Trichopoulou, Antonia; Ordovas, Jose M; Trichopoulos, Dimitrios

    2014-01-01

    Objectives An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for several conventional cardiovascular risk factors (ConvRFs), including smoking, hypertension, type-2 diabetes mellitus (T2DM), body mass index (BMI), physical activity and adherence to the Mediterranean diet. Design A case–control study. Setting The general Greek population of the EPIC study. Participants and outcome measures 477 patients with medically confirmed incident CHD and 1271 controls participated in this study. We estimated the ORs for CHD by dividing participants at higher or lower GRS and, alternatively, at higher or lower ConvRF, and calculated the relative excess risk due to interaction (RERI) as a measure of deviation from additivity. Results The joint presence of higher GRS and higher risk ConvRF was in all instances associated with an increased risk of CHD, compared with the joint presence of lower GRS and lower risk ConvRF. The OR (95% CI) was 1.7 (1.2 to 2.4) for smoking, 2.7 (1.9 to 3.8) for hypertension, 4.1 (2.8 to 6.1) for T2DM, 1.9 (1.4 to 2.5) for lower physical activity, 2.0 (1.3 to 3.2) for high BMI and 1.5 (1.1 to 2.1) for poor adherence to the Mediterranean diet. In all instances, RERI values were fairly small and not statistically significant, suggesting that the GRS and the ConvRFs do not have effects beyond additivity. Conclusions Genetic predisposition to CHD, operationalised through a multilocus GRS, and ConvRFs have essentially additive effects on CHD risk. PMID:24500614

  1. 21 CFR 101.82 - Health claims: Soy protein and risk of coronary heart disease (CHD).

    Science.gov (United States)

    2010-04-01

    ... following fashion: FDA will measure total protein content by the appropriate method of analysis given in the... which there is general scientific agreement: A family history of CHD; elevated blood total and LDL...

  2. Paramecium tetraurelia chromatin assembly factor-1-like protein PtCAF-1 is involved in RNA-mediated control of DNA elimination.

    Science.gov (United States)

    Ignarski, Michael; Singh, Aditi; Swart, Estienne C; Arambasic, Miroslav; Sandoval, Pamela Y; Nowacki, Mariusz

    2014-10-29

    Genome-wide DNA remodelling in the ciliate Paramecium is ensured by RNA-mediated trans-nuclear crosstalk between the germline and the somatic genomes during sexual development. The rearrangements include elimination of transposable elements, minisatellites and tens of thousands non-coding elements called internally eliminated sequences (IESs). The trans-nuclear genome comparison process employs a distinct class of germline small RNAs (scnRNAs) that are compared against the parental somatic genome to select the germline-specific subset of scnRNAs that subsequently target DNA elimination in the progeny genome. Only a handful of proteins involved in this process have been identified so far and the mechanism of DNA targeting is unknown. Here we describe chromatin assembly factor-1-like protein (PtCAF-1), which we show is required for the survival of sexual progeny and localizes first in the parental and later in the newly developing macronucleus. Gene silencing shows that PtCAF-1 is required for the elimination of transposable elements and a subset of IESs. PTCAF-1 depletion also impairs the selection of germline-specific scnRNAs during development. We identify specific histone modifications appearing during Paramecium development which are strongly reduced in PTCAF-1 depleted cells. Our results demonstrate the importance of PtCAF-1 for the epigenetic trans-nuclear cross-talk mechanism. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Rac1 augments Wnt signaling by stimulating β-catenin–lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

    Science.gov (United States)

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

    2015-01-01

    ABSTRACT β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1–β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin–lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin–LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  4. Identification of Factors Promoting HBV Capsid Self-Assembly by Assembly-Promoting Antivirals.

    Science.gov (United States)

    Rath, Soumya Lipsa; Liu, Huihui; Okazaki, Susumu; Shinoda, Wataru

    2018-02-26

    Around 270 million individuals currently live with hepatitis B virus (HBV) infection. Heteroaryldihydropyrimidines (HAPs) are a family of antivirals that target the HBV capsid protein and induce aberrant self-assembly. The capsids formed resemble the native capsid structure but are unable to propagate the virus progeny because of a lack of RNA/DNA. Under normal conditions, self-assembly is initiated by the viral genome. The mode of action of HAPs, however, remains largely unknown. In this work, using molecular dynamics simulations, we attempted to understand the action of HAP by comparing the dynamics of capsid proteins with and without HAPs. We found that the inhibitor is more stable in higher oligomers. It retains its stability in the hexamer throughout 1 μs of simulation. Our results also show that the inhibitor might help in stabilizing the C-terminus, the HBc 149-183 arginine-rich domain of the capsid protein. The C-termini of dimers interact with each other, assisted by the HAP inhibitor. During capsid assembly, the termini are supposed to directly interact with the viral genome, thereby suggesting that the viral genome might work in a similar way to stabilize the capsid protein. Our results may help in understanding the underlying molecular mechanism of HBV capsid self-assembly, which should be crucial for exploring new drug targets and structure-based drug design.

  5. Sex differences in risk factors for coronary heart disease: a study in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Oliveira Helena CF

    2001-04-01

    Full Text Available Abstract Background In Brazil coronary heart disease (CHD constitutes the most important cause of death in both sexes in all the regions of the country and interestingly, the difference between the sexes in the CHD mortality rates is one of the smallest in the world because of high rates among women. Since a question has been raised about whether or how the incidence of several CHD risk factors differs between the sexes in Brazil the prevalence of various risk factors for CHD such as high blood cholesterol, diabetes mellitus, hypertension, obesity, sedentary lifestyle and cigarette smoking was compared between the sexes in a Brazilian population; also the relationships between blood cholesterol and the other risk factors were evaluated. Results The population presented high frequencies of all the risk factors evaluated. High blood cholesterol (CHOL and hypertension were more prevalent among women as compared to men. Hypertension, diabetes and smoking showed equal or higher prevalence in women in pre-menopausal ages as compared to men. Obesity and physical inactivity were equally prevalent in both sexes respectively in the postmenopausal age group and at all ages. CHOL was associated with BMI, sex, age, hypertension and physical inactivity. Conclusions In this population the high prevalence of the CHD risk factors indicated that there is an urgent need for its control; the higher or equal prevalences of several risk factors in women could in part explain the high rates of mortality from CHD in females as compared to males.

  6. Dynamical analysis of critical assembly CC-1

    International Nuclear Information System (INIS)

    Aleman Fernandez, J.R.

    1990-01-01

    The computer code CC-1, elaborated for the analysis of transients in Critical Assemblies is described. The results by the program are compared with the ones presented in the Safety Report for the Critical Assembly of ''La Quebrada'' Nuclear Research Centre (CIN). 7 refs

  7. Association between fatness and coronary heart disease risk factors ...

    African Journals Online (AJOL)

    Body fat was measured by bioelectrical impedance analysis (BIA), and lipid profile (cholesterol, triglycerides and glucose) by the fasting blood test. Weak correlations were obtained between fatness and the CHD risk factors for both genders. Positive correlations were reported for fatness against all the CHD variables except ...

  8. Socio-economic status, risk factors and coronary heart disease ...

    African Journals Online (AJOL)

    The relationship of socio-economic status (SES) indicators and coronary risk factors (RFs) with coronary heart disease (CHD) prevalence was examined in 5620 subjects aged 20 ... The SES indicators had Iitlle or no independent effect on CHD prevalence in multivariate logistic analyses after, inclusion of the standard RFs.

  9. Self-assembling peptide amphiphiles and related methods for growth factor delivery

    Science.gov (United States)

    Stupp, Samuel I [Chicago, IL; Donners, Jack J. J. M.; Silva, Gabriel A [Chicago, IL; Behanna, Heather A [Chicago, IL; Anthony, Shawn G [New Stanton, PA

    2009-06-09

    Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

  10. The Cac2 subunit is essential for productive histone binding and nucleosome assembly in CAF-1

    Energy Technology Data Exchange (ETDEWEB)

    Mattiroli, Francesca; Gu, Yajie; Balsbaugh, Jeremy L.; Ahn, Natalie G.; Luger, Karolin

    2017-04-18

    Nucleosome assembly following DNA replication controls epigenome maintenance and genome integrity. Chromatin assembly factor 1 (CAF-1) is the histone chaperone responsible for histone (H3-H4)2 deposition following DNA synthesis. Structural and functional details for this chaperone complex and its interaction with histones are slowly emerging. Using hydrogen-deuterium exchange coupled to mass spectrometry, combined with in vitro and in vivo mutagenesis studies, we identified the regions involved in the direct interaction between the yeast CAF-1 subunits, and mapped the CAF-1 domains responsible for H3-H4 binding. The large subunit, Cac1 organizes the assembly of CAF-1. Strikingly, H3-H4 binding is mediated by a composite interface, shaped by Cac1-bound Cac2 and the Cac1 acidic region. Cac2 is indispensable for productive histone binding, while deletion of Cac3 has only moderate effects on H3-H4 binding and nucleosome assembly. These results define direct structural roles for yeast CAF-1 subunits and uncover a previously unknown critical function of the middle subunit in CAF-1.

  11. Factors Associated with Readmission of Patients with Congenital Heart Disease in a Swiss University Hospital.

    Science.gov (United States)

    Chave, Morgane; Marques-Vidal, Pedro

    2017-04-01

    Congenital heart defects (CHD) lead to extensive use of healthcare resources. Still, there is little information available regarding readmission rates or associated factors. We sought to evaluate readmission rates and their determinants among patients with CHD hospitalized in a Swiss university hospital. We conducted a retrospective study using data from all non-adult (readmissions, 83 (86.5%) were related to the CHD. Median time to readmission was 10 days (interquartile range 6-20) and median length of readmission was 12 days (interquartile range 6-20). After multivariate adjustment, foreign nationality, greater distance to hospital and length of index hospitalization readmission. Patients who underwent surgery were less likely to be readmitted (8.7%). We conclude that readmissions were frequent, almost 1 in 10 patients, and associated with several socio-clinical factors. Providing patients who live far from hospital with specialized care closer to home may help reduce the rate of readmission.

  12. resources 1..1

    Indian Academy of Sciences (India)

    http://www.ias.ac.in/jgenet/OnlineResources/90/e34.pdf. Morinha F., Carvalho M., Ferro A., Guedes-Pinto H., Rodrigues R. and Bastos E. 2011 Molecular sexing and analysis of CHD1-Z and. CHD1-W sequence variations in wild common quail (Coturnix c. coturnix) and domesticated Japanese quail (Coturnix c. japonica).

  13. Turkish assessment of SURF (SUrvey of Risk Factor Management) study: Control rates of cardiovascular risk factors derived from databases of 15 different levels of health centers in Turkey.

    Science.gov (United States)

    Tokgözoğlu, Lale; Oğuz, Aytekin; Balcı, Mustafa Kemal; Temizhan, Ahmet; Güldal Altunoğlu, Esma; Bektaş, Osman; Aslan, Güler; Iyigün, Özgün; Kara, Ahmet; Tanrıverdi Pınar, Handan; Yavuz, Saffet; Tekin, Murat; Ercan, Saffet; Çelik, Selda; Sezgin Meriçliler, Özlem; Bozkurt Çakır, İrem

    2017-07-01

    The aim of this study was to evaluate the adherence to recommendations for secondary prevention and the achievement of treatment targets for the control of risk factors in patients with established coronary heart disease (CHD) who were followed-up at various healthcare facilities in Turkey. According to the protocol of the international Survey of Risk Factor Management study, questionnaire forms were completed and demographic, anthropometric, and laboratory data of CHD patients who were followed-up at a total of 15 selected primary, secondary, and tertiary healthcare centers were recorded. Among a total of 724 CHD patients (69.8% male; mean age: 63.3±10.7 years) included in the study, 18.4% were current smokers, only 19.1% had normal body mass index, and 22.1% had waist circumference below the limit of abdominal obesity. Physical activity was insufficient in 53% of the patients, 47.3% had low high-density lipoprotein cholesterol value, 46% had triglyceride level above 150 mg/dL, and 67% had glycated hemoglobin value of 6.5% or above. Of all the patients, 88.1% were using antiplatelet drugs, 71.4% were using beta-blockers, 55.7% were using statins, and 41.9% were using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Blood pressure was under control in 56.7% of the hypertensive patients using antihypertensive drugs, and the proportion of diabetic patients who reached glycemic control targets using antidiabetic drugs was 35.9%. Low-density lipoprotein cholesterol was below 70 mg/dL in 12.2% of the patients using statins. According to the data obtained, among Turkish CHD patients, the control rate of cardiovascular risk factors is low, and implementation of the recommendations regarding lifestyle modification and medication use for secondary prevention in the current guidelines are insufficient.

  14. CHD8, A Novel Beta-Catenin Associated Chromatin Remodeling Enzyme, Regulates Androgen Receptor Mediated Gene Transcription

    National Research Council Canada - National Science Library

    Bochar, Daniel A

    2008-01-01

    .... To better understand the function of beta-catenin in AR mediated transcription, we have identified a novel chromatin remodeling enzyme, CHD8, that can associate with beta-catenin and functions in AR...

  15. Knowledge of Coronary Heart Disease Risk Factors among a Community Sample in Oman; Pilot study

    Directory of Open Access Journals (Sweden)

    Ali A. Ammouri

    2016-05-01

    Full Text Available Objectives: The aim of this study was to assess the knowledge of Omani adults regarding conventional coronary heart disease (CHD risk factors and to identify demographic variables associated with these knowledge levels. Methods: This descriptive cross-sectional pilot study was carried out among a convenience sample of 130 adults attending a health awareness fair held in a local shopping mall in Muscat, Oman, in November 2012. A modified version of the Heart Disease Facts Questionnaire in both English and Arabic was used to assess knowledge of CHD risk factors. Scores were calculated by summing the correct answers for each item (range: 0–21. Inadequate knowledge was indicated by a mean score of <70%. Descriptive and multivariate logistic regression analyses were performed to establish the participants’ knowledge levels and identify associated demographic variables. Results: A total of 114 subjects participated in the study (response rate: 87.7%. Of these, 69 participants (60.5% had inadequate mean CHD knowledge scores. Knowledge of CHD risk factors was significantly associated with body mass index (odds ratio [OR] = 0.739; P = 0.023, marital status (OR = 0.057; P = 0.036 and education level (OR = 9.243; P = 0.006. Conclusion: Low knowledge levels of CHD risk factors were observed among the studied community sample in Oman; this is likely to limit the participants’ ability to engage in preventative practices. These findings support the need for education programmes to enhance awareness of risk factors and prevention of CHD in Oman.

  16. Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.

    Directory of Open Access Journals (Sweden)

    Guillaume Lettre

    2011-02-01

    Full Text Available Coronary heart disease (CHD is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C, hypertension, smoking, and type-2 diabetes in individuals of African ancestry, we performed a genome-wide association study (GWAS in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1, we could leverage the distinct linkage disequilibrium (LD patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.

  17. Clinical significance of determination of the levels of serum IL-6, TNF-α and hs-CRP in patients with DM2 complicated with coronary heart disease (CHD)

    International Nuclear Information System (INIS)

    Li Juan; Zhao Qian; Zhang Dajun

    2007-01-01

    Objective: To investigate the significance of changes of serum IL-6, TNF-α, hs-CRP levels in development of coronary heart disease in patients with type 2 diabetes mellitus. Methods: Serum IL-6, TNF-α (with RIA). hs-CRP (with CLIA) and FPG, TG, cholesterol (with biochemistry) contents were measured in (1) DM2 patients complicated with CHD, n=40 and (2) DlVI2 patients without CHD, n=48. Results: The BMI and FPG, TG levels were significantly higher in patients complicated with heart disease than those in patients without CHD (P<0.05) with the exception of cholesterol. The levels of IL-6, TNF-α and hs-CRP were also significantly higher in patients with heart disease than those in patients without heart disease (P<0.05). Conclusion: The high levels of IL-6, TNF-α and hs-CRP played important role in the development of coronary heart disease. Monitoring those levels might be helpful in assessment of treatment efficacy and outcome prediction. (authors)

  18. Bridging together: teamwork in caring for the family touched by CHD.

    Science.gov (United States)

    Jonas, Richard A

    2017-12-01

    In the opening plenary address of the 2017 7th World Congress of Pediatric Cardiology and Cardiac Surgery the author, who represented the World Society for Pediatric and Congenital Heart Surgery at the Congress and is currently the Society's president, described the history of the formation of the World Society. He listed accomplishments of the World Society including publication of the only journal devoted to congenital cardiac surgery, development of a global database, and convening several international conferences dating back to the inaugural conference in Washington, DC in 2007. The general theme of the presentation is the importance of teamwork in managing patients and families with CHD. Challenges facing congenital heart teams are discussed including the fragility of cardiac programmes, that can be heavily influenced by the administrative structure of a paediatric hospital; the difficulty of recruiting skilled surgeons into the field as training in general cardiothoracic surgery contracts and general surgery becomes predominantly laparoscopic with few open procedures; and increasing barriers to the international movement of surgeons including the opportunities for United States of America-based surgeons to acquire international experience at leading global centres. Finally, the author focusses on the danger that the team approach poses to maintaining empathy and emotional support for the family with CHD undergoing a stressful hospitalisation. He discusses strategies to optimise holistic support of the child and family.

  19. Coronary Heart Disease Risk Factors in Young People of Differing Socio-Economic Status

    Science.gov (United States)

    Thomas, Non-Eleri; Cooper, Stephen-Mark; Williams, Simon P.; Baker, Julien S.; Davies, Bruce

    2005-01-01

    This study determined the prevalence of coronary heart disease (CHD) risk factors in young people of differing socio-economic status (SES). A cohort of 100 boys and 108 girls, aged 12.9, SD 0.3 years drawn of differing SES were assessed for CHD risk factors. Measurements included indices of obesity, blood pressure, aerobic fitness, diet, blood…

  20. Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4.

    Science.gov (United States)

    Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

    2012-07-30

    CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which provide a structural explanation for the regulation of CHD4 activities by intramolecular domain communication. Our results demonstrate functional interdependency between domains within a chromatin remodeller. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients

    DEFF Research Database (Denmark)

    Marcos, Séverine; Sarfati, Julie; Leroy, Chrystel

    2014-01-01

    CONTEXT: Mutations in CHD7, a gene previously implicated in CHARGE (coloboma, heart defect, choanal atresia, retardation of growth and/or development, genital hypoplasia, ear anomalies) syndrome, have been reported in patients presenting with Kallmann syndrome (KS) or congenital hypogonadotropic...... hypogonadism (CHH). Most mutations causing CHARGE syndrome result in premature stop codons and occur de novo, but the proportion of truncating vs nontruncating mutations in KS and CHH patients is still unknown. OBJECTIVE: The objective of the study was to determine the nature, prevalence, mode of transmission......, and clinical spectrum of CHD7 mutations in a large series of patients. DESIGN: We studied 209 KS and 94 CHH patients. These patients had not been diagnosed with CHARGE syndrome according to the current criteria. We searched for mutations in 16 KS and CHH genes including CHD7. RESULTS: We found presumably...

  2. Social and Behavioral Risk Marker Clustering Associated with Biological Risk Factors for Coronary Heart Disease: NHANES 2001–2004

    Directory of Open Access Journals (Sweden)

    Nicholas J. Everage

    2014-01-01

    Full Text Available Background. Social and behavioral risk markers (e.g., physical activity, diet, smoking, and socioeconomic position cluster; however, little is known whether clustering is associated with coronary heart disease (CHD risk. Objectives were to determine if sociobehavioral clustering is associated with biological CHD risk factors (total cholesterol, HDL cholesterol, systolic blood pressure, body mass index, waist circumference, and diabetes and whether associations are independent of individual clustering components. Methods. Participants included 4,305 males and 4,673 females aged ≥20 years from NHANES 2001–2004. Sociobehavioral Risk Marker Index (SRI included a summary score of physical activity, fruit/vegetable consumption, smoking, and educational attainment. Regression analyses evaluated associations of SRI with aforementioned biological CHD risk factors. Receiver operator curve analyses assessed independent predictive ability of SRI. Results. Healthful clustering (SRI = 0 was associated with improved biological CHD risk factor levels in 5 of 6 risk factors in females and 2 of 6 risk factors in males. Adding SRI to models containing age, race, and individual SRI components did not improve C-statistics. Conclusions. Findings suggest that healthful sociobehavioral risk marker clustering is associated with favorable CHD risk factor levels, particularly in females. These findings should inform social ecological interventions that consider health impacts of addressing social and behavioral risk factors.

  3. EBNA1 efficiently assembles on chromatin containing the Epstein-Barr virus latent origin of replication

    International Nuclear Information System (INIS)

    Avolio-Hunter, Tina M.; Frappier, Lori

    2003-01-01

    The Epstein-Barr virus (EBV) protein, EBNA1, activates the replication of latent EBV episomes and the transcription of EBV latency genes by binding to recognition sites in the DS and FR elements of oriP. Since EBV episomes exist as chromatin, we have examined the interaction of EBNA1 with oriP templates assembled with physiologically spaced nucleosomes. We show that EBNA1 retains the ability to efficiently bind its recognition sites within the DS and FR elements in oriP chromatin and that this property is intrinsic to the EBNA1 DNA binding domain. The efficient assembly of EBNA1 on oriP chromatin does not require ATP-dependent chromatin remodeling factors and does not cause the precise positioning of nucleosomes within or adjacent to the FR and DS elements. Thus EBNA1 belongs to a select group of proteins that can efficiently access their recognition sites within nucleosomes without the need for additional chromatin remodeling factors

  4. A Framework for Geometric Reasoning About Human Figures and Factors in Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)

    Calton, Terri L.

    1999-07-20

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be perfectly valid operations, but in reality some operations cannot physically be carried out by a human. For example, the use of a ratchet may be reasoned feasible for an assembly operation; however, when a hand is placed on the tool the operation is no longer feasible, perhaps because of inaccessibility, insufficient strength or human interference with assembly components. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications, however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem, HFFMs must be integrated with automated assembly planning which allows engineers to quickly verify that assembly operations are possible and to see ways to make the designs even better. This paper presents a framework for integrating geometry-based assembly planning algorithms with commercially available human figure modeling software packages. Experimental results to selected applications along with lessons learned are presented.

  5. Can an Internet-based health risk assessment highlight problems of heart disease risk factor awareness? A cross-sectional analysis.

    Science.gov (United States)

    Dickerson, Justin B; McNeal, Catherine J; Tsai, Ginger; Rivera, Cathleen M; Smith, Matthew Lee; Ohsfeldt, Robert L; Ory, Marcia G

    2014-04-18

    Health risk assessments are becoming more popular as a tool to conveniently and effectively reach community-dwelling adults who may be at risk for serious chronic conditions such as coronary heart disease (CHD). The use of such instruments to improve adults' risk factor awareness and concordance with clinically measured risk factor values could be an opportunity to advance public health knowledge and build effective interventions. The objective of this study was to determine if an Internet-based health risk assessment can highlight important aspects of agreement between respondents' self-reported and clinically measured CHD risk factors for community-dwelling adults who may be at risk for CHD. Data from an Internet-based cardiovascular health risk assessment (Heart Aware) administered to community-dwelling adults at 127 clinical sites were analyzed. Respondents were recruited through individual hospital marketing campaigns, such as media advertising and print media, found throughout inpatient and outpatient facilities. CHD risk factors from the Framingham Heart Study were examined. Weighted kappa statistics were calculated to measure interrater agreement between respondents' self-reported and clinically measured CHD risk factors. Weighted kappa statistics were then calculated for each sample by strata of overall 10-year CHD risk. Three samples were drawn based on strategies for treating missing data: a listwise deleted sample, a pairwise deleted sample, and a multiple imputation (MI) sample. The MI sample (n=16,879) was most appropriate for addressing missing data. No CHD risk factor had better than marginal interrater agreement (κ>.60). High-density lipoprotein cholesterol (HDL-C) exhibited suboptimal interrater agreement that deteriorated (eg, κInternet-based health risk assessments such as Heart Aware may contribute to public health surveillance, but they must address selection bias of Internet-based recruitment methods.

  6. A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure

    DEFF Research Database (Denmark)

    Luijsterburg, Martijn S; Acs, Klara; Ackermann, Leena

    2012-01-01

    The ubiquitin ligases RNF8 and RNF168 orchestrate DNA damage signalling through the ubiquitylation of histone H2A and the recruitment of downstream repair factors. Here, we demonstrate that RNF8, but not RNF168 or the canonical H2A ubiquitin ligase RNF2, mediates extensive chromatin decondensation....... Our data show that CHD4, the catalytic subunit of the NuRD complex, interacts with RNF8 and is essential for RNF8-mediated chromatin unfolding. The chromatin remodelling activity of CHD4 promotes efficient ubiquitin conjugation and assembly of RNF168 and BRCA1 at DNA double-strand breaks....... Interestingly, RNF8-mediated recruitment of CHD4 and subsequent chromatin remodelling were independent of the ubiquitin-ligase activity of RNF8, but involved a non-canonical interaction with the forkhead-associated (FHA) domain. Our study reveals a new mechanism of chromatin remodelling-assisted ubiquitylation...

  7. Coronary Heart Disease Knowledge and Risk Factors among Tri-Ethnic College Students

    Science.gov (United States)

    Koutoubi, Samer; Huffman, Fatma G.; Ciccazzo, Michele W.; Himburg, Susan P.; Johnson, Paulette

    2005-01-01

    Objectives: Coronary heart disease (CHD) is the leading cause of death in the United States and Europe. This study identified and compared nutritional knowledge associated with CHD risk factors among tri-ethnic college students. Design: A quantitative, cross-sectional, observational study using questionnaires. Setting: University laboratory.…

  8. 1-Dodecanethiol based highly stable self-assembled monolayers for germanium passivation

    International Nuclear Information System (INIS)

    Cai, Qi; Xu, Baojian; Ye, Lin; Di, Zengfeng; Huang, Shanluo; Du, Xiaowei; Zhang, Jishen; Jin, Qinghui; Zhao, Jianlong

    2015-01-01

    Highlights: • A simple and effective approach for higly stable germanium passivation. • 1-Dodecanethiol self-assembled monolayers for germanium oxidation resistance. • The influence factors of germanium passivation were systematically studied. • The stability of the passivated Ge was more than 10 days even in water conditions. - Abstract: As a typical semiconductor material, germanium has the potential to replace silicon for future-generation microelectronics, due to its better electrical properties. However, the lack of stable surface state has limited its extensive use for several decades. In this work, we demonstrated highly stable self-assembled monolayers (SAMs) on Ge surface to prevent oxidization for further applications. After the pretreatment in hydrochloric acid, the oxide-free and Cl-terminated Ge could be further coated with 1-dodecanethiol (NDM) SAMs. The influence factors including reaction time, solvent component and reaction temperature were optimized to obtain stable passivated monolayer for oxidation resistance. Contact angle analysis, atomic force microscopy, ellipsometer and X-ray photoelectron spectroscopy were performed to characterize the functionalized Ge surface respectively. Meanwhile, the reaction mechanism and stability of thiols SAMs on Ge (1 1 1) surface were investigated. Finally, highly stable passivated NDM SAMs on Ge surface could be formed through immersing oxide-free Ge in mixture solvent (water/ethanol, v/v = 1:1) at appropriately elevated temperature (∼80 °C) for 24 h. And the corresponding optimized passivated Ge surface was stable for more than 10 days even in water condition, which was much longer than the data reported and paved the way for the future practical applications of Ge.

  9. 1-Dodecanethiol based highly stable self-assembled monolayers for germanium passivation

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Qi [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); University of Chinese Academy of Sciences, No. 19A, Yuquan Road, Beijing 100049 (China); Xu, Baojian, E-mail: xbj@mail.sim.ac.cn [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); Shanghai Internet of Things Co., LTD, No. 1455, Pingcheng Road, Shanghai 201899 (China); Ye, Lin [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); University of Chinese Academy of Sciences, No. 19A, Yuquan Road, Beijing 100049 (China); Di, Zengfeng [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); Huang, Shanluo; Du, Xiaowei [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); University of Chinese Academy of Sciences, No. 19A, Yuquan Road, Beijing 100049 (China); Zhang, Jishen; Jin, Qinghui [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); Zhao, Jianlong, E-mail: jlzhao@mail.sim.ac.cn [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China)

    2015-10-30

    Highlights: • A simple and effective approach for higly stable germanium passivation. • 1-Dodecanethiol self-assembled monolayers for germanium oxidation resistance. • The influence factors of germanium passivation were systematically studied. • The stability of the passivated Ge was more than 10 days even in water conditions. - Abstract: As a typical semiconductor material, germanium has the potential to replace silicon for future-generation microelectronics, due to its better electrical properties. However, the lack of stable surface state has limited its extensive use for several decades. In this work, we demonstrated highly stable self-assembled monolayers (SAMs) on Ge surface to prevent oxidization for further applications. After the pretreatment in hydrochloric acid, the oxide-free and Cl-terminated Ge could be further coated with 1-dodecanethiol (NDM) SAMs. The influence factors including reaction time, solvent component and reaction temperature were optimized to obtain stable passivated monolayer for oxidation resistance. Contact angle analysis, atomic force microscopy, ellipsometer and X-ray photoelectron spectroscopy were performed to characterize the functionalized Ge surface respectively. Meanwhile, the reaction mechanism and stability of thiols SAMs on Ge (1 1 1) surface were investigated. Finally, highly stable passivated NDM SAMs on Ge surface could be formed through immersing oxide-free Ge in mixture solvent (water/ethanol, v/v = 1:1) at appropriately elevated temperature (∼80 °C) for 24 h. And the corresponding optimized passivated Ge surface was stable for more than 10 days even in water condition, which was much longer than the data reported and paved the way for the future practical applications of Ge.

  10. Comparing primary prevention with secondary prevention to explain decreasing coronary heart disease death rates in Ireland, 1985-2000.

    LENUS (Irish Health Repository)

    Kabir, Zubair

    2007-01-01

    BACKGROUND: To investigate whether primary prevention might be more favourable than secondary prevention (risk factor reduction in patients with coronary heart disease(CHD)). METHODS: The cell-based IMPACT CHD mortality model was used to integrate data for Ireland describing CHD patient numbers, uptake of specific treatments, trends in major cardiovascular risk factors, and the mortality benefits of these specific risk factor changes in CHD patients and in healthy people without recognised CHD. RESULTS: Between 1985 and 2000, approximately 2,530 fewer deaths were attributable to reductions in the three major risk factors in Ireland. Overall smoking prevalence declined by 14% between 1985 and 2000, resulting in about 685 fewer deaths (minimum estimate 330, maximum estimate 1,285) attributable to smoking cessation: about 275 in healthy people and 410 in known CHD patients. Population total cholesterol concentrations fell by 4.6%, resulting in approximately 1,300 (minimum estimate 1,115, maximum estimate 1,660) fewer deaths attributable to dietary changes(1,185 in healthy people and 115 in CHD patients) plus 305 fewer deaths attributable to statin treatment (45 in people without CHD and 260 in CHD patients). Mean population diastolic blood pressure fell by 7.2%, resulting in approximately 170 (minimum estimate 105, maximum estimate 300) fewer deaths attributable to secular falls in blood pressure (140 in healthy people and 30 in CHD patients), plus approximately 70 fewer deaths attributable to antihypertensive treatments in people without CHD. Of all the deaths attributable to risk factor falls, some 1,715 (68%) occurred in people without recognized CHD and 815(32%) in CHD patients. CONCLUSION: Compared with secondary prevention, primary prevention achieved a two-fold larger reduction in CHD deaths. Future national CHD policies should therefore prioritize nationwide interventions to promote healthy diets and reduce smoking.

  11. Assessment of TRAC-PF1/MOD3 Mark-22 assembly model using SRL ''A'' tank single-assembly flow experiments

    International Nuclear Information System (INIS)

    Fischer, S.R.; Lam, K.; Lin, J.C.

    1991-01-01

    This paper summarizes the results of an assessment of our TRAC-PF1/MOD3 Mark-22 prototype fuel assembly model against single-assembly data obtained from the ''A'' Tank single-assembly tests that were performed at the Savannah River Laboratory. We felt the data characterize prototypic assembly behavior over a range of air-water flow conditions of interest for loss-of-coolant accident (LOCA) calculations. This study was part of a benchmarking effort performed to evaluate and validate a multiple-assembly, full-plant model that is being developed by Los Alamos National Laboratory to study various aspects of the Savannah River plant operating conditions, including LOCA transients, using TRAC-PF1/MOD3 Version 1.10. The results of this benchmarking effort demonstrate that TRAC-PF1/MOD3 is capable pf calculating plenum conditions and assembly flows during conditions thought to be typical of the Emergency Cooling System (ECS) phase of a LOCA. 10 refs., 12 fig

  12. Assembly and activation of neurotrophic factor receptor complexes.

    Science.gov (United States)

    Simi, Anastasia; Ibáñez, Carlos F

    2010-04-01

    Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

  13. Kalirin and CHD7: novel endothelial dysfunction indicators in circulating extracellular vesicles from hypertensive patients with albuminuria

    Science.gov (United States)

    de la Cuesta, Fernando; Baldan-Martin, Montserrat; Moreno-Luna, Rafael; Alvarez-Llamas, Gloria; Gonzalez-Calero, Laura; Mourino-Alvarez, Laura; Sastre-Oliva, Tamara; López, Juan A.; Vázquez, Jesús; Ruiz-Hurtado, Gema; Segura, Julian; Vivanco, Fernando; Ruilope, Luis M.; Barderas, Maria G.

    2017-01-01

    Despite of the great advances in anti-hypertensive therapies, many patients under Renin-Angiotensin- System (RAS) suppression develop albuminuria, which is a clear indicator of therapeutic inefficiency. Hence, indicators of vascular function are needed to assess patients’ condition and help deciding future therapies. Proteomic analysis of circulating extracellular vesicles (EVs) showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients. A positive correlation of both with the expression of the endothelial activation marker E-selectin was found in EVs. In vitro analysis using TNFα-treated adult human endothelial cells proved their involvement in endothelial cell activation. Hence, we propose protein levels of kalirin and CHD7 in circulating EVs as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria. PMID:28152519

  14. Quantitative measurement of exchange dynamics in proteins via {sup 13}C relaxation dispersion of {sup 13}CHD{sub 2}-labeled samples

    Energy Technology Data Exchange (ETDEWEB)

    Rennella, Enrico; Schuetz, Anne K.; Kay, Lewis E., E-mail: kay@pound.med.utoronto.ca [University of Toronto, Departments of Molecular Genetics, Biochemistry and Chemistry (Canada)

    2016-06-15

    Methyl groups have emerged as powerful probes of protein dynamics with timescales from picoseconds to seconds. Typically, studies involving high molecular weight complexes exploit {sup 13}CH{sub 3}- or {sup 13}CHD{sub 2}-labeling in otherwise highly deuterated proteins. The {sup 13}CHD{sub 2} label offers the unique advantage of providing {sup 13}C, {sup 1}H and {sup 2}H spin probes, however a disadvantage has been the lack of an experiment to record {sup 13}C Carr–Purcell–Meiboom–Gill relaxation dispersion that monitors millisecond time-scale dynamics, implicated in a wide range of biological processes. Herein we develop an experiment that eliminates artifacts that would normally result from the scalar coupling between {sup 13}C and {sup 2}H spins that has limited applications in the past. The utility of the approach is established with a number of applications, including measurement of ms dynamics of a disease mutant of a 320 kDa p97 complex.

  15. Assembly of presynaptic filaments. Factors affecting the assembly of RecA protein onto single-stranded DNA

    DEFF Research Database (Denmark)

    Thresher, RJ; Christiansen, Gunna; Griffith, JD

    1988-01-01

    We have previously shown that the assembly of RecA protein onto single-stranded DNA (ssDNA) facilitated by SSB protein occurs in three steps: (1) rapid binding of SSB protein to the ssDNA; (2) nucleation of RecA protein onto this template; and (3) co-operative polymerization of additional Rec......M in the presence of 12 mM-Mg2+), and relatively low concentrations of SSB protein (1 monomer per 18 nucleotides). Assembly was depressed threefold when SSB protein was added to one monomer per nine nucleotides. These effects appeared to be exerted at the nucleation step. Following nucleation, RecA protein...... assembled onto ssDNA at net rates that varied from 250 to 900 RecA protein monomers per minute, with the rate inversely related to the concentration of SSB protein. Combined sucrose sedimentation and electron microscope analysis established that SSB protein was displaced from the ssDNA during RecA protein...

  16. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  17. Association between polymorphisms in the coagulation factor VII gene and coronary heart disease risk in different ethnicities: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Mo Xingbo

    2011-08-01

    Full Text Available Abstract Background Previous studies have examined the association between polymorphisms in the coagulation factor VII gene and the risk of coronary heart disease (CHD, but those studies have been inconclusive. This study was conducted to assess the associations between these polymorphisms and CHD and evaluated the associations in different ethnicities. Methods Literature-based searching was conducted to collect data and two methods, namely fixed-effects and random-effects, were performed to pool the odds ratio (OR, together with the 95% confidence interval (CI. Publication bias and between-study heterogeneity were also examined. Results Thirty-nine case-control studies of the three polymorphisms, R353Q (rs6046, HVR4 and -323Ins10 (rs36208070 in factor VII gene and CHD were enrolled in this meta-analysis, including 9,151 cases of CHD and 14,099 controls for R353Q, 2,863 cases and 2,727 controls for HVR4, and 2,862 cases and 4,240 controls for -323Ins10. Significant association was only found in Asian population for R353Q (Q vs R, with pooled OR of 0.70(95%CI: 0.55, 0.90. For the -323Ins10 polymorphism (10 vs 0, we found significant associations in both Asian and European populations, with pooled ORs of 0.74(95%CI: 0.61, 0.88 and 0.63(95%CI: 0.53, 0.74, respectively. Marginal significant association was found between HVR4 (H7 vs H5+H6 and CHD (OR = 0.88, 95% CI: 0.78, 1.00. There was no evidence of publication bias, but between-study heterogeneity was found in the analyses. Conclusions The -323Ins10 polymorphism in factor VII gene is significantly associated with CHD in both Asian and European populations, while R353Q polymorphism showed trend for association with CHD in Asians. Lack of association was found for HVR4 polymorphism. Further studies are needed to confirm the association, especially for -323Ins10 polymorphism.

  18. Does maternal environmental tobacco smoke interact with social-demographics and environmental factors on congenital heart defects?

    Science.gov (United States)

    Liu, Xiaoqing; Nie, Zhiqiang; Chen, Jimei; Guo, Xiaoling; Ou, Yanqiu; Chen, Guanchun; Mai, Jinzhuang; Gong, Wei; Wu, Yong; Gao, Xiangmin; Qu, Yanji; Bell, Erin M; Lin, Shao; Zhuang, Jian

    2018-03-01

    Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004-2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25-1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD

  19. Stable assembly of HIV-1 export complexes occurs cotranscriptionally

    DEFF Research Database (Denmark)

    Nawroth, Isabel; Mueller, Florian; Basyuk, Eugenia

    2014-01-01

    The HIV-1 Rev protein mediates export of unspliced and singly spliced viral transcripts by binding to the Rev response element (RRE) and recruiting the cellular export factor CRM1. Here, we investigated the recruitment of Rev to the transcription sites of HIV-1 reporters that splice either post......- or cotranscriptionally. In both cases, we observed that Rev localized to the transcription sites of the reporters and recruited CRM1. Rev and CRM1 remained at the reporter transcription sites when cells were treated with the splicing inhibitor Spliceostatin A (SSA), showing that the proteins associate with RNA prior...... to or during early spliceosome assembly. Fluorescence recovery after photobleaching (FRAP) revealed that Rev and CRM1 have similar kinetics as the HIV-1 RNA, indicating that Rev, CRM1, and RRE-containing RNAs are released from the site of transcription in one single export complex. These results suggest...

  20. Is diet an essential risk factor for coronary heart disease?

    OpenAIRE

    Ball, K. P.

    1980-01-01

    Cigarette smoking, hypertension and diet each play a major role in the development of coronary heart attacks in most industrialized nations. In some countries where cigarette smoking and hypertension are prevalent there is a low risk of coronary heart disease (CHD). Hyperlipidaemia resulting from national food habits appears to be the essential factor in the high rates of CHD in developed countries.

  1. The nucleosome assembly activity of NAP1 is enhanced by Alien.

    Science.gov (United States)

    Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

    2007-05-01

    The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitamin D receptor (VDR), binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. Furthermore, Alien reduces the accessibility of the histones H3 and H4 for NAP1-promoted assembly reaction. This indicates that Alien sustains and reinforces the formation of nucleosomes. Employing deletion mutants of Alien suggests that different regions of Alien are involved in enhancement of NAP1-mediated nucleosome assembly and in inhibiting the accessibility of the histones H3 and H4. In addition, we provide evidence that Alien is associated with chromatin and with micrococcus nuclease-prepared nucleosome fractions and interacts with the histones H3 and H4. Furthermore, chromatin immunoprecipitation and reimmunoprecipitation experiments suggest that NAP1 and Alien localize to the endogenous CYP24 promoter in vivo, a VDR target gene. Based on these findings, we present here a novel pathway linking corepressor function with nucleosome assembly activity.

  2. The Relationship Between Coronary Heart Disease (CHD and Major Depressive Disorder (MDD: Key Mechanisms and the Role of Quality of Life

    Directory of Open Access Journals (Sweden)

    Adrienne O’Neil

    2013-02-01

    Full Text Available Various trials have been conducted evaluating depression management programs for patients with Coronary Heart Disease (CHD. However, to date, the most effective way to manage this co-morbidity in the real world setting remains unclear. To better understand the past successes and failures of previous trials and subsequently develop suitable interventions that target key components of health related quality of life (HRQOL such as mental, physical and vocational functioning, we first need to understand the mechanisms underpinning the relationship between the two conditions. This paper will draw on the key literature in this field as identified by psychiatric, medical and social sciences databases (Cochrane Central Register of Controlled Trials, PubMed, OVID, Medline available up to January 2012, with the aim to conduct a narrative review which explores: the aetiological relationship between depression and CHD; its association with HRQOL; the relationship between CHD, depression and vocational functioning; and the impact of depression treatment on these outcomes. Key recommendations are made regarding the management of this prevalent co-morbidity in clinical settings.

  3. Risk factors for coronary heart disease in the white comm.unity ...

    African Journals Online (AJOL)

    major risk factors showed that 35,1% (age and sex adjusted) had at least one major risk factor at the higher level (level A) and 33,8% (age and sex adjusted) ... in a number of other countries with a high CHD mor- ... Afrikaans-speaking community in the south-western ... in an average week; (viI) physical activity both at work.

  4. Stackable Form-Factor Peripheral Component Interconnect Device and Assembly

    Science.gov (United States)

    Somervill, Kevin M. (Inventor); Ng, Tak-kwong (Inventor); Torres-Pomales, Wilfredo (Inventor); Malekpour, Mahyar R. (Inventor)

    2013-01-01

    A stackable form-factor Peripheral Component Interconnect (PCI) device can be configured as a host controller or a master/target for use on a PCI assembly. PCI device may comprise a multiple-input switch coupled to a PCI bus, a multiplexor coupled to the switch, and a reconfigurable device coupled to one of the switch and multiplexor. The PCI device is configured to support functionality from power-up, and either control function or add-in card function.

  5. Membrane omega-3 Fatty Acid deficiency as a preventable risk factor for comorbid coronary heart disease in major depressive disorder.

    Science.gov (United States)

    McNamara, Robert K

    2009-01-01

    Major depression disorder (MDD) significantly increases the risk for coronary heart disease (CHD) which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS) and increases risk for mortality. Here evidence implicating omega-3 (n-3) fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

  6. A preliminary study of the relationship between promoter methylation of the ABCG1, GALNT2 and HMGCR genes and coronary heart disease.

    Directory of Open Access Journals (Sweden)

    Ping Peng

    Full Text Available To investigate the association of ABCG1, GALNT2 and HMGCR genes promoter DNA methylation with coronary heart disease (CHD and explore the interaction between their methylation status and the CHD patients' clinical characteristics in Han Chinese population.Methylation-specific polymerase chain reaction (MSP technology was used to examine the role of the aberrant gene promoter methylation in CHD in Han Chinese population. A total of 85 CHD patients and 54 participants without CHD confirmed by angiography were recruited. 82.8% of the participants with ABCG1 gene promoter hypermethylation have CHD, while only 17.4% of the participants without hypermethylation have it. The average age of the participants with GALNT2 gene promoter hypermethylation is 62.10 ± 8.21, while that of the participants without hypermethylation is 57.28 ± 9.87; in the former group, 75.4% of the participants have CHD, compared to only 50% in the latter group. As for the HMGCR gene, the average age of the participants with promoter hypermethylation is 63.24 ± 8.10 and that of the participants without hypermethylation is 57.79 ± 9.55; its promoter hypermethylation is likely to be related to smoking. Our results indicated a significant statistical association of promoter methylation of the ABCG1 gene with increased risk of CHD (OR = 19.966; 95% CI, 7.319-54.468; P*<0.001; P*: adjusted for age, gender, smoking, lipid level, hypertension, and diabetes. Similar results were obtained for that of the GALNT2 gene (OR = 2.978; 95% CI, 1.335-6.646; P* = 0.008, but not of HMGCR gene (OR = 1.388; 95% CI, 0.572-3.371; P*  = 0.469.The present work provides evidence to support the association of promoter DNA methylation status with the risk profile of CHD. Our data indicates that promoter DNA hypermethylation of the ABCG1 and GALNT2 genes, but not the HMGCR gene, is associated with an increased risk of CHD. CHD, smoking and aging are likely to be the important factors influencing DNA

  7. [The epidemiological study of work-related musculoskeletal disorders and related factors among automobile assembly workers].

    Science.gov (United States)

    Wang, Zhong-Xu; Qin, Ru-Li; Li, Yu-Zhen; Zhang, Xue-Yan; Jia, Ning; Zhang, Qiu-Ling; Li, Gang; Zhao, Jie; Li, Huan-Huan; Jiang, Hai-Qiang

    2011-08-01

    To investigate the work-related musculoskeletal disorders among automobile assembly workers, to discusses the related risk factors and their relationship. The selected 1508 automobile assembly workers from a north car manufacturing company were regarded as the study object. The hazard zone jobs checklist, Nordic musculoskeletal symptom questionnaire (NMQ) and pain questionnaire were used to perform the epidemiological cross-sectional and retrospective survey and study for the General status, awkward ergonomics factors and related influencing factors, and musculoskeletal disorders of workers. The predominant body sites of occurring WMSDs among automobile assembly workers were mainly low back, wrist, neck and shoulders, the predominant workshop section of occurring WMSDs were mostly concentrated in engine compartment, interior ornament, door cover, chassis and debugging section. The predominant body site of WMSDs among engine compartment and chassis section workers was low back, interior ornament workers were low back and wrist, door cover workers was wrist, chassis workers was low back, debugging workers were neck and low back. Neck musculoskeletal disorders had the trend with the increase of a body height; Smoking may increase the occurrence of musculoskeletal disorders. The WMSDs appears to be a serious ergonomic proble assem among automobile assembly workers, predominant occurring site of WMSDs is with different workshop section, its characteristics is quite obvious, probably related to its existing awkward work position or activities. The worker height and smoking habits may be important factors which affect musculoskeletal disorders happen.

  8. Premature Coronary Heart Disease and Traditional Risk Factors-Can We Do Better?

    Directory of Open Access Journals (Sweden)

    Roxana Sadeghi

    2013-06-01

    Full Text Available Background: Traditional cardiovascular risk factors are strong predictors of an increased likelihood for premature CHD. Considering the benefits of risk factors᾿ management, it is imperative to find and treat them before looking for more unknown and weak risk factors. Objectives: Limited information is available about the demographic and historical characteristics of the patients with premature Coronary Heart Disease (CHD in IR Iran. The main objective of this study was to determine the prevalence of the traditional risk factors in these patients. Also, the researchers hypothesized that there are insufficient risk assessment and preventive intervention methods for the asymptomatic adult population. Methods: This study was conducted on 125 patients with premature CHD (age<50 years who were admitted in two academic hospitals with acute coronary syndromes. The patients were accepted since they had a definite CHD on the basis of acute myocardial infarction (elevated cardiac enzymes or documented CAD in coronary angiography. Results: The mean age of the study population was 42.50±5.65 (26 to 49 years. Among the patients,92 (73.6% were male, 113 (90.4% were married, 58 (46.4% were smokers,19 (15.2% were opium users, 97 (77.6% had dyslipidemia, 44 (35.2% had hypertension, and 33 (26.4% had diabetes mellitus. In addition, family history was presented in 54 patients (43.2%. Conclusions: Premature Coronary Heart Disease is a public health problem. However, there is lack of effective and intensive treatments of well-defined traditional risk factors and prevention methods for the majority of the patients experiencing premature CHD. In sum, there is still plenty of room for improvement of risk management in IR Iran.

  9. Hepatic trans-Golgi action coordinated by the GTPase ARFRP1 is crucial for lipoprotein lipidation and assembly[S

    Science.gov (United States)

    Hesse, Deike; Radloff, Katrin; Jaschke, Alexander; Lagerpusch, Merit; Chung, Bomee; Tailleux, Anne; Staels, Bart; Schürmann, Annette

    2014-01-01

    The liver is a major organ in whole body lipid metabolism and malfunctioning can lead to various diseases including dyslipidemia, fatty liver disease, and type 2 diabetes. Triglycerides and cholesteryl esters are packed in the liver as very low density lipoproteins (VLDLs). Generation of these lipoproteins is initiated in the endoplasmic reticulum and further maturation likely occurs in the Golgi. ADP-ribosylation factor-related protein 1 (ARFRP1) is a small trans-Golgi-associated guanosine triphosphatase (GTPase) that regulates protein sorting and is required for chylomicron lipidation and assembly in the intestine. Here we show that the hepatocyte-specific deletion of Arfrp1 (Arfrp1liv−/−) results in impaired VLDL lipidation leading to reduced plasma triglyceride levels in the fasted state as well as after inhibition of lipoprotein lipase activity by Triton WR-1339. In addition, the concentration of ApoC3 that comprises 40% of protein mass of secreted VLDLs is markedly reduced in the plasma of Arfrp1liv−/− mice but accumulates in the liver accompanied by elevated triglycerides. Fractionation of Arfrp1liv−/− liver homogenates reveals more ApoB48 and a lower concentration of triglycerides in the Golgi compartments than in the corresponding fractions from control livers. In conclusion, ARFRP1 and the Golgi apparatus play an important role in lipoprotein maturation in the liver by influencing lipidation and assembly of proteins to the lipid particles. PMID:24186947

  10. Characterization of a Synechocystis double mutant lacking the photosystem II assembly factors YCF48 and Sll0933

    Czech Academy of Sciences Publication Activity Database

    Rengstl, B.; Knoppová, Jana; Komenda, Josef; Nickelsen, J.

    2013-01-01

    Roč. 237, č. 2 (2013), s. 471-480 ISSN 0032-0935 R&D Projects: GA ČR GBP501/12/G055; GA MŠk(CZ) ED2.1.00/03.0110 Institutional support: RVO:61388971 Keywords : Complex assembly * Cyanobacteria * Photosynthesis Subject RIV: EE - Microbiology, Virology Impact factor: 3.376, year: 2013

  11. Otitis Media in a New Mouse Model for CHARGE Syndrome with a Deletion in the Chd7 Gene

    Science.gov (United States)

    Tian, Cong; Yu, Heping; Yang, Bin; Han, Fengchan; Zheng, Ye; Bartels, Cynthia F.; Schelling, Deborah; Arnold, James E.; Scacheri, Peter C.; Zheng, Qing Yin

    2012-01-01

    Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome. PMID:22539951

  12. Mutations in RCA1 and AFG3 inhibit F1-ATPase assembly in Saccharomyces cerevisiae.

    Science.gov (United States)

    Paul, M F; Tzagoloff, A

    1995-10-02

    The RCA1 (YTA12) and AFG3 (YTA10) genes of Saccharomyces cerevisiae code for homologous mitochondrial proteins that belong to the recently described AAA protein-family [Kunau et al. (1993) Biochimie 75,209-224]. Mutations in either gene have been shown to induce a respiratory defect. In the case of rca1 mutants this phenotype has been ascribed to defective assembly of cytochrome oxidase and ubiquinol-cytochrome c reductase. In the present study we show that the respiratory defect of afg3 mutants, like that of rca1 mutants, is also caused by an arrest in assembly of cytochrome oxidase and ubiquinol-cytochrome c reductase. In addition to the absence of the respiratory complexes, rca1 and afg3 mutants exhibit reduced mitochondrial ATPase activity. As a first step to an understanding of the biochemical basis for the ATPase defect we have examined the assembly of the F1 and F0 constituents of the ATPase complex. We present evidence that the ATPase lesion stems at least in part from the failure of rca1 and afg3 mutants to assemble F1. Although the mutants also display lower steady-state concentrations of some F0 subunits, this could be a secondary effect of defective F1 assembly.

  13. Serum insulin-like growth factor II (IGF-II) and adrenomedullin (ADM) in coronary heart disease

    International Nuclear Information System (INIS)

    Tong Lijun; Ji Naijun; Fan Bifu; Wang Chengyao; Mei Yibin; Chen Donghai; Li Fuyuan

    2005-01-01

    Objective: To investigate the changes of serum insulin-like growth factor (IGF-II) and adrenomedullin (ADM) levels in patients with coronary heart disease (CHD). Methods: Serum IGF-II and ADM levels were measured with RIA in 90 CHD patients and 40 controls. Results: Serum IGF-II and ADM levels were significantly higher in CHD patients than those in controls (P 0.05). Serum IGF-II and ADM levels were significantly higher in the patients complicated with myocardial infarction (MI) than those in patients without this complication (t=2.831, t=2.328, both P 0.05). Conclusion: Serum IGF-II and ADM levels were increased in CHD patients, most markedly in those complicated with MI. (authors)

  14. A cross-sectional study on trans-fatty acids and risk markers of CHD among middle-aged men representing a broad range of BMI

    DEFF Research Database (Denmark)

    Nielsen, Birgit M.; Nielsen, Marie M.; Jakobsen, Marianne U.

    2011-01-01

    Intake of trans-fatty acids (TFA), especially industrially produced TFA (I-TFA), has been associated with the risk of CHD through influence on serum lipid levels. Other causal pathways remain less investigated. In the present cross-sectional study of middle-aged men representing a broad range...... of BMI, the association between intake of TFA, I-TFA and ruminant TFA (R-TFA) and obesity-associated risk markers of CHD was assessed. The study comprised 393 Danish men (median age 49 years) with a median BMI of 28·4 kg/m2. Intake of TFA was estimated based on 7 d dietary records, whereas outcomes...... pressure and insulin homeostasis. Among middle-aged men with a generally low intake of TFA, neither I-TFA nor R-TFA was significantly related to obesity-associated risk markers of CHD. The decreased average intake of I-TFA in Denmark since 1995 is suggested to effectively prevent occurrence of the adverse...

  15. Familial [corrected] transmission of coronary heart disease: a cohort study of 80,214 Swedish adoptees linked to their biological and adoptive parents.

    Science.gov (United States)

    Sundquist, Kristina; Winkleby, Marilyn; Li, Xinjun; Ji, Jianguang; Hemminki, Kari; Sundquist, Jan

    2011-08-01

    Studies of adoptees have the potential to disentangle the contributions of genetic versus family environmental factors in the familial [corrected] transmission of coronary heart disease (CHD) because adoptees do not share the same family environment as their biological parents. The aims of this study were as follows: (1) to examine the risk of CHD in adopted men and women with at least one biological parent with CHD and (2) to examine the risk of CHD in adopted men and women with at least one adoptive parent with CHD. The Swedish Multigenerational register was used to follow all Swedish-born adoptees (born in or after 1932, n = 80,214) between January 1, 1973, and December 31, 2008, for CHD. The risk of CHD was estimated in adopted men and women with at least one biological parent with CHD and adopted men and women with at least one adoptive parent with CHD. The control groups consisted of adopted men or women without a biological parent with CHD or adopted men or women without an adoptive parent with CHD. Adopted men and women with at least one biological parent with CHD (n = 749) were 1.4 to 1.6 times (statistically significant, 95% CI) more likely to have CHD than adoptees without a biological parent with CHD. In contrast, men and women with at least one adoptive parent with CHD (n = 1,009) were not at increased risk of the disease. These findings (based on validated hospital diagnoses unbiased by recall) suggest that the familial [corrected] transmission of CHD from parents to offspring is more related to genetic factors than to family environmental factors. Copyright © 2011 Mosby, Inc. All rights reserved.

  16. The Nucleosome Assembly Activity of NAP1 Is Enhanced by Alien▿

    OpenAIRE

    Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

    2007-01-01

    The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitam...

  17. "What I Wish You Knew": Social Barriers toward Physical Activity in Youth with Congenital Heart Disease (CHD)

    Science.gov (United States)

    Moola, Fiona; Fusco, Caroline; Kirsh, Joel A.

    2011-01-01

    Despite the benefits of physical activity for youth with congenital heart disease (CHD), most patients are inactive. Although literature has addressed medical and psychological barriers to participation, little is known about the social barriers that youth encounter. This qualitative study explored sociocultural barriers to physical activity from…

  18. Neutron Detector Signal Processing to Calculate the Effective Neutron Multiplication Factor of Subcritical Assemblies

    International Nuclear Information System (INIS)

    Talamo, Alberto; Gohar, Yousry

    2016-01-01

    This report describes different methodologies to calculate the effective neutron multiplication factor of subcritical assemblies by processing the neutron detector signals using MATLAB scripts. The subcritical assembly can be driven either by a spontaneous fission neutron source (e.g. californium) or by a neutron source generated from the interactions of accelerated particles with target materials. In the latter case, when the particle accelerator operates in a pulsed mode, the signals are typically stored into two files. One file contains the time when neutron reactions occur and the other contains the times when the neutron pulses start. In both files, the time is given by an integer representing the number of time bins since the start of the counting. These signal files are used to construct the neutron count distribution from a single neutron pulse. The built-in functions of MATLAB are used to calculate the effective neutron multiplication factor through the application of the prompt decay fitting or the area method to the neutron count distribution. If the subcritical assembly is driven by a spontaneous fission neutron source, then the effective multiplication factor can be evaluated either using the prompt neutron decay constant obtained from Rossi or Feynman distributions or the Modified Source Multiplication (MSM) method.

  19. Neutron Detector Signal Processing to Calculate the Effective Neutron Multiplication Factor of Subcritical Assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Talamo, Alberto [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Gohar, Yousry [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division

    2016-06-01

    This report describes different methodologies to calculate the effective neutron multiplication factor of subcritical assemblies by processing the neutron detector signals using MATLAB scripts. The subcritical assembly can be driven either by a spontaneous fission neutron source (e.g. californium) or by a neutron source generated from the interactions of accelerated particles with target materials. In the latter case, when the particle accelerator operates in a pulsed mode, the signals are typically stored into two files. One file contains the time when neutron reactions occur and the other contains the times when the neutron pulses start. In both files, the time is given by an integer representing the number of time bins since the start of the counting. These signal files are used to construct the neutron count distribution from a single neutron pulse. The built-in functions of MATLAB are used to calculate the effective neutron multiplication factor through the application of the prompt decay fitting or the area method to the neutron count distribution. If the subcritical assembly is driven by a spontaneous fission neutron source, then the effective multiplication factor can be evaluated either using the prompt neutron decay constant obtained from Rossi or Feynman distributions or the Modified Source Multiplication (MSM) method.

  20. Genetics of coronary artery calcification among African Americans, a meta-analysis

    NARCIS (Netherlands)

    M.K. Wojczynski (Mary ); M. Li (Mingyao); L.F. Bielak (Lawrence F.); K.F. Kerr (Kathleen); A. Reiner (Alexander); N.D. Wong (Nathan); L.R. Yanek (Lisa); L. Qu (Liming); C.C. White (Charles); L.A. Lange (Leslie); J.F. Ferguson (Jane); J. He (Jing); T. Young (Taylor); T.H. Mosley (Thomas); J.A. Smith (Jennifer A); B.G. Kral (Brian); X. Guo (Xiuqing); Q. Wong (Quenna); S.K. Ganesh (Santhi); S.R. Heckbert (Susan); M.D. Griswold (Michael); D.H. O'Leary (Daniel H.); M.J. Budoff (Matthew); J. Carr (Jeffrey); H.A. Taylor (Herman); D.A. Bluemke (David); S. Demissie (Serkalem); S.-J. Hwang (Shih-Jen); D.N. Paltoo (Dina); J.F. Polak (Joseph F.); B.M. Psaty (Bruce); D.M. Becker (Diane); M.A. Province (Mike); W.S. Post (Wendy S.); C.J. O'Donnell (Christopher); J.G. Wilson (James); T.B. Harris (Tamara); M. Kavousi (Maryam); L.A. Cupples (Adrienne); J.I. Rotter (Jerome); M. Fornage (Myriam); L.C. Becker (Lewis); P.A. Peyser (Patricia A.); I.B. Borecki (Ingrid); M.P. Reilly (Muredach)

    2013-01-01

    textabstractBackground: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest

  1. Assembly & Metrology of First Wall Components of SST-1

    Science.gov (United States)

    Parekh, Tejas; Santra, Prosenjit; Biswas, Prabal; Patel, Hiteshkumar; Paravastu, Yuvakiran; Jaiswal, Snehal; Chauhan, Pradeep; Babu, Gattu Ramesh; A, Arun Prakash; Bhavsar, Dhaval; Raval, Dilip C.; Khan, Ziauddin; Pradhan, Subrata

    2017-04-01

    First Wall Components (FWC) of SST-1 tokamak, which are in the immediate vicinity of plasma comprises of limiters, divertors, baffles, passive stabilizers are designed to operate long duration (1000 s) discharges of elongated plasma. All FWC consists of a copper alloy heat sink modules with SS cooling tubes brazed onto it, graphite tiles acting as armour material facing the plasma, and are mounted to the vacuum vessels with suitable Inconel support structures at ring & port locations. The FWC are very recently assembled and commissioned successfully inside the vacuum vessel of SST-1 undergoing a meticulous planning of assembly sequence, quality checks at every stage of the assembly process. This paper will present the metrology aspects & procedure of each FWC, both outside the vacuum vessel, and inside the vessel, assembly tolerances, tools, equipment and jig/fixtures, used at each stage of assembly, starting from location of support bases on vessel rings, fixing of copper modules on support structures, around 3800 graphite tile mounting on 136 copper modules with proper tightening torques, till final toroidal and poloidal geometry of the in-vessel components are obtained within acceptable limits, also ensuring electrical continuity of passive stabilizers to form a closed saddle loop, electrical isolation of passive stabilizers from vacuum vessel.

  2. The impact of obesity on risk factors and prevalence and prognosis of coronary heart disease-the obesity paradox.

    Science.gov (United States)

    De Schutter, Alban; Lavie, Carl J; Milani, Richard V

    2014-01-01

    Obesity is associated with a host of cardiovascular risk factors and its prevalence is rising rapidly. Despite strong evidence that obesity predisposes to the development and progression of coronary heart disease (CHD), numerous studies have shown an inverse relationship between various measures of obesity (most commonly body mass index) and outcomes in established CHD. In this article we review the evidence surrounding the ≪obesity paradox≫ in the secondary care of CHD patients and the CHD presentations where a paradox has been found. Finally we discuss the impact of cardiorespiratory fitness and a number of mechanisms which may offer potential explanations for this puzzling phenomenon. © 2014.

  3. Sugar Industry and Coronary Heart Disease Research: A Historical Analysis of Internal Industry Documents.

    Science.gov (United States)

    Kearns, Cristin E; Schmidt, Laura A; Glantz, Stanton A

    2016-11-01

    Early warning signals of the coronary heart disease (CHD) risk of sugar (sucrose) emerged in the 1950s. We examined Sugar Research Foundation (SRF) internal documents, historical reports, and statements relevant to early debates about the dietary causes of CHD and assembled findings chronologically into a narrative case study. The SRF sponsored its first CHD research project in 1965, a literature review published in the New England Journal of Medicine, which singled out fat and cholesterol as the dietary causes of CHD and downplayed evidence that sucrose consumption was also a risk factor. The SRF set the review's objective, contributed articles for inclusion, and received drafts. The SRF's funding and role was not disclosed. Together with other recent analyses of sugar industry documents, our findings suggest the industry sponsored a research program in the 1960s and 1970s that successfully cast doubt about the hazards of sucrose while promoting fat as the dietary culprit in CHD. Policymaking committees should consider giving less weight to food industry-funded studies and include mechanistic and animal studies as well as studies appraising the effect of added sugars on multiple CHD biomarkers and disease development.

  4. Status of Design and Manufacturing of ITER 1st batch Assembly Tools

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Jin Ho; Nam, Kyoun Go; Chung, Si Kun; Ha, Min Su [ITER Korea National Fusion Research Institute, Daejeon (Korea, Republic of); Kim, Geun Hong [ITER Organization, St Paul lez Durance (France)

    2016-05-15

    The ITER tokamak assembly tools are purpose-built and specially designed to complete the ITER tokamak machine which includes; Vacuum Vessel (VV), VV Thermal Shield (VVTS), Toroidal Field Coil (TFC) and other components contained in the cryostat. KODA has carried out the preliminary and final design of these assembly tools. This paper shows that the current status, first quarter of the 2016, including manufacturing of ITER 1st batch assembly tools and briefly summarized the design process through design work of Sector Sub-assembly Tool (SSAT) that is most important tool representing ITER 1st batch assembly tools. KODA (Korea Domestic Agency) should provide 128 kinds of the purpose-built assembly tools for ITER Tokamak machine, and the ITER 1st batch assembly tools are split into 3 groups. The FDR for Group A was performed in December 2014, and design of SSAT has been verified by FE analysis and engineering calculation using EN cords. The SSAT is now under manufacturing phase to meet the ITER milestone. After factory acceptance test of SSAT on end of 2016, the 1st SSAT will be delivered and arrived in ITER site on second quarter of the 2017.

  5. Self-perceived depression, anxiety, stress and their relationships with psychosocial job factors in male automotive assembly workers.

    Science.gov (United States)

    Edimansyah, Bin Abdin; Rusli, Bin Nordin; Naing, Lin; Mohamed Rusli, Bin Abdullah; Winn, Than; Tengku Mohamed Ariff, Bin Raja Hussin

    2008-01-01

    Depression, anxiety and stress have been recognized as important mental outcome measures in stressful working settings. The present study explores the prevalence of self-perceived depression, anxiety and stress; and their relationships with psychosocial job factors. A cross-sectional study involving 728 male automotive assembly workers was conducted in two major automotive assembly plants in Malaysia using the validated Malay versions of the Depression Anxiety Stress Scales (DASS) and Job Content Questionnaire (JCQ). Based on the DASS cut-off of > or =78 percentile scores, the prevalence of self-perceived depression, anxiety and stress was 35.4%, 47.2% and 31.1%, respectively. Four (0.5%), 29 (4.0%) and 2 (0.3%) workers, respectively, reported extremely severe self-perceived depression, anxiety and stress. Multiple linear regression analyses, controlling for age, education, salary, duration of work and marital status, revealed that psychological job demand, job insecurity and hazardous condition were positively associated with DASS-Depression, DASS-Anxiety and DASS-Stress; supervisor support was inversely associated with DASS-Depression and DASS-Stress. We suggest that reducing psychological job demand, job insecurity and hazardous condition factors may improve the self-perceived depression, anxiety and stress in male automotive assembly workers. Supervisor support is protective for self-perceived depression and stress.

  6. Cardiovascular risk factors associated with the metabolic syndrome are more prevalent in people reporting chronic pain: results from a cross-sectional general population study.

    Science.gov (United States)

    Goodson, Nicola J; Smith, Blair H; Hocking, Lynne J; McGilchrist, Mark M; Dominiczak, Anna F; Morris, Andrew; Porteous, David J; Goebel, Andreas

    2013-09-01

    To explore whether chronic pain is associated with cardiovascular risk factors and identify whether increased distribution or intensity of pain is associated with cardiovascular risk, participants in Generation Scotland: The Scottish Family Health study completed pain questionnaires recording the following: presence of chronic pain, distribution of pain, and intensity of chronic pain. Blood pressure, lipids, blood glucose, smoking history, waist-hip ratio, and body mass index were recorded; Framingham 10-year coronary heart disease (CHD) risk scores were calculated and a diagnosis of metabolic syndrome derived. Associations between chronic pain and cardiovascular risk were explored. Of 13,328 participants, 1100 (8.3%) had high CHD risk. Chronic pain was reported by 5209 (39%), 1294 (9.7%) reported widespread chronic pain, and 707 (5.3%) reported high-intensity chronic pain. In age- and gender-adjusted analyses, chronic pain was associated with elevated CHD risk scores (odds ratio 1.11, 95% confidence interval 1.01-1.23) and the metabolic syndrome (odds ratio 1.42, 95% confidence interval 1.24-1.62). Multivariate analyses identified dyslipidaemia, age, gender, smoking, obesity, and high waist-hip ratio as independently associated with chronic pain. Within the chronic pain subgroup, widespread pain did not confer any additional cardiovascular disease risk. However, cardiovascular disease risk factors contributing to metabolic syndrome were more prevalent in those reporting high-intensity chronic pain. This large population-based study has demonstrated that chronic pain, and in particular high-intensity chronic pain, is associated with an increased prevalence of cardiovascular risk factors and metabolic syndrome. The 10-year CHD risk score and metabolic syndrome correlate well with increased pain intensity, but not with widespread pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  7. Joint associations of obsity and other cardiovascular risk factors in relation to risk of acute coronary syndrome

    DEFF Research Database (Denmark)

    Jensen, Majken K.; Chiuve, Stephanie; Rimm, Eric B.

    as current smoking, Mediterranean diet score, and 25 kg/m2) and obesity (BMI>30 kg/m2) were significantly associated......Background: Obesity is a well-established risk factor for coronary heart disease (CHD). However, the influence of other lifestyle and clinical risk factors on the association between body-mass index (BMI: weight in kg/height in m2) and CHD remains uncertain. Methods and Results: In the Danish Diet...

  8. The NFKB1 ATTG ins/del polymorphism and risk of coronary heart disease in three independent populations

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Jensen, Majken K.; Due, Karen Margrete

    2011-01-01

    AimInflammation is a risk factor for coronary heart disease (CHD). A common deletion-allele in the promoter region of NFKB1 results in lower protein levels of the NF-κB p50 subunit. Recent evidence suggests that the NF-κB p50 dimer has anti-inflammatory effects. We aimed to investigate...... the association of the functional ATTG NFKB1 insertion/deletion variant with risk of CHD in three independent prospective studies of generally healthy men and women. Methods and resultsThe NFKB1 ins/del polymorphism was genotyped in studies of CHD nested within the Diet, Cancer and Health (DCH) study, the Health...... Professionals Follow-up (HPFS) and the Nurses’ Health (NHS) studies, totaling 1008, 428 and 439 cases, respectively. The minor allele frequency in the combined sample was 0.38 among controls. In a pooled analysis, the relative risk (RR) among heterozygous men and women was 1.22 (95% CI: 1.07–1.40), compared...

  9. Design and Testing of the Fusion Virtual Assembly System FVAS1.0

    International Nuclear Information System (INIS)

    Pengcheng Long; Songlin Liu; Yican Wu

    2006-01-01

    Virtual assembly (VA), utilizing virtual reality (VR) technologies to plan and evaluate assembly process, retains the benefits (time-saving, inexpensive and no hazardous) of VR technologies and conquers the shortcoming of physical prototypes, such as long circle, high cost, low precision, and so on. Presented in this paper is the Fusion Virtual Assembly System FVAS 1.0 that makes possible engineering application for assemblies of large-scale complex nuclear facilities. FVAS 1.0 is designed to support the planning, evaluation and demonstration of assembly process, and training assemblers, and to work on PC (personal computer) platform. In this paper, architecture and main features of FVAS are introduced firstly. Then, design of the key sections (such as collision detection, virtual roaming) are described in detail. Finally, some successful application cases are presented. To enhance the real-time performance for large-scale nuclear facilities simulation, a policy based on separation of display scene and collision detection scene has been adopted. The display scene can be predigested to reduce the time of scene refreshment, and the collision detection performance is greatly improved by using the mature interference check ability of commercial CAD systems. Convenient observation mechanism brings more practicability. So a multi-viewpoints roaming scheme has been utilized to facilitate users' assembly operation. Users can obtain much optical information from multiple angles by switching between multi-viewpoints. The ESAT superconducting tokamak is characterized by large volume, complicated constitution and high assembly precision, e.g. the strict precision requirement in the assembly for the three tori (the tori of vacuum vessel, thermal shield, and toroidal coil). FVAS 1.0 has succeeded in demonstrating the assembly process of ESAT components. Furthermore, FVAS 1.0 has been applied to evaluate FDS-I (Fusion-Driven Sub-critical system) concept from assembly point of

  10. Macrophage Migration Inhibitory Factor Polymorphism Is Associated with Susceptibility to Inflammatory Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Kangting Ji

    2015-01-01

    Full Text Available Background. Macrophage migration inhibitory factor (MIF is a proinflammatory cytokine. This study explored the association of 173G/C polymorphism of the MIF gene with coronary heart disease (CHD. Methods. Sequencing was carried out after polymerase chain reaction with DNA specimens from 186 volunteers without CHD and 70 patients with CHD. Plasma MIF levels on admission were measured by ELISA. Patients were classified into either stable angina pectoris (SAP or unstable angina pectoris (UAP. Genotype distribution between cases and controls and the association of patients’ genotypes with MIF level and plaque stability were statistically evaluated (ethical approval number: 2012-01. Results. The frequency of the C genotype was higher in CHD patients than in the control (P=0.014. The frequency of the 173*CC genotype was higher in CHD patients than in the control (P=0.005. The plasma MIF level was higher in MIF173*C carriers than in MIF173*G carriers (P=0.033. CHD patients had higher plasma MIF levels than the control (P=0.000. Patients with UAP had higher plasma MIF levels than patients with SAP (P=0.014. Conclusions. These data suggest that MIF −173G/C polymorphism may be related to the development of CHD in a Chinese population. Plasma MIF level is a predictor of plaque stability. This trial is registered with NCT01750502 .

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  12. Plasma membrane is the site of productive HIV-1 particle assembly.

    Directory of Open Access Journals (Sweden)

    Nolwenn Jouvenet

    2006-12-01

    Full Text Available Recently proposed models that have gained wide acceptance posit that HIV-1 virion morphogenesis is initiated by targeting the major structural protein (Gag to late endosomal membranes. Thereafter, late endosome-based secretory pathways are thought to deliver Gag or assembled virions to the plasma membrane (PM and extracellular milieu. We present several findings that are inconsistent with this model. Specifically, we demonstrate that HIV-1 Gag is delivered to the PM, and virions are efficiently released into the extracellular medium, when late endosome motility is abolished. Furthermore, we show that HIV-1 virions are efficiently released when assembly is rationally targeted to the PM, but not when targeted to late endosomes. Recently synthesized Gag first accumulates and assembles at the PM, but a proportion is subsequently internalized via endocytosis or phagocytosis, thus accounting for observations of endosomal localization. We conclude that HIV-1 assembly is initiated and completed at the PM, and not at endosomal membranes.

  13. Cardiovascular health knowledge and behavior in patient attendants at four tertiary care hospitals in Pakistan – a cause for concern

    Directory of Open Access Journals (Sweden)

    Afzal Atif

    2005-11-01

    Full Text Available Abstract Background Knowledge about coronary heart disease (CHD and its risk factors is an important pre-requisite for an individual to implement behavioral changes leading towards CHD prevention. There is scant data on the status of knowledge about CHD in the general population of Pakistan. The objective of this study was to assess knowledge of CHD in a broad Pakistani population and identify the factors associated with knowledge. Methods Cross sectional study was carried out at four tertiary care hospitals in Pakistan using convenience sampling. Standard questionnaire was used to interview 792 patient attendants (persons accompanying patients. Knowledge was computed as a continuous variable based on correct answers to fifteen questions. Multivariable linear regression was conducted to determine the factors independently associated with knowledge. Results The mean age was 38.1 (±13 years. 27.1% had received no formal education. The median knowledge score was 3.0 out of a possible maximum of 15. Only 14% were able to correctly describe CHD as a condition involving limitation in blood flow to the heart. Majority of respondents could identify only up to two risk factors for CHD. Most commonly identified risk factors were stress (43.4%, dietary fat (39.1%, smoking (31.9% and lack of exercise (17.4%. About 20% were not able to identify even a single risk factor for CHD. Factors significantly associated with knowledge included age (p = 0.023, income (p Conclusion This is the first study assessing the state of CHD knowledge in a relatively diverse non-patient population in Pakistan. There are striking gaps in knowledge about CHD, its risk factors and symptoms. These translate to inadequate preventive behavior patterns. Educational programs are urgently required to improve the level of understanding of CHD in the Pakistani population.

  14. Scientific programme and manufacture of types DK-1 and DK-2 diagnostic assemblies

    International Nuclear Information System (INIS)

    Krett, V.; Kott, J.; Vlcek, J.; Mlady, Z.

    1980-01-01

    The programme is described of measurements to be effected on the Rheinsberg WWER-2 reactor using diagnostic assemblies DK-1 and DK-2. The DK-1 assemblies were manufactured in the USSR and tested in the big water loop at SKODA Works. The insertion of the assemblies in the reactor is being prepared. The DK-2 assemblies are developed by SKODA Works in cooperation with the USSR, Hungary and Poland. (Ha)

  15. Stock volatility as a risk factor for coronary heart disease death.

    Science.gov (United States)

    Ma, Wenjuan; Chen, Honglei; Jiang, Lili; Song, Guixiang; Kan, Haidong

    2011-04-01

    The volatility of financial markets may cause substantial emotional and physical stress among investors. We hypothesize that this may have adverse effects on cardiovascular health. The Chinese stock markets were extremely volatile between 2006 and 2008. We, therefore, examined the relationship between daily change of the Shanghai Stock Exchange (SSE) Composite Index (referred as the Index) and coronary heart disease (CHD) deaths from 1 January 2006 to 31 December 2008 in Shanghai, the financial capital of China. Daily death and stock performance data were collected from the Shanghai Center for Disease Control and Prevention and SSE, respectively. Data were analysed with over-dispersed generalized linear Poisson models, controlling for long-term and seasonal trends of CHD mortality, day of the week, Index closing value, weather conditions, and air pollution levels. We observed a U-shaped relationship between the Index change and CHD deaths: both rising and falling of the Index were associated with more deaths and the fewest deaths coincided with little or no change of the index. We also examined the absolute daily change of the Index in relation to CHD deaths: in a 1-day lag model, each 100-point change of the Index corresponded to 5.17% (95% confidence interval: 1.71, 8.63%) increase in CHD deaths. Further analysis showed that the association was stronger for out-of-hospital CHD death than for in-hospital death. We found that CHD deaths fluctuated with daily stock changes in Shanghai, suggesting that stock volatility may adversely affect cardiovascular health.

  16. Studies on adsorption, reaction mechanisms and kinetics for photocatalytic degradation of CHD, a pharmaceutical waste.

    Science.gov (United States)

    Sarkar, Santanu; Bhattacharjee, Chiranjib; Curcio, Stefano

    2015-11-01

    The photocatalytic degradation of chlorhexidine digluconate (CHD), a disinfectant and topical antiseptic and adsorption of CHD catalyst surface in dark condition has been studied. Moreover, the value of kinetic parameters has been measured and the effect of adsorption on photocatalysis has been investigated here. Substantial removal was observed during the photocatalysis process, whereas 40% removal was possible through the adsorption route on TiO2 surface. The parametric variation has shown that alkaline pH, ambient temperature, low initial substrate concentration, high TiO2 loading were favourable, though at a certain concentration of TiO2 loading, photocatalytic degradation efficiency was found to be maximum. The adsorption study has shown good confirmation with Langmuir isotherm and during the reaction at initial stage, it followed pseudo-first-order reaction, after that Langmuir Hinshelwood model was found to be appropriate in describing the system. The present study also confirmed that there is a significant effect of adsorption on photocatalytic degradation. The possible mechanism for adsorption and photocatalysis has been shown here and process controlling step has been identified. The influences of pH and temperature have been explained with the help of surface charge distribution of reacting particles and thermodynamic point of view respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Risk Factors for Coronary Heart Disease Among Inpatients Who Have Mild Intellectual Disability and Mental Illness

    Science.gov (United States)

    Merriman, S.; Haw, C.; Kirk, J.; Stubbs, J.

    2005-01-01

    Coronary heart disease (CHD) is a major cause of morbidity and mortality in the UK. The aim of this study was to screen inpatients with mild or borderline intellectual disability, many of whom also have mental illness, for risk factors for CHD. Participants were interviewed, measured and had blood samples taken. Of the 53 participants, 20 (37.7%)…

  18. ASF1 is required to load histones on the HIRA complex in preparation of paternal chromatin assembly at fertilization.

    Science.gov (United States)

    Horard, Béatrice; Sapey-Triomphe, Laure; Bonnefoy, Emilie; Loppin, Benjamin

    2018-05-11

    Anti-Silencing Factor 1 (ASF1) is a conserved H3-H4 histone chaperone involved in both Replication-Coupled and Replication-Independent (RI) nucleosome assembly pathways. At DNA replication forks, ASF1 plays an important role in regulating the supply of H3.1/2 and H4 to the CAF-1 chromatin assembly complex. ASF1 also provides H3.3-H4 dimers to HIRA and DAXX chaperones for RI nucleosome assembly. The early Drosophila embryo is an attractive system to study chromatin assembly in a developmental context. The formation of a diploid zygote begins with the unique, genome-wide RI assembly of paternal chromatin following sperm protamine eviction. Then, within the same cytoplasm, syncytial embryonic nuclei undergo a series of rapid, synchronous S and M phases to form the blastoderm embryo. Here, we have investigated the implication of ASF1 in these two distinct assembly processes. We show that depletion of the maternal pool of ASF1 with a specific shRNA induces a fully penetrant, maternal effect embryo lethal phenotype. Unexpectedly, despite the depletion of ASF1 protein to undetectable levels, we show that asf1 knocked-down (KD) embryos can develop to various stages, thus demonstrating that ASF1 is not absolutely required for the amplification of cleavage nuclei. Remarkably, we found that ASF1 is required for the formation of the male pronucleus, although ASF1 protein does not reside in the decondensing sperm nucleus. In asf1 KD embryos, HIRA localizes to the male nucleus but is only capable of limited and insufficient chromatin assembly. Finally, we show that the conserved HIRA B domain, which is involved in ASF1-HIRA interaction, is dispensable for female fertility. We conclude that ASF1 is critically required to load H3.3-H4 dimers on the HIRA complex prior to histone deposition on paternal DNA. This separation of tasks could optimize the rapid assembly of paternal chromatin within the gigantic volume of the egg cell. In contrast, ASF1 is surprisingly dispensable for the

  19. Determination of serum insulinlike growth factor II levels in coronary heart disease patient and its significance

    International Nuclear Information System (INIS)

    Fan Bifu; Ji Naijun; Mei Yibin; Wang Chengyao; Zhao Junfei; Guan Lihua; Gao Meiying; Li Jiangao

    2002-01-01

    Objective: To explore the changes and clinical significance of serum insulinlike growth factor II (IGF II) levels in coronary heart disease (CHD) patients. Methods: The serum IGF II levels were determined by radioimmunoassay in 68 patients with coronary heart disease (CHD) and 30 controls with only mild non-cardiac diseases. Results: Compared with the controls, the serum IGF II level in CHD patients were increased significantly (0.66 ± 0.13 μg/L vs 0.51 ± 0.11 μg/L; t = 5.506, p 0.05). Level in patients dies in hospital (n = 9) were much higher than those in patients recovered (n = 59) (t = 2.402, p < 0.05). Conclusion: Serum IGF II levels seems to be related to the seriousness of CHD; the actual mechanism remains to be defined

  20. The prevalence and risk factors for cholelithiasis and asymptomatic gallstones in adults with congenital heart disease.

    Science.gov (United States)

    Shiina, Yumi; Toyoda, Tomohiko; Kawasoe, Yasutaka; Tateno, Shigeru; Shirai, Takeaki; Matsuo, Kozo; Mizuno, Yoshiko; Ai, Toshiji; Niwa, Koichiro

    2011-10-20

    Cyanosis is considered to be a risk factor for cholelithiasis which is an important complication of cyanotic congenital heart disease (CCHD) in adults. In this study, the prevalence of cholelithiasis and asymptomatic calcium bilirubinate gallstones was evaluated in adults with congenital heart disease (CHD). Furthermore, risk factors for this potentially high risk complication were assessed. Subjects were derived from 114 consecutive congenital patients who visited our center from May 2008 to January 2009. For analyses of risk factors, we divided them into 4 groups: group A, 15 CCHD patients without reparative surgery (7 men, 31.8 ± 7.0 years old); group B, 41 CCHD patients rendered acyanotic by reparative surgery (21 men, 32.5 ± 11.8 years old); group C, 23 unoperated acyanotic CHD patients (11 men, 42.4 ± 16.4 years old); and group D, 35 patients who were acyanotic before and after operation (18 men, 36.3 ± 14.8 years old). Gallstones were identified by abdominal ultrasound and risk factors were analyzed by a multivariate logistic regression model. Cholecystectomy was performed in 5/114 (4.3%), asymptomatic gallstones were seen in 16/114 (14%), and symptomatic gallstones except for patients after cholecystectomy were seen in 7/114 (6.1%). In group A, 4 (27%) with gallstones underwent cholecystectomy (pnobody in group C, and 3 patients (8.6%) in group D. By a multivariate logistic regression model, CCHD by nature regardless of repair, prolonged cyanosis periods, higher frequency of cardiopulmonary bypass (CPB), and lower platelet counts were significant factors predicting gallstones (odds ratio 4.48, 1.08, 3.96, and 0.87, 95% CI, 1.14-17.5, 1.00-1.18, 1.65-9.54, and 0.75-0.99, respectively). The prevalence of cholelithiasis and asymptomatic gallstones is significantly high in CCHD patients regardless of cardiac repairs. CCHD by nature, prolonged cyanosis durations, high frequency of CPB and low platelet counts have influences on gallstone formation in adults

  1. MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol.

    Science.gov (United States)

    Santo, Karla; Chow, Clara K; Thiagalingam, Aravinda; Rogers, Kris; Chalmers, John; Redfern, Julie

    2017-10-08

    The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence. Randomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps. Ethical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via usual scientific forums. ACTRN12616000661471; Pre-results.

  2. Experience with construction and assembly of V-1 nuclear power plant

    International Nuclear Information System (INIS)

    Prochazka, J.; Stepanek, S.; Drahy, J.

    1981-01-01

    The model is discussed of the constructions of the V-1 nuclear power plant at Jaslovske Bohunice with SKODA Trust fulfilling the role of the general supplier of the secondary part technology and the chief and special assembly contractor. The SKODA Trust mediated the Soviet supplies of technology, Soviet assembly and special assembly, and the mounting of the primary part according to Soviet projects. Plant start-up was safeguarded by the investor through Bohunice power plant staff and Soviet experts. The assembly of the primary circuit and the test assembly of reactor parts are described and the experience gained is discussed. The technological requirements are illustrated by the most important characteristics of the individual parts of the primary circuit. Also described are the design specifications of the 220 MW saturated steam turbine and the experience with its assembly and start-up. (B.S.)

  3. Pattern of Coronary Artery Disease Risk Factors in Population Younger than 55 Years and Above 55 Years: A Population Study of 31999 Healthy Individuals

    Directory of Open Access Journals (Sweden)

    Zinat Nadia Hatmi

    2011-06-01

    Full Text Available More than eighty percent of patients with coronary heart diseases (CHD have conventional risk factors. Prevalence of well known risk factors seems to show a different pattern in younger patients and individual above 55 years. To evaluate the pattern of conventional CHD risk factors in healthy individuals in two different age groups. A large scale population based survey of 31999 individuals from ten medical centers was designed. Screening of risk factors was performed upon these protocols: taking medical history, physical examination and blood tests of complete blood cell counts, fasting blood sugar, lipid profile, urinalysis and creatinine. Prevalence of the risk factors in healthy people aged above 55 years were: 8.1% for systolic blood pressure (SBP>140 mmHg, 3.8% for diastolic blood pressure (DBP>90mmHg, 13.9% for fasting blood glucose (FBS≥126 Mg/dl, 36.9% for total cholesterol>200 Mg/dl, 19.2% for triglyceride (TG>200 Mg/dl, 67.8% for HDL-c130 Mg/dl, 4.72 for TC/HDL-c ratio, 2.88 for LDL-c/HDL/c ratio and 4.24 for TG/HDL-c ratio. Prevalence of risk factors in individuals younger than 55 years were: 1.7% for SBP>140 mmHg, 1.2% for DBP>90 mmHg, 5.2% for FBS≥126 Mg/dl, 31.3% for TC>200 Mg/dl, 21.5% for TG>200 Mg/dl, 69.4% for HDL-c130 Mg/dl, 4.7 for TC/HDL-c ratio, 2.83 for LDL-c/HDL-c ratio and 4.43 for TG/HDL-c ratio. In univariate model of analysis: prevalence of the risk factors were significantly higher in age above 55 years than in people younger than 55 years except for hypertriglyceridemia and HDL-c200 Mg/dl P= 0.002, HDL-c140 mmHg P=0.001. Pattern of such a CHD risk factors of FBS≥126 Mg/dl, TG>200 Mg/dl, HDL-c140 mmHg demonstrated a statistically significant difference in the age above 55 years to the healthy people younger than 55 years. These results cab be implicated to set up prediction models for stratifying individuals at higher risk of CHD.

  4. Assembly and metrology of first wall components of SST-1

    International Nuclear Information System (INIS)

    Parekh, Tejas; Santra, Prosenjit; Biswas, Prabal

    2015-01-01

    First Wall components (FWC) of SST-1 tokamak, which are in the immediate vicinity of plasma comprises of limiters, divertors, baffles, passive stabilizers are designed to operate long duration (1000 s) discharges of elongated plasma. All FWC consists of a copper alloy heat sink modules with SS cooling tubes brazed onto it, graphite tiles acting as armour material facing the plasma, and are mounted to the vacuum vessels with suitable Inconel support structures at ring and port locations. The FWC are very recently assembled and commissioned successfully inside the vacuum vessel of SST-1 under going a meticulous planning of assembly sequence, quality checks at every stage of the assembly process. This paper will present the metrology aspects and procedure of each FWC, both outside the vacuum vessel, and inside the vessel, assembly tolerances, tools, equipment and jig/fixtures, used at each stage of assembly, starting from location of support bases on vessel rings, fixing of copper modules on support structures, around 3800 graphite tile mounting on 136 copper modules with proper tightening torques, till final toroidal and poloidal geometry of the in-vessel components are obtained within acceptable limits, also ensuring electrical continuity of passive stabilizers to form a closed saddle loop, electrical isolation of passive stabilizers from vacuum vessel. (author)

  5. AUP1 (Ancient Ubiquitous Protein 1) Is a Key Determinant of Hepatic Very-Low-Density Lipoprotein Assembly and Secretion.

    Science.gov (United States)

    Zhang, Jing; Zamani, Mostafa; Thiele, Christoph; Taher, Jennifer; Amir Alipour, Mohsen; Yao, Zemin; Adeli, Khosrow

    2017-04-01

    AUP1 (ancient ubiquitous protein 1) is an endoplasmic reticulum-associated protein that also localizes to the surface of lipid droplets (LDs), with dual role in protein quality control and LD regulation. Here, we investigated the role of AUP1 in hepatic lipid mobilization and demonstrate critical roles in intracellular biogenesis of apoB100 (apolipoprotein B-100), LD mobilization, and very-low-density lipoprotein (VLDL) assembly and secretion. APPROACH AND RESULTS: siRNA (short/small interfering RNA) knockdown of AUP1 significantly increased secretion of VLDL-sized apoB100-containing particles from HepG2 cells, correcting a key metabolic defect in these cells that normally do not secrete much VLDL. Secreted particles contained higher levels of metabolically labeled triglyceride, and AUP1-deficient cells displayed a larger average size of LDs, suggesting a role for AUP1 in lipid mobilization. Importantly, AUP1 was also found to directly interact with apoB100, and this interaction was enhanced with proteasomal inhibition. Knockdown of AUP1 reduced apoB100 ubiquitination, decreased intracellular degradation of newly synthesized apoB100, and enhanced extracellular apoB100 secretion. Interestingly, the stimulatory effect of AUP1 knockdown on VLDL assembly was reminiscent of the effect previously observed after MEK-ERK (mitogen-activated protein kinase kinase-extracellular signal-regulated kinase) inhibition; however, further studies indicated that the AUP1 effect was independent of MEK-ERK signaling. In summary, our findings reveal an important role for AUP1 as a regulator of apoB100 stability, hepatic LD metabolism, and intracellular lipidation of VLDL particles. AUP1 may be a crucial factor in apoB100 quality control, determining the rate at which apoB100 is degraded or lipidated to enable VLDL particle assembly and secretion. © 2017 American Heart Association, Inc.

  6. Metformin-diet ameliorates coronary heart disease risk factors and facilitates resumption of regular menses in adolescents with polycystic ovary syndrome.

    Science.gov (United States)

    Glueck, Charles J; Goldenberg, Naila; Wang, Ping

    2009-09-01

    In 20 adolescents age PCOS), we assessed efficacy and safety of metformin-diet for 1 year in treatment of endocrinopathy and coronary heart disease (CHD) risk factors. Calories were targeted to 1,500-1,800/ day if body mass index (BMI) was or = 25, along with 2,550 mg metformin. Median weight fell from 85.5 to 78.4 kg (p = 0.004), waist circumference from 91 to 84 cm (p = 0.017), triglyceride from 108 to 71 mg/dl (p = 0.008), insulin from 20.5 to 15 microU/ml (p = 0.018), HOMA-IR from 2.0 to 1.5 (p = 0.026), and testosterone from 45.5 to 31.5 ng/dl (p = 0.03). The percentage of cycles with normal menses rose from a pre-treatment median of 8% to 100%, p PCOS, metformin-diet safely ameliorates CHD risk factors and endocrinopathy while facilitating resumption of regular menses.

  7. MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics

    Directory of Open Access Journals (Sweden)

    Dhanendra Tomar

    2016-05-01

    Full Text Available Mitochondrial Ca2+ Uniporter (MCU-dependent mitochondrial Ca2+ uptake is the primary mechanism for increasing matrix Ca2+ in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1 have severely impaired [Ca2+]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca2+-dependent mitochondrial metabolism.

  8. Quality control of FWC during assembly/commissioning on SST-1

    International Nuclear Information System (INIS)

    Patel, Hiteshkumar; Santra, Prosenjit; Jaiswal, Snehal

    2015-01-01

    First Wall components (FWC) of SST-1 tokamak, which are in the immediate vicinity of plasma comprises of limiters, divertors, baffles, passive stabilizers are designed to operate long duration (1000 s) discharges of elongated plasma. All FWC consists of a copper alloy heat sink modules with SS cooling tubes brazed onto it, graphite tiles acting as armour material facing the plasma, and are mounted to the vacuum vessels with suitable Inconel support structures at ring and port locations. The FWC are very recently assembled and commissioned successfully inside the vacuum vessel of SST-1 under going a rigorous quality control and checks at every stage of the assembly process. This paper will present the quality control and checks of FWC from commencement of assembly procedure, namely material test reports, leak testing of high temperature baked components, assembled dimensional tolerances, leak testing of all welded joints, graphite tile tightening torques, electrical continuity of passive stabilizers, and electrical isolation of passive stabilizers from vacuum vessel, baking and cooling hydraulic connections inside vacuum vessel. (author)

  9. Nondestructive examination of Oconee 1 fuel assemblies after four cycles of irradiation

    International Nuclear Information System (INIS)

    Pyecha, T.D.; Mayer, J.T.; Guthrie, B.A. III; Riordan, J.E.

    1980-12-01

    Five B and W Mark B (15 x 15) pressurized water reactor fuel assemblies were nondestructively examined after four cycles of irradiation in the Oconee 1 reactor. Four of the five assemblies examined had a burnup of 40,000 MWd/mtU; the fifth assembly had a burnup of 36,800 MWd/mtU. This effort is part of a Department of Energy program to improve uranium utilization by extending the burnup of light water reactor fuel. The examinations were conducted in the Oconee 1 and 2 spent fuel storage pool. Data obtained included fuel assembly and fuel rod dimensions, water channel spacings, spacer grid and holddown spring forces, fuel column stack and axial gap lengths, and crud samples. The results indicate that the assemblies performed well through four cycles of operation; all of the data were within design limits

  10. Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility.

    Science.gov (United States)

    Han, Xia; Liu, Lili; Niu, Jiamin; Yang, Jun; Zhang, Zengtang; Zhang, Zhiqiang

    2015-01-01

    Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.

  11. [Risk factors for acute respiratory syncytial virus infection of lower respiratory tract in hospitalized infants].

    Science.gov (United States)

    Zhang, Xiaobo; Liu, Lijuan; Shi, Peng; Jiang, Gaoli; Jia, Pin; Wang, Chuankai; Wang, Libo; Qian, Liling

    2014-05-01

    To investigate the clinical epidemiologic characteristics and analyze risk factors for acute respiratory syncytial virus (RSV) infection in hospitalized infants with acute lower respiratory tract infection (ALRI). ALRI infants admitted to Children's Hospital of Fudan University from March 1st, 2011 to February 29th, 2012, were enrolled in this study. Patient information included demographic characteristics, feeding history, family status, clinical presentation, accessory examination, treatment and prognosis. According to the etiology of ALRI infants, we compared the seasonal distribution, demographic characteristics, household characteristics and underlying diseases between RSV-positive patients and RSV-negative patients. Univariate and multiple Logistic regression analyses were used to determine factors that were associated with risk of RSV infection. Among 1 726 ALRI infants, there were 913 RSV-positive infants (52.9%). The occurrence of RSV infection had a seasonal variation, with a peak in winter (59.1%). The median (P25, P75) age of RSV infants was 64 (21-155) days. The gestational age (GA) and body weight (BW) was (37.5 ± 2.4) weeks and (3.07 ± 0.66) kg, respectively. The male/female ratio among these was 1.9: 1. RSV infection was more popular among infants in the families with smoking members, crowded living conditions, history of atopic mother. Differences of the proportion of patients with underlying disease between RSV-positive and negative groups were statistically significant (59.4% vs. 54.2%, P infection were: GAinfection (OR = 1.351, 95%CI: 1.024-1.783; OR = 1.713, 95%CI: 1.332-2.204). Multivariate logistic regression determined the factors increasing the risk of RSV infection were: underlying CHD (OR = 1.298, 95%CI: 1.002-1.681), mother with atopic diseases (OR = 1.766, 95%CI: 1.237-2.520), autumn or winter infection (OR = 1.481, 95%CI: 1.105-1.985; OR = 1.766, 95%CI: 1.358-2.296). The prevalence of RSV infection was the highest in winter, while

  12. Comparison of exercise and pharmacologic stress in myocardium perfusion imaging for CHD

    International Nuclear Information System (INIS)

    Li Zebo; Zheng Kangni; Cheng Xiaorui; Liu Hui; Cheng Yihai

    1995-01-01

    In order to provide a proper stress test, exercise, dipyridamole and ATP stress were compared. Three modalities were compared with respect to the detecting rate, methodology, hemodynamic and side effects. There are no significant differences in their ability of detecting coronary heart disease (CHD) (P>0.05). Exercise stress causes an increase in heart rate, blood pressure and myocardium oxygen consumption. Pharmacologic stress cause a slight increase in heart rate, but a decrease in blood pressure (P<0.01). Exercise stress is a basic method with good image quality, but it needs a special equipment. Pharmacologic stress is an easier, cheaper and safer method, particularly useful for patients unable to perform exercise test

  13. Testing Whether Defective Chromatin Assembly in S-Phase Contributes to Breast Cancer

    National Research Council Canada - National Science Library

    Adams, Peter

    2003-01-01

    .... We used a dominant negative mutant of (chromatin assembly factor-I) CAF1, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S-phase chromatin assembly and found that this induced S-phase arrest...

  14. Testing Whether Defective Chromatin Assembly in S-Phase Contributes to Breast Cancer

    National Research Council Canada - National Science Library

    Adams, Peter

    2004-01-01

    .... We used a dominant negative mutant of (chromatin assembly factor-I) CAF1, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S-phase chromatin assembly and found that this induced S-phase arrest...

  15. Interactions Between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

    DEFF Research Database (Denmark)

    Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea

    2017-01-01

    between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA:Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged......Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable...... in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle...

  16. Screening results for subclinical coronary artery calcification in asymptomatic individuals in relation to a detailed parental history of premature coronary heart disease

    International Nuclear Information System (INIS)

    Wahl, Stefanie; Möhlenkamp, Stefan; Erbel, Raimund; Moebus, Susanne; Andrich, Silke; Stang, Andreas; Jöckel, Karl-Heinz; Dragano, Nico

    2013-01-01

    A parental history of premature coronary heart disease (CHD) is an established risk factor for CHD events in descendants. The study aim was to investigate whether subclinical coronary artery calcification (CAC) differs between asymptomatic individuals (a) without a parental CHD history, (b) with a parental history and (c) without knowledge of parental CHD history. The inclusion of individuals without knowledge of parental CHD history is a new approach. We also differentiated between CHD of mother and father to gain insight into their individual contributions. Data was obtained for 4,301 subjects aged 45–75 years free of overt CHD from the baseline screening of the population-based Heinz Nixdorf Recall study. CAC, measured by electron-beam computed tomography, was modeled conducting logistic regressions. Model 1 included family history, Model 2 was adjusted for age (and gender) and Model 3 added common CHD risk factors. The CAC score was dichotomized using the age and sex-specific 75th percentile. The odds ratio (OR) for CAC ≥ age and sex-specific 75th percentile was 1.33 among individuals with parental premature CHD history (95 % confidence interval [95 %CI]: 1.08, 1.63), which did not change after full adjustment (OR 1.40, 95 %CI: 1.13, 1.74). Individuals with an unknown biological father or mother had a high chance of elevated CAC scores (fully adjusted; father: OR 1.38, 95 %CI: 1.01, 1.90, mother: OR 1.86, 95 %CI: 0.90, 3.84) compared to the reference group. The current study showed an association between parental CHD history and CAC independent of common CHD risk factors. This association affirms the use of parental CHD history in cardiovascular risk assessment among asymptomatic adults in routine practice. The observation that individuals who did not know their mother or father are prone to increased CAC scores needs further confirmation in large scale studies.

  17. 11-Hydroxyundecyl octadecyl disulfide self-assembled monolayers on Au(1 1 1)

    Energy Technology Data Exchange (ETDEWEB)

    Albayrak, Erol [Department of Materials and Metallurgical Engineering, Ahi Evran University, Kırşehir 40000 (Turkey); Karabuga, Semistan [Department of Chemistry, Kahramanmaraş Sütçü İmam University, Kahramanmaraş 46030 (Turkey); Bracco, Gianangelo [CNR-IMEM and Department of Physics, University of Genoa, via Dodecaneso 33, Genoa 16146 (Italy); Danışman, M. Fatih, E-mail: danisman@metu.edu.tr [Department of Chemistry, Middle East Technical University, Ankara 06800 (Turkey)

    2014-08-30

    Highlights: • 11-Hydroxyundecyl octadecyl disulfide self-assembled monolayers on Au(1 1 1) surface were grown by supersonic molecular beam deposition. • Two different lying down monolayer phases were observed depending on the substrate temperature. • High temperature monolayer phase has a diffraction pattern similar to that of mercaptoundecanol SAMs. • Desorption from several different chemisorbed and physisorbed states were observed. - Abstract: Here, we report a helium atom diffraction study of 11-hydroxyundecyl octadecyl disulfide (CH{sub 3}-(CH{sub 2}){sub 17}-S-S-(CH{sub 2}){sub 11}-OH, HOD) self-assembled monolayers (SAMs) produced by supersonic molecular beam deposition (SMBD). Two different lying down monolayer phases were observed depending on the substrate temperature. At low temperatures a poorly ordered phase was observed, while the diffraction patterns of the film grown at high temperatures were similar to that of mercaptoundecanol (MUD) SAMs reported previously in the literature. The transition from the low temperature phase to the high temperature phase is due to S-S bond cleavage at the surface. Desorption from several different chemisorbed and physisorbed states were observed with energies in the same range as observed for MUD and octadecanelthiol (ODT) SAMs.

  18. Women's Heart Disease: Heart Disease Risk Factors

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk ...

  19. Structural integrity assessment and stress measurement of CHASNUPP-1 fuel assembly

    Directory of Open Access Journals (Sweden)

    Waseem

    2016-01-01

    Full Text Available Fuel assembly of the PWR nuclear power plant is a long and flexible structure. This study has been made in an attempt to find the structural integrity of the fuel assembly (FA of Chashma Nuclear Power Plant-1 (CHASNUPP-1 at room temperature in air. The non-linear contact and structural tensile analysis have been performed using ANSYS 13.0, in order to determine the fuel assembly (FA elongation behaviour as well as the location and values of the stress intensity and stresses developed in axial direction under applied tensile load of 9800 N or 2 g being the fuel assembly handling or lifting load [Y. Zhang et al., Fuel assembly design report, SNERDI, China, 1994]. The finite element (FE model comprises spacer grids, fuel rods, flexible contacts between the fuel rods and grid's supports system and guide thimbles with dash-pots and flow holes, in addition to the spot welds between spacer grids and guide thimbles, has been developed using Shell181, Conta174 and Targe170 elements. FA is a non-straight structure. The actual behavior of the geometry is non-linear due to its curvature or design tolerance. It has been observed that fuel assembly elongation values obtained through FE analysis and experiment [SNERDI Tech. Doc., Mechanical strength and calculation for fuel assembly, Technical Report, F3.2.1, China, 1994] under applied tensile load are comparable and show approximately linear behaviors. Therefore, it seems that the permanent elongation of fuel assembly may not occur at the specified load. Moreover, the values of stresses obtained at different locations of the fuel assembly are also comparable with the stress values of the experiment determined at the same locations through strain gauges. Since the results of both studies (analytical and experimental are comparable, therefore, validation of the FE methodology is confirmed. The stress intensity of the FE model and maximum stresses developed along the guide thimbles in axial direction are

  20. YB-1 promotes microtubule assembly in vitro through interaction with tubulin and microtubules

    Directory of Open Access Journals (Sweden)

    Baconnais Sonia

    2008-09-01

    Full Text Available Abstract Background YB-1 is a major regulator of gene expression in eukaryotic cells. In addition to its role in transcription, YB-1 plays a key role in translation and stabilization of mRNAs. Results We show here that YB-1 interacts with tubulin and microtubules and stimulates microtubule assembly in vitro. High resolution imaging via electron and atomic force microscopy revealed that microtubules assembled in the presence of YB-1 exhibited a normal single wall ultrastructure and indicated that YB-1 most probably coats the outer microtubule wall. Furthermore, we found that YB-1 also promotes the assembly of MAPs-tubulin and subtilisin-treated tubulin. Finally, we demonstrated that tubulin interferes with RNA:YB-1 complexes. Conclusion These results suggest that YB-1 may regulate microtubule assembly in vivo and that its interaction with tubulin may contribute to the control of mRNA translation.

  1. Relationships between coronary heart disease risk factors and serum ionized calcium in Kennedy Space Center Cohort

    Science.gov (United States)

    Goodwin, Lisa Ann; Frey, Mary Anne Bassett; Merz, Marion P.; Alford, William R.

    1987-01-01

    Kennedy Space Center (KSC) employees are reported to be at high risk for coronary heart disease (CHD). Risk factors for CHD include high serum total cholesterol levels, low levels of high-density lipoprotein cholesterol (HDLC), elevated triglyceride, smoking, inactivity, high blood pressure, being male, and being older. Higher dietary and/or serum calcium Ca(++) may be related to a lower risk for CHD. Fifty men and 37 women participated. Subjects were tested in the morning after fasting 12 hours. Information relative to smoking and exercise habits was obtained; seated blood pressures were measured; and blood drawn. KCS men had higher risk values than KCS women as related to HDLC, triglycerides, systolic blood pressure, and diastolic blood pressure. Smoking and nonsmoking groups did not differ for other risk factors or for serum Ca(++) levels. Exercise and sedentary groups differed in total cholesterol and triglyceride levels. Serum Ca(++) levels were related to age, increasing with age in the sedentary group and decreasing in the exercisers, equally for men and women. It is concluded that these relationships may be significant to the risk of CHD and/or the risk of bone demineralization in an aging population.

  2. Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

    Science.gov (United States)

    Davis, Michael E.; Hsieh, Patrick C. H.; Takahashi, Tomosaburo; Song, Qing; Zhang, Shuguang; Kamm, Roger D.; Grodzinsky, Alan J.; Anversa, Piero; Lee, Richard T.

    2006-05-01

    Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy. engineering | maturation | scaffold

  3. Profile of Cardiovascular Risk Factors in Patients with Coronary Heart Disease, Normal and Impaired Carbohydrate Metabolism

    Directory of Open Access Journals (Sweden)

    І.V. Cherniavska

    2015-11-01

    Full Text Available The aim of research was to conduct the comparative analysis of the profile of cardiovascular risk factors in patients with coronary heart disease (CHD and normal either impaired carbohydrate metabolism. Materials and methods. One hundred and forty two patients were observed. In order to estimate the rate of different forms of CHD depending on the state of carbohydrate metabolism such groups were formed: the first group consisted of 83 patients with type 2 diabetes mellitus (DM, the second group involved 34 patients with impaired glucose tolerance (IGT, the third group consisted of 25 patients with normal carbohydrate metabolism. The ischemic changes of myocardium were detected by ambulatory ECG monitoring with the obligatory achievement of submaximal heart rate during the research. Results. Silent myocardial ischemia was educed in 19 (22.9 % patients with type 2 DM, in 3 (8.8 % persons with IGT and in 2 (8.0 % patients with normal carbohydrate metabolism. Smoking, burdened heredity, violation in the haemostatic system more often occurred in the group of patients with type 2 DM and silent myocardial ischemia in comparison with the patients with type 2 DM without CHD. The profile of general population cardiovascular risk factors in patients with CHD and type 2 DM belongs to the most unfavorable. At the same time for patients with early violations of carbohydrate metabolism and normal carbohydrate metabolism such profile statistically does not differentiate meaningfully. Conclusions. Patients with type 2 DM and silent myocardial ischemia as compared to patients with type 2 DM without CHD have more expressed violations of indexes of general population cardiovascular risk factors for certain.

  4. Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1

    Czech Academy of Sciences Publication Activity Database

    Stibůrek, L.; Veselá, K.; Hansíková, H.; Pecina, Petr; Tesařová, M.; Černá, L.; Houštěk, Josef; Zeman, J.

    2005-01-01

    Roč. 392, č. 3 (2005), s. 625-632 ISSN 0264-6021 R&D Projects: GA ČR(CZ) GA303/03/0749; GA MŠk(CZ) 1M0520; GA ČR(CZ) GP303/03/D132 Grant - others:GA UK(CZ) 17/2004/C; Priority 1(XE) LSHMCT-2004-503116 Institutional research plan: CEZ:AV0Z50110509 Keywords : assembly pathway * cytochrome c oxidase * SURF1 Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.224, year: 2005

  5. A longitudinal analysis of the risk factors for diabetes and coronary heart disease in the Framingham Offspring Study

    Directory of Open Access Journals (Sweden)

    Bhargava Alok

    2003-04-01

    Full Text Available Abstract Background The recent trends in sedentary life-styles and weight gain are likely to contribute to chronic conditions such as hypertension, diabetes, and cardiovascular diseases. The temporal sequence and pathways underlying these conditions can be modeled using the knowledge from the biomedical and social sciences. Methods The Framingham Offspring Study in the U.S. collected information on 5124 subjects at baseline, and 8, 12, 16, and 20 years after the baseline. Dynamic random effects models were estimated for the subjects' weight, LDL and HDL cholesterol, and blood pressure using 4 time observations. Logistic and probit models were estimated for the probability of diabetes and coronary heart disease (CHD events. Results The subjects' age, physical activity, alcohol consumption, and cigarettes smoked were important predictors of the risk factors. Moreover, weight and height were found to differentially affect the probabilities of diabetes and CHD events; body weight was positively associated with the risk of diabetes while taller individuals had lower risk of CHD events. Conclusion The results showed the importance of joint modeling of body weight, LDL and HDL cholesterol, and blood pressure that are risk factors for diabetes and CHD events. Lower body weight and LDL concentrations and higher HDL levels achieved via physical exercise are likely to reduce diabetes and CHD events.

  6. Relationship of the MTHFD1 (rs2236225, eNOS (rs1799983, CBS (rs2850144 and ACE (rs4343 gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects

    Directory of Open Access Journals (Sweden)

    Mehri Khatami

    2017-09-01

    Full Text Available Congenital heart defects are structural cardiovascular malformations that arise from abnormal formation of the heart or major blood vessels during the fetal period. To investigate the association of 4 single nucleotide polymorphisms (SNPs in the MTHFD1, eNOS, CBS and ACE genes, we evaluated their relationship with CHD in Iranian patients. In this case–control study, a total of 102 children with CHD and 98 control children were enrolled. Four SNPs including MTHFD1 G1958A, eNOS G894T, CBS C-4673G and ACE A2350G were genotyped by PCR-SSCP, Multiplex ARMS PCR and PCR-RFLP methods and confirmed by direct sequencing. We genotyped 102 patients and 98 controls for four polymorphisms by statistically analysis. There were three SNPs including MTHFD1 G1958A, eNOS G894T and ACE A2350G which might increase the risk of CHD, but CBS C-4673G was not significantly different between patients and controls. (P = 0.017, P = 0.048, P = 0.025 and P = 0.081 respectively. The allele frequencies of three SNPs for MTHFD1 G1958A, eNOS G894T and ACE A2350G in CHD are higher than that in control. Our results show that there is a significant relationship between MTHFD1 G1958A, eNOS G894T and ACE A2350G polymorphisms with CHD. Therefore, The AA and GA genotypes of MTHFD1 G1958A, TT and GT genotypes of eNOS G894T and the AA and GA genotypes of ACE A2350G are susceptible factors for CHD and may increase the risk of CHD.

  7. Relationship of the MTHFD1 (rs2236225), eNOS (rs1799983), CBS (rs2850144) and ACE (rs4343) gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects.

    Science.gov (United States)

    Khatami, Mehri; Ratki, Farzaneh Morteza; Tajfar, Saba; Akrami, Fatemeh

    2017-09-01

    Congenital heart defects are structural cardiovascular malformations that arise from abnormal formation of the heart or major blood vessels during the fetal period. To investigate the association of 4 single nucleotide polymorphisms (SNPs) in the MTHFD1, eNOS, CBS and ACE genes, we evaluated their relationship with CHD in Iranian patients. In this case-control study, a total of 102 children with CHD and 98 control children were enrolled. Four SNPs including MTHFD1 G1958A, eNOS G894T, CBS C-4673G and ACE A2350G were genotyped by PCR-SSCP, Multiplex ARMS PCR and PCR-RFLP methods and confirmed by direct sequencing. We genotyped 102 patients and 98 controls for four polymorphisms by statistically analysis. There were three SNPs including MTHFD1 G1958A, eNOS G894T and ACE A2350G which might increase the risk of CHD, but CBS C-4673G was not significantly different between patients and controls. (P = 0.017, P = 0.048, P = 0.025 and P = 0.081 respectively). The allele frequencies of three SNPs for MTHFD1 G1958A, eNOS G894T and ACE A2350G in CHD are higher than that in control. Our results show that there is a significant relationship between MTHFD1 G1958A, eNOS G894T and ACE A2350G polymorphisms with CHD. Therefore, The AA and GA genotypes of MTHFD1 G1958A, TT and GT genotypes of eNOS G894T and the AA and GA genotypes of ACE A2350G are susceptible factors for CHD and may increase the risk of CHD. Copyright © 2017. Published by Elsevier Taiwan.

  8. On the Role of the SP1 Domain in HIV-1 Particle Assembly: a Molecular Switch?▿

    Science.gov (United States)

    Datta, Siddhartha A. K.; Temeselew, Lakew G.; Crist, Rachael M.; Soheilian, Ferri; Kamata, Anne; Mirro, Jane; Harvin, Demetria; Nagashima, Kunio; Cachau, Raul E.; Rein, Alan

    2011-01-01

    Expression of a retroviral protein, Gag, in mammalian cells is sufficient for assembly of immature virus-like particles (VLPs). VLP assembly is mediated largely by interactions between the capsid (CA) domains of Gag molecules but is facilitated by binding of the nucleocapsid (NC) domain to nucleic acid. We have investigated the role of SP1, a spacer between CA and NC in HIV-1 Gag, in VLP assembly. Mutational analysis showed that even subtle changes in the first 4 residues of SP1 destroy the ability of Gag to assemble correctly, frequently leading to formation of tubes or other misassembled structures rather than proper VLPs. We also studied the conformation of the CA-SP1 junction region in solution, using both molecular dynamics simulations and circular dichroism. Consonant with nuclear magnetic resonance (NMR) studies from other laboratories, we found that SP1 is nearly unstructured in aqueous solution but undergoes a concerted change to an α-helical conformation when the polarity of the environment is reduced by addition of dimethyl sulfoxide (DMSO), trifluoroethanol, or ethanol. Remarkably, such a coil-to-helix transition is also recapitulated in an aqueous medium at high peptide concentrations. The exquisite sensitivity of SP1 to mutational changes and its ability to undergo a concentration-dependent structural transition raise the possibility that SP1 could act as a molecular switch to prime HIV-1 Gag for VLP assembly. We suggest that changes in the local environment of SP1 when Gag oligomerizes on nucleic acid might trigger this switch. PMID:21325421

  9. "Missing pieces": exploring cardiac risk perceptions in older women.

    Science.gov (United States)

    Lefler, Leanne L; McSweeney, Jean C; Garner, Kimberly K

    2013-04-01

    Approximately 95% of older women have factors that put them at risk for developing cardiovascular disease, but research indicates many do not perceive themselves to be at risk. We examined older women's perceived risk for coronary heart disease (CHD) and the factors influencing their perceptions. We conducted a descriptive, qualitative study using in-depth, individual interviews and quantitative measures to assess perceived risk and risk factors. Twenty-four older African American and Caucasian women had a mean 4.46 cardiac risk factors but perceived their own CHD risk as unrealistically low at 1.95 cm (SD = 1.57, on 0-to-8 cm visual analogue scale). Narrative data clustered in themes that represented a lack of fact-based information and multiple misconceptions about CHD and prevention. Major improvements in CHD health are only achievable if risk factors are prevented. This research suggests older women have substantial needs for consistent CHD information and prevention guidance. Copyright 2013, SLACK Incorporated.

  10. Daam1 regulates fascin for actin assembly in mouse oocyte meiosis.

    Science.gov (United States)

    Lu, Yujie; Zhang, Yu; Pan, Meng-Hao; Kim, Nam-Hyung; Sun, Shao-Chen; Cui, Xiang-Shun

    2017-07-18

    As a formin protein, Daam1 (Dishevelled-associated activator of morphogenesis 1) is reported to regulate series of cell processes like endocytosis, cell morphology and migration via its effects on actin assembly in mitosis. However, whether Daam1 plays roles in female meiosis remains uncertain. In this study, we investigated the expression and functions of Daam1 during mouse oocyte meiosis. Our results indicated that Daam1 localized at the cortex of oocytes, which was similar with actin filaments. After Daam1 morpholino (MO) microinjection, the expression of Daam1 significantly decreased, which resulted in the failure of oocyte polar body extrusion. These results might be due to the defects of actin assembly, since the decreased fluorescence intensity of actin filaments in oocyte cortex and cytoplasm were observed. However, Daam1 knockdown seemed not to affect the meiotic spindle movement. In addition, we found that fascin might be the down effector of Daam1, since the protein expression of fascin decreased after Daam1 knockdown. Thus, our data suggested that Daam1 affected actin assembly during oocyte meiotic division via the regulation of fascin expression.

  11. Evaluation of regulatory genetic variants in POU5F1 and risk of congenital heart disease in Han Chinese.

    Science.gov (United States)

    Lin, Yuan; Ding, Chenyue; Zhang, Kai; Ni, Bixian; Da, Min; Hu, Liang; Hu, Yuanli; Xu, Jing; Wang, Xiaowei; Chen, Yijiang; Mo, Xuming; Cui, Yugui; Shen, Hongbing; Sha, Jiahao; Liu, Jiayin; Hu, Zhibin

    2015-10-28

    OCT4 is a transcription factor of the POU family, which plays a key role in embryonic development and stem cell pluripotency. Previous studies have shown that Oct4 is required for cardiomyocyte differentiation in mice and its depletion could result in cardiac morphogenesis in embryo. However, whether the genetic variations in OCT4 coding gene, POU5F1, confer the predisposition to congenital heart disease (CHD) is unclear. This study sought to investigate the associations between low-frequency (defined here as having minor allele frequency (MAF) between 0.1%-5%) and rare (MAF below 0.1%) variants with potential function in POU5F1 and risk of CHD. We conducted association analysis in a two-stage case-control study with a total of 2,720 CHD cases and 3,331 controls in Chinese. The low-frequency variant rs3130933 was observed to be associated with a significantly increased risk of CHD [additive model: adjusted odds ratio (OR) = 2.15, adjusted P = 3.37 × 10(-6)]. Furthermore, luciferase activity assay showed that the variant A allele led to significantly lower expression levels as compared to the G allele. These findings indicate for the first time that low-frequency functional variant in POU5F1 may contribute to the risk of congenital heart malformations.

  12. Evaluation of regulatory genetic variants in POU5F1 and risk of congenital heart disease in Han Chinese

    Science.gov (United States)

    Lin, Yuan; Ding, Chenyue; Zhang, Kai; Ni, Bixian; da, Min; Hu, Liang; Hu, Yuanli; Xu, Jing; Wang, Xiaowei; Chen, Yijiang; Mo, Xuming; Cui, Yugui; Shen, Hongbing; Sha, Jiahao; Liu, Jiayin; Hu, Zhibin

    2015-10-01

    OCT4 is a transcription factor of the POU family, which plays a key role in embryonic development and stem cell pluripotency. Previous studies have shown that Oct4 is required for cardiomyocyte differentiation in mice and its depletion could result in cardiac morphogenesis in embryo. However, whether the genetic variations in OCT4 coding gene, POU5F1, confer the predisposition to congenital heart disease (CHD) is unclear. This study sought to investigate the associations between low-frequency (defined here as having minor allele frequency (MAF) between 0.1%-5%) and rare (MAF below 0.1%) variants with potential function in POU5F1 and risk of CHD. We conducted association analysis in a two-stage case-control study with a total of 2,720 CHD cases and 3,331 controls in Chinese. The low-frequency variant rs3130933 was observed to be associated with a significantly increased risk of CHD [additive model: adjusted odds ratio (OR) = 2.15, adjusted P = 3.37 × 10-6]. Furthermore, luciferase activity assay showed that the variant A allele led to significantly lower expression levels as compared to the G allele. These findings indicate for the first time that low-frequency functional variant in POU5F1 may contribute to the risk of congenital heart malformations.

  13. A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men

    DEFF Research Database (Denmark)

    May, Margaret; Sterne, Jonathan A C; Shipley, Martin

    2007-01-01

    Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors...

  14. [Independent risk factors for severe cardiovascular events in male patients with gout: Results of a 7-year prospective study].

    Science.gov (United States)

    Eliseev, M S; Denisov, I S; Markelova, E I; Glukhova, S I; Nasonov, E L

    To determine risk factors for severe cardiovascular (CV) events (CVEs) in male patients with crystal-verified gout. 251 male patients with crystal-verified gout were prospectively followed up in 2003 to 2013. The mean follow-up period was 6.9±2.0 years. New severe CVE cases and deaths were recorded. Logistic regression was used to analyze the impact of traditional and other risk factors and allopurinol use on the risk for severe CVEs. 32 patients died during the follow-up period. Severe CVEs were recorded in 58 (23.1%) patients; CVE deaths were notified in 22 (8.8%) patients. The risk of all severe CVEs was high for hypertension, increased serum high-sensitivity C-reactive protein (hs-CRP) level (>5 mg/l), ≥ stage III chronic kidney disease (CKD) (glomerular filtration rate, 20 g/day), coronary heart disease (CHD), and a family history of premature CHD. The risk of fatal CVEs was highest for elevated serum hs-CRP level, ≥ stage III CKD, a family history of premature CHD, hypercholesterolemia, upper quartile of serum uric acid levels (>552 µmol/l), and regular intake of allopurinol. In addition to the traditional risk factors of CV catastrophes, the presence of chronic inflammation and the impact of high serum uric acid levels may explain the high frequency of CV catastrophes.

  15. The Association of Fasting Glucose, Insulin, and C-Peptide, with 19-Year Incidence of Coronary Heart Disease in Older Japanese-American Men; the Honolulu Heart Program

    Directory of Open Access Journals (Sweden)

    Nazneem Wahab

    2018-04-01

    Full Text Available The role of fasting glucose, insulin levels, and C-peptide in coronary heart disease (CHD in non-diabetic individuals remains uncertain. We examined the association between fasting glucose, insulin and C-peptide with the long-term incidence of CHD in Japanese-American men. In 1980–1982, from a random sample of the Honolulu Heart Program men (n = 1378, aged 61–81 years, data on several CHD and metabolic risk factors were obtained to examine the relation of fasting glucose, insulin and C-peptide to 19-year CHD incidence. Age-adjusted incidence of CHD increased with increasing quintiles of glucose, insulin and C-peptide. Age-adjusted CHD rates in the glucose quintiles were 11.9, 11.6, 14.4, 18.1 and 24.1 per 1000 person-years (trend p < 0.001. In individual Cox models (lowest quintiles of glucose, insulin and C-peptide as reference the relative risks (95% confidence interval of CHD incidence for the glucose quintiles adjusting for age, smoking, hypertension, cholesterol, physical activity, and body mass index, were 0.9 (0.6–1.4, 1.2 (0.8–1.8, 1.4 (0.9–2.2, and 1.7 (1.1–2.6, respectively (trend p = 0.004. Insulin and C-peptide were not significantly associated with CHD on multivariate analysis. Fasting glucose remained the only significant predictor of increased CHD risk (p = 0.003 in a model combining all 3 metabolic variables. In this cohort, only fasting glucose independently predicts long-term incidence of CHD. Age-adjusted insulin and C-peptide levels were associated with CHD incidence, but after adjustment for other risk factors, do not independently predict CHD.

  16. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force.

    Science.gov (United States)

    Buckley, David I; Fu, Rongwei; Freeman, Michele; Rogers, Kevin; Helfand, Mark

    2009-10-06

    C-reactive protein (CRP) may help to refine global risk assessment for coronary heart disease (CHD), particularly among persons who are at intermediate risk on the basis of traditional risk factors alone. To assist the U.S. Preventive Services Task Force (USPSTF) in determining whether CRP should be incorporated into guidelines for CHD risk assessment. MEDLINE search of English-language articles (1966 to November 2007), supplemented by reference lists of reviews, pertinent studies, editorials, and Web sites and by expert suggestions. Prospective cohort, case-cohort, and nested case-control studies relevant to the independent predictive ability of CRP when used in intermediate-risk persons. Included studies were reviewed according to predefined criteria, and the quality of each study was rated. The validity of the body of evidence and the net benefit or harm of using CRP for CHD risk assessment were evaluated. The combined magnitude of effect was determined by meta-analysis. The body of evidence is of good quality, consistency, and applicability. For good studies that adjusted for all Framingham risk variables, the summary estimate of relative risk for incident CHD was 1.58 (95% CI, 1.37 to 1.83) for CRP levels greater than 3.0 mg/L compared with levels less than 1.0 mg/L. Analyses from 4 large cohorts were consistent in finding evidence that including CRP improves risk stratification among initially intermediate-risk persons. C-reactive protein has desirable test characteristics, and good data exist on the prevalence of elevated CRP levels in intermediate-risk persons. Limited evidence links changes in CRP level to primary prevention of CHD events. Study methods for measuring Framingham risk variables and other covariates varied. Ethnic and racial minority populations were poorly represented in most studies, limiting generalizability. Few studies directly assessed the effect of CRP on risk reclassification in intermediate-risk persons. Strong evidence indicates

  17. CHARGE syndrome: a recurrent hotspot of mutations in CHD7 IVS25 analyzed by bioinformatic tools and minigene assays.

    Science.gov (United States)

    Legendre, Marine; Rodriguez-Ballesteros, Montserrat; Rossi, Massimiliano; Abadie, Véronique; Amiel, Jeanne; Revencu, Nicole; Blanchet, Patricia; Brioude, Frédéric; Delrue, Marie-Ange; Doubaj, Yassamine; Sefiani, Abdelaziz; Francannet, Christine; Holder-Espinasse, Muriel; Jouk, Pierre-Simon; Julia, Sophie; Melki, Judith; Mur, Sébastien; Naudion, Sophie; Fabre-Teste, Jennifer; Busa, Tiffany; Stamm, Stephen; Lyonnet, Stanislas; Attie-Bitach, Tania; Kitzis, Alain; Gilbert-Dussardier, Brigitte; Bilan, Frédéric

    2018-02-01

    CHARGE syndrome is a rare genetic disorder mainly due to de novo and private truncating mutations of CHD7 gene. Here we report an intriguing hot spot of intronic mutations (c.5405-7G > A, c.5405-13G > A, c.5405-17G > A and c.5405-18C > A) located in CHD7 IVS25. Combining computational in silico analysis, experimental branch-point determination and in vitro minigene assays, our study explains this mutation hot spot by a particular genomic context, including the weakness of the IVS25 natural acceptor-site and an unconventional lariat sequence localized outside the common 40 bp upstream the acceptor splice site. For each of the mutations reported here, bioinformatic tools indicated a newly created 3' splice site, of which the existence was confirmed using pSpliceExpress, an easy-to-use and reliable splicing reporter tool. Our study emphasizes the idea that combining these two complementary approaches could increase the efficiency of routine molecular diagnosis.

  18. CRC DEPLETION CALCULATIONS FOR THE RODDED ASSEMBLIES IN BATCHES 1, 2, 3, AND 1X OF CRYSTAL RIVER UNIT 3

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth D. Wright

    1997-09-03

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain rodded fuel assemblies from batches 1, 2, 3, and 1X of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A rodded assembly is one that contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) for some period of time during its irradiation history. The objective of this analysis is to provide SAS2H calculated isotopic compositions of depleted fuel and depleted burnable poison for each fuel assembly to be used in subsequent CRC reactivity calculations containing the fuel assemblies.

  19. CRC DEPLETION CALCULATIONS FOR THE RODDED ASSEMBLIES IN BATCHES 1, 2, 3, AND 1X OF CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wright, Kenneth D.

    1997-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain rodded fuel assemblies from batches 1, 2, 3, and 1X of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A rodded assembly is one that contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) for some period of time during its irradiation history. The objective of this analysis is to provide SAS2H calculated isotopic compositions of depleted fuel and depleted burnable poison for each fuel assembly to be used in subsequent CRC reactivity calculations containing the fuel assemblies

  20. The origin of the supernumerary subunits and assembly factors of complex I: A treasure trove of pathway evolution.

    Science.gov (United States)

    Elurbe, Dei M; Huynen, Martijn A

    2016-07-01

    We review and document the evolutionary origin of all complex I assembly factors and nine supernumerary subunits from protein families. Based on experimental data and the conservation of critical residues we identify a spectrum of protein function conservation between the complex I representatives and their non-complex I homologs. This spectrum ranges from proteins that have retained their molecular function but in which the substrate specificity may have changed or have become more specific, like NDUFAF5, to proteins that have lost their original molecular function and critical catalytic residues like NDUFAF6. In between are proteins that have retained their molecular function, which however appears unrelated to complex I, like ACAD9, or proteins in which amino acids of the active site are conserved but for which no enzymatic activity has been reported, like NDUFA10. We interpret complex I evolution against the background of molecular evolution theory. Complex I supernumerary subunits and assembly factors appear to have been recruited from proteins that are mitochondrial and/or that are expressed when complex I is active. Within the evolution of complex I and its assembly there are many cases of neofunctionalization after gene duplication, like ACAD9 and TMEM126B, one case of subfunctionalization: ACPM1 and ACPM2 in Yarrowia lipolytica, and one case in which a complex I protein itself appears to have been the source of a new protein from another complex: NDUFS6 gave rise to cytochrome c oxidase subunit COX4/COX5b. Complex I and its assembly can therewith be regarded as a treasure trove for pathway evolution. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Pre-exercise screening and health coaching in CHD secondary prevention: a qualitative study of the patient experience.

    Science.gov (United States)

    Shaw, R; Gillies, M; Barber, J; MacIntyre, K; Harkins, C; Findlay, I N; McCloy, K; Gillie, A; Scoular, A; MacIntyre, P D

    2012-06-01

    Secondary prevention programmes can be effective in reducing morbidity and mortality from coronary heart disease (CHD). In particular, UK guidelines, including those from the Department of Health, emphasize physical activity. However, the effects of secondary prevention programmes with an exercise component are moderate and uptake is highly variable. In order to explore patients' experiences of a pre-exercise screening and health coaching programme (involving one-to-one consultations to support exercise behaviour change), semi-structured telephone interviews were undertaken with 84 CHD patients recruited from primary care. The interviews focused on patients' experiences of the intervention including referral and any recommendations for improvement. A thematic analysis of transcribed interviews showed that the majority of patients were positive about referral. However, patients also identified a number of barriers to attending and completing the programme, including a belief they were sufficiently active already, the existence of other health problems, feeling unsupported in community-based exercise classes and competing demands. Our findings highlight important issues around the choice of an appropriate point of intervention for programmes of this kind as well as the importance of appropriate patient selection, suggesting that the effectiveness of health coaching may be under-reported as a result of including patients who are not yet ready to change their behaviours.

  2. Multidisciplinary family-centred psychosocial care for patients with CHD: consensus recommendations from the AEPC Psychosocial Working Group.

    Science.gov (United States)

    Utens, Elisabeth M W J; Callus, Edward; Levert, Eveline M; Groote, Katya De; Casey, Frank

    2018-02-01

    Because of the enormous advances in the medical treatment of CHD, the long-term survival of patients suffering from this disease has increased significantly. Currently, about 90% of patients reach adulthood, which entails many new challenges both for patients and their families and for healthcare professionals. The main objective of family-centred psychosocial care is to strengthen the emotional resilience of chronically ill patients and their families by adopting a holistic approach. During the biannual meeting of the psychosocial working group in 2012, participants expressed the need for general European guidelines. The present recommendations were written to support medical staff and psychosocial healthcare professionals to provide the best care for children and adolescents with CHD as well as for their families. This article describes in detail how the integrated family-centred psychological care modules work, involving different healthcare specialists, including a paediatric/congenital cardiologist or a general paediatrician. The different clinical implications and specific needs have been taken into account and recommendations have been provided on the following: structured follow-up screening; identification of stressful periods related to cardiac surgery or invasive medical procedures; evidence-based, disease-specific, and family-oriented psychosocial interventions; and interactive media links to medical and psychosocial information.

  3. Involvement of interleukin-1 genotypes in the association of coronary heart disease with periodontitis

    DEFF Research Database (Denmark)

    Geismar, Karen; Enevold, Christian; Sørensen, Lars Korsbæk

    2008-01-01

    Epidemiologic studies demonstrated an association between periodontitis (PE) and coronary heart disease (CHD). The coexistence of the two disease entities could be dependent on mutual risk factors, and polymorphism of the interleukin (IL)-1 gene cluster associated with the severity of PE might also...

  4. RISK FACTORS OF THE ERECTILE DYSFUNCTION IN THE PATIENTS WITH CARDIOVASCULAR DISEASES

    Directory of Open Access Journals (Sweden)

    E. V. Minakov

    2009-01-01

    Full Text Available Aim. To study erectile dysfunction prevalence among out-patients with arterial hypertension (HT and/or coronary heart disease (CHD as well as to study risk factors of erectile dysfunction.Material and methods. The anonymous poll was carried out among 103 male patients with HT and/or CHD. General information about patient, medical history, treatment was analyzed. All patients were examined by cardiologists. Erectile function was assessed with The International Index Erectile Function (IIEF questionnaire.Results. 86 (84% questionnaires were returned. 62 (72% patients from 86 responding had erectile dysfunction. Age, blood pressure level, abdominal obesity, beta-blocker therapy and chronic heart failure affected erectile function.Conclusion. The erectile dysfunction was common disorder among male patients with HT and/or CHD. Early erectile dysfunction diagnosis, prevention and therapy are necessary to provide high level of compliance in patients with cardiovascular diseases.

  5. Uncovering the Rare Variants of DLC1 Isoform 1 and Their Functional Effects in a Chinese Sporadic Congenital Heart Disease Cohort

    Science.gov (United States)

    Wang, Zhen; Tan, Huilian; Kong, Xianghua; Shu, Yang; Zhang, Yuchao; Huang, Yun; Zhu, Yufei; Xu, Heng; Wang, Zhiqiang; Wang, Ping; Ning, Guang; Kong, Xiangyin; Hu, Guohong; Hu, Landian

    2014-01-01

    Congenital heart disease (CHD) is the most common birth defect affecting the structure and function of fetal hearts. Despite decades of extensive studies, the genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1 (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart and essential for heart development according to the knowledge of Dlc1-deficient mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and identified 13 non-synonymous rare variants (including 6 private variants) in the case cohort. Importantly, these rare variants (8/13) were enriched in the N-terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the N-terminal variant positions were conserved among the primates. Among the 9 rare variants that were predicted as “damaging”, five were located at the N-terminal region. Ensuing in vitro functional assays showed that three private variants (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell migration or altered the subcellular location of the protein compared to wild-type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated gene in addition to its role as a tumor suppressor in cancer. PMID:24587289

  6. Two sides of the coin. Part 1. Lipid and surfactant self-assembly revisited.

    Science.gov (United States)

    Ninham, Barry W; Larsson, Kåre; Lo Nostro, Pierandrea

    2017-04-01

    Hofmeister, specific ion effects, hydration and van der Waals forces at and between interfaces are factors that determine curvature and microstructure in self assembled aggregates of surfactants and lipids; and in microemulsions. Lipid and surfactant head group interactions and between aggregates vary enormously and are highly specific. They act on the hydrophilic side of a bilayer, micelle or other self assembled aggregate. It is only over the last three decades that the origin of Hofmeister effects has become generally understood. Knowledge of their systematics now provides much flexibility in designing nanostructured fluids. The other side of the coin involves equally specific forces. These (opposing) forces work on the hydrophobic side of amphiphilic interfaces. They are due to the interaction of hydrocarbons and other "oils" with hydrophobic tails of surfactants and lipids. The specificity of oleophilic solutes in microemulsions and lipid membranes provides a counterpoint to Hofmeister effects and hydration. Together with global packing constraints these effects determine microstructure. Another factor that has hardly been recognised is the role of dissolved gas. This introduces further, qualitative changes in forces that prescribe microstructure. The systematics of these effects and their interplay are elucidated. Awareness of these competing factors facilitates formulation of self assembled nanostructured fluids. New and predictable geometries that emerge naturally provide insights into a variety of biological phenomena like anaesthetic and pheromone action and transmission of the nervous impulse (see Part 2). Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4

    OpenAIRE

    Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

    2012-01-01

    CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which prov...

  8. Drosophila Ana1 is required for centrosome assembly and centriole elongation.

    Science.gov (United States)

    Saurya, Saroj; Roque, Hélio; Novak, Zsofia A; Wainman, Alan; Aydogan, Mustafa G; Volanakis, Adam; Sieber, Boris; Pinto, David Miguel Susano; Raff, Jordan W

    2016-07-01

    Centrioles organise centrosomes and cilia, and these organelles have an important role in many cell processes. In flies, the centriole protein Ana1 is required for the assembly of functional centrosomes and cilia. It has recently been shown that Cep135 (also known as Bld10) initially recruits Ana1 to newly formed centrioles, and that Ana1 then recruits Asl (known as Cep152 in mammals) to promote the conversion of these centrioles into centrosomes. Here, we show that ana1 mutants lack detectable centrosomes in vivo, that Ana1 is irreversibly incorporated into centrioles during their assembly and appears to play a more important role in maintaining Asl at centrioles than in initially recruiting Asl to centrioles. Unexpectedly, we also find that Ana1 promotes centriole elongation in a dose-dependent manner: centrioles are shorter when Ana1 dosage is reduced and are longer when Ana1 is overexpressed. This latter function of Ana1 appears to be distinct from its role in centrosome and cilium function, as a GFP-Ana1 fusion lacking the N-terminal 639 amino acids of the protein can support centrosome assembly and cilium function but cannot promote centriole over-elongation when overexpressed. © 2016. Published by The Company of Biologists Ltd.

  9. Rab1A is required for assembly of classical swine fever virus particle.

    Science.gov (United States)

    Lin, Jihui; Wang, Chengbao; Liang, Wulong; Zhang, Jing; Zhang, Longxiang; Lv, Huifang; Dong, Wang; Zhang, Yanming

    2018-01-15

    Rab1A belongs to the small Rab GTPase family and is involved in the lifecycle of numerous viruses. Here, knockdown of Rab1A inhibited CSFV growth. Further study revealed that Rab1A depletion decreased intracellular and extracellular CSFV titers, but did not affect intracellular virus genome copies and E2 protein expression within a virus lifecycle, which suggested that Rab1A is required for CSFV particle assembly rather than for genome replication or virion release. This was proofed by blocking the spread of virus using neutralizing antibodies, through which the negative effects of Rab1A knockdown on multi-cycle replication of CSFV were eliminated. Moreover, co-immunoprecipitation and confocal microscopy assays showed that Rab1A bound to CSFV NS5A protein, indicating that Rab1A and viral NS5A proteins may work cooperatively during CSFV particle assembly. In conclusion, this study demonstrated for the first time that Rab1A is required for CSFV particle assembly and binds to viral particle assembly-related NS5A protein. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Association of the Lipoprotein Receptor SCARB1 Common Missense Variant rs4238001 with Incident Coronary Heart Disease.

    Directory of Open Access Journals (Sweden)

    Ani Manichaikul

    Full Text Available Previous studies in mice and humans have implicated the lipoprotein receptor SCARB1 in association with atherosclerosis and lipid levels. In the current study, we sought to examine association of SCARB1 missense single nucleotide polymorphism (SNP rs4238001 with incident coronary heart disease (CHD.Genotypes for rs4238001 were imputed for 2,319 White, 1,570 African American, and 1,292 Hispanic-American MESA participants using the 1,000 Genomes reference set. Cox proportional hazards models were used to determine association of rs4238001 with incident CHD, with adjustments for age, sex, study site, principal components of ancestry, body mass index, diabetes status, serum creatinine, lipid levels, hypertension status, education and smoking exposure. Meta-analysis across race/ethnic groups within MESA showed statistically significant association of the T allele with higher risk of CHD under a consistent and formally adjudicated definition of CHD events in this contemporary cohort study (hazard ratio [HR] = 1.49, 95% CI [1.04, 2.14], P = 0.028. Analyses combining MESA with additional population-based cohorts expanded our samples in Whites (total n = 11,957 with 871 CHD events and African Americans (total n = 5,962 with 355 CHD events and confirmed an increased risk of CHD overall (HR of 1.19 with 95% CI [1.04, 1.37], P = 0.013, in African Americans (HR of 1.49 with 95% CI [1.07, 2.06], P = 0.019, in males (HR of 1.29 with 95% CI [1.08, 1.54], P = 4.91 x 10(-3 and in White males (HR of 1.24 with 95% CI [1.03, 1.51], P = 0.026.SCARB1 missense rs4238001 is statistically significantly associated with incident CHD across a large population of multiple race/ethnic groups.

  11. Risk factors for infective endocarditis in children with congenital heart diseases - A nationwide population-based case control study.

    Science.gov (United States)

    Sun, Li-Chuan; Lai, Chih-Cheng; Wang, Cheng-Yi; Wang, Ya-Hui; Wang, Jen-Yu; Hsu, Yo-Ling; Hu, Yin-Lan; Wu, En-Ting; Lin, Ming-Tai; Sy, Leticia B; Chen, Likwang

    2017-12-01

    Infective endocarditis (IE) is uncommon in childhood. Its associated epidemiological characteristics in patients with congenital heart disease (CHD) remain unclear. The study population included children born in Taiwan during the years 1997 to 2005 who were diagnosed as having CHD before 3years of age. All children were followed up until the end year of 2010, the diagnosis of infective endocarditis, or death. The demographic characteristics of patients with and without IE, the invasive procedures performed during 6months before the index date, the prophylactic antibiotics related to dental procedures, and in-hospital mortality were collected. Information of 24,729 children with CHD were retrieved for our analysis and 237 patients with newly diagnosed IE were identified. The incidence rate of IE in all CHD lesions was 11.13 per 10,000person-years. Taking ASD for reference, the following CHD lesions were at risk for IE: cyanotic CHD (adjusted OR, 9.58; 95% confidence interval, 5.38-17.05), endocardial cushion defect (ECD) (8.01; 2.73-23.50), Left-sided lesions (4.36; 1.90-10.01) and VSD (2.93; 1.64-5.23). Patients who underwent procedures have a higher risk of acquiring IE which include central venous catheter (CVC) insertion (3.17; 2.36-4.27), cardiac catheterization (3.74; 2.67-5.22), open-heart surgery (2.47; 1.61-3.77), valve surgery (3.20; 1.70-6.02), and shunt surgery (7.43; 2.36-23.41). However, dental procedures did not increase the risk of IE, irrespective of antibiotic usage. The risk of IE varies markedly among CHD lesions in our study. Invasive heart procedures but not dental procedures, are more significantly associated with IE among children with CHD. Copyright © 2017. Published by Elsevier B.V.

  12. A separable domain of the p150 subunit of human chromatin assembly factor-1 promotes protein and chromosome associations with nucleoli.

    Science.gov (United States)

    Smith, Corey L; Matheson, Timothy D; Trombly, Daniel J; Sun, Xiaoming; Campeau, Eric; Han, Xuemei; Yates, John R; Kaufman, Paul D

    2014-09-15

    Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here we present a novel role for the human p150 subunit in regulating nucleolar macromolecular interactions. Acute depletion of p150 causes redistribution of multiple nucleolar proteins and reduces nucleolar association with several repetitive element-containing loci. Of note, a point mutation in a SUMO-interacting motif (SIM) within p150 abolishes nucleolar associations, whereas PCNA or HP1 interaction sites within p150 are not required for these interactions. In addition, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9 reduces α-satellite DNA association with nucleoli. The nucleolar functions of p150 are separable from its interactions with the other subunits of the CAF-1 complex because an N-terminal fragment of p150 (p150N) that cannot interact with other CAF-1 subunits is sufficient for maintaining nucleolar chromosome and protein associations. Therefore these data define novel functions for a separable domain of the p150 protein, regulating protein and DNA interactions at the nucleolus. © 2014 Smith et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  13. An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA).

    Science.gov (United States)

    Liang, C Jason; Budoff, Matthew J; Kaufman, Joel D; Kronmal, Richard A; Brown, Elizabeth R

    2012-07-02

    Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA). Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

  14. An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA

    Directory of Open Access Journals (Sweden)

    Liang C

    2012-07-01

    Full Text Available Abstract Background Extent of atherosclerosis measured by amount of coronary artery calcium (CAC in computed tomography (CT has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS. These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA. Methods Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA. The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Results Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26 and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179. Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224. The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. Conclusions The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

  15. Correlation between plasma angiopoietin-1, angiopoietin-2 and matrix metalloproteinase-2 in coronary heart disease.

    Science.gov (United States)

    Wu, Haoyu; Shou, Xiling; Liang, Lei; Wang, Congxia; Yao, Xiaowei; Cheng, Gong

    2016-12-01

    Angiopoietin-2 (Ang-2) plays a critical role in inducing tumor cell infiltration, and this invasive phenotype is caused by up-regulation of matrix metalloproteinase (MMP)-2. The relationship between Ang-2 and MMP-2 in atherosclerosis has not been reported yet. The aim is to measure the plasma concentrations of Ang-1, Ang-2 and MMP-2 and assess the correlation between the concentrations of these factors in coronary heart disease (CHD) patients. The testing was done in a cross-sectional study. We prospectively enrolled 42 individuals with acute myocardial infarction, 42 individuals with unstable angina pectoris, 42 individuals with stable angina pectoris and 45 healthy control subjects. Concentrations of Ang-1, Ang-2 and MMP-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. Spearman's rank correlation was calculated to evaluate the relationships between MMP-2 and Ang-1, and MMP-2 and Ang-2 in patients with CHD. Patients with acute myocardial infarction and unstable angina pectoris had higher Ang-2 and MMP-2 levels compared with stable angina patients and healthy control subjects ( p correlation showed that Ang-2 levels positively correlated with MMP-2 in patients with CHD ( r = 0.679, p correlated weakly with MMP-2, whereas the Ang-2 and MMP-2 correlation was strong in patients with CHD. Ang-2 may play a role in atherosclerosis, and have an interaction with MMP-2.

  16. The prevalence of cardiovascular risk factors in the young and middle-aged rural population in Sarawak, Malaysia.

    Science.gov (United States)

    Chang, Ching Thon; Lee, Ping Yein; Cheah, Whye Lian

    2012-04-01

    Coronary heart disease (CHD) was the second leading cause of death in Malaysia in 2006. CHD has known risk factors including hypertension, diabetes mellitus, and obesity. This cross-sectional study examined the prevalence of cardiovascular risk factors among 260 participants aged 20 to 65 years in a rural community in Sarawak. The prevalences of overweight and obesity in this study were 39.6% and 11.9%, respectively. Approximately 13% of participants had hypertension, and 1.5% had a random blood sugar greater than 11.1 mmol/L. Chi-square tests showed significant associations between obesity and gender (P = 0.007), low high-density lipoprotein cholesterol and race (P = 0.05), high total cholesterol and age (P = 0.007), age and hypertension (P = 0.011), smoking and gender (P 45 years) were 0.395 times more likely to have high cholesterol and that those with a higher monthly household income (> RM830) were 2.471 times more likely to smoke. These findings indicate that we should be concerned about the high rates of overweight in this rural community to prevent obesity.

  17. Fuel assemblies for nuclear reactor

    International Nuclear Information System (INIS)

    Nishi, Akihito.

    1987-01-01

    Purpose: To control power-up rate at the initial burning stage of new fuel assemblies due to fuel exchange in a pressure tube type power reactor. Constitution: Burnable poisons are disposed to a most portion of fuel pellets in a fuel assembly to such a low concentration as the burn-up rate changes with time at the initial stage of the burning. The most portion means substantially more than one-half part of the pellets and gadolinia is used as burn-up poisons to be dispersed and the concentration is set to less than about 0.2 %. Upon elapse of about 15 days after the charging, the burnable poisons are eliminated and the infinite multiplication factors are about at 1.2 to attain a predetermined power state. Since the power-up rate of the nuclear reactor fuel assembly is about 0.1 % power/hour and the power-up rate of the fuel assembly around the exchanged channel is lower than that, it can be lowered sufficiently than the limit for the power-up rate practiced upon reactor start-up thereby enabling to replace fuels during power operation. (Horiuchi, T.)

  18. Essential Assembly Factor Rpf2 Forms Novel Interactions within the 5S RNP in Trypanosoma brucei.

    Science.gov (United States)

    Kamina, Anyango D; Jaremko, Daniel; Christen, Linda; Williams, Noreen

    2017-01-01

    Ribosome biogenesis is a highly complex and conserved cellular process that is responsible for making ribosomes. During this process, there are several assembly steps that function as regulators to ensure proper ribosome formation. One of these steps is the assembly of the 5S ribonucleoprotein particle (5S RNP) in the central protuberance of the 60S ribosomal subunit. In eukaryotes, the 5S RNP is composed of 5S rRNA, ribosomal proteins L5 and L11, and assembly factors Rpf2 and Rrs1. Our laboratory previously showed that in Trypanosoma brucei , the 5S RNP is composed of 5S rRNA, L5, and trypanosome-specific RNA binding proteins P34 and P37. In this study, we characterize an additional component of the 5S RNP, the T. brucei homolog of Rpf2. This is the first study to functionally characterize interactions mediated by Rpf2 in an organism other than fungi. T . brucei Rpf2 (TbRpf2) was identified from tandem affinity purification using extracts prepared from protein A-tobacco etch virus (TEV)-protein C (PTP)-tagged L5, P34, and P37 cell lines, followed by mass spectrometry analysis. We characterized the binding interactions between TbRpf2 and the previously characterized members of the T. brucei 5S RNP. Our studies show that TbRpf2 mediates conserved binding interactions with 5S rRNA and L5 and that TbRpf2 also interacts with trypanosome-specific proteins P34 and P37. We performed RNA interference (RNAi) knockdown of TbRpf2 and showed that this protein is essential for the survival of the parasites and is critical for proper ribosome formation. These studies provide new insights into a critical checkpoint in the ribosome biogenesis pathway in T. brucei . IMPORTANCE Trypanosoma brucei is the parasitic protozoan that causes African sleeping sickness. Ribosome assembly is essential for the survival of this parasite through the different host environments it encounters during its life cycle. The assembly of the 5S ribonucleoprotein particle (5S RNP) functions as one of

  19. Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities.

    Science.gov (United States)

    Didychuk, Allison L; Montemayor, Eric J; Carrocci, Tucker J; DeLaitsch, Andrew T; Lucarelli, Stefani E; Westler, William M; Brow, David A; Hoskins, Aaron A; Butcher, Samuel E

    2017-09-08

    U6 small nuclear ribonucleoprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood. Here, we report structures of the U6 RNA processing enzyme Usb1 from yeast and a substrate analog bound complex from humans. Unlike the human ortholog, we show that yeast Usb1 has cyclic phosphodiesterase activity that leaves a terminal 3' phosphate which prevents overprocessing. Usb1 processing of U6 RNA dramatically alters its affinity for cognate RNA-binding proteins. We reconstitute the post-transcriptional assembly of yeast U6 snRNP in vitro, which occurs through a complex series of handoffs involving 10 proteins (Lhp1, Prp24, Usb1 and Lsm2-8) and anti-cooperative interactions between Prp24 and Lhp1. We propose a model for U6 snRNP assembly that explains how evolutionarily divergent and seemingly antagonistic proteins cooperate to protect and chaperone the nascent snRNA during its journey to the spliceosome.The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.

  20. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii, and California: prevalence of coronary and hypertensive heart disease and associated risk factors. [Coronary and hypertensive heart disease in Japanese men living in Japan, Hawaii, and California

    Energy Technology Data Exchange (ETDEWEB)

    Marmot, M G; Syme, S L; Kagan, A; Kato, H; Cohen, J B; Belsky, J L

    1974-01-01

    A study of coronary heart disease (CHD) among Japanese migrants compared with Japanese living in Japan provided the opportunity to study factors possibly responsible for the high rates of CHD in America as compared with Japan. Comparable methods were employed in examining 11,900 men of Japanese ancestry aged 45-69 living in Japan, Hawaii, and California. The age-adjusted prevalence rates/1000 for definite CHD as determined by electrocardiogram were: Japan 5.3, Hawaii 5.2, and California 10.8. For definite plus possible CHD the rates were 25.4, 34.7, and 44.6. The prevalence of angina pectoris and pain of possible myocardial infarction, determined by questionnaire, showed a similar gradient. Elevated serum cholesterol showed a Japan < Hawaii < California gradient, but the prevalence of hypertension in Japan was intermediate between the prevalence in Hawaii and the higher prevalence in California. The three geographical locations were compared as to prevalence of CHD at comparable levels of blood pressure and cholesterol. At each blood pressure level and at each cholesterol level, the greater prevalence of CHD in California persisted. These facts, plus the near universality of smoking in Japan, suggest that conventional risk factors only partly explain the observed gradient in CHD. (auth)

  1. Coronary heart disease risk factors in adult premenopausal white women with polycystic ovary syndrome compared with a healthy female population.

    Science.gov (United States)

    Glueck, Charles J; Morrison, John A; Goldenberg, Naila; Wang, Ping

    2009-05-01

    Our specific aim was to determine whether coronary heart disease (CHD) risk factors in polycystic ovary syndrome (PCOS) patients were independent of their higher body mass index (BMI) and centripetal obesity. In adult, premenopausal, white women, CHD risk factors were compared between 488 patients with well-defined PCOS and 351 healthy free-living population controls from the Princeton Follow-up Study (PFS). After excluding women with irregular menses (putative PCOS phenotypes), comparisons were also made between the 261 PFS women with a history of regular menses and the 488 women with PCOS. Fasting lipids, insulin, glucose, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA insulin secretion, blood pressure, BMI, and waist circumference were measured. Compared with both the full cohort of 351 PFS women and the subgroup of 261 PFS women with regular menses, women with PCOS had higher BMI, waist circumference, total and low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, insulin, glucose, and HOMA-IR (all Ps PCOS, compared with the 351 and 261 PFS women, had lower high-density lipoprotein cholesterol (P PCOS women with normal BMI (PCOS cannot be exclusively attributed to their preponderant centripetal obesity. Identification of women with clinical features of PCOS should alert the clinician to potentially increased risk for CHD and prompt CHD risk factor testing.

  2. Understanding the impact of 1q21.1 copy number variant

    Directory of Open Access Journals (Sweden)

    Harvard Chansonette

    2011-08-01

    Full Text Available Abstract Background 1q21.1 Copy Number Variant (CNV is associated with a highly variable phenotype ranging from congenital anomalies, learning deficits/intellectual disability (ID, to a normal phenotype. Hence, the clinical significance of this CNV can be difficult to evaluate. Here we described the consequences of the 1q21.1 CNV on genome-wide gene expression and function of selected candidate genes within 1q21.1 using cell lines from clinically well described subjects. Methods and Results Eight subjects from 3 families were included in the study: six with a 1q21.1 deletion and two with a 1q21.1 duplication. High resolution Affymetrix 2.7M array was used to refine the 1q21.1 CNV breakpoints and exclude the presence of secondary CNVs of pathogenic relevance. Whole genome expression profiling, studied in lymphoblast cell lines (LBCs from 5 subjects, showed enrichment of genes from 1q21.1 in the top 100 genes ranked based on correlation of expression with 1q21.1 copy number. The function of two top genes from 1q21.1, CHD1L/ALC1 and PRKAB2, was studied in detail in LBCs from a deletion and a duplication carrier. CHD1L/ALC1 is an enzyme with a role in chromatin modification and DNA damage response while PRKAB2 is a member of the AMP kinase complex, which senses and maintains systemic and cellular energy balance. The protein levels for CHD1L/ALC1 and PRKAB2 were changed in concordance with their copy number in both LBCs. A defect in chromatin remodeling was documented based on impaired decatenation (chromatid untangling checkpoint (DCC in both LBCs. This defect, reproduced by CHD1L/ALC1 siRNA, identifies a new role of CHD1L/ALC1 in DCC. Both LBCs also showed elevated levels of micronuclei following treatment with a Topoisomerase II inhibitor suggesting increased DNA breaks. AMP kinase function, specifically in the deletion containing LBCs, was attenuated. Conclusion Our studies are unique as they show for the first time that the 1q21.1 CNV not only

  3. Cardiovascular Risk Factors and 10-year Risk for Coronary Heart Disease in Korean Women

    Directory of Open Access Journals (Sweden)

    Sunjoo Boo, RN, PhD

    2012-03-01

    Conclusion: Modifiable cardiovascular risk factors are highly prevalent in Korean women, and the combination of risk factors is common. Development and implementation of multifaceted nursing interventions are required to confront the current epidemic rise of CHD in Korean women.

  4. Lifestyle Risk Factors and Cardiovascular Disease in Cubans and Cuban Americans

    Directory of Open Access Journals (Sweden)

    Melissa S. Burroughs Peña

    2012-01-01

    Full Text Available Cardiovascular disease is the leading cause of mortality in Cuba. Lifestyle risk factors for coronary heart disease (CHD in Cubans have not been compared to risk factors in Cuban Americans. Articles spanning the last 20 years were reviewed. The data on Cuban Americans are largely based on the Hispanic Health and Nutrition Examination Survey (HHANES, 1982–1984, while more recent data on epidemiological trends in Cuba are available. The prevalence of obesity and type 2 diabetes mellitus remains greater in Cuban Americans than in Cubans. However, dietary preferences, low physical activity, and tobacco use are contributing to the rising rates of obesity, type 2 diabetes mellitus, and CHD in Cuba, putting Cubans at increased cardiovascular risk. Comprehensive national strategies for cardiovascular prevention that address these modifiable lifestyle risk factors are necessary to address the increasing threat to public health in Cuba.

  5. Effects of coagulation factors and inflammatory cytokines on ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2016; 15 (4): 827-831. ISSN: 1596-5996 (print); ... fibrinogen (Fg) and von Willebrand factor (vWF) in plasma were analyzed by enzyme-linked ... determined by Western blot analysis. Inflammatory ... Currently, coronary heart disease (CHD) has become one .... membrane.

  6. Self-assembly of a 1-eicosanethiolate layer on InSb(100)

    Energy Technology Data Exchange (ETDEWEB)

    Contreras, Yissel; Muscat, Anthony J., E-mail: muscat@email.arizona.edu

    2016-05-01

    Highlights: • 1-Eicosanethiolate molecules form weak bonds with InSb(100) limiting order in the SAM. • The low interaction energy of the molecules is shown by ATR-FTIR and desorption. • The bond that S makes with the substrate determines the cohesiveness of the molecules. - Abstract: 1-Eicosanethiolate molecules form relatively weak bonds with the surface of InSb(100) limiting the order of the self-assembled monolayer despite the long length of the alkyl chain. Heating to only 225 °C in vacuum completely desorbed the eicosanethiolate layer from the surface based on X-ray photoelectron spectroscopy. Even after deposition times as long as 20 h in ethanol, the asymmetric methylene stretch was at 2925 cm{sup −1} in the attenuated total reflection Fourier transform infrared spectrum, which is indicative of alkane chains that are incompletely ordered. Atomic force microscopy images combined with ellipsometry showed that the eicosanethiolate layer conformed to the rough InSb(100) starting surface (2.3 ± 0.2 nm RMS). The reoxidation kinetics in air of InSb(100) and InSb(111)B covered with eicosanethiolate layers was the same despite the lower surface roughness of the latter (0.64 ± 0.14 nm). The bond that the S head group makes with the substrate is the primary factor that determines the cohesiveness of the molecules on the surface. Although interactions between the alkane chains in the layer are sufficient to form a self-assembled layer, the fluidity of the molecules in the layer compromised the chemical passivation of the surface resulting in reoxidation in air after 20 min.

  7. Molecular sexing and analysis of CHD1-Z and CHD1-W sequence ...

    Indian Academy of Sciences (India)

    eral countries, particularly in China, Japan, Brazil, France and Spain (Minvielle 2004). Due to the small number of commercial explorations of common quail in Europe, hunt- ... Japanese quail to prevent excessive decline of the birds dur- ... status of common quail and developed Natura 2000 manage- ... This work presents.

  8. Forkhead box transcription factors in embryonic heart development and congenital heart disease.

    Science.gov (United States)

    Zhu, Hong

    2016-01-01

    Embryonic heart development is a very complicated process regulated precisely by a network composed of many genes and signaling pathways in time and space. Forkhead box (Fox, FOX) proteins are a family of transcription factors characterized by the presence of an evolutionary conserved "forkhead"or "winged-helix" DNA-binding domain and able to organize temporal and spatial gene expression during development. They are involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. An abundance of studies in model organisms and systems has established that Foxa2, Foxc1/c2, Foxh1 and Foxm1, Foxos and Foxps are important components of the signaling pathways that instruct cardiogenesis and embryonic heart development, playing paramount roles in heart development. The previous studies also have demonstrated that mutations in some of the forkhead box genes and the aberrant expression of forkhead box gene are heavily implicated in the congenital heart disease (CHD) of humans. This review primarily focuses on the current understanding of heart development regulated by forkhead box transcription factors and molecular genetic mechanisms by which forkhead box factors modulate heart development during embryogenesis and organogenesis. This review also summarizes human CHD related mutations in forkhead box genes as well as the abnormal expression of forkhead box gene, and discusses additional possible regulatory mechanisms of the forkhead box genes during embryonic heart development that warrant further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Plutonium assemblies in reload 1 of the Dodewaard Reactor

    International Nuclear Information System (INIS)

    Bairiot, H.; Deramaix, P.; Vandenberg, C.; Leenders, L.; Mostert, P.

    1977-01-01

    Since 1963, Belgonucleaire has been developing the design of plutonium assemblies of the island type (i.e., plutonium rods inserted in the control zone of the assembly and enriched uranium rods at the periphery) for light water reactors. The application to boiling water reactors (BWRs) led to the introduction, in April 1971, of two prototype plutonium island assemblies in the Dodewaard BWR (The Netherlands): Those assemblies incorporating plutonium in 42 percent of the rods are interchangeable with standard uranium assemblies of the same reload. Their design, which had to meet these criteria, was performed using the routine order in use at Belgonucleaire; experimental checks included a mock-up configuration simulated in the VENUS critical facility at Mol and open-vessel cold critical experiments performed in the Dodewaard core. The pelleted plutonium rods were fabricated and controlled by Belgonucleaire following the manufacturing procedures developed at the production plant. In one of the assemblies, three vibrated plutonium fuel rods with a lower fuel density were introduced in the three most highly rated positions to reduce the power rating. Those plutonium assemblies experienced peak pellet ratings up to 535 W/cm and were discharged in April 1974 after having reached a mean burnup of approximately 21,000 MWd/MT. In-core instrumentation during operation, visual examinations, and reactivity substitution experiments during reactor shutdown did not indicate any special feature for those assemblies compared to the standard uranium assemblies, thereby demonstrating their interchangeability

  10. Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease.

    Science.gov (United States)

    Fluschnik, Nina; Ojeda, Francisco; Zeller, Tanja; Jørgensen, Torben; Kuulasmaa, Kari; Becher, Peter Moritz; Sinning, Christoph; Blankenberg, Stefan; Westermann, Dirk

    2018-01-01

    Growth differentiation factor-15 (GDF-15), Cystatin C and C-reactive protein (CRP) have been discussed as biomarkers for prediction of cardiac diseases. The aim of this study was to investigate the predictive value of single and repeated measurements of GDF-15 compared to Cystatin C and CRP for incidence of heart failure (HF) and death due to coronary heart disease (CHD) in the general population. Levels of GDF-15, CRP and Cystatin C were determined in three repeated measurements collected 5 years apart in the DAN-MONICA (Danish-Multinational MONitoring of trends and determinants in Cardiovascular disease) cohort (participants at baseline n = 3785). Cox regression models adjusted for cardiovascular risk factors revealed significantly increased hazard ratios (HR) for GDF-15 for incident HF 1.36 (HR per interquartile range (IQR) increase, 95% confidence interval (CI): 1.16; 1.59) and for death from CHD 1.51 (HR per IQR increase, 95% CI: 1.31, 1.75) (both with p<0.001). Joint modeling of time-to-event and longitudinal GDF-15 over a median 27-year follow-up period showed that the marker evolution was positively associated with death of CHD (HR per IQR increase 3.02 95% CI: (2.26, 4.04), p < 0.001) and HF (HR per IQR increase 2.12 95% CI: (1.54, 2.92), p<0.001). However using Cox models with follow-up time starting at the time of the third examination, serial measurement of GDF-15, modeled as changes between the measurements, did not improve prediction over that of the most recent measurement. GDF-15 is a promising biomarker for prediction of HF and death due to CHD in the general population, which may provide prognostic information to already established clinical biomarkers. Repeated measurements of GDF-15 displayed only a slight improvement in the prediction of these endpoints compared to a single measurement.

  11. Super-resolution imaging of ESCRT-proteins at HIV-1 assembly sites.

    Directory of Open Access Journals (Sweden)

    Jens Prescher

    2015-02-01

    Full Text Available The cellular endosomal sorting complex required for transport (ESCRT machinery is involved in membrane budding processes, such as multivesicular biogenesis and cytokinesis. In HIV-infected cells, HIV-1 hijacks the ESCRT machinery to drive HIV release. Early in the HIV-1 assembly process, the ESCRT-I protein Tsg101 and the ESCRT-related protein ALIX are recruited to the assembly site. Further downstream, components such as the ESCRT-III proteins CHMP4 and CHMP2 form transient membrane associated lattices, which are involved in virus-host membrane fission. Although various geometries of ESCRT-III assemblies could be observed, the actual membrane constriction and fission mechanism is not fully understood. Fission might be driven from inside the HIV-1 budding neck by narrowing the membranes from the outside by larger lattices surrounding the neck, or from within the bud. Here, we use super-resolution fluorescence microscopy to elucidate the size and structure of the ESCRT components Tsg101, ALIX, CHMP4B and CHMP2A during HIV-1 budding below the diffraction limit. To avoid the deleterious effects of using fusion proteins attached to ESCRT components, we performed measurements on the endogenous protein or, in the case of CHMP4B, constructs modified with the small HA tag. Due to the transient nature of the ESCRT interactions, the fraction of HIV-1 assembly sites with colocalizing ESCRT complexes was low (1.5%-3.4%. All colocalizing ESCRT clusters exhibited closed, circular structures with an average size (full-width at half-maximum between 45 and 60 nm or a diameter (determined using a Ripley's L-function analysis of roughly 60 to 100 nm. The size distributions for colocalizing clusters were narrower than for non-colocalizing clusters, and significantly smaller than the HIV-1 bud. Hence, our results support a membrane scission process driven by ESCRT protein assemblies inside a confined structure, such as the bud neck, rather than by large lattices

  12. Hierarchical recruitment of ribosomal proteins and assembly factors remodels nucleolar pre-60S ribosomes.

    Science.gov (United States)

    Biedka, Stephanie; Micic, Jelena; Wilson, Daniel; Brown, Hailey; Diorio-Toth, Luke; Woolford, John L

    2018-04-24

    Ribosome biogenesis involves numerous preribosomal RNA (pre-rRNA) processing events to remove internal and external transcribed spacer sequences, ultimately yielding three mature rRNAs. Removal of the internal transcribed spacer 2 spacer RNA is the final step in large subunit pre-rRNA processing and begins with endonucleolytic cleavage at the C 2 site of 27SB pre-rRNA. C 2 cleavage requires the hierarchical recruitment of 11 ribosomal proteins and 14 ribosome assembly factors. However, the function of these proteins in C 2 cleavage remained unclear. In this study, we have performed a detailed analysis of the effects of depleting proteins required for C 2 cleavage and interpreted these results using cryo-electron microscopy structures of assembling 60S subunits. This work revealed that these proteins are required for remodeling of several neighborhoods, including two major functional centers of the 60S subunit, suggesting that these remodeling events form a checkpoint leading to C 2 cleavage. Interestingly, when C 2 cleavage is directly blocked by depleting or inactivating the C 2 endonuclease, assembly progresses through all other subsequent steps. © 2018 Biedka et al.

  13. Quality control of FWC during assembly and commissioning in SST-1 Tokamak

    Science.gov (United States)

    Patel, Hitesh; Santra, Prosenjit; Parekh, Tejas; Biswas, Prabal; Jayswal, Snehal; Chauhan, Pradeep; Paravastu, Yuvakiran; George, Siju; Semwal, Pratibha; Thankey, Prashant; Ramesh, Gattu; Prakash, Arun; Dhanani, Kalpesh; Raval, D. C.; Khan, Ziauddin; Pradhan, Subrata

    2017-04-01

    First Wall Components (FWC) of SST-1 tokamak, which are in the immediate vicinity of plasma, comprises of limiters, divertors, baffles, passive stabilizers designed to operate long duration (∼1000 s) discharges of elongated plasma. All FWC consist of copper alloy heat sink modules with SS cooling tubes brazed onto it, graphite tiles acting as armour material facing the plasma, and are mounted to the vacuum vessels with suitable Inconel support structures at inter-connected ring & port locations. The FWC are very recently assembled and commissioned successfully inside the vacuum vessel of SST-1 undergoing a rigorous quality control and checks at every stage of the assembly process. This paper will present the quality control aspects and checks of FWC from commencement of assembly procedure, namely material test reports, leak testing of high temperature baked components, assembled dimensional tolerances, leak testing of all welded joints, graphite tile tightening torques, electrical continuity and electrical isolation of passive stabilizers from vacuum vessel, baking and cooling hydraulic connections inside vacuum vessel.

  14. Education and risk of coronary heart disease: Assessment of mediation by behavioural risk factors using the additive hazards model

    DEFF Research Database (Denmark)

    Nordahl, H; Rod, NH; Frederiksen, BL

    2013-01-01

    seven Danish cohort studies were linked to registry data on education and incidence of CHD. Mediation by smoking, low physical activity, and body mass index (BMI) on the association between education and CHD were estimated by applying newly proposed methods for mediation based on the additive hazards...... % CI: 12, 22) for women and 37 (95 % CI: 28, 46) for men could be ascribed to the pathway through smoking. Further, 39 (95 % CI: 30, 49) cases for women and 94 (95 % CI: 79, 110) cases for men could be ascribed to the pathway through BMI. The effects of low physical activity were negligible. Using...... contemporary methods, the additive hazards model, for mediation we indicated the absolute numbers of CHD cases prevented when modifying smoking and BMI. This study confirms previous claims based on the Cox proportional hazards model that behavioral risk factors partially mediates the effect of education on CHD...

  15. Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.

    Science.gov (United States)

    Su, Tsung-Wei; Yang, Chao-Yu; Kao, Wen-Pin; Kuo, Bai-Jiun; Lin, Shan-Meng; Lin, Jung-Yaw; Lo, Yu-Chih; Lin, Su-Chang

    2017-03-07

    Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. An unusual dimeric structure and assembly for TLR4 regulator RP105-MD-1

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Hong, Minsun; Wilson, Ian A [Scripps

    2011-11-16

    RP105-MD-1 modulates the TLR4-MD-2-mediated, innate immune response against bacterial lipopolysaccharide (LPS). The crystal structure of the bovine 1:1 RP105-MD-1 complex bound to a putative endogenous lipid at 2.9 Å resolution shares a similar overall architecture to its homolog TLR4-MD-2 but assembles into an unusual 2:2 homodimer that differs from any other known TLR-ligand assembly. The homodimer is assembled in a head-to-head orientation that juxtaposes the N-terminal leucine-rich repeats (LRRs) of the two RP105 chains, rather than the usual tail-to-tail configuration of C-terminal LRRs in ligand-activated TLR dimers, such as TLR1-TRL2, TLR2-TLR6, TLR3-TLR3 and TLR4-TLR4. Another unusual interaction is mediated by an RP105-specific asparagine-linked glycan, which wedges MD-1 into the co-receptor binding concavity on RP105. This unique mode of assembly represents a new paradigm for TLR complexes and suggests a molecular mechanism for regulating LPS responses.

  17. Selected risk factors for coronary heart disease in m.ale scholars ...

    African Journals Online (AJOL)

    to reduce CHD risk factors in our developed populations and to prevent their emergence in our developing ... parents were poorly educated and unemployment rates were high. .... ethnic group and smoking habits of the boys were recorded.

  18. Nuclear overhauser spectroscopy of chiral CHD methylene groups

    Energy Technology Data Exchange (ETDEWEB)

    Augustyniak, Rafal [Ecole Normale Supérieure – PSL Research University, Département de chimie (France); Stanek, Jan [University of Warsaw, Faculty of Chemistry (Poland); Colaux, Henri; Bodenhausen, Geoffrey [Ecole Normale Supérieure – PSL Research University, Département de chimie (France); Koźmiński, Wiktor [University of Warsaw, Faculty of Chemistry (Poland); Herrmann, Torsten [Université de Lyon/UMR 5280 CNRS/ENS Lyon/UCB Lyon 1, Institut des Sciences Analytiques, Centre de RMN à Très Hauts Champs (France); Ferrage, Fabien, E-mail: Fabien.Ferrage@ens.fr [Ecole Normale Supérieure – PSL Research University, Département de chimie (France)

    2016-01-15

    Nuclear magnetic resonance spectroscopy (NMR) can provide a great deal of information about structure and dynamics of biomolecules. The quality of an NMR structure strongly depends on the number of experimental observables and on their accurate conversion into geometric restraints. When distance restraints are derived from nuclear Overhauser effect spectroscopy (NOESY), stereo-specific assignments of prochiral atoms can contribute significantly to the accuracy of NMR structures of proteins and nucleic acids. Here we introduce a series of NOESY-based pulse sequences that can assist in the assignment of chiral CHD methylene protons in random fractionally deuterated proteins. Partial deuteration suppresses spin-diffusion between the two protons of CH{sub 2} groups that normally impedes the distinction of cross-relaxation networks for these two protons in NOESY spectra. Three and four-dimensional spectra allow one to distinguish cross-relaxation pathways involving either of the two methylene protons so that one can obtain stereospecific assignments. In addition, the analysis provides a large number of stereospecific distance restraints. Non-uniform sampling was used to ensure optimal signal resolution in 4D spectra and reduce ambiguities of the assignments. Automatic assignment procedures were modified for efficient and accurate stereospecific assignments during automated structure calculations based on 3D spectra. The protocol was applied to calcium-loaded calbindin D{sub 9k}. A large number of stereospecific assignments lead to a significant improvement of the accuracy of the structure.

  19. Current status of coronary risk factors among rural Malays in Malaysia.

    Science.gov (United States)

    Nawawi, Hapizah M; Nor, Idris M; Noor, Ismail M; Karim, Norimah A; Arshad, Fatimah; Khan, Rahmattullah; Yusoff, Khalid

    2002-02-01

    Coronary heart disease (CHD) is the leading cause of death in Malaysia, despite its status as a developing country. The rural population is thought to be at low risk. To investigate the prevalence of risk factors and global risk profile among rural Malays in Malaysia. We studied 609 rural Malay subjects (346 females, 263 males; age range 30-65 years). Blood pressure (BP), body mass index (BMI), waist-hip ratio (WHR), smoking habits and family history of premature CHD were documented. Fasting blood samples were analysed for serum lipids, lipoprotein (a), plasma glucose and fibrinogen. Oral glucose tolerance tests were performed using 75 g anhydrous glucose. The prevalence of hypercholesterolaemia for total cholesterol concentrations of > or = 5.2, > or =6.5 and > or =7.8 mmol/l were 67.3, 30.5 and 11.8% respectively. There was a high prevalence of low serum high-density lipoprotein cholesterol (13.1%), hypertension (30.3%), smokers (24.4%), diabetes (6.4%), impaired fasting glucose or glucose tolerance (13.9%), overweight or obesity (44.7%) and increased WHR (48.5%). Global risk assessment showed that 67.3% of the study population were at risk, with 15.9, 18.9 and 32.5% in the mild, moderate and high risk categories respectively. Prevalence of risk factors was high in the rural population. Global risk assessment showed a high-risk profile with two-thirds being at risk, and one-third being categorized into the high-risk group. Although rural communities were considered at low risk of developing CHD, this is changing fast, possibly due to the rapid socio-economic development, in addition to underlying genetic predisposition.

  20. Nondestructive examination of Oconee 1 fuel assemblies after three cycles of irradiation

    International Nuclear Information System (INIS)

    Pyecha, T.D.; Davis, H.H.; Mayer, J.T.; Guthrie, B.A. III; Larson, J.G.

    1979-09-01

    The Babcock and Wilcox Company (B and W) in conjunction with Duke Power Company is participating in a Department of Energy sponsored research and development program to qualify current design pressurized water reactor (PWR) fuel assemblies for extended burnup (>40,000 MWd/mtU). The information obtained from this program will provide a basis for future design improvements in PWR fuel assemblies culminating in an extended burnup assembly having a nominal operating limit of approximately 50,000 MWd/mtU. An extension of the current assembly design to higher burnups will result in the following benefits: (1) lower uranium ore requirements, (2) greater fuel cycle efficiency, (3) reduction in spent fuel storage requirements, and (4) increased flexibility in tailoring fuel batch sizes to better accommodate the varying energy requirements of the utilities

  1. Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study

    Directory of Open Access Journals (Sweden)

    Cunningham Heather

    2010-07-01

    Full Text Available Abstract Background Preventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED population in primary prevention for coronary heart disease (CHD. Methods The primary prevention element of Have a Heart Paisley (HaHP offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a a social marketing campaign and b a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches. Results Various reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1 processes of engagement; (2 issues of understanding; (3 design of the screening service and (4 the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In

  2. Robotically Assembled Aerospace Structures: Digital Material Assembly using a Gantry-Type Assembler

    Science.gov (United States)

    Trinh, Greenfield; Copplestone, Grace; O'Connor, Molly; Hu, Steven; Nowak, Sebastian; Cheung, Kenneth; Jenett, Benjamin; Cellucci, Daniel

    2017-01-01

    This paper evaluates the development of automated assembly techniques for discrete lattice structures using a multi-axis gantry type CNC machine. These lattices are made of discrete components called "digital materials." We present the development of a specialized end effector that works in conjunction with the CNC machine to assemble these lattices. With this configuration we are able to place voxels at a rate of 1.5 per minute. The scalability of digital material structures due to the incremental modular assembly is one of its key traits and an important metric of interest. We investigate the build times of a 5x5 beam structure on the scale of 1 meter (325 parts), 10 meters (3,250 parts), and 30 meters (9,750 parts). Utilizing the current configuration with a single end effector, performing serial assembly with a globally fixed feed station at the edge of the build volume, the build time increases according to a scaling law of n4, where n is the build scale. Build times can be reduced significantly by integrating feed systems into the gantry itself, resulting in a scaling law of n3. A completely serial assembly process will encounter time limitations as build scale increases. Automated assembly for digital materials can assemble high performance structures from discrete parts, and techniques such as built in feed systems, parallelization, and optimization of the fastening process will yield much higher throughput.

  3. A cross-sectional study of the relationship between job demand-control, effort-reward imbalance and cardiovascular heart disease risk factors

    Directory of Open Access Journals (Sweden)

    Söderberg Mia

    2012-12-01

    Full Text Available Abstract Background This cross-sectional study explored relationships between psychosocial work environment, captured by job demand-control (JDC and effort-reward imbalance (ERI, and seven cardiovascular heart disease (CHD risk factors in a general population. Method The sampled consists of randomly-selected men and women from Gothenburg, Sweden and the city’s surrounding metropolitan areas. Associations between psychosocial variables and biomarkers were analysed with multiple linear regression adjusted for age, smoking, education and occupational status. Results The study included 638 men and 668 women aged 24–71. Analysis between JDC and CHD risk factors illustrated that, for men, JDC was associated with impaired scores in several biomarkers, especially among those in high strain jobs. For women, there were no relationships between JDC and biomarkers. In the analysis of links between ERI and CHD risk factors, most associations tested null. The only findings were raised triglycerides and BMI among men in the fourth quartile of the ERI-ratio distribution, and lowered LDL-cholesterol for women. An complementary ERI analysis, combining high/low effort and reward into categories, illustrated lowered triglycerides and elevated HDL-cholesterol values among women reporting high efforts and high rewards, compared to women experiencing low effort and high reward. Conclusions There were some associations between psychosocial stressors and CHD risk factors. The cross-sectional design did not allow conclusions about causality but some results indicated gender differences regarding sensitivity to work stressors and also how the models might capture different psychosocial dimensions.

  4. Chaperoning 5S RNA assembly.

    Science.gov (United States)

    Madru, Clément; Lebaron, Simon; Blaud, Magali; Delbos, Lila; Pipoli, Juliana; Pasmant, Eric; Réty, Stéphane; Leulliot, Nicolas

    2015-07-01

    In eukaryotes, three of the four ribosomal RNAs (rRNAs)—the 5.8S, 18S, and 25S/28S rRNAs—are processed from a single pre-rRNA transcript and assembled into ribosomes. The fourth rRNA, the 5S rRNA, is transcribed by RNA polymerase III and is assembled into the 5S ribonucleoprotein particle (RNP), containing ribosomal proteins Rpl5/uL18 and Rpl11/uL5, prior to its incorporation into preribosomes. In mammals, the 5S RNP is also a central regulator of the homeostasis of the tumor suppressor p53. The nucleolar localization of the 5S RNP and its assembly into preribosomes are performed by a specialized complex composed of Rpf2 and Rrs1 in yeast or Bxdc1 and hRrs1 in humans. Here we report the structural and functional characterization of the Rpf2-Rrs1 complex alone, in complex with the 5S RNA, and within pre-60S ribosomes. We show that the Rpf2-Rrs1 complex contains a specialized 5S RNA E-loop-binding module, contacts the Rpl5 protein, and also contacts the ribosome assembly factor Rsa4 and the 25S RNA. We propose that the Rpf2-Rrs1 complex establishes a network of interactions that guide the incorporation of the 5S RNP in preribosomes in the initial conformation prior to its rotation to form the central protuberance found in the mature large ribosomal subunit. © 2015 Madru et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Novel Coiled-Coil Cell Division Factor ZapB Stimulates Z Ring Assembly and Cell Division

    DEFF Research Database (Denmark)

    Ebersbach, Gitte; Galli, Elizabeth; Møller-Jensen, Jakob

    2008-01-01

    Formation of the Z ring is the first known event in bacterial cell division. However, it is not yet known how the assembly and contraction of the Z ring is regulated. Here, we identify a novel cell division factor ZapB in Escherichia coli that simultaneously stimulates Z ring assembly and cell...... division. Deletion of zapB resulted in delayed cell division and the formation of ectopic Z rings and spirals whereas overexpression of ZapB resulted in nucleoid condensation and aberrant cell divisions. Localization of ZapB to the divisome depended on FtsZ but not FtsA, ZipA or FtsI and ZapB interacted...... with FtsZ in a bacterial two-hybrid analysis. The simultaneous inactivation of FtsA and ZipA prevented Z ring assembly and ZapB localization. Time lapse microscopy showed that ZapB-GFP is present at mid-cell in a pattern very similar to that of FtsZ. Cells carrying a zapB deletion and the ftsZ84ts allele...

  6. Ile-1781-Leu and Asp-2078-Gly Mutations in ACCase Gene, Endow Cross-resistance to APP, CHD, and PPZ in Phalaris minor from Mexico

    Directory of Open Access Journals (Sweden)

    Hugo Cruz-Hipolito

    2015-09-01

    Full Text Available Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor. These herbicides are classified into three major families (ariloxyphenoxypropionates (APP, cyclohexanodiones (CHD, and, recently, phenylpyrazolines (PPZ. In this work, the resistance to ACCase (APP, CHD, and PPZ inhibiting herbicides was studied in a biotype of Phalaris minor (P. minor from Mexico, by carrying out bioassays at the whole-plant level and investigating the mechanism behind this resistance. Dose-response and ACCase in vitro activity assays showed cross-resistance to all ACCase herbicides used. There was no difference in the absorption, translocation, and metabolism of the 14C-diclofop-methyl between the R and S biotypes. The PCR generated CT domain fragments of ACCase from the R biotype and an S reference were sequenced and compared. The Ile-1781-Leu and Asp-2078-Gly point mutations were identified. These mutations could explain the loss of affinity for ACCase by the ACCase-inhibing herbicides. This is the first report showing that this substitution confers resistance to APP, CHD, and PPZ herbicides in P. minor from Mexico. The mutations have been described previously only in a few cases; however, this is the first study reporting on a pattern of cross-resistance with these mutations in P. minor. The findings could be useful for better management of resistant biotypes carrying similar mutations.

  7. Assembly line performance and modeling

    Science.gov (United States)

    Rane, Arun B.; Sunnapwar, Vivek K.

    2017-09-01

    Automobile sector forms the backbone of manufacturing sector. Vehicle assembly line is important section in automobile plant where repetitive tasks are performed one after another at different workstations. In this thesis, a methodology is proposed to reduce cycle time and time loss due to important factors like equipment failure, shortage of inventory, absenteeism, set-up, material handling, rejection and fatigue to improve output within given cost constraints. Various relationships between these factors, corresponding cost and output are established by scientific approach. This methodology is validated in three different vehicle assembly plants. Proposed methodology may help practitioners to optimize the assembly line using lean techniques.

  8. Prevalence of cardiovascular risks factors and 10 year predictions of coronary heart disease in seafarers of Pertamina shipping (Indonesia)

    DEFF Research Database (Denmark)

    Purnawarma, Irwin GNI; Jensen, Olaf Chresten; Canals, ML

    2011-01-01

    independent CHD risk factors were Obesity (BMI >25%, 56%), dislipidemia (TC >200mg/dL and/or TG >150mg/dL, 72.1%), Smoking (43.7%) and Lack of Exercise (43.7%). After adjusting age and comparison to BMI and Cholesterol levels, in older age group seafarers (50-55 yrs old), the risk of a cardiovascular event...

  9. Direct mapping of the angle-dependent barrier to reaction for Cl + CHD3 using polarized scattering data

    Science.gov (United States)

    Pan, Huilin; Wang, Fengyan; Czakó, Gábor; Liu, Kopin

    2017-12-01

    The transition state, which gates and modulates reactive flux, serves as the central concept in our understanding of activated reactions. The barrier height of the transition state can be estimated from the activation energy taken from thermal kinetics data or from the energetic threshold in the measured excitation function (the dependence of reaction cross-sections on initial collision energies). However, another critical and equally important property, the angle-dependent barrier to reaction, has not yet been amenable to experimental determination until now. Here, using the benchmark reaction of Cl + CHD3(v1 = 1) as an example, we show how to map this anisotropic property of the transition state as a function of collision energy from the preferred reactant bond alignment of the backward-scattered products—the imprints of small impact-parameter collisions. The deduced bend potential at the transition state agrees with ab initio calculations. We expect that the method should be applicable to many other direct reactions with a collinear barrier.

  10. The Quest for the 1p36 Tumor Suppressor

    Science.gov (United States)

    Bagchi, Anindya; Mills, Alea A.

    2010-01-01

    Genomic analyses of late-stage human cancers have uncovered deletions encompassing 1p36, thereby providing an extensive body of literature supporting the idea that a potent tumor suppressor resides in this interval. Although a number of genes have been proposed as 1p36 candidate tumor suppressors, convincing evidence that their encoded products protect from cancer has been scanty. A recent functional study identified CHD5 as a novel tumor suppressor mapping to 1p36. Here we discuss evidence supporting CHD5’s tumor suppressive role. Together, these findings suggest that strategies designed to enhance CHD5 activity could provide novel approaches for treating a broad range of human malignancies. PMID:18413720

  11. Effect of diet and physical exercise intervention programmes on coronary heart disease risk in smoking and non-smoking men in Sweden.

    Science.gov (United States)

    Näslund, G K; Fredrikson, M; Hellénius, M L; de Faire, U

    1996-01-01

    STUDY OBJECTIVE: To investigate differences between smokers and non-smokers in health behaviour, cardiovascular risk factors, coronary heart disease (CHD) risks, health knowledge, health attitudes, and compliance with a CHD prevention programme. DESIGN: Differences between smokers and non-smokers were studied via medical examinations, questionnaires, physical exercise activity logs, and food record sheets. Data were analysed using univariate and multivariate analyses. The five and 10 year CHD risks were assessed using the Framingham CHD risk estimate. SETTING: The Karolinska Hospital, Stockholm, and Sollentuna Primary Health Centre, Sollentuna, Sweden. PARTICIPANTS: The analyses were based on 158 healthy smoking and non-smoking men aged 35-60 years with raised cardiovascular risk factors who enrolled in controlled, randomised six month diet and exercise programmes. MAIN RESULTS: Discriminant analysis suggested that smokers, compared with non-smokers, were characterised by a higher alcohol energy percent, lower HDL cholesterol concentration, lower systolic blood pressure, and a higher plasminogen activator inhibitor-1 (PAI-1) value. Knowledge of the risk factors for CHD was not a discriminating factor. Both smokers and non-smokers increased the exercise taken, improved their diet, and lowered their CHD risk. Before, as well as after the intervention, smokers had a higher CHD risk than non-smokers. CONCLUSIONS: The best CHD prevention action that could be taken by smokers would of course be to quit smoking. Those who cannot stop should be encouraged to improve their diet and increase the amount of physical exercise they take in order to reduce the health hazards of their smoking behaviour. PMID:8762375

  12. Reaction Rate Distributions and Ratios in FR0 Assemblies 1, 2 and 3

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, T L

    1966-06-15

    The spatial distribution of different reaction rates and reaction ratios in Assemblies 1, 2 and 3 of the fast reactor FR0 was measured by fission chamber scans and foil activation technique. Assemblies 1 and 2 had cores of undiluted fuel (uranium metal enriched to 20 % U{sup 235}) while the core of Assembly 3 was diluted with about 30 vol. % graphite. All the systems had a thick copper reflector, The experimental results were compared with calculated values obtained from DSN and TDC multigroup spectra and group cross-section sets for the reactions. Good agreement between experiment and calculations is generally obtained in the core region but in the reflector the neutron spectrum is calculated too hard.

  13. Depression risk in patients with coronary heart disease in Germany

    Institute of Scientific and Technical Information of China (English)

    Marcel Konrad; Louis Jacob; Michael A Rapp; Karel Kostev

    2016-01-01

    AIM To determine the prevalence of depression and its risk factors among patients with coronary heart disease(CHD) treated in German primary care practices.METHODS Longitudinal data from nationwide general practices in Germany(n = 1072) were analyzed.Individuals initially diagnosed with CHD(2009-2013) were identified,and 59992 patients were included and matched(1:1) to 59992 controls.The primary outcome measure was an initial diagnosis of depression within five years after the index date among patients with and without CHD.Cox proportional hazards models were used to adjust for confounders.RESULTS Mean age was equal to 68.0 years(SD = 11.3).A total of 55.9% of patients were men.After a five-year follow-up,21.8% of the CHD group and 14.2% of the control group were diagnosed with depression(P < 0.001).In the multivariate regression model,CHD was a strong risk factor for developing depression(HR =1.54,95%CI:1.49-1.59,P < 0.001).Prior depressive episodes,dementia,and eight other chronic conditions were associated with a higher risk of developing depression.Interestingly,older patients and women were also more likely to be diagnosed with depression compared with younger patients and men,respectively.CONCLUSION The risk of depression is significantly increased among patients with CHD compared with patients without CHD treated in primary care practices in Germany.CHD patients should be routinely screened for depression to ensure improved treatment and management.

  14. Functional Analyses of a Novel Splice Variant in the CHD7 Gene, Found by Next Generation Sequencing, Confirm Its Pathogenicity in a Spanish Patient and Diagnose Him with CHARGE Syndrome

    Directory of Open Access Journals (Sweden)

    Olatz Villate

    2018-01-01

    Full Text Available Mutations in CHD7 have been shown to be a major cause of CHARGE syndrome, which presents many symptoms and features common to other syndromes making its diagnosis difficult. Next generation sequencing (NGS of a panel of intellectual disability related genes was performed in an adult patient without molecular diagnosis. A splice donor variant in CHD7 (c.5665 + 1G > T was identified. To study its potential pathogenicity, exons and flanking intronic sequences were amplified from patient DNA and cloned into the pSAD® splicing vector. HeLa cells were transfected with this construct and a wild-type minigene and functional analysis were performed. The construct with the c.5665 + 1G > T variant produced an aberrant transcript with an insert of 63 nucleotides of intron 28 creating a premature termination codon (TAG 25 nucleotides downstream. This would lead to the insertion of 8 new amino acids and therefore a truncated 1896 amino acid protein. As a result of this, the patient was diagnosed with CHARGE syndrome. Functional analyses underline their usefulness for studying the pathogenicity of variants found by NGS and therefore its application to accurately diagnose patients.

  15. Functional Analyses of a Novel Splice Variant in the CHD7 Gene, Found by Next Generation Sequencing, Confirm Its Pathogenicity in a Spanish Patient and Diagnose Him with CHARGE Syndrome.

    Science.gov (United States)

    Villate, Olatz; Ibarluzea, Nekane; Fraile-Bethencourt, Eugenia; Valenzuela, Alberto; Velasco, Eladio A; Grozeva, Detelina; Raymond, F L; Botella, María P; Tejada, María-Isabel

    2018-01-01

    Mutations in CHD7 have been shown to be a major cause of CHARGE syndrome, which presents many symptoms and features common to other syndromes making its diagnosis difficult. Next generation sequencing (NGS) of a panel of intellectual disability related genes was performed in an adult patient without molecular diagnosis. A splice donor variant in CHD7 (c.5665 + 1G > T) was identified. To study its potential pathogenicity, exons and flanking intronic sequences were amplified from patient DNA and cloned into the pSAD ® splicing vector. HeLa cells were transfected with this construct and a wild-type minigene and functional analysis were performed. The construct with the c.5665 + 1G > T variant produced an aberrant transcript with an insert of 63 nucleotides of intron 28 creating a premature termination codon (TAG) 25 nucleotides downstream. This would lead to the insertion of 8 new amino acids and therefore a truncated 1896 amino acid protein. As a result of this, the patient was diagnosed with CHARGE syndrome. Functional analyses underline their usefulness for studying the pathogenicity of variants found by NGS and therefore its application to accurately diagnose patients.

  16. Interactions within the yeast t-SNARE Sso1p that control SNARE complex assembly.

    Science.gov (United States)

    Munson, M; Chen, X; Cocina, A E; Schultz, S M; Hughson, F M

    2000-10-01

    In the eukaryotic secretory and endocytic pathways, transport vesicles shuttle cargo among intracellular organelles and to and from the plasma membrane. Cargo delivery entails fusion of the transport vesicle with its target, a process thought to be mediated by membrane bridging SNARE protein complexes. Temporal and spatial control of intracellular trafficking depends in part on regulating the assembly of these complexes. In vitro, SNARE assembly is inhibited by the closed conformation adopted by the syntaxin family of SNAREs. To visualize this closed conformation directly, the X-ray crystal structure of a yeast syntaxin, Sso1p, has been determined and refined to 2.1 A resolution. Mutants designed to destabilize the closed conformation exhibit accelerated rates of SNARE assembly. Our results provide insight into the mechanism of SNARE assembly and its intramolecular and intermolecular regulation.

  17. STUDY OF A TREND IN THE FREQUENCY OF USING MAIN DRUG CLASSES INDICATED FOR THE TREATMENT OF PATIENTS WITH CHRONIC CORONARY HEART DISEASE IN 2004 TO 2014: DATA FROM THE CHD PROGNOSIS REGISTRY

    Directory of Open Access Journals (Sweden)

    S. N. Tolpygina

    2016-01-01

    Full Text Available Objective: to estimate a trend in the frequency of using drugs with their proven effect on disease outcome in patients with chronic coronary heart disease (CHD in 2004–2014 within the CHD PROGNOSIS registry. Materials and methods. The investigation included data from the CHD PROGNOSIS registry on 303 patients with verified CHD during the 2004–2007 reference hospitalization at the National Research Center for Preventive Medicine, who made a control visit 4 years later, and those on 125 patients who had come following 7 years. Results. There was a low frequency of prescribing the drugs that were able to improve prognosis in patients with stable CHD prior to the 2004–2007 reference hospitalization with an increase at discharge and with a further reduction during outpatient treatment. 7.6 and 86.5% of the patients took statins; 68 and 96 % received disaggregants; 24.8 and 94 % used β-adrenoblockers (β-AB, and 19 and 83 % had angiotensin-converting enzyme (ACE inhibitors before hospitalization and at discharge, respectively (p < 0.001. Four and seven years after discharge, there were reductions in the frequency of using statins to 67 and 70 %, disaggregants to 80 and 90 %, β-AB to 80 and 75 %, and ACE inhibitors to 66 and 65 %, respectively (p < 0.01. At the same time, the above-mentioned drugs were taken by 15 and 69 % of patients on admission and at discharge, respectively (p < 0.001, by 41 and 35 % after 4 and 7 years (p < 0.01. In 2004 to 2014, most drugs were used at low and moderate doses with a gradual increase in the share of generics. Conclusion. The therapy in patients with stable CHD was characterized by a low frequency of using the drugs with their proven effect on prognosis prior to the 2004–2007 reference hospitalization with an increase and a decrease in the frequency of their use on discharge and after 4 and 7 years. During 10 years, β-AB, ACE inhibitors/angiotensin II receptor antagonists, and statins were used mainly at

  18. Frequency and changes in trends of leading risk factors of coronary heart disease in women in the city of Novi Sad during a 20-year period

    Directory of Open Access Journals (Sweden)

    Rakić Dušica

    2012-01-01

    Full Text Available Backround/Aim. From 1984 to 2004 the city of Novi Sad participated through its Health Center “Novi Sad” in the international Multinational MONItoring of Trends and Determinants in CArdiovascular Disease (MONICA project, as one of the 38 research centers in 21 countries around the world. The aim of this study was to determine frequency and changes of trends in leading risk factors of coronary heart disease (CHD and to analyze the previous trend of movement of coronary event in women in Novi Sad during a 20- year period. Methods. In 2004, the fourth survey within MONICA project was conducted in the city of Novi Sad. The representative sample included 1,041 women between the age of 25 and 74. The prevalence of risk factors in CHD such as smoking, high blood pressure, elevated blood cholesterol, elevated blood glucose and obesity was determined. Also, indicators of risk factors and rates of coronary events in women were compared with the results from MONICA project obtained in previous three screens, as well as with the results from other research centres. χ2-test, linear trend and correlartion coefficient were used in statistical analysis of results obtained. Results. It was observed that during a 20-year period covered by the study, the prevalence of the leading risk factors for the development of CHD in the surveyed women was significantly increasing and in positive correlation with the values of linear trend. Also, the increase of morbidity rates and mortality rates of coronary event were in positive correlation. The decrease was only recorded in the period from 1985-1989 (the implementation of the intervention programme. Conclusion. Upon analysing the increase in prevalence of leading risk factors of CHD and significant increase in the rates of coronary event, we can conclude that health status of women in Novi Sad during a 20-year period was deteriorating.

  19. [Occupational stress in assembly line workers in electronics manufacturing service and related influencing factors].

    Science.gov (United States)

    Ji, Y Q; Li, S; Wang, C; Wang, J; Liu, X M

    2016-10-20

    Objective: To investigate occupational stress in assembly line workers in electronics manu-facturing service (EMS) and related influencing factors. Methods: From June to October, 2015, a cross-sectional survey was performed for 5 944 assembly line workers in EMS (observation group) and 6 270 workers from other posts (non-assembly line workers and management personnel; control group) using the self-made questionnaire for basic information, job demand-control (JDC) model questionnaire, and effort-reward imbalance (ERI) model questionnaire to collect respondents' basic information and occupational stress. Results: The observation group had significantly lower work autonomy, social support, and work reward scores than the control group (2.72 ± 0.63/3.64 ± 0.68/4.06 ± 0.80 vs 3.00 ± 0.67/3.83 ± 0.68/4.24 ± 0.75, t =23.53, 15.41, and 12.70, all P occupational stress determined by JDC and ERI models than the control group (64.5%/12.7% vs 52.6%/9.9%, χ 2 =182.26 and 23.41, both P 60 hours/week, and sleeping time occupational stress in JDC model; education background of Bachelor's degree or above, working time >60 hours/week, and sleeping timeoccupational stress in ERI model, while female sex and a high monthly income reduced the risk of occupational stress in ERI model. Conclusion: Assembly line workers in EMS are a relatively vulnerable group and have a high degree of occupational stress. Working time >60 hours/week and sleeping time occupational stress.

  20. DNA repair goes hip-hop: SMARCA and CHD chromatin remodellers join the break dance.

    Science.gov (United States)

    Rother, Magdalena B; van Attikum, Haico

    2017-10-05

    Proper signalling and repair of DNA double-strand breaks (DSB) is critical to prevent genome instability and diseases such as cancer. The packaging of DNA into chromatin, however, has evolved as a mere obstacle to these DSB responses. Posttranslational modifications and ATP-dependent chromatin remodelling help to overcome this barrier by modulating nucleosome structures and allow signalling and repair machineries access to DSBs in chromatin. Here we recap our current knowledge on how ATP-dependent SMARCA- and CHD-type chromatin remodellers alter chromatin structure during the signalling and repair of DSBs and discuss how their dysfunction impacts genome stability and human disease.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Authors.

  1. Modeling and Finite Element Analysis of Load-Carrying Performance of a Wind Turbine Considering the Influence of Assembly Factors

    Directory of Open Access Journals (Sweden)

    Jianmei Wang

    2017-03-01

    Full Text Available In this work, a wind turbine shrink disk is used as the research object to investigate load-carrying performance of a multi-layer interference fit, and the theoretical model and finite element model are constructed. According to those models, a MW-level turbine shrink disk is designed, and a test device is developed to apply torque to this turbine shrink disk by hydraulic jack. Then, the circumferential slip between the contact surfaces is monitored and the slip of all contact surfaces is zero. This conclusion verifies the reasonability of the proposed models. The effect of the key influencing factors, such as machining deviation, assembly clearance and propel stroke, were analyzed. The contact pressure and load torque of the mating surfaces were obtained by building typical models with different parameters using finite element analysis (FEA. The results show that the minimum assembly clearance and the machining deviation within the machining range have little influence on load-carrying performance of multi-layer interference fit, while having a greater influence on the maximum assembly clearance and the propel stroke. The results also show that the load-carrying performance of a multiple-layer interference fit can be ensured only if the key factors are set within a reasonable design range. To avoid the abnormal operation of equipment caused by insufficient load torque, the propel stroke during practical assembly should be at least 0.95 times the designed propel stroke, which is significant in guiding the design and assembly of the multi-layer interference fit.

  2. Evaluation of Carbohydrate-Derived Fulvic Acid (CHD-FA) as a Topical Broad-Spectrum Antimicrobial for Drug-Resistant Wound Infections

    Science.gov (United States)

    2015-10-01

    Tests for Bacteria That Grow Aerobically ; Approved Standard – Eighth Edition” was used to determine the CHD-FA MIC values at a pH range of 3.0 to...preventing absorption of active compound (See Figure 13.) Also the topical cream formulation has been approved for 24 vaginitis to help control...Institute (CLSI) protocol M07-A9 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically ; Approved Standard

  3. Explaining the increase in coronary heart disease mortality in Syria between 1996 and 2006.

    Science.gov (United States)

    Rastam, Samer; Al Ali, Radwan; Maziak, Wasim; Mzayek, Fawaz; Fouad, Fouad M; O'Flaherty, Martin; Capewell, Simon

    2012-09-09

    Despite advances made in treating coronary heart disease (CHD), mortality due to CHD in Syria has been increasing for the past two decades. This study aims to assess CHD mortality trends in Syria between 1996 and 2006 and to investigate the main factors associated with them. The IMPACT model was used to analyze CHD mortality trends in Syria based on numbers of CHD patients, utilization of specific treatments, trends in major cardiovascular risk factors in apparently healthy persons and CHD patients. Data sources for the IMPACT model included official statistics, published and unpublished surveys, data from neighboring countries, expert opinions, and randomized trials and meta-analyses. Between 1996 and 2006, CHD mortality rate in Syria increased by 64%, which translates into 6370 excess CHD deaths in 2006 as compared to the number expected had the 1996 baseline rate held constant. Using the IMPACT model, it was estimated that increases in cardiovascular risk factors could explain approximately 5140 (81%) of the CHD deaths, while some 2145 deaths were prevented or postponed by medical and surgical treatments for CHD. Most of the recent increase in CHD mortality in Syria is attributable to increases in major cardiovascular risk factors. Treatments for CHD were able to prevent about a quarter of excess CHD deaths, despite suboptimal implementation. These findings stress the importance of population-based primary prevention strategies targeting major risk factors for CHD, as well as policies aimed at improving access and adherence to modern treatments of CHD.

  4. Dynamics of HIV-1 RNA Near the Plasma Membrane during Virus Assembly.

    Science.gov (United States)

    Sardo, Luca; Hatch, Steven C; Chen, Jianbo; Nikolaitchik, Olga; Burdick, Ryan C; Chen, De; Westlake, Christopher J; Lockett, Stephen; Pathak, Vinay K; Hu, Wei-Shau

    2015-11-01

    To increase our understanding of the events that lead to HIV-1 genome packaging, we examined the dynamics of viral RNA and Gag-RNA interactions near the plasma membrane by using total internal reflection fluorescence microscopy. We labeled HIV-1 RNA with a photoconvertible Eos protein via an RNA-binding protein that recognizes stem-loop sequences engineered into the viral genome. Near-UV light exposure causes an irreversible structural change in Eos and alters its emitted fluorescence from green to red. We studied the dynamics of HIV-1 RNA by photoconverting Eos near the plasma membrane, and we monitored the population of photoconverted red-Eos-labeled RNA signals over time. We found that in the absence of Gag, most of the HIV-1 RNAs stayed near the plasma membrane transiently, for a few minutes. The presence of Gag significantly increased the time that RNAs stayed near the plasma membrane: most of the RNAs were still detected after 30 min. We then quantified the proportion of HIV-1 RNAs near the plasma membrane that were packaged into assembling viral complexes. By tagging Gag with blue fluorescent protein, we observed that only a portion, ∼13 to 34%, of the HIV-1 RNAs that reached the membrane were recruited into assembling particles in an hour, and the frequency of HIV-1 RNA packaging varied with the Gag expression level. Our studies reveal the HIV-1 RNA dynamics on the plasma membrane and the efficiency of RNA recruitment and provide insights into the events leading to the generation of infectious HIV-1 virions. Nascent HIV-1 particles assemble on plasma membranes. During the assembly process, HIV-1 RNA genomes must be encapsidated into viral complexes to generate infectious particles. To gain insights into the RNA packaging and virus assembly mechanisms, we labeled and monitored the HIV-1 RNA signals near the plasma membrane. Our results showed that most of the HIV-1 RNAs stayed near the plasma membrane for only a few minutes in the absence of Gag, whereas

  5. A telomerase-independent component of telomere loss in chromatin assembly factor 1 mutants of Arabidopsis thaliana

    Czech Academy of Sciences Publication Activity Database

    Jaške, K.; Mokroš, P.; Mozgová, I.; Fojtová, Miloslava; Fajkus, Jiří

    2013-01-01

    Roč. 122, č. 4 (2013), s. 285-293 ISSN 0009-5915 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0068 Grant - others:GA ČR(CZ) GAP501/11/0289 Institutional support: RVO:68081707 Keywords : FACTOR-I * GENOME INSTABILITY * MOLECULAR ANALYSIS Subject RIV: BO - Biophysics Impact factor: 3.260, year: 2013

  6. Aggregation and network formation in self-assembly of protein (H3.1) by a coarse-grained Monte Carlo simulation

    Science.gov (United States)

    Pandey, R. B.; Farmer, B. L.

    2014-11-01

    Multi-scale aggregation to network formation of interacting proteins (H3.1) are examined by a knowledge-based coarse-grained Monte Carlo simulation as a function of temperature and the number of protein chains, i.e., the concentration of the protein. Self-assembly of corresponding homo-polymers of constitutive residues (Cys, Thr, and Glu) with extreme residue-residue interactions, i.e., attractive (Cys-Cys), neutral (Thr-Thr), and repulsive (Glu-Glu), are also studied for comparison with the native protein. Visual inspections show contrast and similarity in morphological evolutions of protein assembly, aggregation of small aggregates to a ramified network from low to high temperature with the aggregation of a Cys-polymer, and an entangled network of Glu and Thr polymers. Variations in mobility profiles of residues with the concentration of the protein suggest that the segmental characteristic of proteins is altered considerably by the self-assembly from that in its isolated state. The global motion of proteins and Cys polymer chains is enhanced by their interacting network at the low temperature where isolated chains remain quasi-static. Transition from globular to random coil transition, evidenced by the sharp variation in the radius of gyration, of an isolated protein is smeared due to self-assembly of interacting networks of many proteins. Scaling of the structure factor S(q) with the wave vector q provides estimates of effective dimension D of the mass distribution at multiple length scales in self-assembly. Crossover from solid aggregates (D ˜ 3) at low temperature to a ramified fibrous network (D ˜ 2) at high temperature is observed for the protein H3.1 and Cys polymers in contrast to little changes in mass distribution (D ˜ 1.6) of fibrous Glu- and Thr-chain configurations.

  7. Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Greenway, Steven C.; Rosenfeld, Jill A.

    2012-01-01

    Congenital heart disease (CHD) occurs in ∼1% of newborns. CHD arises from many distinct etiologies, ranging from genetic or genomic variation to exposure to teratogens, which elicit diverse cell and molecular responses during cardiac development. To systematically explore the relationships between...

  8. Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder: a nationwide population-based longitudinal study.

    Science.gov (United States)

    Tsao, Pei-Chen; Lee, Yu-Sheng; Jeng, Mei-Jy; Hsu, Ju-Wei; Huang, Kai-Lin; Tsai, Shih-Jen; Chen, Mu-Hong; Soong, Wen-Jue; Kou, Yu Ru

    2017-11-01

    In this retrospective nationwide population-based case-control study, we investigated the impact of congenital heart disease (CHD) on the development of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), which remains unclear. Children aged disorders (EDD) that were diagnosed before ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the control group. Multivariate Cox regression analysis revealed that the CHD group had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95% confidence interval CI 1.96-3.25) and ASD (aHR 1.97, 95% CI 1.11-3.52) after adjusting for confounding comorbidities. EDD, but not perinatal comorbidities were also independent risk factors for ADHD and ASD after adjustment. Subgroup analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17-22.60) and ASD (HR 80.68, 95% CI 39.96-176.12) was greatly increased in CHD subjects with EDD than in non-CHD subjects without EDD. These findings suggested that CHD at birth and EDD during early childhood were two independent risk factors for ADHD and ASD and that concurrent CHD and EDD might additively increase these risks.

  9. Bcs1p can rescue a large and productive cytochrome bc(1) complex assembly intermediate in the inner membrane of yeast mitochondria.

    Science.gov (United States)

    Conte, Laura; Trumpower, Bernard L; Zara, Vincenzo

    2011-01-01

    The yeast cytochrome bc(1) complex, a component of the mitochondrial respiratory chain, is composed of ten distinct protein subunits. In the assembly of the bc(1) complex, some ancillary proteins, such as the chaperone Bcs1p, are actively involved. The deletion of the nuclear gene encoding this chaperone caused the arrest of the bc(1) assembly and the formation of a functionally inactive bc(1) core structure of about 500-kDa. This immature bc(1) core structure could represent, on the one hand, a true assembly intermediate or, on the other hand, a degradation product and/or an incorrect product of assembly. The experiments here reported show that the gradual expression of Bcs1p in the yeast strain lacking this protein was progressively able to rescue the bc(1) core structure leading to the formation of the functional homodimeric bc(1) complex. Following Bcs1p expression, the mature bc(1) complex was also progressively converted into two supercomplexes with the cytochrome c oxidase complex. The capability of restoring the bc(1) complex and the supercomplexes was also possessed by the mutated yeast R81C Bcsp1. Notably, in the human ortholog BCS1L, the corresponding point mutation (R45C) was instead the cause of a severe bc(1) complex deficiency. Differently from the yeast R81C Bcs1p, two other mutated Bcs1p's (K192P and F401I) were unable to recover the bc(1) core structure in yeast. This study identifies for the first time a productive assembly intermediate of the yeast bc(1) complex and gives new insights into the molecular mechanisms involved in the last steps of bc(1) assembly. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation.

    Science.gov (United States)

    Conde, Carlos; Osswald, Mariana; Barbosa, João; Moutinho-Santos, Tatiana; Pinheiro, Diana; Guimarães, Sofia; Matos, Irina; Maiato, Helder; Sunkel, Claudio E

    2013-06-12

    Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase-promoting complex/cyclosome-inhibitory complexes to levels that ensure long-term SAC activity. We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function.

  11. Frecuencia y factores de riesgo asociados a desnutrición de niños con cardiopatía congénita Frequency and risk factors associated with malnutrition among children with congenital heart disease in a cardiology hospital

    Directory of Open Access Journals (Sweden)

    Miguel Angel Villasís-Keever

    2001-08-01

    más común en niños más pequeños y con cardiopatías cianógenas. Se necesitan programas orientados a las familias para prevenir y disminuir la desnutricion en estos niños. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlObjectives. To assess the frequency and risk factors of malnutrition among children with congenital heart disease (CHD. Material and methods. Between August 1997 and May 1998, a cross-sectional survey was conducted among 244 children, at the congenital heart disease ward of the Cardiology Hospital, National Medical Center "Siglo XXI", Mexican Institute of Social Security, in Mexico City. Study subjects were male and female children younger than 17 years, diagnosed with CHD and without any other congenital malformation. Weight/Age (W/A, Height/Age (H/A and Weight/Height (W/H were used to measure nutritional status; Z scores greater than -2 was the case definition of malnutrition. Risk factors investigated were age, sex, perinatal history, dietary factors and nutritional supplementation, socioeconomic status, and family composition and functionality. Four CHD groups were studied: acyanotic with and without pulmonary hypertension (APH, AWPH and, cyanotic with and without pulmonary hypertension (CPH, CWPH. Statistical analysis consisted of the chi-squared, Mann Whitney's U, and Kruskal-Wallis tests. Confounding variables were controlled for with a logistic regression model; odds ratios (OR and 95% confidence intervals (95%CI were calculated. Results. APH was the most frequent CHD (62.7%, followed by CWPH (15.6%, AWPH (11.5%, and CPH (10.2%. Malnutrition was identified in 40.9% children with the W/A index, in 24.6% with the H/A index; and in 31.1% with the W/H index. Infants and the CPH group had the worst nutritional status. Risk factors associated with malnutrition were: having a cyanotic CHD (OR 2.54; 95%CI, 0.98-6.58, lack of nutritional supplementation (OR 2.38; 95%CI, 1.06-5.34, and a

  12. Patient-related factors influencing detectability of coronary arteries in 320-row CT angiography in infants with complex congenital heart disease.

    Science.gov (United States)

    Yamasaki, Yuzo; Kawanami, Satoshi; Kamitani, Takeshi; Sagiyama, Koji; Shin, Seitaro; Hino, Takuya; Nagata, Hazumu; Yabuuchi, Hidetake; Nagao, Michinobu; Honda, Hiroshi

    2018-05-05

    To investigate the performance of second-generation 320-row computed tomographic (CT) angiography (CTA) in detecting coronary arteries and identify factors influencing visibility of the coronary arteries in infants with complex congenital heart disease (CHD). Data of 60 infants (aged 0-2 years, median 2 months) with complex CHD who underwent examination using 320-row CTA with low-dose prospective electrocardiogram-triggered volume target scanning were reviewed. The coronary arteries of each infant were assessed using a 0-4-point scoring system based on the number of coronary segments with a visible course. Clinical parameters, the CT value in the ascending aorta, image noise, and the radiation dose were subjected to univariate and multivariate analyses. The mean coronary score for all examinations was 2.6 ± 1.5 points. The mean attenuation in the ascending aorta was 306.7 ± 66.2 HU and the mean standard deviation was 21.7 ± 4.4. The mean effective radiation dose was 1.27 ± 0.39 mSv. Multivariate regression analysis showed significant correlations between coronary score and body weight (p < 0.05) and between coronary score and the CT value in the ascending aorta (p < 0.02). Second-generation 320-row CTA with prospective electrocardiogram-triggered volume target scanning and hybrid iterative reconstruction allows good visibility of the coronary arteries in infants with complex CHD. Body weight and the CT value in the ascending aorta are important factors influencing the visibility of the coronary arteries in infants.

  13. Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hu Frank B

    2009-03-01

    Full Text Available Abstract Background Increased activation of the renin-angiotensin system (RAS may be important in promoting coronary heart disease (CHD and renal dysfunction, but limited data are available on associations between angiotensin type 1 receptor (AGT1R and angiotensinogen (AGT genotypes in type 2 diabetes. Methods Study participants were diabetics from the Health Professionals Follow-Up Study (HPFS and the Nurses' Health Study (NHS. We analyzed single nucleotide polymorphisms (SNPs associated with cardiovascular pathophysiology (including AGT1R T573C, AGT1R A1166C, and AGT M235T and presence of renal dysfunction (eGFR2 or history of CHD. Results The AGT1R 1166 C-allele was associated with eGFR2 (multivariable OR 1.63 [1.01, 2.65] in the HPFS men (n = 733 and in the combined dataset (n = 1566 (OR 1.42 [1.02, 1.98]. The AGT1R 1166 C-allele was also associated with CHD in men (OR 1.57 [1.10, 2.24]. In NHS women (n = 833, AGT 235T-allele was associated with CHD (OR 1.72 [1.20, 2.47]. Removal of hypertension from the fully adjusted models did not influence results, suggesting that the associations may not be mediated by hypertension. There were significant interactions between sex and AGT1R 1166 C-allele (p = 0.008 and AGT M235T (p = 0.03 in models for CHD. No significant associations were seen between AGT1R T573 C-allele and renal dysfunction or CHD. Conclusion Polymorphisms in AGT1R and AGT genes are associated with renal dysfunction and CHD in type 2 diabetes and further support the important role of the RAS in these complications. Sex may modify associations between AGT1R 1166 C-allele and AGT 235T and CHD in type 2 diabetes.

  14. Can personality traits predict the future development of heart disease in hospitalized psychiatric veterans?

    Science.gov (United States)

    Williams, Wright; Kunik, Mark E; Springer, Justin; Graham, David P

    2013-11-01

    To examine which personality traits are associated with the new onset of chronic coronary heart disease (CHD) in psychiatric inpatients within 16 years after their initial evaluation. We theorized that personality measures of depression, anxiety, hostility, social isolation, and substance abuse would predict CHD development in psychiatric inpatients. We used a longitudinal database of psychological test data from 349 Veterans first admitted to a psychiatric unit between October 1, 1983, and September 30, 1987. Veterans Affairs and national databases were assessed to determine the development of new-onset chronic CHD over the intervening 16-year period. New-onset CHD developed in 154 of the 349 (44.1%) subjects. Thirty-one psychometric variables from five personality tests significantly predicted the development of CHD. We performed a factor analysis of these variables because they overlapped and four factors emerged, with positive adaptive functioning the only significant factor (OR=0.798, p=0.038). These results support previous research linking personality traits to the development of CHD, extending this association to a population of psychiatric inpatients. Compilation of these personality measures showed that 31 overlapping psychometric variables predicted those Veterans who developed a diagnosis of heart disease within 16 years after their initial psychiatric hospitalization. Our results suggest that personality variables measuring positive adaptive functioning are associated with a reduced risk of developing chronic CHD.

  15. Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer

    Science.gov (United States)

    2017-02-01

    and will assess if this resistance involves gain-of-function mutations in Ltv1, and if resistance can be overcome with drugs that direct...ribosome assembly factor Ltv1 in both yeast and TNBC cells, and that selective knockdown or silencing of CK1δ, or forced expression of Ltv1 mutant that...cannot be phosphorylated by CK1δ, blocks ribosome assembly in yeast and compromises the growth and survival of TNBC cells. Further, we have shown that

  16. Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease

    DEFF Research Database (Denmark)

    Nathanson, D; Zethelius, B; Berne, C

    2009-01-01

    stimulated GLP-1 levels and: (1) cardiovascular risk factors (blood pressure, lipids, urinary albumin, waist circumference and insulin sensitivity index [M/I] assessed by euglycaemic-hyperinsulinaemic clamp); and (2) impaired glucose tolerance (IGT) and type 2 diabetes mellitus. RESULTS: During the follow......AIMS/HYPOTHESIS: Besides the insulinotropic effects of glucagon-like peptide-1 (GLP-1) mimetics, their effects on endothelial dysfunction and myocardial ischaemia are of interest. No previous study has investigated associations between plasma levels of GLP-1 and CHD. METHODS: We investigated...... longitudinal relationships of fasting GLP-1 with the dynamic GLP-1 response after OGTT (difference between 60 min OGTT-stimulated and fasting GLP-1 levels [DeltaGLP-1]) and CHD in a population-based cohort of 71-year-old men. In the same cohort, we also cross-sectionally investigated the association between...

  17. Coronary heart disease events in Aboriginal Australians: incidence in an urban population.

    Science.gov (United States)

    Bradshaw, Pamela J; Alfonso, Helman S; Finn, Judith C; Owen, Julie; Thompson, Peter L

    2009-05-18

    To determine the incidence of coronary heart disease (CHD) events in an urban Aboriginal population. Cohort study of 906 Aboriginal people without CHD from 998 who had undergone risk-factor assessment in the Perth Aboriginal Atherosclerosis Risk Study (PAARS) in 1998-1999. PAARS cohort data were electronically linked to a range of databases that included Western Australian hospital morbidity data and death registry data. We analysed data from January 1980 to December 2006 to identify previous admissions for CHD from 1980 to baseline (1998-1999) and new events from baseline to 2006. First CHD event (hospital admission or death). There were 891 linked records for the 906 participants without previous CHD. The event rate was 12.6/1000 person-years (95% CI, 10.2-15.6/1000 person-years). Annual CHD event rates ranged from 8 to 18/1000 person-years. After adjustment for age (sex was not associated with the risk factors assessed), factors associated with risk of a CHD event in the PAARS cohort were a history of diabetes, overweight or obesity (indicated by body mass index), smoking, and hypertension, but not waist circumference. People with these risk factors were 1.9-2.7 times more likely to experience a CHD event. Compared with previously published information from a remote Aboriginal community in the Northern Territory, the incidence of CHD events among urban-dwelling Aboriginal people was not significantly different (P > 0.05 overall and for subgroups defined by age and sex). City-dwelling Aboriginal Australians have an incidence of CHD events comparable to that of Aboriginal people living in remote northern Australia.

  18. The Cell Cycle Timing of Centromeric Chromatin Assembly in Drosophila Meiosis Is Distinct from Mitosis Yet Requires CAL1 and CENP-C

    Science.gov (United States)

    Gorgescu, Walter; Tang, Jonathan; Costes, Sylvain V.; Karpen, Gary H.

    2012-01-01

    CENP-A (CID in flies) is the histone H3 variant essential for centromere specification, kinetochore formation, and chromosome segregation during cell division. Recent studies have elucidated major cell cycle mechanisms and factors critical for CENP-A incorporation in mitosis, predominantly in cultured cells. However, we do not understand the roles, regulation, and cell cycle timing of CENP-A assembly in somatic tissues in multicellular organisms and in meiosis, the specialized cell division cycle that gives rise to haploid gametes. Here we investigate the timing and requirements for CID assembly in mitotic tissues and male and female meiosis in Drosophila melanogaster, using fixed and live imaging combined with genetic approaches. We find that CID assembly initiates at late telophase and continues during G1 phase in somatic tissues in the organism, later than the metaphase assembly observed in cultured cells. Furthermore, CID assembly occurs at two distinct cell cycle phases during male meiosis: prophase of meiosis I and after exit from meiosis II, in spermatids. CID assembly in prophase I is also conserved in female meiosis. Interestingly, we observe a novel decrease in CID levels after the end of meiosis I and before meiosis II, which correlates temporally with changes in kinetochore organization and orientation. We also demonstrate that CID is retained on mature sperm despite the gross chromatin remodeling that occurs during protamine exchange. Finally, we show that the centromere proteins CAL1 and CENP-C are both required for CID assembly in meiosis and normal progression through spermatogenesis. We conclude that the cell cycle timing of CID assembly in meiosis is different from mitosis and that the efficient propagation of CID through meiotic divisions and on sperm is likely to be important for centromere specification in the developing zygote. PMID:23300382

  19. Severe obesity, heart disease, and death among white, African American, and Hispanic postmenopausal women.

    Science.gov (United States)

    McTigue, Kathleen M; Chang, Yue-Fang; Eaton, Charles; Garcia, Lorena; Johnson, Karen C; Lewis, Cora E; Liu, Simin; Mackey, Rachel H; Robinson, Jennifer; Rosal, Milagros C; Snetselaar, Linda; Valoski, Alice; Kuller, Lewis H

    2014-03-01

    To compare mortality, nonfatal coronary heart disease (CHD), and congestive heart failure (CHF) risk across BMI categories in white, African American, and Hispanic women, with a focus on severe obesity (BMI ≥ 40), and examine heterogeneity in weight-related CHD risk. Among 156,775 Women's Health Initiative observational study and clinical trial participants (September 1993-12 September 2005), multivariable Cox models estimated relative risk for mortality, CHD, and CHF. CHD incidence was calculated by anthropometry, race, and cardiovascular risk factors (CVRF). Mortality, nonfatal CHD, and CHF incidence generally rose with BMI category. For severe obesity versus normal BMI, hazard ratios (HRs, 95% confidence interval) for mortality were 1.97 (1.77-2.20) in white, 1.55 (1.20-2.00) in African American, and 2.59 (1.55-4.31) in Hispanic women; for CHD, HRs were 2.05 (1.80-2.35), 2.24 (1.57-3.19), and 2.95 (1.60-5.41) respectively; for CHF, HRs were 5.01 (4.33-5.80), 3.60 (2.30-5.62), and 6.05 (2.49-14.69). CVRF variation resulted in substantial variation in CHD rates across BMI categories, even in severe obesity. CHD incidence was similar by race/ethnicity when differences in BMI or CVRF were accounted for. Severe obesity increases mortality, nonfatal CHD, and CHF risk in women of diverse race/ethnicity. CVRF heterogeneity contributes to variation in CHD incidence even in severe obesity. Copyright © 2012 The Obesity Society.

  20. The intermembrane space protein Erv1 of Trypanosoma brucei is essential for mitochondrial Fe-S cluster assembly and operates alone

    Czech Academy of Sciences Publication Activity Database

    Haindrich, Alexander C.; Boudova, M.; Vancová, Marie; Peña-Diaz, Priscila; Horáková, Eva; Lukeš, Julius

    2017-01-01

    Roč. 214, JUN (2017), s. 47-51 ISSN 0166-6851 R&D Projects: GA ČR GA15-21974S; GA ČR(CZ) GA16-18699S Institutional support: RVO:60077344 Keywords : Trypanosoma * Erv1 * Fe-S cluster assembly * mitochondrion Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 2.536, year: 2016

  1. Explaining the increase in coronary heart disease mortality in Syria between 1996 and 2006

    Directory of Open Access Journals (Sweden)

    Rastam Samer

    2012-09-01

    Full Text Available Abstract Background Despite advances made in treating coronary heart disease (CHD, mortality due to CHD in Syria has been increasing for the past two decades. This study aims to assess CHD mortality trends in Syria between 1996 and 2006 and to investigate the main factors associated with them. Methods The IMPACT model was used to analyze CHD mortality trends in Syria based on numbers of CHD patients, utilization of specific treatments, trends in major cardiovascular risk factors in apparently healthy persons and CHD patients. Data sources for the IMPACT model included official statistics, published and unpublished surveys, data from neighboring countries, expert opinions, and randomized trials and meta-analyses. Results Between 1996 and 2006, CHD mortality rate in Syria increased by 64%, which translates into 6370 excess CHD deaths in 2006 as compared to the number expected had the 1996 baseline rate held constant. Using the IMPACT model, it was estimated that increases in cardiovascular risk factors could explain approximately 5140 (81% of the CHD deaths, while some 2145 deaths were prevented or postponed by medical and surgical treatments for CHD. Conclusion Most of the recent increase in CHD mortality in Syria is attributable to increases in major cardiovascular risk factors. Treatments for CHD were able to prevent about a quarter of excess CHD deaths, despite suboptimal implementation. These findings stress the importance of population-based primary prevention strategies targeting major risk factors for CHD, as well as policies aimed at improving access and adherence to modern treatments of CHD.

  2. In situ observation of self-assembled Fe{sub 13}Ge{sub 8} nanowires growth on anisotropic Ge (1 1 0) surface

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhi-Peng, E-mail: LI.Zhipeng@nims.go.jp [Department of Physics, National University of Singapore, 2 Science Drive 3, S117542 (Singapore); Global Research Center for Environment and Energy based on Nanomaterials Science, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Tok, Engsoon [Department of Physics, National University of Singapore, 2 Science Drive 3, S117542 (Singapore); Foo, Yonglim [Institute of Materials Research and Engineering, 3 Research Link, S117602 (Singapore)

    2012-02-15

    Highlights: Black-Right-Pointing-Pointer Epitaxial Fe{sub 13}Ge{sub 8} nanowries growth and shape evolution on Ge (1 1 0) studied by in situ UHV-TEM. Black-Right-Pointing-Pointer Single type of morphology and unique orientation of nanowires formed at elevated temperatures. Black-Right-Pointing-Pointer Uniform control of the nanowires morphology at different temperatures can be succeeded. -- Abstract: Self-assembled iron germanide nanowires (NWs) were grown by directly depositing Fe onto a Ge (1 1 0) substrate, in an in situ ultra-high vacuum transmission electron microscope from 430 to 500 Degree-Sign C. All observed NWs had a similar length/width aspect ratio ({approx}8:1) at all deposition temperatures, as well as the same elongation orientation with respect to the underlying Ge (1 1 0) substrate. The growth dynamics was investigated by real time observations of NWs growth at elevated temperatures. It is elucidated that the formation of NWs in similar shape at all deposited temperatures is attributed to the similar activation energy barriers in length and width of NWs, which can result in the constant growth rate independent of growth temperatures. Furthermore, the difference in pre-exponential factor along the length and width of growing islands arose due to the anisotropic constraint of the Ge (1 1 0) substrate, leading to the unique elongation of NWs. This growth dynamics suggests the possibility of uniform control of the morphology of self-assembled NWs, as well as other morphologies of bottom-up fabricated devices, at different deposition temperatures.

  3. Exercise frequency, health risk factors, and diseases of the elderly.

    Science.gov (United States)

    Kemmler, Wolfgang; von Stengel, Simon

    2013-11-01

    To determine the effect of exercise frequency on various diseases and risk factors of the elderly. Retrospective analysis of a randomized controlled 18-month exercise trial. University ambulatory group setting. Community-dwelling women aged ≥65 years (N=162) in the area of Northern Bavaria. Mixed, intense aerobic, resistance, and balance protocol for 18 months. Subjects were retrospectively subdivided into 2 groups according to their effective attendance over 18 months (>1-exercise group (LF-EG) and the high-frequency exercise group (HF-EG) were observed for lumbar spine BMD (HF-EG, 2.4%±2.8% vs LF-EG, 0.3%±2.2%; Pexercise groups were observed for 10-year CHD risk (-1.94%±4.14% vs -2.00%±3.13%; P=.943) and number of falls (0.95±1.36 vs 1.03±1.21 falls/person). Comparing the LF-EG with the less active control group (n=47), only nonsignificant effects for fall number (P=.065) and 10-year CHD risk (P=.178) were evaluated. Although this result might not be generalizable across all exercise types and cohorts, it indicates that an overall exercise frequency of at least 2 sessions/wk may be crucial for impacting bone and muscle mass of elderly subjects. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  4. Self-assembly of self-assembled molecular triangles

    Indian Academy of Sciences (India)

    While the solution state structure of 1 can be best described as a trinuclear complex, in the solidstate well-fashioned intermolecular - and CH- interactions are observed. Thus, in the solid-state further self-assembly of already self-assembled molecular triangle is witnessed. The triangular panels are arranged in a linear ...

  5. Population assessment of future trajectories in coronary heart disease mortality.

    Directory of Open Access Journals (Sweden)

    Rosa Björk Thorolfsdottir

    Full Text Available BACKGROUND: Coronary heart disease (CHD mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. METHODS AND FINDINGS: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25-74. Calculations were based on combining: i data on population numbers and projections (Statistics Iceland, ii population risk factor levels and projections (Refine Reykjavik study, and iii effectiveness of specific risk factor reductions (published meta-analyses. Projections for three contrasting scenarios were compared: (1 If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. (2 If recent trends in risk factors (past 5 years continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3 Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. CONCLUSIONS: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future.

  6. Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

    Science.gov (United States)

    Sobti, R C; Maithil, Nishi; Thakur, Hitender; Sharma, Yashpaul; Talwar, K K

    2010-08-01

    The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

  7. EB1 is required for primary cilia assembly in fibroblasts

    DEFF Research Database (Denmark)

    Schrøder, Jacob M; Schneider, Linda; Christensen, Søren T

    2007-01-01

    EB1 is a small microtubule (MT)-binding protein that associates preferentially with MT plus ends and plays a role in regulating MT dynamics. EB1 also targets other MT-associated proteins to the plus end and thereby regulates interactions of MTs with the cell cortex, mitotic kinetochores, and diff...... that localization of EB1 at the centriole/basal body is required for primary cilia assembly in fibroblasts....

  8. Scalable Directed Assembly of Highly Crystalline 2,7-Dioctyl[1]benzothieno[3,2- b][1]benzothiophene (C8-BTBT) Films.

    Science.gov (United States)

    Chai, Zhimin; Abbasi, Salman A; Busnaina, Ahmed A

    2018-05-30

    Assembly of organic semiconductors with ordered crystal structure has been actively pursued for electronics applications such as organic field-effect transistors (OFETs). Among various film deposition methods, solution-based film growth from small molecule semiconductors is preferable because of its low material and energy consumption, low cost, and scalability. Here, we show scalable and controllable directed assembly of highly crystalline 2,7-dioctyl[1]benzothieno[3,2- b][1]benzothiophene (C8-BTBT) films via a dip-coating process. Self-aligned stripe patterns with tunable thickness and morphology over a centimeter scale are obtained by adjusting two governing parameters: the pulling speed of a substrate and the solution concentration. OFETs are fabricated using the C8-BTBT films assembled at various conditions. A field-effect hole mobility up to 3.99 cm 2 V -1 s -1 is obtained. Owing to the highly scalable crystalline film formation, the dip-coating directed assembly process could be a great candidate for manufacturing next-generation electronics. Meanwhile, the film formation mechanism discussed in this paper could provide a general guideline to prepare other organic semiconducting films from small molecule solutions.

  9. Fuel assembly reconstitution

    International Nuclear Information System (INIS)

    Morgado, Mario M.; Oliveira, Monica G.N.; Ferreira Junior, Decio B.M.; Santos, Barbara O. dos; Santos, Jorge E. dos

    2009-01-01

    Fuel failures have been happened in Nuclear Power Plants worldwide, without lost of integrity and safety, mainly for the public, environment and power plants workers. The most common causes of these events are corrosion (CRUD), fretting and pellet cladding interaction. These failures are identified by increasing the activity of fission products, verified by chemical analyses of reactor coolant. Through these analyses, during the fourth operation cycle of Angra 2 Nuclear Power Plant, was possible to observe fuel failure indication. This indication was confirmed in the end of the cycle during the unloading of reactor core through leakage tests of fuel assembly, using the equipment called 'In Mast Sipping' and 'Box Sipping'. After confirmed, the fuel assembly reconstitution was scheduled, and happened in April, 2007, where was identified the cause and the fuel rod failure, which was substitute by dummy rods (zircaloy). The cause was fretting by 'debris'. The actions to avoid and prevent fuel assemblies failures are important. The goals of this work are to describe the methodology of fuel assembly reconstitution using the FARE (Fuel Assembly Reconstitution Equipment) system, to describe the results of this task in economic and security factors of the company and show how the fuel assembly failures are identified during operation and during the outage. (author)

  10. The origin of the supernumerary subunits and assembly factors of complex I: A treasure trove of pathway evolution

    NARCIS (Netherlands)

    Elurbe, D.M.; Huynen, M.A.

    2016-01-01

    We review and document the evolutionary origin of all complex I assembly factors and nine supernumerary subunits from protein families. Based on experimental data and the conservation of critical residues we identify a spectrum of protein function conservation between the complex I representatives

  11. The effect of cyanotic and acyanotic congenital heart disease on children’s growth velocity

    Directory of Open Access Journals (Sweden)

    Dewi Awaliyah Ulfah

    2017-06-01

    Full Text Available Background Congenital heart disease (CHD can lead to failure to thrive. Decreased energy intake, malabsorption, increased energy requirements, and decreased growth factors (growth hormone/insulin-like growth factor 1 axis are related to malnutrition and growth retardation in children with CHD. Objective Tocompare the impact of cyanotic and acyanotic CHD on children’s growth velocity (using the 2009 WHO growth velocity chart. Methods This study was conducted in patients less than 24 months of age with CHD in the Pediatric Cardiology Specialist Unit Dr. Moewardi Hospital, Surakarta, Central Java, from December 2016 to February 2017. Subjects’ weights were evaluated at the beginning of the study and two months later. Data were compared to the WHO Growth Velocity chart and analyzed by Chi-square test. Results Of 46 patients with CHD (23 cyanotic, 23 acyanotic, 10 patients (21.7% were identified with failure to thrive, i.e., 5th percentile for growth velocity than were children with cyanotic CHD (OR 5.600; 95%CI 1.038 to 30.204; P=0.032. Acute upper respiratory tract infection was not significantly associated with growth velocity (OR 2.273; 95%CI 0.545 to 9.479; P=0.253. Conclusion Children with cyanotic CHD have 5.6 times higher risk of failure to thrive than children with acyanotic CHD.

  12. Chlamydomonas DYX1C1/PF23 is essential for axonemal assembly and proper morphology of inner dynein arms.

    Directory of Open Access Journals (Sweden)

    Ryosuke Yamamoto

    2017-09-01

    Full Text Available Cytoplasmic assembly of ciliary dyneins, a process known as preassembly, requires numerous non-dynein proteins, but the identities and functions of these proteins are not fully elucidated. Here, we show that the classical Chlamydomonas motility mutant pf23 is defective in the Chlamydomonas homolog of DYX1C1. The pf23 mutant has a 494 bp deletion in the DYX1C1 gene and expresses a shorter DYX1C1 protein in the cytoplasm. Structural analyses, using cryo-ET, reveal that pf23 axonemes lack most of the inner dynein arms. Spectral counting confirms that DYX1C1 is essential for the assembly of the majority of ciliary inner dynein arms (IDA as well as a fraction of the outer dynein arms (ODA. A C-terminal truncation of DYX1C1 shows a reduction in a subset of these ciliary IDAs. Sucrose gradients of cytoplasmic extracts show that preassembled ciliary dyneins are reduced compared to wild-type, which suggests an important role in dynein complex stability. The role of PF23/DYX1C1 remains unknown, but we suggest that DYX1C1 could provide a scaffold for macromolecular assembly.

  13. Mechanics of a crushable pebble assembly using discrete element method

    International Nuclear Information System (INIS)

    Annabattula, R.K.; Gan, Y.; Zhao, S.; Kamlah, M.

    2012-01-01

    The influence of crushing of individual pebbles on the overall strength of a pebble assembly is investigated using discrete element method. An assembly comprising of 5000 spherical pebbles is assigned with random critical failure energies with a Weibull distribution in accordance with the experimental observation. Then, the pebble assembly is subjected to uni-axial compression (ε 33 =1.5%) with periodic boundary conditions. The crushable pebble assembly shows a significant difference in stress–strain response in comparison to a non-crushable pebble assembly. The analysis shows that a ideal plasticity like behaviour (constant stress with increase in strain) is the characteristic of a crushable pebble assembly with sudden damage. The damage accumulation law plays a critical role in determining the critical stress while the critical number of completely failed pebbles at the onset of critical stress is independent of such a damage law. Furthermore, a loosely packed pebble assembly shows a higher crush resistance while the critical stress is insensitive to the packing factor (η) of the assembly.

  14. Increased risk for congenital heart defects in children carrying the ABCB1 Gene C3435T polymorphism and maternal periconceptional toxicants exposure.

    Directory of Open Access Journals (Sweden)

    Chuan Wang

    Full Text Available BACKGROUNDS: The etiology of congenital heart defect (CHD is commonly believed to involve the interaction of multiple environmental and genetic factors. This study aimed to explore the joint effects of the ABCB1 gene C3435T polymorphism and maternal periconceptional toxicants exposure on the CHD risk in a Han Chinese population. METHODS: An age and gender matched case-control study with standardized data collection involving 201 pairs was conducted. Periconceptional toxicants exposure was obtained through a structured questionnaire. A job exposure matrix (JEM was used for toxicants exposure assessment. Genotyping of the ABCB1 C3435T polymorphism was performed by sequencing. Logistic regression analysis was performed to assess the joint effects of the ABCB1 gene C3435T polymorphism and toxicants exposure on the risk of CHD. Placenta tissues and umbilical cords were collected to investigate the impact of C3435T polymorphism on the transcription and translation activities of ABCB1 gene. RESULTS: MATERNAL PERICONCEPTIONAL EXPOSURES TO PHTHALATES (ADJUSTED OR: 1.6; 95%CI: 1.0-2.6 and alkylphenolic compounds (adjusted OR:1.8; 95%CI:1.1-3.0 were associated with a higher incidence of CHDs in general. More cases were carriers of the ABCB1 CC/CT genotypes (OR: 2.0, 95%CI: 1.1-3.5, P-value: 0.021. Children carrying the CC/CT genotype and periconceptionally exposed to phthalates and alkylphenolic compounds suffered almost 3.5-fold increased risk of having CHD than non-exposed children with TT genotype (adjusted OR: 3.5, 95%CI: 1.5-7.9, P-value: 0.003, and the OR changed to 4.4 for septal defects (adjusted OR: 4.4,95%CI:1.8-10.9,P-value:0.001. The ABCB1 mRNA expression of the TT genotype was significantly higher than that of the CC genotype (P = 0.03. Compared with TT genotype, lower P-glycoprotein expression was observed for the CC/CT genotypes. CONCLUSION: The C3435T polymorphism in the ABCB1 gene of fetus increases the risks of CHD in a Han Chinese

  15. Firefighters and on-duty deaths from coronary heart disease: a case control study

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    Soteriades Elpidoforos S

    2003-11-01

    Full Text Available Abstract Background Coronary heart disease (CHD is responsible for 45% of on-duty deaths among United States firefighters. We sought to identify occupational and personal risk factors associated with on-duty CHD death. Methods We performed a case-control study, selecting 52 male firefighters whose CHD deaths were investigated by the National Institute for Occupational Safety and Health. We selected two control populations: 51 male firefighters who died of on-duty trauma; and 310 male firefighters examined in 1996/1997, whose vital status and continued professional activity were re-documented in 1998. Results The circadian pattern of CHD deaths was associated with emergency response calls: 77% of CHD deaths and 61% of emergency dispatches occurred between noon and midnight. Compared to non-emergency duties, fire suppression (OR = 64.1, 95% CI 7.4–556; training (OR = 7.6, 95% CI 1.8–31.3 and alarm response (OR = 5.6, 95% CI 1.1–28.8 carried significantly higher relative risks of CHD death. Compared to the active firefighters, the CHD victims had a significantly higher prevalence of cardiovascular risk factors in multivariate regression models: age ≥ 45 years (OR 6.5, 95% CI 2.6–15.9, current smoking (OR 7.0, 95% CI 2.8–17.4, hypertension (OR 4.7, 95% CI 2.0–11.1, and a prior diagnosis of arterial-occlusive disease (OR 15.6, 95% CI 3.5–68.6. Conclusions Our findings strongly support that most on-duty CHD fatalities are work-precipitated and occur in firefighters with underlying CHD. Improved fitness promotion, medical screening and medical management could prevent many of these premature deaths.

  16. [Relationship between Ghrelin polymorphism and serum lipoprotein levels in Han Chinese with or without coronary heart disease risk factors].

    Science.gov (United States)

    Xie, Xuan; Zhang, Jing; Wang, Yu-huan; Wang, Jun-hong; Zhang, Chun-hong; Ni, Hong-yan; Yuan, Xiao-hong

    2008-04-01

    To investigate the relationship between polymorphism of Ghrelin gene and serum levels of lipoprotein in Han Chinese with or without coronary heart disease (CHD) risk factors. PCR restriction fragment length polymorphism assay was used to detect the distribution of genotypes of Ghrelin gene in 225 Han Chinese (40 to 69 years-old) with CHD risk factors, 78 subjects without CHD risk factors served as normal controls. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein (VLDL) were measured to analyze the relationship with the polymorphism of Ghrelin gene. Ghrelin genotype frequencies of AA, AG, GG (0.975, 0.025, 0.00 in control group and 0.956, 0.040, 0.004 in the high-risk group, all P > 0.05) as well as the allele frequencies of A, G (0.987, 0.013 in control group and 0.976, 0.024 in the high-risk group, all P > 0.05) were similar between the groups. HDL-C levels of the Arg/Gln carriers were significantly lower than those of Arg/Arg carriers in control group and in the high-risk group (all P < 0.05). Arg/Gln carriers were associated lower HDL-C levels in Han Chinese.

  17. Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements.

    Science.gov (United States)

    Haskett, Timothy L; Terpolilli, Jason J; Ramachandran, Vinoy K; Verdonk, Callum J; Poole, Phillip S; O'Hara, Graham W; Ramsay, Joshua P

    2018-03-01

    Tripartite integrative and conjugative elements (ICE3) are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases-or recombination directionality factors-RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a "master controller" of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer.

  18. Assembly, alignment and test of the Transiting Exoplanet Survey Satellite (TESS) optical assemblies

    Science.gov (United States)

    Balonek, Gregory; Brown, Joshua J.; Andre, James E.; Chesbrough, Christian D.; Chrisp, Michael P.; Dalpiaz, Michael; Lennon, Joseph; Richards, B. C.; Clark, Kristin E.

    2017-08-01

    The Transiting Exoplanet Survey Satellite (TESS) will carry four visible waveband, seven-element, refractive F/1.4 lenses, each with a 34 degree diagonal field of view. This paper describes the methods used for the assembly, alignment and test of the four flight optical assemblies. Prior to commencing the build of the four flight optical assemblies, a Risk Reduction Unit (RRU) was successfully assembled and tested [1]. The lessons learned from the RRU were applied to the build of the flight assemblies. The main modifications to the flight assemblies include the inking of the third lens element stray light mitigation, tighter alignment tolerances, and diamond turning for critical mechanical surfaces. Each of the optical assemblies was tested interferometrically and measured with a low coherence distance measuring interferometer (DMI) to predict the optimal shim thickness between the lens assembly and detector before -75°C environmental testing. In addition to individual test data, environmental test results from prior assemblies allow for the exploration of marginal performance differences between each of the optical assemblies.

  19. Overweight Status, Obesity, and Risk Factors for Coronary Heart Disease in Adults with Intellectual Disability

    Science.gov (United States)

    Henderson, C. Michael; Robinson, Laura M.; Davidson, Philip W.; Haveman, Meindert; Janicki, Matthew P.; Albertini, Giorgio

    2008-01-01

    Research indicates that adults with intellectual disabilities (ID) have high rates of overweight status/obesity (OSO). OSO is associated with several important risk factors for coronary heart disease (CHD). This study focused on assessing whether such risk factors are being identified in adults with ID who are receiving their healthcare in…

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

    Science.gov (United States)

    Fiskå, Bendik S; Ariansen, Inger; Graff-Iversen, Sidsel; Tell, Grethe S; Egeland, Grace M; Næss, Øyvind

    2015-01-01

    To investigate self-reported family history (FH) of premature myocardial infarction (MI) in first-degree relatives as a risk factor for coronary heart disease (CHD) mortality, and assess whether any observed effect could be explained by current or life course socioeconomic position. 130,066 participants from Cohort of Norway were examined during 1994-2003. A subgroup (n=84,631) had additional life course socioeconomic data. Using Cox proportional hazard analyses, we calculated hazard ratios (HR) for CHD mortality, assessed by linkages to the Norwegian Cause of Death Registry through 2009. For subgroup analyses, we created an index of life course socioeconomic position, and assessed its role as a potential confounder in the association of FH with CHD. For men, MI in parents and siblings were both a significant risk factor for CHD mortality after adjusting for established risk factors and current socioeconomic conditions; the highest risk was with MI in siblings (HR: 1.44 [1.19-1.75]). For women, FH constituted significant risk after similar adjustment only for those with MI in parents plus siblings (HR: 1.78 [1.16-2.73]). Adjusting for current and life course socioeconomic conditions only marginally lowered the estimates, and those with FH did not have worse life course socioeconomic position than those without. FH of premature MI is an independent risk factor for CHD mortality that differs in magnitude of effect by the sex of the index person and type of familial relationship. Life course socioeconomic position has little impact on the association between FH and CHD, suggesting the effect is not confounded by this. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Incidence, risk factors and heritability of hind limb lameness in dogs with canine hip dysplasia in a 8 year follow up study of a birth cohort of Dutch boxer dogs

    NARCIS (Netherlands)

    Hagen, van M.A.E.; Ducro, B.J.; Broek, van de J.; Knol, B.W.

    2005-01-01

    Objective-To determine incidence, risk factors, and heritability estimates of hind limb lameness caused by hip dysplasia in a birth cohort of Boxers. Animals-1,733 Boxers from 325 litters. Procedure-Status of Boxers with respect to clinical signs of canine hip dysplasia (cCHD) was registered during

  2. Analysis of the initiating events in HIV-1 particle assembly and genome packaging.

    Directory of Open Access Journals (Sweden)

    Sebla B Kutluay

    2010-11-01

    Full Text Available HIV-1 Gag drives a number of events during the genesis of virions and is the only viral protein required for the assembly of virus-like particles in vitro and in cells. Although a reasonable understanding of the processes that accompany the later stages of HIV-1 assembly has accrued, events that occur at the initiation of assembly are less well defined. In this regard, important uncertainties include where in the cell Gag first multimerizes and interacts with the viral RNA, and whether Gag-RNA interaction requires or induces Gag multimerization in a living cell. To address these questions, we developed assays in which protein crosslinking and RNA/protein co-immunoprecipitation were coupled with membrane flotation analyses in transfected or infected cells. We found that interaction between Gag and viral RNA occurred in the cytoplasm and was independent of the ability of Gag to localize to the plasma membrane. However, Gag:RNA binding was stabilized by the C-terminal domain (CTD of capsid (CA, which participates in Gag-Gag interactions. We also found that Gag was present as monomers and low-order multimers (e.g. dimers but did not form higher-order multimers in the cytoplasm. Rather, high-order multimers formed only at the plasma membrane and required the presence of a membrane-binding signal, but not a Gag domain (the CA-CTD that is essential for complete particle assembly. Finally, sequential RNA-immunoprecipitation assays indicated that at least a fraction of Gag molecules can form multimers on viral genomes in the cytoplasm. Taken together, our results suggest that HIV-1 particle assembly is initiated by the interaction between Gag and viral RNA in the cytoplasm and that this initial Gag-RNA encounter involves Gag monomers or low order multimers. These interactions per se do not induce or require high-order Gag multimerization in the cytoplasm. Instead, membrane interactions are necessary for higher order Gag multimerization and subsequent

  3. The gender gap in risk factor control: Effects of age and education on the control of cardiovascular risk factors in male and female coronary patients. The EUROASPIRE IV study by the European Society of Cardiology.

    Science.gov (United States)

    De Smedt, Delphine; De Bacquer, Dirk; De Sutter, Johan; Dallongeville, Jean; Gevaert, Sofie; De Backer, Guy; Bruthans, Jan; Kotseva, Kornelia; Reiner, Željko; Tokgözoğlu, Lale; Clays, Els

    2016-04-15

    The aim of this study was to investigate gender related differences in the management and risk factor control of patients with coronary heart disease (CHD), taking into account their age and educational level. Analyses are based on the EUROASPIRE IV (EUROpean Action on Secondary and Primary Prevention through Intervention to Reduce Events) survey. Males and females between 18 and 80years of age, hospitalized for a first or recurrent coronary event were included in the study. Data were available for 7998 patients of which 75.6% were males. Overall, females had a worse risk factor profile compared to males and were more likely to have 3 or more risk factors (29.5% vs. 34.9%; p<0.001) across all age groups. A significant gender by education interaction (p<0.05) and gender by age interaction effect (p<0.05) was found. Furthermore, males were more likely to have a LDL-cholesterol on target (OR=1.50[1.28-1.76]), a HbA1c on target (OR=1.33[1.07-1.64]), to be non-obese (OR=1.45[1.30-1.62]) and perform adequate physical activity (OR=1.71[1.46-2.00]). In contrast males were less likely to be non-smokers (OR=0.71[0.60-0.83]). Furthermore, males were less likely to have made a dietary change (OR=0.78[0.64-0.95]) or a smoking cessation attempt (OR=0.70[0.50-0.96]) and more likely to have received smoking cessation advice if they were smokers (OR=1.52[1.10-2.09]). Whereas gender differences in CHD treatment are limited, substantial differences were found regarding target achievement. The largest gender difference was seen in less educated and elderly patients. The gender gap declined with decreasing age and higher education. Copyright © 2016. Published by Elsevier Ireland Ltd.

  4. Central Reactivity Measurements on Assemblies 1 and 3 of the Fast Reactor FR0

    International Nuclear Information System (INIS)

    Londen, S.O.

    1966-01-01

    The reactivity effects of small samples of various materials have been measured, by the period method at the core centre of Assemblies 1 and 3 of the fast zero power reactor FR0. For some materials the reactivity change as a function of sample size has also been determined experimentally. The core of Assembly 1 consisted only of uranium enriched to 20 % whereas the core of Assembly 3 was diluted with 30 % graphite. The results have been compared with calculated values obtained with a second-order transport-theoretical perturbation model and using differently shielded cross sections depending upon sample size. Qualitative agreement has generally been found, although discrepancies still exist. The spectrum perturbation caused by the experimental arrangement has been analyzed and found to be rather important

  5. Central Reactivity Measurements on Assemblies 1 and 3 of the Fast Reactor FR0

    Energy Technology Data Exchange (ETDEWEB)

    Londen, S O

    1966-01-15

    The reactivity effects of small samples of various materials have been measured, by the period method at the core centre of Assemblies 1 and 3 of the fast zero power reactor FR0. For some materials the reactivity change as a function of sample size has also been determined experimentally. The core of Assembly 1 consisted only of uranium enriched to 20 % whereas the core of Assembly 3 was diluted with 30 % graphite. The results have been compared with calculated values obtained with a second-order transport-theoretical perturbation model and using differently shielded cross sections depending upon sample size. Qualitative agreement has generally been found, although discrepancies still exist. The spectrum perturbation caused by the experimental arrangement has been analyzed and found to be rather important.

  6. Modelling Future Coronary Heart Disease Mortality to 2030 in the British Isles.

    Directory of Open Access Journals (Sweden)

    John Hughes

    Full Text Available Despite rapid declines over the last two decades, coronary heart disease (CHD mortality rates in the British Isles are still amongst the highest in Europe. This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking and physical activity levels, dietary salt and saturated fat intakes on future CHD mortality in three countries: Northern Ireland (NI, Republic of Ireland (RoI and Scotland.CHD mortality models previously developed and validated in each country were extended to predict potential reductions in CHD mortality from 2010 (baseline year to 2030. Risk factor trends data from recent surveys at baseline were used to model alternative future risk factor scenarios: Absolute decreases in (i smoking prevalence and (ii physical inactivity rates of up to 15% by 2030; relative decreases in (iii dietary salt intake of up to 30% by 2030 and (iv dietary saturated fat of up to 6% by 2030. Probabilistic sensitivity analyses were then conducted.Projected populations in 2030 were 1.3, 3.4 and 3.9 million in NI, RoI and Scotland respectively (adults aged 25-84. In 2030: assuming recent declining mortality trends continue: 15% absolute reductions in smoking could decrease CHD deaths by 5.8-7.2%. 15% absolute reductions in physical inactivity levels could decrease CHD deaths by 3.1-3.6%. Relative reductions in salt intake of 30% could decrease CHD deaths by 5.2-5.6% and a 6% reduction in saturated fat intake might decrease CHD deaths by some 7.8-9.0%. These projections remained stable under a wide range of sensitivity analyses.Feasible reductions in four cardiovascular risk factors (already achieved elsewhere could substantially reduce future coronary deaths. More aggressive polices are therefore needed in the British Isles to control tobacco, promote healthy food and increase physical activity.

  7. Hemolysin coregulated protein 1 as a molecular gluing unit for the assembly of nanoparticle hybrid structures

    Directory of Open Access Journals (Sweden)

    Tuan Anh Pham

    2016-03-01

    Full Text Available Hybrid nanoparticle (NP structures containing organic building units such as polymers, peptides, DNA and proteins have great potential in biosensor and electronic applications. The nearly free modification of the polymer chain, the variation of the protein and DNA sequence and the implementation of functional moieties provide a great platform to create inorganic structures of different morphology, resulting in different optical and magnetic properties. Nevertheless, the design and modification of a protein structure with functional groups or sequences for the assembly of biohybrid materials is not trivial. This is mainly due to the sensitivity of its secondary, tertiary and quaternary structure to the changes in the interaction (e.g., hydrophobic, hydrophilic, electrostatic, chemical groups between the protein subunits and the inorganic material. Here, we use hemolysin coregulated protein 1 (Hcp1 from Pseudomonas aeruginosa as a building and gluing unit for the formation of biohybrid structures by implementing cysteine anchoring points at defined positions on the protein rim (Hcp1_cys3. We successfully apply the Hcp1_cys3 gluing unit for the assembly of often linear, hybrid structures of plasmonic gold (Au NP, magnetite (Fe3O4 NP, and cobalt ferrite nanoparticles (CoFe2O4 NP. Furthermore, the assembly of Au NPs into linear structures using Hcp1_cys3 is investigated by UV–vis spectroscopy, TEM and cryo-TEM. One key parameter for the formation of Au NP assembly is the specific ionic strength in the mixture. The resulting network-like structure of Au NPs is characterized by Raman spectroscopy, showing surface-enhanced Raman scattering (SERS by a factor of 8·104 and a stable secondary structure of the Hcp1_cys3 unit. In order to prove the catalytic performance of the gold hybrid structures, they are used as a catalyst in the reduction reaction of 4-nitrophenol showing similar catalytic activity as the pure Au NPs. To further extend the

  8. The Escherichia coli P and Type 1 Pilus Assembly Chaperones PapD and FimC Are Monomeric in Solution

    Energy Technology Data Exchange (ETDEWEB)

    Sarowar, Samema; Hu, Olivia J.; Werneburg, Glenn T.; Thanassi, David G.; Li, Huilin; Christie, P. J.

    2016-06-27

    ABSTRACT

    The chaperone/usher pathway is used by Gram-negative bacteria to assemble adhesive surface structures known as pili or fimbriae. Uropathogenic strains ofEscherichia coliuse this pathway to assemble P and type 1 pili, which facilitate colonization of the kidney and bladder, respectively. Pilus assembly requires a periplasmic chaperone and outer membrane protein termed the usher. The chaperone allows folding of pilus subunits and escorts the subunits to the usher for polymerization into pili and secretion to the cell surface. Based on previous structures of mutant versions of the P pilus chaperone PapD, it was suggested that the chaperone dimerizes in the periplasm as a self-capping mechanism. Such dimerization is counterintuitive because the chaperone G1 strand, important for chaperone-subunit interaction, is buried at the dimer interface. Here, we show that the wild-type PapD chaperone also forms a dimer in the crystal lattice; however, the dimer interface is different from the previously solved structures. In contrast to the crystal structures, we found that both PapD and the type 1 pilus chaperone, FimC, are monomeric in solution. Our findings indicate that pilus chaperones do not sequester their G1 β-strand by forming a dimer. Instead, the chaperones may expose their G1 strand for facile interaction with pilus subunits. We also found that the type 1 pilus adhesin, FimH, is flexible in solution while in complex with its chaperone, whereas the P pilus adhesin, PapGII, is rigid. Our study clarifies a crucial step in pilus biogenesis and reveals pilus-specific differences that may relate to biological function.

    IMPORTANCEPili are critical virulence factors for many bacterial pathogens. UropathogenicE. colirelies on P and type 1 pili assembled by the chaperone/usher pathway to

  9. Prospective study of breakfast eating and incident coronary heart disease in a cohort of male US health professionals.

    Science.gov (United States)

    Cahill, Leah E; Chiuve, Stephanie E; Mekary, Rania A; Jensen, Majken K; Flint, Alan J; Hu, Frank B; Rimm, Eric B

    2013-07-23

    Among adults, skipping meals is associated with excess body weight, hypertension, insulin resistance, and elevated fasting lipid concentrations. However, it remains unknown whether specific eating habits regardless of dietary composition influence coronary heart disease (CHD) risk. The objective of this study was to prospectively examine eating habits and risk of CHD. Eating habits, including breakfast eating, were assessed in 1992 in 26 902 American men 45 to 82 years of age from the Health Professionals Follow-up Study who were free of cardiovascular disease and cancer. During 16 years of follow-up, 1527 incident CHD cases were diagnosed. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for CHD, adjusted for demographic, diet, lifestyle, and other CHD risk factors. Men who skipped breakfast had a 27% higher risk of CHD compared with men who did not (relative risk, 1.27; 95% confidence interval, 1.06-1.53). Compared with men who did not eat late at night, those who ate late at night had a 55% higher CHD risk (relative risk, 1.55; 95% confidence interval, 1.05-2.29). These associations were mediated by body mass index, hypertension, hypercholesterolemia, and diabetes mellitus. No association was observed between eating frequency (times per day) and risk of CHD. Eating breakfast was associated with significantly lower CHD risk in this cohort of male health professionals.

  10. Dose rate estimates from irradiated light-water-reactor fuel assemblies in air

    International Nuclear Information System (INIS)

    Lloyd, W.R.; Sheaffer, M.K.; Sutcliffe, W.G.

    1994-01-01

    It is generally considered that irradiated spent fuel is so radioactive (self-protecting) that it can only be moved and processed with specialized equipment and facilities. However, a small, possibly subnational, group acting in secret with no concern for the environment (other than the reduction of signatures) and willing to incur substantial but not lethal radiation doses, could obtain plutonium by stealing and processing irradiated spent fuel that has cooled for several years. In this paper, we estimate the dose rate at various distances and directions from typical pressurized-water reactor (PWR) and boiling-water reactor (BWR) spent-fuel assemblies as a function of cooling time. Our results show that the dose rate is reduced rapidly for the first ten years after exposure in the reactor, and that it is reduced by a factor of ∼10 (from the one year dose rate) after 15 years. Even for fuel that has cooled for 15 years, a lethal dose (LD50) of 450 rem would be received at 1 m from the center of the fuel assembly after several minutes. However, moving from 1 to 5 m reduces the dose rate by over a factor of 10, and moving from 1 to 10 m reduces the dose rate by about a factor of 50. The dose rates 1 m from the top or bottom of the assembly are considerably less (about 10 and 22%, respectively) than 1 m from the center of the assembly, which is the direction of the maximum dose rate

  11. Risk Factors of Congenital Heart Diseases: A Case-Control Study inNorthwest Iran.

    Science.gov (United States)

    Naghavi-Behzad, Mohammad; Alizadeh, Mahasti; Azami, Saber; Foroughifar, Shirin; Ghasempour-Dabbaghi, Khazar; Karzad, Nazila; Ahadi, Hamid-Reza; Naghavi-Behzad, Ali

    2013-01-01

    Congenital heart diseases are of immense importance and also a high prevalence. Contributing factors to developing these defects have not been abundantly studied. Therefore, the current study was conducted aiming at determining the effective factors on Congenital Heart Disease (CHD) in newborn infants of Northwest Iran. A case-control study was carried out in North-West of Iran from 2002 to 2012 and a total of 473 infants entered the study. Required data were obtained through check lists completed by the information of hospital records and interview with mothers of 267 newborn infants with CHD together with medical records of mothers as the case group, and 206 medical records of healthy infants at the same period all together with those of their mothers as the control group. The obtained data were statistically analyzed using descriptive statistical methods, T-test, Spearman's correlation coefficient, and Multi-variable Logistic Regression Model (OR with 95% CI), using SPSS.19. In the present study, P value less than 0.05 was considered statistically significant. Based on the results of univariable analyses, the number of previous cesarean sections, past medical history of diseases, gestational age (GA), fetal weight at birth, diastolic blood pressure, fetal heart rate, pulse rate, fetal hemoglobin and hematocrit levels, and fetal head circumference at birth have significant relationship with incidence of congenital abnormalities (Prelationship with CHD incidence. Based on the results of present study, in order to control and reduce the cases of CHD, it is crucial to make proper decisions and implement policies for reducing cesarean cases, lowering consanguineous marriages, providing proper pre-marriage counseling, prompt treatment of mothers' illnesses, improving pregnancy health care and mothers' health status for the purpose of better well-being of newborn infants.

  12. Risk Factors of Congenital Heart Diseases: A Case-Control Study in Northwest Iran

    Directory of Open Access Journals (Sweden)

    Naghavi-Behzad Mohammad

    2013-03-01

    Full Text Available Introduction: Congenital heart diseases are of immense importance and also a high prevalence. Contributing factors to developing these defects have not been abundantly studied. Therefore, the current study was conducted aiming at determining the effective factors on Congenital Heart Disease (CHD in newborn infants of Northwest Iran. Methods: A case-control study was carried out in North-West of Iran from 2002 to 2012 and a total of 473 infants entered the study. Required data were obtained through check lists completed by the information of hospital records and interview with mothers of 267 newborn infants with CHD together with medical records of mothers as the case group, and 206 medical records of healthy infants at the same period all together with those of their mothers as the control group. The obtained data were statistically analyzed using descriptive statistical methods, T-test, Spearman’s correlation coefficient, and Multi-variable Logistic Regression Model (OR with 95% CI, using SPSS.19. In the present study, P value less than 0.05 was considered statistically significant. Results: Based on the results of univariable analyses, the number of previous cesarean sections, past medical history of diseases, gestational age (GA, fetal weight at birth, diastolic blood pressure, fetal heart rate, pulse rate, fetal hemoglobin and hematocrit levels, and fetal head circumference at birth have significant relationship with incidence of congenital abnormalities (P<0.05. Family history, past cesarean sections history, past medical history and GA had significant relationship with CHD incidence. Conclusion: Based on the results of present study, in order to control and reduce the cases of CHD, it is crucial to make proper decisions and implement policies for reducing cesarean cases, lowering consanguineous marriages, providing proper pre-marriage counseling, prompt treatment of mothers’ illnesses, improving pregnancy health care and mothers

  13. Co-occurrence of metabolic factors and the risk of coronary heart disease: A prospective cohort study in the Netherlands

    NARCIS (Netherlands)

    Merry, A.H.; Erkens, P.M.G.; Boer, J.M.A.; Schouten, L.J.; Feskens, E.J.M.; Verschuren, W.M.M.; Gorgels, A.P.; Brandt, van den P.A.

    2012-01-01

    Background -Prevalence of metabolic factors such as diabetes, hypertension, obesity, HDL and total cholesterol that are associated with an increased risk of coronary heart disease (CHD) is increasing worldwide. However, less is known about combinations of these factors that are associated with the

  14. The risk of coronary heart disease of seafarers on vessels sailing under a German flag.

    Science.gov (United States)

    Oldenburg, Marcus; Jensen, Hans-Joachim; Latza, Ute; Baur, Xaver

    2010-01-01

    This study aimed to predict the risk of coronary heart disease (CHD) among seafarers on German-flagged vessels and to assess the association of shipboard job duration at sea with the risk of CHD. During the legally required medical fitness test for nautical service, 161 seafarers in Hamburg participated in a cross-sectional study which included an interview, blood sampling, and blood pressure measurements (response 84.9%). The predicted 10-year risk of an acute coronary event of the examined German seafarers aged 35 to 64 years (n = 46) was assessed in comparison with a sample of male German employees of the same age working ashore (PROCAM study). The number of independent CHD risk factors (according to the PROCAM study) was compared in the groups with 'shorter' and 'longer' median shipboard job duration at sea (15.0 years). The examined German seafarers had a similar age-standardized predicted 10-year CHD risk as the German reference population. Nearly all independent CHD risk factors were significantly more frequent in seamen with job duration at sea of ≥ 15 years than in those with 〈 15 years. After adjusting for age, the number of CHD risk factors was associated with job duration (OR 1.08 [95% CI 1.02-1.14] per year). Seafarers on German-flagged ships have to attend a medical fitness test for nautical service every 2 years. Thus, it can be assumed that seafarers present a healthier population than employees ashore. In this study, however, CHD risk of seafarers was similar to that of the reference population. This may indicate that working onboard implies a high coronary risk. Furthermore, the study results suggest a tendency of increased risk of CHD among seafarers with longer job duration at sea.

  15. Nef enhances HIV-1 infectivity via association with the virus assembly complex

    International Nuclear Information System (INIS)

    Qi Mingli; Aiken, Christopher

    2008-01-01

    The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle

  16. Adenoviral protein V promotes a process of viral assembly through nucleophosmin 1

    Energy Technology Data Exchange (ETDEWEB)

    Ugai, Hideyo; Dobbins, George C.; Wang, Minghui [Division of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology, and Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Le, Long P. [Massachusetts General Hospital, Pathology Service, 55 Fruit St.-GRJ 249, Boston, MA 02114 (United States); Matthews, David A. [School of Cellular and Molecular Medicine, Medical Sciences Building, University of Bristol, Bristol BS8 1TD (United Kingdom); Curiel, David T., E-mail: dcuriel@radonc.wustl.edu [Division of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology, and Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); The Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2012-10-25

    Adenoviral infection induces nucleoplasmic redistribution of a nucleolar nucleophosmin 1/NPM1/B23.1. NPM1 is preferentially localized in the nucleoli of normal cells, whereas it is also present at the nuclear matrix in cancer cells. However, the biological roles of NPM1 during infection are unknown. Here, by analyzing a pV-deletion mutant, Ad5-dV/TSB, we demonstrate that pV promotes the NPM1 translocation from the nucleoli to the nucleoplasm in normal cells, and the NPM1 translocation is correlated with adenoviral replication. Lack of pV causes a dramatic reduction of adenoviral replication in normal cells, but not cancer cells, and Ad5-dV/TSB was defective in viral assembly in normal cells. NPM1 knockdown inhibits adenoviral replication, suggesting an involvement of NPM1 in adenoviral biology. Further, we show that NPM1 interacts with empty adenovirus particles which are an intermediate during virion maturation by immunoelectron microscopy. Collectively, these data implicate that pV participates in a process of viral assembly through NPM1.

  17. Research on Outfitting Virtual Assembly based on Ergonomics

    Directory of Open Access Journals (Sweden)

    Jiang Zuhua

    2018-01-01

    Full Text Available To improve the present situation where the assembly work of ship outfitting depends on manual experiential operation, the thesis, taking outfitting assembly operation as the research object and optimal assembly path as the target, puts forward the simulation method and procedure of outfitting virtual assembly considering operational posture, operational load, reachability and visibility and other ergonomic factors, taking pipe assembly operation of ship section as the application example. The results show that the method can obtain better assembly operation path, avoid interference of workers’ operation process and improve the efficiency of assembly operation.

  18. A spectrum correction method for fuel assembly rehomogenization

    International Nuclear Information System (INIS)

    Lee, Kyung Taek; Cho, Nam Zin

    2004-01-01

    To overcome the limitation of existing homogenization methods based on the single assembly calculation with zero current boundary condition, we propose a new rehomogenization method, named spectrum correction method (SCM), consisting of the multigroup energy spectrum approximation by spectrum correction and the condensed two-group heterogeneous single assembly calculations with non-zero current boundary condition. In SCM, the spectrum shifting phenomena caused by current across assembly interfaces are considered by the spectrum correction at group condensation stage at first. Then, heterogeneous single assembly calculations with two-group cross sections condensed by using corrected multigroup energy spectrum are performed to obtain rehomogenized nodal diffusion parameters, i.e., assembly-wise homogenized cross sections and discontinuity factors. To evaluate the performance of SCM, it was applied to the analytic function expansion nodal (AFEN) method and several test problems were solved. The results show that SCM can reduce the errors significantly both in multiplication factors and assembly averaged power distributions

  19. Saturn V First Stage (S-1C) Ready for Assembly AT KSC

    Science.gov (United States)

    1968-01-01

    This photograph shows the Saturn V first stage (S-1C) in the Vehicle Assembly Building at Kennedy Space Center ready to be mated with the second and third stages to complete the assembly of a Saturn V launch vehicle. This particular Saturn V was used for Apollo 6, which was a systems test flight. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

  20. Contribution to the WWER-440 Gd-assembly evolution

    International Nuclear Information System (INIS)

    Cudrnak, P.; Darilek, P.; Necas, V.

    2009-01-01

    Development activities, presented in the paper, contribute to the evolution of gadolinium fuel for the WWER-440 reactors. Short overview of existing and already proposed Gd-assemblies is given. Two new assembly types with improved features are described. Multiplication coefficients and pin power peaking factors of all mentioned gadolinium assemblies are compared. Animations of power distribution behaviour in selected Gd-assemblies are shown. (Authors)

  1. Pixel Detector Trial Assembly Test in the SR1 building

    CERN Multimedia

    D. Giugni

    2004-01-01

    During the last two months the Pixel group [LBL, Milan and Wuppertal] made a successful integration test on the mechanics of the barrel. The scope of the test was to qualify the integration procedures and the various assembling tools. The test took place in the clean room of the SR1 building at CERN, where the detector has been assembled around a dummy beam pipe made of Stainless Steel. The process is rather complex: the shells come in two parts and they have to be clamped together to get the full shell. This operation is carried out by a dedicated tool which is shown to the right in the picture below. The layer 1 shell is clamped around a "service" pipe that will be used for moving the full layer to the integration tool [ITT] which is visible on the left. View of the tools devoted to the Pixel barrel integration in the SR1 building Also visible in the picture is the global frame that is actually held by the tool. It will engage the layers sliding onto the rails. The first two layers are sequentially...

  2. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Kristen N Stevens

    Full Text Available Congenital heart disease (CHD is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1 is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.

  3. Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal-anchored receptors.

    Science.gov (United States)

    Becker, Thomas; Pfannschmidt, Sylvia; Guiard, Bernard; Stojanovski, Diana; Milenkovic, Dusanka; Kutik, Stephan; Pfanner, Nikolaus; Meisinger, Chris; Wiedemann, Nils

    2008-01-04

    The translocase of the outer membrane (TOM complex) is the central entry gate for nuclear-encoded mitochondrial precursor proteins. All Tom proteins are also encoded by nuclear genes and synthesized as precursors in the cytosol. The channel-forming beta-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly machinery (SAM complex). A further outer membrane protein, Mim1, plays a less defined role in assembly of Tom40 into the TOM complex. The three receptors Tom20, Tom22, and Tom70 are anchored in the outer membrane by a single transmembrane alpha-helix, located at the N terminus in the case of Tom20 and Tom70 (signal-anchored) or in the C-terminal portion in the case of Tom22 (tail-anchored). Insertion of the precursor of Tom22 into the outer membrane requires pre-existing Tom receptors while the import pathway of the precursors of Tom20 and Tom70 is only poorly understood. We report that Mim1 is required for efficient membrane insertion and assembly of Tom20 and Tom70, but not Tom22. We show that Mim1 associates with SAM(core) components to a large SAM complex, explaining its role in late steps of the assembly pathway of Tom40. We conclude that Mim1 is not only required for biogenesis of the beta-barrel protein Tom40 but also for membrane insertion and assembly of signal-anchored Tom receptors. Thus, Mim1 plays an important role in the efficient assembly of the mitochondrial TOM complex.

  4. Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements.

    Directory of Open Access Journals (Sweden)

    Timothy L Haskett

    2018-03-01

    Full Text Available Tripartite integrative and conjugative elements (ICE3 are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases-or recombination directionality factors-RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a "master controller" of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer.

  5. Synthesis and evaluation of 2-pyridinylpyrimidines as inhibitors of HIV-1 structural protein assembly

    Czech Academy of Sciences Publication Activity Database

    Kožíšek, Milan; Štěpánek, Ondřej; Parkan, Kamil; Albinana, C. B.; Pávová, Marcela; Weber, Jan; Kräusslich, H. G.; Konvalinka, Jan; Machara, A.

    2016-01-01

    Roč. 26, č. 15 (2016), s. 3487-3490 ISSN 0960-894X R&D Projects: GA ČR GA13-19561S; GA MŠk(CZ) LK11207 Institutional support: RVO:61388963 Keywords : assay * assembly * capsid * inhibition * pyrimidine Subject RIV: CE - Biochemistry Impact factor: 2.454, year: 2016 http://www.sciencedirect.com/science/article/pii/S0960894X16306503

  6. Is maternal transmission of coronary heart disease risk stronger than paternal transmission?

    Science.gov (United States)

    Kinra, S; Davey Smith, G; Okasha, M; McCarron, P; McEwen, J

    2003-08-01

    To test whether intergenerational transmission of coronary heart disease (CHD) to offspring is greater from the mother than from the father, the association between parental history of CHD and coronary mortality in male offspring was examined. Prospective cohort study with 43 years of follow up. University of Glasgow. Male students (n = 8402) aged 16-30 years when examined in 1948 to 1968. Fatal CHD. Of the 8402 men studied, 615 (7.3%) reported a history of CHD in at least one of the parents: 479 (5.8%) for fathers only, 124 (1.6%) for mothers only, and a further 12 (0.2%) for both their parents. During follow up, 373 (4.4%) men died of CHD. Parental history of disease was associated with fatal CHD and controlling for personal risk factors such as cigarette smoking, body mass index, systolic blood pressure, and father's social class did not attenuate this relation. The fully adjusted hazard ratios were 1.53 (95% confidence interval (CI) 1.08 to 2.18), 1.19 (95% CI 0.61 to 2.32), and 8.65 (95% CI 2.65 to 28.31) for father only, mother only, and both parents with CHD, respectively, compared with men whose parents did not have CHD. There was some evidence for interaction between parental histories (p = 0.049), with particularly high risk if both parents reported a history of CHD. This study found no differential transmission of CHD. Paternal history of CHD was at least as important as maternal history. Data from other comparable cohorts provide no consistent evidence of differential transmission. Intergenerational transmission of CHD does not appear to have differential effects between mothers and fathers.

  7. Canis mtDNA HV1 database: a web-based tool for collecting and surveying Canis mtDNA HV1 haplotype in public database.

    Science.gov (United States)

    Thai, Quan Ke; Chung, Dung Anh; Tran, Hoang-Dung

    2017-06-26

    Canine and wolf mitochondrial DNA haplotypes, which can be used for forensic or phylogenetic analyses, have been defined in various schemes depending on the region analyzed. In recent studies, the 582 bp fragment of the HV1 region is most commonly used. 317 different canine HV1 haplotypes have been reported in the rapidly growing public database GenBank. These reported haplotypes contain several inconsistencies in their haplotype information. To overcome this issue, we have developed a Canis mtDNA HV1 database. This database collects data on the HV1 582 bp region in dog mitochondrial DNA from the GenBank to screen and correct the inconsistencies. It also supports users in detection of new novel mutation profiles and assignment of new haplotypes. The Canis mtDNA HV1 database (CHD) contains 5567 nucleotide entries originating from 15 subspecies in the species Canis lupus. Of these entries, 3646 were haplotypes and grouped into 804 distinct sequences. 319 sequences were recognized as previously assigned haplotypes, while the remaining 485 sequences had new mutation profiles and were marked as new haplotype candidates awaiting further analysis for haplotype assignment. Of the 3646 nucleotide entries, only 414 were annotated with correct haplotype information, while 3232 had insufficient or lacked haplotype information and were corrected or modified before storing in the CHD. The CHD can be accessed at http://chd.vnbiology.com . It provides sequences, haplotype information, and a web-based tool for mtDNA HV1 haplotyping. The CHD is updated monthly and supplies all data for download. The Canis mtDNA HV1 database contains information about canine mitochondrial DNA HV1 sequences with reconciled annotation. It serves as a tool for detection of inconsistencies in GenBank and helps identifying new HV1 haplotypes. Thus, it supports the scientific community in naming new HV1 haplotypes and to reconcile existing annotation of HV1 582 bp sequences.

  8. Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons

    Science.gov (United States)

    Anderson, Fenja; Rother, Franziska; Rudolph, Kathrin; Prank, Ute; Binz, Anne; Hügel, Stefanie; Hartmann, Enno; Bader, Michael; Bauerfeind, Rudolf; Sodeik, Beate

    2018-01-01

    Herpesviruses are large DNA viruses which depend on many nuclear functions, and therefore on host transport factors to ensure specific nuclear import of viral and host components. While some import cargoes bind directly to certain transport factors, most recruit importin β1 via importin α. We identified importin α1 in a small targeted siRNA screen to be important for herpes simplex virus (HSV-1) gene expression. Production of infectious virions was delayed in the absence of importin α1, but not in cells lacking importin α3 or importin α4. While nuclear targeting of the incoming capsids, of the HSV-1 transcription activator VP16, and of the viral genomes were not affected, the nuclear import of the HSV-1 proteins ICP4 and ICP0, required for efficient viral transcription, and of ICP8 and pUL42, necessary for DNA replication, were reduced. Furthermore, quantitative electron microscopy showed that fibroblasts lacking importin α1 contained overall fewer nuclear capsids, but an increased proportion of mature nuclear capsids indicating that capsid formation and capsid egress into the cytoplasm were impaired. In neurons, importin α1 was also not required for nuclear targeting of incoming capsids, but for nuclear import of ICP4 and for the formation of nuclear capsid assembly compartments. Our data suggest that importin α1 is specifically required for the nuclear localization of several important HSV1 proteins, capsid assembly, and capsid egress into the cytoplasm, and may become rate limiting in situ upon infection at low multiplicity or in terminally differentiated cells such as neurons. PMID:29304174

  9. Synthesis and characterization of supramolecule self-assembly polyami-doamine (PAMAM G1-G1 NH2, CO2H end group Megamer

    Directory of Open Access Journals (Sweden)

    Omid Louie

    2014-10-01

    Full Text Available Supramolecule self-assembly polyamidoamine (PAMAM dendrimer refers to the chemical sys-tems made up of a discrete number of assembled molecular subunits or components. These strat-egies involve the covalent assembly of hierarchical components reactive monomers, branch cells or dendrons around atomic or molecular cores according to divergent/convergent dendritic branching principles, systematic filling of space around a core with shells (layers of branch cells. The polydispersity index (PDI for the supramolecule megamer are pretty closed to one, are in agreement with the Poisson probability distribution. Polyamidoamine (PAMAM den-drimer G1-G1 that it was PAMAM Megamer NH2, COOH end groupsynthesized and character-ized by FT-IR, 1H NMR, 13C NMRspectra and GelPermeation Chromatography (GPC.

  10. Prediagnostic plasma antibody levels to periodontopathic bacteria and risk of coronary heart disease.

    Science.gov (United States)

    Ueno, Masayuki; Izumi, Yuichi; Kawaguchi, Yoko; Ikeda, Ai; Iso, Hiroyasu; Inoue, Manami; Tsugane, Shoichiro

    2012-01-01

    Many epidemiological studies have indicated that periodontitis is an important risk factor for coronary heart disease (CHD). We examined whether plasma antibody levels to 3 major periodontal pathogens, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia predicted the risk of CHD events. A nested case-control research design (case: n = 191, control: n = 382), by matching gender, age, study area, date of blood collection, and time since last meal at blood collection, was employed in a large cohort of Japanese community residents.Antibody levels of periodontopathic bacteria were associated with risk of CHD after adjusting for BMI, smoking status, alcohol intake, history of hypertension, history of diabetes mellitus, exercise during leisure time, and perceived mental stress. The association was different by age subgroup. For subjects aged 40-55 years, the medium (31.7-184.9 U/mL) or high tertile plasma antibody level (> 184.9 U/mL) of A. actinomycetemcomitans showed higher risk of CHD (medium: OR = 3.72; 95% CI = 1.20-11.56, high: OR = 4.64; 95% CI = 1.52-14.18) than the low tertile level ( 414.1 U/mL) of P. intermedia was associated with higher risk of CHD (OR = 2.65; 95% CI = 1.18-5.94) in a dose-response fashion (P for trend = 0.007). The possible role of periodontopathic bacteria as a risk factor for CHD incidence was suggested by the results of this study by the elevated antibody level to these bacteria with the increased risk of CHD.

  11. Viral capsid assembly as a model for protein aggregation diseases: Active processes catalyzed by cellular assembly machines comprising novel drug targets.

    Science.gov (United States)

    Marreiros, Rita; Müller-Schiffmann, Andreas; Bader, Verian; Selvarajah, Suganya; Dey, Debendranath; Lingappa, Vishwanath R; Korth, Carsten

    2015-09-02

    Viruses can be conceptualized as self-replicating multiprotein assemblies, containing coding nucleic acids. Viruses have evolved to exploit host cellular components including enzymes to ensure their replicative life cycle. New findings indicate that also viral capsid proteins recruit host factors to accelerate their assembly. These assembly machines are RNA-containing multiprotein complexes whose composition is governed by allosteric sites. In the event of viral infection, the assembly machines are recruited to support the virus over the host and are modified to achieve that goal. Stress granules and processing bodies may represent collections of such assembly machines, readily visible by microscopy but biochemically labile and difficult to isolate by fractionation. We hypothesize that the assembly of protein multimers such as encountered in neurodegenerative or other protein conformational diseases, is also catalyzed by assembly machines. In the case of viral infection, the assembly machines have been modified by the virus to meet the virus' need for rapid capsid assembly rather than host homeostasis. In the case of the neurodegenerative diseases, it is the monomers and/or low n oligomers of the so-called aggregated proteins that are substrates of assembly machines. Examples for substrates are amyloid β peptide (Aβ) and tau in Alzheimer's disease, α-synuclein in Parkinson's disease, prions in the prion diseases, Disrupted-in-schizophrenia 1 (DISC1) in subsets of chronic mental illnesses, and others. A likely continuum between virus capsid assembly and cell-to-cell transmissibility of aggregated proteins is remarkable. Protein aggregation diseases may represent dysfunction and dysregulation of these assembly machines analogous to the aberrations induced by viral infection in which cellular homeostasis is pathologically reprogrammed. In this view, as for viral infection, reset of assembly machines to normal homeostasis should be the goal of protein aggregation

  12. Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors.

    Science.gov (United States)

    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-06-01

    The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive cells, possess strong anti-HIV-1 activity and are sufficient to confer a nonpermissive phenotype. Vif induces the degradation of hA3G and hA3F, suggesting that its main function is to counteract these cellular factors. Most studies focused on the hypermutation induced by the cytidine deaminase activity of hA3G and hA3F and on their Vif-induced degradation by the proteasome. However, recent studies suggested that several mechanisms are involved both in the antiviral activity of hA3G and hA3F and in the way Vif counteracts these antiviral factors. Attempts to reconcile the studies involving Vif in virus assembly and stability with these recent findings suggest that hA3G and hA3F partially exert their antiviral activity independently of their catalytic activity by destabilizing the viral core and the reverse transcription complex, possibly by interfering with the assembly and/or maturation of the viral particles. Vif could then counteract hA3G and hA3F by excluding them from the viral assembly intermediates through competition for the viral genomic RNA, by regulating the proteolytic processing of Pr55(Gag), by enhancing the efficiency of the reverse transcription process, and by inhibiting the enzymatic activities of hA3G and hA3F.

  13. Autographa californica multiple nucleopolyhedrovirus PK-1 is essential for nucleocapsid assembly

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Changyong, E-mail: cyliang@yzu.edu.cn [College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009 (China); Li, Min; Dai, Xuejuan; Zhao, Shuling; Hou, Yanling; Zhang, Yongli; Lan, Dandan [College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009 (China); Wang, Yun; Chen, Xinwen [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)

    2013-09-01

    PK-1 (Ac10) is a baculovirus-encoded serine/threonine kinase and its function is unclear. Our results showed that a pk-1 knockout AcMNPV failed to produce infectious progeny, while the pk-1 repair virus could rescue this defect. qPCR analysis demonstrated that pk-1 deletion did not affect viral DNA replication. Analysis of the repaired recombinants with truncated pk-1 mutants demonstrated that the catalytic domain of protein kinases of PK-1 was essential to viral infectivity. Moreover, those PK-1 mutants that could rescue the infectious BV production defect exhibited kinase activity in vitro. Therefore, it is suggested that the kinase activity of PK-1 is essential in regulating viral propagation. Electron microscopy revealed that pk-1 deletion affected the formation of normal nucleocapsids. Masses of electron-lucent tubular structures were present in cell transfected with pk-1 knockout bacmid. Therefore, PK-1 appears to phosphorylate some viral or cellular proteins that are essential for DNA packaging to regulate nucleocapsid assembly. - Highlights: • A pk-1 knockout AcMNPV failed to produce infectious progeny. • The pk-1 deletion did not affect viral DNA replication. • The catalytic domain of protein kinases (PKc) of PK-1 was essential to viral infectivity. • The kinase activity of PK-1 is essential in regulating viral propagation. • PK-1 appears to phosphorylate some viral proteins that are essential for DNA packaging to regulate nucleocapsid assembly.

  14. Integrated genetic and epigenetic prediction of coronary heart disease in the Framingham Heart Study.

    Directory of Open Access Journals (Sweden)

    Meeshanthini V Dogan

    Full Text Available An improved method for detecting coronary heart disease (CHD could have substantial clinical impact. Building on the idea that systemic effects of CHD risk factors are a conglomeration of genetic and environmental factors, we use machine learning techniques and integrate genetic, epigenetic and phenotype data from the Framingham Heart Study to build and test a Random Forest classification model for symptomatic CHD. Our classifier was trained on n = 1,545 individuals and consisted of four DNA methylation sites, two SNPs, age and gender. The methylation sites and SNPs were selected during the training phase. The final trained model was then tested on n = 142 individuals. The test data comprised of individuals removed based on relatedness to those in the training dataset. This integrated classifier was capable of classifying symptomatic CHD status of those in the test set with an accuracy, sensitivity and specificity of 78%, 0.75 and 0.80, respectively. In contrast, a model using only conventional CHD risk factors as predictors had an accuracy and sensitivity of only 65% and 0.42, respectively, but with a specificity of 0.89 in the test set. Regression analyses of the methylation signatures illustrate our ability to map these signatures to known risk factors in CHD pathogenesis. These results demonstrate the capability of an integrated approach to effectively model symptomatic CHD status. These results also suggest that future studies of biomaterial collected from longitudinally informative cohorts that are specifically characterized for cardiac disease at follow-up could lead to the introduction of sensitive, readily employable integrated genetic-epigenetic algorithms for predicting onset of future symptomatic CHD.

  15. RISC assembly: Coordination between small RNAs and Argonaute proteins.

    Science.gov (United States)

    Kobayashi, Hotaka; Tomari, Yukihide

    2016-01-01

    Non-coding RNAs generally form ribonucleoprotein (RNP) complexes with their partner proteins to exert their functions. Small RNAs, including microRNAs, small interfering RNAs, and PIWI-interacting RNAs, assemble with Argonaute (Ago) family proteins into the effector complex called RNA-induced silencing complex (RISC), which mediates sequence-specific target gene silencing. RISC assembly is not a simple binding between a small RNA and Ago; rather, it follows an ordered multi-step pathway that requires specific accessory factors. Some steps of RISC assembly and RISC-mediated gene silencing are dependent on or facilitated by particular intracellular platforms, suggesting their spatial regulation. In this review, we summarize the currently known mechanisms for RISC assembly of each small RNA class and propose a revised model for the role of the chaperone machinery in the duplex-initiated RISC assembly pathway. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Mechanics of binary and polydisperse spherical pebble assembly

    International Nuclear Information System (INIS)

    Annabattula, R.K.; Gan, Y.; Kamlah, M.

    2012-01-01

    The micromechanical behavior of an assembly of binary and polydisperse spherical pebbles is studied using discrete element method (DEM) accounting for microscopic interactions between individual pebbles. A in-house DEM code has been used to simulate the assemblies consisting of different pebble diameters and the results of the simulations are compared with that of mono-size pebble assemblies. The effect of relative radii and volume fraction of the pebbles on the macroscopic stress–strain response is discussed. Furthermore, the effect of packing factor and coefficient of friction on the overall stress–strain behavior of the system is studied in detail. The shear (tangential) stiffness between the particles is also another influencing parameter. For a very small shear stiffness the system shows a strong dependence on the packing factor while a pebble material dependent shear stiffness shows a rather moderate dependence on the packing factor. For a similar packing factor, the mono-size assembly shows a stiff behavior during loading compared to binary assembly. However, the simulations do not show a significant difference between the two behaviors in contrast to the observations made in the experiments. The discrepancy can be attributed to (i) probable difference in packing factors for mono-size and binary assemblies in the experiments, (ii) arbitrary friction coefficient in the current model and (iii) the tangential interaction (constant shear stiffness) implemented in the present model which needs further modification as a function of the load history on the pebbles. Evolution of other micromechanical characteristics such as coordination number, contact force distribution and stored elastic energy of individual pebbles as a function of external load and system parameters is presented which can be used to estimate important macroscopic properties such as overall thermal conductivity and crushing resistance of the pebble beds.

  17. Mechanics of binary and polydisperse spherical pebble assembly

    Energy Technology Data Exchange (ETDEWEB)

    Annabattula, R.K., E-mail: ratna.annabattula@kit.edu [Institute for Applied Materials (IAM-WBM), Karlsruhe Institute of Technology (KIT), D-76344, Eggenstein-Leopoldshafen (Germany); Gan, Y., E-mail: yixiang.gan@sydney.edu.au [School of Civil Engineering, University of Sydney, 2006 NSW, Sydney (Australia); Kamlah, M., E-mail: marc.kamlah@kit.edu [Institute for Applied Materials (IAM-WBM), Karlsruhe Institute of Technology (KIT), D-76344, Eggenstein-Leopoldshafen (Germany)

    2012-08-15

    The micromechanical behavior of an assembly of binary and polydisperse spherical pebbles is studied using discrete element method (DEM) accounting for microscopic interactions between individual pebbles. A in-house DEM code has been used to simulate the assemblies consisting of different pebble diameters and the results of the simulations are compared with that of mono-size pebble assemblies. The effect of relative radii and volume fraction of the pebbles on the macroscopic stress-strain response is discussed. Furthermore, the effect of packing factor and coefficient of friction on the overall stress-strain behavior of the system is studied in detail. The shear (tangential) stiffness between the particles is also another influencing parameter. For a very small shear stiffness the system shows a strong dependence on the packing factor while a pebble material dependent shear stiffness shows a rather moderate dependence on the packing factor. For a similar packing factor, the mono-size assembly shows a stiff behavior during loading compared to binary assembly. However, the simulations do not show a significant difference between the two behaviors in contrast to the observations made in the experiments. The discrepancy can be attributed to (i) probable difference in packing factors for mono-size and binary assemblies in the experiments, (ii) arbitrary friction coefficient in the current model and (iii) the tangential interaction (constant shear stiffness) implemented in the present model which needs further modification as a function of the load history on the pebbles. Evolution of other micromechanical characteristics such as coordination number, contact force distribution and stored elastic energy of individual pebbles as a function of external load and system parameters is presented which can be used to estimate important macroscopic properties such as overall thermal conductivity and crushing resistance of the pebble beds.

  18. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations

    Directory of Open Access Journals (Sweden)

    Kroeger Cynthia M

    2012-10-01

    Full Text Available Abstract Background The ability of an intermittent fasting (IF-calorie restriction (CR regimen (with or without liquid meals to modulate adipokines in a way that is protective against coronary heart disease (CHD has yet to be tested. Objective Accordingly, we examined the effects of an IFCR diet on adipokine profile, body composition, and markers of CHD risk in obese women. Methods Subjects (n = 54 were randomized to either the IFCR-liquid (IFCR-L or IFCR-food based (IFCR-F diet for 10 weeks. Results Greater decreases in body weight and waist circumference were noted in the IFCR-L group (4 ± 1 kg; 6 ± 1 cm versus the IFCR-F group (3 ± 1 kg; 4 ± 1 cm. Similar reductions (P Conclusion These findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.

  19. The E2F-DP1 Transcription Factor Complex Regulates Centriole Duplication in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Jacqueline G. Miller

    2016-03-01

    Full Text Available Centrioles play critical roles in the organization of microtubule-based structures, from the mitotic spindle to cilia and flagella. In order to properly execute their various functions, centrioles are subjected to stringent copy number control. Central to this control mechanism is a precise duplication event that takes place during S phase of the cell cycle and involves the assembly of a single daughter centriole in association with each mother centriole . Recent studies have revealed that posttranslational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole. In contrast, relatively little is known about how centriole duplication is regulated at a transcriptional level. Here we show that the transcription factor complex EFL-1-DPL-1 both positively and negatively controls centriole duplication in the Caenorhabditis elegans embryo. Specifically, we find that down regulation of EFL-1-DPL-1 can restore centriole duplication in a zyg-1 hypomorphic mutant and that suppression of the zyg-1 mutant phenotype is accompanied by an increase in SAS-6 protein levels. Further, we find evidence that EFL-1-DPL-1 promotes the transcription of zyg-1 and other centriole duplication genes. Our results provide evidence that in a single tissue type, EFL-1-DPL-1 sets the balance between positive and negative regulators of centriole assembly and thus may be part of a homeostatic mechanism that governs centriole assembly.

  20. Hematopoietic stem cell cytokines and fibroblast growth factor-2 stimulate human endothelial cell-pericyte tube co-assembly in 3D fibrin matrices under serum-free defined conditions.

    Directory of Open Access Journals (Sweden)

    Annie O Smith

    Full Text Available We describe a novel 3D fibrin matrix model using recombinant hematopoietic stem cell cytokines under serum-free defined conditions which promotes the assembly of human endothelial cell (EC tubes with co-associated pericytes. Individual ECs and pericytes are randomly mixed together and EC tubes form that is accompanied by pericyte recruitment to the EC tube abluminal surface over a 3-5 day period. These morphogenic processes are stimulated by a combination of the hematopoietic stem cell cytokines, stem cell factor, interleukin-3, stromal derived factor-1α, and Flt-3 ligand which are added in conjunction with fibroblast growth factor (FGF-2 into the fibrin matrix. In contrast, this tube morphogenic response does not occur under serum-free defined conditions when VEGF and FGF-2 are added together in the fibrin matrices. We recently demonstrated that VEGF and FGF-2 are able to prime EC tube morphogenic responses (i.e. added overnight prior to the morphogenic assay to hematopoietic stem cell cytokines in collagen matrices and, interestingly, they also prime EC tube morphogenesis in 3D fibrin matrices. EC-pericyte interactions in 3D fibrin matrices leads to marked vascular basement membrane assembly as demonstrated using immunofluorescence and transmission electron microscopy. Furthermore, we show that hematopoietic stem cell cytokines and pericytes stimulate EC sprouting in fibrin matrices in a manner dependent on the α5β1 integrin. This novel co-culture system, under serum-free defined conditions, allows for a molecular analysis of EC tube assembly, pericyte recruitment and maturation events in a critical ECM environment (i.e. fibrin matrices that regulates angiogenic events in postnatal life.

  1. [CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

    Science.gov (United States)

    Madiyeva, M; Rymbayeva, T

    2017-11-01

    The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

  2. H4 replication-dependent diacetylation and Hat1 promote S-phase chromatin assembly in vivo

    Science.gov (United States)

    Ejlassi-Lassallette, Aïda; Mocquard, Eloïse; Arnaud, Marie-Claire; Thiriet, Christophe

    2011-01-01

    While specific posttranslational modification patterns within the H3 and H4 tail domains are associated with the S-phase, their actual functions in replication-dependent chromatin assembly have not yet been defined. Here we used incorporation of trace amounts of recombinant proteins into naturally synchronous macroplasmodia of Physarum polycephalum to examine the function of H3 and H4 tail domains in replication-coupled chromatin assembly. We found that the H3/H4 complex lacking the H4 tail domain was not efficiently recovered in nuclei, whereas depletion of the H3 tail domain did not impede nuclear import but chromatin assembly failed. Furthermore, our results revealed that the proper pattern of acetylation on the H4 tail domain is required for nuclear import and chromatin assembly. This is most likely due to binding of Hat1, as coimmunoprecipitation experiments showed Hat1 associated with predeposition histones in the cytoplasm and with replicating chromatin. These results suggest that the type B histone acetyltransferase assists in shuttling the H3/H4 complex from cytoplasm to the replication forks. PMID:21118997

  3. Translation elongation factor 1A facilitates the assembly of the tombusvirus replicase and stimulates minus-strand synthesis.

    OpenAIRE

    Zhenghe Li; Judit Pogany; Steven Tupman; Anthony M Esposito; Terri Goss Kinzy; Peter D Nagy

    2010-01-01

    Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with w...

  4. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.

    Directory of Open Access Journals (Sweden)

    John Danesh

    2008-04-01

    Full Text Available The relevance to coronary heart disease (CHD of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6, may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context.Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y. Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65 per 2 standard deviation (SD increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15 with long-term average ("usual" IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death. Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83 per 2 SD increase in baseline IL-6

  5. Association between HOMA-IR, fasting insulin and fasting glucose with coronary heart disease mortality in nondiabetic men: a 20-year observational study.

    Science.gov (United States)

    Kurl, Sudhir; Zaccardi, Francesco; Onaemo, Vivian N; Jae, Sae Young; Kauhanen, Jussi; Ronkainen, Kimmo; Laukkanen, Jari A

    2015-02-01

    Whether glucose and insulin are differently associated with the risk of coronary heart disease (CHD) mortality is unclear. We aimed to estimate the association between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR), fasting serum insulin (FI) and fasting plasma glucose (FPG) with incident CHD mortality in a prospective study including middle-aged nondiabetic Finnish men. During an average follow-up of 20 years, 273 (11 %) CHD deaths occurred. In a multivariable Cox regression analysis adjusted for age, body mass index, systolic blood pressure, serum LDL-cholesterol, cigarette smoking, history of CHD, alcohol consumption, blood leukocytes and plasma fibrinogen, the hazard ratios (HRs) for CHD mortality comparing top versus bottom quartiles were as follows: 1.69 (95 % CI: 1.15-2.48; p = 0.008) for HOMA-IR; 1.59 (1.09-2.32; p = 0.016) for FI; and 1.26 (0.90-1.76; p = 0.173) for FPG. These findings suggest that IR and FI, but not FPG, are independent risk factors for CHD mortality. Further studies could help clarify these results in terms of screening and risk stratification, causality of the associations, and therapeutical implications.

  6. Molecular Self-Assembly of Enantiopure Heptahelicene-2-Carboxylic Acid on Calcite (10(1)over-bar4)

    Czech Academy of Sciences Publication Activity Database

    Hauke, Ch. M.; Rahe, P.; Nimmrich, M.; Schütte, J.; Kittelmann, M.; Stará, Irena G.; Starý, Ivo; Rybáček, Jiří; Kühnle, A.

    2012-01-01

    Roč. 116, č. 7 (2012), s. 4637-4641 ISSN 1932-7447 R&D Projects: GA ČR(CZ) GAP207/10/2207 Institutional research plan: CEZ:AV0Z40550506 Keywords : helicene * nc-AFM * molecular self assembly Subject RIV: CC - Organic Chemistry Impact factor: 4.814, year: 2012

  7. Adult congenital heart disease nurse coordination: Essential skills and role in optimizing team-based care a position statement from the International Society for Adult Congenital Heart Disease (ISACHD).

    Science.gov (United States)

    Sillman, Christina; Morin, Joanne; Thomet, Corina; Barber, Deena; Mizuno, Yoshiko; Yang, Hsiao-Ling; Malpas, Theresa; Flocco, Serena Francesca; Finlay, Clare; Chen, Chi-Wen; Balon, Yvonne; Fernandes, Susan M

    2017-02-15

    Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with congenital heart disease (CHD) worldwide. Among ISACHD's objectives is to "promote a holistic team-based approach to the care of the adult with CHD that is comprehensive, patient-centered, and interdisciplinary" (http://www.isachd.org). This emphasis on team-based care reflects the fact that adults with CHD constitute a heterogeneous population with a wide spectrum of disease complexity, frequent association with other organ involvement, and varied co-morbidities and psychosocial issues. Recognizing the vital role of the adult CHD (ACHD) nurse coordinator (ACHD-NC) in optimizing team-based care, ISACHD established a task force to elucidate and provide guidance on the roles and responsibilities of the ACHD-NC. Acknowledging that nursing roles can vary widely from region to region based on factors such as credentials, scopes of practice, regulations, and local culture and tradition, an international panel was assembled with experts from North America, Europe, East Asia, and Oceania. The writing committee was tasked with reviewing key aspects of the ACHD-NC's role in team-based ACHD care. The resulting ISACHD position statement addresses the ACHD-NC's role and skills required in organizing, coordinating, and facilitating the care of adults with CHD, holistic assessment of the ACHD patient, patient education and counseling, and support for self-care management and self-advocacy. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  8. Synthesis and characterization of designed BMHP1-derived self-assembling peptides for tissue engineering applications.

    Science.gov (United States)

    Silva, Diego; Natalello, Antonino; Sanii, Babak; Vasita, Rajesh; Saracino, Gloria; Zuckermann, Ronald N; Doglia, Silvia Maria; Gelain, Fabrizio

    2013-01-21

    The importance of self-assembling peptides (SAPs) in regenerative medicine is becoming increasingly recognized. The propensity of SAPs to form nanostructured fibers is governed by multiple forces including hydrogen bonds, hydrophobic interactions and π-π aromatic interactions among side chains of the amino acids. Single residue modifications in SAP sequences can significantly affect these forces. BMHP1-derived SAPs is a class of biotinylated oligopeptides, which self-assemble in β-structured fibers to form a self-healing hydrogel. In the current study, selected modifications in previously described BMHP1-derived SAPs were designed in order to investigate the influence of modified residues on self-assembly kinetics and scaffold formation properties. The Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis demonstrated the secondary structure (β-sheet) formation in all modified SAP sequences, whereas atomic force microscopy (AFM) analysis further confirmed the presence of nanofibers. Furthermore, the fiber shape and dimension analysis by AFM showed flattened and twisted fiber morphology ranging from ∼8 nm to ∼70 nm. The mechanical properties of the pre-assembled and post assembled solution were investigated by rheometry. The shear-thinning behavior and rapid re-healing properties of the pre-assembled solutions make them a preferable choice for injectable scaffolds. The wide range of stiffnesses (G')--from ∼1000 to ∼27,000 Pa--exhibited by the post-assembled scaffolds demonstrated their potential for a variety of tissue engineering applications. The extra cellular matrix (ECM) mimicking (physically and chemically) properties of SAP scaffolds enhanced cell adhesion and proliferation. The capability of the scaffold to facilitate murine neural stem cell (mNSC) proliferation was evaluated in vitro: the increased mNSCs adhesion and proliferation demonstrated the potential of newly synthesized SAPs for regenerative medicine

  9. Spatial pattern and variations in the prevalence of congenital heart disease in children aged 4-18 years in the Qinghai-Tibetan Plateau.

    Science.gov (United States)

    Ma, Li-Guang; Chen, Qiu-Hong; Wang, Yuan-Yuan; Wang, Jing; Ren, Zhou-Peng; Cao, Zong-Fu; Cao, Yan-Rong; Ma, Xu; Wang, Bin-Bin

    2018-06-15

    This study aimed to investigate the spatial distribution pattern of the prevalence of congenital heart disease (CHD) in children in Qinghai-Tibetan Plateau (QTP), a high-altitude region in China. Epidemiological data from a survey on the prevalence of CHD in Qinghai Province including 288,066 children (4-18 years) were used in this study. The prevalence and distribution pattern of CHD was determined by sex, CHD subtype, and nationality and altitude. Spatial pattern analysis using Getis-Ord Gi ⁎ was used to identify the spatial distribution of CHD. Bayesian spatial binomial regression was performed to examine the relationship between the prevalence of CHD and environmental risk factors in the QTP. The prevalence of CHD showed a significant spatial clustering pattern. The Tibetan autonomous prefecture of Yushu (average altitude > 4000 m) and the Mongolian autonomous county of Henan (average altitude > 3600 m) in Huangnan had the highest prevalence of CHD. Univariate analysis showed that with ascending altitude, the total prevalence of CHD, that in girls and boys with CHD, and that of the subtypes PDA and ASD increasing accordingly. Thus, environmental factors greatly contributed to the prevalence of CHD. The prevalence of CHD shows significant spatial clustering pattern in the QTP. The CHD subtype prevalence clustering pattern has statistical regularity which would provide convenient clues of environmental risk factors. Our results may provide support to make strategies of CHD prevention, to reduce the incidence of CHD in high altitude regions of China. Copyright © 2018. Published by Elsevier B.V.

  10. Soldering in electronics assembly

    CERN Document Server

    Judd, Mike

    2013-01-01

    Soldering in Electronics Assembly discusses several concerns in soldering of electronic assemblies. The book is comprised of nine chapters that tackle different areas in electronic assembly soldering. Chapter 1 discusses the soldering process itself, while Chapter 2 covers the electronic assemblies. Chapter 3 talks about solders and Chapter 4 deals with flux. The text also tackles the CS and SC soldering process. The cleaning of soldered assemblies, solder quality, and standards and specifications are also discussed. The book will be of great use to professionals who deal with electronic assem

  11. Association of six CpG-SNPs in the inflammation-related genes with coronary heart disease.

    Science.gov (United States)

    Chen, Xiaomin; Chen, Xiaoying; Xu, Yan; Yang, William; Wu, Nan; Ye, Huadan; Yang, Jack Y; Hong, Qingxiao; Xin, Yanfei; Yang, Mary Qu; Deng, Youping; Duan, Shiwei

    2016-07-25

    Chronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammation-related CpG-SNPs, including IL1B rs16944, IL1R2 rs2071008, PLA2G7 rs9395208, FAM5C rs12732361, CD40 rs1800686, and CD36 rs2065666). Allele and genotype frequencies were compared between CHD and non-CHD individuals using the CLUMP22 software with 10,000 Monte Carlo simulations. Allelic tests showed that PLA2G7 rs9395208 and CD40 rs1800686 were significantly associated with CHD. Moreover, IL1B rs16944, PLA2G7 rs9395208, and CD40 rs1800686 were shown to be associated with CHD under the dominant model. Further gender-based subgroup tests showed that one SNP (CD40 rs1800686) and two SNPs (FAM5C rs12732361 and CD36 rs2065666) were associated with CHD in females and males, respectively. And the age-based subgroup tests indicated that PLA2G7 rs9395208, IL1B rs16944, and CD40 rs1800686 were associated with CHD among individuals younger than 55, younger than 65, and over 65, respectively. In conclusion, all the six inflammation-related CpG-SNPs (rs16944, rs2071008, rs12732361, rs2065666, rs9395208, and rs1800686) were associated with CHD in the combined or subgroup tests, suggesting an important role of inflammation in the risk of CHD.

  12. HIV-1 Viral RNA Dynamics at the Plasma Membrane May Provide Insight into Viral Assembly | Poster

    Science.gov (United States)

    Many aspects of how infectious viruses assemble in cells have yet to be completely deciphered. However, as reported in a recent Journal of Virology paper, researchers may be one step closer to understanding how HIV-1, the virus that causes AIDS, assembles and replicates.

  13. Meta-analyses of KIF6 Trp719Arg in coronary heart disease and statin therapeutic effect.

    Directory of Open Access Journals (Sweden)

    Ping Peng

    Full Text Available The goal of our study is to assess the contribution of KIF6 Trp719Arg to both the risk of CHD and the efficacy of statin therapy in CHD patients.Meta-analysis of 8 prospective studies among 77,400 Caucasians provides evidence that 719Arg increases the risk of CHD (P<0.001, HR = 1.27, 95% CI = 1.15-1.41. However, another meta-analysis of 7 case-control studies among 65,200 individuals fails to find a significant relationship between Trp719Arg and the risk of CHD (P = 0.642, OR = 1.02, 95% CI = 0.95-1.08. This suggests that the contribution of Trp719Arg to CHD varies in different ethnic groups. Additional meta-analysis also shows that statin therapy only benefit the vascular patients carry 719Arg allele (P<0.001, relative ratio (RR = 0.60, 95% CI = 0.54-0.67. To examine the role of this genetic variant in CHD risk in Han Chinese, we have conducted a case-control study with 289 CHD cases, 193 non-CHD controls, and 329 unrelated healthy volunteers as healthy controls. On post hoc analysis, significant allele frequency difference of 719Arg is observed between female CHD cases and female total controls under the dominant model (P = 0.04, χ(2 = 4.228, df = 1, odd ratio (OR = 1.979, 95% confidence interval (CI = 1.023-3.828. Similar trends are observed for post hoc analysis between female CHD cases and female healthy controls (dominant model: P = 0.04, χ(2 = 4.231, df = 1, OR = 2.015, 95% CI = 1.024-3.964. Non-genetic CHD risk factors are not controlled in these analyses.Our meta-analysis demonstrates the role of Trp719Arg of KIF6 gene in the risk of CHD in Caucasians. The meta-analysis also suggests the role of this variant in statin therapeutic response in vascular diseases. Our case-control study suggests that Trp719Arg of KIF6 gene is associated with CHD in female Han Chinese through a post hoc analysis.

  14. Cardiovascular diseases and risk factors among Chinese immigrants.

    Science.gov (United States)

    Gong, Zhizhong; Zhao, Dong

    2016-04-01

    The aim of this study is to identify the prevalence of cardiovascular disease (CVD) and major CVD risk factors, including diabetes, hypertension, dyslipidemia, obesity and smoking among Chinese immigrants by a systematic review of studies from various countries. PubMed and the China National Knowledge Infrastructure databases were searched for studies of the prevalence of major CVDs and risk factors, and of CVD mortality among Chinese immigrants. The search identified 386 papers, 16 of which met the inclusion criteria for this review. In mainland China, there is a pattern of high stroke prevalence but low coronary heart disease (CHD) prevalence. Among Chinese immigrants, there is a much lower prevalence and mortality of stroke, but a higher prevalence and mortality of CHD, even though these are lower than the rates in immigrants of other ethnicities in the host country. The prevalence of CVD risk factors is also markedly different in immigrants. Compared with mainland Chinese, Chinese immigrants have a higher prevalence of diabetes and hypertension, higher serum cholesterol, poorer dietary patterns, and higher prevalence of obesity and smoking. Thus, the epidemiological pattern of CVD among Chinese immigrants changes compared with resident mainland Chinese. The less healthy environmental factor after immigration may be a major trigger in the adverse CVD status of Chinese immigrants. It is important for policy-makers to pay more attention to specific minority immigrant groups, and to implement more effective preventive measures to improve the health of immigrant populations.

  15. Coronary artery disease: the role of lipids, hypertension and smoking.

    Science.gov (United States)

    Keil, U

    2000-01-01

    Pioneering epidemiological projects such as the Seven Countries study, and the Framingham Heart study established the classical risk factor concept for coronary heart disease (CAD). These landmark studies showed that a raised serum total cholesterol, high blood pressure (systolic and diastolic) and smoking increase the risk of developing CHD in men and women in a graded fashion. Women develop CHD about 10 years later than men and women's risk is smaller. In the years and decades following these early studies many more prospective cohort studies primarily in the US and Europe have confirmed the early findings. In Germany two occupational and one population based cohort studies have contributed further information on this topic. In addition interactions between the three classical risk factors have been quantified, demonstrating for example that smoking carries a much higher risk for CHD in persons with high cholesterol values. Most cohort studies have confirmed that the relative risks for the classical risk factors are very similar. However, the respective absolute risks can differ tremendously, indicating that many more factors such as socio-economic conditions, nutrition, physical activity and others are of importance for the development of CHD. The scientific community, however, did not accept the consistent findings from the many observational studies as proof of causality. They required evidence that the risk for CHD could be reduced when the respective risk factor(s) was (were) diminished or eliminated. The late 1960s early 1970s thus saw the beginning of the era of randomized controlled trials (RCTs) following the advice of Archibald Cochrane who once wrote "we have to find that point on the distribution curve where therapy does more good than harm". We now know from meta-analyses of RCTs that a 1% reduction in serum cholesterol produces a 2-3% decline in risk for CHD and we can achieve reductions in total cholesterol of 20% or more. Regarding treatment of

  16. Association of TLL1 Gene Polymorphism (rs1503298, T > C) with Coronary Heart Disease in PREDICT, UDACS and ED Cohorts

    International Nuclear Information System (INIS)

    Zain, M.; Cooper, J. A.; Li, K. W.; Palmen, J.; Acharya, J.; Howard, P.; Ireland, H.; Humphries, S. E.; Awan, F. R.; Baig, S. M.; Elkeles, R. S.

    2014-01-01

    Objective: To determine the sequence variant of TLL1 gene (rs1503298, T > C) in three British cohorts (PREDICT, UDACS and ED) of patients with type-2 Diabetes mellitus (T2DM) in order to assess its association with coronary heart disease (CHD). Study Design: Analytical study. Place and Duration of Study: UCL, London, UK. Participants were genotyped in 2011-2012 for TLL1 SNP. Samples and related information were previously collected in 2001-2003 for PREDICT, and in 2001-2002 for UDACS and ED groups. Methodology: Patients included in PREDICT (n=600), UDACS (n=1020) and ED (n=1240) had Diabetes. TLL1 SNP (rs1503298, T > C) was genotyped using TaqMan technology. Allele frequencies were compared using c2 test, and tested for Hardy-Weinberg equilibrium. The risk of disease was assessed from Odds ratios (OR) with 95% Confidence Intervals (95% CI). Moreover, for the PREDICT cohort, the SNP association was tested with Coronary Artery Calcification (CAC) scores. Results: No significant association was found for this SNP with CHD or CAC scores in these cohorts. Conclusion: This SNP could not be confirmed as a risk factor for CHD in T2DM patients. However, the low power of the small sample size available is a limitation to the modest effect on risk. Further studies in larger samples would be useful. (author)

  17. The Assembly-Activating Protein Promotes Stability and Interactions between AAV’s Viral Proteins to Nucleate Capsid Assembly

    Directory of Open Access Journals (Sweden)

    Anna C. Maurer

    2018-05-01

    Full Text Available Summary: The adeno-associated virus (AAV vector is a preferred delivery platform for in vivo gene therapy. Natural and engineered variations of the AAV capsid affect a plurality of phenotypes relevant to gene therapy, including vector production and host tropism. Fundamental to these aspects is the mechanism of AAV capsid assembly. Here, the role of the viral co-factor assembly-activating protein (AAP was evaluated in 12 naturally occurring AAVs and 9 putative ancestral capsid intermediates. The results demonstrate increased capsid protein stability and VP-VP interactions in the presence of AAP. The capsid’s dependence on AAP can be partly overcome by strengthening interactions between monomers within the assembly, as illustrated by the transfer of a minimal motif defined by a phenotype-to-phylogeny mapping method. These findings suggest that the emergence of AAP within the Dependovirus genus relaxes structural constraints on AAV assembly in favor of increasing the degrees of freedom for the capsid to evolve. : Maurer et al. describe a phenotype-to-phylogeny mapping strategy correlating phenotypic variation in AAVs to a reconstructed phylogeny, revealing capsid structure-function relationships relevant to that phenotype. Dependence on the viral co-factor AAP for capsid assembly is examined, and capsid functional motifs, in addition to mechanistic roles of AAP, are elucidated. Keywords: AAV, AAP, adeno-associated virus, capsid assembly, manufacturing, capsid, vector engineering, structure-function, gene therapy

  18. Deterministic nanoparticle assemblies: from substrate to solution

    International Nuclear Information System (INIS)

    Barcelo, Steven J; Gibson, Gary A; Yamakawa, Mineo; Li, Zhiyong; Kim, Ansoon; Norris, Kate J

    2014-01-01

    The deterministic assembly of metallic nanoparticles is an exciting field with many potential benefits. Many promising techniques have been developed, but challenges remain, particularly for the assembly of larger nanoparticles which often have more interesting plasmonic properties. Here we present a scalable process combining the strengths of top down and bottom up fabrication to generate deterministic 2D assemblies of metallic nanoparticles and demonstrate their stable transfer to solution. Scanning electron and high-resolution transmission electron microscopy studies of these assemblies suggested the formation of nanobridges between touching nanoparticles that hold them together so as to maintain the integrity of the assembly throughout the transfer process. The application of these nanoparticle assemblies as solution-based surface-enhanced Raman scattering (SERS) materials is demonstrated by trapping analyte molecules in the nanoparticle gaps during assembly, yielding uniformly high enhancement factors at all stages of the fabrication process. (paper)

  19. X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3.

    NARCIS (Netherlands)

    Olcese, C.; Patel, M.P.; Shoemark, A.; Kiviluoto, S.; Legendre, M.; Williams, H.J.; Vaughan, C.K.; Hayward, J.; Goldenberg, A.; Emes, R.D.; Munye, M.M.; Dyer, L.; Cahill, T.; Bevillard, J.; Gehrig, C.; Guipponi, M.; Chantot, S.; Duquesnoy, P.; Thomas, L.; Jeanson, L.; Copin, B.; Tamalet, A.; Thauvin-Robinet, C.; Papon, J.F.; Garin, A.; Pin, I.; Vera, G.; Aurora, P.; Fassad, M.R.; Jenkins, L.; Boustred, C.; Cullup, T.; Dixon, M.; Onoufriadis, A.; Bush, A.; Chung, E.M.; Antonarakis, S.E.; Loebinger, M.R.; Wilson, R.; Armengot, M.; Escudier, E.; Hogg, C.; Amselem, S.; Sun, Z.; Bartoloni, L.; Blouin, J.L.; Mitchison, H.M.; Schmidts, M.; et al.,

    2017-01-01

    By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of

  20. Bir1 Deletion Causes Malfunction of the Spindle Assembly Checkpoint and Apoptosis in Yeast

    International Nuclear Information System (INIS)

    Ren, Qun; Liou, Liang-Chun; Gao, Qiuqiang; Bao, Xiaoming; Zhang, Zhaojie

    2012-01-01

    Cell division in yeast is a highly regulated and well studied event. Various checkpoints are placed throughout the cell cycle to ensure faithful segregation of sister chromatids. Unexpected events, such as DNA damage or oxidative stress, cause the activation of checkpoint(s) and cell cycle arrest. Malfunction of the checkpoints may induce cell death. We previously showed that under oxidative stress, the budding yeast cohesin Mcd1, a homolog of human Rad21, was cleaved by the caspase-like protease Esp1. The cleaved Mcd1 C-terminal fragment was then translocated to mitochondria, causing apoptotic cell death. In the present study, we demonstrated that Bir1 plays an important role in spindle assembly checkpoint and cell death. Similar to H 2 O 2 treatment, deletion of BIR1 using a BIR1-degron strain caused degradation of the securin Pds1, which binds and inactivates Esp1 until metaphase-anaphase transition in a normal cell cycle. BIR1 deletion caused an increase level of ROS and mis-location of Bub1, a major protein for spindle assembly checkpoint. In wild type, Bub1 was located at the kinetochores, but was primarily in the cytoplasm in bir1 deletion strain. When BIR1 was deleted, addition of nocodazole was unable to retain the Bub1 localization on kinetochores, further suggesting that Bir1 is required to activate and maintain the spindle assembly checkpoint. Our study suggests that the BIR1 function in cell cycle regulation works in concert with its anti-apoptosis function.

  1. Analysis of the rotation accident of assemblies in boiling water reactors

    International Nuclear Information System (INIS)

    Becerril-Gonzalez M, J. J.; Fuentes M, L.; Castillo M, J. A.; Ortiz S, J. J.; Perusquia de Cueto, R.

    2012-10-01

    For this work was analyzed the impact that would cause the load of a rotated fuel assembly in the behaviour of the core in the Cycle 14 of the Unit 1 of the nuclear power plant of Laguna Verde. To carry out this analysis the code Simulate-3 was used, with which was possible to analyze the behavior of the effective multiplication factor and the thermal limits (MAPRAT, MFLPD and MFLCPR). The rotation of fuel assemblies to 90, 180 and 270 grades was analyzed with regard to the design position, with 0, 1, 2 and 3 burnt cycles for these assemblies. The results show that the thermal limits remain inside the allowed values, therefore if this accident type happened the reactor could continue operating in a sure way. (Author)

  2. Dual personality of Mad1: regulation of nuclear import by a spindle assembly checkpoint protein.

    Science.gov (United States)

    Cairo, Lucas V; Ptak, Christopher; Wozniak, Richard W

    2013-01-01

    Nuclear transport is a dynamic process that can be modulated in response to changes in cellular physiology. We recently reported that the transport activity of yeast nuclear pore complexes (NPCs) is altered in response to kinetochore-microtubule (KT-MT) interaction defects. Specifically, KT detachment from MTs activates a signaling pathway that prevents the nuclear import of cargos by the nuclear transport factor Kap121p. This loss of Kap121p-mediated import is thought to influence the nuclear environment, including the phosphorylation state of nuclear proteins. A key regulator of this process is the spindle assembly checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss the underlying mechanisms and the physiological relevance of Mad1p cycling and the inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions within the pathway.

  3. Congenital Heart Disease: Vascular Risk Factors and Medication

    NARCIS (Netherlands)

    H.P.M. Smedts (Dineke)

    2011-01-01

    textabstractCongenital heart disease (CHD) is among the most common congenital abnormalities and involves structural anomalies of the heart and/or related major blood vessels. Congenital heart disease arises in the fi rst trimester of pregnancy, occurring often and in many forms. The reported CHD

  4. Self-assembled magnetic filter for highly efficient immunomagnetic separation.

    Science.gov (United States)

    Issadore, David; Shao, Huilin; Chung, Jaehoon; Newton, Andita; Pittet, Mikael; Weissleder, Ralph; Lee, Hakho

    2011-01-07

    We have developed a compact and inexpensive microfluidic chip, the self-assembled magnetic filter, to efficiently remove magnetically tagged cells from suspension. The self-assembled magnetic filter consists of a microfluidic channel built directly above a self-assembled NdFeB magnet. Micrometre-sized grains of NdFeB assemble to form alternating magnetic dipoles, creating a magnetic field with a very strong magnitude B (from the material) and field gradient ▽B (from the configuration) in the microfluidic channel. The magnetic force imparted on magnetic beads is measured to be comparable to state-of-the-art microfabricated magnets, allowing for efficient separations to be performed in a compact, simple device. The efficiency of the magnetic filter is characterized by sorting non-magnetic (polystyrene) beads from magnetic beads (iron oxide). The filter enriches the population of non-magnetic beads to magnetic beads by a factor of >10(5) with a recovery rate of 90% at 1 mL h(-1). The utility of the magnetic filter is demonstrated with a microfluidic device that sorts tumor cells from leukocytes using negative immunomagnetic selection, and concentrates the tumor cells on an integrated membrane filter for optical detection.

  5. Sex Factors in the Metabolic Syndrome as a Predictor of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Sunghwan Suh

    2014-12-01

    Full Text Available BackgroundMetabolic syndrome (MetS is a condition characterized by a cluster of metabolic disorders and is associated with increased risk of cardiovascular disease (CVD. This study analyzed data from the Korean Health and Genome Study to examine the impact of MetS on CVD.MethodsA total of 8,898 subjects (4,241 males and 4,657 females, 40 to 69 years of age, were enrolled and evaluated for the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow-up.ResultsThe prevalence of MetS at baseline was 22.0% (932/4,241 and 29.7% (1,383/4,657 in males and females, respectively. MetS was associated with increased risk of coronary heart disease (CHD; hazard ratio [HR], 1.818; 95% confidence interval [CI], 1.312 to 2.520 in males; HR, 1.789; 95% CI, 1.332 to 2.404 in females and CVD (HR, 1.689; 95% CI, 1.295 to 2.204 in males; HR, 1.686; 95% CI, 1.007 to 2.192 in females. Specifically, MetS was associated with risk of future stroke in females only (HR, 1.486; 95% CI, 1.007 to 2.192. Among MetS components, abdominal obesity and hypertension were independent predictors of both CHD and CVD. In addition, a higher number of MetS components correlated with higher CVD risk.ConclusionMetS is a significant risk factor for the development of CVD although its impact varies between sexes.

  6. NEDDylation promotes stress granule assembly.

    Science.gov (United States)

    Jayabalan, Aravinth Kumar; Sanchez, Anthony; Park, Ra Young; Yoon, Sang Pil; Kang, Gum-Yong; Baek, Je-Hyun; Anderson, Paul; Kee, Younghoon; Ohn, Takbum

    2016-07-06

    Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly.

  7. Nutrition and physical activity educational intervention on CHD risk factors: a systematic review study.

    Science.gov (United States)

    Rahmati Najarkolaei, Fatemeh; Ghaffarpasand, Eiman; Gholami Fesharaki, Mohammad; Jonaidi Jafari, Nematollah

    2015-01-01

    Fast growing epidemic of chronic diseases causes many health challenges over the world. Regarding reported pros and cons, the aim of the current study is to review the effect of nutrition and physical educational intervention in decreasing cardiovascular risk factors. In this review study, searching has done through the English and Persian databases. Articles with other languages, lack of important information, and score 3 or less in the JADAD standard checklist were exluded from the study. In the primary search, 194 articles have been found.Through four stages of secondary search and further evaluation, 43 articles were selected. These articles were published between 1989 to 2013. According to these findings, the majority of articles showed a positive effect of nutrition and physical activity educational interventions on cardiovascular risk factors- blood cholesterol, systolic and diastolic blood pressure, as well as smoking cigarette in high risk patients. These results, suggest the necessity of continiuting nutrition and physical educational intervention for individuals with cardiovascular risk factors.

  8. An artificial neural network prediction model of congenital heart disease based on risk factors: A hospital-based case-control study.

    Science.gov (United States)

    Li, Huixia; Luo, Miyang; Zheng, Jianfei; Luo, Jiayou; Zeng, Rong; Feng, Na; Du, Qiyun; Fang, Junqun

    2017-02-01

    An artificial neural network (ANN) model was developed to predict the risks of congenital heart disease (CHD) in pregnant women.This hospital-based case-control study involved 119 CHD cases and 239 controls all recruited from birth defect surveillance hospitals in Hunan Province between July 2013 and June 2014. All subjects were interviewed face-to-face to fill in a questionnaire that covered 36 CHD-related variables. The 358 subjects were randomly divided into a training set and a testing set at the ratio of 85:15. The training set was used to identify the significant predictors of CHD by univariate logistic regression analyses and develop a standard feed-forward back-propagation neural network (BPNN) model for the prediction of CHD. The testing set was used to test and evaluate the performance of the ANN model. Univariate logistic regression analyses were performed on SPSS 18.0. The ANN models were developed on Matlab 7.1.The univariate logistic regression identified 15 predictors that were significantly associated with CHD, including education level (odds ratio  = 0.55), gravidity (1.95), parity (2.01), history of abnormal reproduction (2.49), family history of CHD (5.23), maternal chronic disease (4.19), maternal upper respiratory tract infection (2.08), environmental pollution around maternal dwelling place (3.63), maternal exposure to occupational hazards (3.53), maternal mental stress (2.48), paternal chronic disease (4.87), paternal exposure to occupational hazards (2.51), intake of vegetable/fruit (0.45), intake of fish/shrimp/meat/egg (0.59), and intake of milk/soymilk (0.55). After many trials, we selected a 3-layer BPNN model with 15, 12, and 1 neuron in the input, hidden, and output layers, respectively, as the best prediction model. The prediction model has accuracies of 0.91 and 0.86 on the training and testing sets, respectively. The sensitivity, specificity, and Yuden Index on the testing set (training set) are 0.78 (0.83), 0.90 (0.95), and 0

  9. Quantification of Stereochemical Communication in Metal–Organic Assemblies

    NARCIS (Netherlands)

    Castilla, Ana M.; Miller, Mark A.; Nitschke, Jonathan R.; Smulders, Maarten M.J.

    2016-01-01

    The derivation and application of a statistical mechanical model to quantify stereochemical communication in metal–organic assemblies is reported. The factors affecting the stereochemical communication within and between the metal stereocenters of the assemblies were experimentally studied by

  10. Sex determination in Turdus amaurochalinus (Passeriformes: Muscicapidae: morphometrical analysis supported by CHD gene

    Directory of Open Access Journals (Sweden)

    Katyucha Von Kossel de Andrade Silva

    2011-06-01

    Full Text Available Sex determination is important for conservation and population studies, particularly for reproduction programs of threatened species and behavioural ecology. Turdus amaurochalinus, Creamy-bellied Thrush, only exhibits sexual dimorphism during the breeding season, when males are considered to show intense yellow bills, and females and immature males show dark brown bills. The objectives of this study were: 1 to determine the sex of individuals using genetic techniques, and 2 to test the hypothesis that sex dimorphism can be detected by morphometry. This study was carried out at Parque Nacional da Restinga de Jurubatiba, a preserved area located on the North coast of Rio de Janeiro State. The birds were captured using ornithological nets, singly marked with metal rings, weighed, measured and had blood samples collected before being released. The sex of 42 T. amaurochalinus individuals was determined using the CHD gene marker. A total of 20 males and 22 females were identified from June to August, with peak capture frequency in June. Turdus amaurochalinus females and males differed significantly in morphometrical measures. The most important traits to distinguish males from females were wing length (Student t-test=4.34, df=40, p=0.0001 and weight (Student t-test=2.08,df=40, p=0.044: females were heavier and had significantly shorter wing length than males. Females and males were correctly classified in 86% and 75% of cases, respectively, using Discriminant Analysis. The molecular analysis was the most secure method for sex determination in the studied species. Rev. Biol. Trop. 59 (2: 789- 794. Epub 2011 June 01.

  11. Dissection of β-barrel Outer Membrane Protein Assembly Pathways through Characterizing BamA POTRA 1 Mutants of Escherichia coli

    Science.gov (United States)

    Bennion, Drew; Charlson, Emily S.; Coon, Eric; Misra, Rajeev

    2010-01-01

    Summary BamA of Escherichia coli is an essential component of the hetero-oligomeric machinery that mediates β-barrel outer membrane protein (OMP) assembly. The C- and N-termini of BamA fold into trans-membrane β-barrel and five soluble POTRA domains, respectively. Detailed characterization of BamA POTRA 1 missense and deletion mutants revealed two competing OMP assembly pathways, one of which is followed by the archetypal trimeric β-barrel OMPs, OmpF and LamB, and is dependent on POTRA 1. Interestingly, our data suggest that BamA also requires its POTRA 1 domain for proper assembly. The second pathway is independent of POTRA 1 and is exemplified by TolC. Site-specific cross-linking analysis revealed that the POTRA 1 domain of BamA interacts with SurA, a periplasmic chaperone required for the assembly of OmpF and LamB, but not that of TolC and BamA. The data suggest that SurA and BamA POTRA 1 domain function in concert to assist folding and assembly of most β-barrel OMPs except for TolC, which folds into a unique soluble α-helical barrel and an OM-anchored β-barrel. The two assembly pathways finally merge at some step beyond POTRA 1 but presumably before membrane insertion, which is thought to be catalyzed by the trans-membrane β-barrel domain of Bam A. PMID:20598079

  12. Guided assembly of nanoparticles on electrostatically charged nanocrystalline diamond thin films

    Directory of Open Access Journals (Sweden)

    Verveniotis Elisseos

    2011-01-01

    Full Text Available Abstract We apply atomic force microscope for local electrostatic charging of oxygen-terminated nanocrystalline diamond (NCD thin films deposited on silicon, to induce electrostatically driven self-assembly of colloidal alumina nanoparticles into micro-patterns. Considering possible capacitive, sp2 phase and spatial uniformity factors to charging, we employ films with sub-100 nm thickness and about 60% relative sp2 phase content, probe the spatial material uniformity by Raman and electron microscopy, and repeat experiments at various positions. We demonstrate that electrostatic potential contrast on the NCD films varies between 0.1 and 1.2 V and that the contrast of more than ±1 V (as detected by Kelvin force microscopy is able to induce self-assembly of the nanoparticles via coulombic and polarization forces. This opens prospects for applications of diamond and its unique set of properties in self-assembly of nano-devices and nano-systems.

  13. Supplemental description of ROSA-IV/LSTF with No.1 simulated fuel-rod assembly

    International Nuclear Information System (INIS)

    1989-09-01

    Forty-two integral simulation tests of PWR small break LOCA (loss-of-coolant accident) and transient were conducted at the ROSA-IV Large-Scale Test Facility (LSTF) with the No.1 simulated fuel-rod assembly between March 1985 and August 1988. Described in the report are supplemental information on modifications of the system hardware and measuring systems, results of system characteristics tests including the initial fluid mass inventory and heat loss distribution for the primary system, and thermal properties for the heater rod materials. These are necessary to establish the correct boundary conditions of each LSTF experiment with the No.1 core assembly in addition to the system data given in the system description report (JAERI-M 84-237). (author)

  14. High frequency of submicroscopic genomic aberrations detected by tiling path array comparative genome hybridisation in patients with isolated congenital heart disease

    DEFF Research Database (Denmark)

    Erdogan, F; Larsen, Lars Allan; Zhang, L

    2008-01-01

    BACKGROUND: Congenital heart disease (CHD) is the most common birth defect and affects nearly 1% of newborns. The aetiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnanc...

  15. HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation.

    Science.gov (United States)

    Ho, Yik-Khuan; Zhi, Huijun; Bowlin, Tara; Dorjbal, Batsukh; Philip, Subha; Zahoor, Muhammad Atif; Shih, Hsiu-Ming; Semmes, Oliver John; Schaefer, Brian; Glover, J N Mark; Giam, Chou-Zen

    2015-08-01

    Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-κB kinase (IKK)/NF-κB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1-infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFβ-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto-phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IκBα and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-κB activation by Tax. Activation of the non-canonical NF-κB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells.

  16. Associations between interleukin-1 gene polymorphisms and coronary heart disease risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Liang Zhou

    Full Text Available OBJECTIVE: A great number of studies regarding the associations between IL-1B-511, IL-1B+3954 and IL-1RN VNTR polymorphisms within the IL-1gene cluster and coronary heart disease (CHD have been published. However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. METHODS: Published literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs with 95% confidence intervals (CIs were calculated using random- or fixed- effect model. RESULTS: Thirteen studies (3,219 cases/2,445 controls for IL-1B-511 polymorphism, nine studies (1,828 cases/1,818 controls for IL-1B+3954 polymorphism and twelve studies (2,987 cases/ 2,208 controls for IL-1RN VNTR polymorphism were included in this meta analysis. The results indicated that both IL-1B-511 and IL-1B+3954 polymorphisms were not associated with CHD risk (IL-1B-511 T vs. C: OR = 0.98, 95%CI 0.87-1.09; IL-1B+3954 T vs. C: OR = 1.06, 95%CI 0.95-1.19. Similarly, there was no association between IL-1RN VNTR polymorphism and CHD risk (*2 vs. L: OR = 1.00, 95%CI 0.85-1.17. CONCLUSIONS: This meta-analysis suggested that there were no associations between IL-1 gene cluster polymorphisms and CHD.

  17. Arabidopsis Chromatin Assembly Factor 1 is required for occupancy and position of a subset of nucleosomes

    Czech Academy of Sciences Publication Activity Database

    Munoz-Viana, R.; Wildhaber, T.; Trejo-Arellano, M.S.; Mozgová, Iva; Hennig, L.

    2017-01-01

    Roč. 92, č. 3 (2017), s. 363-374 ISSN 0960-7412 Institutional support: RVO:61388971 Keywords : Arabidopsis thaliana * chromatin * CAF-1 Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 5.901, year: 2016

  18. Vascular endothelial growth factor attachment to hydroxyapatite via self-assembled monolayers promotes angiogenic activity of endothelial cells

    International Nuclear Information System (INIS)

    Solomon, Kimberly D.; Ong, Joo L.

    2013-01-01

    Currently, tissue engineered constructs for critical sized bone defects are non-vascularized. There are many strategies used in order to promote vascularization, including delivery of growth factors such as vascular endothelial growth factor (VEGF). In this study, hydroxyapatite (HA) was coated with self-assembled monolayers (SAMs). The SAMs were in turn used to covalently bind VEGF to the surface of HA. The different SAM chain length ratios (phosphonoundecanoic acid (11-PUDA):16-phosphonohexadecanoic acid (16-PHDA) utilized in this study were 0:100, 25:75, 50:50, 75:25, and 100:0. Surfaces were characterized by contact angle (CA) and atomic force microscopy, and an in vitro VEGF release study was performed. It was observed that CA and root-mean-squared roughness were not significantly affected by the addition of SAMs, but that CA was significantly lowered with the addition of VEGF. VEGF release profiles of bound VEGF groups all demonstrated less initial burst release than adsorbed control, indicating that VEGF was retained on the HA surface when bound by SAMs. An in vitro study using human aortic endothelial cells (HAECs) demonstrated that bound VEGF increased metabolic activity and caused sustained production of angiopoietin-2, an angiogenic marker, over 28 days. In conclusion, SAMs provide a feasible option for growth factor delivery from HA surfaces, enhancing angiogenic activity of HAECs in vitro. - Highlights: • Vascular endothelial growth factor (VEGF) is attached to hydroxyapatite (HA). • Self-assembled monolayers (SAMs) delay the release of VEGF from hydroxyapatite. • SAM chain length ratio affects the total mass of VEGF released. • VEGF on HA up-regulates proliferation and angiogenic activity of endothelial cells

  19. Human Assisted Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  20. Analysis of irradiation temperature in fuel rods of OGL-1 fuel assembly

    International Nuclear Information System (INIS)

    Fukuda, Kousaku; Kobayashi, Fumiaki; Minato, Kazuo; Ikawa, Katsuichi; Iwamoto, Kazumi

    1984-10-01

    Irradiation temperature in the fuel rods of 5th OGL-1 fuel assembly was analysed by the system composed by STPDSP2 and TRUMP codes. As the measured input-data, following parameters were allowed for; circumferential heating distribution around the fuel rod, which was measured in the JMTR critical assembly, axial heating distribution through the fuel rod, ratio of peak heatings of three fuel rods, and pre- and post-irradiation outer radii of the fuel compacts and inner radii of the graphite sleeves, which had been measured in PIE of the 5th OGL-1 fuel assembly. In computation the axial distributions of helium coolant temperature through the fuel rod and the heating value of each fuel rod were, firstly, calculated as input data for TRUMP. The TRUMP calculation yielded the temperatures which were fitted in those measured by all of the thermo-couples installed in the fuel rods, by adjusting only the value of the surface heat transfer coefficient, and consequently, the temperatures in all portions of the fuel rod were obtained. The apparent heat transfer coefficient changed to 60% of the initial values in the middle period of irradiation. For this reduction it was deduced that shoot had covered the surface of the fuel rod during irradiation, which was confirmed in PIE. Beside it, several things were found in this analysis. (author)

  1. The association of C-reactive protein and CRP genotype with coronary heart disease: findings from five studies with 4,610 cases amongst 18,637 participants.

    Directory of Open Access Journals (Sweden)

    Debbie A Lawlor

    Full Text Available BACKGROUND: It is unclear whether C-reactive protein (CRP is causally related to coronary heart disease (CHD. Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864 and CHD risk in the largest study to date of this association. METHODS AND RESULTS: We estimated the association of CRP genetic variant +1444C>T (rs1130864 with CRP levels and with CHD in five studies and then pooled these analyses (N = 18,637 participants amongst whom there were 4,610 cases. CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass whereas genotype (rs1130864 was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95%CI: 1.06, 1.21, and after further adjustment for confounding factors it was 1.07 (95%CI: 1.02, 1.13. Genotype (rs1130864 was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95%CI: 1.15, 1.28 and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95%CI: 1.11, 1.18, with no strong evidence in either analyses of between study heterogeneity (I(2 = 0%, p>0.9 for both analyses. There was no association of genotype (rs1130864 with CHD: pooled odds ratio 1.01 (95%CI: 0.88, 1.16 comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95%CI: 0.90, 1.03 per additional T allele (I(20.6 for both meta-analyses. An instrumental variables analysis (in which the proportion of CRP levels explained by rs1130864 was related to CHD suggested that circulating CRP was not associated with CHD: the odds ratio for a doubling of CRP level was 1.04 (95%CI: 0.61, 1.80. CONCLUSIONS

  2. ACTH-induced caveolin-1 tyrosine phosphorylation is related to podosome assembly in Y1 adrenal cells

    International Nuclear Information System (INIS)

    Colonna, Cecilia; Podesta, Ernesto J.

    2005-01-01

    Y1 adrenocortical cells respond to ACTH with a characteristic rounding-up that facilitates cAMP signaling, critical for transport of cholesterol to the mitochondria and increase in steroid secretion. We here demonstrate that caveolin-1 participates in coupling activation of protein kinase A (PKA) to the control of cell shape. ACTH/8-Br-cAMP induced reorganization of caveolin-1-positive structures in correlation with the cellular rounding-up. Concomitant with this change, there was an increase in the phosphorylation of caveolin-1 (Tyr-14) localized at focal adhesions (FA) with reorganization of FA to rounded, ringlike structures. Colocalization with phalloidin showed that phosphocaveolin is present at the edge of actin filaments and that after ACTH stimulation F-actin dots at the cell periphery become surrounded by phosphocaveolin-1. These observations along with electron microscopy studies revealed these structures as podosomes. Podosome assembly was dependent on both PKA and tyrosine kinase activities because their formation was impaired after treatment with specific inhibitors [myristoylated PKI (mPKI) or PP2, respectively] previous to ACTH/8-Br-cAMP stimulation. These results show for the first time that ACTH induces caveolin-1 phosphorylation and podosome assembly in Y1 cells and support the view that the morphological and functional responses to PKA activation in steroidogenic cells are related to cytoskeleton dynamics

  3. The association of 83 plasma proteins with CHD mortality, BMI, HDL-, and total-cholesterol in men: Applying multivariate statistics to identify proteins with prognostic value and biological relevance

    NARCIS (Netherlands)

    Geert Heidema, A.; Thissen, U.; Boer, J.M.A.; Bouwman, F.G.; Feskens, E.J.M.; Mariman, E.C.M.

    2009-01-01

    In this study, we applied the multivariate statistical tool Partial Least Squares (PLS) to analyze the relative importance of 83 plasma proteins in relation to coronary heart disease (CHD) mortality and the intermediate end points body mass index, HDL-cholesterol and total cholesterol. From a Dutch

  4. Thermal structural analysis of SST-1 vacuum vessel and cryostat assembly using ANSYS

    International Nuclear Information System (INIS)

    Santra, Prosenjit; Bedakihale, Vijay; Ranganath, Tata

    2009-01-01

    Steady state super-conducting tokamak-1 (SST-1) is a medium sized tokamak, which has been designed to produce a 'D' shaped double null divertor plasma and operate in quasi steady state (1000 s). SST-1 vacuum system comprises of plasma chamber (vacuum vessel, interconnecting rings, baking and cooling channels), and cryostat all made of SS 304L material designed to meet ultra high vacuum requirements for plasma generation and confinement. Prior to plasma shot and operation the vessel assembly is baked to 250/150 deg. C from room temperature and discharge cleaned to remove impurities/trapped gases from wall surfaces. Due to baking the non-uniform temperature pattern on the vessel assembly coupled with atmospheric pressure loading and self-weight give rise to high thermal-structural stresses, which needs to be analyzed in detail. In addition the vessel assembly being a thin shell vessel structure needs to be checked for critical buckling load caused by atmospheric and baking thermal loads. Considering symmetry of SST-1, 1/16th of the geometry is modeled for finite element (FE) analysis using ANSYS for different loading scenarios, e.g. self-weight, pressure loading considering normal operating conditions, and off-normal loads coupled with baking of vacuum vessel from room temperature 250 deg. C to 150 deg. C, buckling and modal analysis for future dynamic analysis. The paper will discuss details about SST-1 vacuum system/cryostat, solid and FE model of SST-1, different loading scenarios, material details and the stress codes used. We will also present the thermal structural results of FE analysis using ANSYS for various load cases being investigated and our observations under different loading conditions.

  5. Measurement of gamma and neutron radiations inside spent fuel assemblies with passive detectors

    Czech Academy of Sciences Publication Activity Database

    Viererbl, L.; Lahodová, Z.; Voljanskij, A.; Klupák, V.; Koleška, M.; Cabalka, M.; Turek, Karel

    2011-01-01

    Roč. 652, č. 1 (2011), s. 90-93 ISSN 0168-9002 Institutional research plan: CEZ:AV0Z10480505 Keywords : fuel assembly * spent fuel * track detector Subject RIV: JF - Nuclear Energetics Impact factor: 1.207, year: 2011

  6. IMPROVEMENT FOR AN ASSEMBLY FLOW FOR A GIVEN COMPONENT (1

    Directory of Open Access Journals (Sweden)

    Ancuţa BĂLTEANU,

    2017-05-01

    Full Text Available This study is carried out in a line of assembly of a finite wiring product. The assembly of this finished product is done in two specific sections. For the analysis of the activities in the assembly section, the timing method of the work stations was used. On the basis of the work times obtained and their centralization, the Keizen method was subsequently applied to obtain an improvement in the installation flow. Finally, a reduction in working times was achieved, as well as a more ergonomic arrangement of jobs. This paper is the first in a series of 3 papers to deal with this subject.

  7. Exploring the effects of transfers and readmissions on trends in population counts of hospital admissions for coronary heart disease: a Western Australian data linkage study.

    Science.gov (United States)

    Lopez, Derrick; Nedkoff, Lee; Knuiman, Matthew; Hobbs, Michael S T; Briffa, Thomas G; Preen, David B; Hung, Joseph; Beilby, John; Mathur, Sushma; Reynolds, Anna; Sanfilippo, Frank M

    2017-11-17

    To develop a method for categorising coronary heart disease (CHD) subtype in linked data accounting for different CHD diagnoses across records, and to compare hospital admission numbers and ratios of unlinked versus linked data for each CHD subtype over time, and across age groups and sex. Cohort study. Person-linked hospital administrative data covering all admissions for CHD in Western Australia from 1988 to 2013. Ratios of (1) unlinked admission counts to contiguous admission (CA) counts (accounting for transfers), and (2) 28-day episode counts (accounting for transfers and readmissions) to CA counts stratified by CHD subtype, sex and age group. In all CHD subtypes, the ratios changed in a linear or quadratic fashion over time and the coefficients of the trend term differed across CHD subtypes. Furthermore, for many CHD subtypes the ratios also differed by age group and sex. For example, in women aged 35-54 years, the ratio of unlinked to CA counts for non-ST elevation myocardial infarction admissions in 2000 was 1.10, and this increased in a linear fashion to 1.30 in 2013, representing an annual increase of 0.0148. The use of unlinked counts in epidemiological estimates of CHD hospitalisations overestimates CHD counts. The CA and 28-day episode counts are more aligned with epidemiological studies of CHD. The degree of overestimation of counts using only unlinked counts varies in a complex manner with CHD subtype, time, sex and age group, and it is not possible to apply a simple correction factor to counts obtained from unlinked data. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. The educational gradient in coronary heart disease

    DEFF Research Database (Denmark)

    Ariansen, Inger; Mortensen, Laust Hvas; Igland, Jannicke

    2015-01-01

    BACKGROUND: Independently of cardiovascular disease (CVD) risk factors, cognitive ability may account for some of the excess risk of coronary heart disease (CHD) associated with lower education. We aimed to assess how late adolescence cognitive ability and midlife CVD risk factors are associated...... with the educational gradient in CHD in Norway. METHODS: In a cohort of 57 279 men born during 1949-1959, health survey information was linked to military conscription records of cognitive ability, to national educational data, to hospitalisation records from the Cardiovascular Disease in Norway (CVDNOR) project...... and to the Norwegian Cause of Death Registry. RESULTS: Age and period adjusted HR for incident CHD events was 3.62 (95% CI 2.50 to 5.24) for basic relative to tertiary education, and was attenuated after adjustment; to 2.86 (1.87 to 4.38) for cognitive ability, to 1.90 (1.30 to 2.78) for CVD risk factors, and to 1...

  9. The carbohydrate-binding module (CBM)-like sequence is crucial for rice CWA1/BC1 function in proper assembly of secondary cell wall materials.

    Science.gov (United States)

    Sato, Kanna; Ito, Sachiko; Fujii, Takeo; Suzuki, Ryu; Takenouchi, Sachi; Nakaba, Satoshi; Funada, Ryo; Sano, Yuzou; Kajita, Shinya; Kitano, Hidemi; Katayama, Yoshihiro

    2010-11-01

    We recently reported that the cwa1 mutation disturbed the deposition and assembly of secondary cell wall materials in the cortical fiber of rice internodes. Genetic analysis revealed that cwa1 is allelic to bc1, which encodes glycosylphosphatidylinositol (GPI)-anchored COBRA-like protein with the highest homology to Arabidopsis COBRA-like 4 (COBL4) and maize Brittle Stalk 2 (Bk2). Our results suggested that CWA1/BC1 plays a role in assembling secondary cell wall materials at appropriate sites, enabling synthesis of highly ordered secondary cell wall structure with solid and flexible internodes in rice. The N-terminal amino acid sequence of CWA1/BC1, as well as its orthologs (COBL4, Bk2) and other BC1-like proteins in rice, shows weak similarity to a family II carbohydrate-binding module (CBM2) of several bacterial cellulases. To investigate the importance of the CBM-like sequence of CWA1/BC1 in the assembly of secondary cell wall materials, Trp residues in the CBM-like sequence, which is important for carbohydrate binding, were substituted for Val residues and introduced into the cwa1 mutant. CWA1/BC1 with the mutated sequence did not complement the abnormal secondary cell walls seen in the cwa1 mutant, indicating that the CBM-like sequence is essential for the proper function of CWA1/BC1, including assembly of secondary cell wall materials.

  10. Risk Factors for Gross Motor Dysfunction in Infants with Congenital Heart Disease

    Science.gov (United States)

    Long, Suzanne H.; Eldridge, Bev J.; Galea, Mary P.; Harris, Susan R.

    2011-01-01

    Infants with congenital heart disease (CHD) that is severe enough to require early surgery are at risk for cognitive and motor delays, as well as musculoskeletal impairments, and are best managed by an interdisciplinary team during their hospital stay and after discharge. The purpose of this article is to review some of the risk factors associated…

  11. Dietary glycemic load and glycemic index and risk of coronary heart disease and stroke in Dutch men and women: the EPIC-MORGEN study.

    Directory of Open Access Journals (Sweden)

    Koert N J Burger

    Full Text Available BACKGROUND: The associations of glycemic load (GL and glycemic index (GI with the risk of cardiovascular diseases (CVD are not well-established, particularly in men, and may be modified by gender. OBJECTIVE: To assess whether high dietary GL and GI increase the risk of CVD in men and women. METHODS: A large prospective cohort study (EPIC-MORGEN was conducted within the general Dutch population among 8,855 men and 10,753 women, aged 21-64 years at baseline (1993-1997 and free of diabetes and CVD. Dietary intake was assessed with a validated food-frequency questionnaire and GI and GL were calculated using Foster-Powell's international table of GI. Information on morbidity and mortality was obtained through linkage with national registries. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs for incident coronary heart disease (CHD and stroke, while adjusting for age, CVD risk factors, and dietary factors. RESULTS: During a mean follow-up of 11.9 years, 581 CHD cases and 120 stroke cases occurred among men, and 300 CHD cases and 109 stroke cases occurred among women. In men, GL was associated with an increased CHD risk (adjusted HR per SD increase, 1.17 [95% CI, 1.02-1.35], while no significant association was found in women (1.09 [0.89-1.33]. GI was not associated with CHD risk in both genders, while it was associated with increased stroke risk in men (1.27 [1.02-1.58] but not in women (0.96 [0.75-1.22]. Similarly, total carbohydrate intake and starch intake were associated with a higher CHD risk in men (1.23 [1.04-1.46]; and 1.24 [1.07-1.45], but not in women. CONCLUSION: Among men, high GL and GI, and high carbohydrate and starch intake, were associated with increased risk of CVD.

  12. The Current Working Conditions in Ugandan Apparel Assembly Plants

    Directory of Open Access Journals (Sweden)

    Mike Tebyetekerwa

    2017-12-01

    Full Text Available Background: The present rapid shift of industrialization from developed to developing countries requires developing countries to understand issues related to work organization, management, and working conditions. There are many factors slackening production, of which working conditions is part. A complete inquiry into the workers' working conditions can enable managements to reduce risks in the workplaces and improve productivity. Understanding and awareness of the benefits of workplace research and a probe into the working conditions in the Ugandan apparel assembly plants are urgently required. Methods: A total of 103 (70 women and 33 men workers from five different plants were interviewed. Together with the top management of various plants, questionnaires about the workers' opinions of their physical working conditions were prepared. Data was collected using two methods: (1 questionnaire; and (2 observation of the workers during their work. Results: The results indicated that poor plant working conditions were mainly contributed by the workers' social factors and the management policies. Conclusion: The government, together with the management, should work to improve the working conditions in the apparel assembly plants, as it greatly affects both. Keywords: apparel assembly plants, ergonomics, musculoskeletal disorders, Uganda, working conditions

  13. Elevated dimethylglycine in blood of children with congenital heart defects and their mothers.

    Science.gov (United States)

    Alsayed, Ranwa; Al Quobaili, Faizeh; Srour, Samir; Geisel, Jürgen; Obeid, Rima

    2013-08-01

    Congenital Heart Defects (CHD) may be related to nutritional deficiencies affecting the methylation cycle. We aimed to study the metabolic markers of the betaine homocysteine methyl transferase (BHMT) pathway in children with CHD and their mothers compared to children without CHD and their mothers. Children with CHD (n=105, age DMG). Children with CHD had higher plasma SAM (131 vs. 100 nmol/L) and DMG (8.7 vs. 6.0 μmol/L) and lower betaine/DMG ratio (7.5 vs. 10.2) compared to the controls. Mothers of CHD children showed also higher DMG (6.1 vs. 4.1 µmol/L) and lower betaine/DMG ratio compared with the mothers of the controls. Higher SAM levels were related to higher cystathionine, MMA, betaine, choline, and DMG. MMA elevation in the patients was related to higher HCY, SAM, betaine and DMG. Elevated DMG in CHD children and their mothers compared to the controls can indicate upregulation of the BHMT pathway in this disease group. Nutritional factors are related to metabolic imbalance during pregnancy that may be related to worse birth outcome. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Analysis of hospitalization expenditures and influencing factors for inpatients with coronary heart disease in a tier-3 hospital in Xi'an, China: A retrospective study.

    Science.gov (United States)

    Ding, Jing-Mei; Zhang, Xian-Zhi; Hu, Xue-Jun; Chen, Huo-Liang; Yu, Min

    2017-12-01

    The medical costs for inpatients with coronary heart disease (CHD) have risen to unprecedented levels, putting tremendous financial pressure on their families and the entire society. The objective of this study was to examine the actual direct medical costs of inpatients with CHD and to analyze the influencing factors of those costs, to provide advice on the prevention and control of high medical costs of patients with CHD. A retrospective descriptive analysis of hospitalization expenditures data examined 10,301 inpatients with coronary heart disease of a tier-3 hospital in Xi'an from January 1, 2015 to December 31, 2015. The data included demographic information, the average length of stay, and different types of expenses incurred during the hospitalization period. The difference between different groups was analyzed using a univariate analysis, and the influencing factors of hospitalization expenditures were explored by the multiple linear stepwise regression analysis. The average age of these patients was 60.0 years old, the average length of stay was 4.0 days, and the majority were males (7172, 69.6%). The average hospitalization expenses were $6791.38 (3294.16-9, 732.59), and the top 3 expenses were medical consumables, operation fees, and drugs. The influencing factors of hospitalization expenditures included the length of stay, the number of times of admission, the type of medical insurance schemes, whether have a surgery or not, the gender, the age, and the marriage status. The inpatients with CHD in this tier-3 hospital were mostly over 45 years old. The average medical cost of males was much higher than that of females. Our findings suggest that the solution for tremendous hospitalization expenditures should be that more attention is paid to controlling the high expense of medical consumables and that the traditional method of reducing medical expenses by shortening the length of stay is still important in nowadays. Furthermore, the type of medical

  15. Reliability of CCGA and PBGA assemblies

    Science.gov (United States)

    Ghaffarian, Reza

    2005-01-01

    Area Array Packages (AAPs) with 1.27 mm pitch have been the packages of the choice for commercial applications; they are now started to be implemented for use in military and aerospace applications. Thermal cycling characteristics of plastic BGA (PBGA) and CSP assemblies, because of their wide usage for commercial applications, have been extensively reported in literature. Thermal cycling represents the on-off environmental condition for most electronic products and therefore is a key factor that defines reliability.

  16. Dynamic Multi-Component Hemiaminal Assembly

    Science.gov (United States)

    You, Lei; Long, S. Reid; Lynch, Vincent M.

    2012-01-01

    A simple approach to generating in situ metal templated tris-(2-picolyl)amine-like multi-component assemblies with potential applications in molecular recognition and sensing is reported. The assembly is based on the reversible covalent association between di-(2-picolyl)amine and aldehydes. Zinc ion is the best for inducing assembly among the metal salts investigated, while 2-picolinaldehyde is the best among the heterocyclic aldehydes studied. Although an equilibrium constant of 6.6 * 103 M-1 was measured for the assembly formed by 2-picolinaldehdye, di-(2-picolyl)amine, and zinc triflate, the equilibrium constants for other systems are in the 102 M-1 range. X-ray structural analysis revealed that zinc adopts a trigonal bipyramidal geometry within the assembled ligand. The diversity and equilibrium of the assemblies are readily altered by simply changing concentrations, varying components, or adding counter anions. PMID:21919095

  17. Southern Dietary Pattern is Associated with Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

    Science.gov (United States)

    Shikany, James M.; Safford, Monika M.; Newby, P. K.; Durant, Raegan W.; Brown, Todd M.; Judd, Suzanne E.

    2015-01-01

    Background The association of overall diet, as characterized by dietary patterns, with risk of incident acute coronary heart disease (CHD) has not been studied extensively in samples including sociodemographic and regional diversity. Methods and Results We used data from 17,418 participants in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal study of white and black adults aged ≥45 years, enrolled from 2003-2007. We derived dietary patterns with factor analysis, and used Cox proportional hazards regression to examine hazard of incident acute CHD events – nonfatal myocardial infarction and acute CHD death – associated with quartiles of consumption of each pattern, adjusted for various levels of covariates. Five primary dietary patterns emerged: Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad. A total of 536 acute CHD events occurred over a median (IQR) 5.8 (2.1) years of follow-up. After adjustment for sociodemographics, lifestyle factors, and energy intake, highest consumers of the Southern pattern (characterized by added fats, fried food, eggs, organ and processed meats, and sugar-sweetened beverages) experienced a 56% higher hazard of acute CHD (comparing quartile 4 to quartile 1: HR = 1.56; 95% CI: 1.17, 2.08; P for trend across quartiles = 0.003). Adding anthropometric and medical history variables to the model attenuated the association somewhat (HR = 1.37; 95% CI: 1.01, 1.85; P = 0.036). Conclusions A dietary pattern characteristic of the southern US was associated with greater hazard of CHD in this sample of white and black adults in diverse regions of the US. PMID:26260732

  18. NDA measurements on spent fuel assemblies at Tihange 1 by means of the ION 1/FORK

    International Nuclear Information System (INIS)

    Carchon, R.; Smaers, G.; Verrecchia, G.P.D.; Arlt, R.; Stoyanova, I.; Satinet, J.

    1986-06-01

    This report describes field tests performed at Tihange 1 Nuclear Power Station on PWR spent fuel by means of the ION 1-FORK detector. Two detector systems and three electronics systems were used to investigate the same fuel assemblies with various burn-ups and cooling times. The purpose of the exercise was to test the performance of the instrument for as well inspection purposes as for fuel management. The results are presented and discussed. (Author)

  19. [Association of human epicardial adipose tissue volume and inflammatory mediators with atherosclerosis and vulnerable coronary atherosclerotic plaque].

    Science.gov (United States)

    Zhou, Liangliang; Gong, Jianbin; Li, Demin; Lu, Guangming; Chen, Dong; Wang, Jing

    2015-02-01

    To investigate the relation of epicardial adipose tissue volume (EATV) determined by dual-source CT (DSCT) cardiac angiography and EAT-derived inflammatory factors to coronary heart disease (CHD) and vulnerable plaque. A total of 260 patients underwent cardiac computed tomography to evaluate stenosis of coronary artery, and blood samples were obtained from each patient. CHD was confirmed in 180 patients by DSA and CHD was excluded in the remaining 80 patients (NCHD). Vascular remodeling index and plaque vulnerability parameters (fatty volume, fibrous volume and calcification volume and fiber volume) were measured in CHD patients and correlation with EATV was analyzed. Epicardial adipose tissue (EAT) and intrathoracic adipose tissue (TAT) were collected from 40 CHD patients undergoing CABG surgery, and, mRNA and protein expressions of leptin and MMP9 were detected by RT-PCR and Western blot analysis. (1) The EATV was significantly higher in the CHD group than in NCHD group ((121.2 ± 40.6) mm³ vs. (74.7 ± 18.1) mm³, P = 0.01). (2) Subgroup analysis of the CHD patients demonstrated that EATV was significantly higher in patients with positive remodeling than in patients without positive remodeling ((97.6 ± 42.0) cm³ vs. (75.5 ± 25.4) cm³, P = 0.01). Lipid plaque volume was positively correlated with EATV (r = 0.34, P = 0.002); however, fiber plaque volume was negatively correlated with EATV (r = -0.30, P = 0.008). (3) Logistic regression analysis indicated that EATV was an independent risk factor for positive vascular remodeling (OR = 2.01, 95% CI: 1.30-2.32, P = 0.01). (4) mRNA and protein expression of leptin and MMP9 in EAT was significantly upregulated in 40 CHD patients who received CABG surgery compared to 40 NCHD patients (P 0.05) in mRNA and protein expression of leptin and MMP9 from the SAT between CHD and NCHD patients. (5) In the CHD group, leptin and MMP9 levels in EAT and EATV were positively correlated with lipid plaque volume and fibrous plaque

  20. Radiological characterization of spent control rod assemblies

    International Nuclear Information System (INIS)

    Lepel, E.A.; Robertson, D.E.; Thomas, C.W.; Pratt, S.L.; Haggard, D.L.

    1995-10-01

    This document represents the final report of an ongoing study to provide radiological characterizations, classifications, and assessments in support of the decommissioning of nuclear power stations. This report describes the results of non-destructive and laboratory radionuclide measurements, as well as waste classification assessments, of BWR and PWR spent control rod assemblies. The radionuclide inventories of these spent control rods were determined by three separate methodologies, including (1) direct assay techniques, (2) calculational techniques, and (3) by sampling and laboratory radiochemical analyses. For the BWR control rod blade (CRB) and PWR burnable poison rod assembly (BPRA), 60 Co and 63 Ni, present in the stainless steel cladding, were the most abundant neutron activation products. The most abundant radionuclide in the PWR rod cluster control assembly (RCCA) was 108m Ag (130 yr halflife) produced in the Ag-In-Cd alloy used as the neutron poison. This radionuclide will be the dominant contributor to the gamma dose rate for many hundreds of years. The results of the direct assay methods agree very well (±10%) with the sampling/radiochemical measurements. The results of the calculational methods agreed fairly well with the empirical measurements for the BPRA, but often varied by a factor of 5 to 10 for the CRB and the RCCA assemblies. If concentration averaging and encapsulation, as allowed by 10CFR61.55, is performed, then each of the entire control assemblies would be classified as Class C low-level radioactive waste

  1. Quantifying the contributions of behavioral and biological risk factors to socioeconomic disparities in coronary heart disease incidence: the MORGEN study

    NARCIS (Netherlands)

    Kershaw, Kiarri N.; Droomers, Mariël; Robinson, Whitney R.; Carnethon, Mercedes R.; Daviglus, Martha L.; Verschuren, W. M. Monique

    2013-01-01

    Quantifying the impact of different modifiable behavioral and biological risk factors on socioeconomic disparities in coronary heart disease (CHD) may help inform targeted, population-specific strategies to reduce the unequal distribution of the disease. Previous studies have used analytic

  2. Clinical implications of plasma Nogo-A levels in patients with coronary heart disease.

    Science.gov (United States)

    Ding, Yu; Gao, Bei-Bei; Zhou, Liang; Ye, Xian-Hua; Li, Hong; Lai, Lei; Huang, Jin-Yu

    2017-06-01

    Nogo-A is an important neurite growth-regulatory protein in the adult and developing nervous system. Recently, increasing evidence has shown that Nogo-A plays important roles in cardiac development and may act as a potential indicator for heart failure. In addition, increased oxidative stress has been found in individuals with cardiovascular diseases. However, not much is known regarding the expression levels of Nogo-A and reactive oxygen species (ROS) in patients with coronary heart disease (CHD). Therefore, we sought to investigate the relationship between Nogo-A, ROS levels and CHD. The plasma Nogo-A and ROS concentrations of 122 acute coronary syndrome (ACS), 101 unstable angina pectoris (UAP), and 21 acute myocardial infarction (AMI) patients and 56 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). We further generated a receiver operating characteristic (ROC) curve to assess the diagnostic accuracy of Nogo-A and ROS in CHD. The Nogo-A and ROS levels were significantly higher in patients with CHD than those in healthy controls. In addition, multivariate logistic regression analysis revealed that the level of Nogo-A (odds ratio (OR) = 1.624, 95% confidence interval: 1.125-2.293, p = 0.009) is a risk factor for prediction of CHD. Nogo-A has diagnostic value, with an optimal threshold of 5.466 ng/ml for maximized diagnostic performance (59% sensitivity and 78.6% specificity, area under curve, p < 0.05). However, ROS concentration is not a risk factor for prediction of CHD (OR = 0.999, 95% confidence interval: 0.997-1.001, p = 0.320). Increased plasma Nogo-A level may be associated with CHD.

  3. Dietary fatty acids and risk factors for coronary heart disease : controlled studies in healthy volunteers

    NARCIS (Netherlands)

    Zock, P.L.

    1995-01-01

    High levels of LDL cholesterol, blood pressure and Lp(a), and low levels of HDL cholesterol increase the risk for coronary heart disease (CHD). This thesis describes the effects of dietary fatty acids on these risk factors. In each of three trials we fed diets with tailored fatty acid

  4. Identification of a tetrameric assembly domain in the C terminus of heat-activated TRPV1 channels.

    Science.gov (United States)

    Zhang, Feng; Liu, Shuang; Yang, Fan; Zheng, Jie; Wang, KeWei

    2011-04-29

    Transient receptor potential (TRP) channels as cellular sensors are thought to function as tetramers. Yet, the molecular determinants governing channel multimerization remain largely elusive. Here we report the identification of a segment comprising 21 amino acids (residues 752-772 of mouse TRPV1) after the known TRP-like domain in the channel C terminus that functions as a tetrameric assembly domain (TAD). Purified recombinant C-terminal proteins of TRPV1-4, but not the N terminus, mediated the protein-protein interaction in an in vitro pulldown assay. Western blot analysis combined with electrophysiology and calcium imaging demonstrated that TAD exerted a robust dominant-negative effect on wild-type TRPV1. When fused with the membrane-tethered peptide Gap43, the TAD blocked the formation of stable homomultimers. Calcium imaging and current recordings showed that deletion of the TAD in a poreless TRPV1 mutant subunit suppressed its dominant-negative phenotype, confirming the involvement of the TAD in assembly of functional channels. Our findings suggest that the C-terminal TAD in TRPV1 channels functions as a domain that is conserved among TRPV1-4 and mediates a direct subunit-subunit interaction for tetrameric assembly.

  5. High Thermoelectric Power Factor Organic Thin Films through Combination of Nanotube Multilayer Assembly and Electrochemical Polymerization.

    Science.gov (United States)

    Culebras, Mario; Cho, Chungyeon; Krecker, Michelle; Smith, Ryan; Song, Yixuan; Gómez, Clara M; Cantarero, Andrés; Grunlan, Jaime C

    2017-02-22

    In an effort to produce effective thermoelectric nanocomposites with multiwalled carbon nanotubes (MWCNT), layer-by-layer assembly was combined with electrochemical polymerization to create synergy that would produce a high power factor. Nanolayers of MWCNT stabilized with poly(diallyldimethylammonium chloride) or sodium deoxycholate were alternately deposited from water. Poly(3,4-ethylene dioxythiophene) [PEDOT] was then synthesized electrochemically by using this MWCNT-based multilayer thin film as the working electrode. Microscopic images show a homogeneous distribution of PEDOT around the MWCNT. The electrical resistance, conductivity (σ) and Seebeck coefficient (S) were measured before and after the PEDOT polymerization. A 30 bilayer MWCNT film (<1 μm thick) infused with PEDOT is shown to achieve a power factor (PF = S 2 σ) of 155 μW/m K 2 , which is the highest value ever reported for a completely organic MWCNT-based material and competitive with lead telluride at room temperature. The ability of this MWCNT-PEDOT film to generate power was demonstrated with a cylindrical thermoelectric generator that produced 5.5 μW with a 30 K temperature differential. This unique nanocomposite, prepared from water with relatively inexpensive ingredients, should open up new opportunities to recycle waste heat in portable/wearable electronics and other applications where low weight and mechanical flexibility are needed.

  6. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 1, 2, AND 3 OF CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wright, Kenneth D.

    1997-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 1, 2, and 3 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

  7. Three-dimensional assemblies of graphene prepared by a novel chemical reduction-induced self-assembly method

    KAUST Repository

    Zhang, Lianbin

    2012-01-01

    In this study, three-dimensional (3D) graphene assemblies are prepared from graphene oxide (GO) by a facile in situ reduction-assembly method, using a novel, low-cost, and environment-friendly reducing medium which is a combination of oxalic acid (OA) and sodium iodide (NaI). It is demonstrated that the combination of a reducing acid, OA, and NaI is indispensable for effective reduction of GO in the current study and this unique combination (1) allows for tunable control over the volume of the thus-prepared graphene assemblies and (2) enables 3D graphene assemblies to be prepared from the GO suspension with a wide range of concentrations (0.1 to 4.5 mg mL-1). To the best of our knowledge, the GO concentration of 0.1 mg mL-1 is the lowest GO concentration ever reported for preparation of 3D graphene assemblies. The thus-prepared 3D graphene assemblies exhibit low density, highly porous structures, and electrically conducting properties. As a proof of concept, we show that by infiltrating a responsive polymer of polydimethylsiloxane (PDMS) into the as-resulted 3D conducting network of graphene, a conducting composite is obtained, which can be used as a sensing device for differentiating organic solvents with different polarity. © 2012 The Royal Society of Chemistry.

  8. Formation of RNA Granule-Derived Capsid Assembly Intermediates Appears To Be Conserved between Human Immunodeficiency Virus Type 1 and the Nonprimate Lentivirus Feline Immunodeficiency Virus.

    Science.gov (United States)

    Reed, Jonathan C; Westergreen, Nick; Barajas, Brook C; Ressler, Dylan T B; Phuong, Daryl J; Swain, John V; Lingappa, Vishwanath R; Lingappa, Jaisri R

    2018-05-01

    During immature capsid assembly in cells, human immunodeficiency virus type 1 (HIV-1) Gag co-opts a host RNA granule, forming a pathway of intracellular assembly intermediates containing host components, including two cellular facilitators of assembly, ABCE1 and DDX6. A similar assembly pathway has been observed for other primate lentiviruses. Here we asked whether feline immunodeficiency virus (FIV), a nonprimate lentivirus, also forms RNA granule-derived capsid assembly intermediates. First, we showed that the released FIV immature capsid and a large FIV Gag-containing intracellular complex are unstable during analysis, unlike for HIV-1. We identified harvest conditions, including in situ cross-linking, that overcame this problem, revealing a series of FIV Gag-containing complexes corresponding in size to HIV-1 assembly intermediates. Previously, we showed that assembly-defective HIV-1 Gag mutants are arrested at specific assembly intermediates; here we identified four assembly-defective FIV Gag mutants, including three not previously studied, and demonstrated that they appear to be arrested at the same intermediate as the cognate HIV-1 mutants. Further evidence that these FIV Gag-containing complexes correspond to assembly intermediates came from coimmunoprecipitations demonstrating that endogenous ABCE1 and the RNA granule protein DDX6 are associated with FIV Gag, as shown previously for HIV-1 Gag, but are not associated with a ribosomal protein, at steady state. Additionally, we showed that FIV Gag associates with another RNA granule protein, DCP2. Finally, we validated the FIV Gag-ABCE1 and FIV Gag-DCP2 interactions with proximity ligation assays demonstrating colocalization in situ Together, these data support a model in which primate and nonprimate lentiviruses form intracellular capsid assembly intermediates derived from nontranslating host RNA granules. IMPORTANCE Like HIV-1 Gag, FIV Gag assembles into immature capsids; however, it is not known whether

  9. Integrating succession and community assembly perspectives [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Cynthia Chang

    2016-09-01

    Full Text Available Succession and community assembly research overlap in many respects, such as through their focus on how ecological processes like dispersal, environmental filters, and biotic interactions influence community structure. Indeed, many recent advances have been made by successional studies that draw on modern analytical techniques introduced by contemporary community assembly studies. However, community assembly studies generally lack a temporal perspective, both on how the forces structuring communities might change over time and on how historical contingency (e.g. priority effects and legacy effects and complex transitions (e.g. threshold effects might alter community trajectories. We believe a full understanding of the complex interacting processes that shape community dynamics across large temporal scales can best be achieved by combining concepts, tools, and study systems into an integrated conceptual framework that draws upon both succession and community assembly theory.

  10. Coupling Considerations in Assembly Language. Revision 1

    Science.gov (United States)

    2018-02-13

    practice of dynamically changing code. This can easily be done in assembly languages—just write a command that modifies the opcode of another command...November 2017, http://martinfowler.com. Email is fowler@acm.org. 4. “Thoughts on Coupling in Software Design,” by Ioan Fagarasan, posted 25 July 2016

  11. Temporally controlled growth factor delivery from a self-assembling peptide hydrogel and electrospun nanofibre composite scaffold.

    Science.gov (United States)

    Bruggeman, Kiara F; Wang, Yi; Maclean, Francesca L; Parish, Clare L; Williams, Richard J; Nisbet, David R

    2017-09-21

    Tissue-specific self-assembling peptide (SAP) hydrogels designed based on biologically relevant peptide sequences have great potential in regenerative medicine. These materials spontaneously form 3D networks of physically assembled nanofibres utilising non-covalent interactions. The nanofibrous structure of SAPs is often compared to that of electrospun scaffolds. These electrospun nanofibers are produced as sheets that can be engineered from a variety of polymers that can be chemically modified to incorporate many molecules including drugs and growth factors. However, their macroscale morphology limits them to wrapping and bandaging applications. Here, for the first time, we combine the benefits of these systems to describe a two-component composite scaffold from these biomaterials, with the design goal of providing a hydrogel scaffold that presents 3D structures, and also has temporal control over drug delivery. Short fibres, cut from electrospun scaffolds, were mixed with our tissue-specific SAP hydrogel to provide a range of nanofibre sizes found in the extracellular matrix (10-300 nm in diameter). The composite material maintained the shear-thinning and void-filling properties of SAP hydrogels that have previously been shown to be effective for minimally invasive material injection, cell delivery and subsequent in vivo integration. Both scaffold components were separately loaded with growth factors, important signaling molecules in tissue regeneration whose rapid degradation limits their clinical efficacy. The two biomaterials provided sequential growth factor delivery profiles: the SAP hydrogel provided a burst release, with the release rate decreasing over 12 hours, while the electrospun nanofibres provided a more constant, sustained delivery. Importantly, this second release commenced 6 days later. The design rules established here to provide temporally distinct release profiles can enable researchers to target specific stages in regeneration, such as the

  12. Fuel assembly

    International Nuclear Information System (INIS)

    Ueda, Sei; Ando, Ryohei; Mitsutake, Toru.

    1995-01-01

    The present invention concerns a fuel assembly suitable to a BWR-type reactor and improved especially with the nuclear characteristic, heat performance, hydraulic performance, dismantling or assembling performance and economical property. A part of poison rods are formed as a large-diameter/multi-region poison rods having a larger diameter than a fuel rod. A large number of fuel rods are disposed surrounding a large diameter water rod and a group of the large-diameter/multi-region poison rods in adjacent with the water rod. The large-diameter water rod has a burnable poison at the tube wall portion. At least a portion of the large-diameter poison rods has a coolant circulation portion allowing coolants to circulate therethrough. Since the large-diameter poison rods are disposed at a position of high neutron fluxes, a large neutron multiplication factor suppression effect can be provided, thereby enabling to reduce the number of burnable poison rods relative to fuels. As a result, power peaking in the fuel assembly is moderated and a greater amount of plutonium can be loaded. In addition the flow of cooling water which tends to gather around the large diameter water rod can be controlled to improve cooling performance of fuels. (N.H.)

  13. New Insights into HTLV-1 Particle Structure, Assembly, and Gag-Gag Interactions in Living Cells

    Directory of Open Access Journals (Sweden)

    Jolene L. Johnson

    2011-06-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 has a reputation for being extremely difficult to study in cell culture. The challenges in propagating HTLV-1 has prevented a rigorous analysis of how these viruses replicate in cells, including the detailed steps involved in virus assembly. The details for how retrovirus particle assembly occurs are poorly understood, even for other more tractable retroviral systems. Recent studies on HTLV-1 using state-of-the-art cryo-electron microscopy and fluorescence-based biophysical approaches explored questions related to HTLV-1 particle size, Gag stoichiometry in virions, and Gag-Gag interactions in living cells. These results provided new and exciting insights into fundamental aspects of HTLV-1 particle assembly—which are distinct from those of other retroviruses, including HIV-1. The application of these and other novel biophysical approaches promise to provide exciting new insights into HTLV-1 replication.

  14. Effects of early age at natural menopause on coronary heart disease and stroke in Chinese women.

    Science.gov (United States)

    Shen, Lijun; Song, Lulu; Liu, Bingqing; Li, Hui; Zheng, Xiaoxuan; Zhang, Lina; Yuan, Jing; Liang, Yuan; Wang, Youjie

    2017-08-15

    Menopause is identified as a risk factor for cardiovascular disease because of the change of estrogen. The objective of the study was to explore the associations between early age at natural menopause (menopause at an age≤45years) and the presence of CHD and stroke. The study subjects were from the first follow-up survey of the Dongfeng-Tongji cohort study. A total of 16,515 postmenopausal women were included for the analysis. Logistic regression models were used to examine the associations between age at natural menopause (≤45, 45-52, >52years) and the presence of CHD and stroke adjusted for sociodemographic characteristics, lifestyle, reproductive history and metabolic factors. In the fully adjusted model, for each 1-year delay in menopausal age, the prevalence of CHD and stroke was reduced by 3% (OR, 0.97; 95% CI, 0.95-0.98) and 5% (OR, 0.95; 95% CI, 0.92-0.98), respectively. Women with early menopause (≤45years) had a higher prevalence of CHD (OR, 1.33; 95% CI, 1.13-1.57) compared with those with menopause at ages 45-52years. Similarly, women with early menopause (≤45years) was associated with higher prevalence of stroke (OR, 1.69; 95% CI, 1.25-2.30) compared with those with menopause at ages 45-52years. Early age at natural menopause is significantly associated with the presence of CHD and stroke among Chinese women. Copyright © 2017. Published by Elsevier B.V.

  15. CFD analysis of flow distribution of reactor core and temperature rise of coolant in fuel assembly for VVER reactor

    International Nuclear Information System (INIS)

    Du Daiquan; Zeng Xiaokang; Xiong Wanyu; Yang Xiaoqiang

    2015-01-01

    Flow field of VVER-1000 reactor core was investigated by using computational fluid dynamics code CFX, and the temperature rise of coolant in hot assembly was calculated. The results show that the maximum value of flow distribution factor is 1.12 and the minimum value is 0.92. The average value of flow distribution factor in hot assembly is 0.97. The temperature rise in hot assembly is higher than current warning limit value ΔT t under the deviated operation condition. The results can provide reference for setting ΔT t during the operation of nuclear power plant. (authors)

  16. Sex determination in Turdus amaurochalinus (Passeriformes: Muscicapidae: morphometrical analysis supported by CHD gene

    Directory of Open Access Journals (Sweden)

    Katyucha Von Kossel de Andrade Silva

    2011-06-01

    Full Text Available Sex determination is important for conservation and population studies, particularly for reproduction programs of threatened species and behavioural ecology. Turdus amaurochalinus, Creamy-bellied Thrush, only exhibits sexual dimorphism during the breeding season, when males are considered to show intense yellow bills, and females and immature males show dark brown bills. The objectives of this study were: 1 to determine the sex of individuals using genetic techniques, and 2 to test the hypothesis that sex dimorphism can be detected by morphometry. This study was carried out at Parque Nacional da Restinga de Jurubatiba, a preserved area located on the North coast of Rio de Janeiro State. The birds were captured using ornithological nets, singly marked with metal rings, weighed, measured and had blood samples collected before being released. The sex of 42 T. amaurochalinus individuals was determined using the CHD gene marker. A total of 20 males and 22 females were identified from June to August, with peak capture frequency in June. Turdus amaurochalinus females and males differed significantly in morphometrical measures. The most important traits to distinguish males from females were wing length (Student t-test=4.34, df=40, p=0.0001 and weight (Student t-test=2.08,df=40, p=0.044: females were heavier and had significantly shorter wing length than males. Females and males were correctly classified in 86% and 75% of cases, respectively, using Discriminant Analysis. The molecular analysis was the most secure method for sex determination in the studied species. Rev. Biol. Trop. 59 (2: 789- 794. Epub 2011 June 01.La determinación del sexo es importante para la conservación y los estudios poblacionales. Turdus amaurochalinus no presenta aparente dimorfismo sexual. El objetivo de este estudio fue determinar el sexo a través de una técnica genética, mediante el uso del marcador del gen CHD y se puso a prueba la hipótesis de que el dimorfismo

  17. Effects of coagulation factors and inflammatory cytokines on ...

    African Journals Online (AJOL)

    Currently, coronary heart disease (CHD) has become one of the leading global threats to human health [1]. ... episodes of cardiovascular disease and none used antihypertensive or lipid-lowering drugs. .... phenotype or subclinical Cushing's syndrome: a 15-year retrospective study. Lancet Diabetes Endocrinol 2014;.

  18. Vertical pump assembly

    International Nuclear Information System (INIS)

    Dohnal, M.; Rosel, J.; Skarka, V.

    1988-01-01

    The mounting is described of the drive assembly of a vertical pump for nuclear power plants in areas with seismic risk. The assembly is attached to the building floor using flexible and damping elements. The design allows producing seismically resistant pumps without major design changes in the existing types of vertical pumps. (E.S.). 1 fig

  19. Does high intelligence improve prognosis? The association of intelligence with recurrence and mortality among Swedish men with coronary heart disease.

    Science.gov (United States)

    Sörberg Wallin, Alma; Falkstedt, Daniel; Allebeck, Peter; Melin, Bo; Janszky, Imre; Hemmingsson, Tomas

    2015-04-01

    Lower intelligence early in life is associated with increased risks for coronary heart disease (CHD) and mortality. Intelligence level might affect compliance to treatment but its prognostic importance in patients with CHD is unknown. A cohort of 1923 Swedish men with a measure of intelligence from mandatory military conscription in 1969-1970 at age 18-20, who were diagnosed with CHD 1991-2007, were followed to the end of 2008. recurrent CHD event. Secondary outcome: case fatality from the first event, cardiovascular and all-cause mortality. National registers provided information on CHD events, comorbidity, mortality and socioeconomic factors. The fully adjusted HRs for recurrent CHD for medium and low intelligence, compared with high intelligence, were 0.98, (95% CIs 0.83 to 1.16) and 1.09 (0.89 to 1.34), respectively. The risks were increased for cardiovascular and all-cause mortality with lower intelligence, but were attenuated in the fully adjusted models (fully adjusted HRs for cardiovascular mortality 1.92 (0.94 to 3.94) and 1.98 (0.89 to 4.37), respectively; for all-cause mortality 1.63 (1.00 to 2.65) and 1.62 (0.94 to 2.78), respectively). There was no increased risk for case-fatality at the first event (fully adjusted ORs 1.06 (0.73 to 1.55) and 0.97 (0.62 to 1.50), respectively). Although we found lower intelligence to be associated with increased mortality in middle-aged men with CHD, there was no evidence for its possible effect on recurrence in CHD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. National Ignition Facility subsystem design requirements final optics assembly subsystem SSDR 1.8.7

    International Nuclear Information System (INIS)

    Adams, C.

    1996-01-01

    This SSDR establishes the performance, design, development and test requirements for the Final Optic Assembly (FOA). The FOA (WBS 1.8.7) as part of the Target Experimental System (1.8) includes vacuum windows, frequency conversion crystals, focus lens, debris shields and supporting mechanical equipment