Science.gov

Sample records for addition significant associations

  1. Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome.

    PubMed

    Yoon, Sung-Jae; Rahman, Md Saidur; Kwon, Woo-Sung; Park, Yoo-Jin; Pang, Myung-Geol

    2016-01-01

    Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p < 0.05). Ten proteins were differentially expressed (two decreased and eight increased) (>3 fold, p < 0.05) after CPA, whereas NADH dehydrogenase flavoprotein 2, f-actin-capping protein subunit beta, superoxide dismutase 2, and outer dense fiber protein 2 were associated with several important signaling pathways (p < 0.05). The present study provides a mechanistic basis for specific cryostresses and potential markers of CPA-induced stress. Therefore, these might provide information about the development of safe biomaterials for cryopreservation and basic ground for sperm cryopreservation. PMID:27031703

  2. Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome

    PubMed Central

    Yoon, Sung-Jae; Rahman, Md Saidur; Kwon, Woo-Sung; Park, Yoo-Jin; Pang, Myung-Geol

    2016-01-01

    Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p < 0.05). Ten proteins were differentially expressed (two decreased and eight increased) (>3 fold, p < 0.05) after CPA, whereas NADH dehydrogenase flavoprotein 2, f-actin-capping protein subunit beta, superoxide dismutase 2, and outer dense fiber protein 2 were associated with several important signaling pathways (p < 0.05). The present study provides a mechanistic basis for specific cryostresses and potential markers of CPA-induced stress. Therefore, these might provide information about the development of safe biomaterials for cryopreservation and basic ground for sperm cryopreservation. PMID:27031703

  3. Significant association between DRD3 gene body methylation and schizophrenia.

    PubMed

    Dai, Dongjun; Cheng, Jia; Zhou, Kena; Lv, Yuelong; Zhuang, Qidong; Zheng, Rongjiong; Zhang, Kai; Jiang, Danjie; Gao, Shugui; Duan, Shiwei

    2014-12-30

    The current study was the first one to reveal the contribution of DRD3 methylation to the risk of different (SCZ) subtypes. This study comprised a total of 30 paranoid (15 males and 15 females) and 29 undifferentiated (15 males and 14 females) SCZ patients and 26 age- and gender-matched controls. Our results showed a significant association of CpG2 with SCZ. A breakdown analysis by gender showed that CpG2 and CpG3 methylation were significantly higher in male patients than male controls, and that CpG5 methylation was significantly higher in female patients than female controls. A further breakdown analysis by both gender and SCZ subtype showed that CpG2 and CpG3 methylation were significantly higher in male paranoid SCZ and male undifferentiated SCZ than male controls. In contrast, CpG2 and CpG3 methylation were significantly lower in female undifferentiated SCZ than female controls. Additionally, CpG5 methylation was significantly higher in female paranoid SCZ than female controls. In conclusion, our findings supported that DRD3 gene body hypermethylation was significantly associated with the risk of SCZ. Future study is needed to clarify the mechanisms by which DRD3 gene body hypermethylation contributes to the risk of SCZ.

  4. Significant Association Between Adiponutrin and Hepatocellular Carcinoma Risk

    PubMed Central

    Li, Hong-Guang; Liu, Fang-Feng; Zhu, Hua-Qiang; Zhou, Xu; Lu, Jun; Chang, Hong; Hu, Jin-Hua

    2015-01-01

    Abstract ADPN I148M polymorphism has been consistently reported to play a role in liver-associated diseases, such as alcoholic liver disease, chronic hepatitis C, and liver fat and fibrosis in nonalcoholic fatty liver disease. This significant association was also indicated in a series of hepatocellular carcinoma (HCC) studies, where the significance may be affected due to the small sample sizes. The aim of this study was to reexamine the ADPN-HCC association by use of meta-analysis. Biweekly computer-based literature searches plus manual screening were undertaken in an effort to identify all studies that met the predefined inclusion criteria. The Mantel–Haenszel method was selected to estimate risk effects (odds ratio [OR] and 95% confidence interval [CI]). To examine reliability of the pooled risk effects, we additionally performed sensitivity analysis and publication bias tests. Ten studies (1335 HCC patients and 2927 HCC-free controls) were identified for the meta-analysis. We found significantly increased risk of HCC attributable to presence of ADPN I148M polymorphism, with the highest risk associated with the M/M genotype under the recessive model of inheritance (OR = 2.23, 95% CI = 1.87–2.67, between-study heterogeneity: P = 0.468). The significant increase persisted in Caucasian and African when data were stratified by ethnicity. Subgroup analysis according to source of controls revealed similar risk effects. Our meta-analysis indicates that I148M polymorphism in the ADPN gene may independently contribute to the progression of HCC irrespective of the etiologies. PMID:26632699

  5. Assessing statistical significance in multivariable genome wide association analysis

    PubMed Central

    Buzdugan, Laura; Kalisch, Markus; Navarro, Arcadi; Schunk, Daniel; Fehr, Ernst; Bühlmann, Peter

    2016-01-01

    Motivation: Although Genome Wide Association Studies (GWAS) genotype a very large number of single nucleotide polymorphisms (SNPs), the data are often analyzed one SNP at a time. The low predictive power of single SNPs, coupled with the high significance threshold needed to correct for multiple testing, greatly decreases the power of GWAS. Results: We propose a procedure in which all the SNPs are analyzed in a multiple generalized linear model, and we show its use for extremely high-dimensional datasets. Our method yields P-values for assessing significance of single SNPs or groups of SNPs while controlling for all other SNPs and the family wise error rate (FWER). Thus, our method tests whether or not a SNP carries any additional information about the phenotype beyond that available by all the other SNPs. This rules out spurious correlations between phenotypes and SNPs that can arise from marginal methods because the ‘spuriously correlated’ SNP merely happens to be correlated with the ‘truly causal’ SNP. In addition, the method offers a data driven approach to identifying and refining groups of SNPs that jointly contain informative signals about the phenotype. We demonstrate the value of our method by applying it to the seven diseases analyzed by the Wellcome Trust Case Control Consortium (WTCCC). We show, in particular, that our method is also capable of finding significant SNPs that were not identified in the original WTCCC study, but were replicated in other independent studies. Availability and implementation: Reproducibility of our research is supported by the open-source Bioconductor package hierGWAS. Contact: peter.buehlmann@stat.math.ethz.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153677

  6. Novel loci and pathways significantly associated with longevity.

    PubMed

    Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James W

    2016-01-01

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity. PMID:26912274

  7. Novel loci and pathways significantly associated with longevity.

    PubMed

    Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James W

    2016-02-25

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

  8. Novel loci and pathways significantly associated with longevity

    PubMed Central

    Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C.; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W.; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James W.

    2016-01-01

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10−5). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity. PMID:26912274

  9. The environment associated with significant tornadoes in Bangladesh

    NASA Astrophysics Data System (ADS)

    Bikos, Dan; Finch, Jonathan; Case, Jonathan L.

    2016-01-01

    This paper investigates the environmental parameters favoring significant tornadoes in Bangladesh through a simulation of ten high-impact events. A climatological perspective is first presented on classifying significant tornadoes in Bangladesh, noting the challenges since reports of tornadoes are not documented in a formal manner. The statistical relationship between United States and Bangladesh tornado-related deaths suggests that significant tornadoes do occur in Bangladesh so this paper identifies the most significant tornadic events and analyzes the environmental conditions associated with these events. Given the scarcity of observational data to assess the near-storm environment in this region, high-resolution (3-km horizontal grid spacing) numerical weather prediction simulations are performed for events identified to be associated with a significant tornado. In comparison to similar events over the United States, significant tornado environments in Bangladesh are characterized by relatively high convective available potential energy, sufficient deep-layer vertical shear, and a propensity for deviant (i.e., well to the right of the mean flow) storm motion along a low-level convergence boundary.

  10. Papuloerythroderma associated with monoclonal gammopathy of undetermined significance.

    PubMed

    Fujimura, Taku; Okuyama, Ryuhei; Ogawa, Eisaku; Aiba, Setsuya

    2009-04-01

    We describe a 73-year-old Japanese man with papuloerythroderma overlapped with monoclonal gammopathy of undetermined significance (MGUS). Clinically, prominent erythroderma was associated with disseminated pruriginous papules, which were characteristically spared on the axillary and inguinal regions, the cubital and popliteal fossae as well as abdominal and small positional folds. Histopathologically, there was a significant perivascular infiltrate of lymphohistiocytic cells intermingled with eosinophils in the upper dermis. A biochemical profile revealed the presence of immunoglobulin G kappa chain type monoclonal protein in the serum but the absence of hematological neoplasms. We diagnosed the patient as papuloerythroderma with MGUS, and treated him with narrow-band ultraviolet B and topical steroid. His skin changes were improved, but the sharp gamma-globulin peak remained in the electrophoresis of serum protein. This case suggests an association between papuloerythroderma and MGUS. PMID:19348662

  11. Papuloerythroderma associated with monoclonal gammopathy of undetermined significance.

    PubMed

    Fujimura, Taku; Okuyama, Ryuhei; Ogawa, Eisaku; Aiba, Setsuya

    2009-04-01

    We describe a 73-year-old Japanese man with papuloerythroderma overlapped with monoclonal gammopathy of undetermined significance (MGUS). Clinically, prominent erythroderma was associated with disseminated pruriginous papules, which were characteristically spared on the axillary and inguinal regions, the cubital and popliteal fossae as well as abdominal and small positional folds. Histopathologically, there was a significant perivascular infiltrate of lymphohistiocytic cells intermingled with eosinophils in the upper dermis. A biochemical profile revealed the presence of immunoglobulin G kappa chain type monoclonal protein in the serum but the absence of hematological neoplasms. We diagnosed the patient as papuloerythroderma with MGUS, and treated him with narrow-band ultraviolet B and topical steroid. His skin changes were improved, but the sharp gamma-globulin peak remained in the electrophoresis of serum protein. This case suggests an association between papuloerythroderma and MGUS.

  12. Peripheral neuropathies associated with monoclonal gammopathies of undetermined significance.

    PubMed

    Kelly, John J

    2008-01-01

    Monoclonal gammopathies (MGs) or plasma cell dyscrasias (PCDs) are hematologic disorders that may affect peripheral nerves. An MG is a proliferation of a single clone of neoplastic or nonneoplastic plasma that usually secretes a monoclonal protein (M-protein) serum or urine. If a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is established, a sudden increase in M-protein levels can indicate malignant transformation of a benign PCD. Roughly 50% of MGUS neuropathies are associated with an IgM gammopathy and the remaining 50% with IgG- and IgA-MGUS-associated neuropathies. MGUS is the most common of the PCDs associated with neurologic disorders, which are easily approached clinically by classifying them as IgM or non-IgM types.

  13. Significant enhancement of the superconducting properties of MgB2 by polyvinyl alcohol additives

    NASA Astrophysics Data System (ADS)

    Zeng, R.; Lu, L.; Dou, S. X.

    2008-08-01

    We report a systematic study of the effects of polymer addition on the lattice parameters, microstructure and superconducting properties of MgB2. Polyvinyl alcohol [-C2H4O-]n (PVA) as a typical polymer was used as an additive to MgB2. It was found that PVA additions have the following features: (1) the polymer can have a very low oxygen (O) content or even none at all, and PVA has a low O content (C:O = 2:1), which reduces the impurities brought into MgB2 from the doping, and (2) PVA decomposes at a temperature of 400-650 °C, which means that the reaction occurs in the same temperature range as MgB2 formation, providing highly reactive C, which homogeneously substitutes for B at this low-temperature range. The above considerations significantly enhance the critical current, Jc, the irreversibility field, Hirr, and the upper critical field, Hc2, of MgB2 compared to un-doped samples or those doped with other carbon sources. In this work, suitable PVA doping levels improved both the connectivity and flux pinning, so that the Jc of PVA-doped MgB2 was improved over the whole field range.

  14. Genome-wide significant risk associations for mucinous ovarian carcinoma.

    PubMed

    Kelemen, Linda E; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; Lee, Janet M; Seo, Ji-Heui; Phelan, Catherine M; Beesley, Jonathan; Chen, Xiaoqing; Spindler, Tassja J; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia

    2015-08-01

    Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10(-8)), rs711830 at 2q31.1 (P = 7.5 × 10(-12)) and rs688187 at 19q13.2 (P = 6.8 × 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790

  15. Lenz microphthalmia syndrome: three additional cases with rare associated anomalies.

    PubMed

    Temtamy, S A; Ismail, S I; Meguid, N A

    2000-01-01

    Lenz microphthalmia syndrome is an extremely rare inherited disorder, characterized by unilateral or bilateral microphthalmia. In rare cases affected patients exhibit complete absence of eye or blepharoptosis resulting in visual impairment. Additional physical abnormalities are often associated with this disorder, orofacial, digital, skeletal and urogenital abnormalities. Here we present three cases of Lenz microphthalmia with additional manifestations: two brothers of first cousin mating, the elder one has bilateral congenital cataract which is a rare ophthalmological finding in this syndrome and a third case who presented to us because of ambiguous genitalia. She was 12 years old, and reared as a female. Chromosomal analysis showed 46,XY karyotype, and hormonal studies indicated 5-alpha reductase deficiency. This is the first report of the association of 5-alpha reductase deficiency with Lenz microphthalmia syndrome.

  16. Genome-wide significant risk associations for mucinous ovarian carcinoma

    PubMed Central

    Kelemen, Linda E.; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; M. Lee, Janet; Seo, Ji-Heui; Phelan, Catherine M.; Beesley, Jonathan; Chen, Xiaoqin; Spindler, Tassja J.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chen, Y. Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Engelholm, Svend Aage; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moes-Sosnowska, Joanna; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wlodzimierz, Sawicki; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Freedman, Matthew L.; Chenevix-Trench, Georgia; Pharoah, Paul D.; Gayther, Simon A.; Berchuck, Andrew

    2015-01-01

    Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790

  17. Significantly improved cyclability of lithium manganese oxide under elevated temperature by an easily oxidized electrolyte additive

    NASA Astrophysics Data System (ADS)

    Zhu, Yunmin; Rong, Haibo; Mai, Shaowei; Luo, Xueyi; Li, Xiaoping; Li, Weishan

    2015-12-01

    Spinel lithium manganese oxide, LiMn2O4, is a promising cathode for lithium ion battery in large-scale applications, because it possesses many advantages compared with currently used layered lithium cobalt oxide (LiCoO2) and olivine phosphate (LiFePO4), including naturally abundant resource, environmental friendliness and high and long work potential plateau. Its poor cyclability under high temperature, however, limits its application. In this work, we report a significant cyclability improvement of LiMn2O4 under elevated temperature by using dimethyl phenylphonite (DMPP) as an electrolyte additive. Charge/discharge tests demonstrate that the application of 0.5 wt.% DMPP yields a capacity retention improvement from 16% to 82% for LiMn2O4 after 200 cycles under 55 °C at 1 C (1C = 148 mAh g-1) between 3 and 4.5 V. Electrochemical and physical characterizations indicate that DMPP is electrochemically oxidized at the potential lower than that for lithium extraction, forming a protective cathode interphase on LiMn2O4, which suppresses the electrolyte decomposition and prevents LiMn2O4 from crystal destruction.

  18. Allergic Contact Dermatitis Is Associated with Significant Oxidative Stress

    PubMed Central

    Kaur, S.; Zilmer, K.; Leping, V.; Zilmer, M.

    2014-01-01

    Background. Research has confirmed the involvement of oxidative stress (OxS) in allergic contact dermatitis whilst other inflammation-related biomarkers have been less studied. Objective. To evaluate systemic levels of selected inflammatory markers, OxS indices and adipokines as well as their associations in allergic contact dermatitis. Methods. In 40 patients, interleukin- (IL-) 6, monocyte chemoattractant protein (MCP-1), and IL-10 levels were measured in sera with the Evidence Investigator Cytokine & Growth factors High-Sensitivity Array, total peroxide concentration (TPX) and total antioxidant capacity (TAC) by means of spectrophotometry, and the plasma concentrations of adiponectin and leptin by the quantitative sandwich enzyme immunoassay technique. Results. TNF-α level (P < 0.01) and TPX (P < 0.0001) were increased whilst IL-10 (P < 0.05) and TAC (P < 0.0001) were decreased in the patients as compared to controls. Correlation and multiple linear regression analysis identified both, TPX and TAC (inversely), as possible independent markers for evaluating allergic contact dermatitis. Adiponectin level in patients was increased (P < 0.0001), but neither adiponectin nor leptin correlated significantly with the biomarkers of inflammation or OxS. Conclusion. OxS parameters, especially TPX and OSI, reflect the degree of systemic inflammation associated with allergic contact dermatitis in the best way. The relation between OxS and adiponectin level warrants further studies. PMID:25183967

  19. TLR3 Plays Significant Roles against HBV-Associated HCC

    PubMed Central

    Chen, Xiao-lan; Xu, Yu-yin; Chen, Li; Wang, Gui-lan; Shen, Yin

    2015-01-01

    Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). The role of TLR3 in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infections is not well understood. To investigate the ability of TLR3 in regulating HBV replication in HCC, 80 cases of human HCC were collected and their tissue microarray was made. In HCC cells, the expression and location of TLR3, hepatitis-associated virus, and interstitial immunoreactive cells were assayed with immunohistochemical staining. The apoptosis of tumor cells was also detected by TUNEL stain. Correlations between TLR3 expression and HBV infection, interstitial immunoreactive cells, and cells apoptosis in HCC were investigated. In addition, we explored whether TLR3 agonist dsRNA can inhibit HepG2.2.15 cells secreting HBV. We found that the cytoplasmic expression of TLR3 in HCC is positively related to HBsAg infection and HCC with cirrhosis and promotes interstitial immunoreactive cells infiltration and cancer cells apoptosis. In HepG2.2.15 cells, dsRNA inhibited the secretion of HBV and induced apoptosis. These results indicate that TLR3 signaling activity may be involved in immune responses against HBV in HCC. PMID:25983748

  20. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  1. Significant reserve additions from oligocene Hackberry Sands utilizing 3-D seismic, upper Texas and Louisiana Gulf Coast

    SciTech Connect

    Zamboras, R.L.

    1995-10-01

    The Oligocene Hackberry sands of the Hackberry Embayment represent a complex and elusive exploration target. 3-D seismic evaluation along the headward erosional limits of the embayment provides a reconstructive framework of tectonic and sedimentation patterns which facilitate hydrocarbon exploration. The 3-D seismic along the Orange County, Texas portion of the Oligocene Hackberry trend indicates: (1) similarities of Hackberry structural and depositional setting to that of the underlying Eocene Yegua Formation; (2) four distinct cyclical sedimentation episodes associated with basin floor slump faulting: (3) the usefulness of seismic attributes as direct hydrocarbon indicators, and (4) the potential for significant oil and gas reserves additions in a mature trend. The Hackberry embayment represents a microcosm of the basin structural and depositional processes. Utilizing 3-D seismic to lower risk and finding cost will renew interest in trends such as the Hackberry of the Upper Texas-Louisiana Gulf Coast.

  2. Injection route and TLR9 agonist addition significantly impact heroin vaccine efficacy.

    PubMed

    Bremer, Paul T; Schlosburg, Joel E; Lively, Jenny M; Janda, Kim D

    2014-03-01

    Active immunization is an effective means of blocking the pharmacodynamic effects of drugs and holds promise as a treatment for heroin addiction. Previously, we demonstrated the efficacy of our first-generation vaccine in blocking heroin self-administration in rats, however, many vaccine components can be modified to further improve performance. Herein we examine the effects of varying heroin vaccine injection route and adjuvant formulation. Mice immunized via subcutaneous (sc) injection exhibited inferior anti-heroin titers compared to intraperitoneal (ip) and sc/ip coadministration injection routes. Addition of TLR9 agonist cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) to the original alum adjuvant elicited superior antibody titers and opioid affinities compared to alum alone. To thoroughly assess vaccine efficacy, full dose-response curves were generated for heroin-induced analgesia in both hot plate and tail immersion tests. Mice treated with CpG ODN 1826 exhibited greatly shifted dose-response curves (10-13-fold vs unvaccinated controls) while non-CpG ODN vaccine groups did not exhibit the same robust effect (2-7-fold shift for ip and combo, 2-3-fold shift for sc). Our results suggest that CpG ODN 1826 is a highly potent adjuvant, and injection routes should be considered for development of small molecule-protein conjugate vaccines. Lastly, this study has established a new standard for assessing drugs of abuse vaccines, wherein a full dose-response curve should be performed in an appropriate behavioral task.

  3. Addition of Zn to the ternary Mg-Ca-Sr alloys significantly improves their antibacterial property

    PubMed Central

    He, Guanping; Wu, Yuanhao; Zhang, Yu; Zhu, Ye; Liu, Yang; Li, Nan; Li, Mei; Zheng, Guan; He, Baohua; Yin, Qingshui; Zheng, Yufeng; Mao, Chuanbin

    2015-01-01

    Most of the magnesium (Mg) alloys possess excellent biocompatibility, mechanical property and biodegradability in orthopedic applications. However, these alloys may suffer from bacterial infections due to their insufficient antibacterial capability. In order to reduce the post-surgical infections, a series of biocompatible Mg–1Ca-0.5Sr-xZn (x=0, 2, 4, 6) alloys were fabricated with the addition of antibacterial Zn with variable content and evaluated in terms of their biocompatibility and antibacterial property. The in vitro corrosion study showed that Mg-1Ca-0.5Sr-6Zn alloys exhibited a higher hydrogen evolution volume after 100 h immersion and resulted in a higher pH value of the immersion solution. Our work indicated that Zn-containing Mg alloys exhibited good biocompatibility with high cell viability. The antibacterial studies reveal that the number of bacteria adhered on all of these Mg alloy samples diminished remarkably compared to the Ti-6Al-4V control group. We also found that the proliferation of the bacteria was inhibited by these Mg alloys extracts. Among the prepared alloys, Mg-1Ca-0.5Sr-6Zn alloy not only exhibited a strong antibacterial effect, but also promoted the proliferation of MC3T3-E1 osteoblasts, suggesting that it is a promising alloy with both good antibacterial property and good biocompatibility for use as an orthopedic implant. PMID:26693010

  4. Injection Route and TLR9 Agonist Addition Significantly Impact Heroin Vaccine Efficacy

    PubMed Central

    2015-01-01

    Active immunization is an effective means of blocking the pharmacodynamic effects of drugs and holds promise as a treatment for heroin addiction. Previously, we demonstrated the efficacy of our first-generation vaccine in blocking heroin self-administration in rats, however, many vaccine components can be modified to further improve performance. Herein we examine the effects of varying heroin vaccine injection route and adjuvant formulation. Mice immunized via subcutaneous (sc) injection exhibited inferior anti-heroin titers compared to intraperitoneal (ip) and sc/ip coadministration injection routes. Addition of TLR9 agonist cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) to the original alum adjuvant elicited superior antibody titers and opioid affinities compared to alum alone. To thoroughly assess vaccine efficacy, full dose–response curves were generated for heroin-induced analgesia in both hot plate and tail immersion tests. Mice treated with CpG ODN 1826 exhibited greatly shifted dose–response curves (10–13-fold vs unvaccinated controls) while non-CpG ODN vaccine groups did not exhibit the same robust effect (2–7-fold shift for ip and combo, 2–3-fold shift for sc). Our results suggest that CpG ODN 1826 is a highly potent adjuvant, and injection routes should be considered for development of small molecule–protein conjugate vaccines. Lastly, this study has established a new standard for assessing drugs of abuse vaccines, wherein a full dose–response curve should be performed in an appropriate behavioral task. PMID:24517171

  5. Significance of genome-wide association studies in molecular anthropology.

    PubMed

    Gupta, Vipin; Khadgawat, Rajesh; Sachdeva, Mohinder Pal

    2009-12-01

    The successful advent of a genome-wide approach in association studies raises the hopes of human geneticists for solving a genetic maze of complex traits especially the disorders. This approach, which is replete with the application of cutting-edge technology and supported by big science projects (like Human Genome Project; and even more importantly the International HapMap Project) and various important databases (SNP database, CNV database, etc.), has had unprecedented success in rapidly uncovering many of the genetic determinants of complex disorders. The magnitude of this approach in the genetics of classical anthropological variables like height, skin color, eye color, and other genome diversity projects has certainly expanded the horizons of molecular anthropology. Therefore, in this article we have proposed a genome-wide association approach in molecular anthropological studies by providing lessons from the exemplary study of the Wellcome Trust Case Control Consortium. We have also highlighted the importance and uniqueness of Indian population groups in facilitating the design and finding optimum solutions for other genome-wide association-related challenges.

  6. [Ophthalmological complications associated with clinically significant carotid stenosis].

    PubMed

    Rozegnał-Madej, Agnieszka; Bielecka, Emilia; Swiech-Zubilewicz, Anna; Zarnowski, Tomasz; Karakuła, Wacław; Zubilewicz, Tomasz

    2012-01-01

    The aim of the study was to show ocular manifestations in carotid artery occlusive disease, with pathogenesis, diagnostic and therapeutic abilities of this changes. Carotid arteries are the main route by which the blood is supplied to the cerebrum and eyes. Clinical significant carotid artery stenosis is mainly caused by atherosclerosis. Most frequent neurological symptoms are transient ischemic attacks (TIA) and temporary visual loss (amaurosos fugax) are most common ocular symptoms. Other ocular pathologies in fundus examination are retinal embolies, retinal vein occlusion, anterior ischemic optic neuropathy, ocular ischemic syndrome or glaucoma. Most dangerous complications are stroke, blindness, or even patients death. Besides clinical examination the diagnosis is usually confirmed by carotid artery color Doppler ultrasound, magnetic resonance angiography and retinal fluorescein angiography. It is important to refer a patient with suspected or confirmed significant carotid artery stenosis for appropriate evaluation and treatment to a endovascular surgeon. PMID:22783748

  7. Significant increase in travel-associated dengue fever in Germany.

    PubMed

    Allwinn, Regina

    2011-08-01

    Increasing numbers of dengue fever (DF) cases reflect the increasing travel mobility together with the expanding geographical distribution of the vector Aedes aegypti. Compared with earlier surveys in Germany, higher incidences occur and correlate well with ongoing outbreaks. Therefore, we investigated 767 serum samples from 594 returning travellers with suspected DF between 2005 and 2010, which where sent from different hospitals in the drainage area Frankfurt/Main. Established diagnostic assays were ELISA, immunofluorescence and chromatographic tests. We obtained 112 dengue-seropositive serum samples from totally 60 patients: the detection rate was 10.1% (60 out of 594). A significant increase was found in 2010. Most patients were aged between 40 and 49, and indirect immunofluorescence technique indicated mainly DF serotype 2. Actual data reveal a significant rise in imported DF cases in 2010 according to an increasing risk to acquire DF virus infection. Nevertheless, dengue haemorrhagic fever and dengue shock syndrome are still rare in travellers, but those with a history of dengue should be tested for DF serotypes and advised to protect themselves well from mosquitoes when travelling to endemic areas.

  8. Solubility increases associated with crystalline drug nanoparticles: methodologies and significance.

    PubMed

    Van Eerdenbrugh, Bernard; Vermant, Jan; Martens, Johan A; Froyen, Ludo; Humbeeck, Jan Van; Van den Mooter, Guy; Augustijns, Patrick

    2010-10-01

    In this manuscript, the determination of solubility of crystalline drug nanosuspensions by a range of methods is critically investigated. As the determinations of solubility were performed in the presence of the solubilizing nanosuspension stabilizer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), the potential effects of this excipient on the measurements were studied first. Solubility data of nanosuspensions of itraconazole, loviride, phenytoin and naproxen were generated using different methodologies. Data obtained using separation-based methodologies (centrifugation, filtration and ultracentrifugation) proved to be of limited use, due to poor nanoparticle separation efficiencies and/or significant adsorption of TPGS onto the nanoparticle surfaces. Light scattering and turbidity were found to be more suitable for the determination of nanosuspension solubility. The obtained data show that, unlike earlier reports, the solubility increases due to nanosizing are small, with measured increases of only 15%. These solubility increases are in fair agreement with what would be predicted based on the Ostwald-Freundlich equation.

  9. Additional red and reddened stars in Cyg OB2 association

    NASA Technical Reports Server (NTRS)

    Parthasarathy, M.; Jain, S. K.

    1989-01-01

    Several new red and reddened stars are detected in the most heavily reddened associations Cyg OB2. About 47 IRAS sources are detected in Cyg OB2. Their flux distributions, and colors, suggest that they are young stellar objects embedded in dust envelopes or disks (some of them may be proto stars) and are most likely members of the Cyg OB2 association. The large values of the flux ratio L sub IR/L sub VIS suggests that the central objects are obscured because of very large extinction.

  10. Association of Arterial Pressure Volume Index With the Presence of Significantly Stenosed Coronary Vessels

    PubMed Central

    Ueda, Takashi; Miura, Shin-ichiro; Suematsu, Yasunori; Shiga, Yuhei; Kuwano, Takashi; Sugihara, Makoto; Ike, Amane; Iwata, Atsushi; Nishikawa, Hiroaki; Fujimi, Kanta; Saku, Keijiro

    2016-01-01

    Background A blood pressure (BP) monitoring system (PASESA®) can be used to easily analyze the characteristics of central and peripheral arteries during the measurement of brachial BP. Methods We enrolled 108 consecutive patients (M/F = 86/22, age 70 ± 10 years) who underwent coronary angiography (CAG) due to suspected coronary artery disease (CAD) in whom we could measure various parameters using PASESA® in addition to brachial-ankle pulse wave velocity (baPWV). The patients were divided into two groups: patients who did not have significantly stenosed coronary vessel disease (n = 33, non-SVD group) and those who had at least one significantly stenosed coronary vessel (n = 75, SVD group). The characteristics of central and peripheral arteries (arterial velocity pulse index (AVI) and arterial pressure volume index (API), respectively) and baPWV were measured. Estimated central BP (eCBP) was calculated from the data obtained from PASESA®, and CBP was also measured simultaneously by invasive catheterization. Results API, but not AVI and baPWV, in the SVD group was significantly higher than that in the non-SVD group. Although eCBP was significantly associated with CBP, there was no difference in eCBP between the groups. There were significant associations among API, AVI and baPWV, albeit these associations were relatively weak. A multivariate logistic regression revealed that API and β-blocker were significant independent variables that were associated with the presence of significant coronary stenosis. The cut-off level of API that gave the greatest sensitivity and specificity for the presence of SVD was 24 units (sensitivity 0.636 and specificity 0.667). Conclusion In conclusion, API, but not AVI or baPWV, is associated with the presence of significant coronary stenosis. PMID:27429681

  11. ADDITIONAL MASSIVE BINARIES IN THE CYGNUS OB2 ASSOCIATION

    SciTech Connect

    Kiminki, Daniel C.; Kobulnicky, Henry A.; Ewing, Ian; Lundquist, Michael; Alexander, Michael; Vargas-Alvarez, Carlos; Choi, Heather; Bagley Kiminki, Megan M.; Henderson, C. B.

    2012-03-01

    We report the discovery and orbital solutions for two new OB binaries in the Cygnus OB2 Association, MT311 (B2V + B3V) and MT605 (B0.5V + B2.5:V). We also identify the system MT429 as a probable triple system consisting of a tight eclipsing 2.97 day B3V+B6V pair and a B0V at a projected separation of 138 AU. We further provide the first spectroscopic orbital solutions to the eclipsing, double-lined, O-star binary MT696 (O9.5V + B1:V), the double-lined, early B binary MT720 (B0-1V + B1-2V), and the double-lined, O-star binary MT771 (O7V + O9V). These systems exhibit orbital periods between 1.5 days and 12.3 days, with the majority having P <6 days. The two new binary discoveries and six spectroscopic solutions bring the total number of known massive binaries in the central region of the Cygnus OB2 Association to 20, with all but two having full orbital solutions.

  12. The Association of Genome-Wide Significant Spirometric Loci with Chronic Obstructive Pulmonary Disease Susceptibility

    PubMed Central

    Cho, Michael H.; Litonjua, Augusto A.; Bakke, Per; Gulsvik, Amund; Lomas, David A.; Anderson, Wayne; Beaty, Terri H.; Hokanson, John E.; Crapo, James D.; Laird, Nan; Silverman, Edwin K.

    2011-01-01

    Two recent metaanalyses of genome-wide association studies conducted by the CHARGE and SpiroMeta consortia identified novel loci yielding evidence of association at or near genome-wide significance (GWS) with FEV1 and FEV1/FVC. We hypothesized that a subset of these markers would also be associated with chronic obstructive pulmonary disease (COPD) susceptibility. Thirty-two single-nucleotide polymorphisms (SNPs) in or near 17 genes in 11 previously identified GWS spirometric genomic regions were tested for association with COPD status in four COPD case-control study samples (NETT/NAS, the Norway case-control study, ECLIPSE, and the first 1,000 subjects in COPDGene; total sample size, 3,456 cases and 1,906 controls). In addition to testing the 32 spirometric GWS SNPs, we tested a dense panel of imputed HapMap2 SNP markers from the 17 genes located near the 32 GWS SNPs and in a set of 21 well studied COPD candidate genes. Of the previously identified GWS spirometric genomic regions, three loci harbored SNPs associated with COPD susceptibility at a 5% false discovery rate: the 4q24 locus including FLJ20184/INTS12/GSTCD/NPNT, the 6p21 locus including AGER and PPT2, and the 5q33 locus including ADAM19. In conclusion, markers previously associated at or near GWS with spirometric measures were tested for association with COPD status in data from four COPD case-control studies, and three loci showed evidence of association with COPD susceptibility at a 5% false discovery rate. PMID:21659657

  13. Does the addition of writing into a pharmacy communication skills course significantly impact student communicative learning outcomes? A pilot study.

    PubMed

    Lonie, John M; Rahim, Hamid

    2010-12-01

    The objective of this study was to determine if the addition of a reflective writing component in a fourth year (P-2) pharmacy communication skills course would significantly affect 2 measures of learning: (1) objective multiple choice examination questions and (2) a patient counseling Objective Structured Clinical Examination (OSCE) score. Using a nonequivalent group quasi-experimental retrospective comparison design, 98 randomly selected final examination scores from students taking a non-writing intensive (NWI) communication skills course were compared with 112 randomly selected final examination scores from students that took a communication skills course in which students engaged in several reflective writing assignments. In addition, 91 randomly selected patient counseling OSCE scores from a NWI course were statistically compared with 112 scores from students that took the writing intensive (WI) course. There were statistically significant improvements in multiple choice examination scores in the group that took the reflective writing communication skills course. There was not a statistically significant difference in patient counseling OSCE scores after students completed the WI course. Studying the effects of using reflective writing assignments in communication skills courses may improve the retention and retrieval of information presented within the course.

  14. Significant chemical burns associated with dermal exposure to laundry pod detergent.

    PubMed

    Russell, Jason L; Wiles, Devin A; Kenney, Brian; Spiller, Henry A

    2014-09-01

    Concentrated laundry pods have been reported to cause significant clinical effects including oropharyngeal burns and respiratory distress requiring intubation. Dermal burns have been reported, but no incidents of serious isolated dermal injury have been published. We report a case of significant, isolated dermal injury as a result of dermal exposure to a concentrated laundry detergent pod. Total body surface area partial thickness burns in this case were estimated at approximately 2 % with an additional 4-5 % of total body surface area (TBSA) displaying superficial burns/chemical dermatitis. Health-care providers should be aware of this complication and should perform thorough dermal decontamination in the event of an exposure. Parents should be educated regarding the dangers associated with dermal exposure to laundry pod compounds and the need to secure these items away from children as well as proper decontamination techniques should an exposure occur.

  15. Mechanical and Electrical Properties of a Polyimide Film Significantly Enhanced by the Addition of Single-Wall Carbon Nanotubes

    NASA Technical Reports Server (NTRS)

    Meador, Michael A.

    2005-01-01

    Single-wall carbon nanotubes have been shown to possess a combination of outstanding mechanical, electrical, and thermal properties. The use of carbon nanotubes as an additive to improve the mechanical properties of polymers and/or enhance their thermal and electrical conductivity has been a topic of intense interest. Nanotube-modified polymeric materials could find a variety of applications in NASA missions including large-area antennas, solar arrays, and solar sails; radiation shielding materials for vehicles, habitats, and extravehicular activity suits; and multifunctional materials for vehicle structures and habitats. Use of these revolutionary materials could reduce vehicle weight significantly and improve vehicle performance and capabilities.

  16. Whole-stream nitrate addition affects litter decomposition and associated fungi but not invertebrates.

    PubMed

    Ferreira, Verónica; Gulis, Vladislav; Graça, Manuel A S

    2006-10-01

    We assessed the effect of whole-stream nitrate enrichment on decomposition of three substrates differing in nutrient quality (alder and oak leaves and balsa veneers) and associated fungi and invertebrates. During the 3-month nitrate enrichment of a headwater stream in central Portugal, litter was incubated in the reference site (mean NO3-N 82 microg l-1) and four enriched sites along the nitrate gradient (214-983 microg NO3-N l-1). A similar decomposition experiment was also carried out in the same sites at ambient nutrient conditions the following year (33-104 microg NO3-N l-1). Decomposition rates and sporulation of aquatic hyphomycetes associated with litter were determined in both experiments, whereas N and P content of litter, associated fungal biomass and invertebrates were followed only during the nitrate addition experiment. Nitrate enrichment stimulated decomposition of oak leaves and balsa veneers, fungal biomass accrual on alder leaves and balsa veneers and sporulation of aquatic hyphomycetes on all substrates. Nitrate concentration in stream water showed a strong asymptotic relationship (Michaelis-Menten-type saturation model) with temperature-adjusted decomposition rates and percentage initial litter mass converted into aquatic hyphomycete conidia for all substrates. Fungal communities did not differ significantly among sites but some species showed substrate preferences. Nevertheless, certain species were sensitive to nitrogen concentration in water by increasing or decreasing their sporulation rate accordingly. N and P content of litter and abundances or richness of litter-associated invertebrates were not affected by nitrate addition. It appears that microbial nitrogen demands can be met at relatively low levels of dissolved nitrate, suggesting that even minor increases in nitrogen in streams due to, e.g., anthropogenic eutrophication may lead to significant shifts in microbial dynamics and ecosystem functioning.

  17. Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs

    PubMed Central

    Zhang, Liang; Hu, Changyuan; Guo, Gangqiang; Mao, Chenchen; Xu, Jianfeng; Ye, Sisi; Huang, Guanli; Xue, Xiangyang; Guo, Aizhen; Shen, Xian

    2016-01-01

    Background Colorectal cancer (CRC) is one of the deadliest tumours, but its pathogenesis remains unclear. The involvement of differentially expressed long non-coding RNAs (lncRNAs) in CRC tumorigenesis makes them suitable tumour biomarkers. Methods/Findings Here, we screened 150 cases of CRC and 85 cases of paracancerous tissues in the GEO database for differentially expressed lncRNAs. The levels of lncRNA candidates in 84 CRC and paracancerous tissue samples were validated by qRT-PCR and their clinical significance was analyzed. We identified 15 lncRNAs with differential expression in CRC tumours; among them, AK098081 was significantly up-regulated, whereas AK025209, BC040303, BC037331, AK026659, and CR749831 were down-regulated in CRC. In a receiver operating characteristic curve analysis, the area under the curve for the six lncRNAs was 0.914. High expression of AK098081 and low expression of BC040303, CR749831, and BC037331 indicated poor CRC differentiation. CRC patients with lymph node metastasis had lower expression of BC037331. In addition, the group with high AK098081 expression presented significantly lower overall survival and disease-free survival rates than the low-expression group, confirming AK098081 as an independent risk factor for CRC patients. Conclusion/Significance In conclusion, we have identified multiple CRC-associated lncRNAs from microarray expression profiles that can serve as novel biomarkers for the diagnosis and prognosis of CRC. PMID:27788162

  18. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    PubMed Central

    Liu, Yiwen; Ni, Bing-Jie

    2015-01-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d−1 compared to 0.118 d−1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment. PMID:25644239

  19. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    NASA Astrophysics Data System (ADS)

    Liu, Yiwen; Ni, Bing-Jie

    2015-02-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d-1 compared to 0.118 d-1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment.

  20. Appropriate Fe (II) addition significantly enhances anaerobic ammonium oxidation (Anammox) activity through improving the bacterial growth rate.

    PubMed

    Liu, Yiwen; Ni, Bing-Jie

    2015-01-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d(-1) compared to 0.118 d(-1) at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment. PMID:25644239

  1. A significant association between BDNF promoter methylation and the risk of drug addiction.

    PubMed

    Xu, Xuting; Ji, Huihui; Liu, Guili; Wang, Qinwen; Liu, Huifen; Shen, Wenwen; Li, Longhui; Xie, Xiaohu; Zhou, Wenhua; Duan, Shiwei

    2016-06-10

    As a member of the neurotrophic factor family, brain derived neurotrophic factor (BDNF) plays an important role in the survival and differentiation of neurons. The aim of our work was to evaluate the role of BDNF promoter methylation in drug addiction. A total of 60 drug abusers (30 heroin and 30 methylamphetamine addicts) and 52 healthy age- and gender-matched controls were recruited for the current case control study. Bisulfite pyrosequencing technology was used to determine the methylation levels of five CpGs (CpG1-5) on the BDNF promoter. Among the five CpGs, CpG5 methylation was significantly lower in drug abusers than controls. Moreover, significant associations were found between CpG5 methylation and addictive phenotypes including tension-anxiety, anger-hostility, fatigue-inertia, and depression-dejection. In addition, luciferase assay showed that the DNA fragment of BDNF promoter played a key role in the regulation of gene expression. Our results suggest that BDNF promoter methylation is associated with drug addiction, although further studies are needed to understand the mechanisms by which BDNF promoter methylation contributes to the pathophysiology of drug addiction. PMID:26976342

  2. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

    PubMed Central

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80–11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density. PMID:26314987

  3. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C.; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  4. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption.

    PubMed

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  5. Serum Homocysteine Concentration Is Significantly Associated with Inflammatory/Immune Factors

    PubMed Central

    Yang, Xiaobo; Zhang, Haiying; Qin, Xue; Hu, Yanling; Mo, Zengnan

    2015-01-01

    Recent studies suggest that serum homocysteine (HCY) level is correlated to inflammatory/immune factors that influence the development and progression of many diseases, such as cardiovascular disease. However, the association between serum HCY level and inflammatory/immune factors in healthy populations has not been systematically investigated. This study was conducted based on the Fangchenggang Area Male Health and Examination Survey (FAMHES) project. After comprehensive baseline analysis, we could not find any significant association between HCY level and inflammatory/immune factors. However, in the next linear regression analysis, serum C4 [age-adjusted: Beta = -0.053, 95%CI = (-3.798, -0.050), P = 0.044; multivariate adjusted: Beta = -0.064, 95%CI = (-4.271, -0.378), P = 0.019] and C-reactive protein (CRP) concentration [unadjusted: Beta = 0.056, 95%CI = (0.037, 0.740), P = 0.030] were positively related with HCY. In further binary regression analysis, a significant correlation was confirmed for C4 and HCY [age-adjusted: OR = 0.572, 95%CI = (0.359, 0.911); multivariate adjusted: OR = 0.558, 95%CI = (0.344, 0.905)]. In order to discover more potential associations, multivariate logistic regression analysis was applied and suggested that HCY and C4 were significantly correlated [age-adjusted: OR = 0.703, 95%CI = (0.519, 0.951); multivariate adjusted: OR = 0.696, 95%CI = (0.509, 0.951)]. In addition, immunoglobulin M (IgM) may influence the HCY level to some extent [unadjusted: OR = 1.427, 95%CI = (1.052, 1.936); age-adjusted: OR = 1.446, 95%CI = (1.061, 1.970); multivariate adjusted: OR = 1.447, 95%CI = (1.062, 1.973)]. Combining our results with recent studies, we propose that C4, CRP, and IgM in serum are significantly associated with HCY concentration. Further studies are needed on the mechanism of the interaction, especially among cardiovascular disease subjects. PMID:26367537

  6. Additional Value of Transluminal Attenuation Gradient in CT Angiography to Predict Hemodynamic Significance of Coronary Artery Stenosis

    PubMed Central

    Stuijfzand, Wynand J.; Danad, Ibrahim; Raijmakers, Pieter G.; Marcu, C. Bogdan; Heymans, Martijn W.; van Kuijk, Cornelis C.; van Rossum, Albert C.; Nieman, Koen; Min, James K.; Leipsic, Jonathon; van Royen, Niels; Knaapen, Paul

    2015-01-01

    OBJECTIVES The current study evaluates the incremental value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (CCO), and TAG with exclusion of calcified coronary segments (ExC) over coronary computed tomography angiogram (CTA) alone using fractional flow reserve (FFR) as the gold standard. BACKGROUND TAG is defined as the contrast opacification gradient along the length of a coronary artery on a coronary CTA. Preliminary data suggest that TAG provides additional functional information. Interpretation of TAG is hampered by multiple heartbeat acquisition algorithms and coronary calcifications. Two correction models have been proposed based on either dephasing of contrast delivery by relating coronary density to corresponding descending aortic opacification (TAG-CCO) or excluding calcified coronary segments (TAG-ExC). METHODS Eighty-five patients with intermediate probability of coronary artery disease were prospectively included. All patients underwent step-and-shoot 256-slice coronary CTA. TAG, TAG-CCO, and TAG-ExC analyses were performed followed by invasive coronary angiography in conjunction with FFR measurements of all major coronary branches. RESULTS Thirty-four patients (40%) were diagnosed with hemodynamically-significant coronary artery disease (i.e., FFR ≤0.80). On a per-vessel basis (n = 253), 59 lesions (23%) were graded as hemodynamically significant, and the diagnostic accuracy of coronary CTA (diameter stenosis ≥50%) was 95%, 75%, 98%, and 54% for sensitivity, specificity, negative predictive value, and positive predictive value, respectively. TAG and TAG-ExC did not discriminate between vessels with or without hemodynamically significant lesions (−13.5 ± 17.1 HU [Hounsfield units] × 10 mm−1 vs. −11.6 ± 13.3 HU × 10 mm−1, p = 0.36; and 13.1 ± 15.9 HU × 10 mm−1 vs. −11.4 ± 11.7 HU × 10 mm−1, p = 0.77, respectively). TAG-CCO was lower in vessels with a hemodynamically-significant lesion (−0

  7. Association of invasion-promoting tenascin-C additional domains with breast cancers in young women

    PubMed Central

    2010-01-01

    Introduction Tenascin-C (TNC) is a large extracellular matrix glycoprotein that shows prominent stromal expression in many solid tumours. The profile of isoforms expressed differs between cancers and normal breast, with the two additional domains AD1 and AD2 considered to be tumour associated. The aim of the present study was to investigate expression of AD1 and AD2 in normal, benign and malignant breast tissue to determine their relationship with tumour characteristics and to perform in vitro functional assays to investigate the role of AD1 in tumour cell invasion and growth. Methods Expression of AD1 and AD2 was related to hypoxanthine phosphoribosyltransferase 1 as a housekeeping gene in breast tissue using quantitative RT-PCR, and the results were related to clinicopathological features of the tumours. Constructs overexpressing an AD1-containing isoform (TNC-14/AD1/16) were transiently transfected into breast carcinoma cell lines (MCF-7, T-47 D, ZR-75-1, MDA-MB-231 and GI-101) to assess the effect in vitro on invasion and growth. Statistical analysis was performed using a nonparametric Mann-Whitney test for comparison of clinicopathological features with levels of TNC expression and using Jonckheere-Terpstra trend analysis for association of expression with tumour grade. Results Quantitative RT-PCR detected AD1 and AD2 mRNA expression in 34.9% and 23.1% of 134 invasive breast carcinomas, respectively. AD1 mRNA was localised by in situ hybridisation to tumour epithelial cells, and more predominantly to myoepithelium around associated normal breast ducts. Although not tumour specific, AD1 and AD2 expression was significantly more frequent in carcinomas in younger women (age ≤40 years; P < 0.001) and AD1 expression was also associated with oestrogen receptor-negative and grade 3 tumours (P < 0.05). AD1 was found to be incorporated into a tumour-specific isoform, not detected in normal tissues. Overexpression of the TNC-14/AD1/16 isoform significantly enhanced

  8. Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan.

    PubMed

    Nomura, Toshifumi; Akiyama, Masashi; Sandilands, Aileen; Nemoto-Hasebe, Ikue; Sakai, Kaori; Nagasaki, Akari; Ota, Mitsuhito; Hata, Hiroo; Evans, Alan T; Palmer, Colin N A; Shimizu, Hiroshi; McLean, W H Irwin

    2008-06-01

    Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and shown to be major predisposing factors for atopic dermatitis (AD). However, these studies have been mainly carried out in European populations. In early 2007, we identified two Oriental-specific FLG mutations in four Japanese families with IV and reported that filaggrin mutations were also significant predisposing factors for AD in Japan. However, the frequency of FLG mutations observed in our Japanese AD cohort (5.6%), was much lower than that seen in Europeans (up to 48%). Here, we studied a further seven Japanese families with IV and identified two additional nonsense mutations in FLG, S2889X, and S3296X. We found that more than 20% of patients in our Japanese AD case series carry FLG mutations, and there is significant statistical association between the four mutations and AD (chi(2) P=8.4 x 10(-6); heterozygote odds ratio 7.57, 95% CI 2.84-23.03). These data emphasize that skin-barrier impairment due to reduced filaggrin expression plays an important role in the pathogenesis of AD and sheds further light on the genetic architecture of atopy in Japan.

  9. New Classification Method Based on Support-Significant Association Rules Algorithm

    NASA Astrophysics Data System (ADS)

    Li, Guoxin; Shi, Wen

    One of the most well-studied problems in data mining is mining for association rules. There was also research that introduced association rule mining methods to conduct classification tasks. These classification methods, based on association rule mining, could be applied for customer segmentation. Currently, most of the association rule mining methods are based on a support-confidence structure, where rules satisfied both minimum support and minimum confidence were returned as strong association rules back to the analyzer. But, this types of association rule mining methods lack of rigorous statistic guarantee, sometimes even caused misleading. A new classification model for customer segmentation, based on association rule mining algorithm, was proposed in this paper. This new model was based on the support-significant association rule mining method, where the measurement of confidence for association rule was substituted by the significant of association rule that was a better evaluation standard for association rules. Data experiment for customer segmentation from UCI indicated the effective of this new model.

  10. A Genome-Wide Association Analysis Reveals Epistatic Cancellation of Additive Genetic Variance for Root Length in Arabidopsis thaliana.

    PubMed

    Lachowiec, Jennifer; Shen, Xia; Queitsch, Christine; Carlborg, Örjan

    2015-01-01

    Efforts to identify loci underlying complex traits generally assume that most genetic variance is additive. Here, we examined the genetics of Arabidopsis thaliana root length and found that the genomic narrow-sense heritability for this trait in the examined population was statistically zero. The low amount of additive genetic variance that could be captured by the genome-wide genotypes likely explains why no associations to root length could be found using standard additive-model-based genome-wide association (GWA) approaches. However, as the broad-sense heritability for root length was significantly larger, and primarily due to epistasis, we also performed an epistatic GWA analysis to map loci contributing to the epistatic genetic variance. Four interacting pairs of loci were revealed, involving seven chromosomal loci that passed a standard multiple-testing corrected significance threshold. The genotype-phenotype maps for these pairs revealed epistasis that cancelled out the additive genetic variance, explaining why these loci were not detected in the additive GWA analysis. Small population sizes, such as in our experiment, increase the risk of identifying false epistatic interactions due to testing for associations with very large numbers of multi-marker genotypes in few phenotyped individuals. Therefore, we estimated the false-positive risk using a new statistical approach that suggested half of the associated pairs to be true positive associations. Our experimental evaluation of candidate genes within the seven associated loci suggests that this estimate is conservative; we identified functional candidate genes that affected root development in four loci that were part of three of the pairs. The statistical epistatic analyses were thus indispensable for confirming known, and identifying new, candidate genes for root length in this population of wild-collected A. thaliana accessions. We also illustrate how epistatic cancellation of the additive genetic variance

  11. A Genome-Wide Association Analysis Reveals Epistatic Cancellation of Additive Genetic Variance for Root Length in Arabidopsis thaliana

    PubMed Central

    Lachowiec, Jennifer; Shen, Xia; Queitsch, Christine; Carlborg, Örjan

    2015-01-01

    Efforts to identify loci underlying complex traits generally assume that most genetic variance is additive. Here, we examined the genetics of Arabidopsis thaliana root length and found that the genomic narrow-sense heritability for this trait in the examined population was statistically zero. The low amount of additive genetic variance that could be captured by the genome-wide genotypes likely explains why no associations to root length could be found using standard additive-model-based genome-wide association (GWA) approaches. However, as the broad-sense heritability for root length was significantly larger, and primarily due to epistasis, we also performed an epistatic GWA analysis to map loci contributing to the epistatic genetic variance. Four interacting pairs of loci were revealed, involving seven chromosomal loci that passed a standard multiple-testing corrected significance threshold. The genotype-phenotype maps for these pairs revealed epistasis that cancelled out the additive genetic variance, explaining why these loci were not detected in the additive GWA analysis. Small population sizes, such as in our experiment, increase the risk of identifying false epistatic interactions due to testing for associations with very large numbers of multi-marker genotypes in few phenotyped individuals. Therefore, we estimated the false-positive risk using a new statistical approach that suggested half of the associated pairs to be true positive associations. Our experimental evaluation of candidate genes within the seven associated loci suggests that this estimate is conservative; we identified functional candidate genes that affected root development in four loci that were part of three of the pairs. The statistical epistatic analyses were thus indispensable for confirming known, and identifying new, candidate genes for root length in this population of wild-collected A. thaliana accessions. We also illustrate how epistatic cancellation of the additive genetic variance

  12. Prognostic significance of USP10 as a tumor-associated marker in gastric carcinoma.

    PubMed

    Zeng, Zhi; Wu, Hong-Xue; Zhan, Na; Huang, Ya-Bing; Wang, Ze-Sheng; Yang, Gui-Fang; Wang, Ping; Fu, Guo-Hui

    2014-04-01

    Ubiquitin-specific protease 10 (USP10), a novel deubiquitinating enzyme, had been associated with growth of tumor cell. However, the role of USP10 in gastric cancer carcinogenesis had not been elucidated yet. The aim of this study was to investigate the expression level of USP10 in gastric carcinoma (GC) tissues and cell lines, then to evaluate the clinical significance of USP10 in GC patients. USP10, E-cadherin, Ki67 and p53 expressions were detected in 365 GC and 40 non-cancerous mucosa tissues by immunohistochemistry. Western blot for USP10 was performed on additional fresh GC tissues and GC cell lines. The expression level of USP10 in GC tissues was proved lower than that in non-cancerous mucosa tissues (p < 0.05). It was also lower in GC cell lines (AGS, BGC-823 and MKN45 cells) than that in gastric epithelial immortalized cell line (GES-1). Clinicopathological analysis showed that USP10 expression was negatively correlated with gastric wall invasion (p = 0.009), nodal metastasis (p = 0.002), and TNM stage (p = 0.000). In contrast, a positively correlation between the expression of USP10 and E-cadherin was found (p < 0.05), but there was no relationship proved between Ki67, p53 and USP10 (p > 0.05). On the Kaplan-Meier survival curves, we found poor prognosis in GC patients was associated with negative USP10 expression (p < 0.05). Moreover, USP10 expression was an independent prognostic factor for the overall survival in multivariate analysis. Our findings suggested that USP10 was an independent predictor of prognosis of GC patients.

  13. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

    PubMed

    Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

    2015-01-01

    A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations. PMID:26339413

  14. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance

    PubMed Central

    Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

    2015-01-01

    A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations. PMID:26339413

  15. Is risk associated with drinking water in Australia of significant concern to justify mandatory regulation?

    PubMed

    McKay, J; Moeller, A

    2001-10-01

    Presently in Australia there are no mandatory drinking water standards. Here we argue that the risk associated with drinking water in Australia is of a dimension discernible to warrant mandatory regulations. The catchments that supply the major metropolitan areas of Sydney and Adelaide, and the groundwater for the city of Perth have been seriously compromised by the encroachment of development and activities. Melbourne in the past has generally relied on a closed catchment reservoir system; however, population growth in the near future will sequester the full online operation of additional reservoirs, which have multiple land use catchments. In addition to the current landscape circumstances, the management of a water system in itself proposes significant issues of risk. Two critical assumptions that are unique to a mass medium substance like water and dramatically alter the appraisal of risk are: (1) very large numbers of people are potentially exposed, and (2) small changes in contaminant levels may have adverse population outcomes. It is also known that water reticulation systems frequently suffer from contamination problems caused solely by the distribution system, and optimal management of these facilities would best be served by statutory protected transparency and dedicated water quality programs. In 1979, an Australian parliamentary committee stated that an "uncontaminated water supply is" a "basic requirement for the obtainment of good health"; however, recent surveys of Australian water systems show many are not meeting basic water quality criteria, and many communities are not receiving regular monitoring or testing as required by government authorized Australian drinking water guidelines. Exacerbating this situation is the lack of reporting and statutory endorsed standardized procedures to ensure information is properly and promptly recorded and that data are centralized for maximum benefit. The evaluation of risk associated with drinking water in

  16. Analyzing large-scale samples highlights significant association between rs10411210 polymorphism and colorectal cancer.

    PubMed

    He, Dongfeng; Ma, Lihong; Feng, Rennan; Zhang, Liangcai; Jiang, Yongshuai; Zhang, Yanqiao; Liu, Guiyou

    2015-08-01

    Colorectal cancer (CRC) is the third most common form of cancer and the second leading cause of cancer-related death in the Western countries. In order to detect common CRC genetic variants, genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. RHPN2 is located on 9q13.11, which encodes a member of the rhophilin family of Ras-homologous (Rho)-GTPase binding proteins. RHPN2 gene rs10411210 polymorphism was identified to be significantly associated with CRC in European ancestry. GWAS and candidate studies investigate whether rs10411210 polymorphism is associated with CRC risk in European, Asian and American populations. However, most studies reported no association. Evidence shows that RHPN2 rs10411210 variant may be a prognostic biomarker for patients with surgically resected CRC. Here we reevaluated this association using large-scale samples from 15 studies (131580 samples including 53564 CRC cases and 78016 controls) using meta-analysis method by searching the PubMed and Google Scholar databases. We did not identify significant heterogeneity among these 15 studies (P=0.4201 and I(2)=2.8%). Our results showed significant association between rs10411210 and CRC (P=9.17E-14, odds ratio (OR)=1.10, 95% confidence interval (CI) 1.07-1.13). In subgroup analysis, we found significant association between rs10411210 and CRC in European population with P=5.70E-09, OR=1.14, 95% CI 1.10-1.20 and Asian population with P=3.36E-07, OR=1.11, 95% CI 1.07-1.16, but not American population with P=0.0576, OR=1.05, 95% CI 1.00-1.09. Collectively, our analysis further highlights significant association between rs10411210 polymorphism and colorectal cancer.

  17. Gluten-free dough-making of specialty breads: Significance of blended starches, flours and additives on dough behaviour.

    PubMed

    Collar, Concha; Conte, Paola; Fadda, Costantino; Piga, Antonio

    2015-10-01

    The capability of different gluten-free (GF) basic formulations made of flour (rice, amaranth and chickpea) and starch (corn and cassava) blends, to make machinable and viscoelastic GF-doughs in absence/presence of single hydrocolloids (guar gum, locust bean and psyllium fibre), proteins (milk and egg white) and surfactants (neutral, anionic and vegetable oil) have been investigated. Macroscopic (high deformation) and macromolecular (small deformation) mechanical, viscometric (gelatinization, pasting, gelling) and thermal (gelatinization, melting, retrogradation) approaches were performed on the different matrices in order to (a) identify similarities and differences in GF-doughs in terms of a small number of rheological and thermal analytical parameters according to the formulations and (b) to assess single and interactive effects of basic ingredients and additives on GF-dough performance to achieve GF-flat breads. Larger values for the static and dynamic mechanical characteristics and higher viscometric profiles during both cooking and cooling corresponded to doughs formulated with guar gum and Psyllium fibre added to rice flour/starch and rice flour/corn starch/chickpea flour, while surfactant- and protein-formulated GF-doughs added to rice flour/starch/amaranth flour based GF-doughs exhibited intermediate and lower values for the mechanical parameters and poorer viscometric profiles. In addition, additive-free formulations exhibited higher values for the temperature of both gelatinization and retrogradation and lower enthalpies for the thermal transitions. Single addition of 10% of either chickpea flour or amaranth flour to rice flour/starch blends provided a large GF-dough hardening effect in presence of corn starch and an intermediate effect in presence of cassava starch (chickpea), and an intermediate reinforcement of GF-dough regardless the source of starch (amaranth). At macromolecular level, both chickpea and amaranth flours, singly added, determined

  18. Gluten-free dough-making of specialty breads: Significance of blended starches, flours and additives on dough behaviour.

    PubMed

    Collar, Concha; Conte, Paola; Fadda, Costantino; Piga, Antonio

    2015-10-01

    The capability of different gluten-free (GF) basic formulations made of flour (rice, amaranth and chickpea) and starch (corn and cassava) blends, to make machinable and viscoelastic GF-doughs in absence/presence of single hydrocolloids (guar gum, locust bean and psyllium fibre), proteins (milk and egg white) and surfactants (neutral, anionic and vegetable oil) have been investigated. Macroscopic (high deformation) and macromolecular (small deformation) mechanical, viscometric (gelatinization, pasting, gelling) and thermal (gelatinization, melting, retrogradation) approaches were performed on the different matrices in order to (a) identify similarities and differences in GF-doughs in terms of a small number of rheological and thermal analytical parameters according to the formulations and (b) to assess single and interactive effects of basic ingredients and additives on GF-dough performance to achieve GF-flat breads. Larger values for the static and dynamic mechanical characteristics and higher viscometric profiles during both cooking and cooling corresponded to doughs formulated with guar gum and Psyllium fibre added to rice flour/starch and rice flour/corn starch/chickpea flour, while surfactant- and protein-formulated GF-doughs added to rice flour/starch/amaranth flour based GF-doughs exhibited intermediate and lower values for the mechanical parameters and poorer viscometric profiles. In addition, additive-free formulations exhibited higher values for the temperature of both gelatinization and retrogradation and lower enthalpies for the thermal transitions. Single addition of 10% of either chickpea flour or amaranth flour to rice flour/starch blends provided a large GF-dough hardening effect in presence of corn starch and an intermediate effect in presence of cassava starch (chickpea), and an intermediate reinforcement of GF-dough regardless the source of starch (amaranth). At macromolecular level, both chickpea and amaranth flours, singly added, determined

  19. A fast method for computing high-significance disease association in large population-based studies.

    PubMed

    Kimmel, Gad; Shamir, Ron

    2006-09-01

    Because of rapid progress in genotyping techniques, many large-scale, genomewide disease-association studies are now under way. Typically, the disorders examined are multifactorial, and, therefore, researchers seeking association must consider interactions among loci and between loci and other factors. One of the challenges of large disease-association studies is obtaining accurate estimates of the significance of discovered associations. The linkage disequilibrium between SNPs makes the tests highly dependent, and dependency worsens when interactions are tested. The standard way of assigning significance (P value) is by a permutation test. Unfortunately, in large studies, it is prohibitively slow to compute low P values by this method. We present here a faster algorithm for accurately calculating low P values in case-control association studies. Unlike with several previous methods, we do not assume a specific distribution of the traits, given the genotypes. Our method is based on importance sampling and on accounting for the decay in linkage disequilibrium along the chromosome. The algorithm is dramatically faster than the standard permutation test. On data sets mimicking medium-to-large association studies, it speeds up computation by a factor of 5,000-100,000, sometimes reducing running times from years to minutes. Thus, our method significantly increases the problem-size range for which accurate, meaningful association results are attainable. PMID:16909386

  20. Determining the significance of associations between two series of discrete events : bootstrap methods /

    SciTech Connect

    Niehof, Jonathan T.; Morley, Steven K.

    2012-01-01

    We review and develop techniques to determine associations between series of discrete events. The bootstrap, a nonparametric statistical method, allows the determination of the significance of associations with minimal assumptions about the underlying processes. We find the key requirement for this method: one of the series must be widely spaced in time to guarantee the theoretical applicability of the bootstrap. If this condition is met, the calculated significance passes a reasonableness test. We conclude with some potential future extensions and caveats on the applicability of these methods. The techniques presented have been implemented in a Python-based software toolkit.

  1. Effects of litter addition on ectomycorrhizal associates of a lodgepole pine (Pinus contorta) stand in Yellowstone National Park.

    PubMed

    Cullings, Kenneth W; New, Michael H; Makhija, Shilpa; Parker, V Thomas

    2003-07-01

    Increasing soil nutrients through litter manipulation, pollution, or fertilization can adversely affect ectomycorrhizal (EM) communities by inhibiting fungal growth. In this study, we used molecular genetic methods to determine the effects of litter addition on the EM community of a Pinus contorta stand in Yellowstone National Park that regenerated after a stand-replacing fire. Two controls were used; in unmodified control plots nothing was added to the soil, and in perlite plots perlite, a chemically neutral substance, was added to maintain soil moisture and temperature at levels similar to those under litter. We found that (i) species richness did not change significantly following perlite addition (2.6 +/- 0.3 species/core in control plots, compared with 2.3 +/- 0.3 species/core in perlite plots) but decreased significantly (P < 0.05) following litter addition (1.8 +/- 0.3 species/core); (ii) EM infection was not affected by the addition of perlite but increased significantly (P < 0.001) in response to litter addition, and the increase occurred only in the upper soil layer, directly adjacent to the added litter; and (iii) Suillus granulatus, Wilcoxina mikolae, and agaricoid DD were the dominant organisms in controls, but the levels of W. mikolae and agaricoid DD decreased significantly in response to both perlite and litter addition. The relative levels of S. granulatus and a fourth fungus, Cortinariaceae species 2, increased significantly (P < 0.01 and P < 0.05, respectively) following litter addition. Thus, litter addition resulted in some negative effects that may be attributable to moisture-temperature relationships rather than to the increased nutrients associated with litter. Some species respond positively to litter addition, indicating that there are differences in their physiologies. Hence, changes in the EM community induced by litter accumulation also may affect ecosystem function. PMID:12839743

  2. Effects of litter addition on ectomycorrhizal associates of a lodgepole pine (Pinus contorta) stand in Yellowstone National Park

    NASA Technical Reports Server (NTRS)

    Cullings, Kenneth W.; New, Michael H.; Makhija, Shilpa; Parker, V. Thomas

    2003-01-01

    Increasing soil nutrients through litter manipulation, pollution, or fertilization can adversely affect ectomycorrhizal (EM) communities by inhibiting fungal growth. In this study, we used molecular genetic methods to determine the effects of litter addition on the EM community of a Pinus contorta stand in Yellowstone National Park that regenerated after a stand-replacing fire. Two controls were used; in unmodified control plots nothing was added to the soil, and in perlite plots perlite, a chemically neutral substance, was added to maintain soil moisture and temperature at levels similar to those under litter. We found that (i) species richness did not change significantly following perlite addition (2.6 +/- 0.3 species/core in control plots, compared with 2.3 +/- 0.3 species/core in perlite plots) but decreased significantly (P < 0.05) following litter addition (1.8 +/- 0.3 species/core); (ii) EM infection was not affected by the addition of perlite but increased significantly (P < 0.001) in response to litter addition, and the increase occurred only in the upper soil layer, directly adjacent to the added litter; and (iii) Suillus granulatus, Wilcoxina mikolae, and agaricoid DD were the dominant organisms in controls, but the levels of W. mikolae and agaricoid DD decreased significantly in response to both perlite and litter addition. The relative levels of S. granulatus and a fourth fungus, Cortinariaceae species 2, increased significantly (P < 0.01 and P < 0.05, respectively) following litter addition. Thus, litter addition resulted in some negative effects that may be attributable to moisture-temperature relationships rather than to the increased nutrients associated with litter. Some species respond positively to litter addition, indicating that there are differences in their physiologies. Hence, changes in the EM community induced by litter accumulation also may affect ecosystem function.

  3. Oxytocin and vasopressin genes are significantly associated with schizophrenia in a large Arab-Israeli pedigree.

    PubMed

    Teltsh, Omri; Kanyas-Sarner, Kyra; Rigbi, Amihai; Greenbaum, Lior; Lerer, Bernard; Kohn, Yoav

    2012-04-01

    We have previously studied the genetics of schizophrenia in a large inbred Arab-Israeli pedigree and found evidence for linkage on chromosome 20p13. This locus harbours four strong candidate genes for schizophrenia: atractin (ATRN), pantonate-kinase2 (PANK2), oxytocin (OXT) and arginine-vasopressin (AVP). In this study we further explored the association of these genes with schizophrenia in the pedigree and searched for the disease-causing variants. A mutation screening of affected individuals from the pedigree was performed by using intensive sequencing in these four genes of interest. Then, we studied the prevalence of the identified variants in all family members (n=56) as well as in Arab-Israeli nuclear families (n=276) and a Jewish case-control sample (n=545). We also studied the possible functional role of these variants by examining their association with gene expression in the brain (n=104). We identified seven genetic variants in the OXT-AVP cluster in affected individuals from the pedigree. Three of these variants were significantly associated with schizophrenia in this pedigree. A 7-SNP haplotype was also significantly associated with disease. We found significant association of some of these variants in the two samples from the general population. Expression data analysis showed a possible functional role of two of these variants in regulation of gene expression. Involvement of OXT and AVP in the aetiology of schizophrenia has been suggested in the past. This study demonstrates, for the first time, a significant genetic association of these neuropeptides with schizophrenia and strongly supports this hypothesis.

  4. Pattern of intake of food additives associated with hyperactivity in Irish children and teenagers.

    PubMed

    Connolly, A; Hearty, A; Nugent, A; McKevitt, A; Boylan, E; Flynn, A; Gibney, M J

    2010-04-01

    A double-blind randomized intervention study has previously shown that a significant relationship exists between the consumption of various mixes of seven target additives by children and the onset of hyperactive behaviour. The present study set out to ascertain the pattern of intake of two mixes (A and B) of these seven target additives in Irish children and teenagers using the Irish national food consumption databases for children (n = 594) and teenagers (n = 441) and the National Food Ingredient Database. The majority of additive-containing foods consumed by both the children and teenagers contained one of the target additives. No food consumed by either the children or teenagers contained all seven of the target food additives. For each additive intake, estimates for every individual were made assuming that the additive was present at the maximum legal permitted level in those foods identified as containing it. For both groups, mean intakes of the food additives among consumers only were far below the doses used in the previous study on hyperactivity. Intakes at the 97.5th percentile of all food colours fell below the doses used in Mix B, while intakes for four of the six food colours were also below the doses used in Mix A. However, in the case of the preservative sodium benzoate, it exceeded the previously used dose in both children and teenagers. No child or teenager achieved the overall intakes used in the study linking food additives with hyperactivity.

  5. Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease

    PubMed Central

    Martinez, Raquel M.; Hulten, Kristina G.; Bui, Uyen

    2014-01-01

    Lactobacillus spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100 Lactobacillus isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥105 CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each Lactobacillus sp. We identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While Lactobacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus paracasei were associated with infections, L. gasseri was also a common colonizing/contaminating species. Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus delbrueckii were associated with at least one infection. Species commonly used in probiotic products (e.g., L. rhamnosus and L. casei) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of Lactobacillus spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each Lactobacillus sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry. PMID:24131686

  6. A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration

    PubMed Central

    Winter, Benjamin J.; O'Connell, Helen E.; Bowden, Scott; Carey, Marcus; Eisen, Damon P.

    2015-01-01

    Objectives To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. Subjects and Methods A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Results Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4). Conclusion The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation. PMID:26325074

  7. The addition of GTN to capsaicin cream reduces the discomfort associated with application of capsaicin alone. A volunteer study.

    PubMed

    McCleane, G J; McLaughlin, M

    1998-11-01

    In a double blind, placebo controlled trial of 40 volunteers, the burning discomfort associated with application of capsaicin cream (0.025%) was compared to placebo, GTN cream (1.33%) and to the combination of capsaicin cream (0.025%) plus GTN cream 1.33%. Median VAS for burning pain were 0 for the placebo, GTN and GTN + capsaicin groups and 3 for the capsaicin group after single application of each cream at daily intervals. This study demonstrates that after single application the addition of GTN to capsaicin significantly reduces the burning discomfort associated with application of capsaicin alone.

  8. Identifying significant associations of orthologous simple sequence repeats with gene ontologies.

    PubMed

    Chen, Chien-Ming; Pai, Tun-Wen; Chuang, Chia-Sheng; Huang, Jhen-Li; Tzou, Wen-Shyong; Hu, Chin-Hua

    2014-01-01

    Simple Sequence Repeats (SSRs), also known as microsatellites, regulate gene functions. SSR mutations in a disease gene may cause various genetic disorders. To identify putative functional SSRs, a web-based system, Gene Ontology SSR Hierarchy (GOSH), was developed to facilitate discovery of significant associations between SSRs and Gene Ontology (GO) terms. Using the GO hierarchy term structure, GOSH assists users with selecting functional or biological gene subsets. Significant SSR patterns are retrieved and identified via comprehensive overrepresentation analysis within a target gene subset and by comparing results with orthologous genes. Pattern relationships between different biological subsets or supersets can be observed by using the GO hierarchy structure directly. GOSH also supports GO searching through identified significant SSR patterns and all GO terms possessing such patterns are listed for consultation. GOSH is the first comprehensive and efficient online mining tool for discovering significant orthologous SSR patterns in GO terms and is available at http://gosh.cs.ntou.edu.tw/.

  9. Diabetes is associated with impaired myocardial performance in patients without significant coronary artery disease

    PubMed Central

    2010-01-01

    Background Patients with diabetes mellitus (DM) have high risk of heart failure. Whether some of the risk is directly linked to metabolic derangements in the myocardium or whether the risk is primarily caused by coronary artery disease (CAD) and hypertension is incompletely understood. Echocardiographic tissue Doppler imaging was therefore performed in DM patients without significant CAD to examine whether DM per se influenced cardiac function. Methods Patients with a left ventricular (LV) ejection fraction (EF) > 35% and without significant CAD, prior myocardial infarction, cardiac pacemaker, atrial fibrillation, or significant valve disease were identified from a tertiary invasive center register. DM patients were matched with controls on age, gender and presence of hypertension. Results In total 31 patients with diabetes and 31 controls were included. Mean age was 58 ± 12 years, mean LVEF was 51 ± 7%, and 48% were women. No significant differences were found in LVEF, left atrial end systolic volume, or left ventricular dimensions. The global longitudinal strain was significantly reduced in patients with DM (15.9 ± 2.9 vs. 17.7 ± 2.9, p = 0.03), as were peak longitudinal systolic (S') and early diastolic (E') velocities (5.7 ± 1.1 vs. 6.4 ± 1.1 cm/s, p = 0.02 and 6.1 ± 1.7 vs. 7.7 ± 2.0 cm/s, p = 0.002). In multivariable regression analyses, DM remained significantly associated with impairments of S' and E', respectively. Conclusion In patients without significant CAD, DM is associated with an impaired systolic longitudinal LV function and global diastolic dysfunction. These abnormalities are likely to be markers of adverse prognosis. PMID:20082690

  10. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis

    PubMed Central

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  11. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis.

    PubMed

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  12. Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer.

    PubMed

    Galdiero, Maria Rosaria; Bianchi, Paolo; Grizzi, Fabio; Di Caro, Giuseppe; Basso, Gianluca; Ponzetta, Andrea; Bonavita, Eduardo; Barbagallo, Marialuisa; Tartari, Silvia; Polentarutti, Nadia; Malesci, Alberto; Marone, Gianni; Roncalli, Massimo; Laghi, Luigi; Garlanda, Cecilia; Mantovani, Alberto; Jaillon, Sébastien

    2016-07-15

    Inflammatory cells are an essential component of the tumor microenvironment. Neutrophils have emerged as important players in the orchestration and effector phase of innate and adaptive immunity. The significance of tumor-associated neutrophils (TAN) in colorectal cancer (CRC) has been the subject of conflicting reports and the present study was designed to set up a reliable methodology to assess TAN infiltration in CRC and to evaluate their clinical significance. CD66b and myeloperoxidase (MPO) were assessed as candidate neutrophil markers in CRC using immunohistochemistry. CD66b was found to be a reliable marker to identify TAN in CRC tissues, whereas MPO also identified a subset of CD68(+) macrophages. CRC patients (n = 271) (Stages I-IV) were investigated retrospectively by computer-assisted imaging on whole tumor sections. TAN density dramatically decreases in Stage IV patients as compared to Stage I-III. At Cox analysis, higher TAN density was associated with better prognosis. Importantly, multivariate analysis showed that prognostic significance of TAN can be influenced by clinical stage and 5-fluorouracil(5-FU)-based chemotherapy. On separate analysis of Stage III patients (n = 178), TAN density had a dual clinical significance depending on the use of 5-FU-based chemotherapy. Unexpectedly, higher TAN density was associated with better response to 5-FU-based chemotherapy. Thus, TAN are an important component of the immune cell infiltrate in CRC and assessment of TAN infiltration may help identify patients likely to benefit from 5-FU-based chemotherapy. These results call for a reassessment of the role of neutrophils in cancer using rigorous quantitative methodology. PMID:26939802

  13. Inter-professional education unveiling significant association between asthma knowledge and inhaler technique

    PubMed Central

    Basheti, Iman A.; Hamadi, Salim A.; Reddel, Helen K.

    2015-01-01

    Objectives: To explore whether an association exists between health care professionals’ (HCPs) asthma knowledge and inhaler technique demonstration skills. Methods: HCPs’ asthma knowledge and inhaler technique demonstration skills were assessed at baseline at an inter-professional educational workshop focusing on asthma medication use. Asthma knowledge was assessed via a published questionnaire. Correct inhaler technique for the three inhalers, the Accuhaler, Turbuhaler and pressurized Metered Dose Inhaler (pMDI) was assessed using published checklists. Results: Two hundred HCPs agreed to participate: 10 specialists (medical doctors specialized in respiratory diseases) (5%), 46 general practitioners (23%), 79 pharmacists (39%), 15 pharmacists’ assistants (8%), 40 nurses (20%) and 10 respiratory therapists (5%). Backwards stepwise multiple regression conducted to determine predictors of HCPs’ inhaler technique, showed that out of many independent variables (asthma knowledge score, profession, age, gender, place of work, years in practice and previous personal use of the study inhaler/s), asthma knowledge score was the only variable showing significant association with inhaler technique (R2=0.162, p<0.001). Conclusion: This study revealed significant associations between asthma knowledge and inhaler technique scores for all HCPs. Providing inter-professional workshops for all HCPs involved integrating education on asthma knowledge and practice of inhaler technique skills are looked-for. PMID:27011779

  14. Stress Exposure in Significant Relationships Is Associated with Lymph Node Status in Breast Cancer

    PubMed Central

    Renzi, Chiara; Vadilonga, Valeria; Gandini, Sara; Perinel, Giada; Rotmensz, Nicole; Didier, Florence; Rescigno, Maria; Pravettoni, Gabriella

    2016-01-01

    Objective Life stress exposure may impact on health and disease. Previous literature showed that stressful life events are associated with cancer incidence, survival and mortality. In animal models, patterns of maternal care have been shown to critically affect stress sensitivity and immunity trajectories later in life, by modifying DNA methylation during critical periods early in life. However, the role of parental care in breast cancer progression and survival has only limitedly been explored. Here, we investigated whether these factors may be linked to biological prognostic variables. Methods One hundred twenty-three women hospitalized for surgery of primary breast cancer completed a questionnaire assessing parental bonding. Stressful events throughout the life span were also assessed. Results We found that the absence of optimal parental relationships is significantly associated with an increased risk of lymph node involvement, adjusting for confounders, while cumulative stress in the area of sentimental relationships is borderline significantly associated with the same prognostic factor. Conclusions Our results suggest that parental bonding and sentimental relations may have a role in breast cancer progression. These variables represent an important evolutionary aspect which may modulate cancer progression through psycho-physiological stress pathways and influence the immune system. PMID:26910901

  15. Genetic Polymorphisms of the Bovine NOV Gene Are Significantly Associated with Carcass Traits in Korean Cattle

    PubMed Central

    Kim, B. S.; Kim, S. C.; Park, C. M.; Lee, S. H.; Cho, S. H.; Kim, N. K.; Jang, G. W.; Yoon, D. H.; Yang, B. S.; Hong, S. K.; Seong, H. H.; Choi, B. H.

    2013-01-01

    The objective of this study was to investigate single nucleotide polymorphisms (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate whether these polymorphisms affect carcass traits in the Korean cattle population. We resequenced to detect SNPs from 24 unrelated individuals and identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter region. Of these 19 SNPs, four were selected for genotyping based on linkage disequilibrium (LD). We genotyped 429 steers to assess the associations of these four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p = 0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings suggest that polymorphisms in the NOV gene may be among the important genetic factors affecting carcass yield in beef cattle. PMID:25049850

  16. Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study

    PubMed Central

    Wang, Yongbo; Gao, Xiang; Pedram, Pardis; Shahidi, Mariam; Du, Jianling; Yi, Yanqing; Gulliver, Wayne; Zhang, Hongwei; Sun, Guang

    2016-01-01

    Selenium (Se) is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%–27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile. PMID:26742059

  17. Increase in federal match associated with significant gains in coverage for children through Medicaid and CHIP.

    PubMed

    Patrick, Stephen W; Choi, Hwajung; Davis, Matthew M

    2012-08-01

    As the number of children living in poverty has increased steadily over the past decade, Medicaid and the Children's Health Insurance Program (CHIP) have enrolled millions of additional youths. Federal and state governments jointly finance both programs, with the federal portion determined by the Federal Medical Assistance Percentage, commonly known as the "federal match." The federal government has used intermittent increases in the federal match as a way to provide fiscal relief to states during economic downturns. The most recent broad increase ended in June 2011, but the precise impact on Medicaid and CHIP enrollment for children is not known. No previous study has evaluated the association of the federal match with children's enrollment in state Medicaid or CHIP programs in the context of other state factors. To shed light on the degree to which public coverage for children varies with differences in the federal match, we examined publicly available data from all fifty states from 1999 to 2009. We found that a ten-percentage-point increase in the federal match was associated with a 1.9 percent increase in Medicaid and CHIP enrollment, equivalent to approximately 500,000 children. This association persisted when adjusted for multiple state-level factors, including the proportion of children living in poverty. This analysis underscores the central role of the federal match in supporting expansion of Medicaid and CHIP coverage for children.

  18. A significant causal association between C-reactive protein levels and schizophrenia

    PubMed Central

    Inoshita, Masatoshi; Numata, Shusuke; Tajima, Atsushi; Kinoshita, Makoto; Umehara, Hidehiro; Nakataki, Masahito; Ikeda, Masashi; Maruyama, Souichiro; Yamamori, Hidenaga; Kanazawa, Tetsufumi; Shimodera, Shinji; Hashimoto, Ryota; Imoto, Issei; Yoneda, Hiroshi; Iwata, Nakao; Ohmori, Tetsuro

    2016-01-01

    Many observational studies have shown elevated blood CRP levels in schizophrenia compared with controls, and one population-based prospective study has reported that elevated plasma CRP levels were associated with late- and very-late-onset schizophrenia. Furthermore, several clinical studies have reported the efficacy of anti-inflammatory drugs on the symptoms in patients with schizophrenia. However, whether elevated CRP levels are causally related to schizophrenia is not still established because of confounding factors and reverse causality. In the present study, we demonstrated that serum CRP levels were significantly higher in patients with schizophrenia than in the controls by conducting a case-control study and a meta-analysis of case-control studies between schizophrenia and serum CRP levels. Furthermore, we provided evidence for a causal association between elevated CRP levels and increased schizophrenia risk by conducting a Mendelian randomization analysis. Our findings suggest that elevated CRP itself may be a causal risk factor for schizophrenia. PMID:27193331

  19. Significant association of methylenetetrahydrofolate reductase single nucleotide polymorphisms with prostate cancer susceptibility in taiwan.

    PubMed

    Wu, Hsi-Chin; Chang, Chao-Hsiang; Tsai, Ru-Yin; Lin, Chih-Hsueh; Wang, Rou-Fen; Tsai, Chia-Wen; Chen, Kuen-Bao; Yao, Chun-Hsu; Chiu, Chang-Fang; Bau, Da-Tian; Lin, Cheng-Chieh

    2010-09-01

    Prostate cancer is the most common cause of cancer death in men and is a major health problem worldwide. Methylene tetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and is also an important source of DNA methylation and DNA synthesis (nucleotide synthesis). To assess the association and interaction of genotypic polymorphisms in MTHFR and lifestyle factors with prostate cancer in Taiwan, we investigated two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), analyzed the association of specific genotypes with prostate cancer susceptibility, and discussed their joint effects with individual habits on prostate cancer risk. In total, 218 patients with prostate cancer and 436 healthy controls recruited from the China Medical Hospital in central Taiwan were genotyped for these polymorphisms with prostate cancer susceptibility. We found the MTHFR C677T but not the A1298C genotype was differently distributed between the prostate cancer and control groups. The T allele of MTHFR C677T conferred a significantly (p=0.0011) decreased risk of prostate cancer. As for the A1298C polymorphism, there was no difference in distribution between the prostate cancer and control groups. Gene interactions with smoking were significant for MTHFR C677T polymorphism. The MTHFR C677T CT and TT genotypes in association with smoking conferred a decreased risk of 0.501 (95% confidence interval=0.344-0.731) for prostate cancer. Our results provide the first evidence that the C allele of MTHFR C677T may be associated with the development of prostate cancer and may be a novel useful marker for primary prevention and anticancer intervention.

  20. Selective neurocognitive deficits and poor life functioning are associated with significant depressive symptoms in alcoholism-HIV infection comorbidity.

    PubMed

    Sassoon, Stephanie A; Rosenbloom, Margaret J; Fama, Rosemary; Sullivan, Edith V; Pfefferbaum, Adolf

    2012-09-30

    Alcoholism, HIV, and depressive symptoms frequently co-occur and are associated with impairment in cognition and life function. We administered the Beck Depression Inventory-II (BDI-II), measures of life function, and neurocognitive tests to 67 alcoholics, 56 HIV+ patients, 63 HIV+ alcoholics, and 64 controls to examine whether current depressive symptom level (significant, BDI-II>14 vs. minimal, BDI-II<14) was associated with poorer cognitive or psychosocial function in alcoholism-HIV comorbidity. Participants with significant depressive symptoms demonstrated slower manual motor speed and poorer visuospatial memory than those with minimal depressive symptoms. HIV patients with depressive symptoms showed impaired manual motor speed. Alcoholics with depressive symptoms showed impaired visuospatial memory. HIV+ alcoholics with depressive symptoms reported the poorest quality of life; alcoholics with depressive symptoms, irrespective of HIV status, had poorest life functioning. Thus, significant depressive symptoms were associated with poorer selective cognitive and life functioning in alcoholism and in HIV infection, even though depressive symptoms had neither synergistic nor additive effects on cognition in alcoholism-HIV comorbidity. The results suggest the relevance of assessing and treating current depressive symptoms to reduce cognitive compromise and functional disability in HIV infection, alcoholism, and their comorbidity.

  1. Ultimate strength performance of tankers associated with industry corrosion addition practices

    NASA Astrophysics Data System (ADS)

    Kim, Do Kyun; Kim, Han Byul; Zhang, Xiaoming; Li, Chen Guang; Paik, Jeom Kee

    2014-09-01

    In the ship and offshore structure design, age-related problems such as corrosion damage, local denting, and fatigue damage are important factors to be considered in building a reliable structure as they have a significant influence on the residual structural capacity. In shipping, corrosion addition methods are widely adopted in structural design to prevent structural capacity degradation. The present study focuses on the historical trend of corrosion addition rules for ship structural design and investigates their effects on the ultimate strength performance such as hull girder and stiffened panel of double hull oil tankers. Three types of rules based on corrosion addition models, namely historic corrosion rules (pre-CSR), Common Structural Rules (CSR), and harmonised Common Structural Rules (CSRH) are considered and compared with two other corrosion models namely UGS model, suggested by the Union of Greek Shipowners (UGS), and Time-Dependent Corrosion Wastage Model (TDCWM). To identify the general trend in the effects of corrosion damage on the ultimate longitudinal strength performance, the corrosion addition rules are applied to four representative sizes of double hull oil tankers namely Panamax, Aframax, Suezmax, and VLCC. The results are helpful in understanding the trend of corrosion additions for tanker structures

  2. Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality

    PubMed Central

    Lau, Susanna K. P.; Chow, Wang-Ngai; Foo, Chuen-Hing; Curreem, Shirly O. T.; Lo, George Chi-Shing; Teng, Jade L. L.; Chen, Jonathan H. K.; Ng, Ricky H. Y.; Wu, Alan K. L.; Cheung, Ingrid Y. Y.; Chau, Sandy K. Y.; Lung, David C.; Lee, Rodney A.; Tse, Cindy W. S.; Fung, Kitty S. C.; Que, Tak-Lun; Woo, Patrick C. Y.

    2016-01-01

    Unlike Elizabethkingia meningoseptica, the clinical importance of E. anophelis is poorly understood. We determined the clinical and molecular epidemiology of bacteremia caused by Elizabethkingia-like species from five regional hospitals in Hong Kong. Among 45 episodes of Elizabethkingia-like bacteremia, 21 were caused by Elizabethkingia, including 17 E. anophelis, three E. meningoseptica and one E. miricola; while 24 were caused by other diverse genera/species, as determined by 16S rRNA gene sequencing. Of the 17 cases of E. anophelis bacteremia, 15 (88%) were clinically significant. The most common diagnosis was pneumonia (n = 5), followed by catheter-related bacteremia (n = 4), neonatal meningitis (n = 3), nosocomial bacteremia (n = 2) and neutropenic fever (n = 1). E. anophelis bacteremia was commonly associated with complications and carried 23.5% mortality. In contrast, of the 24 episodes of bacteremia due to non-Elizabethkingia species, 16 (67%) were clinically insignificant. Compared to non-Elizabethkingia bacteremia, Elizabethkingia bacteremia was associated with more clinically significant infections (P < 0.01) and positive cultures from other sites (P < 0.01), less polymicrobial bacteremia (P < 0.01), and higher complication (P < 0.05) and mortality (P < 0.05) rates. Elizabethkingia bacteremia is predominantly caused by E. anophelis instead of E. meningoseptica. Elizabethkingia bacteremia, especially due to E. anophelis, carries significant morbidity and mortality, and should be considered clinically significant unless proven otherwise. PMID:27185741

  3. Position Weight Matrix, Gibbs Sampler, and the Associated Significance Tests in Motif Characterization and Prediction

    PubMed Central

    Xia, Xuhua

    2012-01-01

    Position weight matrix (PWM) is not only one of the most widely used bioinformatic methods, but also a key component in more advanced computational algorithms (e.g., Gibbs sampler) for characterizing and discovering motifs in nucleotide or amino acid sequences. However, few generally applicable statistical tests are available for evaluating the significance of site patterns, PWM, and PWM scores (PWMS) of putative motifs. Statistical significance tests of the PWM output, that is, site-specific frequencies, PWM itself, and PWMS, are in disparate sources and have never been collected in a single paper, with the consequence that many implementations of PWM do not include any significance test. Here I review PWM-based methods used in motif characterization and prediction (including a detailed illustration of the Gibbs sampler for de novo motif discovery), present statistical and probabilistic rationales behind statistical significance tests relevant to PWM, and illustrate their application with real data. The multiple comparison problem associated with the test of site-specific frequencies is best handled by false discovery rate methods. The test of PWM, due to the use of pseudocounts, is best done by resampling methods. The test of individual PWMS for each sequence segment should be based on the extreme value distribution. PMID:24278755

  4. Effects of feed additives on ileal mucosa-associated microbiota composition of broiler chickens.

    PubMed

    Ruiz, R; Peinado, M J; Aranda-Olmedo, I; Abecia, L; Suárez-Pereira, E; Ortiz Mellet, C; García Fernández, J M; Rubio, L A

    2015-07-01

    The effects of dietary supplementation with 2 recently developed feed additives on the composition of the mucosa-associated microbiota of the ileum were studied in growing broiler chickens. A total of 48 male 1-d-old broiler chickens of the Cobb 500 strain were distributed in 4 treatments with 2 replicates of 6 birds each. The 2 additives tested were a di-d-fructose dianhydride–enriched caramel (FC) and the garlic derivative propyl propane thiosulfonate (PTS-O). Dietary treatments were a control (commercial diet with no additive), INU (20 g inulin/kg diet), CAR (20 g FC/kg diet), and GAR (90 mgPTS-O/kg diet). As a result of this study, inulin supplementation resulted in lower (P < 0.05) and FC feeding resulted in higher (P < 0.05) Blautia coccoides/Eubacterium rectale log10 number of copies respect to controls. Higher (P < 0.05) bifidobacteria log10 number of copies with respect to the controls was determined in the ileal mucosa of birds fed the PTS-O–supplemented diet. Denaturing gradient gel electrophoresis and PCR analysis on Bifidobacterium spp. revealed the presence of Bifidobacterium longum, Bifidobacterium pseudolongum, and Bifidobacterium pseudocatenulatum in samples from chickens fed the control and the PTS-O–supplemented diet. Bifidobacterium longum was exclusively found in poultry fed the control diet, whereas B. pseudocatenulatum was found only in poultry fed the PTS-O–supplemented diet. This study showed that both PTS-O and FC were able to modulate the composition of the ileal mucosa-associated microbiota of growing broiler chickens. Finally, in addition to B. pseudolongum, the presence of B. longum and B. pseudocatenulatum, species not previously described in intestinal samples of broilers, was also demonstrated. PMID:26440010

  5. Origin and significance of a late Wisconsin glacigenic sequence and associated periglacial features at Cary, Illinois

    SciTech Connect

    Hooyer, T.S.; Tulaczyk, S.M.; Stravers, J.A. . Dept. of Geology)

    1993-03-01

    The glacigenic sequence exposed in Cary, Illinois, provides insight into the depositional processes that shaped the Woodstock End Moraine of the Lake Michigan Lobe. The Moraine was formed by a short re-advance which occurred during the last deglaciation approximately 15,000--16,000 years B.P. In order to determine the sedimentary processes that dominated this ice marginal setting, the authors described lithofacies and their associations, glaciotectonic and sedimentary structures, as well as clast fabric. In addition, they performed laboratory analyses of grain size, lithology and shape. The glacigenic sequence represents one single ice advance/retreat as represented by five distinct facies. The complex of deposits that overlie the homogeneous diamicton layer originate from a stagnant ice environment. Their presence extends the northern limit for documented relict patterned ground in NE Illinois.

  6. Genome-Wide Significant Association between Alcohol Dependence and a Variant in the ADH Gene Cluster

    PubMed Central

    Frank, Josef; Cichon, Sven; Treutlein, Jens; Ridinger, Monika; Mattheisen, Manuel; Hoffmann, Per; Herms, Stefan; Wodarz, Norbert; Soyka, Michael; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Kiefer, Falk; Rietschel, Marcella

    2011-01-01

    Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1,333 male in-patients with severe DSM-IV AD and 2,168 controls. These included 487 patients and 1,358 controls from a previous GWAS study by our group. All individuals were of German descent. Single marker tests and a polygenic score based analysis to assess the combined contribution of multiple markers with small effects were performed. The SNP rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance (p=1.27E–8; OR=1.46). Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (p=1.24E–7, OR=1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score based approach produced a significant result (p=9.66E–9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result suggests that many more AD susceptibility genes still await identification. PMID:22004471

  7. Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster.

    PubMed

    Frank, Josef; Cichon, Sven; Treutlein, Jens; Ridinger, Monika; Mattheisen, Manuel; Hoffmann, Per; Herms, Stefan; Wodarz, Norbert; Soyka, Michael; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Kiefer, Falk; Rietschel, Marcella

    2012-01-01

    Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1333 male in-patients with severe AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 2168 controls. These included 487 patients and 1358 controls from a previous GWAS study by our group. All individuals were of German descent. Single-marker tests and a polygenic score-based analysis to assess the combined contribution of multiple markers with small effects were performed. The single nucleotide polymorphism (SNP) rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance [P = 1.27E-8, odds ratio (OR) = 1.46]. Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (P = 1.24E-7, OR = 1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score-based approach produced a significant result (P = 9.66E-9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result may indicate that many more AD susceptibility genes still await identification.

  8. Ventilator-Associated Pneumonia Prevention Bundle Significantly Reduces the Risk of Ventilator-Associated Pneumonia in Critically Ill Burn Patients.

    PubMed

    Sen, Soman; Johnston, Charles; Greenhalgh, David; Palmieri, Tina

    2016-01-01

    Ventilator-associated pneumonia (VAP) is a common cause of morbidity and mortality for critically ill burn patients. Prevention of VAP through bundled preventative measures may reduce the risk and incidence of VAP in burn patients. A retrospective chart review was performed of all mechanically ventilated adult (age ≥ 18 years) burn patients before and after VAP prevention bundle implementation. Data collected included age, TBSA, gender, diagnosis of inhalation injury, mechanism of injury, comorbid illnesses, length of mechanical ventilation, length of hospital stay, development of VAP, discharge disposition, and mortality. Burn patients with VAP had larger burn injuries (47.6 ± 22.2 vs 23.9 ± 23.01), more inhalation injuries (44.6% vs 27%), prolonged mechanical ventilation, and longer intensive care unit (ICU) and hospital stays. Mortality was also higher in burn patients who developed VAP (34% vs 19%). On multivariate regression analysis, TBSA and ventilator days were independent risk factors for VAP. In 2010, a VAP prevention bundle was implemented in the burn ICU and overseen by a nurse champion. Compliance with bundle implementation was more than 95%. By 2012, independent of age, TBSA, inhalation injury, ventilator days, ICU and hospital length of stay, VAP prevention bundles resulted in a significantly reduced risk of developing VAP (odds ratio of 0.15). Burn patients with an inhalation injury and a large burn injury are at increased risk of developing VAP. The incidence and risk of VAP can be significantly reduced in burn patients with VAP prevention bundles.

  9. The Unique and Additive Associations of Family Functioning and Parenting Practices with Disordered Eating Behaviors in Diverse Adolescents

    PubMed Central

    Berge, Jerica M.; Wall, Melanie; Larson, Nicole; Eisenberg, Marla E.; Loth, Katie A.; Neumark-Sztainer, Dianne

    2012-01-01

    Objective To examine the unique and additive associations of family functioning and parenting practices with adolescent disordered eating behaviors (i.e., dieting, unhealthy weight control behaviors, binge eating). Methods Data from EAT (Eating and Activity in Teens) 2010, a population-based study assessing eating and activity among racially/ethnically and socio-economically diverse adolescents (n = 2,793; mean age = 14.4, SD = 2.0; age range = 11–19) was used. Logistic regression models were used to examine associations between adolescent dieting and disordered eating behaviors and family functioning and parenting variables, including interactions. All analyses controlled for demographics and body mass index. Results Higher family functioning, parent connection, and parental knowledge about child’s whereabouts (e.g. who child is with, what they are doing, where they are at) were significantly associated with lower odds of engaging in dieting and disordered eating behaviors in adolescents, while parent psychological control was associated with greater odds of engaging in dieting and disordered eating behaviors. Although the majority of interactions were non-significant, parental psychological control moderated the protective relationship between family functioning and disordered eating behaviors in adolescent girls. Conclusions Clinicians and health care providers may want to discuss the importance of balancing specific parenting behaviors, such as increasing parent knowledge about child whereabouts while decreasing psychological control in order to enhance the protective relationship between family functioning and disordered eating behaviors in adolescents. PMID:23196919

  10. The unique and additive associations of family functioning and parenting practices with disordered eating behaviors in diverse adolescents.

    PubMed

    Berge, Jerica M; Wall, Melanie; Larson, Nicole; Eisenberg, Marla E; Loth, Katie A; Neumark-Sztainer, Dianne

    2014-04-01

    To examine the unique and additive associations of family functioning and parenting practices with adolescent disordered eating behaviors (i.e., dieting, unhealthy weight control behaviors, binge eating). Data from EAT (Eating and Activity in Teens) 2010, a population-based study assessing eating and activity among racially/ethnically and socio-economically diverse adolescents (n = 2,793; mean age = 14.4, SD = 2.0; age range = 11-19) was used. Logistic regression models were used to examine associations between adolescent dieting and disordered eating behaviors and family functioning and parenting variables, including interactions. All analyses controlled for demographics and body mass index. Higher family functioning, parent connection, and parental knowledge about child's whereabouts (e.g. who child is with, what they are doing, where they are at) were significantly associated with lower odds of engaging in dieting and disordered eating behaviors in adolescents, while parent psychological control was associated with greater odds of engaging in dieting and disordered eating behaviors. Although the majority of interactions were non-significant, parental psychological control moderated the protective relationship between family functioning and disordered eating behaviors in adolescent girls. Clinicians and health care providers may want to discuss the importance of balancing specific parenting behaviors, such as increasing parent knowledge about child whereabouts while decreasing psychological control in order to enhance the protective relationship between family functioning and disordered eating behaviors in adolescents.

  11. Significant Racial Differences in the Key Factors Associated with Early Graft Loss in Kidney Transplant Recipients

    PubMed Central

    Taber, David J; Douglass, Kevin; Srinivas, Titte; McGillicuddy, John W; Bratton, Charles F; Chavin, Kenneth D; Baliga, Prabhakar K; Egede, Leonard E

    2014-01-01

    Background There is continued and significant debate regarding the salient etiologies associated with graft loss and racial disparities in kidney transplant (KTX) recipients. Methods This was a longitudinal cohort study of all adult KTX recipients, comparing patients with early graft loss (<5 yrs) to those with graft longevity (surviving graft with at least 5 yrs of follow-up) across racial cohorts (African-American (AA) and non-AA) to discern risk factors. Results 524 patients were included, 55% AA, 151 with early graft loss (29%) and 373 with graft longevity (71%). Consistent within both races, early graft loss was significantly associated with disability income (adjusted odds-ratio [AOR] 2.2, 95% CI: 1.1-4.5), kidney donor risk index (AOR 3.2, 1.4-7.5), rehospitalization (AOR 2.1, 1.0-4.4) and acute rejection (AOR 4.4, 1.7-11.6) Unique risk factors in AAs included Medicare only insurance (AOR 8.0, 2.3-28) and BK infectio (AOR 5.6, 1.3-25). Unique protective factors in AAs included cardiovascular risk factor control: AAs with a mean systolic BP <150 mmHg had 80% lower risk of early graft loss (AOR 0.2, 0.1-0.7), while LDL <100 mg/dL (AOR 0.4, 0.2-0.8), triglycerides <150 mg/dL (AOR 0.4, 0.2-1.0) and HgbA1C <7% (AOR 0.2, 0.1-0.6) were also protective against early graft loss in AA, but no in non-AA recipients. Conclusions AA recipients have a number of unique risk factors for early graft loss, suggesting that controlling cardiovascular comorbidities may be an important mechanism to reduce racial disparities in kidney transplantation. PMID:24969370

  12. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    PubMed Central

    Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

    2014-01-01

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target. PMID:24978437

  13. Significant association between TIM1 promoter polymorphisms and protection against cerebral malaria in Thailand.

    PubMed

    Nuchnoi, P; Ohashi, J; Kimura, R; Hananantachai, H; Naka, I; Krudsood, S; Looareesuwan, S; Tokunaga, K; Patarapotikul, J

    2008-05-01

    Although cerebral malaria is a major life-threatening complication of Plasmodium falciparum infection, its pathophysiology is not well understood. Prolonged activation of the T helper type 1 (Th1) response characterized by the production of pro-inflammatory cytokines such as IFN-gamma and TNF-alpha has been suggested to be responsible for immunopathological process leading to cerebral malaria unless they are downregulated by the anti-inflamatory cytokines produced by the Th2 response. The T cell immunoglobulin and mucin domain (TIM) family of proteins are cell surface proteins involved in regulating Th1 and Th2 immune responses. In this study, the possible association between the polymorphisms of TIM1, TIM3, and TIMD4 genes and the severity of malaria was examined in 478 adult Thai patients infected with P. falciparum malaria. The TIM1 promoter haplotype comprising three derived alleles, -1637A (rs7702919), -1549C (rs41297577) and -1454A (rs41297579), which were in complete linkage disequilibrium, was significantly associated with protection against cerebral malaria (OR = 0.41; 95% CI = 0.24-0.71; P= 0.0009). Allele-specific transcription quantification analysis revealed that the level of mRNA transcribed from TIM1 was higher for the protective promoter haplotype than for the other promoter haplotype (P= 0.004). Engagement with TIM1 in combination with T cell receptor stimulation induces anti-inflammatory Th2 cytokine production, which can protect the development of cerebral malaria caused by overproduction of pro-inflammatory Th1 cytokines. The present results suggest that the higher TIM1 expression associated with the protective TIM1 promoter haplotype confers protection against cerebral malaria.

  14. Neurohumoral mechanisms associated with orthostasis: reaffirmation of the significant contribution of the heart rate response

    PubMed Central

    Convertino, Victor A.

    2014-01-01

    The inability to compensate for acute central hypovolemia underlies the clinical development of orthostatic hypotension and instability (e.g., syncope). Although neuro-humoral control of both cardiac output and peripheral vascular resistance contributes to hemodynamic stability during orthostasis, a notion has been proposed that the failure of adequate peripheral vascular constriction rather than cardiac responses represents the primary mechanism underlying the development of orthostatic intolerance. This review article provides an opportunity to present compelling evidence captured over the past 30 years in our laboratory to support the concept that neural-mediated tachycardia during orthostasis in healthy individuals represents a critical response to tolerating acute reduction in central blood volume in addition to, and independent of, peripheral vascular constriction. In this review paper, data are presented from experiments using graded lower body negative pressure (LBNP) as a method to induce orthostatic intolerance in two experimental human models: (1) comparison of heart rate and autonomic responses in individuals with relatively high and low tolerance to LBNP; and (2) vagal and sympathetic blockade of cardiac neural control. These experiments revealed that: (1) greater elevations in heart rate are associated with higher orthostatic (LBNP) tolerance; (2) higher orthostatic heart rate is associated with greater sympathetic nerve activity and withdrawal of vagally-mediated cardiac baroreflex response; and (3) non-specific sympathetic blockade causes a pronounced reduction in heart rate and LBNP tolerance. Cardiac parasympathetic withdrawal contributes to protection against development of hypotension during the initial seconds of transition to an orthostatic challenge, while the primary mechanism by which tachycardia defends orthostatic stability in healthy subjects for extended durations is mediated predominantly through sympathetic adrenergic control. PMID

  15. A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses

    PubMed Central

    2014-01-01

    Background Thoroughbred racehorses are subject to non-traumatic distal limb bone fractures that occur during racing and exercise. Susceptibility to fracture may be due to underlying disturbances in bone metabolism which have a genetic cause. Fracture risk has been shown to be heritable in several species but this study is the first genetic analysis of fracture risk in the horse. Results Fracture cases (n = 269) were horses that sustained catastrophic distal limb fractures while racing on UK racecourses, necessitating euthanasia. Control horses (n = 253) were over 4 years of age, were racing during the same time period as the cases, and had no history of fracture at the time the study was carried out. The horses sampled were bred for both flat and National Hunt (NH) jump racing. 43,417 SNPs were employed to perform a genome-wide association analysis and to estimate the proportion of genetic variance attributable to the SNPs on each chromosome using restricted maximum likelihood (REML). Significant genetic variation associated with fracture risk was found on chromosomes 9, 18, 22 and 31. Three SNPs on chromosome 18 (62.05 Mb – 62.15 Mb) and one SNP on chromosome 1 (14.17 Mb) reached genome-wide significance (p < 0.05) in a genome-wide association study (GWAS). Two of the SNPs on ECA 18 were located in a haplotype block containing the gene zinc finger protein 804A (ZNF804A). One haplotype within this block has a protective effect (controls at 1.95 times less risk of fracture than cases, p = 1 × 10-4), while a second haplotype increases fracture risk (cases at 3.39 times higher risk of fracture than controls, p = 0.042). Conclusions Fracture risk in the Thoroughbred horse is a complex condition with an underlying genetic basis. Multiple genomic regions contribute to susceptibility to fracture risk. This suggests there is the potential to develop SNP-based estimators for genetic risk of fracture in the Thoroughbred racehorse, using methods

  16. Postranslational modifications significantly alter the binding-folding pathways of proteins associating with DNA

    NASA Astrophysics Data System (ADS)

    Papoian, Garegin

    2012-02-01

    Many important regulators of gene activity are natively disordered, but fully or partially order when they bind to their targets on DNA. Interestingly, the ensembles of disordered states for such free proteins are not structurally featureless, but can qualitatively differ from protein to protein. In particular, in random coil like states the chains are swollen, making relatively few contacts, while in molten globule like states a significant collapse occurs, with ensuing high density of intra-protein interactions. Furthermore, since many DNA binding proteins are positively charged polyelectrolytes, the electrostatic self-repulsion also influences the degree of collapse of the chain and its conformational preferences in the free state and upon binding to DNA. In our work, we have found that the nature of the natively disordered ensemble significantly affects the way the protein folds upon binding to DNA. In particular, we showed that posttranslational modifications of amino acid residues, such as lysine acetylation, can alter the degree of collapse and conformational preferences for a free protein, and also profoundly impact the binding affinity and pathways for the protein DNA association. These trends will be discussed in the context of DNA interacting with various histone tails and the p53 protein.

  17. PERSONAL AND ENVIRONMENTAL RISK FACTORS SIGNIFICANTLY ASSOCIATED WITH ELEVATED BLOOD LEAD LEVELS IN RURAL THAI CHILDREN.

    PubMed

    Swaddiwudhipong, Witaya; Kavinum, Suporn; Papwijitsil, Ratchadaporn; Tontiwattanasap, Worawit; Khunyotying, Wanlee; Umpan, Jiraporn; BoonthuM, Ratchaneekorn; Kaewnate, Yingyot; Boonmee, Sasis; Thongchub, Winai; Rodsung, Thassanee

    2014-11-01

    A community-based study was conducted to determine personal risk factors and environmental sources of lead exposure for elevated blood lead levels (≥ 10 µg/dl, EBLLs) among rural children living at the Thailand-Myanmar border in Tak Province, northwestern Thailand. Six hundred ninety-five children aged 1-14 years old were screened for BLLs. Environmental specimens for lead measurements included samples of water from the streams, taps, and household containers, house floor dust, and foods. Possible lead release from the cooking ware was determined using the leaching method with acetic acid. The overall prevalence of EBLLs was 47.1% and the geometric mean level of blood lead was 9.16 µg/dl. Personal risk factors significantly associated with EBLLs included being male, younger age, anemia, and low weight-for-age. Significant environmental risk factors were exposure to a lead-acid battery of solar energy system and use of a non-certified metal cooking pot. Some families whose children had high BLLs reported production of lead bullets from the used batteries at home. About one-third of the house dust samples taken near batteries contained lead content above the recommended value, compared with none of those taken from other areas and from the houses with no batteries. The metal pots were safe for cooking rice but might be unsafe for acidic food preparation. Both nutritional intervention and lead exposure prevention programs are essential to reduce EBLLs in this population. PMID:26466436

  18. PERSONAL AND ENVIRONMENTAL RISK FACTORS SIGNIFICANTLY ASSOCIATED WITH ELEVATED BLOOD LEAD LEVELS IN RURAL THAI CHILDREN.

    PubMed

    Swaddiwudhipong, Witaya; Kavinum, Suporn; Papwijitsil, Ratchadaporn; Tontiwattanasap, Worawit; Khunyotying, Wanlee; Umpan, Jiraporn; BoonthuM, Ratchaneekorn; Kaewnate, Yingyot; Boonmee, Sasis; Thongchub, Winai; Rodsung, Thassanee

    2014-11-01

    A community-based study was conducted to determine personal risk factors and environmental sources of lead exposure for elevated blood lead levels (≥ 10 µg/dl, EBLLs) among rural children living at the Thailand-Myanmar border in Tak Province, northwestern Thailand. Six hundred ninety-five children aged 1-14 years old were screened for BLLs. Environmental specimens for lead measurements included samples of water from the streams, taps, and household containers, house floor dust, and foods. Possible lead release from the cooking ware was determined using the leaching method with acetic acid. The overall prevalence of EBLLs was 47.1% and the geometric mean level of blood lead was 9.16 µg/dl. Personal risk factors significantly associated with EBLLs included being male, younger age, anemia, and low weight-for-age. Significant environmental risk factors were exposure to a lead-acid battery of solar energy system and use of a non-certified metal cooking pot. Some families whose children had high BLLs reported production of lead bullets from the used batteries at home. About one-third of the house dust samples taken near batteries contained lead content above the recommended value, compared with none of those taken from other areas and from the houses with no batteries. The metal pots were safe for cooking rice but might be unsafe for acidic food preparation. Both nutritional intervention and lead exposure prevention programs are essential to reduce EBLLs in this population.

  19. Family-based Association Analyses of Imputed Genotypes Reveal Genome-Wide Significant Association of Alzheimer’s disease with OSBPL6, PTPRG and PDCL3

    PubMed Central

    Herold, Christine; Hooli, Basavaraj V.; Mullin, Kristina; Liu, Tian; Roehr, Johannes T; Mattheisen, Manuel; Parrado, Antonio R.; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph E.

    2015-01-01

    The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1 and PSEN2 cause a subset of early-onset familial Alzheimer's disease (EOFAD). On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ε4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3,500 subjects from 1,070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value = 3.98·10−08), rs1347297 in the gene OSBPL6 (P-value = 4.53·10−08), and rs1513625 near PDCL3 (P-value = 4.28·10−08). In addition, rs72953347 in OSBPL6 (P-value = 6.36·10−07) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value: 4.76·10−07; rs62400067, P-value: 3.54·10−07). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance. PMID:26830138

  20. Phthalates and other additives in plastics: human exposure and associated health outcomes

    PubMed Central

    Meeker, John D.; Sathyanarayana, Sheela; Swan, Shanna H.

    2009-01-01

    Concern exists over whether additives in plastics to which most people are exposed, such as phthalates, bisphenol A or polybrominated diphenyl ethers, may cause harm to human health by altering endocrine function or through other biological mechanisms. Human data are limited compared with the large body of experimental evidence documenting reproductive or developmental toxicity in relation to these compounds. Here, we discuss the current state of human evidence, as well as future research trends and needs. Because exposure assessment is often a major weakness in epidemiological studies, and in utero exposures to reproductive or developmental toxicants are important, we also provide original data on maternal exposure to phthalates during and after pregnancy (n = 242). Phthalate metabolite concentrations in urine showed weak correlations between pre- and post-natal samples, though the strength of the relationship increased when duration between the two samples decreased. Phthalate metabolite levels also tended to be higher in post-natal samples. In conclusion, there is a great need for more human studies of adverse health effects associated with plastic additives. Recent advances in the measurement of exposure biomarkers hold much promise in improving the epidemiological data, but their utility must be understood to facilitate appropriate study design. PMID:19528058

  1. Performance on paced serial addition tasks indicates an associative network for calculation.

    PubMed

    Hiscock, M; Caroselli, J S; Kimball, L E; Panwar, N

    2001-06-01

    Although paced serial addition (PSA) tasks are considered to be tests of general information-processing capacity, recent work suggests that performance on such tasks is influenced by arithmetic-specific variables. We designed two visual PSA experiments to determine whether the performance of normal adults would support predictions derived from the cognitive psychology of calculation. Experiment 1 showed that mixing familiar (Arabic numeral) and less familiar (Roman numeral) stimulus formats reduced scores below the averaged scores for pure Arabic and Roman lists. The Roman-Arabic order of addends was more difficult than the Arabic-Roman order. Experiment 2, which involved only Arabic numerals as addends, showed that performance could be impaired by constraining the trial-to-trial variability of sums. The results of both experiments confirm the importance of arithmetic-specific variables in PSA and provide support for an associative network model of calculation. In addition, the findings implicate interference from extraneous addends and responses as the performance-limiting factor. PMID:11404809

  2. Submicroscopic and Asymptomatic Plasmodium Parasitaemia Associated with Significant Risk of Anaemia in Papua, Indonesia

    PubMed Central

    Handayuni, Irene; Trianty, Leily; Utami, Retno A. S.; Tirta, Yusrifar Kharisma; Kenangalem, Enny; Lampah, Daniel; Kusuma, Andreas; Wirjanata, Grennady; Kho, Steven; Simpson, Julie A.; Auburn, Sarah; Douglas, Nicholas M.; Noviyanti, Rintis; Anstey, Nicholas M.; Poespoprodjo, Jeanne R.; Marfurt, Jutta

    2016-01-01

    Submicroscopic Plasmodium infections are an important parasite reservoir, but their clinical relevance is poorly defined. A cross-sectional household survey was conducted in southern Papua, Indonesia, using cluster random sampling. Data were recorded using a standardized questionnaire. Blood samples were collected for haemoglobin measurement. Plasmodium parasitaemia was determined by blood film microscopy and PCR. Between April and July 2013, 800 households and 2,830 individuals were surveyed. Peripheral parasitaemia was detected in 37.7% (968/2,567) of individuals, 36.8% (357) of whom were identified by blood film examination. Overall the prevalence of P. falciparum parasitaemia was 15.4% (396/2567) and that of P. vivax 18.3% (471/2567). In parasitaemic individuals, submicroscopic infection was significantly more likely in adults (adjusted odds ratio (AOR): 3.82 [95%CI: 2.49–5.86], p<0.001) compared to children, females (AOR = 1.41 [1.07–1.86], p = 0.013), individuals not sleeping under a bednet (AOR = 1.4 [1.0–1.8], p = 0.035), and being afebrile (AOR = 3.2 [1.49–6.93], p = 0.003). The risk of anaemia (according to WHO guidelines) was 32.8% and significantly increased in those with asymptomatic parasitaemia (AOR 2.9 [95% 2.1–4.0], p = 0.007), and submicroscopic P. falciparum infections (AOR 2.5 [95% 1.7–3.6], p = 0.002). Asymptomatic and submicroscopic infections in this area co-endemic for P. falciparum and P. vivax constitute two thirds of detectable parasitaemia and are associated with a high risk of anaemia. Novel public health strategies are needed to detect and eliminate these parasite reservoirs, for the benefit both of the patient and the community. PMID:27788243

  3. Gut microbiota associated with HIV infection is significantly enriched in bacteria tolerant to oxygen

    PubMed Central

    Dubourg, Grégory; Lagier, Jean-Christophe; Hüe, Sophie; Surenaud, Mathieu; Bachar, Dipankar; Robert, Catherine; Michelle, Caroline; Ravaux, Isabelle; Mokhtari, Saadia; Million, Matthieu; Stein, Andreas; Brouqui, Philippe; Levy, Yves; Raoult, Didier

    2016-01-01

    Objectives Gut microbiota modifications occurring during HIV infection have recently been associated with inflammation and microbial translocation. However, discrepancies between studies justified a comprehensive analysis performed on a large sample size. Design and methods In a case–control study, next-generation sequencing of the 16S rRNA gene was applied to the faecal microbiota of 31 HIV-infected patients, of whom 18 were treated with antiretroviral treatment (ART), compared with 27 healthy controls. 21 sera samples from HIV-infected patients and 7 sera samples from control participants were used to test the presence of 25 markers of inflammation and/or immune activation. Results Diversity was significantly reduced in HIV individuals when compared with controls and was not restored in the ART group. The relative abundance of several members of Ruminococcaceae such as Faecalibacterium prausnitzii was critically less abundant in the HIV-infected group and inversely correlated with inflammation/immune activation markers. Members of Enterobacteriaceae and Enterococcaceae were found to be enriched and positively correlated with these markers. There were significantly more aerotolerant species enriched in HIV samples (42/52 species, 80.8%) when compared with the control group (14/87 species, 16.1%; χ2 test, p<10−5, conditional maximum-likelihood estimate (CMLE) OR=21.9). Conclusions Imbalance between aerobic and anaerobic flora observed in HIV faecal microbiota could be a consequence of the gut impairment classically observed in HIV infection via the production of oxygen. Overgrowth of proinflammatory aerobic species during HIV infection raises the question of antioxidant supplementation, such as vitamin C, E or N-acetylcysteine. PMID:27547442

  4. Arthroscopic Latarjet and Capsular Shift (ALCS) procedure: a new "freehand" technique for anterior shoulder instability associated with significant bone defects.

    PubMed

    Bhatia, Deepak N

    2015-03-01

    Anterior shoulder instability associated with significant bone loss has been described as "bony-instability," and this condition is usually treated with an anterior glenoid bone grafting procedure (Latarjet procedure). The Latarjet procedure involves transfer of the horizontal limb of the coracoid process along with the conjoint tendon to the anterior glenoid rim, and is traditionally performed as an open surgical procedure. Recently, an arthroscopic technique for the Latarjet procedure has been described; the technique necessitates the use of specialized instrumentation and involves excision of the entire anterior capsule to facilitate coracoid fixation. We describe a new "freehand" arthroscopic technique for the Latarjet procedure, and, in addition, a simultaneous capsular shift to further optimize mid and end range stability. This technique eliminates the use of additional instrumentation and can be done using routine arthroscopic instruments. Preliminary experience with this technique suggests that the arthroscopic Latarjet and capsular shift is a technically demanding procedure. Glenohumeral capsule can be preserved, and this should be attempted wherever possible to optimize stability. Additional specialized instrumentation would probably reduce surgical time; however, the procedure can be performed with routine instruments.

  5. Significant obesity-associated gene expression changes occur in the stomach but not intestines in obese mice.

    PubMed

    Chen, Jing; Chen, Lihong; Sanseau, Philippe; Freudenberg, Johannes M; Rajpal, Deepak K

    2016-05-01

    The gastrointestinal (GI) tract can have significant impact on the regulation of the whole-body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analysis in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, significant changes in the gene expression were observed in both obese mouse groups in the stomach (ob/ob: 959; HFD: 542). In addition, these changes were quantitatively much higher than in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes, and insulin resistance. In addition, the gene expression profiles strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity in murine models extensively used in research.

  6. A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia

    PubMed Central

    Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

    2014-01-01

    Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

  7. SULF 1 gene polymorphism, rs6990375 is in significant association with fetus failure in IVF technique

    PubMed Central

    Taghizadeh, Eskandar; Kalantar, Seyed Mehdi; Mahdian, Reza; Sheikhha, Mohammad Hasan; Farashahi-Yazd, Ehsan; Ghasemi, Saeed; Shahbazi, Zahra

    2015-01-01

    Background: Sulfatase 1 (SULF1) function is to remove the 6-O-sulphate group from heparan sulfate. This action changes the binding sites of extracellular growth factors. SULF1 expression has been reported to be changed in angiogenesis. We hypothesized that single nucleotide polymorphisms (SNPs) of SULF1 would impact clinicopathologic characteristics. Objective: Study of SULF1 gene polymorphism with fetus failure in in vitro fertilization (IVF) technique. Materials and Methods: We studied one common (minor allele frequency >0.05) regulatory SNP, rs6990375, with polymerase chain reaction and restriction fragment length polymorphism method, in 53 infertile women with fetus failure in IVF technique and 53 women with at least one healthy child as controls. Results: We found that rs6990375 is significantly associated with an early failure in IVF and frequency of G allele is high in women with fetus failure in IVF technique (p<0.001). Conclusion: These findings suggest that SULF1genetic variations may play a role in IVF technique fetus failure. Further studies with large sample sizes on SULF1 SNPs may be useful in support of this claim. PMID:26131010

  8. Significant associations among hemostatic parameters, adipokines, and components of the metabolic syndrome in Japanese preschool children.

    PubMed

    Horigome, Hitoshi; Katayama, Yasutomi; Yoshinaga, Masao; Kato, Yoshiaki; Takahashi, Hideto; Sumazaki, Ryo

    2012-01-01

    Development of cardiovascular diseases could originate in early childhood. However, reference values of hemostatic parameters and adipokines in preschool children remain to be explored. We measured blood levels of adipokines and parameters of the hemostatic/fibrinolytic systems in 167 healthy children aged 4 to 6 years at 9:00 to 10:30 am after a strictly enforced overnight fast. Participants with body mass index (BMI) values ≥90th percentile had significantly higher values of systolic blood pressure and heart rate, as well as blood levels of insulin, coagulation factor (F) VII, FX, protein S, leptin, and homeostasis model assessment of insulin resistance (HOMA-IR), and lower values of desacyl-ghrelin than children with BMI < 90th percentile. Circulating levels of fibrinogen and leptin increased with increased number of cardiovascular risk factors. Stepwise regression analysis identified many hematological variables to be associated with features of the metabolic syndrome. The results implicated the hemostatic/fibrinolytic system or adipokines in the insidious progression of cardiovascular diseases from an early age. PMID:21949035

  9. Prevalence of Malaria, Dengue, and Chikungunya Significantly Associated with Mosquito Breeding Sites

    PubMed Central

    Islam, Mohammad Nazrul; ZulKifle, Mohammad; Sherwani, Arish Mohammad Khan; Ghosh, Susanta Kumar; Tiwari, Satyanarayan

    2011-01-01

    Objectives: To observe the prevalence of malaria, dengue, and chikungunya and their association with mosquito breeding sites. Methods: The study was observational and analytical. A total of 162 houses and 670 subjects were observed during the study period. One hundred forty-two febrile patients were eligible for the study. After obtaining informed consent from all febrile patients, 140 blood samples were collected to diagnose malaria, dengue, and chikungunya. Larval samples were collected by the standard protocol that follows. Correlation of data was performed by Pearson correlation test. Results: Forty-seven blood samples were found positive: 33 for chikungunya, 3 for dengue, and 11 for malaria. Fifty-one out of 224 larval samples were found positive. Out of the 51 positive samples, 37 were positive for Aedes, 12 were positive for Anopheles, and two were positive for Culex larvae. Interpretation and Conclusion: Mosquito-borne fevers, especially malaria, dengue, and chikungunya, have shown a significant relationship with mosquito breeding sites. PMID:23610486

  10. Healthcare-associated Staphylococcus aureus bloodstream infection: length of stay, attributable mortality, and additional direct costs.

    PubMed

    Primo, Mariusa Gomes Borges; Guilarde, Adriana Oliveira; Martelli, Celina M Turchi; Batista, Lindon Johnson de Abreu; Turchi, Marília Dalva

    2012-01-01

    This study aimed to determine the excess length of stay, extra expenditures, and attributable mortality to healthcare-associated S. aureus bloodstream infection (BSI) at a teaching hospital in central Brazil. The study design was a matched (1:1) case-control. Cases were defined as patients >13 years old, with a healthcare-associated S. aureus BSI. Controls included patients without an S. aureus BSI, who were matched to cases by gender, age (± 7 years), morbidity, and underlying disease. Data were collected from medical records and from the Brazilian National Hospital Information System (Sistema de Informações Hospitalares do Sistema Único de Saúde - SIH/SUS). A Wilcoxon rank sum test was performed to compare length of stay and costs between cases and controls. Differences in mortality between cases and controls were compared using McNemar's tests. The Mantel-Haenzel stratified analysis was performed to compare invasive device utilization. Data analyses were conducted using Epi Info 6.0 and Statistical Package for Social Sciences (SPSS 13.0). 84 case-control pairs matched by gender, age, admission period, morbidity, and underlying disease were analyzed. The mean lengths of hospital stay were 48.3 and 16.2 days for cases and controls, respectively (p<0.01), yielding an excess hospital stay among cases of 32.1 days. The excess mortality among cases compared to controls that was attributable to S. aureus bloodstream infection was 45.2%. Cases had a higher risk of dying compared to controls (OR 7.3, 95% CI 3.1-21.1). Overall costs of hospitalization (SIH/SUS) reached US$ 123,065 for cases versus US$ 40,247 for controls (p<0.01). The cost of antimicrobial therapy was 6.7 fold higher for cases compared to controls. Healthcare-associated S. aureus BSI was associated with statistically significant increases in length of hospitalization, attributable mortality, and economic burden. Implementation of measures to minimize the risk of healthcare-associated bacterial

  11. Two Cases of Generalized Seizures and the Velocardiofacial Syndrome - A Clinically Significant Association?

    ERIC Educational Resources Information Center

    El Tahir, M. O.; Kerr, M.; Jones, R. G.

    2004-01-01

    Velocardiofacial syndrome (VCFS) is caused by a micro deletion of chromosome 22q11 and associated with multiple system abnormalities. There is an increasing recognition of associations with psychiatric disorders. Neurological and brain abnormalities have been reported but to date no association with generalized epilepsy has been reported in…

  12. Revealing Significant Relations between Chemical/Biological Features and Activity: Associative Classification Mining for Drug Discovery

    ERIC Educational Resources Information Center

    Yu, Pulan

    2012-01-01

    Classification, clustering and association mining are major tasks of data mining and have been widely used for knowledge discovery. Associative classification mining, the combination of both association rule mining and classification, has emerged as an indispensable way to support decision making and scientific research. In particular, it offers a…

  13. Additivity and associative effects of metabolizable energy and amino acid digestibility in barley and canola meal for White Pekin ducks.

    PubMed

    Hong, D; Ragland, D; Adeola, O

    2001-11-01

    An experiment was conducted using the TMEn bioassay method to investigate the additivity and associative effects of metabolizable energy and amino acid digestibility in barley and canola meal for White Pekin ducks. Additivity was tested by comparing the difference between observed values determined in a complete diet and predicted values from measurements determined with individual ingredients (barley and canola meal). Six ducks each were assigned to diets of barley, canola meal, the complete diet, and dextrose. Dextrose-fed ducks were used for estimation of endogenous losses for calculation of true amino acid digestibility. The observed AME, TME, AMEn, and TMEn values in the complete diet were 0.065, 0.083, 0.016, and 0.023 (kcal/g), respectively, numerically higher than predicted values. Differences between observed and predicted values were not significant (P > 0.05), indicating that the AME, AMEn, TME, and TMEn in barley and canola meal were all additive. In general, observed values for apparent amino acid digestibility (AAAD) and true amino acid digestibility (TAAD) in the complete diet were higher than those predicted from individual ingredients. Observed AAAD for lysine, histidine, tryptophan, alanine, and aspartate were higher (P < 0.05) than predicted values, indicating that digestibilities of these amino acids were not additive. The mean of AAAD in canola meal (77.29%) was higher (P < 0.05) than the observed values of barley (52.2%) and complete diet (64.55%). For TAAD values, differences between observed and predicted values were significant for lysine, histidine, and tryptophan (P < 0.05). The mean of TAAD in canola meal, barley, and complete diet were 85.88, 80.87, and 81.33%, respectively. The average difference between observed and predicted values for TAAD (1.18 %) was smaller than that of AAAD (5.41%). These results indicated that ME values for barley and canola meal were additive in the complete diet but that digestibilities of some amino acids

  14. Human disodium octaborate tetrahydrate exposure following carpet flea treatment is not associated with significant dermal absorption.

    PubMed

    Krieger, R I; Dinoff, T M; Peterson, J

    1996-01-01

    Disodium octaborate tetrahydrate is used for indoor flea control on carpets and furniture. Disodium octaborate tetrahydrate was applied to a 100% nylon carpet as a solution using a powered rug brush at a rate of approximately 200 micrograms/cm2 carpet. Two randomly chosen groups of volunteers (18 females, 4 males) wore either bathing suits which provided 75% or more skin exposure or whole-body, cotton dosimeters consisting of socks, union suits, and gloves. The volunteers performed a 20-minute set of Jazzercise routines. The availability of boron was demonstrated by covering portions of the carpet with a cotton dosimeter and rolling it with a weighted roller. Additionally, disodium octaborate tetrahydrate was transferred to the whole-body dosimeter. Volunteers also collected 24-hour urine specimens prior to and following the exercise period. The specimens were analyzed for total boron by inductively coupled plasma emission spectroscopy. No evidence of contact transfer and dermal absorption was obtained. The mean daily boron levels (mg/g creatinine) were 1.17, 1.33, and 1.31 for the group with exposed skin and 1.26, 1.12, and 1.26 for those who wore dosimeters which prevented contact. Daily urine boron levels were not significantly different when compared using a two sample t-test assuming equal variances (P > 0.05). Direct dermal contact with disodium octaborate tetrahydrate-treated carpet at a nominal rate of 200 micrograms/cm2 did not produce any adverse effects or change urinary boron clearance. PMID:8889949

  15. Scoliosis and vertebral anomalies: additional abnormal phenotypes associated with chromosome 16p11.2 rearrangement.

    PubMed

    Al-Kateb, Hussam; Khanna, Geetika; Filges, Isabel; Hauser, Natalie; Grange, Dorothy K; Shen, Joseph; Smyser, Christopher D; Kulkarni, Shashikant; Shinawi, Marwan

    2014-05-01

    The typical chromosome 16p11.2 rearrangements are estimated to occur at a frequency of approximately 0.6% of all samples tested clinically and have been identified as a major cause of autism spectrum disorders, developmental delay, behavioral abnormalities, and seizures. Careful examination of patients with these rearrangements revealed association with abnormal head size, obesity, dysmorphism, and congenital abnormalities. In this report, we extend this list of phenotypic abnormalities to include scoliosis and vertebral anomalies. We present detailed characterization of phenotypic and radiological data of 10 new patients, nine with the 16p11.2 deletion and one with the duplication within the coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555 kb. We discuss the phenotypical and radiological findings in our patients and review 5 previously reported patients with 16p11.2 rearrangement and similar skeletal abnormalities. Our data suggest that patients with the recurrent 16p11.2 rearrangement have increased incidence of scoliosis and vertebral anomalies. However, additional studies are required to confirm this observation and to establish the incidence of these anomalies. We discuss the potential implications of our findings on the diagnosis, surveillance and genetic counseling of patients with 16p11.2 rearrangement. PMID:24458548

  16. Tribological characteristics of bisphenol AF bis(diphenyl phosphate) as an antiwear additive in polyalkylene glycol and polyurea grease for significantly improved lubrication

    NASA Astrophysics Data System (ADS)

    Zhu, Lili; Wu, Xinhu; Zhao, Gaiqing; Wang, Xiaobo

    2016-02-01

    A new antiwear additive of Bisphenol AF bis(diphenyl phosphate) (BAFDP) was synthesized and characterized. The tribological behaviors of the additive for polyalkylene glycol (PAG) and polyurea grease (PG) application in steel/steel contacts were evaluated on an Optimol SRV-IV oscillating reciprocating friction and wear tester at elevated temperature. The results revealed that BAFDP could drastically reduce friction and wear of sliding pairs in both PAG and also in PG at 100 °C. The tribological properties of BAFDP are superior to the normally used zinc dialkyldithiophosphate-based additive package (ZDDP) in PAG and PG. Moreover, BAFDP as additive for PAG and PG displays relatively significant tribological properties in temperature-ramp tests by performing well at 50-300 °C, indicating the excellent high temperature friction reduction and anti-wear capacity of BAFDP. XPS results showed that boundary lubrication films composed of Fe(OH)O, Fe3O4, FePO4, FeF2, FeF3, compounds containing the Psbnd O bonds, nitrogen oxide, and so forth, were formed on the worn surface, which contributed to excellent friction reduction and antiwear performance.

  17. The potential therapeutic applications and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) in cancers

    PubMed Central

    2016-01-01

    The metastasis-associated in colon cancer-1 (MACC1) gene was identified in 2009. Expression of MACC1 was found to be significantly upregulated in primary and metastatic colon carcinomas compared to normal tissues or adenomas. The induction of MACC1 occurs at the crucial step of transition from a benign to a malignant phenotype. The aim of this review was to summarise current results of non-clinical and clinical studies on the role of MACC1 in the carcinogenesis and progression of cancer, as well its potential therapeutic and prognostic significance. The gene encoding the HGF receptor MET is a transcriptional target of MACC1. In addition to promoting the proliferation, invasion, and migration of colon cancer cells in cell culture and tumour growth and metastasis in mouse models, MACC1 also contributes to carcinogenesis and progression of colorectal cancer through the β-catenin signalling pathway and mesenchymal-epithelial transition. MACC1 knockdown with si/sh RNA was investigated in cell lines of different types of cancer. MACC1 is a promising therapeutic target for antitumour and antimetastatic intervention strategies for cancers. Here, it is presented as a potential independent prognostic indicator of reduced overall survival as well as of the occurrence of distant metastasis in patients with different types of cancer.

  18. The potential therapeutic applications and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) in cancers

    PubMed Central

    2016-01-01

    The metastasis-associated in colon cancer-1 (MACC1) gene was identified in 2009. Expression of MACC1 was found to be significantly upregulated in primary and metastatic colon carcinomas compared to normal tissues or adenomas. The induction of MACC1 occurs at the crucial step of transition from a benign to a malignant phenotype. The aim of this review was to summarise current results of non-clinical and clinical studies on the role of MACC1 in the carcinogenesis and progression of cancer, as well its potential therapeutic and prognostic significance. The gene encoding the HGF receptor MET is a transcriptional target of MACC1. In addition to promoting the proliferation, invasion, and migration of colon cancer cells in cell culture and tumour growth and metastasis in mouse models, MACC1 also contributes to carcinogenesis and progression of colorectal cancer through the β-catenin signalling pathway and mesenchymal-epithelial transition. MACC1 knockdown with si/sh RNA was investigated in cell lines of different types of cancer. MACC1 is a promising therapeutic target for antitumour and antimetastatic intervention strategies for cancers. Here, it is presented as a potential independent prognostic indicator of reduced overall survival as well as of the occurrence of distant metastasis in patients with different types of cancer. PMID:27688722

  19. The potential therapeutic applications and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) in cancers.

    PubMed

    Kopczyńska, Ewa Katarzyna

    2016-01-01

    The metastasis-associated in colon cancer-1 (MACC1) gene was identified in 2009. Expression of MACC1 was found to be significantly upregulated in primary and metastatic colon carcinomas compared to normal tissues or adenomas. The induction of MACC1 occurs at the crucial step of transition from a benign to a malignant phenotype. The aim of this review was to summarise current results of non-clinical and clinical studies on the role of MACC1 in the carcinogenesis and progression of cancer, as well its potential therapeutic and prognostic significance. The gene encoding the HGF receptor MET is a transcriptional target of MACC1. In addition to promoting the proliferation, invasion, and migration of colon cancer cells in cell culture and tumour growth and metastasis in mouse models, MACC1 also contributes to carcinogenesis and progression of colorectal cancer through the β-catenin signalling pathway and mesenchymal-epithelial transition. MACC1 knockdown with si/sh RNA was investigated in cell lines of different types of cancer. MACC1 is a promising therapeutic target for antitumour and antimetastatic intervention strategies for cancers. Here, it is presented as a potential independent prognostic indicator of reduced overall survival as well as of the occurrence of distant metastasis in patients with different types of cancer. PMID:27688722

  20. Significance of Additional Non-Mass Enhancement in Patients with Breast Cancer on Preoperative 3T Dynamic Contrast Enhanced MRI of the Breast

    PubMed Central

    Cho, Yun Hee; Cho, Kyu Ran; Park, Eun Kyung; Seo, Bo Kyoung; Woo, Ok Hee; Cho, Sung Bum; Bae, Jeoung Won

    2016-01-01

    Background In preoperative assessment of breast cancer, MRI has been shown to identify more additional breast lesions than are detectable using conventional imaging techniques. The characterization of additional lesions is more important than detection for optimal surgical treatment. Additional breast lesions can be included in focus, mass, and non-mass enhancement (NME) on MRI. According to the fifth edition of the breast imaging reporting and data system (BI-RADS®), which includes several changes in the NME descriptors, few studies to date have evaluated NME in preoperative assessment of breast cancer. Objectives We investigated the diagnostic accuracy of BI-RADS descriptors in predicting malignancy for additional NME lesions detected on preoperative 3T dynamic contrast enhanced MRI (DCE-MRI) in patients with newly diagnosed breast cancer. Patients and Methods Between January 2008 and December 2012, 88 patients were enrolled in our study, all with NME lesions other than the index cancer on preoperative 3T DCE-MRI and all with accompanying histopathologic examination. The MRI findings were analyzed according to the BI-RADS MRI lexicon. We evaluated the size, distribution, internal enhancement pattern, and location of NME lesions relative to the index cancer (i.e., same quadrant, different quadrant, or contralateral breast). Results On histopathologic analysis of the 88 NME lesions, 73 (83%) were malignant and 15 (17%) were benign. Lesion size did not differ significantly between malignant and benign lesions (P = 0.410). Malignancy was more frequent in linear (P = 0.005) and segmental (P = 0.011) distributions, and benignancy was more frequent in focal (P = 0.004) and regional (P < 0.001) NME lesions. The highest positive predictive value (PPV) for malignancy occurred in segmental (96.8%), linear (95.1%), clustered ring (100%), and clumped (92.0%) enhancement. Asymmetry demonstrated a high positive predictive value of 85.9%. The frequency of malignancy was higher

  1. When neutral turns significant: brain dynamics of rapidly formed associations between neutral stimuli and emotional contexts.

    PubMed

    Ventura-Bort, Carlos; Löw, Andreas; Wendt, Julia; Dolcos, Florin; Hamm, Alfons O; Weymar, Mathias

    2016-09-01

    The ability to associate neutral stimuli with motivationally relevant outcomes is an important survival strategy. In this study, we used event-related potentials (ERPs) to investigate brain dynamics of associative emotional learning when participants were confronted with multiple heterogeneous information. Participants viewed 144 different objects in the context of 144 different emotional and neutral background scenes. During each trial, neutral objects were shown in isolation and then paired with the background scene. All pairings were presented twice to compare ERPs in response to neutral objects before and after single association. After single pairing, neutral objects previously encoded in the context of emotional scenes evoked a larger P100 over occipital electrodes compared to objects that were previously paired with neutral scenes. Likewise, larger late positive potentials (LPPs) were observed over parieto-occipital electrodes (450-750 ms) for objects previously associated with emotional relative to neutral contexts. The LPP - but not P100 - enhancement was also related to subjective object/context binding. Taken together, our ERP data provide evidence for fast emotional associative learning, as reflected by heightened perceptual and sustained elaborative processing for neutral information previously encountered in emotional contexts. These findings could assist in understanding binding mechanisms in stress and anxiety, as well as in addiction and eating-related disorders. PMID:27337689

  2. Lack of significant association between spina bifida and the fragile X syndrome

    SciTech Connect

    Schiano, C.M.; Demb, H.B.; Brown, W.T.

    1995-12-04

    Folic acid is involved in two common disorders associated with developmental disabilities. Spina bifida is a malformation that may be associated with mental retardation, learning disabilities, and epilepsy. Its incidence can be reduced by the ingestion of folic acid before, and at the time of, conception. The fragile X syndrome is a genetic disorder which is the most common form of inherited mental retardation. This disorder can be diagnosed by the induction of fragile sites on the X chromosome which is cultured in a medium deficient in folic acid. In several studies, folic acid was reported to alleviate some of the developmental and behavioral manifestations associated in the fragile X syndrome, while in others, it has no effect. 9 refs.

  3. Genetic association studies in complex disease: disentangling additional predisposing loci from associated neutral loci using a constrained - permutation approach.

    PubMed

    Spijker, G T; Nolte, I M; Jansen, R C; Te Meerman, G J

    2005-01-01

    In the process of genetically mapping a complex disease, the question may arise whether a certain polymorphism is the only causal variant in a region. A number of methods can answer this question, but unfortunately these methods are optimal for bi-allelic loci only. We wanted to develop a method that is more suited for multi-allelic loci, such as microsatellite markers. We propose the Additional Disease Loci Test (ADLT): the alleles at an additional locus are permuted within the subsample of haplotypes that have identical alleles at the predisposing locus. The hypothesis being tested is, whether the predisposing locus is the sole factor predisposing to the trait that is in LD with the additional locus under study. We applied ADLT to simulated datasets and a published dataset on Type 1 Diabetes, genotyped for microsatellite markers in the HLA-region. The method showed the expected number of false-positive results in the absence of additional loci, but proved to be more powerful than existing methods in the presence of additional disease loci. ADLT was especially superior in datasets with less LD or with multiple predisposing alleles. We conclude that the ADLT can be useful in identifying additional disease loci.

  4. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

    ERIC Educational Resources Information Center

    Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

    2012-01-01

    Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

  5. Additional Radiative Cooling of the Mesopause Region due to Small-Scale Temperature Fluctuations Associated with Gravity Waves

    NASA Astrophysics Data System (ADS)

    Kutepov, A.; Feofilov, A.; Medvedev, A.; Pauldrach, A.; Hartogh, P.

    2008-05-01

    We address a previously unknown effect of the radiative cooling of the mesosphere and lower thermosphere (MLT) produced by small-scale irregular temperature fluctuations (ITFs) associated with gravity waves. These disturbances are not resolved by present GCMs, but they alter the radiative transfer and the heating/cooling rates significantly. We apply a statistical model of gravity waves superimposed on large-scale temperature profiles, and perform direct calculations of the radiative cooling/heating in the MLT in the IR bands of CO2, O3 and H2O molecules taking into account the breakdown of the local thermodynamic equilibrium (non-LTE). We found that in the periods of strong wave activity the subgrid ITFs can cause an additional cooling up to 3 K/day near the mesopause. The effect is produced mainly by the fundamental 15 μm band of the main CO2 isotope. We derived a simple expression for the correction to mean (resolved by GCMs) temperature profiles using the variance of the temperature perturbations to account for the additional cooling effect. The suggested parameterization can be applied in GCMs in conjunction with existing gravity wave drag parameterizations.

  6. A Study to Determine if Addition of Palatal Petechiae to Centor Criteria Adds More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children.

    PubMed

    Nibhanipudi, Kumara V

    2016-01-01

    Objective. A study to determine if addition of palatal petechiae to Centor criteria adds more value for clinical diagnosis of acute strep pharyngitis in children. Hypothesis. In children, Centor Criteria does not cover all the symptoms and signs of acute strep pharyngitis. We hypothesize that addition of palatal petechiae to Centor Criteria will increase the possibility of clinical diagnosis of group A streptococcal pharyngitis in children. Methods. One hundred patients with a complaint of sore throat were enrolled in the study. All the patients were examined clinically using the Centor Criteria. They were also examined for other signs and symptoms like petechial lesions over the palate, abdominal pain, and skin rash. All the patients were given rapid strep tests, and throat cultures were sent. No antibiotics were given until culture results were obtained. Results. The sample size was 100 patients. All 100 had fever, sore throat, and erythema of tonsils. Twenty of the 100 patients had tonsillar exudates, 85/100 had tender anterior cervical lymph nodes, and 86/100 had no cough. In total, 9 out of the 100 patients had positive throat cultures. We observed that petechiae over the palate, a very significant sign, is not included in the Centor Criteria. Palatal petechiae were present in 8 out of the 100 patients. Six out of these 8 with palatal petechiae had positive throat culture for strep (75%). Only 7 out of 20 with exudates had positive strep culture. Sixteen out of the 100 patients had rapid strep test positive. Those 84/100 who had negative rapid strep also had negative throat culture. Statistics. We used Fisher's exact test, comparing throat culture positive and negative versus presence of exudates and palatal hemorrhages with positive and negative throat cultures and the resultant P value <.0001. Conclusion. Our study concludes that addition of petechiae over the palate to Centor Criteria will increase the possibility of diagnosing acute group A streptococcal

  7. A Study to Determine if Addition of Palatal Petechiae to Centor Criteria Adds More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children

    PubMed Central

    Nibhanipudi, Kumara V.

    2016-01-01

    Objective. A study to determine if addition of palatal petechiae to Centor criteria adds more value for clinical diagnosis of acute strep pharyngitis in children. Hypothesis. In children, Centor Criteria does not cover all the symptoms and signs of acute strep pharyngitis. We hypothesize that addition of palatal petechiae to Centor Criteria will increase the possibility of clinical diagnosis of group A streptococcal pharyngitis in children. Methods. One hundred patients with a complaint of sore throat were enrolled in the study. All the patients were examined clinically using the Centor Criteria. They were also examined for other signs and symptoms like petechial lesions over the palate, abdominal pain, and skin rash. All the patients were given rapid strep tests, and throat cultures were sent. No antibiotics were given until culture results were obtained. Results. The sample size was 100 patients. All 100 had fever, sore throat, and erythema of tonsils. Twenty of the 100 patients had tonsillar exudates, 85/100 had tender anterior cervical lymph nodes, and 86/100 had no cough. In total, 9 out of the 100 patients had positive throat cultures. We observed that petechiae over the palate, a very significant sign, is not included in the Centor Criteria. Palatal petechiae were present in 8 out of the 100 patients. Six out of these 8 with palatal petechiae had positive throat culture for strep (75%). Only 7 out of 20 with exudates had positive strep culture. Sixteen out of the 100 patients had rapid strep test positive. Those 84/100 who had negative rapid strep also had negative throat culture. Statistics. We used Fisher’s exact test, comparing throat culture positive and negative versus presence of exudates and palatal hemorrhages with positive and negative throat cultures and the resultant P value <.0001. Conclusion. Our study concludes that addition of petechiae over the palate to Centor Criteria will increase the possibility of diagnosing acute group A streptococcal

  8. Association between significant decrease in barometric pressure and onset of labor.

    PubMed

    King, E A; Fleschler, R G; Cohen, S M

    1997-01-01

    To determine whether there is any correlation between sudden decrease in barometric pressure and onset of labor, a non-experimental, retrospective study at a 948-bed tertiary care hospital was done. Pregnant patients of 36 weeks gestation or more who presented with spontaneous onset of labor during the 48 hours surrounding the 12 occurrences of significant drop in barometric pressure in 1992 were included in the study. Significantly more occurrences of onset of labor were identified in the 24 hours after a drop in barometric pressure than were identified in the 24 hours prior to the drop in barometric pressure (P < 0.05). Therefore, the overall number of labor onsets increased in the 24 hours following a significant drop in barometric pressure.

  9. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

    PubMed

    Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen; Lin, Ching-Yuang; Wu, Ming-Ju

    2014-01-01

    Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

  10. Tectonic state: its significance and characterization in the assessment of seismic effects associated with reservoir impounding

    USGS Publications Warehouse

    Castle, R.O.; Clark, M.M.; Grantz, A.; Savage, J.C.

    1980-01-01

    Any analysis of seismicity associated with the filling of large reservoirs requires an evaluation of the natural tectonic state in order to determine whether impoundment is the basic source, a mechanically unrelated companion feature, or a triggering stimulus of the observed seismicity. Several arguments indicate that the associated seismicity is usually a triggered effect. Among the elements of tectonic state considered here (existing fractures, accumulated elastic strain, and deformational style), deformational style is especially critical in forecasting the occurrence of impoundment-induced seismicity. The observational evidence indicates that seismicity associated with impounding generally occurs in areas that combine steeply dipping faults, relatively high strain rates, and either extensional or horizontal-shear strain. Simple physical arguments suggest: (1) that increased fluid pressures resulting from increased reservoir head should enhance the likelihood of seismic activity, whatever the tectonic environment; (2) that stress changes resulting from surface loading may increase the likelihood of crustal failure in areas of normal and transcurrent faulting, whereas they generally inhibit failure in areas of thrust faulting. Comparisons with other earthquake-producing artificial and natural processes (underground explosions, fluid injection, underground mining, fluid extraction, volcanic emissions) indicate that reservoir loading may similarly modify the natural tectonic state. Subsurface loading resulting from fluid extraction may be a particularly close analogue of reservoir loading; "seismotectonic" events associated with fluid extraction have been recognized in both seismically active and otherwise aseismic regions. Because the historic record of seismicity and surface faulting commonly is short in comparison with recurrence intervals of earthquake and fault-slip events, tectonic state is most reliably appraised through combined studies of historic

  11. Recurrent Hypoglycaemia due to Insulin Autoimmune Disease (Hirata Disease) Associated with Monoclonal Gammopathy of Unknown Significance.

    PubMed

    Gite, Jayant; Shrivastav, Rohit; Bhasin, Nikhil; Mashru, Puneet; Itolikar, Manish; Nadkar, Milind Y

    2015-10-01

    Hirata disease is a rare disease characterised by recurrent episodes of hypoglycaemia due to anti-insulin antibody. In most of these cases causative agents were sulfhydryl containing compounds like Penicillamine, Glutathione, and Methimazole. The presentation of disease closely mimics insulinoma. We report 52 years female patient presenting with recurrent episodes of hypoglycaemia due to anti-insulin antibody. On evaluation, underlying cause of antibody was found to be monoclonal gammopathy of unknown significance (MGUS). PMID:27608696

  12. Identifying reproducible cancer-associated highly expressed genes with important functional significances using multiple datasets

    PubMed Central

    Huang, Haiyan; Li, Xiangyu; Guo, You; Zhang, Yuncong; Deng, Xusheng; Chen, Lufei; Zhang, Jiahui; Guo, Zheng; Ao, Lu

    2016-01-01

    Identifying differentially expressed (DE) genes between cancer and normal tissues is of basic importance for studying cancer mechanisms. However, current methods, such as the commonly used Significance Analysis of Microarrays (SAM), are biased to genes with low expression levels. Recently, we proposed an algorithm, named the pairwise difference (PD) algorithm, to identify highly expressed DE genes based on reproducibility evaluation of top-ranked expression differences between paired technical replicates of cells under two experimental conditions. In this study, we extended the application of the algorithm to the identification of DE genes between two types of tissue samples (biological replicates) based on several independent datasets or sub-datasets of a dataset, by constructing multiple paired average gene expression profiles for the two types of samples. Using multiple datasets for lung and esophageal cancers, we demonstrated that PD could identify many DE genes highly expressed in both cancer and normal tissues that tended to be missed by the commonly used SAM. These highly expressed DE genes, including many housekeeping genes, were significantly enriched in many conservative pathways, such as ribosome, proteasome, phagosome and TNF signaling pathways with important functional significances in oncogenesis. PMID:27796338

  13. Significance of the Sm-Nd isotopic systematics of the Akilia Association

    NASA Technical Reports Server (NTRS)

    Gruau, G.; Nutman, A.; Jahn, B. M.

    1986-01-01

    Samarium-Neodymium analyses were carried out on fourteen samples of basic to ultrabasic metavolcanics from several enclaves of the Amitsoq gneisses (T = to or approximately 3,700 Ma). Field observations suggest that all the analyzed rocks belong to the pre-Amitsoq Akilia Association. Consequently, a minimum age of 3,700 Ma is postulated for the emplacement of their protoliths. When all the data points are put together in a conventional isochron diagram, no clear isochron relationship can be discerned. However, the points seem to fall within a band broadly corresponding to an age of 3,600 Ma. The isotopic results are difficult to interpret satisfactorily. Two contrasting interpretations are offered and summarized: (1) data scatter as a result of open system behavior; and (2) data scatter due to a melange of data sets defining two distinct isochrons.

  14. Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance

    PubMed Central

    Rentoft, Matilda; Lindell, Kristoffer; Tran, Phong; Chabes, Anna Lena; Watt, Danielle L.; Marjavaara, Lisette; Nilsson, Anna Karin; Melin, Beatrice; Trygg, Johan; Johansson, Erik

    2016-01-01

    Even small variations in dNTP concentrations decrease DNA replication fidelity, and this observation prompted us to analyze genomic cancer data for mutations in enzymes involved in dNTP metabolism. We found that sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1), a deoxyribonucleoside triphosphate triphosphohydrolase that decreases dNTP pools, is frequently mutated in colon cancers, that these mutations negatively affect SAMHD1 activity, and that several SAMHD1 mutations are found in tumors with defective mismatch repair. We show that minor changes in dNTP pools in combination with inactivated mismatch repair dramatically increase mutation rates. Determination of dNTP pools in mouse embryos revealed that inactivation of one SAMHD1 allele is sufficient to elevate dNTP pools. These observations suggest that heterozygous cancer-associated SAMHD1 mutations increase mutation rates in cancer cells. PMID:27071091

  15. Reframing the association and significance of co-morbidities in heart failure.

    PubMed

    Triposkiadis, Filippos; Giamouzis, Gregory; Parissis, John; Starling, Randall C; Boudoulas, Harisios; Skoularigis, John; Butler, Javed; Filippatos, Gerasimos

    2016-07-01

    Several co-existing diseases and/or conditions (co-morbidities) are present in patients with heart failure (HF), with diverse clinical relevance. Multiple mechanisms may underlie the co-existence of HF and co-morbidities, including direct causation, associated risk factors, heterogeneity, and independence. The complex inter-relationship of co-morbidities and their impact on the cardiovascular system contribute to the features of HF, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). The purpose of this work is to provide an overview of the contribution of major cardiac and non-cardiac co-morbidities to HF development and outcomes, in the context of both HFpEF and HFrEF. Accordingly, epidemiological evidence linking co-morbidities to HF and the effect of prevalent and incident co-morbidities on HF outcome will be reviewed. PMID:27358242

  16. Significant Association of Multiple Human Cytomegalovirus Genomic Loci with Glioblastoma Multiforme Samples

    PubMed Central

    Ranganathan, Padhma; Clark, Paul A.; Kuo, John S.; Salamat, M. Shahriar

    2012-01-01

    Viruses are appreciated as etiological agents of certain human tumors, but the number of different cancer types induced or exacerbated by viral infections is unknown. Glioblastoma multiforme (GBM)/astrocytoma grade IV is a malignant and lethal brain cancer of unknown origin. Over the past decade, several studies have searched for the presence of a prominent herpesvirus, human cytomegalovirus (HCMV), in GBM samples. While some have detected HCMV DNA, RNA, and proteins in GBM tissues, others have not. Therefore, any purported association of HCMV with GBM remains controversial. In most of the previous studies, only one or a select few viral targets were analyzed. Thus, it remains unclear the extent to which the entire viral genome was present when detected. Here we report the results of a survey of GBM specimens for as many as 20 different regions of the HCMV genome. Our findings indicate that multiple HCMV loci are statistically more likely to be found in GBM samples than in other brain tumors or epileptic brain specimens and that the viral genome was more often detected in frozen samples than in paraffin-embedded archival tissue samples. Finally, our experimental results indicate that cellular genomes substantially outnumber viral genomes in HCMV-positive GBM specimens, likely indicating that only a minority of the cells found in such samples harbor viral DNA. These data argue for the association of HCMV with GBM, defining the virus as oncoaccessory. Furthermore, they imply that, were HCMV to enhance the growth or survival of a tumor (i.e., if it is oncomodulatory), it would likely do so through mechanisms distinct from classic tumor viruses that express transforming viral oncoproteins in the overwhelming majority of tumor cells. PMID:22090104

  17. Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population

    PubMed Central

    Li, Cong; Wang, Fan; Yang, Yanzong; Fu, Fenfen; Xu, Chengqi; Shi, Lisong; Li, Sisi; Xia, Yunlong; Wu, Gang; Cheng, Xiang; Liu, Hui; Wang, Chuchu; Wang, Pengyun; Hao, Jianjun; Ke, Yuhe; Zhao, Yuanyuan; Liu, Mugen; Zhang, Rongfeng; Gao, Lianjun; Yu, Bo; Zeng, Qiutang; Liao, Yuhua; Yang, Bo

    2016-01-01

    Atrial fibrillation (AF) is the most common cardiac rhythm disorder at the clinical setting and accounts for up to 15% of all strokes. Recent genome-wide association studies (GWAS) identified two single nucleotide polymorphisms (SNPs), rs2106261 and rs7193343 in ZFHX3 (zinc finger homeobox 3 gene) and rs13376333 in KCNN3 (encoding a potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3) that showed significant association with AF in multiple populations of European ancestry. Here, we studied a Chinese Han, GeneID cohort consisting of 650 AF patients and 1,447 non-AF controls to test whether the GWAS findings on ZFHX3/KCNN3 and AF can be expanded to a different ethnic population. No significant association was detected for rs7193343 in ZFHX3 and rs13376333 in KCNN3. However, significant association was identified between rs2106261 in ZFHX3 and AF in the GeneID population for both allelic frequencies (P = 0.001 after adjusting for covariates of age, gender, hypertension, coronary artery disease, and diabetes mellitus; OR = 1.32), and genotypic frequencies assuming either an additive or recessive model (OR = 1.29, P = 0.001 and OR = 1.77, P = 0.00018, respectively). When only lone AF cases were analyzed, the association remained significant (OR = 1.50, P = 0.001 for allelic association; OR = 1.45, P = 0.001 for an additive model; OR = 2.24, P = 0.000043 for a recessive model). Our results indicate that rs2106261 in ZFHX3 confers a significant risk of AF in a Chinese Han population. The study expands the association between ZFHX3 and AF to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of the 16q22 AF locus. PMID:21107608

  18. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed Central

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-01-01

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations.

  19. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-09-28

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations. PMID:27688652

  20. Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island.

    PubMed

    Santana-Casiano, J M; Fraile-Nuez, E; González-Dávila, M; Baker, E T; Resing, J A; Walker, S L

    2016-01-01

    The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 10(5) ± 1.1 10(5 )kg d(-1) which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%.

  1. Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island

    NASA Astrophysics Data System (ADS)

    Santana-Casiano, J. M.; Fraile-Nuez, E.; González-Dávila, M.; Baker, E. T.; Resing, J. A.; Walker, S. L.

    2016-05-01

    The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 105 ± 1.1 105 kg d‑1 which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%.

  2. Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island.

    PubMed

    Santana-Casiano, J M; Fraile-Nuez, E; González-Dávila, M; Baker, E T; Resing, J A; Walker, S L

    2016-01-01

    The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 10(5) ± 1.1 10(5 )kg d(-1) which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%. PMID:27157062

  3. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed Central

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-01-01

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations. PMID:27688652

  4. Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island

    PubMed Central

    Santana-Casiano, J. M.; Fraile-Nuez, E.; González-Dávila, M.; Baker, E. T.; Resing, J. A.; Walker, S. L.

    2016-01-01

    The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 105 ± 1.1 105 kg d−1 which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%. PMID:27157062

  5. CNV-based genome wide association study reveals additional variants contributing to meat quality in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pork quality is important both to the meat processing industry and consumers’ purchasing attitudes. Copy number variation (CNV) is a burgeoning kind of variant that may influence meat quality. Herein, a genome-wide association study (GWAS) was performed between CNVs and meat quality traits in swine....

  6. Associating cooking additives with sodium hydroxide to pretreat bamboo residues for improving the enzymatic saccharification and monosaccharides production.

    PubMed

    Huang, Caoxing; He, Juan; Wang, Yan; Min, Douyong; Yong, Qiang

    2015-10-01

    Cooking additive pulping technique is used in kraft mill to increase delignification degree and pulp yield. In this work, cooking additives were firstly applied in the sodium hydroxide pretreatment for improving the bioconversion of bamboo residues to monosaccharides. Meanwhile, steam explosion and sulfuric acid pretreatments were also carried out on the sample to compare their impacts on monosaccharides production. Results indicated that associating anthraquinone with sodium hydroxide pretreatment showed the best performance in improving the original carbohydrates recovery, delignification, enzymatic saccharification, and monosaccharides production. After consecutive pretreatment and enzymatic saccharification process, 347.49 g, 307.48 g, 142.93 g, and 87.15 g of monosaccharides were released from 1000 g dry bamboo residues pretreated by sodium hydroxide associating with anthraquinone, sodium hydroxide, steam explosion and sulfuric acid, respectively. The results suggested that associating cooking additive with sodium hydroxide is an effective pretreatment for bamboo residues to enhance enzymatic saccharification for monosaccharides production.

  7. Early detection of illness associated with poisonings of public health significance.

    PubMed

    Wolkin, Amy F; Patel, Manish; Watson, William; Belson, Martin; Rubin, Carol; Schier, Joshua; Kilbourne, Edwin M; Crawford, Carol Gotway; Wattigney, Wendy; Litovitz, Toby

    2006-02-01

    Since September 11, 2001, concern about potential terrorist attacks has increased in the United States. To reduce morbidity and mortality from outbreaks of illness from the intentional release of chemical agents, we examine data from the Toxic Exposure Surveillance System (TESS). TESS, a national system for timely collection of reports from US poison control centers, can facilitate early recognition of outbreaks of illness from chemical exposures. TESS data can serve as proxy markers for a diagnosis and may provide early alerts to potential outbreaks of covert events. We use 3 categories of information from TESS to detect potential outbreaks, including call volume, clinical effect, and substance-specific data. Analysis of the data identifies aberrations by comparing the observed number of events with a threshold based on historical data. Using TESS, we have identified several events of potential public health significance, including an arsenic poisoning at a local church gathering in Maine, the TOPOFF 2 national preparedness exercise, and contaminated food and water during the northeastern US blackout. Integration of poison control centers into the public health network will enhance the detection and response to emerging chemical threats. Traditionally, emergency physicians and other health care providers have used poison control centers for management information; their reporting to these centers is crucial in poisoning surveillance efforts.

  8. Ubiquity and quantitative significance of detoxification catabolism of chlorophyll associated with protistan herbivory.

    PubMed

    Kashiyama, Yuichiro; Yokoyama, Akiko; Kinoshita, Yusuke; Shoji, Sunao; Miyashiya, Hideaki; Shiratori, Takashi; Suga, Hisami; Ishikawa, Kanako; Ishikawa, Akira; Inouye, Isao; Ishida, Ken-ichiro; Fujinuma, Daiki; Aoki, Keisuke; Kobayashi, Masami; Nomoto, Shinya; Mizoguchi, Tadashi; Tamiaki, Hitoshi

    2012-10-23

    Chlorophylls are essential components of the photosynthetic apparati that sustain all of the life forms that ultimately depend on solar energy. However, a drawback of the extraordinary photosensitizing efficiency of certain chlorophyll species is their ability to generate harmful singlet oxygen. Recent studies have clarified the catabolic processes involved in the detoxification of chlorophylls in land plants, but little is understood about these strategies in aquatic ecosystem. Here, we report that a variety of heterotrophic protists accumulate the chlorophyll a catabolite 13(2),17(3)-cyclopheophorbide a enol (cPPB-aE) after their ingestion of algae. This chlorophyll derivative is nonfluorescent in solution, and its inability to generate singlet oxygen in vitro qualifies it as a detoxified catabolite of chlorophyll a. Using a modified analytical method, we show that cPPB-aE is ubiquitous in aquatic environments, and it is often the major chlorophyll a derivative. Our findings suggest that cPPB-aE metabolism is one of the most important, widely distributed processes in aquatic ecosystems. Therefore, the herbivorous protists that convert chlorophyll a to cPPB-aE are suggested to play more significant roles in the modern oceanic carbon flux than was previously recognized, critically linking microscopic primary producers to the macroscopic food web and carbon sequestration in the ocean.

  9. Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population - The Nagahama study.

    PubMed

    Terao, Chikashi; Asai, Keita; Hashimoto, Motomu; Yamazaki, Toru; Ohmura, Koichiro; Yamaguchi, Akihiko; Takahashi, Katsu; Takei, Noriko; Ishii, Takanori; Kawaguchi, Takahisa; Tabara, Yasuharu; Takahashi, Meiko; Nakayama, Takeo; Kosugi, Shinji; Sekine, Akihiro; Fujii, Takao; Yamada, Ryo; Mimori, Tsuneyo; Matsuda, Fumihiko; Bessho, Kazuhisa

    2015-05-01

    Anti-citrullinated peptide antibody (ACPA) is a highly specific autoantibody to rheumatoid arthritis (RA). Recent studies have revealed that periodontal disease (PD) is closely associated with RA and production of ACPA in RA. Analyses of associations between PD and ACPA production in a healthy population may deepen our understandings. Here, we analyzed a total of 9554 adult healthy subjects. ACPA and IgM-rheumatoid factor (RF) was quantified and PD status was evaluated using the number of missing teeth (MT), the Community Periodontal Index (CPI) and Loss of Attachment (LA) for these subjects. PD status was analyzed for its association with the positivity and categorical levels of ACPA and RF conditioned for covariates which were shown to be associated with PD, ACPA or RF. As a result, all of MT, CPI and LA showed suggestive or significant associations with positivity (p = 0.024, 0.0042 and 0.037, respectively) and levels of ACPA (p ≤ 0.00031), but none of the PD parameters were associated with those of RF. These association patterns were also observed when we analyzed 6206 non-smokers of the participants. The significant associations between PD parameters and positivity and levels of ACPA in healthy population support the fundamental involvement of PD with ACPA production.

  10. MTUS1 and its targeting miRNAs in colorectal carcinoma: significant associations.

    PubMed

    Ozcan, Onder; Kara, Murat; Yumrutas, Onder; Bozgeyik, Esra; Bozgeyik, Ibrahim; Celik, Ozgur Ilhan

    2016-05-01

    Deregulated microRNA (miRNA) expression has been shown to be involved in the pathogenesis of several types of cancers including colorectal cancer (CRC). Thus, determining miRNA targets of genes that play critical role in the malignant transformation is very important. Here, expression levels of tumor suppressor microtubule-associated tumor suppressor 1 (MTUS1) and its regulatory miRNAs were reported. Predicted and validated targets of MTUS1 gene was determined by a computational approach. Expressions of MTUS1 and miRNAs were determined by using 96.96 Dynamic Array™ integrated fluidic circuit (Fluidigm). As a result, MTUS1 levels were found to be diminished in formalin-fixed, paraffin-embedded (FFPE) tissue samples of CRC patients compared to controls. Also, several of MTUS1 targeting miRNAs were found to be upregulated in CRC samples (miR-373-3p, 183-5p, 142-5p, 200c-3p, 19a-3p, -20a-5p, -181a-5p, -184, -181d-5p, -372-3p, 27b-3p, 98-5p, -let-7i-5p, -let-7d-5p, -let-7g-5p, -let-7b-5p, and -let-7c-5p). Of these miRNAs, miR-135b-5p, -373-3p, 183-5p, 142-5p, 200c-3p, 19a-3p showed marked expression levels. In contrast, expression levels of let-7a-5p, 7e-5p, 7f-5p, hsa-miR-125a-5p, and 125b-5p were found to be downregulated in CRC tissues. Accordingly, some of the overexpressed miRNAs especially the miR-135b-5p, -373-3p, 183-5p, 142-5p, 200c-3p, and 19a-3p may play key roles in CRC pathophysiology through MTUS1. In contrast, let-7a-5p, 7e-5p, 7f-5p, miR-125a-5p, and 125b-5p may play important roles in CRC carcinogenesis independent from the MTUS1. In conclusion, MTUS1 targeting miRNAs may play key roles in the development of CRC by downregulating tumor suppressor MTUS1.

  11. Temporal and spatial paleoproductivity patterns associated with Eastern Mediterranean sapropels: paleoceanographic significance.

    NASA Astrophysics Data System (ADS)

    Gallego-Torres, D.; Martinez-Ruiz, F.; Meyers, P. A.; Paytan, A.; Jimenez-Espejo, F. J.; Ortega-Huertas, M.

    2007-12-01

    Deposition of Eastern Mediterranean sapropels has been discussed in terms of enhanced primary productivity and/or preferential preservation due to anoxic conditions in the deep basin. However, formation of these organic enriched layers is not homogeneous across the basin and through time, and temporal and spatial patterns can be observed in organic carbon concentrations and depositional conditions. We used a transect of ODP sites in the Eastern Mediterranean for the study of such variations, covering the area of major influence of the European continent and incoming waters from the Western Mediterranean basin (Ionian basin, Site 964), a region of influence of the Nile River (Levantine basin, Site 967), the central region of the basin with minor continental influence (Mediterranean Ridge, Site 969), and shallower bathymetries (Eratosthenes Seamount, Site 966). A set of paleoproductivity related proxies has been applied in order to reconstruct the paleoceanographic conditions that led to the formation of sapropels. As a whole, sapropel formation corresponds to wetter periods occurring during precessional minima and appears associated to increased productivity, evidenced by Ba/Al, and TOC-Ba mass accumulation rates maxima. δ13C data indicate intensified carbon fixation during organic carbon entrapment in sediment, where as low δ15N values provide evidence of nitrogen fixation through cyanobacteria activity as a source of increased primary and export productivity. This overwhelming export productivity led to the depletion of deep water dissolved oxygen, thus improving organic matter preservation. The above mentioned proxies show that sapropels represent periods of high productivity in an otherwise oligotrophic basin. This productivity was initiated and sustained by a change in bacterial community to nitrogen-fixing organism favored by intensified continental drainage and nutrient input. In agreement to this observation, sapropel onset generally occurred earlier in

  12. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance

    PubMed Central

    Kwok, Brian; Hall, Jeff M.; Witte, John S.; Xu, Yin; Reddy, Prashanti; Lin, Keming; Flamholz, Rachel; Dabbas, Bashar; Yung, Aine; Al-Hafidh, Jenan; Balmert, Emily; Vaupel, Christine; El Hader, Carlos; McGinniss, Matthew J.; Nahas, Shareef A.; Kines, Julie

    2015-01-01

    Establishing a diagnosis in patients suspected of having a myelodysplastic syndrome (MDS) can be challenging and could be informed by the identification of somatic mutations. We performed a prospective study to examine the frequency and types of mutations encountered in 144 patients with unexplained cytopenias. Based on bone marrow findings, 17% were diagnosed with MDS, 15% with idiopathic cytopenias of undetermined significance (ICUS) and some evidence of dysplasia, and 69% with ICUS and no dysplasia. Bone marrow DNA was sequenced for mutations in 22 frequently mutated myeloid malignancy genes. Somatic mutations were identified in 71% of MDS patients, 62% of patients with ICUS and some dysplasia, and 20% of ICUS patients and no dysplasia. In total, 35% of ICUS patients carried a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis. We validated these results in a cohort of 91 lower-risk MDS and 249 ICUS cases identified over a 6-month interval. Mutations were found in 79% of those with MDS, in 45% of those with ICUS with dysplasia, and in 17% of those with ICUS without dysplasia. The spectrum of mutated genes was similar with the exception of SF3B1 which was rarely mutated in patients without dysplasia. Variant allele fractions were comparable between clonal ICUS (CCUS) and MDS as were mean age and blood counts. We demonstrate that CCUS is a more frequent diagnosis than MDS in cytopenic patients. Clinical and mutational features are similar in these groups and may have diagnostic utility once outcomes in CCUS patients are better understood. PMID:26429975

  13. Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk

    PubMed Central

    Farr, Olivia M.; Ko, Byung-Joon; Joung, Kyoung Eun; Zaichenko, Lesya; Usher, Nicole; Tsoukas, Michael; Thakkar, Bindiya; Davis, Cynthia R.; Crowell, Judith A.; Mantzoros, Christos S.

    2015-01-01

    Background and Aims There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. Methods We analyzed data from a cross-sectional and a longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. Results PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, ICAM, and TNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. Conclusions Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk. PMID:25770759

  14. Unilateral renal agenesis associated with additional congenital abnormalities of the urinary tract in a Pekingese bitch.

    PubMed

    Agut, A; Fernandez del Palacio, M J; Laredo, F G; Murciano, J; Bayon, A; Soler, M

    2002-01-01

    An eight-month-old Pekingese bitch with urinary incontinence was found to have three congenital anomalies of the urinary tract: left renal agenesis, bilateral ectopic ureters with a left cranial blind-ending ureter, and urinary bladder hypoplasia. The diagnoses were made by retrograde vaginourethrography, excretory urography, ultrasonography and duplex Doppler ultrasonography. Although urological anomalies associated with renal agenesis have been frequently observed, a cranial blind-end ectopic ureter has not, to the authors' knowledge, been described in the bitch. The dog was managed medically with a restricted protein diet because of a compromised unilateral kidney with hydronephrosis and hydroureter.

  15. Properties of HIV-1 associated cholesterol in addition to raft formation are important for virus infection.

    PubMed

    Hawkes, David; Jones, Kate L; Smyth, Redmond P; Pereira, Cândida F; Bittman, Robert; Jaworowski, Anthony; Mak, Johnson

    2015-12-01

    The overall HIV-1 membrane lipid contents resemble lipid rafts, and we have previously demonstrated that raft-promoting properties of virus-associated cholesterol (with modifications in either the 3β-OH group or AB rings) are important for HIV-1 infectivity. As cholesterol is present in both rafts and non-rafts domains of HIV-1 membrane, we question whether the interpretation of rafts property of virus-associated cholesterol being an absolute requirement for HIV-1 function is too simplistic. The carbon side chain of cholesterol is the third component of cholesterol that can affect the fluidity of membrane depending on its context within the lipid membrane bilayers. In this work, we have used synthetic cholesterol analogues that have different lengths of carbon side chain for our investigation. In contrast to our previous report, we have found that cholesterol side chain analogues that lack in vitro defined raft promoting-property is able to support HIV-1 replication. More specifically, cholesterol analogues with side chains of intermediate length have greater capacity to support HIV-1 infection, suggesting HIV-1 is able to maintain function using cholesterol variants that promote a range of non-rafts- to rafts-properties. Our data demonstrate cholesterol properties other than raft-promoting function also contribute to the infectivity of HIV-1.

  16. Patient Outcomes in Association With Significant Other Responses to Chronic Fatigue Syndrome: A Systematic Review of the Literature

    PubMed Central

    Band, Rebecca; Wearden, Alison; Barrowclough, Christine

    2015-01-01

    Social processes have been suggested as important in the maintenance of chronic fatigue syndrome (also known as myalgic encephalomyelitis; CFS/ME), but the specific role of close interpersonal relationships remains unclear. We reviewed 14 articles investigating significant other responses to close others with CFS/ME and the relationships between these responses and patient outcomes. Significant other beliefs attributing patient responsibility for the onset and ongoing symptoms of CFS/ME were associated with increased patient distress. Increased symptom severity, disability, and distress were also associated with both solicitous and negative significant other responses. Specific aspects of dyadic relationship quality, including high Expressed Emotion, were identified as important. We propose extending current theoretical models of CFS/ME to include two potential perpetuating interpersonal processes; the evidence reviewed suggests that the development of significant other–focused interventions may also be beneficial. PMID:26617440

  17. Instructions for additional qualitative scoring of the initial-letter Word-association Test.

    PubMed

    Zivković, M

    1994-04-01

    An additional scoring method is based on grouping test-words according to whether the same sign is given by subjects to the test-words. In this way five test-word categories are formed, Eros (test-words with double plus signs), demi-Eros (single plus sign), demi-Thanatos (single minus), Thanatos (double minus), and Deviant (+/- and theta signs). The next step in scoring is to count the number of test-words in a given scoring category whose meanings do not conform. The greater the discrepancy between the test-word category and its meaning, the less well adapted is the subject. Several illustrative protocols are discussed. PMID:8022674

  18. RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hanss⃞

    PubMed Central

    Wu, Ying; Li, Huaixing; Loos, Ruth J. F.; Qi, Qibin; Hu, Frank B.; Liu, Yong; Lin, Xu

    2009-01-01

    We previously found that plasma RBP4 levels were strongly associated with metabolic syndrome components. This study aimed to determine whether RBP4 variants are associated with the metabolic syndrome components and plasma RBP4 levels, and to investigate whether the associations between plasma RBP4 and the metabolic syndrome components are causal. Five tagSNPs were tested for their associations with plasma RBP4 levels and metabolic syndrome components in a population-based sample of 3,210 Chinese Hans. A possible causal relationship between plasma RBP4 levels and hypertriglyceridemia was explored by Mendelian randomization. Plasma RBP4 levels were significantly associated with rs10882273 (βz −0.10SD[−0.17, −0.03], P = 0.0050), rs3758538 (βz −0.13SD[−0.24, −0.02], P = 0.0249) in all participants, and with rs17108993 in Shanghai participants (βz −0.19SD[−0.32, −0.05], P = 0.0061). The single nucleotide polymorphism (SNP) rs3758538 was significantly associated with hypertriglyceridemia (OR 0.62[0.45–0.85], P = 0.0026) and triglycerides (βz −0.19SD[−0.30, −0.07], P = 0.001) in all participants. In Mendelian randomization analysis, the observed effect size of association between rs3758538 and hypertriglyceridemia was different from the expected effect size (P = 0.0213). This is the first study to show that the RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans. However, results of Mendelian randomization do not support the hypothesis that RBP4 levels are causally related to hypertriglyceridemia risk. PMID:19287041

  19. Evaluation of the Potential Excess of Statistically Significant Findings in Published Genetic Association Studies: Application to Alzheimer's Disease

    PubMed Central

    Kavvoura, Fotini K.; McQueen, Matthew B.; Khoury, Muin J.; Tanzi, Rudolph E.; Bertram, Lars

    2008-01-01

    The authors evaluated whether there is an excess of statistically significant results in studies of genetic associations with Alzheimer's disease reflecting either between-study heterogeneity or bias. Among published articles on genetic associations entered into the comprehensive AlzGene database (www.alzgene.org) through January 31, 2007, 1,348 studies included in 175 meta-analyses with 3 or more studies each were analyzed. The number of observed studies (O) with statistically significant results (P = 0.05 threshold) was compared with the expected number (E) under different assumptions for the magnitude of the effect size. In the main analysis, the plausible effect size of each association was the summary effect presented in the respective meta-analysis. Overall, 19 meta-analyses (all with eventually nonsignificant summary effects) had a documented excess of O over E: Typically single studies had significant effects pointing in opposite directions and early summary effects were dissipated over time. Across the whole domain, O was 235 (17.4%), while E was 164.8 (12.2%) (P < 10−6). The excess showed a predilection for meta-analyses with nonsignificant summary effects and between-study heterogeneity. The excess was seen for all levels of statistical significance and also for studies with borderline P values (P = 0.05–0.10). The excess of significant findings may represent significance-chasing biases in a setting of massive testing. PMID:18779388

  20. Aripiprazole Improves Associated Comorbid Conditions in Addition to Tics in Adult Patients with Gilles de la Tourette Syndrome.

    PubMed

    Gerasch, Sarah; Kanaan, Ahmad Seif; Jakubovski, Ewgeni; Müller-Vahl, Kirsten R

    2016-01-01

    Gilles de la Tourette Syndrome (GTS) is characterized by motor and vocal tics, as well as associated comorbid conditions including obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), depression, and anxiety which are present in a substantial number of patients. Although randomized controlled trials including a large number of patients are still missing, aripiprazole is currently considered as a first choice drug for the treatment of tics. The aim of this study was to further investigate efficacy and safety of aripiprazole in a group of drug-free, adult patients. Specifically, we investigated the influence of aripiprazole on tic severity, comorbidities, premonitory urge (PU), and quality of life (QoL). Moreover, we were interested in the factors that influence a patient's decision in electing for-or against- pharmacological treatment. In this prospective uncontrolled open-label study, we included 44 patients and used a number of rating scales to assess tic severity, PU, comorbidities, and QoL at baseline and during treatment with aripiprazole. Eighteen out of fortyfour patients decided for undergoing treatment for their tics with aripiprazole and completed follow-up assessments after 4-6 weeks. Our major findings were (1) aripiprazole resulted in significant reduction of tics, but did not affect PU; (2) aripiprazole significantly improved OCD and showed a trend toward improvement of other comorbidities including depression, anxiety, and ADHD; (3) neither severity of tics, nor PU or QoL influenced patients' decisions for or against treatment of tics with aripiprazole; instead patients with comorbid OCD tended to decide in favor of, while patients with comorbid ADHD tended to decide against tic treatment; (4) most frequently reported adverse effects were sleeping problems; (5) patients' QoL was mostly impaired by comorbid depression. Our results suggest that aripiprazole may improve associated comorbid conditions in addition to tics

  1. Aripiprazole Improves Associated Comorbid Conditions in Addition to Tics in Adult Patients with Gilles de la Tourette Syndrome

    PubMed Central

    Gerasch, Sarah; Kanaan, Ahmad Seif; Jakubovski, Ewgeni; Müller-Vahl, Kirsten R.

    2016-01-01

    Gilles de la Tourette Syndrome (GTS) is characterized by motor and vocal tics, as well as associated comorbid conditions including obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), depression, and anxiety which are present in a substantial number of patients. Although randomized controlled trials including a large number of patients are still missing, aripiprazole is currently considered as a first choice drug for the treatment of tics. The aim of this study was to further investigate efficacy and safety of aripiprazole in a group of drug-free, adult patients. Specifically, we investigated the influence of aripiprazole on tic severity, comorbidities, premonitory urge (PU), and quality of life (QoL). Moreover, we were interested in the factors that influence a patient's decision in electing for-or against- pharmacological treatment. In this prospective uncontrolled open-label study, we included 44 patients and used a number of rating scales to assess tic severity, PU, comorbidities, and QoL at baseline and during treatment with aripiprazole. Eighteen out of fortyfour patients decided for undergoing treatment for their tics with aripiprazole and completed follow-up assessments after 4–6 weeks. Our major findings were (1) aripiprazole resulted in significant reduction of tics, but did not affect PU; (2) aripiprazole significantly improved OCD and showed a trend toward improvement of other comorbidities including depression, anxiety, and ADHD; (3) neither severity of tics, nor PU or QoL influenced patients' decisions for or against treatment of tics with aripiprazole; instead patients with comorbid OCD tended to decide in favor of, while patients with comorbid ADHD tended to decide against tic treatment; (4) most frequently reported adverse effects were sleeping problems; (5) patients' QoL was mostly impaired by comorbid depression. Our results suggest that aripiprazole may improve associated comorbid conditions in addition to tics

  2. Aripiprazole Improves Associated Comorbid Conditions in Addition to Tics in Adult Patients with Gilles de la Tourette Syndrome.

    PubMed

    Gerasch, Sarah; Kanaan, Ahmad Seif; Jakubovski, Ewgeni; Müller-Vahl, Kirsten R

    2016-01-01

    Gilles de la Tourette Syndrome (GTS) is characterized by motor and vocal tics, as well as associated comorbid conditions including obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), depression, and anxiety which are present in a substantial number of patients. Although randomized controlled trials including a large number of patients are still missing, aripiprazole is currently considered as a first choice drug for the treatment of tics. The aim of this study was to further investigate efficacy and safety of aripiprazole in a group of drug-free, adult patients. Specifically, we investigated the influence of aripiprazole on tic severity, comorbidities, premonitory urge (PU), and quality of life (QoL). Moreover, we were interested in the factors that influence a patient's decision in electing for-or against- pharmacological treatment. In this prospective uncontrolled open-label study, we included 44 patients and used a number of rating scales to assess tic severity, PU, comorbidities, and QoL at baseline and during treatment with aripiprazole. Eighteen out of fortyfour patients decided for undergoing treatment for their tics with aripiprazole and completed follow-up assessments after 4-6 weeks. Our major findings were (1) aripiprazole resulted in significant reduction of tics, but did not affect PU; (2) aripiprazole significantly improved OCD and showed a trend toward improvement of other comorbidities including depression, anxiety, and ADHD; (3) neither severity of tics, nor PU or QoL influenced patients' decisions for or against treatment of tics with aripiprazole; instead patients with comorbid OCD tended to decide in favor of, while patients with comorbid ADHD tended to decide against tic treatment; (4) most frequently reported adverse effects were sleeping problems; (5) patients' QoL was mostly impaired by comorbid depression. Our results suggest that aripiprazole may improve associated comorbid conditions in addition to tics

  3. Aripiprazole Improves Associated Comorbid Conditions in Addition to Tics in Adult Patients with Gilles de la Tourette Syndrome

    PubMed Central

    Gerasch, Sarah; Kanaan, Ahmad Seif; Jakubovski, Ewgeni; Müller-Vahl, Kirsten R.

    2016-01-01

    Gilles de la Tourette Syndrome (GTS) is characterized by motor and vocal tics, as well as associated comorbid conditions including obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), depression, and anxiety which are present in a substantial number of patients. Although randomized controlled trials including a large number of patients are still missing, aripiprazole is currently considered as a first choice drug for the treatment of tics. The aim of this study was to further investigate efficacy and safety of aripiprazole in a group of drug-free, adult patients. Specifically, we investigated the influence of aripiprazole on tic severity, comorbidities, premonitory urge (PU), and quality of life (QoL). Moreover, we were interested in the factors that influence a patient's decision in electing for-or against- pharmacological treatment. In this prospective uncontrolled open-label study, we included 44 patients and used a number of rating scales to assess tic severity, PU, comorbidities, and QoL at baseline and during treatment with aripiprazole. Eighteen out of fortyfour patients decided for undergoing treatment for their tics with aripiprazole and completed follow-up assessments after 4–6 weeks. Our major findings were (1) aripiprazole resulted in significant reduction of tics, but did not affect PU; (2) aripiprazole significantly improved OCD and showed a trend toward improvement of other comorbidities including depression, anxiety, and ADHD; (3) neither severity of tics, nor PU or QoL influenced patients' decisions for or against treatment of tics with aripiprazole; instead patients with comorbid OCD tended to decide in favor of, while patients with comorbid ADHD tended to decide against tic treatment; (4) most frequently reported adverse effects were sleeping problems; (5) patients' QoL was mostly impaired by comorbid depression. Our results suggest that aripiprazole may improve associated comorbid conditions in addition to tics

  4. Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

    PubMed

    Cantani, A

    2006-01-01

    The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by quality-control failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen expressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians.

  5. Additional research on instabilities in atmospheric flow systems associated with clear air turbulence

    NASA Technical Reports Server (NTRS)

    Stoeffler, R. C.

    1972-01-01

    Analytical and experimental fluid mechanics studies were conducted to investigate instabilities in atmospheric flow systems associated with clear air turbulence. The experimental portion of the program was conducted using an open water channel which allows investigation of flows having wide ranges of shear and density stratification. The program was primarily directed toward studies of the stability of straight, stratified shear flows with particular emphasis on the effects of velocity profile on stability; on studies of three-dimensional effects on the breakdown region in shear layers; on the the interaction of shear flows with long-wave length internal waves; and on the stability of shear flows consisting of adjacent stable layers. The results of these studies were used to evaluate methods used in analyses of CAT encounters in the atmosphere involving wave-induced shear layer instabilities of the Kelvin-Helmholta type. A computer program was developed for predicting shear-layer instability and CAT induced by mountain waves. This technique predicts specific altitudes and locations where CAT would be expected.

  6. Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

    PubMed

    Cantani, A

    2009-01-01

    The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by qualitycontrol failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen ex-pressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians.

  7. Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

    PubMed

    Cantani, A

    2006-01-01

    The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by quality-control failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen expressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians. PMID:16910351

  8. Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

    PubMed

    Cantani, A

    2009-01-01

    The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by qualitycontrol failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen ex-pressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians. PMID:19364084

  9. Associations and prognostic significance of p27Kip1, Jab1 and Skp2 in non-Hodgkin lymphoma

    PubMed Central

    Ma, Yan; Yan, Meijuan; Huang, Hua; Zhang, Li; Wang, Qian; Zhao, Yaqi; Zhao, Jianmei

    2016-01-01

    Non-Hodgkin lymphoma (NHL) is a primary tumor arising in lymph nodes and lymphoid tissue. The incidence of NHL is increasing at an annual rate of 3%. The human Jun activation domain-binding protein 1/COP9 signalosome subunit 5 (Jab1/CSN5) is a negative regulator of the cell cycle inhibitor p27Kip1 and abnormal expression of Jab1 is correlated with reduced p27 expression and associated with advanced tumor stage and poor prognosis in several human cancers. F-box protein S-phase kinase-interacting protein-2 (Skp2), the substrate recognition subunit of the Skp1-Cul1-F-box protein ubiquitin protein ligase complex, is required for the ubiquitination and consequent degradation of p27. The Skp2 protein is overexpressed in several human cancers and is associated with the degree of differentiation and the prognosis. The aim of the present study was to investigate the expression status of p27Kip1, Jab1 and Skp2 by immunohistochemistry, and assess their prognostic significance in patients with NHL. Immunohistochemical analysis revealed an inverse association between Jab1 and p27 in NHL tissue samples. Kaplan-Meier analysis demonstrated that Jab1 overexpression, Skp2 overexpression and low p27 expression were significantly associated with poor prognosis. Among clinicopathological parameters, overexpression of Jab1 was significantly associated with tumor size and International Prognostic Index (IPI), whereas Skp2 expression was significantly associated with metastasis and IPI. These findings suggest that the overexpression of Jab1 or Skp2 plays an important role in the pathogenesis of NHL. Thus, the expression of p27Kip1, Jab1 and Skp2 provided a clinical reference for the treatment of NHL.

  10. Haplotypes of the D-Amino Acid Oxidase Gene Are Significantly Associated with Schizophrenia and Its Neurocognitive Deficits

    PubMed Central

    Hwu, Hai-Gwo; Fann, Cathy Shen-Jang; Yang, Ueng-Cheng; Yang, Wei-Chih; Hsu, Pei-Chun; Chang, Chien-Ching; Wen, Chun-Chiang; Tsai-Wu, Jyy-Jih; Hwang, Tzung-Jeng; Hsieh, Ming H.; Liu, Chen-Chung; Chien, Yi-Ling; Fang, Chiu-Ping; Faraone, Stephen V.; Tsuang, Ming T.; Chen, Wei J.; Liu, Chih-Min

    2016-01-01

    D-amino acid oxidase (DAO) has been reported to be associated with schizophrenia. This study aimed to search for genetic variants associated with this gene. The genomic regions of all exons, highly conserved regions of introns, and promoters of this gene were sequenced. Potentially meaningful single-nucleotide polymorphisms (SNPs) obtained from direct sequencing were selected for genotyping in 600 controls and 912 patients with schizophrenia and in a replicated sample consisting of 388 patients with schizophrenia. Genetic associations were examined using single-locus and haplotype association analyses. In single-locus analyses, the frequency of the C allele of a novel SNP rs55944529 located at intron 8 was found to be significantly higher in the original large patient sample (p = 0.016). This allele was associated with a higher level of DAO mRNA expression in the Epstein-Barr virus-transformed lymphocytes. The haplotype distribution of a haplotype block composed of rs11114083-rs2070586-rs2070587-rs55944529 across intron 1 and intron 8 was significantly different between the patients and controls and the haplotype frequencies of AAGC were significantly higher in patients, in both the original (corrected p < 0.0001) and replicated samples (corrected p = 0.0003). The CGTC haplotype was specifically associated with the subgroup with deficits in sustained attention and executive function and the AAGC haplotype was associated with the subgroup without such deficits. The DAO gene was a susceptibility gene for schizophrenia and the genomic region between intron 1 and intron 8 may harbor functional genetic variants, which may influence the mRNA expression of DAO and neurocognitive functions in schizophrenia. PMID:26986737

  11. Improvement rate of acute otitis media caused by Haemophilus influenzae at 1 week is significantly associated with time to recovery.

    PubMed

    Yano, Hisakazu; Yamazaki, Yoshitaka; Qin, Liang; Okitsu, Naohiro; Yahara, Koji; Irimada, Mihoko; Hirakata, Yoichi; Kaku, Mitsuo; Kobayashi, Toshimitsu; Watanabe, Hiroshi

    2013-11-01

    Acute otitis media (AOM) is the most common upper respiratory tract infection in childhood. Children with AOM were enrolled at Tohoku Rosai Hospital between July 2006 and June 2011 if their middle ear fluid cultures after tympanocentesis yielded only Haemophilus influenzae. The susceptibilities of the isolates to ampicillin were determined, and microtiter biofilm assays and invasion assays using BEAS-2B cells were performed. The association between these bacterial characteristics and clinical relapses of AOM and treatment failures was evaluated. Seventy-four children (39 boys and 35 girls) with a median age of 1 year (interquartile range [IQR], 0.25 to 2 years) were enrolled. Among 74 H. influenzae isolates, 37 showed intermediate resistance or resistance to ampicillin (MIC, ≥ 2 μg/ml). In the microtiter biofilm assay, the median optical density at 600 nm (OD600) was 0.68 (IQR, 0.24 to 1.02), and 70 isolates formed biofilms. The median invasion rate was 15% (IQR, 0 to 10%), and 46 isolates invaded BEAS-2B cells. Relapses and treatment failures occurred in 19 and 6 children, respectively. There was no significant difference in the invasion rates between patients with and those without relapses or treatment failures. Also, there was no significant association between biofilm formation and relapse or treatment failure. The improvements in the severity scores after 1 week were significantly associated with the recovery time (P < 0.0001). We did not identify any significant association between relapse or treatment failure and bacterial factors. AOM has a multifactorial etiology, and this may explain why we could not find a significant association. An improvement in the severity score after 1 week of treatment may be a useful predictor of the outcome of AOM.

  12. Endothelial nitric oxide synthase gene haplotypes and circulating nitric oxide levels significantly associate with risk of essential hypertension.

    PubMed

    Nejatizadeh, Azim; Kumar, Rahul; Stobdan, Tsering; Goyal, A K; Sikdar, Sunandan; Gupta, Mohit; Javed, Saleem; Pasha, M A Qadar

    2008-06-01

    Nitric oxide (NO), a potent vasodilator, plays a pivotal role in blood pressure regulation. Endothelial NO synthase gene (NOS3) polymorphisms influence NO levels. Here, we investigated the role of the -922A/G, -786T/C, 4b/4a, and 894G/T polymorphisms of the NOS3 and NO(x) levels in 800 consecutive unrelated subjects comprising 455 patients of essential hypertension and 345 controls. The polymorphisms were investigated independently and as haplotypes. Plasma NO(x) levels (nitrate and nitrite) were estimated by the Griess method. Genotype frequencies for the -786T/C, 4b/4a, and 894G/T polymorphisms differed significantly (P<0.001) between patients and controls and were associated with an increased risk of hypertension (OR=2.0, OR=3.8, OR=1.6, respectively). The 4-locus haplotypes ATaG (H1), ATaT (H2), and GCaG (H3) were significantly associated with essential hypertension and served as susceptible haplotypes (Passociated with hypertension and served as protective haplotypes (P<0.0001). NO(x) levels were significantly lower in patients than controls (P<0.0001). The individual polymorphisms showed marginal association with NO(x) level; however, the susceptible haplotype H2 associated significantly with lower NO(x) levels in patients (P<0.001) and conversely the haplotype H4 with higher NO(x) levels in controls (P<0.001). In conclusion, the 4b/4a and likely -786T/C polymorphisms were identified as the determinants modifying the risk of hypertension. This study identifies the NOS3 variants and haplotypes as genetic risk factors and as useful markers of increased susceptibility to the risk of essential hypertension. PMID:18325347

  13. Many QTLs with minor additive effects are associated with a large difference in growth between two selection lines in chickens.

    PubMed

    Jacobsson, Lina; Park, Hee-Bok; Wahlberg, Per; Fredriksson, Robert; Perez-Enciso, Miguel; Siegel, Paul B; Andersson, Leif

    2005-10-01

    Two growth-selected lines in chickens have been developed from a single founder population by divergent selection for body weight at 56 days of age. After more than 40 generations of selection they show a nine-fold difference in body weight at selection age and large differences in growth rate, appetite, fat deposition and metabolic characteristics. We have generated a large intercross between these lines comprising more than 800 F2 birds. QTL mapping revealed 13 loci affecting growth. The most striking observation was that the allele in the high weight line in all cases was associated with enhanced growth, but each locus explained only a small proportion of the phenotypic variance using a standard QTL model (1.3-3.1%). This result is in sharp contrast to our previous study where we reported that the two-fold difference in adult body size between the red junglefowl and White Leghorn domestic chickens is explained by a small number of QTLs with large additive effects. Furthermore, no QTLs for anorexia or antibody response were detected despite large differences for these traits between the founder lines. The result is an excellent example where a large phenotypic difference between populations occurs in the apparent absence of any single locus with large phenotypic effects. The study underscores the need for powerful experimental designs in genetic studies of multifactorial traits. No QTL at all would have reached genome-wide significance using a less powerful design (e.g. approx. 200 F2 individuals) regardless of the nine-fold phenotypic difference between the founder lines for the selected trait. PMID:16356285

  14. Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men.

    PubMed

    Sato, Y; Shinka, T; Nozawa, S; Yoshiike, M; Koh, E; Kanaya, J; Namiki, M; Matsumiya, K; Tsujimura, A; Komatsu, K; Itoh, N; Eguchi, J; Yamauchi, A; Iwamoto, T; Nakahori, Y

    2015-05-01

    The association between the Y chromosome haplogroup D2 and risk of azoospermia and low sperm motility has been previously studied, and it was indicated that haplogroups DE (YAP lineage) are associated with prostate cancer risk in Japanese males. Our assumption had been that Y chromosome haplogroups may be associated with sex hormone levels, because sex hormones have been deemed responsible for spermatogenesis and carcinogenesis. In this study, we assessed the association between Y chromosome haplogroups and sex hormone levels, including those of testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin-B, and calculated free testosterone (cFT), in 901 young men from the general Japanese population (cohort 1) and 786 Japanese men of proven fertility (cohort 2). We found that the haplogroup D2a1 was significantly associated with high LH levels in a combined analysis involving two cohorts (β = 0.068, SE = 0.025, p = 0.0075), following correction for multiple testing. To date, this result is the first evidence that implicates Y chromosome haplogroups in an association with sex hormone levels.

  15. Polymorphisms in the TLR4 and TLR5 gene are significantly associated with inflammatory bowel disease in German shepherd dogs.

    PubMed

    Kathrani, Aarti; House, Arthur; Catchpole, Brian; Murphy, Angela; German, Alex; Werling, Dirk; Allenspach, Karin

    2010-12-23

    Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease.

  16. Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population

    PubMed Central

    Chen, Shanshan; Wang, Chuchu; Wang, Xiaojing; Xu, Chengqi; Wu, Manman; Wang, Pengxia; Tu, Xin; Wang, Qing K

    2015-01-01

    Background Recent genome-wide association studies (GWAS) in European ancestry populations revealed several genomic loci for atrial fibrillation (AF). We previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial results were reported in 2 Chinese replication studies. Methods and Results Six remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1, rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were analyzed in a Chinese Han population with 941 cases and 562 controls. Only rs3807989 showed significant association with AF (Padj=4.77×10−5), and the finding was replicated in 2 other independent populations with 709 cases and 2175 controls, 463 cases and 644 controls, and the combined population with a total of 2113 cases and 3381 controls (Padj=2.20×10−9; odds ratio [OR]=1.34 for major allele G). Meta-analysis, together with data from previous reports in Chinese and Japanese populations, also showed a significant association between rs3807989 and AF (P=3.40×10−4; OR=1.24 for allele G). We also found that rs3807989 showed a significant association with lone AF in 3 independent populations and in the combined population (Padj=3.85×10−8; OR=1.43 for major allele G). Conclusions The data in this study revealed a significant association between rs3807989 and AF in the Chinese Han population. Together with the findings that caveolin-1 interacts with potassium channels Kir2.1, KCNH2, and HCN4 and sodium channels Nav1.5 and Nav1.8, CAV1 becomes a strong candidate susceptibility gene for AF across different ethnic populations. This study is the first to show a significant association between rs3807989 and lone AF. PMID:25953654

  17. Significant association between rare IPO11-HTR1A variants and attention deficit hyperactivity disorder in Caucasians.

    PubMed

    Zuo, Lingjun; Saba, Laura; Lin, Xiandong; Tan, Yunlong; Wang, Kesheng; Krystal, John H; Tabakoff, Boris; Luo, Xingguang

    2015-10-01

    We comprehensively examined the rare variants in the IPO11-HTR1A region to explore their roles in neuropsychiatric disorders. Five hundred seventy-three to 1,181 rare SNPs in subjects of European descent and 1,234-2,529 SNPs in subjects of African descent (0 < minor allele frequency (MAF) < 0.05) were analyzed in a total of 49,268 subjects in 21 independent cohorts with 11 different neuropsychiatric disorders. Associations between rare variant constellations and diseases and associations between individual rare variants and diseases were tested. RNA expression changes of this region were also explored. We identified a rare variant constellation across the entire IPO11-HTR1A region that was associated with attention deficit hyperactivity disorder (ADHD) in Caucasians (T5: P = 7.9 × 10(-31) ; Fp: P = 1.3 × 10(-32) ), but not with any other disorder examined; association signals mainly came from IPO11 (T5: P = 3.6 × 10(-10) ; Fp: P = 3.2 × 1 0(-10) ) and the intergenic region between IPO11 and HTR1A (T5: P = 4.1 × 10(-30) ; Fp: P = 5.4 × 10(-32) ). One association between ADHD and an intergenic rare variant, i.e., rs10042956, exhibited region- and cohort-wide significance (P = 5.2 × 10(-6) ) and survived correction for false discovery rate (q = 0.006). Cis-eQTL analysis showed that, 29 among the 41 SNPs within or around IPO11 had replicable significant regulatory effects on IPO11 exon expression (1.5 × 10(-17) ≤P < 0.002) in human brain or peripheral blood mononuclear cell tissues. We concluded that IPO11-HTR1A was a significant risk gene region for ADHD in Caucasians.

  18. The CLU gene rs11136000 variant is significantly associated with Alzheimer's disease in Caucasian and Asian populations.

    PubMed

    Liu, Guiyou; Wang, Haiyang; Liu, Jiafeng; Li, Jingbo; Li, Hali; Ma, Guoda; Jiang, Yongshuai; Chen, Zugen; Zhao, Bin; Li, Keshen

    2014-03-01

    Large-scale genomewide association studies have reported that the CLU rs11136000 polymorphism is significantly associated with Alzheimer's disease (AD) in people of Caucasian ancestry. Recently, this association was investigated in Asian populations (Chinese, Japanese, and Korean). However, these studies reported either a weak association or no association between the rs11136000 polymorphism and AD. We believe that this discrepancy may be caused by the relatively small sample size of the previous studies and the genetic heterogeneity of the rs11136000 polymorphism in AD among different populations. For this study, we searched the PubMed and AlzGene databases. We selected 18 independent studies (6 studies of Asian populations and 12 of populations of Caucasian ancestry) that evaluated the association between the rs11136000 polymorphism and AD using a case-control experimental design. We evaluated the genetic heterogeneity of the rs11136000 polymorphism in Caucasian and Asian populations. We then investigated the rs11136000 polymorphism by a meta-analysis in Asian populations using allele, dominant, and recessive models. We identified a significant association between rs11136000 and AD with the allele model (P = 2.00 × 10(-4)) and the dominant model (P = 5.00 × 10(-3)). Meanwhile, a similar genetic risk of the rs11136000 polymorphism in AD was observed in Asian and Caucasian populations. Further meta-analysis in pooled Asian and Caucasian populations indicated a more significant association with the allele (P = 8.30 × 10(-24)), dominant (P = 4.46 × 10(-17)), and recessive (P = 3.92 × 10(-12)) models. Collectively, our findings from this meta-analysis indicate that the effect of the CLU rs11136000 polymorphism on AD risk in Asian cohorts (Chinese, Japanese, and Korean) is consistent with the protective effect observed in Caucasian AD cohorts.

  19. Frequencies of polymorphisms associated with BSE resistance differ significantly between Bos taurus, Bos indicus, and composite cattle

    PubMed Central

    Brunelle, Brian W; Greenlee, Justin J; Seabury, Christopher M; Brown, Charles E; Nicholson, Eric M

    2008-01-01

    Background Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to classical bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus × B. taurus composite cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to classical BSE in B. indicus purebred and composite cattle. Results No novel or TSE-associated PRNP-encoded amino acid polymorphisms were observed for B. indicus purebred and composite cattle, and all had the typical number of octapeptide repeats. However, differences were observed in the frequencies of the 23-bp and 12-bp insertion/deletion (indel) polymorphisms associated with two bovine PRNP transcription regulatory sites. Compared to B. taurus, B. indicus purebred and composite cattle had a significantly lower frequency of 23-bp insertion alleles and homozygous genotypes. Conversely, B. indicus purebred cattle had a significantly higher frequency of 12-bp insertion alleles and homozygous genotypes in relation to both B. taurus and composite cattle. The origin of these disparities can be attributed to a significantly different haplotype structure within each species. Conclusion The frequencies of the 23-bp and 12-bp indels were significantly different between B. indicus and B. taurus cattle. No other known or potential risk factors were detected for the B. indicus purebred and composite cattle. To date, no consensus exists regarding which bovine PRNP indel region is more influential with respect to classical BSE. Should one particular indel region and

  20. Polymyxin Resistance Caused by mgrB Inactivation Is Not Associated with Significant Biological Cost in Klebsiella pneumoniae

    PubMed Central

    Cannatelli, Antonio; Santos-Lopez, Alfonso; Giani, Tommaso; Gonzalez-Zorn, Bruno

    2015-01-01

    The inactivation of the mgrB gene, which encodes a negative-feedback regulator of the PhoPQ signaling system, was recently shown to be a common mutational mechanism responsible for acquired polymyxin resistance among carbapenemase-producing Klebsiella pneumoniae strains from clinical sources. In this work, we show that mgrB mutants can easily be selected in vitro from different K. pneumoniae lineages, and mgrB inactivation is not associated with a significant biological cost. PMID:25691629

  1. Phase stabilization of magnetite (Fe3O4) nanoparticles with B2O3 addition: A significant enhancement on the phase transition temperature

    NASA Astrophysics Data System (ADS)

    Topal, Uğur; Aksan, Mehmet Ali

    2016-05-01

    Magnetite nanoparticles (MNPs) are extensively investigated for biomedical applications, particularly as contrast agents for Magnetic Resonance Imaging and as drug delivery agent and heat mediators for cancer therapy. Tuning the magnetic properties of the magnetite nanoparticles with doping of foreign atoms has a crucial importance for determining the application areas of these materials and so attracts much interests. On the other hand the doping with foreign atoms requires high temperature annealing, and it causes a phase transition to the hematite phase above 400 °C. In this work the phase transition temperature from the magnetite to the hematite phase has been increased by 200 °C, which is the highest enhancement reported in literature. It was achieved by addition of the appropriate amounts of B2O3. Our experiments indicates that the 5.0 wt% of B2O3 addition stabilizes and keeps the existence of single phase magnetite up to 600 °C.

  2. Immunohistologic detection of estrogen receptor alpha in canine mammary tumors: clinical and pathologic associations and prognostic significance.

    PubMed

    Nieto, A; Peña, L; Pérez-Alenza, M D; Sánchez, M A; Flores, J M; Castaño, M

    2000-05-01

    Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-alpha) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3-4 months. ER-alpha expression was higher in tumors of genitally intact and young bitches (P < 0.01, P < 0.01) and in animals with regular estrous periods (P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-alpha (P = 0.04). Immunoexpression of ER-alpha decreased significantly with tumor size (P = 0.05) and skin ulceration (P = 0.01). Low levels of ER-alpha were significantly associated with lymph node involvement (P < 0.01). Malignant tumors had lower ER-alpha expression than did benign tumors (P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-alpha scores (P = 0.05) in all tumors. Low ER-alpha levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up (P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-alpha value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-alpha index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-alpha in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy.

  3. Significant Promotion Effect of Mo Additive on a Novel Ce-Zr Mixed Oxide Catalyst for the Selective Catalytic Reduction of NO(x) with NH3.

    PubMed

    Ding, Shipeng; Liu, Fudong; Shi, Xiaoyan; Liu, Kuo; Lian, Zhihua; Xie, Lijuan; He, Hong

    2015-05-13

    A novel Mo-promoted Ce-Zr mixed oxide catalyst prepared by a homogeneous precipitation method was used for the selective catalytic reduction (SCR) of NO(x) with NH3. The optimal catalyst showed high NH3-SCR activity, SO2/H2O durability, and thermal stability under test conditions. The addition of Mo inhibited growth of the CeO2 particle size, improved the redox ability, and increased the amount of surface acidity, especially the Lewis acidity, all of which were favorable for the excellent NH3-SCR performance. It is believed that the catalyst is promising for the removal of NO(x) from diesel engine exhaust.

  4. Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis

    PubMed Central

    Alba, P; Bento, L; Cuadrado, M; Karim, Y; Tungekar, M; Abbs, I; Khamashta, M; D'Cruz, D; Hughes, G

    2003-01-01

    Background: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial. Objective: To study the immunological and demographic factors associated with the development of LN. Patients and methods: A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing. Results: Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes. Conclusions: Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN. PMID:12759294

  5. Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression.

    PubMed

    Lintas, C; Sacco, R; Garbett, K; Mirnics, K; Militerni, R; Bravaccio, C; Curatolo, P; Manzi, B; Schneider, C; Melmed, R; Elia, M; Pascucci, T; Puglisi-Allegra, S; Reichelt, K-L; Persico, A M

    2009-07-01

    Protein kinase C enzymes play an important role in signal transduction, regulation of gene expression and control of cell division and differentiation. The fsI and betaII isoenzymes result from the alternative splicing of the PKCbeta gene (PRKCB1), previously found to be associated with autism. We performed a family-based association study in 229 simplex and 5 multiplex families, and a postmortem study of PRKCB1 gene expression in temporocortical gray matter (BA41/42) of 11 autistic patients and controls. PRKCB1 gene haplotypes are significantly associated with autism (P<0.05) and have the autistic endophenotype of enhanced oligopeptiduria (P<0.05). Temporocortical PRKCB1 gene expression was reduced on average by 35 and 31% for the PRKCB1-1 and PRKCB1-2 isoforms (P<0.01 and <0.05, respectively) according to qPCR. Protein amounts measured for the PKCbetaII isoform were similarly decreased by 35% (P=0.05). Decreased gene expression characterized patients carrying the 'normal' PRKCB1 alleles, whereas patients homozygous for the autism-associated alleles displayed mRNA levels comparable to those of controls. Whole genome expression analysis unveiled a partial disruption in the coordinated expression of PKCbeta-driven genes, including several cytokines. These results confirm the association between autism and PRKCB1 gene variants, point toward PKCbeta roles in altered epithelial permeability, demonstrate a significant downregulation of brain PRKCB1 gene expression in autism and suggest that it could represent a compensatory adjustment aimed at limiting an ongoing dysreactive immune process. Altogether, these data underscore potential PKCbeta roles in autism pathogenesis and spur interest in the identification and functional characterization of PRKCB1 gene variants conferring autism vulnerability.

  6. Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Nie, Chao; Liu, Xiaomin; Feng, Lei; Zhang, Fengyu; Lu, Jiehua; Li, Jianxin; Li, Yang; Tao, Wei; Gregory, Simon G; Gottschalk, William; Lutz, Michael W; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Ming, Qi; Yang, Huanming; Min, Junxia; Willcox, D Craig; Willcox, Bradley J; Gu, Jun; Hauser, Elizabeth; Tian, Xiao-Li; Vaupel, James W

    2016-06-01

    On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs.

  7. Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Nie, Chao; Liu, Xiaomin; Feng, Lei; Zhang, Fengyu; Lu, Jiehua; Li, Jianxin; Li, Yang; Tao, Wei; Gregory, Simon G; Gottschalk, William; Lutz, Michael W; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Ming, Qi; Yang, Huanming; Min, Junxia; Willcox, D Craig; Willcox, Bradley J; Gu, Jun; Hauser, Elizabeth; Tian, Xiao-Li; Vaupel, James W

    2016-06-01

    On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs. PMID:26414954

  8. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease.

    PubMed

    Lerner, Aaron; Matthias, Torsten

    2015-06-01

    The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression.

  9. Higher Physical Activity Is Associated With Lower Aortic Stiffness but Not With Central Blood Pressure: The ADDITION-Pro Study

    PubMed Central

    Laursen, Anne Sofie Dam; Hansen, Anne-Louise Smidt; Wiinberg, Niels; Brage, Søren; Sandbæk, Annelli; Lauritzen, Torsten; Witte, Daniel R.; Jørgensen, Marit Eika; Johansen, Nanna Borup

    2015-01-01

    Abstract Physical activity is associated with reduced cardiovascular disease risk. However, improvements in conventional risk factors due to physical activity do not explain its full benefit. Therefore, we examined associations of objectively measured physical activity energy expenditure and intensity with central hemodynamics to provide new insight into the link between physical activity and cardiovascular disease. We analyzed data from 1816 Danes (median age: 66 years) without cardiovascular disease. Physical activity was estimated using combined accelerometry and heart rate monitoring. Aortic stiffness was assessed by applanation tonometry, as aortic pulse wave velocity, and central blood pressure was estimated from radial waveforms. Associations between physical activity energy expenditure and central hemodynamics were examined by linear regression. Furthermore, the consequence of substituting 1 hour sedentary behavior with 1 hour light or moderate-to-vigorous physical activity on central hemodynamics was examined. Median physical activity energy expenditure was 28.0 kJ/kg/d (IQR: 19.8; 38.7). A 10 kJ/kg/d higher energy expenditure was associated with 0.75% lower aortic pulse wave velocity (CI: −1.47; −0.03). Associations with central systolic blood pressure and central pulse pressure were not statistically significant. We observed no difference in central hemodynamics when substituting 1 hour sedentary behavior with 1 hour light or moderate-to-vigorous physical activity. In this relatively inactive population, higher physical activity energy expenditure was associated with lower aortic stiffness, while there was no statistically significant association between substitution of activity intensity and central hemodynamics. This suggests that lower aortic stiffness is one of a number of health benefits attributed to higher habitual physical activity. PMID:25654392

  10. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

    PubMed Central

    Anderson, Carl A.; Boucher, Gabrielle; Lees, Charlie W.; Franke, Andre; D’Amato, Mauro; Taylor, Kent D.; Lee, James C.; Goyette, Philippe; Imielinski, Marcin; Latiano, Anna; Lagacé, Caroline; Scott, Regan; Amininejad, Leila; Bumpstead, Suzannah; Baidoo, Leonard; Baldassano, Robert N.; Barclay, Murray; Bayless, Theodore M.; Brand, Stephan; Büning, Carsten; Colombel, Jean-Frédéric; Denson, Lee A.; De Vos, Martine; Dubinsky, Marla; Edwards, Cathryn; Ellinghaus, David; Fehrmann, Rudolf S.N.; Floyd, James A.B.; Florin, Tim; Franchimont, Denis; Franke, Lude; Georges, Michel; Glas, Jürgen; Glazer, Nicole L.; Guthery, Stephen L.; Haritunians, Talin; Hayward, Nicholas K.; Hugot, Jean-Pierre; Jobin, Gilles; Laukens, Debby; Lawrance, Ian; Lémann, Marc; Levine, Arie; Libioulle, Cecile; Louis, Edouard; McGovern, Dermot P.; Milla, Monica; Montgomery, Grant W.; Morley, Katherine I.; Mowat, Craig; Ng, Aylwin; Newman, William; Ophoff, Roel A; Papi, Laura; Palmieri, Orazio; Peyrin-Biroulet, Laurent; Panés, Julián; Phillips, Anne; Prescott, Natalie J.; Proctor, Deborah D.; Roberts, Rebecca; Russell, Richard; Rutgeerts, Paul; Sanderson, Jeremy; Sans, Miquel; Schumm, Philip; Seibold, Frank; Sharma, Yashoda; Simms, Lisa; Seielstad, Mark; Steinhart, A. Hillary; Targan, Stephan R.; van den Berg, Leonard H.; Vatn, Morten; Verspaget, Hein; Walters, Thomas; Wijmenga, Cisca; Wilson, David C.; Westra, Harm-Jan; Xavier, Ramnik J.; Zhao, Zhen Z.; Ponsioen, Cyriel Y.; Andersen, Vibeke; Torkvist, Leif; Gazouli, Maria; Anagnou, Nicholas P.; Karlsen, Tom H.; Kupcinskas, Limas; Sventoraityte, Jurgita; Mansfield, John C.; Kugathasan, Subra; Silverberg, Mark S.; Halfvarson, Jonas; Rotter, Jerome I.; Mathew, Christopher G.; Griffiths, Anne M.; Gearry, Richard; Ahmad, Tariq; Brant, Steven R.; Chamaillard, Mathias; Satsangi, Jack; Cho, Judy H.; Schreiber, Stefan; Daly, Mark J.; Barrett, Jeffrey C.; Parkes, Miles; Annese, Vito; Hakonarson, Hakon; Radford-Smith, Graham; Duerr, Richard H.; Vermeire, Séverine; Weersma, Rinse K.; Rioux, John D.

    2011-01-01

    Genome-wide association studies (GWAS) and candidate gene studies in ulcerative colitis (UC) have identified 18 susceptibility loci. We conducted a meta-analysis of 6 UC GWAS, comprising 6,687 cases and 19,718 controls, and followed-up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P<5×10-8), increasing the number of UC associated loci to 47. After annotating associated regions using GRAIL, eQTL data and correlations with non-synonymous SNPs, we identified many candidate genes providing potentially important insights into disease pathogenesis, including IL1R2, IL8RA/B, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease (IBD) risk loci is now 99, including a minimum of 28 shared association signals between Crohn’s disease (CD) and UC. PMID:21297633

  11. Systemic neutralization of IL-17A significantly reduces breast cancer associated metastasis in arthritic mice by reducing CXCL12/SDF-1 expression in the metastatic niches

    PubMed Central

    2014-01-01

    Background IL-17A is a pro-inflammatory cytokine that is normally associated with autoimmune arthritis and other pro-inflammatory conditions. Recently, IL-17A has emerged as a critical factor in enhancing breast cancer (BC)-associated metastases. We generated immune competent arthritic mouse models that develop spontaneous BC-associated bone and lung metastasis. Using these models, we have previously shown that neutralization of IL-17A resulted in significant reduction in metastasis. However, the underlying mechanism/s remains unknown. Methods We have utilized two previously published mouse models for this study: 1) the pro-arthritic mouse model (designated SKG) injected with metastatic BC cell line (4T1) in the mammary fat pad, and 2) the PyV MT mice that develop spontaneous mammary gland tumors injected with type II collagen to induce autoimmune arthritis. Mice were treated with anti-IL-17A neutralizing antibody and monitored for metastasis and assessed for pro-inflammatory cytokines and chemokines associated with BC-associated metastasis. Results We first corroborate our previous finding that in vivo neutralization of IL-17A significantly reduced metastasis to the bones and lungs in both models. Next, we report that treatment with anti-IL17A antibody significantly reduced the expression of a key chemokine, CXCL12 (also known as stromal derived factor-1 (SDF - 1)) in the bones and lungs of treated mice. CXCL12 is a ligand for CXCR4 (expressed on BC cells) and their interaction is known to be critical for metastasis. Interestingly, levels of CXCR4 in the tumor remained unchanged with treatment. Consequently, protein lysates derived from the bones and lungs of treated mice were significantly less chemotactic for the BC cells than lysates from untreated mice; and addition of exogenous SDF-1 to the lysates from treated mice completely restored BC cell migration. In addition, cytokines such as IL-6 and M-CSF were significantly reduced in the lung and bone lysates

  12. CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma.

    PubMed

    Wagner, Steffen; Wittekindt, Claus; Reuschenbach, Miriam; Hennig, Ben; Thevarajah, Mauran; Würdemann, Nora; Prigge, Elena-Sophie; von Knebel Doeberitz, Magnus; Dreyer, Thomas; Gattenlöhner, Stefan; Klussmann, Jens Peter

    2016-05-01

    Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by bead-based hybridization (Luminex technology). HPV prevalence was 24.3% as determined by positive staining of p16INK4a and detection of high risk HPV-DNA. We found significantly higher numbers of CD56 positive (CD56+) cells in tumor and surrounding microenvironment in HPV-associated compared to HPV-negative OSCC (t-test: p = 0.004 and p = 0.002). For the entire cohort presence of CD56+ cells was associated with increased overall survival independent from HPV (Kaplan-Meier: p = 0.002; Cox regression: p = 0.042). Presence of CD56+ cells also correlated with a better outcome in HPV-negative and especially in HPV-negative OSCC with alcohol consumption ≤ 2 standard drinks per day (Kaplan-Meier: p = 0.05 and p = 0.003). Immunofluorescence localization of granular Granzyme B (GZMB) within CD56+ cells and coexpression of CD16 and CD56 suggests that detected CD56+ cells mainly represent cytotoxic Natural Killer (NK) cells. The fraction of potentially cytotoxic NK cells was significantly higher in HPV-associated compared to HPV-negative OSCC (Mann-Whitney-U-Test: p = 0.011). The elevated abundance and activity of cytotoxic NK cells in OSCC with HPV driven carcinogenesis might contribute to favorable outcome in HPV-related OSCC.

  13. The prion protein gene polymorphisms associated with bovine spongiform encephalopathy susceptibility differ significantly between cattle and buffalo.

    PubMed

    Zhao, Hui; Du, Yanli; Chen, Shunmei; Qing, Lili; Wang, Xiaoyan; Huang, Jingfei; Wu, Dongdong; Zhang, Yaping

    2015-12-01

    Prion protein, encoded by the prion protein gene (PRNP), plays a crucial role in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Several polymorphisms within the PRNP are known to be associated with influencing bovine spongiform encephalopathy (BSE) susceptibility in cattle, namely two insertion/deletion (indel) polymorphisms (a 23-bp indel in the putative promoter and a 12-bp indel in intron 1), the number of octapeptide repeats (octarepeats) present in coding sequence (CDS) and amino acid polymorphisms. The domestic buffaloes, Bubalus bubalis, are a ruminant involved in various aspects of agriculture. It is of interest to ask whether the PRNP polymorphisms differ between cattle and buffalo. In this study, we analyzed the previously reported polymorphisms associated with BSE susceptibility in Chinese buffalo breeds, and compared these polymorphisms in cattle with BSE, healthy cattle and buffalo by pooling data from the literature. Our analysis revealed three significant findings in buffalo: 1) extraordinarily low deletion allele frequencies of the 23- and 12-bp indel polymorphisms; 2) significantly low allelic frequencies of six octarepeats in CDS and 3) the presence of S4R, A16V, P54S, G108S, V123M, S154N and F257L substitutions in buffalo CDSs. Sequence alignments comparing the buffalo coding sequence to other species were analyzed using the McDonald-Kreitman test to reveal five groups (Bison bonasus, Bos indicus, Bos gaurus, Boselaphus tragocamelus, Syncerus caffer caffer) with significantly divergent non-synonymous substitutions from buffalo, suggesting potential divergence of buffalo PRNP and others. To the best of our knowledge this is the first study of PRNP polymorphisms associated with BSE susceptibility in Chinese buffalo. Our findings have provided evidence that buffaloes have a unique genetic background in the PRNP gene in comparison with cattle. PMID:26319996

  14. The prion protein gene polymorphisms associated with bovine spongiform encephalopathy susceptibility differ significantly between cattle and buffalo.

    PubMed

    Zhao, Hui; Du, Yanli; Chen, Shunmei; Qing, Lili; Wang, Xiaoyan; Huang, Jingfei; Wu, Dongdong; Zhang, Yaping

    2015-12-01

    Prion protein, encoded by the prion protein gene (PRNP), plays a crucial role in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Several polymorphisms within the PRNP are known to be associated with influencing bovine spongiform encephalopathy (BSE) susceptibility in cattle, namely two insertion/deletion (indel) polymorphisms (a 23-bp indel in the putative promoter and a 12-bp indel in intron 1), the number of octapeptide repeats (octarepeats) present in coding sequence (CDS) and amino acid polymorphisms. The domestic buffaloes, Bubalus bubalis, are a ruminant involved in various aspects of agriculture. It is of interest to ask whether the PRNP polymorphisms differ between cattle and buffalo. In this study, we analyzed the previously reported polymorphisms associated with BSE susceptibility in Chinese buffalo breeds, and compared these polymorphisms in cattle with BSE, healthy cattle and buffalo by pooling data from the literature. Our analysis revealed three significant findings in buffalo: 1) extraordinarily low deletion allele frequencies of the 23- and 12-bp indel polymorphisms; 2) significantly low allelic frequencies of six octarepeats in CDS and 3) the presence of S4R, A16V, P54S, G108S, V123M, S154N and F257L substitutions in buffalo CDSs. Sequence alignments comparing the buffalo coding sequence to other species were analyzed using the McDonald-Kreitman test to reveal five groups (Bison bonasus, Bos indicus, Bos gaurus, Boselaphus tragocamelus, Syncerus caffer caffer) with significantly divergent non-synonymous substitutions from buffalo, suggesting potential divergence of buffalo PRNP and others. To the best of our knowledge this is the first study of PRNP polymorphisms associated with BSE susceptibility in Chinese buffalo. Our findings have provided evidence that buffaloes have a unique genetic background in the PRNP gene in comparison with cattle.

  15. Clinical significance of the administration of cytarabine or thiotepa in addition to total body irradiation and cyclophosphamide for allogeneic hematopoietic cell transplantation in patients with acute leukemia.

    PubMed

    Tachibana, Takayoshi; Tanaka, Masatsugu; Hagihara, Maki; Kawasaki, Rika; Yamazaki, Etsuko; Koharazawa, Hideyuki; Taguchi, Jun; Tomita, Naoto; Fujimaki, Katsumichi; Sakai, Rika; Fujita, Hiroyuki; Fujisawa, Shin; Maruta, Atsuo; Ishigatsubo, Yoshiaki; Kanamori, Heiwa

    2015-10-01

    A multicenter retrospective study was performed to determine the significance of adding cytarabine (CA) or thiotepa (TT) in the context of total body irradiation (TBI) and cyclophosphamide (CY). A total of 322 patients who underwent allogeneic hematopoietic cell transplantation (HCT) were distributed to the following three groups: TBI/CY (n = 75), TBI/CY/CA (n = 77), and TBI/CY/TT (n = 170). In the TBI/CY/TT group, 164 of patients (96 %) received HCT during the previous year (2000-2005). Multivariate analysis revealed that the TBI/CY/TT group demonstrated a trend of poorer survival rate than the TBI/CY group, [hazard ratio (HR) = 1.49, 95 % confidence interval (CI) 0.99-2.24, P = 0.055] with a higher non-relapse mortality (NRM) (HR = 2.34, 95 % CI 1.35-4.06, P = 0.002) rates, while TBI/CY/CA group demonstrated similar outcomes. Even in the subgroup analyses of disease type or disease risk, the outcomes with intensified conditioning regimens were not superior to those with TBI/CY. In conclusion, although the significant bias has to be carefully considered, the clinical benefit of adding CA or TT to the TBI/CY regimen was not demonstrated.

  16. FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes.

    PubMed

    Al-Shahrour, Fátima; Díaz-Uriarte, Ramón; Dopazo, Joaquín

    2004-03-01

    We present a simple but powerful procedure to extract Gene Ontology (GO) terms that are significantly over- or under-represented in sets of genes within the context of a genome-scale experiment (DNA microarray, proteomics, etc.). Said procedure has been implemented as a web application, FatiGO, allowing for easy and interactive querying. FatiGO, which takes the multiple-testing nature of statistical contrast into account, currently includes GO associations for diverse organisms (human, mouse, fly, worm and yeast) and the TrEMBL/Swissprot GOAnnotations@EBI correspondences from the European Bioinformatics Institute.

  17. Significant association between the C(-1019)G functional polymorphism of the HTR1A gene and impulsivity.

    PubMed

    Benko, Anita; Lazary, Judit; Molnar, Eszter; Gonda, Xenia; Tothfalusi, Laszlo; Pap, Dorottya; Mirnics, Zsuzsanna; Kurimay, Tamas; Chase, Diana; Juhasz, Gabriella; Anderson, Ian M; Deakin, John F W; Bagdy, Gyorgy

    2010-03-01

    Serotonin-1A (5-HT(1A)) receptors are known to play a role in impulsivity-related behavior. The C(-1019)G functional polymorphism (rs6295) has been suggested to regulate the 5-HT(1A) receptor gene (HTR(1A)) expression in presynaptic raphe neurons, namely, increased receptor concentration and reduced neuronal firing could be associated with the G allele. Previous studies indicate that this polymorphism is associated with aggression, suicide, and several psychiatric disorders, yet its association with impulsivity has rarely been investigated. We studied the relationship between impulsivity and the C(-1019)G polymorphism of the HTR(1A) in a population sample of 725 volunteers using the Impulsiveness subscale (IVE-I) of the Eysenck Impulsiveness, Venturesomeness, and Empathy scale and also the Barratt Impulsiveness Scale (BIS-11). Data were analyzed using analysis of variance with age and gender as covariates and Tukey's HSD post-hoc test. Post-hoc analysis revealed that the study had 0.958 power to detect 0.15 effect size. Significant differences between the C(-1019)G genotype groups (GG vs. GC vs. CC) were found. Subjects carrying GG genotype showed significantly higher impulsiveness scores compared to GC or CC carriers for the IVE-I scale (P = 0.014), for the Motor (P = 0.021), Cognitive Impulsiveness (P = 0.002), and for the BIS total score (P = 0.008) but not for the Nonplanning Impulsiveness (P = 0.520) subscale of the BIS-11. Our results suggest the involvement of the HTR(1A) in the continuum phenotype of impulsivity. PMID:19725031

  18. Significant associations between hemostatic/fibrinolytic systems and accumulation of cardiovascular risk factors in Japanese elementary schoolchildren.

    PubMed

    Lin, Lisheng; Horigome, Hitoshi; Kato, Yoshiaki; Kikuchi, Toshihiro; Nakahara, Satoko; Sumazaki, Ryo

    2015-01-01

    The aim of this study was to establish the reference values of hemostatic/fibrinolytic markers and investigate their relationship with physical constitution and cardiovascular risk factors in a normal schoolchildren population. This study comprised 148 healthy Japanese children aged 9-10 years (males 73; females 75). We performed laboratory tests including blood levels of leptin, high-sensitive C-reactive protein (hs-CRP), hemostatic and fibrinolytic markers [plasminogen activator inhibitor 1 (PAI-1), coagulation factor VII (FVII), coagulation factor X (FX), fibrinogen (Fbg), protein C, protein S], as well as common biochemical markers in the morning after an overnight fast. We investigated the mean, 10th, 50th and 90th percentile values of these markers. All parameters were compared between two groups, that is those with body mass index (BMI) 90th percentile or higher and BMI less than 90th percentile, and between subgroups based on the number of cardiovascular risk factors. Multiple-linear regression was used to assess associations between these hematological parameters and the components related to metabolic syndrome (MetS). Alanine aminotransferase (ALT), uric acid, leptin, hs-CRP, and all hemostatic/fibrinolytic markers (PAI-1, FVII, FX, Fbg, protein C, protein S) tested were significantly higher in the group with BMI 90th percentile or higher, and increased with accumulation of cardiovascular risk factors. Multiple-linear regression analysis showed that these values were associated with one or more components related to MetS. Reference values of hemostatic/fibrinolytic markers in Japanese schoolchildren were obtained. Many hemostatic/fibrinolytic markers showed significant association with BMI and accumulation of cardiovascular risk factors in normal Japanese schoolchildren. PMID:25185676

  19. Multi-species data integration and gene ranking enrich significant results in an alcoholism genome-wide association study

    PubMed Central

    2012-01-01

    Background A variety of species and experimental designs have been used to study genetic influences on alcohol dependence, ethanol response, and related traits. Integration of these heterogeneous data can be used to produce a ranked target gene list for additional investigation. Results In this study, we performed a unique multi-species evidence-based data integration using three microarray experiments in mice or humans that generated an initial alcohol dependence (AD) related genes list, human linkage and association results, and gene sets implicated in C. elegans and Drosophila. We then used permutation and false discovery rate (FDR) analyses on the genome-wide association studies (GWAS) dataset from the Collaborative Study on the Genetics of Alcoholism (COGA) to evaluate the ranking results and weighting matrices. We found one weighting score matrix could increase FDR based q-values for a list of 47 genes with a score greater than 2. Our follow up functional enrichment tests revealed these genes were primarily involved in brain responses to ethanol and neural adaptations occurring with alcoholism. Conclusions These results, along with our experimental validation of specific genes in mice, C. elegans and Drosophila, suggest that a cross-species evidence-based approach is useful to identify candidate genes contributing to alcoholism. PMID:23282140

  20. Copy number variation-based genome wide association study reveals additional variants contributing to meat quality in Swine

    PubMed Central

    Wang, Ligang; Xu, Lingyang; Liu, Xin; Zhang, Tian; Li, Na; Hay, El Hamidi; Zhang, Yuebo; Yan, Hua; Zhao, Kebin; Liu, George E; Zhang, Longchao; Wang, Lixian

    2015-01-01

    Pork quality is important both to the meat processing industry and consumers’ purchasing attitude. Copy number variation (CNV) is a burgeoning kind of variants that may influence meat quality. In this study, a genome-wide association study (GWAS) was performed between CNVs and meat quality traits in swine. After false discovery rate (FDR) correction, a total of 8 CNVs on 6 chromosomes were identified to be significantly associated with at least one meat quality trait. All of the 8 CNVs were verified by next generation sequencing and six of them were verified by qPCR. Only the haplotype block containing CNV12 is adjacent to significant SNPs associated with meat quality, suggesting the effects of those CNVs were not likely captured by tag SNPs. The DNA dosage and EST expression of CNV12, which overlap with an obesity related gene Netrin-1 (Ntn1), were consistent with Ntn1 RNA expression, suggesting the CNV12 might be involved in the expression regulation of Ntn1 and finally influence meat quality. We concluded that CNVs may contribute to the genetic variations of meat quality beyond SNPs, and several candidate CNVs were worth further exploration. PMID:26234186

  1. Serum Vitamin D Is Significantly Inversely Associated with Disease Severity in Caucasian Adults with Obstructive Sleep Apnea Syndrome

    PubMed Central

    Kerley, Conor P.; Hutchinson, Katrina; Bolger, Kenneth; McGowan, Aisling; Faul, John; Cormican, Liam

    2016-01-01

    Study Objectives: To evaluate vitamin D (25(OH)D) levels in obstructive sleep apnea syndrome (OSAS) and possible relationships to OSAS severity, sleepiness, lung function, nocturnal heart rate (HR), and body composition. We also aimed to compare the 25(OH)D status of a subset of OSAS patients compared to controls matched for important determinants of both OSAS and vitamin D deficiency (VDD). Methods: This was a cross-sectional study conducted at an urban, clinical sleep medicine outpatient center. We recruited newly diagnosed, Caucasian adults who had recently undergone nocturnal polysomnography. We compared body mass index (BMI), body composition (bioelectrical impedance analysis), neck circumference, sleepiness (Epworth Sleepiness Scale), lung function, and vitamin D status (serum 25-hydrpoxyvitamin D (25(OH)D) across OSAS severity categories and non-OSAS subjects. Next, using a case-control design, we compared measures of serum 25(OH)D from OSAS cases to non-OSAS controls who were matched for age, gender, skin pigmentation, sleepiness, season, and BMI. Results: 106 adults (77 male; median age = 54.5; median BMI = 34.3 kg/m2) resident in Dublin, Ireland (latitude 53°N) were recruited and categorized as non-OSAS or mild/moderate/severe OSAS. 98% of OSAS cases had insufficient 25(OH)D (< 75 nmol/L), including 72% with VDD (< 50 nmol/L). 25(OH)D levels decreased with OSAS severity (P = 0.003). 25(OH)D was inversely correlated with BMI, percent body fat, AHI, and nocturnal HR. Subsequent multivariate regression analysis revealed that 25(OH)D was independently associated with both AHI (P = 0.016) and nocturnal HR (P = 0.0419). Our separate case-control study revealed that 25(OH)D was significantly lower in OSAS cases than matched, non-OSAS subjects (P = 0.001). Conclusions: We observed widespread vitamin D deficiency and insufficiency in a Caucasian, OSAS population. There were significant, independent, inverse relationships between 25(OH)D and AHI as well as

  2. Single-nucleotide polymorphism rs41736 located in MET was significantly associated with prognosis of small cell lung cancer patients.

    PubMed

    Cao, Xu; Hong, Xuan; Jia, Xiaoli; Zhang, Liping; Chen, Gang

    2014-12-01

    MET has been suggested to have an intimate relationship with small cell lung cancer (SCLC) and might be a promising therapeutic target. To date, relatively limited reports have been explored on MET mutational status in SCLC patients. To investigate the relationship between MET mutations and SCLC, 68 Chinese patients surgically treated for SCLC were enrolled. MET mutational analyses were performed in tumors, adjacent normal tissues as well as in lymph nodes with no metastasis nonadherent to tumor tissues using Sanger sequencing after PCR. The same mutation types were found in tumors, adjacent normal tissues as well as lymph nodes, including the only missense mutation N375S encoding semaphorin domain in exon 2 in 4 patients (5.9%), one single-nucleotide polymorphism (SNP) rs35775721: C>T also encoding semaphorin domain as heterozygous in 10 cases (14.7%) and another SNP rs41736: C>T encoding tyrosine kinase domain in exon 20 existing in 49 cases (72.1%). In survival analysis, the wild genotype CC-carriers of rs41736 conferred a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to CT + TT-carriers (HR 0.455, 95% CI 0.229-0.904; HR 0.226, 95% CI 0.099-0.515, for PFS and OS, respectively) in limited-stage SCLC patients. We also found that the lymph node status was significantly associated with OS, and the shorter OS was present in positive group (HR 2.187, 95% CI 1.170-4.088). In this study, rs41736 polymorphism of MET was first found to be associated with prognosis of limited-stage SCLC patients and could be considered as a prognostic marker for limited-stage SCLC.

  3. Characterization of a new wheat-Aegilops biuncialis addition line conferring quality-associated HMW glutenin subunits.

    PubMed

    Zhou, J P; Yao, C H; Yang, E N; Yin, M Q; Liu, C; Ren, Z L

    2014-01-28

    In this study, a new disomic addition line, 12-5-2, with 44 chromosomes that was derived from BC3F2 descendants of the hybridization between Triticum aestivum cv. CN19 and Aegilops biuncialis was created and reported. 12-5-2 was immune to both powdery mildew and stripe rust and has stable fertility. Fluorescence in situ hybridization and C-banding revealed that 12-5-2 was a 1U(b) disomic addition line (ADL1U(b)). The seed storage protein electrophoresis showed that 12-5-2 presented all high molecular weight glutenin subunits (7 + 8 and 2 + 12) of CN19 and 2 new subunits that were designated Ux and Uy. Additionally, the flour quality parameters showed that the protein content, Zeleny sedimentation value, wet gluten content, and grain hardness of 12-5-2 were significantly higher than those of its parent CN19. Moreover, 5 pairs of the chromosome 1U(b)-specific polymerase chain reaction-based landmark unique gene markers, TNAC1021, TNAC1041, TNAC1071, TNAC1-01, and TNAC1-04, were also obtained. The new ADL1U(b) 12-5-2 could be a valuable source for wheat improvement, especially for wheat end-product quality and resistance to disease.

  4. Characterization of a new wheat-Aegilops biuncialis addition line conferring quality-associated HMW glutenin subunits.

    PubMed

    Zhou, J P; Yao, C H; Yang, E N; Yin, M Q; Liu, C; Ren, Z L

    2014-01-01

    In this study, a new disomic addition line, 12-5-2, with 44 chromosomes that was derived from BC3F2 descendants of the hybridization between Triticum aestivum cv. CN19 and Aegilops biuncialis was created and reported. 12-5-2 was immune to both powdery mildew and stripe rust and has stable fertility. Fluorescence in situ hybridization and C-banding revealed that 12-5-2 was a 1U(b) disomic addition line (ADL1U(b)). The seed storage protein electrophoresis showed that 12-5-2 presented all high molecular weight glutenin subunits (7 + 8 and 2 + 12) of CN19 and 2 new subunits that were designated Ux and Uy. Additionally, the flour quality parameters showed that the protein content, Zeleny sedimentation value, wet gluten content, and grain hardness of 12-5-2 were significantly higher than those of its parent CN19. Moreover, 5 pairs of the chromosome 1U(b)-specific polymerase chain reaction-based landmark unique gene markers, TNAC1021, TNAC1041, TNAC1071, TNAC1-01, and TNAC1-04, were also obtained. The new ADL1U(b) 12-5-2 could be a valuable source for wheat improvement, especially for wheat end-product quality and resistance to disease. PMID:24615031

  5. The prognostic significance of expression of the multidrug resistance-associated protein (MRP) in primary breast cancer.

    PubMed Central

    Nooter, K.; Brutel de la Riviere, G.; Look, M. P.; van Wingerden, K. E.; Henzen-Logmans, S. C.; Scheper, R. J.; Flens, M. J.; Klijn, J. G.; Stoter, G.; Foekens, J. A.

    1997-01-01

    In the present study, we determined the frequency and intensity of MRP protein expression by monoclonal antibody immunohistochemistry in a series of 259 resected invasive primary breast carcinomas, and we evaluated MRP immunoreactivity in relation to patient and tumour characteristics, relapse-free (RFS) and overall survival (OS). The immunostaining was graded on a semiquantitative scale that ranged from (-) to ( ). Overall, 34% of the tumours were positive for anti-MRP antibody: 19% showed weak cytoplasmic staining (+), 14% had clear cytoplasmic staining (++) and only 1% of the tumours had a strong cytoplasmic as well as membranous staining ( ). MRP expression was not related to patient's age, menopausal status, tumour size, differentiation grade, oestrogen and progesterone receptor level or lymph node involvement. In an exploratory univariate analysis of all patients, only primary tumour size and number of lymph nodes involved were significantly associated with shortened RFS (P < 0.001 and P < 0.001 respectively) and OS (P = 0.02 and P < 0.001 respectively). In Cox univariate analysis for RFS in subgroups of patients stratified by menopausal status, tumour size, nodal status, adjuvant systemic therapy and oestrogen and progesterone receptor status, MRP expression was associated with increased risk for failure in patients with small tumours (T1), in node-negative patients and in node-positive patients who received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF); the relative hazard rate (RHR) for relapse was increased in the presence of MRP, with RHR values with 95% confidence limits (CL) of 2.8 (1.2-6.9), 2.1 (1.0-4.2) and 2.8 (0.8-9.9) respectively. In analysis for OS, expression of MRP was also associated with increased risk for failure in patients with small tumours (T1) [RHR (95% CL) 2.3 (0.9-6.0)] and in node-positive patients who received adjuvant systemic chemotherapy with CMF [RHR (95% CL) 3.7 (0.8-17.1)] but

  6. Two additional cases of metformin-associated encephalopathy in patients with end-stage renal disease undergoing hemodialysis.

    PubMed

    Kang, Yeo-Jin; Bae, Eun Jin; Seo, Jong Woo; Jeon, Dae-Hong; Cho, Hyun Seop; Kim, Hyun-Jung; Chang, Se-Ho; Park, Dong Jun

    2013-01-01

    We report on two additional cases of metformin-associated encephalopathy in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Two patients were seen at our hospital with abnormal neurological signs and symptoms. Magnetic resonance imaging (MRI) revealed the same pattern of high signal intensity in both basal ganglia in T2-weighted images in the two patients. The two patients had started taking metformin 5 and 6 weeks earlier at the same dose of 1000 mg per day. Metformin was immediately stopped, and regular hemodialysis was conducted. Their signs and symptoms resolved completely after these measures. The high signal intensity in both ganglia in T2-weighted MRI also disappeared. We should suspect metformin-induced encephalopathy and withdraw the drug when presented with diabetic patients with chronic kidney disease and neurological signs and symptoms of unknown cause.

  7. A Raman Spectroscopic Study of the Structural Modifications Associated with the Addition of Calcium Oxide and Boron Oxide to Silica

    NASA Astrophysics Data System (ADS)

    Kline, Jeff; Tangstad, Merete; Tranell, Gabriella

    2015-02-01

    Raman spectroscopy as an instrumental technique for the determination of silicate structure is widely accepted. This method was utilized for analysis of structural modifications associated with the addition of network modifying species. Silicate melts are described by the extent of oxygen bridging. Therefore, understanding the effect different oxides have on modifying the silicate structure will provide valuable information regarding the removal of boron from silicon in slag refining processes. Samples in the range CaO/SiO2 = 0.56 to 1.2 were evaluated with and without varying concentrations of B2O3. As expected, increasing the CaO content resulted in an increase in the Q 0 and Q 1 species and a decrease in the Q 3 species indicating a depolymerization of the silicate network. The addition of B2O3 to the 36 wt pct CaO-64 wt pct SiO2 system resulted in a decrease in ring-typed structures associated with the vibrational mode near 600 cm-1, an increase in the Q 3 species and a decrease in the Q 2 species. Adding B2O3 to the 54.5 wt pct CaO-45.5 wt pct SiO2 system resulted in decrease in the Q 0 and Q 2 species and an increase in the Q 3 species. Thus, both systems indicate the introduction of B2O3 to the more polymerized structural units in the silicate network. The increase in the peak near 630 cm-1 signifies some formation of ring-type metaborate groups or ring-type danburite groups. A correlation between the experimentally determined Q n distribution and optical basicity is proposed. Viscosity and optical basicity are correlated for the CaO-SiO2 system as well as viscosity and.

  8. A Raman Spectroscopic Study of the Structural Modifications Associated with the Addition of Calcium Oxide and Boron Oxide to Silica

    NASA Astrophysics Data System (ADS)

    Kline, Jeff; Tangstad, Merete; Tranell, Gabriella

    2014-09-01

    Raman spectroscopy as an instrumental technique for the determination of silicate structure is widely accepted. This method was utilized for analysis of structural modifications associated with the addition of network modifying species. Silicate melts are described by the extent of oxygen bridging. Therefore, understanding the effect different oxides have on modifying the silicate structure will provide valuable information regarding the removal of boron from silicon in slag refining processes. Samples in the range CaO/SiO2 = 0.56 to 1.2 were evaluated with and without varying concentrations of B2O3. As expected, increasing the CaO content resulted in an increase in the Q 0 and Q 1 species and a decrease in the Q 3 species indicating a depolymerization of the silicate network. The addition of B2O3 to the 36 wt pct CaO-64 wt pct SiO2 system resulted in a decrease in ring-typed structures associated with the vibrational mode near 600 cm-1, an increase in the Q 3 species and a decrease in the Q 2 species. Adding B2O3 to the 54.5 wt pct CaO-45.5 wt pct SiO2 system resulted in decrease in the Q 0 and Q 2 species and an increase in the Q 3 species. Thus, both systems indicate the introduction of B2O3 to the more polymerized structural units in the silicate network. The increase in the peak near 630 cm-1 signifies some formation of ring-type metaborate groups or ring-type danburite groups. A correlation between the experimentally determined Q n distribution and optical basicity is proposed. Viscosity and optical basicity are correlated for the CaO-SiO2 system as well as viscosity and Q_{{exp}}^n.

  9. Epidemiology and the prognosis of healthcare-associated infective endocarditis in China: the significance of non-nosocomial acquisition.

    PubMed

    Yang, Feifei; Zhang, Bingyan; Yu, Jie; Shao, Lingyun; Zhou, Pu; Zhu, Liping; Chen, Shu; Zhang, Wenhong; Weng, Xinhua; Zhang, Jiming; Huang, Yuxian

    2015-07-01

    Limited research has been conducted on healthcare-associated infective endocarditis (HAIE), although it is of increasing importance. The aim of this study is to compare the epidemiology, clinical characteristics, and prognosis of community-acquired IE (CA-IE) with HAIE and non-nosocomial healthcare-associated IE (NNHCA-IE). A retrospective, consecutive case-series analysis was organized and performed during the 20-year study period in Huashan Hospital, Shanghai, China. A total of 154 patients were enrolled, including 126 (81.8%) who had CA-IE and 28 (18.2%) who had HAIE, among whom 20 (71.4%) had non-nosocomial IE. Patients with HAIE compared to patients with CA-IE had poorer clinical conditions (Charlson comorbidity index ≥2: 35.7% vs. 15.1%, P = 0.012; immunosuppressive therapy: 21.4% vs. 4.0%, P = 0.005), underwent more prosthetic valve replacement (35.7% vs. 7.1%, P <0.001), had less streptococcus infection (16.7% vs. 51.1%, P = 0.007) but more atypical bacterial infection (50.0% vs. 21.1%, P = 0.017) and poorer outcomes (17.9% vs. 4.0%, P = 0.019). It is noteworthy that the results were quite similar between the comparison of patients with NNHCA-IE and those with CA-IE. Overall, in-hospital mortality was 6.5%. The IE acquisition site and low serum albumin levels (odds ratio (OR): 0.8; P = 0.04) were significantly associated with an increased risk of mortality. Nosocomial IE patients had an 8.3-fold and NNHCA-IE patients had 6.5-fold increase in the risk of mortality compared to CA-IE patients. In conclusion, HAIE and NNHCA-IE have important epidemiological and prognostic implications. Because NNHCA-IE usually occurs in patients residing in the community, it is suggested that these patients should be identified and treated by the community primary care clinical staff as early as possible.

  10. Young coconut juice, a potential therapeutic agent that could significantly reduce some pathologies associated with Alzheimer's disease: novel findings.

    PubMed

    Radenahmad, Nisaudah; Saleh, Farid; Sawangjaroen, Kitja; Vongvatcharanon, Uraporn; Subhadhirasakul, Patchara; Rundorn, Wilart; Withyachumnarnkul, Boonsirm; Connor, James R

    2011-03-01

    Brains from ovariectomised (ovx) rats can display features similar to those observed in menopausal women with Alzheimer's disease (AD), and oestrogen seems to play a key role. Preliminary studies on young coconut juice (YCJ) have reported the presence of oestrogen-like components in it. The aim of the study was to investigate the effects of YCJ on the AD pathological changes in the brains of ovx rats. Rat groups included sham-operated, ovx, ovx+oestradiol benzoate (EB) and ovx+YCJ. Brain sections (4 μm) were taken and were immunostained with β-amyloid (Aβ) 1-42, glial fibrillary acidic protein (GFAP) (an intermediate neurofilament of astrocytes) and Tau-1 antibodies. Aβ 1-42, GFAP and Tau-1 are considered as reliable biomarkers of amyloidosis, astrogliosis and tauopathy (neurofibrillary tangles), respectively, which in turn are characteristic features associated with AD. The serum oestradiol (E2) level was measured using a chemiluminescent immunoassay technique. YCJ restored the serum E2 to levels significantly (P < 0·001) higher than that of the ovx group, and even that of the sham group. Aβ deposition was significantly (P < 0·0001) reduced in the cerebral cortex of the YCJ group, as compared with the ovx group and with the sham and ovx+EB groups (P < 0·01). A similar trend was observed in relation to GFAP expression in the cerebral cortex and to Tau-1 expression in the hippocampus. This is a novel study demonstrating that YCJ could have positive future implications in the prevention and treatment of AD in menopausal women.

  11. Association between the Delta Estimated Glomerular Filtration Rate and the Prevalence of Monoclonal Gammopathy of Undetermined Significance in Korean Males

    PubMed Central

    Chun, Sail; Min, Won-Ki

    2014-01-01

    Background. We investigated the association between the reduction in the estimated glomerular filtration rate (eGFR) and the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in Korean males. Methods. We enrolled 723 healthy Korean males. Serum creatinine concentration, serum electrophoresis, serum immunofixation, and the serum free light chain assay were performed. We calculated delta eGFR per year (ΔeGFR/yr). The prevalence of MGUS was compared based on the ΔeGFR/yr and age group. Results. Thirteen (1.8%) of 723 participants exhibited the monoclonal band on serum immunofixation. Prevalence of MGUS by age group was 0.00% (0/172 for 40 years), 1.63% (6/367 for 60 years), and 3.80% (7/184 for >60 years). The median decrease in ΔeGFR/yr was 5.3%. The prevalence of MGUS in participants in their 50s with >5.3% decline in ΔeGFR/yr was significantly higher than those with <5.3% decrease in ΔeGFR/yr (3.16% versus 0.00%; P = 0.049). The prevalence of MGUS in participants in their 50s with >5.3% decrease in ΔeGFR/yr was similar to that of healthy males in their 60s. Conclusion. Using the rate of reduction in ΔeGFR/yr in healthy Korean males who had their serum creatinine level checked regularly may increase the MGUS detection rate in clinical practice. PMID:24895568

  12. Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation.

    PubMed

    Bartolome, Aleksandar; Boskovic, Srdjan; Paunovic, Ivan; Bozic, Vesna; Cvejic, Dubravka

    2016-04-01

    Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p < 0.001), pT status (p < 0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients.

  13. Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation.

    PubMed

    Bartolome, Aleksandar; Boskovic, Srdjan; Paunovic, Ivan; Bozic, Vesna; Cvejic, Dubravka

    2016-04-01

    Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p < 0.001), pT status (p < 0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients. PMID:26750533

  14. The association with Turner syndrome significantly affects the course of Hashimoto's thyroiditis in children, irrespective of karyotype.

    PubMed

    Aversa, Tommaso; Messina, Maria Francesca; Mazzanti, Laura; Salerno, Mariacarolina; Mussa, Alessandro; Faienza, Maria Felicia; Scarano, Emanuela; De Luca, Filippo; Wasniewska, Malgorzata

    2015-12-01

    Only few studies have investigated to now whether the association with Turner syndrome (TS) may affect the course of Hashimoto's thyroiditis (HT) in children. Aim of this study was to ascertain whether the presentation and long-term course of HT in TS children may be characterized by a peculiar and atypical pattern. The clinical and biochemical findings at HT diagnosis in 90 TS children (group A) were compared with those recorded in 449 girls with HT but without TS (group B); in group A patients, thyroid function tests were re-evaluated after a median time interval of 4.9 years. At HT diagnosis median TSH levels and the rate of cases presenting with a thyroid dysfunction picture were significantly lower in group A, irrespective of karyotype abnormalities. In group A only 34.8 % of the girls who had initially presented with euthyroidism remained euthyroid even at re-evaluation, whilst 67.7 % of those who had presented with subclinical hypothyroidism became overtly hypothyroid over time; also such evolutive pattern was irrespective of karyotype abnormalities. (1) In TS girls, HT presents with a milder hormonal pattern, which often deteriorates over time; (2) these biochemical features are not necessarily linked with a specific karyotype.

  15. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring.

    PubMed

    Bertino, J S; Booker, L A; Franck, P A; Jenkins, P L; Franck, K R; Nafziger, A N

    1993-01-01

    Incidence of and risk factors for aminoglycoside-associated nephrotoxicity (AAN) were evaluated in 1489 patients prospectively monitored with individualized pharmacokinetic monitoring (IPM). Incidence of AAN was 7.9% with individual (univariate) risk factors including advanced age, decreased albumin, poor nutritional status, pneumonia, concurrent furosemide, amphotericin B, vancomycin, cephalosporin, or piperacillin, intensive care unit treatment, leukemia, rapidly fatal illness, liver or renal disease, reduced aminoglycoside clearance, elevated initial steady-state trough concentration (Cminss), volume of distribution or half-life, duration of therapy, total dose, fever, male gender, shock, pleural effusion, and ascites. Multiple logistic regression revealed that Cminss, concurrent clindamycin, vancomycin, piperacillin, or cephalosporin, ascites, advanced age, male gender, decreased albumin, duration of therapy, and leukemia were significant independent risk factors for AAN. Positive predictive value of the model was 30.8%; negative predictive value was 91.7%. No identifiable risk factor alone or in combination was of sufficient sensitivity to reliably predict AAN, but use of IPM may lower the incidence of AAN. PMID:8418164

  16. Tectonic significance of lithicwacke-polymictic conglomerate petrofacies association within Upper Cretaceous torchlight sandstone, Big Horn basin, Wyoming

    SciTech Connect

    Khandaker, N.I.; Vondra, C.F.

    1987-05-01

    The Torchlight Sandstone belonging to the Upper Cretaceous Frontier Formation in the Big Horn basin, Wyoming, shows a distinctive lithicwacke-polymictic conglomerate is composed of granule-cobble-sized clasts of quartzite, chert, andesite, and argillite, and phyllite. The survival of phyllite, argillite, and neovolcanic andesite clasts indicate that the detritus underwent very little subaerial transport before it was deposited along the proximal margin of the foreland basin. A petrologically heterogeneous upland source of high to moderate relief is indicated by the clast size and composition. Hydrodynamic structures, in conjunction with textural attributes, and compositional data indicate that detritus moved southeast from its source terrane and was deposited by a high-energy distributary complex. The lithicwacke petrofacies is dominated by higher chert and quartz content with a subordinate amount of labile components including paleovolcanic clasts and fine-grained matrix. The development of phyllosilicate matrix around quartz and chert grains preserved the primary porosity and permeability of the sandstone. Absence of any noticeable quartz overgrowth apparently contributed to the preservation of good reservoir quality in this petrofacies. Considering its (Torchlight Sandstone) close proximity to the thrust belt and to the locus of andesite volcanism in the northwest and west, it is suggested that the extrabasinal detritus within the foreland basin can provide significant clues as to the timing of the thrust events and volcanicity in the adjacent region. New perspectives for hydrocarbon exploration and regional correlation may be gained by employing this petrofacies association.

  17. Significant Differences in Markers of Oxidant Injury between Idiopathic and Bronchopulmonary-Dysplasia-Associated Pulmonary Hypertension in Children

    PubMed Central

    Vera, Kimberly B.; Moore, Donald; Flack, English; Liske, Michael; Summar, Marshall

    2012-01-01

    While oxidant stress is elevated in adult forms of pulmonary hypertension (PH), levels of oxidant stress in pediatric PH are unknown. The objective of this study is to measure F2-isoprostanes, a marker of oxidant stress, in children with idiopathic pulmonary hypertension (IPH) and PH due to bronchopulmonary dysplasia (BPD). We hypothesized that F2-isoprostanes in pediatric IPH and PH associated with BPD will be higher than in controls. Plasma F2-isoprostanes were measured in pediatric PH patients during clinically indicated cardiac catheterization and compared with controls. F2-Isoprostane levels were compared between IPH, PH due to BD, and controls. Five patients with IPH, 12 with PH due to BPD, and 20 control subjects were studied. Patients with IPH had statistically higher isoprostanes than controls 62 pg/mL (37–210) versus 20 pg/mL (16–27), P < 0.01). The patients with PH and BPD had significantly lower isoprostanes than controls 15 pg/mL (8–17) versus 20 pg/ml (16–27), P < 0.02. F2-isoprostanes are elevated in children with IPH compared to both controls and patients with PH secondary to BPD. Furthermore, F2-isoprostanes in PH secondary to BPD are lower than control levels. These findings suggest that IPH and PH secondary to BPD have distinct mechanisms of disease pathogenesis. PMID:22848815

  18. Addition of Bevacizumab to Standard Radiation Therapy and Daily Temozolomide Is Associated With Minimal Toxicity in Newly Diagnosed Glioblastoma Multiforme

    SciTech Connect

    Vredenburgh, James J.; Desjardins, Annick; Kirkpatrick, John P.; Reardon, David A.; Peters, Katherine B.; Herndon, James E.; Marcello, Jennifer; Bailey, Leighann; Threatt, Stevie; Sampson, John; Friedman, Allan; Friedman, Henry S.

    2012-01-01

    Purpose: To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). Methods and Materials: A total of 125 patients with newly diagnosed GBM were enrolled in the study, and received standard radiation therapy and daily temozolomide. All patients underwent a craniotomy and were at least 2 weeks postoperative. Radiation therapy was administered in 1.8-Gy fractions, with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy, followed by a boost of 9 to 14.4 Gy, to a total dose of 59.4 Gy. Patients received temozolomide at 75 mg/m{sup 2} daily throughout the course of radiation therapy. Bevacizumab was given at 10 mg/kg intravenously every 14 days, beginning a minimum of 4 weeks postoperatively. Results: Of the 125 patients, 120 (96%) completed the protocol-specified radiation therapy. Five patients had to stop the protocol therapy, 2 patients with pulmonary emboli, and 1 patient each with a Grade 2 central nervous system hemorrhage, Grade 4 pancytopenia, and wound dehiscence requiring surgical intervention. All 5 patients ultimately finished the radiation therapy. After radiation therapy, 3 patients had progressive disease, 2 had severe fatigue and decreased performance status, 1 patient had a colonic perforation, and 1 had a rectal fissure; these 7 patients therefore did not proceed with the protocol-specified adjuvant temozolomide, bevacizumab, and irinotecan. However, 113 patients (90%) were able to continue on study. Conclusions: The addition of bevacizumab to standard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM.

  19. The expression of beclin-1, an autophagic gene, in hepatocellular carcinoma associated with clinical pathological and prognostic significance

    PubMed Central

    2014-01-01

    Background A role for autophagy, a conserved cellular response to stress, has recently been demonstrated in human cancers. Aberrant expression of Beclin-1, an important autophagic gene, has been reported in various human cancers. In the present study, we investigated the significance and relationship between Beclin-1 expression and cell proliferation, apoptosis, microvessel density (MVD) and clinical pathological changes or prognosis in human hepatocellular carcinoma (HCC). Methods A total of 103 primary HCC patients were involved in the study. Expression of Beclin-1, PCNA, NET-1, Bcl-2, Bax, Survivin in cancer cells and CD34 in stromal microvessels were evaluated immunohistochemically in tissue microarrays comprising 103 cases of HCC and 57 matched adjacent nontumor liver tissues. Correlations between clinicopathological characteristics and survival of HCC patients were explored. Results The positive rate of Beclin-1 was significantly lower in HCC tissues than adjacent tissues (72.8 vs. 89.5%, χ2 = 6.085, P = 0.015). In HCC, Beclin-1 expression was negatively correlated with cirrhosis background (r = −0.216, P = 0.029), Edmondson grade (r = −0.249, P = 0.011), vascular invasion (r = −0.246, P = 0.012), PCNA (r = −0.242, P = 0.014), NET-1 (r = −0.245, P = 0.013), anti-apoptosis protein Bcl-2 (r = −0.245, P = 0.013) and MVD (r = −0.292, P = 0.003), and positively correlated with pro-apoptosis protein Bax (r = 0.242, P = 0.014). Significant differences in the 5-year survival rates were seen among patients with Beclin-1 strong positive (++) (59.1%, 13/22), moderate positive (+) (28.3%, 15/53) and weak negative expression (−) (14.6%, 7/28) (P = 0.043). Significant differences were detected between Beclin-1 (++) and either Beclin-1 (+) (P = 0.036) or Beclin-1 (−) groups (P = 0.008), but no significant difference between Beclin-1 (+) and Beclin-1 (−) groups (P = 0

  20. Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma

    PubMed Central

    Chun, Hyung Wook; Hong, Ran

    2016-01-01

    It has been found that abnormal activation of the hedgehog (Hh) signaling pathway is involved in the occurrence, invasion and metastasis of malignant tumors. In addition, epithelial-mesenchymal transition (EMT) also performs an important function in the invasion and metastasis of malignant tumors. However, the significance of the Hh signaling pathway and EMT in hepatocellular carcinoma (HCC) remains unknown. In the present study, the expression of Gli family zinc finger 1 (Gli-1) and Gli family zinc finger 2 (Gli-2), which are key transcriptional factors in the Hh signaling pathway, and Twist and E-cadherin, which are two factors involved in EMT, was examined in 42 patients with HCC and 20 cases of non-tumorous liver (NTL) tissue by immunohistochemistry. Clinicopathological information was collected in order to analyze the correlation of the Hh signaling pathway with EMT. The present study aimed to examine the difference in the expression of Gli-1, Gli-2, E-cadherin and Twist in HCC and NTL to assess the diagnostic value of these factors in HCC. Additionally, the present study aimed to elucidate the correlation between those proteins and other clinicopathological parameters. Whether abnormal activation of the Hh signaling pathway is closely associated with EMT was also evaluated. Gli-1 and Twist expression was found to be significantly increased and E-cadherin expression was found to be decreased in HCC in contrast to NTL (Gli-1, P=0.019; Twist, P=0.003; E-cadherin, P<0.001). Increased Twist expression was associated with the tumor size (P=0.043), and loss of or decreased E-cadherin expression was associated with the histological type of HCC (P=0.021). There was an inverse association between the expression of Twist and E-cadherin (P=0.006). These results showed that Twist overexpression by induction of EMT changes is involved in the occurrence and progression of HCC. However, the role of Hh signaling pathway-associated proteins in HCC may require elucidation by

  1. Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma

    PubMed Central

    Chun, Hyung Wook; Hong, Ran

    2016-01-01

    It has been found that abnormal activation of the hedgehog (Hh) signaling pathway is involved in the occurrence, invasion and metastasis of malignant tumors. In addition, epithelial-mesenchymal transition (EMT) also performs an important function in the invasion and metastasis of malignant tumors. However, the significance of the Hh signaling pathway and EMT in hepatocellular carcinoma (HCC) remains unknown. In the present study, the expression of Gli family zinc finger 1 (Gli-1) and Gli family zinc finger 2 (Gli-2), which are key transcriptional factors in the Hh signaling pathway, and Twist and E-cadherin, which are two factors involved in EMT, was examined in 42 patients with HCC and 20 cases of non-tumorous liver (NTL) tissue by immunohistochemistry. Clinicopathological information was collected in order to analyze the correlation of the Hh signaling pathway with EMT. The present study aimed to examine the difference in the expression of Gli-1, Gli-2, E-cadherin and Twist in HCC and NTL to assess the diagnostic value of these factors in HCC. Additionally, the present study aimed to elucidate the correlation between those proteins and other clinicopathological parameters. Whether abnormal activation of the Hh signaling pathway is closely associated with EMT was also evaluated. Gli-1 and Twist expression was found to be significantly increased and E-cadherin expression was found to be decreased in HCC in contrast to NTL (Gli-1, P=0.019; Twist, P=0.003; E-cadherin, P<0.001). Increased Twist expression was associated with the tumor size (P=0.043), and loss of or decreased E-cadherin expression was associated with the histological type of HCC (P=0.021). There was an inverse association between the expression of Twist and E-cadherin (P=0.006). These results showed that Twist overexpression by induction of EMT changes is involved in the occurrence and progression of HCC. However, the role of Hh signaling pathway-associated proteins in HCC may require elucidation by

  2. A significant association between rs8067378 at 17q12 and invasive cervical cancer originally identified by a genome-wide association study in Han Chinese is replicated in a Japanese population.

    PubMed

    Miura, Kiyonori; Mishima, Hiroyuki; Yasunami, Michio; Kaneuchi, Masanori; Kitajima, Michio; Abe, Shuhei; Higashijima, Ai; Fuchi, Naoki; Miura, Shoko; Yoshiura, Koh-Ichiro; Masuzaki, Hideaki

    2016-09-01

    In this study, associations between invasive cervical cancer and four cervical cancer susceptibility loci (rs13117307 at 4q12, rs8067378 at 17q12, and rs4282438 and rs9277952 at 6p21.32) in the Han Chinese population were investigated in a Japanese population. Human leukocyte antigen (HLA)-DPB1 alleles were also investigated for their association with cervical cancer risk in the Japanese population. After receiving written informed consent, 214 unrelated Japanese women with invasive cervical cancer and 288 cancer-free Japanese women were recruited, and DNA samples were obtained (study protocol approved by Institutional Review Board of Nagasaki University). Of the four single-nucleotide polymorphisms, rs8067378 showed a significant association with invasive cervical cancer (P=0.0071). Under a recessive model, the minor allele G of rs8067378 contributed to the risk of invasive cervical cancer (odds ratio=2.92, 95% confidence interval=1.40-6.36; P=0.0021). No association was detected between HLA-DPB1 alleles and cervical cancer risk in the Japanese population. In conclusion, we show for the first time, to the best of our knowledge, that an association between increased risk of invasive cervical cancer and rs8067378 in the Han Chinese population is replicated in a Japanese population. In addition, Japanese women with the GG genotype of rs8067378 are a candidate high-risk group for invasive cervical carcinoma.

  3. Predicting contamination by the fuel additive cerium oxide engineered nanoparticles within the United Kingdom and the associated risks.

    PubMed

    Johnson, Andrew C; Park, Barry

    2012-11-01

    As a fuel additive, cerium oxide nanoparticles may become widely dispersed throughout the environment. Commercial information from the United Kingdom (UK) on the use of cerium oxide nanoparticles was used to perform a modeling and risk assessment exercise. Discharge from exhausts took into account the likely removal by filters fitted to these vehicles. For predicting current soil exposure, scenarios were examined, ranging from dispersion occurring across the entire UK landmass to only within the urban area to only 20 m on either side of road networks. For soils, the highest predicted contamination level was 0.016 mg/kg within 20 m of a road following seven years of continuous deposition. This value would represent 0.027% of reported natural background cerium. If usage were to double for five more years, levels would not be expected to exceed 0.04 mg/kg. River water contamination considered direct aerial deposition and indirect contamination via runoff in the water and entrained soil sediment, with the highest level of 0.02 ng/L predicted. The highest predicted water concentration of 300 ng/L was associated with water draining from a road surface, assuming a restricted deposition spread. These predictions are well below most toxicological levels of concern.

  4. Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

    PubMed

    Talaei, Mohammad; Lee, Bee L; Ong, Choon N; van Dam, Rob M; Yuan, Jian M; Koh, Woon P; Pan, An

    2016-05-01

    We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults.

  5. STAT4 Associates with SLE Through Two Independent Effects that Correlate with Gene Expression and Act Additively with IRF5 to Increase Risk

    PubMed Central

    Abelson, Anna-Karin; Delgado-Vega, Angélica M.; Kozyrev, Sergey V.; Sánchez, Elena; Velázquez-Cruz, Rafael; Eriksson, Niclas; Wojcik, Jerome; Reddy, Prasad Linga; Lima, Guadalupe; D’Alfonso, Sandra; Migliaresi, Sergio; Baca, Vicente; Orozco, Lorena; Witte, Torsten; Ortego-Centeno, Norberto; Abderrahim, Hadi; Pons-Estel, Bernardo A.; Gutiérrez, Carmen; Suárez, Ana; González-Escribano, Maria Francisca; Martin, Javier; Alarcón-Riquelme, Marta E.

    2013-01-01

    Objectives To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. Methods 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5’-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. Results In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. Conclusions These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE. PMID:19019891

  6. Antibodies against Proinsulin and Homologous MAP Epitopes Are Detectable in Hashimoto's Thyroiditis Sardinian Patients, an Additional Link of Association.

    PubMed

    Niegowska, Magdalena; Paccagnini, Daniela; Burrai, Carlo; Palermo, Mario; Sechi, Leonardo A

    2015-01-01

    Hashimoto's thyroiditis (HT) is the prevailing organ-specific autoimmune disease in Sardinia, often complicated with other autoimmune disorders, most commonly type 1 diabetes (T1D). While numerous studies describe levels of anty-thyroid antibodies (Abs) in T1D patients, few papers evaluate the status of anti-islet autoimmunity in subjects affected by HT. Previously, we portrayed Mycobacterium avium subspecies paratuberculosis (MAP) as an environmental factor strongly associated with both diseases. In this study, we analyzed plasma of Sardinian HT patients (n=177) and healthy controls (HCs; n=175) for the presence of Abs against proinsulin and MAP-derived homologous epitopes: MAP1,4αgbp157-173/PI64-80 were recognized by 5,08% and 18,64% of HT vs 0,57% and 7,43% of HCs (AUC=0,6 for both; p<0,0003 and 0,002, respectively), whereas the prevalence of Abs against MAP2404c70-85/PI46-61 peptides was higher but not significant in patients when compared to HCs. In women (n=152), Abs against MAP1,4αgbp157-173 were detected in 12,50% of HT vs 2,75% of HCs (AUC=0,63; p<0,0002), while positivity to its human homolog PI64-80 was observed in 16,42% of HT vs 6,42% of HCs (AUC=0,61; p<0,001). In men (n=25), a significant anti-PI46-61 Abs levels were detected in 4% of HT vs none of the HCs (AUC=0,7; p<0,003). Age-related analyses revealed the highest prevalence between 31-40 years old (45,83%) in the total study population and among males (33,33%); in contrast, women had a higher seroreactivity between 51-60 years (42,11%). A further follow-up and determination of anti-islet Abs levels is needed to evaluate the association of immune responses directed against the MAP/PI homologous peptides with progression to overt diabetes in HT subjects. PMID:26192189

  7. Antibodies against Proinsulin and Homologous MAP Epitopes Are Detectable in Hashimoto's Thyroiditis Sardinian Patients, an Additional Link of Association.

    PubMed

    Niegowska, Magdalena; Paccagnini, Daniela; Burrai, Carlo; Palermo, Mario; Sechi, Leonardo A

    2015-01-01

    Hashimoto's thyroiditis (HT) is the prevailing organ-specific autoimmune disease in Sardinia, often complicated with other autoimmune disorders, most commonly type 1 diabetes (T1D). While numerous studies describe levels of anty-thyroid antibodies (Abs) in T1D patients, few papers evaluate the status of anti-islet autoimmunity in subjects affected by HT. Previously, we portrayed Mycobacterium avium subspecies paratuberculosis (MAP) as an environmental factor strongly associated with both diseases. In this study, we analyzed plasma of Sardinian HT patients (n=177) and healthy controls (HCs; n=175) for the presence of Abs against proinsulin and MAP-derived homologous epitopes: MAP1,4αgbp157-173/PI64-80 were recognized by 5,08% and 18,64% of HT vs 0,57% and 7,43% of HCs (AUC=0,6 for both; p<0,0003 and 0,002, respectively), whereas the prevalence of Abs against MAP2404c70-85/PI46-61 peptides was higher but not significant in patients when compared to HCs. In women (n=152), Abs against MAP1,4αgbp157-173 were detected in 12,50% of HT vs 2,75% of HCs (AUC=0,63; p<0,0002), while positivity to its human homolog PI64-80 was observed in 16,42% of HT vs 6,42% of HCs (AUC=0,61; p<0,001). In men (n=25), a significant anti-PI46-61 Abs levels were detected in 4% of HT vs none of the HCs (AUC=0,7; p<0,003). Age-related analyses revealed the highest prevalence between 31-40 years old (45,83%) in the total study population and among males (33,33%); in contrast, women had a higher seroreactivity between 51-60 years (42,11%). A further follow-up and determination of anti-islet Abs levels is needed to evaluate the association of immune responses directed against the MAP/PI homologous peptides with progression to overt diabetes in HT subjects.

  8. Modeling external carbon addition in biological nutrient removal processes with an extension of the international water association activated sludge model.

    PubMed

    Swinarski, M; Makinia, J; Stensel, H D; Czerwionka, K; Drewnowski, J

    2012-08-01

    The aim of this study was to expand the International Water Association Activated Sludge Model No. 2d (ASM2d) to account for a newly defined readily biodegradable substrate that can be consumed by polyphosphate-accumulating organisms (PAOs) under anoxic and aerobic conditions, but not under anaerobic conditions. The model change was to add a new substrate component and process terms for its use by PAOs and other heterotrophic bacteria under anoxic and aerobic conditions. The Gdansk (Poland) wastewater treatment plant (WWTP), which has a modified University of Cape Town (MUCT) process for nutrient removal, provided field data and mixed liquor for batch tests for model evaluation. The original ASM2d was first calibrated under dynamic conditions with the results of batch tests with settled wastewater and mixed liquor, in which nitrate-uptake rates, phosphorus-release rates, and anoxic phosphorus uptake rates were followed. Model validation was conducted with data from a 96-hour measurement campaign in the full-scale WWTP. The results of similar batch tests with ethanol and fusel oil as the external carbon sources were used to adjust kinetic and stoichiometric coefficients in the expanded ASM2d. Both models were compared based on their predictions of the effect of adding supplemental carbon to the anoxic zone of an MUCT process. In comparison with the ASM2d, the new model better predicted the anoxic behaviors of carbonaceous oxygen demand, nitrate-nitrogen (NO3-N), and phosphorous (PO4-P) in batch experiments with ethanol and fusel oil. However, when simulating ethanol addition to the anoxic zone of a full-scale biological nutrient removal facility, both models predicted similar effluent NO3-N concentrations (6.6 to 6.9 g N/m3). For the particular application, effective enhanced biological phosphorus removal was predicted by both models with external carbon addition but, for the new model, the effluent PO4-P concentration was approximately one-half of that found from

  9. Health Effects Associated with Inhalation Exposure to Diesel Emission Generated with and without CeO2 Nano Fuel Additive

    EPA Science Inventory

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Addition of nano cerium (Ce) oxide additive to diesel fuel (DECe) increases fuel burning efficiency resulting in altered emission characteristics and potentially altered health effects. We hypothesized that inh...

  10. Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

    PubMed Central

    Fan, Qiao; Verhoeven, Virginie J. M.; Wojciechowski, Robert; Barathi, Veluchamy A.; Hysi, Pirro G.; Guggenheim, Jeremy A.; Höhn, René; Vitart, Veronique; Khawaja, Anthony P.; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W.; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E.; Williams, Katie M.; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F.; Joshi, Peter K.; McMahon, George; St Pourcain, Beate; Evans, David M.; Simpson, Claire L.; Schwantes-An, Tae-Hwi; Igo, Robert P.; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S.; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M.; Amin, Najaf; Uitterlinden, André G.; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R.; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M. Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E. H.; Lim, Wan'e; Beuerman, Roger W.; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N.; Foster, Paul J.; Klein, Barbara E. K.; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L.; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M.; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B.; Teo, Yik-Ying; Mackey, David A.; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D.; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N.; Stambolian, Dwight; Wilson, Joan E. Bailey; Cheng, Ching-Yu; Hammond, Christopher J.; Klaver, Caroline C. W.; Saw, Seang-Mei; Rahi, Jugnoo S.; Korobelnik, Jean-François; Kemp, John P.; Timpson, Nicholas J.; Smith, George Davey; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G.; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F.; Fondran, Jeremy R.; Lass, Jonathan H.; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J.; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O.; Jhanji, Vishal; Young, Alvin L.; Döring, Angela; Raffel, Leslie J.; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K.H.; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L.; Tedja, Milly; Deangelis, Margaret M.; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10−5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia. PMID:27020472

  11. ACC Neuro-over-Connectivity Is Associated with Mathematically Modeled Additional Encoding Operations of Schizophrenia Stroop-Task Performance

    PubMed Central

    Taylor, Reggie; Théberge, Jean; Williamson, Peter C.; Densmore, Maria; Neufeld, Richard W. J.

    2016-01-01

    Functional magnetic resonance imaging at 7.0 Tesla was undertaken among Schizophrenia participants (Sz), and clinical (major mood disorder; MDD) and healthy controls (HC), during performance of the Stoop task. Stroop conditions included congruent and incongruent word color items, color-only items, and word-only items. Previous modeling results extended to this most widely used selective-attention task. All groups executed item-encoding operations (subprocesses of the item encoding process) at the same rate (performance accuracy being similarly high throughout), thus displaying like processing capacity; Sz participants, however, employed more subprocesses for item completions than did the MDD participants, who in turn used more subprocesses than the HC group. The reduced efficiency in deploying cognitive-workload capacity among the Sz participants was paralleled by more diffuse neuroconnectivity (Blood-Oxygen-Level-Dependent co-activation) with the anterior cingulate cortex (ACC) (Broadman Area 32), spreading away from this encoding-intensive region; and by less evidence of network dissociation across Stroop conditions. Estimates of cognitive work done to accomplish item completion were greater for the Sz participants, as were estimates of entropy in both the modeled trial-latency distribution, and its associated neuro-circuitry. Findings are held to be symptom and assessment significant, and to have potential implications for clinical intervention.

  12. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

    PubMed

    Fan, Qiao; Verhoeven, Virginie J M; Wojciechowski, Robert; Barathi, Veluchamy A; Hysi, Pirro G; Guggenheim, Jeremy A; Höhn, René; Vitart, Veronique; Khawaja, Anthony P; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E; Williams, Katie M; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F; Joshi, Peter K; McMahon, George; St Pourcain, Beate; Evans, David M; Simpson, Claire L; Schwantes-An, Tae-Hwi; Igo, Robert P; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M; Amin, Najaf; Uitterlinden, André G; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E H; Lim, Wan'e; Beuerman, Roger W; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B; Teo, Yik-Ying; Mackey, David A; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N; Stambolian, Dwight; Wilson, Joan E Bailey; Cheng, Ching-Yu; Hammond, Christopher J; Klaver, Caroline C W; Saw, Seang-Mei; Rahi, Jugnoo S; Korobelnik, Jean-François; Kemp, John P; Timpson, Nicholas J; Smith, George Davey; Craig, Jamie E; Burdon, Kathryn P; Fogarty, Rhys D; Iyengar, Sudha K; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F; Fondran, Jeremy R; Lass, Jonathan H; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O; Jhanji, Vishal; Young, Alvin L; Döring, Angela; Raffel, Leslie J; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K H; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L; Tedja, Milly; Deangelis, Margaret M; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-03-29

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

  13. ACC Neuro-over-Connectivity Is Associated with Mathematically Modeled Additional Encoding Operations of Schizophrenia Stroop-Task Performance

    PubMed Central

    Taylor, Reggie; Théberge, Jean; Williamson, Peter C.; Densmore, Maria; Neufeld, Richard W. J.

    2016-01-01

    Functional magnetic resonance imaging at 7.0 Tesla was undertaken among Schizophrenia participants (Sz), and clinical (major mood disorder; MDD) and healthy controls (HC), during performance of the Stoop task. Stroop conditions included congruent and incongruent word color items, color-only items, and word-only items. Previous modeling results extended to this most widely used selective-attention task. All groups executed item-encoding operations (subprocesses of the item encoding process) at the same rate (performance accuracy being similarly high throughout), thus displaying like processing capacity; Sz participants, however, employed more subprocesses for item completions than did the MDD participants, who in turn used more subprocesses than the HC group. The reduced efficiency in deploying cognitive-workload capacity among the Sz participants was paralleled by more diffuse neuroconnectivity (Blood-Oxygen-Level-Dependent co-activation) with the anterior cingulate cortex (ACC) (Broadman Area 32), spreading away from this encoding-intensive region; and by less evidence of network dissociation across Stroop conditions. Estimates of cognitive work done to accomplish item completion were greater for the Sz participants, as were estimates of entropy in both the modeled trial-latency distribution, and its associated neuro-circuitry. Findings are held to be symptom and assessment significant, and to have potential implications for clinical intervention. PMID:27695425

  14. The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth.

    PubMed

    Kim, Chong Jai; Romero, Roberto; Kusanovic, Juan Pedro; Yoo, Wonsuk; Dong, Zhong; Topping, Vanessa; Gotsch, Francesca; Yoon, Bo Hyun; Chi, Je Geun; Kim, Jung-Sun

    2010-07-01

    Acute chorioamnionitis is a well-established lesion of the placenta in cases with intra-amniotic infection. In contrast, the clinicopathological significance of chronic chorioamnionitis is unclear. This study was conducted to determine the frequency and severity of chronic chorioamnionitis in normal pregnancy and in various pregnancy complications. Placentas from the following patient groups were studied: (1) term not in labor (n=100), (2) term in labor (n=100), (3) preterm labor (n=100), (4) preterm prelabor rupture of membranes (n=100), (5) preeclampsia at term (n=100), (6) preterm preeclampsia (n=100), and (7) small-for-gestational-age at term (n=100). Amniotic fluid CXCL10 concentration was measured in 64 patients. CXCL9, CXCL10, and CXCL11 mRNA expressions in the chorioamniotic membranes were assessed using real-time quantitative reverse transcription-PCR. The frequency of chronic chorioamnionitis in the preterm labor group and the preterm prelabor rupture of membranes group was 34 and 39%, respectively, which was higher than that of normal-term placentas (term not in labor, 19%; term in labor, 8%; P<0.05 each). The frequency of chronic chorioamnionitis in the preeclampsia at term group, preterm preeclampsia group, and small-for-gestational-age group was 23, 16, and 13%, respectively. Concomitant villitis of unknown etiology was found in 38 and 36% of preterm labor cases and preterm prelabor rupture of membranes cases with chronic chorioamnionitis, respectively. Interestingly, the median gestational age of preterm chronic chorioamnionitis cases was higher than that of acute chorioamnionitis cases (P<0.05). The median amniotic fluid CXCL10 concentration was higher in cases with chronic chorioamnionitis than in those without, in both the preterm labor group and preterm prelabor rupture of membranes group (P<0.05 and P<0.01, respectively). CXCL9, CXCL10, and CXCL11 mRNA expression in the chorioamniotic membranes was also higher in cases with chronic

  15. Yeast-containing feed additive alters gene expression profiles associated with innate immunity in whole blood of a rodent model.

    PubMed

    Branson, Jennifer A; McLean, Derek J; Forsberg, Neil E; Bobe, Gerd

    2016-05-01

    Feeding a yeast-containing additive (YCA; OmniGen-AF) improves immune responses in ruminant livestock and reduces subsequent production losses. The objective was to identify molecular pathways by which dietary YCA may modify immune responses using a rodent model. Thirty-seven healthy, unchallenged CD rats received a diet containing 0 (control; n = 5, only 28 d), 0.5% (n = 15) or 1% (n = 17) YCA for 7 (n = 4/group), 14 (n = 3 or 4/group), 21 (n = 3 or 4/group) or 28 (n = 5/group) d. At the end of the feeding periods, whole blood was collected and the isolated RNA was analyzed for the expression of 84 genes involved in innate and cell-mediated adaptive immune responses. Three bacterial pattern recognition receptors TLR1 (0.5%: + 2.01; 1%: + 2.38), TLR6 (0.5%: + 2.11; 1%: + 2.34) and NOD2 (0.5%: + 2.32; 1%: + 2.23), two APC surface receptors CD1D1 (0.5%: + 1.75; 1%: + 2.33) and CD80 (0.5%: +2.45; 1%: +3.00), and the cell signaling molecule MAPK8 (0.5%: +1.87; 1%: +2.35) were significantly up-regulated by YCA at both inclusion rates. In conclusion, feeding YCA may potentially increase recognition and responses to bacterial pathogens and T-cell activation and differentiation and thereby maintain health and prevent production losses. PMID:27033362

  16. Clinical significance of anti-Ro52 (TRIM21) antibodies non-associated with anti-SSA 60kDa antibodies: results of a multicentric study.

    PubMed

    Ghillani, P; André, C; Toly, C; Rouquette, A M; Bengoufa, D; Nicaise, P; Goulvestre, C; Gleizes, A; Dragon-Durey, M A; Alyanakian, M A; Chretien, P; Chollet-Martin, S; Musset, L; Weill, B; Johanet, C

    2011-07-01

    Ro52 antigen has recently been identified as TRIM21 protein, but the clinical significance of anti-Ro52/TRIM21 antibodies remains controversial. The aim of this multicentric study was to investigate the significance of anti-Ro52 antibodies without anti-SSA/Ro60 antibodies in various connective diseases. Sera were selected by each laboratory using its own method (ELISA, immunodot or Luminex technology), and then performed with ANA Screen BioPlex™ reagent (BIO-RAD). Among the 247 screened sera, 155/247 (63%) were confirmed as anti-Ro52 positive and anti-SSA/Ro60 negative. These sera were analyzed for the detection of other antibodies in relation with clinical settings. Isolated anti-Ro52 antibodies were detected in 89/155 (57%) sera. For the remaining sera (66/155), the main antibodies associations were Sm/SmRNP or Chromatin (n=38; 57%), Jo1 (n=17; 26%) and CenpB (n=9; 14%). Clinical data from the 155 patients showed high prevalence in autoimmune diseases (73%) including myositis or dermatomyositis (n=30), lupus (n=23); Sjögren and/or sicca syndrome (n=27); CREST or Systemic sclerosis (n=11) and autoimmune hepatitis (n=11). We found that pulmonary manifestations were often associated with the presence of anti-Ro52 antibodies (n=34, 22%), in addition with anti-tRNA synthetases, anti-SRP or anti-Ku antibodies (18/34) or isolated in half of cases (16/34). Separate detection of anti-Ro52 antibodies might be useful in related antisynthetase syndrome diagnosis. The presence of anti-Ro52 antibodies should probably precede development of autoimmune disease and must induce sequential follow-up of positive patients, particularly in interstitial lung disease progression.

  17. Diplotype Trend Regression Analysis of the ADH Gene Cluster and the ALDH2 Gene: Multiple Significant Associations with Alcohol Dependence

    PubMed Central

    Luo, Xingguang; Kranzler, Henry R.; Zuo, Lingjun; Wang, Shuang; Schork, Nicholas J.; Gelernter, Joel

    2006-01-01

    The set of alcohol-metabolizing enzymes has considerable genetic and functional complexity. The relationships between some alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes and alcohol dependence (AD) have long been studied in many populations, but not comprehensively. In the present study, we genotyped 16 markers within the ADH gene cluster (including the ADH1A, ADH1B, ADH1C, ADH5, ADH6, and ADH7 genes), 4 markers within the ALDH2 gene, and 38 unlinked ancestry-informative markers in a case-control sample of 801 individuals. Associations between markers and disease were analyzed by a Hardy-Weinberg equilibrium (HWE) test, a conventional case-control comparison, a structured association analysis, and a novel diplotype trend regression (DTR) analysis. Finally, the disease alleles were fine mapped by a Hardy-Weinberg disequilibrium (HWD) measure (J). All markers were found to be in HWE in controls, but some markers showed HWD in cases. Genotypes of many markers were associated with AD. DTR analysis showed that ADH5 genotypes and diplotypes of ADH1A, ADH1B, ADH7, and ALDH2 were associated with AD in European Americans and/or African Americans. The risk-influencing alleles were fine mapped from among the markers studied and were found to coincide with some well-known functional variants. We demonstrated that DTR was more powerful than many other conventional association methods. We also found that several ADH genes and the ALDH2 gene were susceptibility loci for AD, and the associations were best explained by several independent risk genes. PMID:16685648

  18. Identification and characterization of a genome-wide significant region associated with red blood cell phenotypes in domestic sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A genome wide association study (GWAS) investigating red blood cell (RBC) phenotypes was performed with over 500 domestic sheep (Ovis aries) from three economically important breeds in the US (Columbia, Polypay, and Rambouillet). A single nucleotide polymorphism (SNP, hereafter the discovery SNP) sh...

  19. Genetic Variants in SDC3 Gene are Significantly Associated with Growth Traits in Two Chinese Beef Cattle Breeds.

    PubMed

    Huang, Yong-Zhen; Wang, Qin; Zhang, Chun-Lei; Fang, Xing-Tang; Song, En-Liang; Chen, Hong

    2016-01-01

    Identification of the genes and polymorphisms underlying quantitative traits, and understanding these genes and polymorphisms affect economic growth traits, are important for successful marker-assisted selection and more efficient management strategies in commercial cattle (Bos taurus) population. Syndecan-3 (SDC3), a member of the syndecan family of type I transmembrane heparan sulfate proteoglycans is a novel regulator of feeding behavior and body weight. The aim of this study is to examine the association of the SDC3 polymorphism with growth traits in Chinese Jiaxian and Qinchuan cattle breeds (). Four single nucleotide polymorphisms (SNPs: 1-4) were detected in 555 cows from three Chinese native cattle breeds by means of sequencing pooled DNA samples and polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) methods. We found one SNP (g.28362A > G) in intron and three SNPs (g.30742T > G, g.30821C > T and 33418 A > G) in exons. The statistical analyses indicated that these SNPs of SDC3 gene were associated with bovine body height, body length, chest circumference, and circumference of cannon bone (P < 0.05). The mutant-type variant was superior for growth traits; the heterozygote was associated with higher growth traits compared to wild-type homozygote. Our result confirms the polymorphisms in the SDC3 gene are associated with growth traits that may be used for marker-assisted selection in beef cattle breeding programs. PMID:27119984

  20. Functional significance of membrane associated proteolysis in the toxicity of Bacillus thuringiensis Cry3Aa toxin against Colorado potato beetle.

    PubMed

    García-Robles, Inmaculada; Ochoa-Campuzano, Camila; Sánchez, Jorge; Contreras, Estefanía; Real, M Dolores; Rausell, Carolina

    2012-11-01

    Bacillus thuringiensis Cry toxins are widely used as biocontrol agents in bioinsecticides and transgenic plants. In the three domain-Cry toxins, domain II has been identified as an important determinant of their highly specific activity against insects. In this work, we assessed the role in membrane associated proteolysis and toxicity in Colorado potato beetle (CPB) of a previously reported ADAM recognition motif present in Cry3Aa toxin domain II. We used site-directed mutagenesis to modify the Bacillus thuringiensis cry3A gene in amino acid residues 344, 346, 347, 351 and 353 of the ADAM recognition motif in Cry3Aa toxin. Cry3Aa toxin mutants displayed decreased toxicity when compared to the wild type toxin and impaired ability to compete CPB brush border membrane associated cleavage of an ADAM fluorogenic substrate. Although the proteolytic profile of Cry3Aa toxin mutants generated by brush border membrane associated proteases was similar to that of Cry3Aa toxin, the metalloprotease inhibitor 1,10-phenanthroline was less efficient on the proteolysis of mutants than on that of the wild type toxin. The relevance of the Cry3Aa-ADAM interaction through the predicted recognition sequence was further confirmed by analyzing the effect of membrane integrity disturbance on Cry3Aa toxin membrane associated proteolysis and CPB larvae toxicity. Data support that Cry3Aa proteolysis, as a result of the interaction with ADAM through the Cry3Aa recognition motif, is essential for Cry3Aa toxic action in CPB. Detailed knowledge of Cry3Aa interaction with CPB midgut membrane should facilitate the development of more effective Bt based products against this devastating pest and other Coleoptera. PMID:22884605

  1. Functional significance of membrane associated proteolysis in the toxicity of Bacillus thuringiensis Cry3Aa toxin against Colorado potato beetle.

    PubMed

    García-Robles, Inmaculada; Ochoa-Campuzano, Camila; Sánchez, Jorge; Contreras, Estefanía; Real, M Dolores; Rausell, Carolina

    2012-11-01

    Bacillus thuringiensis Cry toxins are widely used as biocontrol agents in bioinsecticides and transgenic plants. In the three domain-Cry toxins, domain II has been identified as an important determinant of their highly specific activity against insects. In this work, we assessed the role in membrane associated proteolysis and toxicity in Colorado potato beetle (CPB) of a previously reported ADAM recognition motif present in Cry3Aa toxin domain II. We used site-directed mutagenesis to modify the Bacillus thuringiensis cry3A gene in amino acid residues 344, 346, 347, 351 and 353 of the ADAM recognition motif in Cry3Aa toxin. Cry3Aa toxin mutants displayed decreased toxicity when compared to the wild type toxin and impaired ability to compete CPB brush border membrane associated cleavage of an ADAM fluorogenic substrate. Although the proteolytic profile of Cry3Aa toxin mutants generated by brush border membrane associated proteases was similar to that of Cry3Aa toxin, the metalloprotease inhibitor 1,10-phenanthroline was less efficient on the proteolysis of mutants than on that of the wild type toxin. The relevance of the Cry3Aa-ADAM interaction through the predicted recognition sequence was further confirmed by analyzing the effect of membrane integrity disturbance on Cry3Aa toxin membrane associated proteolysis and CPB larvae toxicity. Data support that Cry3Aa proteolysis, as a result of the interaction with ADAM through the Cry3Aa recognition motif, is essential for Cry3Aa toxic action in CPB. Detailed knowledge of Cry3Aa interaction with CPB midgut membrane should facilitate the development of more effective Bt based products against this devastating pest and other Coleoptera.

  2. Self induced digital pressure associated with significant transient corneal distortions in a pediatric patient – A multi disciplinary approach

    PubMed Central

    Shames, Haya; Goldberg, Sharon; Kahloun, Cyril; Fine, Philip; Gal, Eyal; Rosen, Dov; Goldstein, Jennie; Gordon-Shaag, Ariela

    2013-01-01

    The present case study is of an 8-year old male who was found to have refractive instability due to corneal distortions that were associated with chronic habit of abnormal eye rubbing (CHAR). Psychiatric evaluation and treatment alleviated the CHAR and at the same time refraction stabilized and the cornea resumed a regular shape. Treatment of this case was made possible by close collaboration between the health care professionals caring for this child.

  3. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial

    PubMed Central

    Rule, Simon; Smith, Paul; Johnson, Peter W.M.; Bolam, Simon; Follows, George; Gambell, Joanne; Hillmen, Peter; Jack, Andrew; Johnson, Stephen; Kirkwood, Amy A; Kruger, Anton; Pocock, Christopher; Seymour, John F.; Toncheva, Milena; Walewski, Jan; Linch, David

    2016-01-01

    Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network. PMID:26611473

  4. Presence of anomalous coronary seen on angiogram is not associated with increased risk of significant coronary artery disease.

    PubMed

    Suryanarayana, Prakash; Kollampare, Shubha; Riaz, Irbaz Bin; Lee, Justin; Husnain, Muhammad; Luni, Faraz Khan; Movahed, Mohammad Reza

    2014-12-01

    It is unclear if anomalous coronary arteries are at higher risk for atherosclerosis. The link between anomalous coronary artery and early coronary artery disease has been suggested. The aim of this study is to determine whether the coronary artery anomaly predisposes to development of significant coronary disease. Using retrospective chart review, patients with documented anomalous coronary arteries recognized during coronary angiography between years 2000 to 2007 were analyzed. Prevalence of significant atherosclerotic coronary artery disease (defined as more than 50% luminal narrowing) was compared between normal and anomalous coronaries. A total of 147 patients with anomalous coronary arteries were found. Right coronary artery was the most common anomalous artery 128 of 148 (86.5%) in our dataset. There was no difference in the occurrence of atherosclerosis between anomalous and nonanomalous coronaries. Significant atherosclerosis was present in 59 of the 148 anomalous coronary arteries (37.8%), and 112 of the 293 nonanomalous coronary arteries (38.2%, p = 0.9). On the basis of our study, there is no evidence that anomalous coronary arteries predispose to significant coronary artery disease in comparison to normal coronary arteries.

  5. Addition of aerobic exercise to a weight loss program increases BMD, with an associated reduction in inflammation in overweight postmenopausal women.

    PubMed

    Silverman, Natalie E; Nicklas, Barbara J; Ryan, Alice S

    2009-04-01

    Increased inflammation and weight loss are associated with a reduction in bone mineral density (BMD). Aerobic exercise may minimize the loss of bone and weight loss may contribute to a decrease in cytokines. We tested the hypothesis that aerobic exercise in combination with a weight loss program would decrease circulating concentrations of inflammatory markers, thus mediating changes in BMD. This was a nonrandomized controlled trial. Eighty-six overweight and obese postmenopausal women (50-70 years of age; BMI, 25-40 kg/m(2)) participated in a weight loss (WL; n = 40) or weight loss plus walking (WL + AEX; n = 46) program. Outcome measures included BMD and bone mineral content of the femoral neck and lumbar spine measured by dual energy X-ray absorptiometry, interleukin-6, tumor necrosis factor-alpha, soluble receptors of IL-6, and TNF-alpha (sTNFR1 and sTNFR2; receptors in a subset of the population), VO(2) max, fat mass, and lean mass. Weight decreased in the WL (p < 0.001) and WL + AEX (p < 0.001) groups. VO(2) max increased (p < 0.001) after WL + AEX. There was a 2% increase in femoral neck BMD in the WL + AEX group (p = 0.001), which was significantly different from the WL group. The change in sTNFR1 was significantly associated with the change in femoral neck BMD (p < 0.05). The change in VO(2) max was an independent predictor of the change in femoral neck BMD. Our findings suggest that the addition of aerobic exercise is recommended to decrease inflammation and increase BMD during weight loss in overweight postmenopausal women.

  6. Decreased expression of Beclin-1 is significantly associated with a poor prognosis in oral tongue squamous cell carcinoma

    PubMed Central

    Hu, Zedong; Zhong, Zhaoming; Huang, Shaohui; Wen, Haojie; Chen, Xue; Chu, Hongying; Li, Qiuli; Sun, Chuanzheng

    2016-01-01

    The autophagy-related gene Beclin-1 is critical in the regulation of tumourigenesis and progression, but its role in oral tongue squamous cell carcinoma (OTSCC) has not yet been reported. This study aimed to investigate Beclin-1 expression and its significance in OTSCC. Beclin-1 expression was assessed by reverse transcription-quantitative polymerase chain reaction or western blot analysis in 14 OTSCC tissues and matched adjacent noncancerous tissues as well as in 5 OTSCC cell lines and a normal tongue epithelial cell line. Beclin-1 protein expression was examined by immunohistochemistry in 133 OTSCC specimens, and the correlation between Beclin-1 expression and clinicopathological features was investigated. Furthermore, MTT and colony formation assays were performed to investigate the effect of Beclin-1 on the proliferation and clonogenicity of OTSCC cells. It was demonstrated that Beclin-1 expression was significantly decreased in the majority of the 14 OTSCC tissues and the 5 OTSCC cell lines relative to the matched non-cancerous tissues and the normal tongue epithelial cell line, respectively. Immunohistochemistry analysis revealed that decreased Beclin-1 expression was significantly correlated with poor differentiation, lymph node metastasis, advanced clinical tumour-node-metastasis stage, and a poor prognosis in patients with OTSCC. The in vitro assays indicated that the overexpression of Beclin-1 significantly inhibits the proliferation and clonogenicity of OTSCC cells. These results demonstrate that Beclin-1 acts as a tumour suppressor in the development or progression of OTSCC and that Beclin-1 may represent a novel prognostic marker for patients with OTSCC. PMID:27356955

  7. Activation energy associated with the electromigration of oligosaccharides through viscosity modifier and polymeric additive containing background electrolytes.

    PubMed

    Kerékgyártó, Márta; Járvás, Gábor; Novák, Levente; Guttman, András

    2016-02-01

    The activation energy related to the electromigration of oligosaccharides can be determined from their measured electrophoretic mobilities at different temperatures. The effects of a viscosity modifier (ethylene glycol) and a polymeric additive (linear polyacrylamide) on the electrophoretic mobility of linear sugar oligomers with α1-4 linked glucose units (maltooligosaccharides) were studied in CE using the activation energy concept. The electrophoretic separations of 8-aminopyrene-1,3,6-trisulfonate-labeled maltooligosaccharides were monitored by LIF detection in the temperature range of 20-50°C, using either 0-60% ethylene glycol (viscosity modifier) or 0-3% linear polyacrylamide (polymeric additive) containing BGEs. Activation energy curves were constructed based on the slopes of the Arrhenius plots. With the use of linear polyacrylamide additive, solute size-dependent activation energy variations were found for the maltooligosaccharides with polymerization degrees below and above maltoheptaose (DP 7), probably due to molecular conformation changes and possible matrix interaction effects.

  8. Associations between hurtful weight-related comments by family and significant other and the development of disordered eating behaviors in young adults

    PubMed Central

    Eisenberg, Marla E.; Berge, Jerica M.; Fulkerson, Jayne A.; Neumark-Sztainer, Dianne

    2012-01-01

    Background Research has found that weight-teasing is associated with disordered eating in adolescents. This study expands on the existing research by examining associations between hurtful weight comments by family and a significant other and disordered eating in young adults. Methods Data come from 1,902 young adults (mean age 25) who completed surveys in 1998, 2003 and 2009. Correlations were examined between receiving hurtful comments from family and significant others, and four disordered eating behaviors in young adulthood, adjusting for prior disordered eating and prior teasing. Results Disordered eating behaviors were common in young adulthood, and were associated with hearing hurtful weight-related comments from family members and a significant other, for both females and males. Conclusion Disordered eating prevention activities, which include messages about the potential harm associated with hurtful weight-related comments, should be expanded to address young adults, and programs may want to target relationship partners. PMID:21898148

  9. Love is the triumph of the imagination: Daydreams about significant others are associated with increased happiness, love and connection.

    PubMed

    Poerio, Giulia L; Totterdell, Peter; Emerson, Lisa-Marie; Miles, Eleanor

    2015-05-01

    Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others.

  10. The Longitudinal Transcriptomic Response of the Substantia Nigra to Intrastriatal 6-Hydroxydopamine Reveals Significant Upregulation of Regeneration-Associated Genes

    PubMed Central

    Cole-Strauss, Allyson; Grabinski, Tessa; Mattingly, Zachary R.; Winn, Mary E.; Steece-Collier, Kathy; Sortwell, Caryl E.; Manfredsson, Fredric P.; Lipton, Jack W.

    2015-01-01

    We hypothesized that the study of gene expression at 1, 2, 4, 6 and 16 weeks in the substantia nigra (SN) after intrastriatal 6-OHDA in the Sprague-Dawley rat (rattus norvegicus) would identify cellular responses during the degenerative process that could be axoprotective. Specifically, we hypothesized that genes expressed within the SN that followed a profile of being highly upregulated early after the lesion (during active axonal degeneration) and then progressively declined to baseline over 16 weeks as DA neurons died are indicative of potential protective responses to the striatal 6-OHDA insult. Utilizing a κ-means cluster analysis strategy, we demonstrated that one such cluster followed this hypothesized expression pattern over time, and that this cluster contained several interrelated transcripts that are classified as regeneration-associated genes (RAGs) including Atf3, Sprr1a, Ecel1, Gadd45a, Gpnmb, Sox11, Mmp19, Srgap1, Rab15,Lifr, Trib3, Tgfb1, and Sema3c. All exemplar transcripts tested from this cluster (Sprr1a, Ecel1, Gadd45a, Atf3 and Sox11) were validated by qPCR and a smaller subset (Sprr1a, Gadd45a and Sox11) were shown to be exclusively localized to SN DA neurons using a dual label approach with RNAScope in situ hybridization and immunohistochemistry. Upregulation of RAGs is typically associated with the response to axonal injury in the peripheral nerves and was not previously reported as part of the axodegenerative process for DA neurons of the SN. Interestingly, as part of this cluster, other transcripts were identified based on their expression pattern but without a RAG provenance in the literature. These "RAG-like" transcripts need further characterization to determine if they possess similar functions to or interact with known RAG transcripts. Ultimately, it is hoped that some of the newly identified axodegeneration-reactive transcripts could be exploited as axoprotective therapies in PD and other neurodegenerative diseases. PMID:25992874

  11. Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans.

    PubMed

    Ciubotaru, Irina; Green, Stefan J; Kukreja, Subhash; Barengolts, Elena

    2015-11-01

    The importance of gut microbiota in pathogenesis of diabetes remains unknown. This study investigated the relationship between microbiota and metabolic markers in African American men (AAM) with prediabetes and hypovitaminosis D. The study was ancillary to a randomized trial of vitamin D supplementation with weekly ergocalciferol (50,000 IU) conducted in AAM veterans over 12 months (D Intervention in Veterans Affairs). Glycemic groups (Gr) were characterized based on changes in oral glucose tolerance between baseline and exit. Subjects with stable normal glucose tolerance were assigned to Gr-1 and those with stable prediabetes (impaired glucose tolerance and impaired fasting glucose) to Gr-2. Microbiota composition was analyzed in stool collected at the exit (n = 115) and compared between Gr-1 and Gr-2, as well as between the lowest and highest quartiles of dietary intake of energy and fat, hemoglobin A1c, and serum 25-hydroxyvitamin D (25[OH]D) level. Differences between Gr-1 and Gr-2 included the Bacteroidetes/Firmicutes and Bacteroidales/Clostridia ratios and differences in genera such as Ruminococcus and Dialister. Changes in specific taxa associated with the lowest and highest quartiles of 25(OH)D (eg, Ruminococcus, Roseburia, Blautia, Dorea) were clearly distinct from those of dietary intake (eg, Bacteroides, Bacteroides/Prevotella ratio) or A1c (eg, Faecalibacterium, Catenibacterium, Streptococcus). These findings suggest a novel interaction between microbiota and vitamin D and a role for microbiota in early stages of diabetes development. Although results suggest that specific taxa are associated with glycemic stability over time, a causative relationship between microbiota makeup and dysglycemia is still to be demonstrated. PMID:26209747

  12. Two poplar-associated bacterial isolates induce additive favorable responses in a constructed plant-microbiome system

    DOE PAGES

    Jawdy, Sara S.; Gunter, Lee E.; Engle, Nancy L.; Yang, Zamin Koo; Lu, Tse-Yuan S.; Tschaplinski, Timothy J.; Tuskan, Gerald A.; Doktycz, Mitchel John; Pelletier, Dale A.; Weston, David J.; et al

    2016-04-26

    Here, the biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. In this work we study the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Inoculation individually with either bacterial isolate increased root growth relative to uninoculated controls. Root area, photosynthetic efficiency, gene expression and metabolite expression data in individual and dual inoculated treatments indicate that the effects of these bacteria are unique and additive, suggesting that the function of a microbiome communitymore » may be predicted from the additive functions of the individual members.« less

  13. Lipase catalysis and thiol-Michael addition: a relevant association for the synthesis of new surface-active carbohydrate esters.

    PubMed

    Boyère, Cédric; Favrelle, Audrey; Broze, Guy; Laurent, Pascal; Nott, Katherine; Paquot, Michel; Blecker, Christophe; Jérôme, Christine; Debuigne, Antoine

    2011-10-18

    A novel class of surface-active carbohydrate esters is prepared by a two-step strategy that takes advantage of the selectivity of enzymatic catalysis and the versatility of the thiol-Michael addition reaction. The surfactant performance of the produced aliphatic, fluorinated and silicon based sugar esters are evaluated by surface tension measurements. The novel thiolated mannose, made available in this work, appears as a powerful building block for the incorporation of unprotected sugar moieties into complex molecules.

  14. Two Poplar-Associated Bacterial Isolates Induce Additive Favorable Responses in a Constructed Plant-Microbiome System

    PubMed Central

    Timm, Collin M.; Pelletier, Dale A.; Jawdy, Sara S.; Gunter, Lee E.; Henning, Jeremiah A.; Engle, Nancy; Aufrecht, Jayde; Gee, Emily; Nookaew, Intawat; Yang, Zamin; Lu, Tse-Yuan; Tschaplinski, Timothy J.; Doktycz, Mitchel J.; Tuskan, Gerald A.; Weston, David J.

    2016-01-01

    The biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. The Populus root microbiome is a diverse community that has high abundance of β- and γ-Proteobacteria, both classes which include multiple plant-growth promoting representatives. To understand the contribution of individual microbiome members in a community, we studied the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Both strains increased lateral root formation and root hair production in Arabidopsis plate assays and are predicted to encode for different functions related to growth and plant growth promotion in Populus hosts. Inoculation individually, with either bacterial isolate, increased root growth relative to uninoculated controls, and while root area was increased in mixed inoculation, the interaction term was insignificant indicating additive effects of root phenotype. Complementary data including photosynthetic efficiency, whole-transcriptome gene expression and GC-MS metabolite expression data in individual and mixed inoculated treatments indicate that the effects of these bacterial strains are unique and additive. These results suggest that the function of a microbiome community may be predicted from the additive functions of the individual members. PMID:27200001

  15. Total testosterone and sex hormone-binding globulin are significantly associated with metabolic syndrome in middle-aged and elderly men.

    PubMed

    Chin, K-Y; Ima-Nirwana, S; Mohamed, I N; Aminuddin, A; Ngah, W Z W

    2013-07-01

    Testosterone and sex hormone-binding globulin (SHBG) have been shown to be associated with metabolic syndrome (MS) in men. This study aimed at validating these relationships in a group of middle-aged and elderly men and assessing their strength of association to MS. A cross-sectional study of 332 Malaysian men aged 40 years and above was conducted. The blood of subject was collected under fasting condition for determination of testosterone, SHBG, glucose and lipid levels. Their medical history, smoking and alcohol consumption status, waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. All testosterone and SHBG levels were significantly reduced in MS subjects compared to non-MS subjects (p<0.05). Testosterone and SHBG were correlated significantly with most of the MS indicators without adjustments. In multiple regression analysis, the triglyceride level was the only MS indicator that was significantly, inversely and independently associated with all testosterone measurements and SHBG (p<0.05). Waist circumference was significantly and negatively associated with SHBG level (p<0.05) though not independent of BMI. Total testosterone and SHBG were significantly and inversely associated with the presence of MS. Testosterone and SHBG are potential intervention targets for the prevention of MS in men.

  16. Effects of arginine and other solution additives on the self-association of different surfactants: an investigation at single-molecule resolution.

    PubMed

    Haldar, Shubhasis; Chattopadhyay, Krishnananda

    2011-05-17

    Fluorescence correlation spectroscopy is used to monitor the self-association of SDS and DTAB monomers at single-molecule resolution. Tetramethylrhodamine-5-maleimide (TMR) has been chosen as a probe because rhodamine dyes have been shown to bind surfactant micelles. Correlation functions obtained by FCS experiments have been fit using conventional discrete diffusional component analysis as well as the more recent maximum entropy method (MEM). Hydrodynamic radii calculated from the diffusion time values increase with surfactant concentration as the monomers self-associate. Effects of several solution additives on the self-association property of the surfactants have been studied. Urea and glycerol inhibit self-association, and arginine shows a dual nature. With SDS, arginine favors self-association, and with DTAB, it inhibits micelle formation. We propose surfactant self-association to be a "supersimplified" model of protein aggregation.

  17. The dynamics of the Breccia Museo eruption (Campi Flegrei, Italy) and the significance of spatter clasts associated with lithic breccias

    NASA Astrophysics Data System (ADS)

    Perrotta, Annamaria; Scarpati, Claudio

    1994-02-01

    The Breccia Museo Member is a pyroclastic deposit produced during an eruptive event that occurred in the southwestern sector of Campi Flegrei about 20,000 years ago. Two depositional units divided by a co-ignimbrite ash-fall deposit have been recognized. Facies variations in the deposits resulted from the interaction between the flow and paleomorphology, from the relative abundance of the lithic and juvenile components supplied by the source, and from the variations of the flow regime. The Lower Depositional Unit is a pyroclastic flow deposit characterized by a thick, coarse valley facies laterally grading into a thin, layered and fine-grained overbank facies. These different facies are due to the interaction between a density-stratified flow and topography. The more basal, high-concentration part of the flow was deposited along the axis of the paleovalleys (valley facies), whereas the upper, low-concentration part was deposited on the slopes (overbank facies). Vertical variations of the structures observed in the deposits of the Lower Depositional Unit resulted from flow unsteadiness during emplacement and, hence, on the variations of the suspended load fallout from the low-concentration upper part of the flow to the high-concentration boundary layer. The Upper Depositional Unit, made up of the Breccia, Spatter and Upper Pumice Flow Units, consists of horizons of lithic breccias and coarse welded spatter which thicken into the valleys. They are closely related to a gas-pipe-rich ash and pumice flow deposit. The strongly fines-poor character of the breccias and spatter beds is due to a very rapid segregation of the dense and coarse clasts and to the high rates of gas ascent through the hindered-settling zone in the basal part of the flow. After deposition of the majority of the dense and coarse material, the subsequent high-density depositional system came to rest immediately, thus yielding a pyroclastic flow deposit that is closely associated with the breccia. The

  18. How significant is submarine groundwater discharge and its associated dissolved inorganic carbon in a river-dominated shelf system?

    NASA Astrophysics Data System (ADS)

    Liu, Q.; Dai, M.; Chen, W.; Huh, C.-A.; Wang, G.; Li, Q.; Charette, M. A.

    2012-05-01

    In order to assess the role of submarine groundwater discharge (SGD) and its impact on the carbonate system on the northern South China Sea (NSCS) shelf, we measured seawater concentrations of four radium isotopes 223,224,226,228Ra along with carbonate system parameters in June-July, 2008. Complementary groundwater sampling was conducted in coastal areas in December 2008 and October 2010 to constrain the groundwater end-members. The distribution of Ra isotopes in the NSCS was largely controlled by the Pearl River plume and coastal upwelling. Long-lived Ra isotopes (228Ra and 226Ra) were enriched in the river plume but low in the offshore surface water and subsurface water/upwelling zone. In contrast, short-lived Ra isotopes (224Ra and 223Ra) were elevated in the subsurface water/upwelling zone as well as in the river plume but depleted in the offshore surface water. In order to quantify SGD, we adopted two independent mathematical approaches. Using a three end-member mixing model with total alkalinity (TAlk) and Ra isotopes, we derived a SGD flux into the NSCS shelf of 2.3-3.7 × 108 m3 day-1. Our second approach involved a simple mass balance of 228Ra and 226Ra and resulted in a first order but consistent SGD flux estimate of 2.2-3.7 × 108 m3 day-1. These fluxes were equivalent to 12-21 % of the Pearl River discharge, but the source of the SGD was mostly recirculated seawater. Despite the relatively small SGD volume flow compared to the river, the associated material fluxes were substantial given their elevated concentrations of dissolved inorganic solutes. In this case, dissolved inorganic carbon (DIC) flux through SGD was 153-347 × 109 mol yr-1, or ~23-53 % of the riverine DIC export flux. Our estimates of the groundwater-derived phosphate flux ranged 3-68 × 107 mol yr-1, which may be responsible for new production on the shelf up to 0.3-6.3 mmol C m-2 d-1. This rate of new production would at most consume 11 % of the DIC contribution delivered by SGD. Hence

  19. A genome-wide association study of posttraumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus

    PubMed Central

    Logue, Mark W.; Baldwin, Clinton; Guffanti, Guia; Melista, Efi; Wolf, Erika J.; Reardon, Annemarie F.; Uddin, Monica; Wildman, Derek; Galea, Sandro; Koenen, Karestan C.; Miller, Mark W.

    2012-01-01

    We describe the results of the first genome-wide association study of PTSD performed using trauma-exposed white non-Hispanic participants from a cohort of veterans and their intimate partners (295 cases and 196 controls). Several SNPs yielded evidence of association. One SNP (rs8042149), located in the retinoid-related orphan receptor alpha gene (RORA), reached genome-wide significance. Nominally significant associations were observed for other RORA SNPs in two African American replication samples—one from the veteran cohort (43 cases and 41 controls) and another independent cohort (100 cases and 421 controls). However, only the associated SNP from the veteran African American replication sample survived gene-level multiple testing correction. RORA has been implicated in prior GWAS studies of psychiatric disorders and is known to play an important role in neuroprotection and other behaviorally-relevant processes. This study represents an important step towards identifying the genetic underpinnings of PTSD. PMID:22869035

  20. Surface deformation associated with the 2013 Mw7.7 Balochistan earthquake: Geologic slip rates may significantly underestimate strain release

    NASA Astrophysics Data System (ADS)

    Gold, Ryan; Reitman, Nadine; Briggs, Richard; Barnhart, William; Hayes, Gavin

    2015-04-01

    sections with narrow deformation zones in order to capture the full deformation field. Our results imply that hazard analyses based on geologically-determined fault slip rates (e.g., near-field) should consider the significant and heterogeneous mismatch we document between on- and off-fault coseismic deformation.

  1. Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases

    PubMed Central

    Pei, Wuhong; Xu, Lisha; Varshney, Gaurav K.; Carrington, Blake; Bishop, Kevin; Jones, MaryPat; Huang, Sunny C.; Idol, Jennifer; Pretorius, Pamela R.; Beirl, Alisha; Schimmenti, Lisa A.; Kindt, Katie S.; Sood, Raman; Burgess, Shawn M.

    2016-01-01

    Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis, and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5, and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish. Zebrafish prps1a mutants and prps1a;prps1b double mutants showed similar morphological phenotypes with increasingly severe phenotypes as the number of mutant alleles increased. Phenotypes included smaller eyes and reduced hair cell numbers, consistent with the optic atrophy and hearing impairment observed in human patients. The double mutant also showed abnormal development of primary motor neurons, hair cell innervation, and reduced leukocytes, consistent with the neuropathy and recurrent infection of the human patients possessing the most severe reductions of PRPS1 activity. Further analyses indicated the phenotypes were associated with a prolonged cell cycle likely resulting from reduced nucleotide synthesis and energy production in the mutant embryos. We further demonstrated the phenotypes were caused by delays in the tissues most highly expressing the prps1 genes. PMID:27425195

  2. Serum Sialic Acid Level Is Significantly Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Chinese Population: A Cross-Sectional Study

    PubMed Central

    Lu, Zhenya; Ma, Han; Xu, Chengfu; Shao, Zhou; Cen, Chao; Li, Youming

    2016-01-01

    Background/Aim. To investigate the association between serum sialic acid (SA) levels and nonalcoholic fatty liver disease (NAFLD) in a nonobese Chinese population. Methods. A cross-sectional study was performed among the 5916 adults who took their annual health examinations at International Health Care Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, from December 2013 to November 2014. Results. A total of 693 (11.71%) subjects fulfilled the diagnostic criteria of NAFLD, and NAFLD patients had significantly higher serum SA levels than controls (P < 0.001). The prevalence of NAFLD was positively associated with serum SA levels (P for trend <0.001). Serum sialic acid levels are significantly associated with features of metabolic syndrome (Ps < 0.01). Multivariate logistic regression analysis showed that serum SA level was significantly associated with risk for NAFLD (odds ratio: 1.018, 95%; confidence interval: 1.007–1.030; P = 0.002). Conclusions. Our results suggest for the first time that NAFLD patients had higher serum SA level than controls, and increased serum SA level is significantly associated with risk for NAFLD in a large nonobese Chinese population. PMID:27042666

  3. Administrators' Perceptions of Factors Related to Student Retention at Colleges with a Significant Black Student Enrollment Affiliated with the Association for Biblical Higher Education

    ERIC Educational Resources Information Center

    Wilson, Wesley B.

    2013-01-01

    This study described and explored the factors perceived as relevant to student retention by administrators at colleges and universities with significant Black student populations. The sample was 31 institutions affiliated with the Association for Biblical Higher Education (ABHE) that had Black student enrollment of 20% or more. The study sought to…

  4. Significant association between glycemic status and increased estimated postglomerular resistance in nondiabetic subjects - study of inulin and para-aminohippuric acid clearance in humans.

    PubMed

    Yasumoto, Mari; Tsuda, Akihiro; Ishimura, Eiji; Uedono, Hideki; Ohno, Yoshiteru; Ichii, Mitsuru; Ochi, Akinobu; Nakatani, Shinya; Mori, Katsuhito; Uchida, Junji; Emoto, Masanori; Nakatani, Tatsuya; Inaba, Masaaki

    2015-03-01

    We investigated whether glomerular hemodynamic parameters in nondiabetic subjects, including healthy subjects, are associated with glycemic status indices, by simultaneous measurement of inulin (Cin) and para-aminohippuric acid (CPHA) clearance. Twenty-six subjects (age 49.5 ± 13.3 years; 13 men and 13 women; 14 healthy subjects and 12 subjects with mild proteinuria) were enrolled. Cin and CPAH were measured simultaneously. All 26 subjects were nondiabetics. Estimated preglomerular resistance, estimated postglomerular resistance, and estimated glomerular hydrostatic pressure (Pglo) were calculated according to Gomez' formula. Pglo correlated significantly and positively with hemoglobin A1c (HbA1c) in both healthy subjects (r = 0.532, P = 0.0498) and subjects with mild proteinuria (r = 0.681, P = 0.015). While there was no significant correlation between estimated preglomerular resistance and HbA1c, estimated postglomerular resistance correlated significantly and positively with HbA1c both in healthy subjects (r = 0.643, P = 0.013) and subjects with mild proteinuria (r = 0.589, P = 0.044). Glomerular filtration fraction, estimated Pglo and estimated postglomerular resistance in total subjects were associated significantly with HbA1c after adjustment for age, gender, and body mass index. These results demonstrate that, even in nondiabetic subjects, glycemic status is associated with estimated postglomerular resistance, but not estimated preglomerular resistance. It is suggested that increased estimated postglomerular resistance associated with higher HbA1c levels, even within the normal range, causes increased estimated Pglo, leading to increased FF. Thus, hemodynamic abnormalities associated with higher HbA1c levels may be related to glomerular hypertension, even in nondiabetic subjects.

  5. ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis.

    PubMed

    Al-Rubeaan, Khalid; Siddiqui, Khalid; Saeb, Amr T M; Nazir, Nyla; Al-Naqeb, Dhekra; Al-Qasim, Sara

    2013-05-15

    In this meta-analysis study, SNPs were investigated for their association with type 2 diabetes (T2D) in both Arab and Caucasian ethnicities. A total of 55 SNPs were analyzed, of which 11 fulfilled the selection criteria, and were used for analysis. It was found that TCF7L2 rs7903146 was significantly associated with a pooled OR of 1.155 (95%C.I.=1.059-1.259), p<0.0001 and I(2)=78.30% among the Arab population, whereas among Caucasians, the pooled OR was 1.45 (95%C.I.=1.386-1.516), p<0.0001 and I(2)=77.20%. KCNJ11 rs5219 was significantly associated in both the populations with a pooled OR of 1.176(1.092-1.268), p<0.0001 and I(2)=32.40% in Caucasians and a pooled OR of 1.28(1.111-1.475), p=0.001 among Arabs. The ACE I/D polymorphism was found to be significantly associated with a pooled OR of 1.992 (95%C.I.=1.774-2.236), p<0.0001 and I(2)=83.20% among the Arab population, whereas among Caucasians, the pooled OR was 1.078 (95%C.I.=0.993-1.17), p=0.073 and I(2)=0%. Similarly, MTHFR C677T polymorphism was also found to be significantly associated among Arabs with a pooled OR of 1.924 (95%C.I.=1.606-2.304), p<0.0001 and I(2)=27.20%, whereas among Caucasians, the pooled OR was 0.986 (95%C.I.=0.868-1.122), p=0.835 and I(2)=0%. Meanwhile PPARG-2 Pro12Ala, CDKN2A/2B rs10811661, IGF2BP2 rs4402960, HHEX rs7923837, CDKAL1 rs7754840, EXT2 rs1113132 and SLC30A8 rs13266634 were found to have no significant association with T2D among Arabs. In conclusion, it seems from this study that both Arabs and Caucasians have different SNPs associated with T2D. Moreover, this study sheds light on the profound necessity for further investigations addressing the question of the genetic components of T2D in Arabs.

  6. Association analysis of bitter receptor genes in five isolated populations identifies a significant correlation between TAS2R43 variants and coffee liking.

    PubMed

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M; Pistis, Giorgio; d'Adamo, Pio; Amin, Najaf; d'Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

    2014-01-01

    Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people's health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics.

  7. Association analysis for detecting significant single nucleotide polymorphisms for phosphorus-deficiency tolerance at the seedling stage in soybean [Glycine max (L) Merr].

    PubMed

    Ning, Lihua; Kan, Guizhen; Du, Wenkai; Guo, Shiwei; Wang, Qing; Zhang, Guozheng; Cheng, Hao; Yu, Deyue

    2016-03-01

    Tolerance to low-phosphorus soil is a desirable trait in soybean cultivars. Previous quantitative trait locus (QTL) studies for phosphorus-deficiency tolerance were mainly derived from bi-parental segregating populations and few reports from natural population. The objective of this study was to detect QTLs that regulate phosphorus-deficiency tolerance in soybean using association mapping approach. Phosphorus-deficiency tolerance was evaluated according to five traits (plant shoot height, shoot dry weight, phosphorus concentration, phosphorus acquisition efficiency and use efficiency) comprising a conditional phenotype at the seedling stage. Association mapping of the conditional phenotype detected 19 SNPs including 13 SNPs that were significantly associated with the five traits across two years. A novel cluster of SNPs, including three SNPs that consistently showed significant effects over two years, that associated with more than one trait was detected on chromosome 3. All favorable alleles, which were determined based on the mean of conditional phenotypic values of each trait over the two years, could be pyramided into one cultivar through parental cross combination. The best three cross combinations were predicted with the aim of simultaneously improving phosphorus acquisition efficiency and use efficiency. These results will provide a thorough understanding of the genetic basis of phosphorus deficiency tolerance in soybean.

  8. Association analysis for detecting significant single nucleotide polymorphisms for phosphorus-deficiency tolerance at the seedling stage in soybean [Glycine max (L) Merr.

    PubMed Central

    Ning, Lihua; Kan, Guizhen; Du, Wenkai; Guo, Shiwei; Wang, Qing; Zhang, Guozheng; Cheng, Hao; Yu, Deyue

    2016-01-01

    Tolerance to low-phosphorus soil is a desirable trait in soybean cultivars. Previous quantitative trait locus (QTL) studies for phosphorus-deficiency tolerance were mainly derived from bi-parental segregating populations and few reports from natural population. The objective of this study was to detect QTLs that regulate phosphorus-deficiency tolerance in soybean using association mapping approach. Phosphorus-deficiency tolerance was evaluated according to five traits (plant shoot height, shoot dry weight, phosphorus concentration, phosphorus acquisition efficiency and use efficiency) comprising a conditional phenotype at the seedling stage. Association mapping of the conditional phenotype detected 19 SNPs including 13 SNPs that were significantly associated with the five traits across two years. A novel cluster of SNPs, including three SNPs that consistently showed significant effects over two years, that associated with more than one trait was detected on chromosome 3. All favorable alleles, which were determined based on the mean of conditional phenotypic values of each trait over the two years, could be pyramided into one cultivar through parental cross combination. The best three cross combinations were predicted with the aim of simultaneously improving phosphorus acquisition efficiency and use efficiency. These results will provide a thorough understanding of the genetic basis of phosphorus deficiency tolerance in soybean. PMID:27162491

  9. Genome-wide significant association between a ‘negative mood delusions' dimension in bipolar disorder and genetic variation on chromosome 3q26.1

    PubMed Central

    Meier, S; Mattheisen, M; Vassos, E; Strohmaier, J; Treutlein, J; Josef, F; Breuer, R; Degenhardt, F; Mühleisen, T W; Müller-Myhsok, B; Steffens, M; Schmael, C; McMahon, F J; Kelsoe, John R; Greenwood, Tiffany A; Nievergelt, Caroline M; Barrett, Thomas B; McKinney, Rebecca; Shilling, Paul D; Schork, Nicholas J; Smith, Erin N; Bloss, Cinnamon S; Nurnberger, John; Edenberg, Howard J; Foroud, Tatiana; Koller, Daniel L; Gershon, Elliot S; Liu, Chun-Yu; Badner, Judith A; Scheftner, William; Lawson, William B; Nwulia, Evaristus A; Hipolito, Maria; Coryell, William; Rice, John; Byerley, William; McMahon, Francis; Chen, David TW; Schulze, Thomas G; Berrettini, Wade; Potash, James B; Zandi, Peter P; Mahon, Pamela B; McInnis, Melvin; Craig, David; Szelinger, Szabolcs; Nöthen, M M; Cichon, S; Schulze, T G; Rietschel, M

    2012-01-01

    Research suggests that clinical symptom dimensions may be more useful in delineating the genetics of bipolar disorder (BD) than standard diagnostic models. To date, no study has applied this concept to data from genome-wide association studies (GWAS). We performed a GWAS of factor dimensions in 927 clinically well-characterized BD patients of German ancestry. Rs9875793, which is located in an intergenic region of 3q26.1 and in the vicinity of the solute carrier family 2 (facilitated glucose transporter), member 2 gene (SLC2A2), was significantly associated with the factor analysis-derived dimension ‘negative mood delusions' (n=927; P=4.65 × 10−8, odds ratio (OR)=2.66). This dimension was comprised of the symptoms delusions of poverty, delusions of guilt and nihilistic delusions. In case–control analyses, significant association with the G allele of rs9875793 was only observed in the subgroup of BD patients who displayed symptoms of ‘negative mood delusions' (allelic χ2 model: PG=0.0001, OR=1.92; item present, n=89). Further support for the hypothesis that rs9875793 is associated with BD in patients displaying ‘negative mood delusions' symptom, such as delusions of guilt, was obtained from an European American sample (GAIN/TGEN), which included 1247 BD patients and 1434 controls (PEA=0.028, OR=1.27). PMID:23010768

  10. Genome-wide Association Study and Meta-Analysis Identify ISL1 as Genome-wide Significant Susceptibility Gene for Bladder Exstrophy

    PubMed Central

    Draaken, Markus; Knapp, Michael; Pennimpede, Tracie; Schmidt, Johanna M.; Ebert, Anne-Karolin; Rösch, Wolfgang; Stein, Raimund; Utsch, Boris; Hirsch, Karin; Boemers, Thomas M.; Mangold, Elisabeth; Heilmann, Stefanie; Ludwig, Kerstin U.; Jenetzky, Ekkehart; Zwink, Nadine; Moebus, Susanne; Herrmann, Bernhard G.; Mattheisen, Manuel; Nöthen, Markus M.

    2015-01-01

    The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10−12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region. PMID:25763902

  11. Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy.

    PubMed

    Draaken, Markus; Knapp, Michael; Pennimpede, Tracie; Schmidt, Johanna M; Ebert, Anne-Karolin; Rösch, Wolfgang; Stein, Raimund; Utsch, Boris; Hirsch, Karin; Boemers, Thomas M; Mangold, Elisabeth; Heilmann, Stefanie; Ludwig, Kerstin U; Jenetzky, Ekkehart; Zwink, Nadine; Moebus, Susanne; Herrmann, Bernhard G; Mattheisen, Manuel; Nöthen, Markus M; Ludwig, Michael; Reutter, Heiko

    2015-03-01

    The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10-12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region.

  12. Multidrug resistance-associated protein 2 (MRP2/ABCC2) haplotypes significantly affect the pharmacokinetics of tacrolimus in kidney transplant recipients

    PubMed Central

    Ogasawara, Ken; Chitnis, Shripad D.; Gohh, Reginald Y.; Christians, Uwe; Akhlaghi, Fatemeh

    2013-01-01

    BACKGROUND AND OBJECTIVE Tacrolimus is an immunosuppressive drug used for the prevention of the allograft rejection in the kidney allograft recipients. It exhibits a narrow therapeutic index and a large pharmacokinetic variability. Tacrolimus is mainly metabolized by cytochrome P450 (CYP) 3A4 and 3A5, and effluxed via ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), encoded by ABCB1 gene. The influence of CYP3A5*3 on the pharmacokinetics of tacrolimus has been well characterized. On the other hand, the contribution of polymorphisms in other genes is controversial. In addition, the involvement of other efflux transporter than P-gp in tacrolimus disposition is uncertain. The present study was designed to investigate the effects of genetic polymorphisms of CYP3As and efflux transporters on the pharmacokinetics of tacrolimus. SUBJECTS AND METHODS A total of 500 blood concentrations of tacrolimus from 102 adult stable kidney transplant recipients were included in the analyses. Genetic polymorphisms in CYP3A4 and CYP3A5 genes as well as the genes of efflux transporters including P-gp (ABCB1), multidrug resistance-associated protein (MRP2/ABCC2) and breast cancer resistance protein (BCRP/ABCG2) were genotyped. For ABCC2 gene, haplotypes were determined as follows: H1 (wild type), H2 (1249G>A), H9 (3972C>T) and H12 (−24C>T and 3972C>T). Population pharmacokinetic analysis was performed using nonlinear mixed effects modeling. RESULTS Analyses revealed that CYP3A5 expressers (CYP3A5*1 carriers) and MRP2 high activity group (ABCC2 H2/H2 and H1/H2) decreased the dose-normalized trough concentration of tacrolimus by 2.3-fold (p<0.001) and 1.5-fold (p=0.007), respectively. The pharmacokinetics of tacrolimus was best described using a two-compartment model with first order absorption and an absorption lag time. In the population pharmacokinetic analysis, CYP3A5 expressers and MRP2 high activity groups were identified as the significant covariates for

  13. Expression of proteins associated with adipocyte lipolysis was significantly changed in the adipose tissues of the obese spontaneously hypertensive/NDmcr-cp rat

    PubMed Central

    2014-01-01

    Background The etiology of the metabolic syndrome is complex, and is determined by the interplay of both genetic and environmental factors. The present study was designed to identify genes and proteins in the adipose tissues with altered expression in the spontaneously hypertensive/NIH –corpulent rat, SHR/NDmcr-cp (CP) and to find possible molecular targets associated with the pathogenesis or progression of obesity related to the metabolic syndrome. Methods We extracted RNAs and proteins from the epididymal adipose tissues in CP, SHR/Lean (Lean), and Wistar Kyoto (WKY) rats and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS). Results The results showed different mRNA and protein expression levels in the adipose tissue: oligo DNA microarray identified 33 genes that were significantly (P < 0.01) up-regulated and 17 genes significantly down-regulated in CP compared with WKY and Lean rats at both 6 and 25 weeks of age. The affected genes-proteins were associated with lipolytic enzymes stimulated by peroxisome proliferator-activated receptor (PPAR) signaling. Further analysis using the 2D-DIGE connected with MALDI-TOF/TOF analysis, the expression of monoglyceride lipase (MGLL) was significantly up-regulated and that of carboxylesterase 3 (CES3) was significantly down-regulated in 6- and 25-week-old CP compared with age-matched control (WKY and Lean rats). Conclusions Our results suggest the possible involvement of proteins associated with adipocyte lipolysis in obesity related to the metabolic syndrome. PMID:24468282

  14. The polymorphism interleukin-8 -251A/T is associated with a significantly increased risk of cancers from a meta-analysis.

    PubMed

    Wang, Ziliang; Liu, Yang; Yang, Lina; Yin, Sheng; Zang, Rongyu; Yang, Gong

    2014-07-01

    Emerging evidences show that interleukin-8 (IL-8) has important regulatory functions in tumorigenesis. IL-8 -251A/T is a single nucleotide polymorphism in the promoter region of the IL-8 gene and affects IL-8 production. Analysis of previous studies on the association of -251A/T polymorphism with different cancer types remained to be illustrated. To further assess the effect of -251A/T polymorphism on cancer risks, we performed this meta-analysis, up to November 2013, of 12,917 cases with different cancer types and 17,689 controls from 47 published case-control designed studies. Statistical analyses were performed using STATA 11.0 software. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. ORs with 95 % CIs for IL-8 -251A/T polymorphism and cancer were estimated using fixed- and random-effects models when appropriate. Significantly increased risks were found in overall under the models of A allele vs. T allele, AA vs. TT, and AA vs. AT/TT. Significantly elevated risks were observed in breast cancer under the models of A allele vs. T allele, AT vs. TT, AA/AT vs. TT, and AA vs. AT/TT, and in nasopharyngeal carcinoma under the models of AT vs. TT, AA/AT vs. TT, and AA vs. AT/TT. We found that significantly elevated risks were observed in the Asian population and hospital-based studies in all comparison models. Thus, this meta-analysis indicates that IL-8 -251A/T polymorphism is associated with a significantly increased risk of cancers and may provide evidence-based medical certificate to study the cancer susceptibility.

  15. Synonymous single nucleotide polymorphisms in the MC4R gene that are significantly associated with milk production traits in water buffaloes.

    PubMed

    Deng, T X; Pang, C Y; Liu, M Q; Zhang, C; Liang, X W

    2016-07-14

    Melanocortin-4 receptor (MC4R) is associated with feed intake, growth, fatness, and carcass composition in many domestic animals. The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in MC4R with milk production traits in water buffalo. Eight SNPs were identified by direct polymerase chain reaction sequencing of samples from 18 buffaloes. SNPs were then genotyped using the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) method in 332 buffaloes. Two of eight SNPs were not in Hardy-Weinberg equilibrium. Based on the SNP data, seven haplotypes were constructed. Three SNPs H1 (AGT), H2 (GAT), and H3 (GAC) accounted for 93.0% of the total individuals. Statistical analysis indicated that the SNP g.1104C>T was significantly associated with milk yield, protein, and fat percentage (P < 0.05). In conclusion, these results provide evidence that polymorphisms in the buffalo MC4R gene are associated with milk production traits and might be potential biomarkers for water buffalo breeding.

  16. Synonymous single nucleotide polymorphisms in the MC4R gene that are significantly associated with milk production traits in water buffaloes.

    PubMed

    Deng, T X; Pang, C Y; Liu, M Q; Zhang, C; Liang, X W

    2016-01-01

    Melanocortin-4 receptor (MC4R) is associated with feed intake, growth, fatness, and carcass composition in many domestic animals. The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in MC4R with milk production traits in water buffalo. Eight SNPs were identified by direct polymerase chain reaction sequencing of samples from 18 buffaloes. SNPs were then genotyped using the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) method in 332 buffaloes. Two of eight SNPs were not in Hardy-Weinberg equilibrium. Based on the SNP data, seven haplotypes were constructed. Three SNPs H1 (AGT), H2 (GAT), and H3 (GAC) accounted for 93.0% of the total individuals. Statistical analysis indicated that the SNP g.1104C>T was significantly associated with milk yield, protein, and fat percentage (P < 0.05). In conclusion, these results provide evidence that polymorphisms in the buffalo MC4R gene are associated with milk production traits and might be potential biomarkers for water buffalo breeding. PMID:27420995

  17. Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of high-sensitivity C-reactive protein in apparently healthy Japanese.

    PubMed

    Oda, Eiji; Kawai, Ryu; Aizawa, Yoshifusa

    2012-07-01

    The aim of this study was to investigate the association between leukocyte subtype counts and hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia. Logistic regressions using hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia as a dependent variable and total leukocyte, basophil, eosinophil, neutrophil, lymphocyte, and monocyte counts as an independent variable were calculated adjusting for age, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), smoking, drinking, and physical activity in apparently healthy Japanese men (1,803) and women (1,150). The odds ratio (OR) of hyper-LDL cholesterolemia for total leukocyte, eosinophil, and lymphocyte counts, the OR of hypertriglyceridemia for total leukocyte, eosinophil, neutrophil, and lymphocyte counts, and the OR of hypo-HDL cholesterolemia for total leukocyte, neutrophil, and lymphocyte counts were significant in men, and the OR of hyper-LDL cholesterolemia, for lymphocyte count, and the OR of hypo-HDL cholesterolemia for eosinophil count were significant in women. Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of hs-CRP in apparently healthy Japanese. PMID:21655904

  18. Significant association among the Fas -670 A/G (rs1800682) polymorphism and esophageal cancer, hepatocellular carcinoma, and prostate cancer susceptibility: a meta-analysis.

    PubMed

    Liu, Tao; Zuo, Li; Li, Lin; Yin, Lei; Liang, Kai; Yu, Hongyuan; Ren, Hui; Zhou, Wen; Jing, Hongwei; Liu, Yang; Kong, Chuize

    2014-11-01

    The Fas gene plays a key role in regulation of apoptotic cell death, and corruption of this signaling pathway has been shown to participate in immune escape and tumorgenesis. Single-nucleotide polymorphism in the promoter of Fas gene at position -670 A/G may affect its expression and play an important role in the pathology of many kinds of cancer. The association between Fas -670 A/G polymorphism and cancer risk is still controversial and ambiguous. Therefore, we conducted a meta-analysis of the currently literature to clarify this relationship. We conducted a search in the PubMed, EMbase, CNKI, and WanFang databases, covering all papers published by May 5, 2014. Overall, 59 case-control studies with 17,035 cases and 23,155 controls were retrieved based on the search criteria for cancer susceptibility related to -670 A/G polymorphism in Fas gene. Odds ratios (OR) and 95% confidence intervals (CI) revealed association strengths. Although no significant relationship was detected between Fas -670 A/G polymorphism and whole cancer risk, in the ethnicity subgroup, significant associations were found in three types of cancer: prostate cancer (OR = 1.06, 95% CI = 1.01-1.11 for A-allele vs. G-allele); hepatocellular carcinoma (OR = 0.89, 95% CI = 0.80-0.99 for AG vs. GG); esophageal cancer (OR = 0.95, 95% CI = 0.92-0.99 for AA + AG vs. GG). Moreover, lower cancer risk was found in smokers carried A-allele, when compared to smokers carried the GG genotype. The Fas -670 A/G polymorphism may be associated with esophageal cancer, hepatocellular carcinoma, and prostate cancer susceptibility from our meta-analysis. Studies with larger samples and gene-environment interactions are warranted to understand the role of Fas -670 A/G polymorphism for cancer risk.

  19. Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence.

    PubMed

    Rivero, Guadalupe; Martín-Guerrero, Idoia; de Prado, Elena; Gabilondo, Ane M; Callado, Luis F; García-Sevilla, Jesús A; García-Orad, África; Meana, J Javier

    2016-06-01

    Objectives α2C-adrenoceptors (α2C-AR) are involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism α2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated α2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of α2CDel322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. Methods Post-mortem brain DNA was extracted (n = 516) and genotyping performed by HaeIII restriction endonuclease digestion of PCR products and DNA fragment analysis on capillary sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. Results The frequency of α2CDel322-325-AR in suicide (9%, n = 236) and non-suicide victims (11%, n = 280) was similar. Genotype frequencies for the α2CDel322-325-AR polymorphism in depressed (15%, n = 39) and schizophrenic subjects (18%, n = 39) were higher than in controls (7%, n = 187), but these differences did not reach statistical significance (P = 0.125 and P = 0.063, respectively). A selective and significant association of α2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, n = 35, P = 0.011). Conclusions Our results indicate that α2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for larger genetic associative studies. PMID:27007576

  20. Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence.

    PubMed

    Rivero, Guadalupe; Martín-Guerrero, Idoia; de Prado, Elena; Gabilondo, Ane M; Callado, Luis F; García-Sevilla, Jesús A; García-Orad, África; Meana, J Javier

    2016-06-01

    Objectives α2C-adrenoceptors (α2C-AR) are involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism α2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated α2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of α2CDel322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. Methods Post-mortem brain DNA was extracted (n = 516) and genotyping performed by HaeIII restriction endonuclease digestion of PCR products and DNA fragment analysis on capillary sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. Results The frequency of α2CDel322-325-AR in suicide (9%, n = 236) and non-suicide victims (11%, n = 280) was similar. Genotype frequencies for the α2CDel322-325-AR polymorphism in depressed (15%, n = 39) and schizophrenic subjects (18%, n = 39) were higher than in controls (7%, n = 187), but these differences did not reach statistical significance (P = 0.125 and P = 0.063, respectively). A selective and significant association of α2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, n = 35, P = 0.011). Conclusions Our results indicate that α2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for larger genetic associative studies.

  1. The significant association of Taq1A genotypes in DRD2/ANKK1 with smoking cessation in a large-scale meta-analysis of Caucasian populations

    PubMed Central

    Ma, Y; Wang, M; Yuan, W; Su, K; Li, M D

    2015-01-01

    Although a number of studies have analyzed the relation between the DRD2/ANKK1 gene Taq1A polymorphism and smoking cessation, the results remain controversial. The primary objective of the present study was to determine whether this variant indeed has any effect on smoking cessation. The A1-dominant model that considers A1/* (*=A1 or A2) and A2/A2 as two genotypes and compares their frequencies in current and former smokers was applied. A total of 22 studies with 11 075 subjects were included in the meta-analyses. Considering the potential influence of between-study heterogeneity, we conducted stratified meta-analyses with the Comprehensive Meta-Analysis statistical software (version 2.0). Results based on either cross-sectional or longitudinal studies consistently showed a statistically significant association between Taq1A A1/* genotypes and smoking cessation. Further, a more significant association of the variant with smoking cessation was detected when both types of studies were combined. However, there was marginal evidence of heterogeneity among studies (I2=33.9% P=0.06). By excluding other ethnicities and subjects with cancer, the meta-analysis on the basis of 9487 Caucasians demonstrated that Taq1A A1/* genotypes indeed were significantly associated with smoking cessation under both the fixed- and random-effects models (pooled OR 1.22; 95% CI 1.11–1.34; P=3.9 × 10−5 for both models). No evidence of between-study heterogeneity or publication bias was observed. Thus, we conclude that the polymorphism of Taq1A has an important role in the process of abstaining from smoking, and smokers carrying A2/A2 genotype have a higher likelihood of smoking cessation than those who carry A1/A1 or A1/A2. PMID:26624925

  2. Lack of significant association between type 2 diabetes mellitus with longitudinal change in diurnal salivary cortisol: the multiethnic study of atherosclerosis

    PubMed Central

    Spanakis, Elias K.; Wang, Xu; Sánchez, Brisa N.; Diez Roux, Ana V.; Needham, Belinda L.; Wand, Gary S.; Seeman, Teresa; Golden, Sherita Hill

    2016-01-01

    Cross-sectional association has been shown between type 2 diabetes and hypothalamic–pituitary–adrenal (HPA) axis dysregulation; however, the temporality of this association is unknown. Our aim was to determine if type 2 diabetes is associated with longitudinal change in daily cortisol curve features. We hypothesized that the presence of type 2 diabetes may lead to a more blunted and abnormal HPA axis profile over time, suggestive of increased HPA axis dysregulation. This was a longitudinal cohort study, including 580 community-dwelling individuals (mean age 63.7 ± 9.1 years; 52.8 % women) with (n = 90) and without (n = 490) type 2 diabetes who attended two MultiEthnic Study of Atherosclerosis Stress ancillary study exams separated by 6 years. Outcome measures that were collected were wake-up and bedtime cortisol, cortisol awakening response (CAR), total area under the curve (AUC), and early, late, and overall decline slopes. In univariate analyses, wake-up and AUC increased over 6 years more in persons with as compared to those without type 2 diabetes (11 vs. 7 % increase for wake-up and 17 vs. 11 % for AUC). The early decline slope became flatter over time with a greater flattening observed in diabetic compared to non-diabetic individuals (23 vs. 9 % flatter); however, the change was only statistically significant for wake-up cortisol (p-value: 0.03). Over time, while CAR was reduced more, late decline and overall decline became flatter, and bedtime cortisol increased less in those with as compared to those without type 2 diabetes, none of these changes were statistically significant in adjusted models. We did not identify any statistically significant change in cortisol curve features over 6 years by type 2 diabetes status. PMID:26895003

  3. Association Analysis of Bitter Receptor Genes in Five Isolated Populations Identifies a Significant Correlation between TAS2R43 Variants and Coffee Liking

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M.; Pistis, Giorgio; d’Adamo, Pio; Amin, Najaf; d’Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C.; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

    2014-01-01

    Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people’s health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics. PMID:24647340

  4. Meta-analysis reveals significant association of 3'-UTR VNTR in SLC6A3 with smoking cessation in Caucasian populations.

    PubMed

    Ma, Y; Yuan, W; Cui, W; Li, M D

    2016-02-01

    Many studies have examined the association between SLC6A3 3'-untranslated region (UTR) variable number tandem repeat (VNTR) polymorphism and smoking cessation; however, the results are inconclusive, primarily because of the small-to-moderate size samples. The primary goal of this study was to determine whether this polymorphism has any effect on smoking cessation by a meta-analysis of all reported studies. We adopted a 9-repeat dominant model that considers 9-repeat and non-9-repeat as two genotypes and compared their frequencies in former vs current smokers. Eleven studies with 5480 participants were included. Considering the presence of study heterogeneity and differences in the availability of information from each study, three separate meta-analyses were performed with the Comprehensive Meta-Analysis statistical software (version 2.0). The first meta-analysis provided evidence of association between the 9-repeat genotype and smoking cessation under the fixed-effects model (pooled odds ratio (OR)=1.13; 95% confidence interval (CI)=1.01, 1.27; P=0.037) but not in the random-effects model (pooled OR=1.11; 95% CI=0.96, 1.29; P=0.159). Given the marginal evidence of heterogeneity among studies (P=0.10; I2=35.9%), which likely was caused by inclusion of an Asian population treatment study with an opposite effect of the polymorphism on smoking cessation, we excluded the data of this study, revealing a significant association between the 9-repeat genotype and smoking cessation under both the fixed- and random-effects models (pooled OR=1.15; 95% CI=1.02, 1.29; P=0.02 for both models). By analyzing adjusted and unadjusted results, we performed the third meta-analysis, which showed consistently that the 9-repeat genotype was significantly associated with smoking cessation under both the fixed- and random-effects models (pooled OR=1.17; 95% CI=1.04, 1.31; P=0.009 for both models). We conclude that the 3'-UTR VNTR polymorphism is significantly associated with smoking

  5. High Malnutrition Rate in Venezuelan Yanomami Compared to Warao Amerindians and Creoles: Significant Associations WITH Intestinal Parasites and Anemia

    PubMed Central

    Verhagen, Lilly M.; Incani, Renzo N.; Franco, Carolina R.; Ugarte, Alejandra; Cadenas, Yeneska; Sierra Ruiz, Carmen I.; Hermans, Peter W. M.; Hoek, Denise; Campos Ponce, Maiza; de Waard, Jacobus H.; Pinelli, Elena

    2013-01-01

    Background Children in rural areas experience the interrelated problems of poor growth, anemia and parasitic infections. We investigated the prevalence of and associations between intestinal helminth and protozoan infections, malnutrition and anemia in school-age Venezuelan children. Methods This cross-sectional study was conducted in 390 children aged 4-16 years from three rural areas of Venezuela: the Amazon Region, Orinoco Delta and Carabobo State. Stool samples were collected for direct parasitic examinations. Anthropometric indicators of chronic (height-for-age Z score) and acute (weight-for-height and Body Mass Index (BMI)-for-age Z score in respectively children under 5 years of age and children aged 5 years and above) malnutrition were calculated. Multivariate linear and logistic regression models were built to determine factors associated with nutritional status and polyparasitism. Results Hookworm and Strongyloides stercoralis prevalences were highest in children from the Amazon rainforest (respectively 72% and 18%) while children from the Orinoco Delta and Carabobo State showed higher rates of Ascaris lumbricoides (respectively 28% and 37%) and Trichuris trichiura (40% in both regions). The prevalence of Giardia lamblia infection was not significantly different between regions (average: 18%). Anemia prevalence was highest in the Amazon Region (24%). Hemoglobin levels were significantly decreased in children with a hookworm infection. Malnutrition was present in respectively 84%, 30% and 13% of children from the Amazon Region, Orinoco Delta and Carabobo State. In multivariate analysis including all regions, G. lamblia and helminth infections were significantly and negatively associated with respectively height-for-age and weight-for-height/BMI-for-age Z scores. Furthermore, hemoglobin levels were positively associated with the height-for-age Z score (0.11, 95% CI 0.02 - 0.20). Conclusions In rural populations in Venezuela helminthiasis and giardiasis were

  6. Treatment-influenced associations of PML-RARα mutations, FLT3 mutations, and additional chromosome abnormalities in relapsed acute promyelocytic leukemia

    PubMed Central

    Moser, Barry K.; Racevskis, Janis; Poiré, Xavier; Bloomfield, Clara D.; Carroll, Andrew J.; Ketterling, Rhett P.; Roulston, Diane; Schachter-Tokarz, Esther; Zhou, Da-cheng; Chen, I-Ming L.; Harvey, Richard; Koval, Greg; Sher, Dorie A.; Feusner, James H.; Tallman, Martin S.; Larson, Richard A.; Powell, Bayard L.; Appelbaum, Frederick R.; Paietta, Elisabeth; Willman, Cheryl L.; Stock, Wendy

    2012-01-01

    Mutations in the all-trans retinoic acid (ATRA)–targeted ligand binding domain of PML-RARα (PRα/LBD+) have been implicated in the passive selection of ATRA-resistant acute promyelocytic leukemia clones leading to disease relapse. Among 45 relapse patients from the ATRA/chemotherapy arm of intergroup protocol C9710, 18 patients harbored PRα/LBD+ (40%), 7 of whom (39%) relapsed Off-ATRA selection pressure, suggesting a possible active role of PRα/LBD+. Of 41 relapse patients coanalyzed, 15 (37%) had FMS-related tyrosine kinase 3 internal tandem duplication mutations (FLT3-ITD+), which were differentially associated with PRα/LBD+ depending on ATRA treatment status at relapse: positively, On-ATRA; negatively, Off-ATRA. Thirteen of 21 patients (62%) had additional chromosome abnormalities (ACAs); all coanalyzed PRα/LBD mutant patients who relapsed off-ATRA (n = 5) had associated ACA. After relapse Off-ATRA, ACA and FLT3-ITD+ were negatively associated and were oppositely associated with presenting white blood count and PML-RARα type: ACA, low, L-isoform; FLT3-ITD+, high, S-isoform. These exploratory results suggest that differing PRα/LBD+ activities may interact with FLT3-ITD+ or ACA, that FLT3-ITD+ and ACA are associated with different intrinsic disease progression pathways manifest at relapse Off-ATRA, and that these different pathways may be short-circuited by ATRA-selectable defects at relapse On-ATRA. ACA and certain PRα/LBD+ were also associated with reduced postrelapse survival. PMID:22734072

  7. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  8. Serum osteocalcin is associated with dietary vitamin D, body weight and serum magnesium in postmenopausal women with and without significant coronary artery disease.

    PubMed

    Alissa, Eman M; Alnahdi, Wafa A; Alama, Nabeel; Ferns, Gordon A

    2014-01-01

    Osteoporosis and atherosclerosis often present atypically in postmenopausal women, making clinical recognition difficult. Prospective studies suggest independent associations between bone mass and vascular calcification through vitamin D deficiency as an established predictor of both conditions. We aimed to examine the relationship between serum osteocalcin and vitamin D status in postmenopausal women with and without angiographic evidence of coronary artery disease (CAD). One hundred and eighty postmenopausal women undergoing coronary angiography were selected sequentially from the Catheterization unit of King Abdulaziz University Hospital. Socio-demographic, anthropometric parameters and dietary habits were measured. Biochemical variables were estimated in blood samples. Half of the postmenopausal women did not have significant CAD, 24% had significant CAD in a single and/or double coronary vessels, 26% had significant CAD in three coronary vessels. Mean serum vitamin D concentrations showed that vitamin D deficiency was a common finding in the whole population. Vitamin D and calcium intakes were uniformly low in the study cohort. Serum osteocalcin was significantly correlated with dietary vitamin D in all subgroups (r=-0.172, p<0.05) and positively correlated among the patients (r=0.269, p=0.01). Serum magnesium, alkaline phosphatase, dietary vitamin D, and body weight were independent variables of serum osteocalcin level. In conclusion, elevated levels of serum C reactive protein and vitamin D were associated with low serum osteocalcin levels. Therefore, osteocalcin may be a potential cardiovascular risk marker. However, further studies are needed to clarify the pathophysiological processes underlying the relationship between serum osteocalcin level and atherosclerosis parameters.

  9. Food Additives and Hyperkinesis

    ERIC Educational Resources Information Center

    Wender, Ester H.

    1977-01-01

    The hypothesis that food additives are causally associated with hyperkinesis and learning disabilities in children is reviewed, and available data are summarized. Available from: American Medical Association 535 North Dearborn Street Chicago, Illinois 60610. (JG)

  10. Quantitative-trait homozygosity and association mapping and empirical genomewide significance in large, complex pedigrees: fasting serum-insulin level in the Hutterites.

    PubMed

    Abney, Mark; Ober, Carole; McPeek, Mary Sara

    2002-04-01

    We present methods for linkage and association mapping of quantitative traits for a founder population with a large, known genealogy. We detect linkage to quantitative-trait loci (QTLs) through a multipoint homozygosity-mapping method. We propose two association methods, one of which is single point and uses a general two-allele model and the other of which is multipoint and uses homozygosity by descent for a particular allele. In all three methods, we make extensive use of the pedigree and genotype information, while keeping the computations simple and efficient. To assess significance, we have developed a permutation-based test that takes into account the covariance structure due to relatedness of individuals and can be used to determine empirical genomewide and locus-specific P values. In the case of multivariate-normally distributed trait data, the permutation-based test is asymptotically exact. The test is broadly applicable to a variety of mapping methods that fall within the class of linear statistical models (e.g., variance-component methods), under the assumption of random ascertainment with respect to the phenotype. For obtaining genomewide P values, our proposed method is appropriate when positions of markers are independent of the observed linkage signal, under the null hypothesis. We apply our methods to a genome screen for fasting insulin level in the Hutterites. We detect significant genomewide linkage on chromosome 19 and suggestive evidence of QTLs on chromosomes 1 and 16.

  11. Prognostic significance of L1CAM expression and its association with mutant p53 expression in high-risk endometrial cancer.

    PubMed

    Van Gool, Inge C; Stelloo, Ellen; Nout, Remi A; Nijman, Hans W; Edmondson, Richard J; Church, David N; MacKay, Helen J; Leary, Alexandra; Powell, Melanie E; Mileshkin, Linda; Creutzberg, Carien L; Smit, Vincent T H B M; Bosse, Tjalling

    2016-02-01

    Studies in early-stage, predominantly low- and intermediate-risk endometrial cancer have demonstrated that L1 cell adhesion molecule (L1CAM) overexpression identifies patients at increased risk of recurrence, yet its prognostic significance in high-risk endometrial cancer is unclear. To evaluate this, its frequency, and the relationship of L1CAM with the established endometrial cancer biomarker p53, we analyzed the expression of both markers by immunohistochemistry in a pilot series of 116 endometrial cancers (86 endometrioid, 30 non-endometrioid subtype) with high-risk features (such as high tumor grade and deep myometrial invasion) and correlated results with clinical outcome. We used The Cancer Genome Atlas (TCGA) endometrial cancer series to validate our findings. Using the previously reported cutoff of 10% positive staining, 51/116 (44%) tumors were classified as L1CAM-positive, with no significant association between L1CAM positivity and the rate of distant metastasis (P=0.195). However, increasing the threshold for L1CAM positivity to 50% resulted in a reduction of the frequency of L1CAM-positive tumors to 24% (28/116), and a significant association with the rate of distant metastasis (P=0.018). L1CAM expression was strongly associated with mutant p53 in the high-risk and TCGA series (P<0.001), although a substantial fraction (36% of endometrioid, 10% of non-endometrioid morphology) of p53-mutant endometrial cancers displayed <10% L1CAM positivity. Moreover, 30% of p53-wild-type non-endometrioid endometrial cancers demonstrated diffuse L1CAM staining, suggesting p53-independent mechanisms of L1CAM overexpression. In conclusion, the previously proposed threshold for L1CAM positivity of >10% does not predict prognosis in high-risk endometrial cancer, whereas an alternative threshold (>50%) does. L1CAM expression is strongly, but not universally, associated with mutant p53, and may be strong enough for clinical implementation as prognostic marker in combination

  12. Expression of FoxM1 and the EMT-associated protein E-cadherin in gastric cancer and its clinical significance

    PubMed Central

    Zhang, Jing; Chen, Xiao-Yu; Huang, Ke-Jian; Wu, Wei-Dong; Jiang, Tao; Cao, Jun; Zhou, Li-Sheng; Qiu, Zheng-Jun; Huang, Chen

    2016-01-01

    The aim of the present study was to investigate the expression of forkhead box M1 (FoxM1) and E-cadherin in tissues of gastric cancer in order to reveal any correlation between FoxM1, E-cadherin and clinicopathological parameters. The association between FoxM1 and E-cadherin in the development and progression of gastric cancer was also investigated. The expression of FoxM1 and E-cadherin in gastric cancer and adjacent normal tissue on tissue microarray was detected using immunohistochemistry. The clinicopathological significance of FoxM1 and E-cadherin in gastric cancer was explored, and the association between FoxM1 and E-cadherin was further examined using statistical techniques. In gastric cancer tissues, the expression of FoxM1 and E-cadherin was strongly positive, but it was weak in normal gastric mucosa. Overexpression of FoxM1 was evident in gastric cancer, and was associated with poor tumor differentiation (P<0.05), advanced tumor state (P<0.05) and lymph node (or distant) metastasis (P<0.05), whereas E-cadherin had the opposite effects. Furthermore, the correlation between FoxM1 and E-cadherin expression in gastric cancer tissue was negative. In conclusion, the high FoxM1 expression and low E-cadherin expression in gastric cancer tissue suggests that these proteins play a critical role in the development and progression of gastric cancer.

  13. The association of HMGB1 expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma: a meta-analysis and literature review

    PubMed Central

    Zhang, Xiaoli; Yu, Jinming; Li, Minghuan; Zhu, Hui; Sun, Xindong; Kong, Li

    2016-01-01

    Background The association of high mobility group box 1 (HMGB1) expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma (CRC) remains controversial. The purpose of this study was to conduct a meta-analysis and literature review to identify the role of HMGB1 in the development and prognosis of CRC in Asians. Methods All eligible studies regarding the association between HMGB1 expression in tissue with clinicopathological significance and prognosis in Asian patients with CRC published up to January 2015 were identified by searching PubMed, Web of Science, Chinese National Knowledge Infrastructure, and WanFang database. Analysis of pooled data was performed, while odds ratio (OR) or hazard radio with 95% confidence interval (CI) was calculated and summarized to evaluate the strength of this association in fixed- or random-effects model. Results The expression level of HMGB1 in CRC tissues was much higher than normal colorectal tissues (OR =27.35, 95% CI 9.32–80.26, P<0.0001) and para-tumor colorectal tissues (OR =10.06, 95% CI 4.61–21.95, P<0.0001). There was no relation between the HMGB1 expression and sex, age, clinical T stage, tumor size, and location (colon or rectum cancer). However, a significant relation was detected between the HMGB1 expression and clinical stage (American Joint Committee on Cancer 7), lymph node metastasis, distant metastasis, tumor invasion depth, and differentiation rate (P=0.002, P≤0.0001, P<0.0001, P<0.0001, and P=0.007, respectively). Patients with higher HMGB1 expression had shorter overall survival time, whereas patients with lower level of HMGB1 had better survival (hazard ratio =1.40, 95% CI 0.98–1.82, P<0.0001). Conclusion In this meta-analysis, our results illustrated the significant relationship of HMGB1 protein overexpression in tissues with clinicopathological characteristics and prognosis of CRC. Thus, HMGB1 may be a promising marker in predicting the clinical outcome

  14. Prognostic Significance of Anti-Aminoacyl-tRNA Synthetase Antibodies in Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease: A Retrospective Case Control Study

    PubMed Central

    Hozumi, Hironao; Enomoto, Noriyuki; Kono, Masato; Fujisawa, Tomoyuki; Inui, Naoki; Nakamura, Yutaro; Sumikawa, Hiromitsu; Johkoh, Takeshi; Nakashima, Ran; Imura, Yoshitaka; Mimori, Tsuneyo; Suda, Takafumi

    2015-01-01

    Background In polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established. Objective We aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients. Methods Forty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group). Results Anti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, P = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, P = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08–0.80; P = 0.01). Conclusions The presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD. PMID:25789468

  15. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

    PubMed Central

    Zeggini, Eleftheria; Scott, Laura J.; Saxena, Richa; Voight, Benjamin F.; Marchini, Jonathan L; Hu, Tainle; de Bakker, Paul IW; Abecasis, Gonçalo R; Almgren, Peter; Andersen, Gitte; Ardlie, Kristin; Boström, Kristina Bengtsson; Bergman, Richard N; Bonnycastle, Lori L; Borch-Johnsen, Knut; Burtt, Noël P; Chen, Hong; Chines, Peter S; Daly, Mark J; Deodhar, Parimal; Ding, Charles; Doney, Alex S F; Duren, William L; Elliott, Katherine S; Erdos, Michael R; Frayling, Timothy M; Freathy, Rachel M; Gianniny, Lauren; Grallert, Harald; Grarup, Niels; Groves, Christopher J; Guiducci, Candace; Hansen, Torben; Herder, Christian; Hitman, Graham A; Hughes, Thomas E; Isomaa, Bo; Jackson, Anne U; Jørgensen, Torben; Kong, Augustine; Kubalanza, Kari; Kuruvilla, Finny G; Kuusisto, Johanna; Langenberg, Claudia; Lango, Hana; Lauritzen, Torsten; Li, Yun; Lindgren, Cecilia M; Lyssenko, Valeriya; Marvelle, Amanda F; Meisinger, Christa; Midthjell, Kristian; Mohlke, Karen L; Morken, Mario A; Morris, Andrew D; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Palmer, Colin NA; Payne, Felicity; Perry, John RB; Pettersen, Elin; Platou, Carl; Prokopenko, Inga; Qi, Lu; Qin, Li; Rayner, Nigel W; Rees, Matthew; Roix, Jeffrey J; Sandbæk, Anelli; Shields, Beverley; Sjögren, Marketa; Steinthorsdottir, Valgerdur; Stringham, Heather M; Swift, Amy J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Timpson, Nicholas J; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Walker, Mark; Watanabe, Richard M; Weedon, Michael N; Willer, Cristen J; Illig, Thomas; Hveem, Kristian; Hu, Frank B; Laakso, Markku; Stefansson, Kari; Pedersen, Oluf; Wareham, Nicholas J; Barroso, Inês; Hattersley, Andrew T; Collins, Francis S; Groop, Leif; McCarthy, Mark I; Boehnke, Michael; Altshuler, David

    2009-01-01

    Genome-wide association (GWA) studies have identified multiple new genomic loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)1-11. Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to discover loci at which common alleles have modest effects, we performed meta-analysis of three T2D GWA scans encompassing 10,128 individuals of European-descent and ~2.2 million SNPs (directly genotyped and imputed). Replication testing was performed in an independent sample with an effective sample size of up to 53,975. At least six new loci with robust evidence for association were detected, including the JAZF1 (p=5.0×10−14), CDC123/CAMK1D (p=1.2×10−10), TSPAN8/LGR5 (p=1.1×10−9), THADA (p=1.1×10−9), ADAMTS9 (p=1.2×10−8), and NOTCH2 (p=4.1×10−8) gene regions. The large number of loci with relatively small effects indicates the value of large discovery and follow-up samples in identifying additional clues about the inherited basis of T2D. PMID:18372903

  16. A Putatively Functional Polymorphism in the HTR2C Gene is Associated with Depressive Symptoms in White Females Reporting Significant Life Stress

    PubMed Central

    Brummett, Beverly H.; Babyak, Michael A.; Williams, Redford B.; Harris, Kathleen Mullan; Jiang, Rong; Kraus, William E.; Singh, Abanish; Costa, Paul T.; Georgiades, Anastasia; Siegler, Ilene C.

    2014-01-01

    Psychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys), is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366) and White women (N = 2,712) in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022) but not for men (p = .471). Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress. PMID:25514629

  17. The Functional SNPs in the 5’ Regulatory Region of the Porcine PPARD Gene Have Significant Association with Fat Deposition Traits

    PubMed Central

    Hu, Shanyao; Lin, Bin; Yan, Dechao; Xu, Zaiyan; Zhang, Zijun; Mao, Yuanliang; Mao, Huimin; Wang, Litong; Wang, Guoshui; Xiong, Yuanzhu; Zuo, Bo

    2015-01-01

    Peroxisome proliferator-activated receptor delta (PPARD) is a key regulator of lipid metabolism, insulin sensitivity, cell proliferation and differentiation. In this study, we identified two Single Nucleotide Polymorphisms (SNPs, g.1015 A>G and g.1018 T>C) constituting four haplotypes (GT, GC, AC and AT) in the 5’ regulatory region of porcine PPARD gene. Functional analysis of the four haplotypes showed that the transcriptional activity of the PPARD promoter fragment carrying haplotype AC was significantly lower than that of the other haplotypes in 3T3-L1, C2C12 and PK-15 cells, and haplotype AC had the lowest binding capacities to the nuclear extracts. Transcription factor 7-like 2 (TCF7L2) enhanced the transcription activities of promoter fragments of PPARD gene carrying haplotypes GT, GC and AT in C2C12 and 3T3-L1 cells, and increased the protein expression of PPARD gene in C2C12 myoblasts. TCF7L2 differentially bound to the four haplotypes, and the binding capacity of TCF7L2 to haplotype AC was the lowest. There were significant associations between -655A/G and fat deposition traits in three pig populations including the Large White × Meishan F2 pigs, France and American Large White pigs. Pigs with genotype GG had significantly higher expression of PPARD at both mRNA and protein level than those with genotype AG. These results strongly suggested that the SNPs in 5’ regulatory region of PPARD genes had significant impact on pig fat deposition traits. PMID:26599230

  18. Homozygosis for (12) CA repeats in the first intron of the human IFN-gamma gene is significantly associated with the risk of aplastic anaemia in Caucasian population.

    PubMed

    Dufour, Carlo; Capasso, Mario; Svahn, Johanna; Marrone, Agnese; Haupt, Riccardo; Bacigalupo, Andrea; Giordani, Lucia; Longoni, Daniela; Pillon, Marta; Pistorio, Angela; Di Michele, Paola; Iori, Anna Paola; Pongiglione, Carola; Lanciotti, Marina; Iolascon, Achille

    2004-09-01

    Interferon-gamma (IFN-gamma) mediates the final damage of the stem cell compartment in Aplastic Anaemia (AA). Normal subjects homozygous for 12 (CA) repeats of polymorphism variable number of dinucleotide (CA) repeat (VNDR) in position 1349 of the IFN-gamma gene (IFNG) were shown to overproduce IFN-gammain vitro. We studied the distribution of polymorphism VNDR 1349 of IFNG in 67 Caucasian AA patients and in normal controls. Genotype (CA)12-12, (homozygosis for allele 2) and the single allele 12 were significantly more frequent (P = 0.005 and 0.004 respectively) in patients versus controls. The polymorphism was equally distributed in AA patients regardless of their response to immunosuppression. Homozygosity for 12 (CA) repeats of polymorphism VNDR 1349 of IFNG is strongly associated with the risk of AA in Caucasian subjects.

  19. Significant Association Between Fc Receptor-Like 3 Polymorphisms (-1901A>G and -658C>T) and Neuromyelitis Optica (NMO) Susceptibility in the Chinese Population.

    PubMed

    Wang, Xinling; Yu, Tao; Yan, Qichang; Wang, Wei; Meng, Nan; Li, Xuejiao; Luo, Yahong

    2016-01-01

    Neuromyelitis optica (NMO) is an autoimmune disorder. In pathogenesis, NMO-immunoglobulin G (NMO-IgG) selectively binds to aquaporin-4 (AQP4) and resulted in neuritis, myelitis, and brain lesion. Fc receptor-like 3 (FCRL3) gene encodes a member of the immunoglobulin receptor superfamily, which plays an important part in regulating immune activities. This study aimed at investigating the association between FCRL3 polymorphisms and NMO susceptibility and, hopefully, to contribute to the development of novel methods for diagnosis and treatment of NMO. We selected 150 NMO patients and 300 healthy controls from the Chinese population. Tag single nucleotide polymorphisms (SNPs) were identified with reference to CBI-dbSNP and HapMap databases. DNA were extracted and amplified. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was applied to determine the polymorphisms. χ (2), odds ratio (OR), and 95 % confidence interval (95 % CI) were presented to evaluate genotype distribution and association between SNPs and NMO susceptibility. Six out of 15 SNPs were selected according to the filter. No significant altered genotype distribution was observed concerning -11G>C, -166C>T, -219G>C, and -1629C>G polymorphisms. The G allele of -1901A>G variation was demonstrated to be more frequent in patients compared with controls (P < 0.001). The T allele of -658C>T polymorphism was significantly more prevalent in NMO patients than controls (P = 0.009). In summary, the study revealed that the G allele in -1901A>G polymorphism and T allele in -658C>T polymorphism are genetic risk factors for NMO in the Chinese population. Further research is needed to account for different ethnicities and clarify the mechanisms behind, which might contribute to the elucidation of novel diagnosis methods.

  20. Single nucleotide polymorphism (SNP) analysis demonstrates a significant association of tumour necrosis factor-alpha (TNFA) with primary immune thrombocytopenia among Caucasian adults.

    PubMed

    Sarpatwari, Ameet; Bussel, James B; Ahmed, Momin; Erqou, Sebhat; Semple, John W; Newland, Adrian C; Bennett, Dimitri; Pharoah, Paul; Provan, Drew

    2011-07-01

    T-helper 1 polarization in patients with primary immune thrombocytopenia (ITP) is well documented. However, the genetic contribution to this imbalance remains unclear. To address this question, we selected six candidate single nucleotide polymorphisms within cytokine or cytokine receptor genes for association testing among Caucasian adults. Patients from the United Kingdom Adult ITP Registry were gender-matched (1:3) with healthy controls from the Wellcome Trust Case Control Consortium. Variants IL10 -819 c>t, TNFA -308 g>a, TGFB1 -509 c>t, IL1A -889 c>t, IL10 -592 c>t, and IL4R q576r were measured in cases and retrieved for controls from the European Genome-phenome Archive. Associations were evaluated using logistic regression models. In total, 206 patients with primary ITP were matched with 618 controls. A significant per allele odds ratio of 1·34 (95% confidence interval, 1·03-1·75; P = 0·03) was observed for TNFA -308 g>a, implicating an increased disease susceptibility among Caucasian carriers of the rare allele.

  1. GxE Interactions between FOXO Genotypes and Tea Drinking Are Significantly Associated with Cognitive Disability at Advanced Ages in China

    PubMed Central

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Feng, Lei; Nie, Chao; Cheng, Lingguo; Li, Yang; Tao, Wei; Gu, Jun; Land, Kenneth C.; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Yang, Huanming; Hauser, Elizabeth; Willcox, D. Craig; Willcox, Bradley J.; Tian, Xiao-Li; Vaupel, James W.

    2015-01-01

    Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles. PMID:24895270

  2. GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Feng, Lei; Nie, Chao; Cheng, Lingguo; Li, Yang; Tao, Wei; Gu, Jun; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Yang, Huanming; Hauser, Elizabeth; Willcox, D Craig; Willcox, Bradley J; Tian, Xiao-Li; Vaupel, James W

    2015-04-01

    Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles.

  3. GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Feng, Lei; Nie, Chao; Cheng, Lingguo; Li, Yang; Tao, Wei; Gu, Jun; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Yang, Huanming; Hauser, Elizabeth; Willcox, D Craig; Willcox, Bradley J; Tian, Xiao-Li; Vaupel, James W

    2015-04-01

    Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles. PMID:24895270

  4. The need for annual echocardiography to detect cabergoline-associated valvulopathy in patients with prolactinoma: a systematic review and additional clinical data.

    PubMed

    Caputo, Carmela; Prior, David; Inder, Warrick J

    2015-11-01

    Present recommendations by the US Food and Drug Administration advise that patients with prolactinoma treated with cabergoline should have an annual echocardiogram to screen for valvular heart disease. Here, we present new clinical data and a systematic review of the scientific literature showing that the prevalence of cabergoline-associated valvulopathy is very low. We prospectively assessed 40 patients with prolactinoma taking cabergoline. Cardiovascular examination before echocardiography detected an audible systolic murmur in 10% of cases (all were functional murmurs), and no clinically significant valvular lesion was shown on echocardiogram in the 90% of patients without a murmur. Our systematic review identified 21 studies that assessed the presence of valvular abnormalities in patients with prolactinoma treated with cabergoline. Including our new clinical data, only two (0·11%) of 1811 patients were confirmed to have cabergoline-associated valvulopathy (three [0·17%] if possible cases were included). The probability of clinically significant valvular heart disease is low in the absence of a murmur. On the basis of these findings, we challenge the present recommendations to do routine echocardiography in all patients taking cabergoline for prolactinoma every 12 months. We propose that such patients should be screened by a clinical cardiovascular examination and that echocardiogram should be reserved for those patients with an audible murmur, those treated for more than 5 years at a dose of more than 3 mg per week, or those who maintain cabergoline treatment after the age of 50 years.

  5. Association Between Single-Nucleotide Polymorphisms in Hormone Metabolism and DNA Repair Genes and Epithelial Ovarian Cancer: Results from Two Australian Studies and an Additional Validation Set

    PubMed Central

    Beesley, Jonathan; Jordan, Susan J.; Spurdle, Amanda B.; Song, Honglin; Ramus, Susan J.; Kjaer, Suzanne Kruger; Hogdall, Estrid; DiCioccio, Richard A.; McGuire, Valerie; Whittemore, Alice S.; Gayther, Simon A.; Pharoah, Paul D.P.; Webb, Penelope M.; Chenevix-Trench, Georgia

    2009-01-01

    Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then genotyped another SNP in this gene (rs632148; r2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition. PMID:18086758

  6. Additive and epistatic genome-wide association for growth and ultrasound scan measures of carcass-related traits in Brahman cattle.

    PubMed

    Ali, A A; Khatkar, M S; Kadarmideen, H N; Thomson, P C

    2015-04-01

    Genome-wide association studies are routinely used to identify genomic regions associated with traits of interest. However, this ignores an important class of genomic associations, that of epistatic interactions. A genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) using highly dense markers can detect epistatic interactions, but is a difficult task due to multiple testing and computational demand. However, It is important for revealing complex trait heredity. This study considers analytical methods that detect statistical interactions between pairs of loci. We investigated a three-stage modelling procedure: (i) a model without the SNP to estimate the variance components; (ii) a model with the SNP using variance component estimates from (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for genome-wide epistasis analysis. We fitted these three-stage models to field data for growth and ultrasound measures for subcutaneous fat thickness in Brahman cattle. The study demonstrated the usefulness of modelling epistasis in the analysis of complex traits as it revealed extra sources of genetic variation and identified potential candidate genes affecting the concentration of insulin-like growth factor-1 and ultrasound scan measure of fat depth traits. Information about epistasis can add to our understanding of the complex genetic networks that form the fundamental basis of biological systems. PMID:25754883

  7. Additive and epistatic genome-wide association for growth and ultrasound scan measures of carcass-related traits in Brahman cattle.

    PubMed

    Ali, A A; Khatkar, M S; Kadarmideen, H N; Thomson, P C

    2015-04-01

    Genome-wide association studies are routinely used to identify genomic regions associated with traits of interest. However, this ignores an important class of genomic associations, that of epistatic interactions. A genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) using highly dense markers can detect epistatic interactions, but is a difficult task due to multiple testing and computational demand. However, It is important for revealing complex trait heredity. This study considers analytical methods that detect statistical interactions between pairs of loci. We investigated a three-stage modelling procedure: (i) a model without the SNP to estimate the variance components; (ii) a model with the SNP using variance component estimates from (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for genome-wide epistasis analysis. We fitted these three-stage models to field data for growth and ultrasound measures for subcutaneous fat thickness in Brahman cattle. The study demonstrated the usefulness of modelling epistasis in the analysis of complex traits as it revealed extra sources of genetic variation and identified potential candidate genes affecting the concentration of insulin-like growth factor-1 and ultrasound scan measure of fat depth traits. Information about epistasis can add to our understanding of the complex genetic networks that form the fundamental basis of biological systems.

  8. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    PubMed Central

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Schmack, Bastian; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Darche, Fabrice F; Schweizer, Patrick A; Thomas, Dierk; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2016-01-01

    Background Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX). Aim The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX. Methods Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or <1 year of amiodarone). Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan–Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival. Results Of the 530 patients, 74 (14.0%) received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff–Parkinson–White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105). Further, Kaplan–Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this group (P=0.0123). There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596), 2-year (P=0.8620), 5-year (P=0.2737), or overall follow-up mortality after HTX (P=0.1049). Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786). Conclusion Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with

  9. Clinical significance of high c-MYC and low MYCBP2 expression and their association with Ikaros dysfunction in adult acute lymphoblastic leukemia.

    PubMed

    Ge, Zheng; Guo, Xing; Li, Jianyong; Hartman, Melanie; Kawasawa, Yuka Imamura; Dovat, Sinisa; Song, Chunhua

    2015-12-01

    Increased expression of c-MYC is observed in both Acute Myeloid Leukemia (AML) and T-cell Acute Lymphoblastic Leukemia (T-ALL). MYC binding protein 2 (MYCBP2) is a probable E3 ubiquitin ligase and its function in leukemia is unknown. IKZF1 deletion is associated with the development and poor outcome of ALL. Here, we observed significant high c-MYC expression and low MYCBP2 expression in adult ALL patients. Patients with high c-MYC expression and/or low MYCBP2 expression had higher WBC counts and a higher percentage of CD34+ or CD33+ cells, as well as splenomegaly, liver infiltration, higher BM blasts, and lower CR rate. Ikaros bound to the regulatory regions of c-MYC and MYCBP2, suppressed c-MYC and increased MYCBP2 expression in ALL cells. Expression of c-MYC mRNA was significantly higher in patients with IKZF1 deletion; conversely MYCBP2 mRNA expression was significantly lower in those patients. A CK2 inhibitor, which acts as an Ikaros activator, also suppressed c-MYC and increased MYCBP2 expression in an Ikaros (IKZF1) dependent manner in the ALL cells. In summary, our data indicated the correlation of high c-MYC expression, low MYCBP2 expression and high c-MYC plus low MYCBP2 expression with high-risk factors and proliferation markers in adult ALL patients. Our data also revealed an oncogenic role for an Ikaros/MYCBP2/c-MYC axis in adult ALL, providing a mechanism of target therapies that activate Ikaros in adult ALL.

  10. Restoration of bone mineralization by cinacalcet is associated with a significant reduction in calcitriol-induced vascular calcification in uremic rats.

    PubMed

    De Schutter, Tineke M; Behets, Geert J; Jung, Susanne; Neven, Ellen; D'Haese, Patrick C; Querfeld, Uwe

    2012-11-01

    The present study investigated to what extent normalization of bone turnover goes along with a reduction of high-dose calcitriol-induced vascular calcifications in uremic rats. Five groups of male Sprague-Dawley rats were studied: sham-operated controls (n = 7), subtotally nephrectomized (SNX) uremic (CRF) animals (n = 12), CRF + calcitriol (vitD) (0.25 μg/kg/day) (n = 12), CRF + vitD + cinacalcet (CIN) (10 mg/kg/day) (n = 12), and CRF + vitD + parathyroidectomy (PTX) (n = 12). Treatment started 2 weeks after SNX and continued for the next 14 weeks. High-dose calcitriol treatment in hyperparathyroid rats went along with the development of distinct vascular calcification, which was significantly reduced by >50 %, in both CIN-treated and PTX animals. Compared to control animals and those of the CRF group, calcitriol treatment either in combination with CIN or PTX or not was associated with a significant increase in bone area comprising ±50 % of the total tissue area. However, whereas excessive woven bone accompanied by a dramatically increased osteoid width/area was seen in the CRF + vitD group, CIN treatment and PTX resulted in significantly reduced serum PTH level, which was accompanied by a distinct reduction of both the bone formation rate and the amount of osteoid. These data indicate that less efficient calcium and phosphorus incorporation in bone inherent to the severe hyperparathyroidism in vitamin D-treated uremic rats goes along with excessive vascular calcification, a process which is partially reversed by CIN treatment in combination with a more efficacious bone mineralization, thus restricting the availability of calcium and phosphate for being deposited in the vessel wall.

  11. Adenovirus type 12 DNA firmly associates with mammalian chromosomes early after virus infection or after DNA transfer by the addition of DNA to the cell culture medium.

    PubMed

    Schröer, J; Hölker, I; Doerfler, W

    1997-10-01

    hamster cells early after infection was previously documented, and recombination between viral and cellular DNAs in human cells was also shown. The FISH data on extensive chromosomal association of Ad12 DNA suggest a means to study the pathway of Ad12 DNA from early steps in viral infection via chromosomal interactions to integration events. In a different approach, Ad12 DNA, Ad12 DNA with the terminal protein covalently linked to its ends (Ad12 DNA-TP), or Ad2 DNA was simply added to the culture medium of HeLa or BHK21 cells. Precipitation or selection procedures were avoided. Depending on the experimental conditions, up to 25 to 30% of the interphase nuclei of HeLa cells and 9 to 19% of the interphase nuclei of BHK21 cells showed positive FISH signals at 24 h after the addition of DNA. Viral DNA also became associated in some cases with both chromatids. The uptake of Ad12 DNA-TP appeared to be 10 to 20 times more efficient than that of Ad12 DNA completely freed of proteins. Control bacteriophage lambda, M13, or plasmid DNA could not be detected in the nuclei under these conditions. PMID:9311883

  12. Mixtures of 3,4-methylenedioxymethamphetamine (ecstasy) and its major human metabolites act additively to induce significant toxicity to liver cells when combined at low, non-cytotoxic concentrations.

    PubMed

    da Silva, Diana Dias; Silva, Elisabete; Carvalho, Félix; Carmo, Helena

    2014-06-01

    Hepatic injury after 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) intoxications is highly unpredictable and does not seem to correlate with either dosage or frequency of use. The mechanisms involved include the drug metabolic bioactivation and the hyperthermic state of the liver triggered by its thermogenic action and exacerbated by the environmental circumstances of abuse at hot and crowded venues. We became interested in understanding the interaction between ecstasy and its metabolites generated in vivo as users are always exposed to mixtures of parent drug and metabolites. With this purpose, Hep G2 cells were incubated with MDMA and its main human metabolites methylenedioxyamphetamine (MDA), α-methyldopamine (α-MeDA) and N-methyl-α-methyldopamine (N-Me-α-MeDA), individually and in mixture (drugs combined in proportion to their individual EC01 ), at normal (37 °C) and hyperthermic (40.5 °C) conditions. After 48 h, viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Extensive concentration-response analysis was performed with single drugs and the parameters of the individual non-linear logit fits were used to predict joint effects using the well-founded models of concentration addition (CA) and independent action (IA). Experimental testing revealed that mixture effects on cell viability conformed to CA, for both temperature settings. Additionally, substantial combination effects were attained even when each substance was present at concentrations that individually produced unnoticeable effects. Hyperthermic incubations dramatically increased the toxicity of the tested drug and metabolites, both individually and combined. These outcomes suggest that MDMA metabolism has hazard implications to liver cells even when metabolites are found in low concentrations, as they contribute additively to the overall toxic effect of MDMA.

  13. Adeno-associated virus serotype 8 gene therapy leads to significant lowering of plasma cholesterol levels in humanized mouse models of homozygous and heterozygous familial hypercholesterolemia.

    PubMed

    Kassim, Sadik H; Li, Hui; Bell, Peter; Somanathan, Suryanarayan; Lagor, William; Jacobs, Frank; Billheimer, Jeffrey; Wilson, James M; Rader, Daniel J

    2013-01-01

    Familial hypercholesterolemia (FH) is a life-threatening genetic disease caused by mutations in the gene encoding low-density lipoprotein receptor (LDLR). As a bridge to clinical trials, we generated a "humanized" mouse model lacking LDLR and apolipoprotein B (ApoB) mRNA editing catalytic polypeptide-1 (APOBEC-1) expression and expressing a human ApoB100 transgene in order to permit more authentic simulation of in vivo interactions between the clinical transgene product, human LDLR (hLDLR), and its endogenous ligand, human ApoB100. On a chow diet, the humanized LDLR-deficient mice have substantial hypercholesterolemia and a lipoprotein phenotype more closely resembling human homozygous FH (hoFH) than in previous mouse models of FH. On injection of an adeno-associated virus serotype 8 (AAV8) vector encoding the human LDLR cDNA, significant correction of hypercholesterolemia was realized at doses as low as 1.5 × 10(11) genome copies (GC)/kg. Given that some patients with heterozygous FH (heFH) cannot be adequately treated with current therapy, we then extended our studies to similarly "humanized" mice that were heterozygous for LDLR deficiency, and that have a lipoprotein phenotype resembling heterozygous FH. Injection of AAV8-hLDLR brought about significant reduction in total and LDL cholesterol at doses as low as 5 × 10(11) GC/kg. Collectively, these data demonstrate the safety and efficacy of the liver-specific AAV8-hLDLR vector in the treatment of humanized mice modeling both hoFH and heFH. PMID:22985273

  14. Adeno-Associated Virus Serotype 8 Gene Therapy Leads to Significant Lowering of Plasma Cholesterol Levels in Humanized Mouse Models of Homozygous and Heterozygous Familial Hypercholesterolemia

    PubMed Central

    Kassim, Sadik H.; Li, Hui; Bell, Peter; Somanathan, Suryanarayan; Lagor, William; Jacobs, Frank; Billheimer, Jeffrey; Rader, Daniel J.

    2013-01-01

    Abstract Familial hypercholesterolemia (FH) is a life-threatening genetic disease caused by mutations in the gene encoding low-density lipoprotein receptor (LDLR). As a bridge to clinical trials, we generated a “humanized” mouse model lacking LDLR and apolipoprotein B (ApoB) mRNA editing catalytic polypeptide-1 (APOBEC-1) expression and expressing a human ApoB100 transgene in order to permit more authentic simulation of in vivo interactions between the clinical transgene product, human LDLR (hLDLR), and its endogenous ligand, human ApoB100. On a chow diet, the humanized LDLR-deficient mice have substantial hypercholesterolemia and a lipoprotein phenotype more closely resembling human homozygous FH (hoFH) than in previous mouse models of FH. On injection of an adeno-associated virus serotype 8 (AAV8) vector encoding the human LDLR cDNA, significant correction of hypercholesterolemia was realized at doses as low as 1.5×1011 genome copies (GC)/kg. Given that some patients with heterozygous FH (heFH) cannot be adequately treated with current therapy, we then extended our studies to similarly “humanized” mice that were heterozygous for LDLR deficiency, and that have a lipoprotein phenotype resembling heterozygous FH. Injection of AAV8-hLDLR brought about significant reduction in total and LDL cholesterol at doses as low as 5×1011 GC/kg. Collectively, these data demonstrate the safety and efficacy of the liver-specific AAV8-hLDLR vector in the treatment of humanized mice modeling both hoFH and heFH. PMID:22985273

  15. Phosphazene additives

    DOEpatents

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  16. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  17. mp-MRI Prostate Characterised PIRADS 3 Lesions are Associated with a Low Risk of Clinically Significant Prostate Cancer - A Retrospective Review of 92 Biopsied PIRADS 3 Lesions

    PubMed Central

    Liddell, Heath; Jyoti, Rajeev; Haxhimolla, Hodo Z.

    2015-01-01

    associated with malignant disease compared with lesions identified within the transition zone (10.8 vs. 3.8%). Those with malignant disease had a higher median PSA (8.1 vs. 6.4 ng/ml) and higher median PSA density (0.12 vs. 0.08) than those without malignant disease. Those with benign pathology had a higher prevalence of inflammation (31.4 vs. 16.7%). As per Epstein's criteria, 4 (4.3%) of the biopsied lesions represented clinically significant disease. Conclusion We have demonstrated in our series, that prostate lesions characterized on a 3T multiparametric MRI examination of the prostate as PIRADS 3, according to the current prevalent scoring systems, are associated with a low likelihood of the presence of clinically significant prostate cancer. PMID:26889125

  18. Nitrate addition to groundwater impacted by ethanol-blended fuel accelerates ethanol removal and mitigates the associated metabolic flux dilution and inhibition of BTEX biodegradation.

    PubMed

    Corseuil, Henry Xavier; Gomez, Diego E; Schambeck, Cássio Moraes; Ramos, Débora Toledo; Alvarez, Pedro J J

    2015-03-01

    A comparison of two controlled ethanol-blended fuel releases under monitored natural attenuation (MNA) versus nitrate biostimulation (NB) illustrates the potential benefits of augmenting the electron acceptor pool with nitrate to accelerate ethanol removal and thus mitigate its inhibitory effects on BTEX biodegradation. Groundwater concentrations of ethanol and BTEX were measured 2 m downgradient of the source zones. In both field experiments, initial source-zone BTEX concentrations represented less than 5% of the dissolved total organic carbon (TOC) associated with the release, and measurable BTEX degradation occurred only after the ethanol fraction in the multicomponent substrate mixture decreased sharply. However, ethanol removal was faster in the nitrate amended plot (1.4 years) than under natural attenuation conditions (3.0 years), which led to faster BTEX degradation. This reflects, in part, that an abundant substrate (ethanol) can dilute the metabolic flux of target pollutants (BTEX) whose biodegradation rate eventually increases with its relative abundance after ethanol is preferentially consumed. The fate and transport of ethanol and benzene were accurately simulated in both releases using RT3D with our general substrate interaction module (GSIM) that considers metabolic flux dilution. Since source zone benzene concentrations are relatively low compared to those of ethanol (or its degradation byproduct, acetate), our simulations imply that the initial focus of cleanup efforts (after free-product recovery) should be to stimulate the degradation of ethanol (e.g., by nitrate addition) to decrease its fraction in the mixture and speed up BTEX biodegradation.

  19. High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis.

    PubMed

    Kao, Hsiao-Wen; Liang, D Cherng; Kuo, Ming-Chung; Wu, Jin-Hou; Dunn, Po; Wang, Po-Nan; Lin, Tung-Liang; Shih, Yu-Shu; Liang, Sung-Tzu; Lin, Tung-Huei; Lai, Chen-Yu; Lin, Chun-Hui; Shih, Lee-Yung

    2015-10-20

    The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL-PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML.

  20. Nitrate addition to groundwater impacted by ethanol-blended fuel accelerates ethanol removal and mitigates the associated metabolic flux dilution and inhibition of BTEX biodegradation

    NASA Astrophysics Data System (ADS)

    Corseuil, Henry Xavier; Gomez, Diego E.; Schambeck, Cássio Moraes; Ramos, Débora Toledo; Alvarez, Pedro J. J.

    2015-03-01

    A comparison of two controlled ethanol-blended fuel releases under monitored natural attenuation (MNA) versus nitrate biostimulation (NB) illustrates the potential benefits of augmenting the electron acceptor pool with nitrate to accelerate ethanol removal and thus mitigate its inhibitory effects on BTEX biodegradation. Groundwater concentrations of ethanol and BTEX were measured 2 m downgradient of the source zones. In both field experiments, initial source-zone BTEX concentrations represented less than 5% of the dissolved total organic carbon (TOC) associated with the release, and measurable BTEX degradation occurred only after the ethanol fraction in the multicomponent substrate mixture decreased sharply. However, ethanol removal was faster in the nitrate amended plot (1.4 years) than under natural attenuation conditions (3.0 years), which led to faster BTEX degradation. This reflects, in part, that an abundant substrate (ethanol) can dilute the metabolic flux of target pollutants (BTEX) whose biodegradation rate eventually increases with its relative abundance after ethanol is preferentially consumed. The fate and transport of ethanol and benzene were accurately simulated in both releases using RT3D with our general substrate interaction module (GSIM) that considers metabolic flux dilution. Since source zone benzene concentrations are relatively low compared to those of ethanol (or its degradation byproduct, acetate), our simulations imply that the initial focus of cleanup efforts (after free-product recovery) should be to stimulate the degradation of ethanol (e.g., by nitrate addition) to decrease its fraction in the mixture and speed up BTEX biodegradation.

  1. An Individual with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome (BPES) and Additional Features Expands the Phenotype Associated with Mutations in KAT6B

    PubMed Central

    Yu, Hung-Chun; Geiger, Elizabeth A.; Medne, Livija; Zackai, Elaine H.; Shaikh, Tamim H.

    2015-01-01

    Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome (BPES) is an autosomal dominant disorder caused by mutations in FOXL2. We identified an individual with BPES and additional phenotypic features who did not have a FOXL2 mutation. We used whole exome sequencing to identify a de novo mutation in KAT6B (lysine acetyltransferase 6B) in this individual. The mutation was a 2 bp insertion leading to a frameshift which resulted in a premature stop codon. The resulting truncated protein does not have the C-terminal serine/methionine transcription activation domain necessary for interaction with other transcriptional and epigenetic regulators. This mutation likely has a dominant-negative or gain-of-function effect, similar to those observed in other genetic disorders resulting from KAT6B mutations, including Say-Barber-Biesecker-Young-Simpson (SBBYSS) and Genitopatellar syndrome (GTPTS). Thus, our subject’s phenotype broadens the spectrum of clinical findings associated with mutations in KAT6B. Furthermore, our results suggest that individuals with BPES without a FOXL2 mutation should be tested for KAT6B mutations. The transcriptional and epigenetic regulation mediated by KAT6B appears crucial to early developmental processes, which when perturbed can lead to a wide spectrum of phenotypic outcomes. PMID:24458743

  2. Array-Based Transcript Profiling and Limiting-Dilution Reverse Transcription-PCR Analysis Identify Additional Latent Genes in Kaposi's Sarcoma-Associated Herpesvirus▿ †

    PubMed Central

    Chandriani, Sanjay; Ganem, Don

    2010-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a B-lymphotropic herpesvirus strongly linked to both lymphoproliferative diseases and Kaposi's sarcoma. The viral latency program of KSHV is central to persistent infection and plays important roles in the pathogenesis of KSHV-related tumors. Up to six polypeptides and 18 microRNAs are known to be expressed in latency, but it is unclear if all major latency genes have been identified. Here, we have employed array-based transcript profiling and limiting-dilution reverse transcription-PCR (RT-PCR) methodologies to explore this issue in several KSHV-infected cell lines. Our results show that RNAs encoding the K1 protein are found at low levels in most latently infected cell lines. The gene encoding v-IL-6 is also expressed as a latent transcript in some contexts. Both genes encode powerful signaling molecules with particular relevance to B cell biology: K1 mimics signaling through the B cell receptor, and v-IL-6 promotes B cell survival. These data resolve earlier controversies about K1 and v-IL-6 expression and indicate that, in addition to core latency genes, some transcripts can be expressed in KSHV latency in a context-dependent manner. PMID:20219929

  3. Significant Association between Sulfate-Reducing Bacteria and Uranium-Reducing Microbial Communities as Revealed by a Combined Massively Parallel Sequencing-Indicator Species Approach

    SciTech Connect

    Cardenas, Erick; Leigh, Mary Beth; Marsh, Terence; Tiedje, James M.; Wu, Wei-min; Luo, Jian; Ginder-Vogel, Matthew; Kitanidis, Peter K.; Criddle, Craig; Carley, Jack M; Carroll, Sue L; Gentry, Terry J; Watson, David B; Gu, Baohua; Jardine, Philip M; Zhou, Jizhong

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 M and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared.

  4. Significant association between sulfate-reducing bacteria and uranium-reducing microbial communities as revealed by a combined massively parallel sequencing-indicator species approach.

    PubMed

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K; Jardine, Philip M; Zhou, Jizhong; Criddle, Craig S; Marsh, Terence L; Tiedje, James M

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared. PMID:20729318

  5. A combined massively parallel sequencing indicator species approach revealed significant association between sulfate-reducing bacteria and uranium-reducing microbial communities

    SciTech Connect

    Cardenas, Erick; Wu, Wei-min; Leigh, Mary Beth; Carley, Jack M; Carroll, Sue L; Gentry, Terry; Luo, Jian; Watson, David B; Gu, Baohua; Ginder-Vogel, Matthew A.; Kitanidis, Peter K.; Jardine, Philip; Kelly, Shelly D; Zhou, Jizhong; Criddle, Craig; Marsh, Terence; Tiedje, James

    2010-08-01

    Massively parallel sequencing has provided a more affordable and high throughput method to study microbial communities, although it has been mostly used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium (VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee, USA. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 {micro}M, and created geochemical gradients in electron donors from the inner loop injection well towards the outer loop and down-gradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical created conditions. Castellaniella, and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity; while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. Abundance of these bacteria as well as the Fe(III)- and U(VI)-reducer Geobacter correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to the electron donor addition and by the groundwater flow path. A false discovery rate approach was implemented to discard false positives by chance given the large amount of data compared.

  6. Significant Association between Sulfate-Reducing Bacteria and Uranium-Reducing Microbial Communities as Revealed by a Combined Massively Parallel Sequencing-Indicator Species Approach▿ †

    PubMed Central

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K.; Jardine, Philip M.; Zhou, Jizhong; Criddle, Craig S.; Marsh, Terence L.; Tiedje, James M.

    2010-01-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared. PMID:20729318

  7. Significant association between sulfate-reducing bacteria and uranium-reducing microbial communities as revealed by a combined massively parallel sequencing-indicator species approach.

    PubMed

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K; Jardine, Philip M; Zhou, Jizhong; Criddle, Craig S; Marsh, Terence L; Tiedje, James M

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared.

  8. Diagnosing Clostridium difficile-associated diarrhea using enzyme immunoassay: the clinical significance of toxin negativity in glutamate dehydrogenase-positive patients

    PubMed Central

    Yuhashi, Kazuhito; Yagihara, Yuka; Misawa, Yoshiki; Sato, Tomoaki; Saito, Ryoichi; Okugawa, Shu; Moriya, Kyoji

    2016-01-01

    Purpose The enzyme immunoassay (EIA) has lower sensitivity for Clostridium difficile toxins A and B than the polymerase chain reaction in the diagnosis of C. difficile-associated diarrhea (CDAD). Furthermore, toxin positivity with EIA performed on C. difficile isolates from stool cultures may be observed even in patients with EIA glutamate dehydrogenase (GDH)-positive and toxin-negative stool specimens. It is unclear whether such patients should be treated as having CDAD. Methods The present study retrospectively compared patient characteristics, treatment, and diarrhea duration among three groups of patients who underwent stool EIA testing for CDAD diagnosis: a toxin-positive stool group (positive stool group; n=39); a toxin-negative stool/toxin-positive isolate group (discrepant negative/positive group, n=14); and a dual toxin-negative stool and isolate group (dual negative group, n=15). All cases included were confirmed to be GDH positive on EIA test. Results Patients’ backgrounds and comorbidities were not significantly different among three groups. No difference was observed among the three groups with regard to antimicrobial drug use before diarrhea onset. Treatment was received by 82.1% of the positive stool group compared to 7.1% of the discrepant positive/negative group and 0% of the dual negative group, while mean diarrhea duration was 10.6 days compared to 7.9 days (P=0.6006) and 3.4 days (P=0.0312), respectively. Conclusion Even without treatment, patients with toxin-negative stool specimens had shorter diarrhea duration than those with toxin-positive stool specimens even with toxin-positive isolates. These findings may suggest a limited need for CDAD treatment for GDH-positive patients and toxin-negative stool specimens. PMID:27313472

  9. Are the stray 60-Hz electromagnetic fields associated with the distribution and use of electric power a significant cause of cancer?

    PubMed

    Jackson, J D

    1992-04-15

    The putative causal relation between ambient low-frequency (50 or 60 Hz) electromagnetic fields (necessarily present in living and working environments because of our ever increasing use of electrical devices) and cancer, especially leukemia, can be tested on the large scale by examining historical data on the growth of the generation and consumption of electric power since 1900 and corresponding data on cancer death and incidence rates. The United States per capita generation and residential consumption of electric power have grown roughly exponentially since 1900; total per capita generation has increased by a factor of 10 since 1940, and per capita residential consumption has increased by a factor of 20 in the same period. The ubiquitous stray fields from power distribution lines and internal and external wiring in buildings have grown in the same proportions. In contrast to the explosive increase in the generation and use of electricity, the age-adjusted cancer death rate for the population as a whole shows only a slight rise since 1900. When respiratory cancers (largely caused by tobacco use) are subtracted, the remaining death rate has actually fallen since 1940. That the death rate may have fallen because of better diagnosis and treatment, despite a rising incidence rate, is not substantiated, especially for leukemia, including childhood leukemia, where the incidence rate has been constant or declining slightly for the past 25 yr. The absence of any appreciable change in the national cancer incidence rates during a period in which residential use of electric power has increased dramatically shows that the associated stray 50- or 60-Hz electromagnetic fields pose no significant hazard to the average individual. PMID:1565645

  10. Antibodies against Proinsulin and Homologous MAP Epitopes Are Detectable in Hashimoto’s Thyroiditis Sardinian Patients, an Additional Link of Association

    PubMed Central

    Niegowska, Magdalena; Paccagnini, Daniela; Burrai, Carlo; Palermo, Mario; Sechi, Leonardo A.

    2015-01-01

    Hashimoto’s thyroiditis (HT) is the prevailing organ-specific autoimmune disease in Sardinia, often complicated with other autoimmune disorders, most commonly type 1 diabetes (T1D). While numerous studies describe levels of anty-thyroid antibodies (Abs) in T1D patients, few papers evaluate the status of anti-islet autoimmunity in subjects affected by HT. Previously, we portrayed Mycobacterium avium subspecies paratuberculosis (MAP) as an environmental factor strongly associated with both diseases. In this study, we analyzed plasma of Sardinian HT patients (n=177) and healthy controls (HCs; n=175) for the presence of Abs against proinsulin and MAP-derived homologous epitopes: MAP1,4αgbp157-173/PI64-80 were recognized by 5,08% and 18,64% of HT vs 0,57% and 7,43% of HCs (AUC=0,6 for both; p<0,0003 and 0,002, respectively), whereas the prevalence of Abs against MAP2404c70-85/PI46-61 peptides was higher but not significant in patients when compared to HCs. In women (n=152), Abs against MAP1,4αgbp157-173 were detected in 12,50% of HT vs 2,75% of HCs (AUC=0,63; p<0,0002), while positivity to its human homolog PI64-80 was observed in 16,42% of HT vs 6,42% of HCs (AUC=0,61; p<0,001). In men (n=25), a significant anti-PI46-61 Abs levels were detected in 4% of HT vs none of the HCs (AUC=0,7; p<0,003). Age-related analyses revealed the highest prevalence between 31-40 years old (45,83%) in the total study population and among males (33,33%); in contrast, women had a higher seroreactivity between 51-60 years (42,11%). A further follow-up and determination of anti-islet Abs levels is needed to evaluate the association of immune responses directed against the MAP/PI homologous peptides with progression to overt diabetes in HT subjects. PMID:26192189

  11. Additive roles of PthAs in bacterial growth and pathogenicity associated with nucleotide polymorphisms in effector-binding elements of citrus canker susceptibility genes.

    PubMed

    Abe, Valeria Yukari; Benedetti, Celso Eduardo

    2016-10-01

    Citrus canker, caused by Xanthomonas citri, affects most commercial citrus varieties. All X. citri strains possess at least one transcription activator-like effector of the PthA family that activates host disease susceptibility (S) genes. The X. citri strain 306 encodes four PthA effectors; nevertheless, only PthA4 is known to elicit cankers on citrus. As none of the PthAs act as avirulence factors on citrus, we hypothesized that PthAs 1-3 might also contribute to pathogenicity on certain hosts. Here, we show that, although PthA4 is indispensable for canker formation in six Brazilian citrus varieties, PthAs 1 and 3 contribute to canker development in 'Pera' sweet orange, but not in 'Tahiti' lemon. Deletions in two or more pthA genes reduce bacterial growth in planta more pronouncedly than single deletions, suggesting an additive role of PthAs in pathogenicity and bacterial fitness. The contribution of PthAs 1 and 3 in canker formation in 'Pera' plants does not correlate with the activation of the canker S gene, LOB1 (LATERAL ORGAN BOUNDARIES 1), but with the induction of other PthA targets, including LOB2 and citrus dioxygenase (DIOX). LOB1, LOB2 and DIOX show differential PthA-dependent expression between 'Pera' and 'Tahiti' plants that appears to be associated with nucleotide polymorphisms found at or near PthA-binding sites. We also present evidence that LOB1 activation alone is not sufficient to elicit cankers on citrus, and that DIOX acts as a canker S gene in 'Pera', but not 'Tahiti', plants. Our results suggest that the activation of multiple S genes, such as LOB1 and DIOX, is necessary for full canker development.

  12. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more.

    PubMed

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-07-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized 'Given X, find all associated Ys' query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: 'Find all diseases associated with Bisphenol A'. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation.

  13. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more

    PubMed Central

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-01-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized ‘Given X, find all associated Ys’ query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: ‘Find all diseases associated with Bisphenol A’. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation. PMID:25925572

  14. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more.

    PubMed

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-07-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized 'Given X, find all associated Ys' query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: 'Find all diseases associated with Bisphenol A'. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation. PMID:25925572

  15. Temporal association of Ca(2+)-dependent protein kinase with oil bodies during seed development in Santalum album L.: its biochemical characterization and significance.

    PubMed

    Anil, Veena S; Harmon, Alice C; Rao, K Sankara

    2003-04-01

    Calcium-dependent protein kinase (CDPK) is expressed in sandalwood (Santalum album L.) seeds under developmental regulation, and it is localized with spherical storage organelles in the endosperm [Anil et al. (2000) Plant Physiol. 122: 1035]. This study identifies these storage organelles as oil bodies. A 55 kDa protein associated with isolated oil bodies, showed Ca(2+)-dependent autophosphorylation and also cross-reacted with anti-soybean CDPK. The CDPK activity detected in the oil body-protein fraction was calmodulin-independent and sensitive to W7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide) inhibition. Differences in Michaelis Menton kinetics, rate of histone phosphorylation and sensitivity to W7 inhibition between a soluble CDPK from embryos and the oil body-associated CDPK of endosperm suggest that these are tissue-specific isozymes. The association of CDPK with oil bodies of endosperm was found to show a temporal pattern during seed development. CDPK protein and activity, and the in vivo phosphorylation of Ser and Thr residues were detected strongly in the oil bodies of endosperm from maturing seed. Since oil body formation occurs during seed maturation, the observations indicate that CDPK and Ca(2+) may have a regulatory role during oil accumulation/oil body biogenesis. The detection of CDPK-protein and activity in oil bodies of groundnut, sesame, cotton, sunflower, soybean and safflower suggests the ubiquity of the association of CDPKs with oil bodies. PMID:12721377

  16. Upregulation of Dicer is more frequent in monoclonal gammopathies of undetermined significance than in multiple myeloma patients and is associated with longer survival in symptomatic myeloma patients

    PubMed Central

    Sarasquete, María E.; Gutiérrez, Norma C.; Misiewicz-Krzeminska, Irena; Paiva, Bruno; Chillón, María C.; Alcoceba, Miguel; García-Sanz, Ramón; Hernández, Jesús M.; González, Marcos; San-Miguel, Jesús F.

    2011-01-01

    Dicer and Drosha are key enzymes in the miRNA-processing pathway which is altered in many human cancers. We analyzed Dicer and Drosha expression levels by quantitative PCR in 151 patients with monoclonal gammopathies: 102 symptomatic myeloma patients, 23 smoldering myelomas and 26 monoclonal gammopathy of undetermined significance. We found that Dicer expression values were significantly higher in monoclonal gammopathy of undetermined significance than in smoldering myelomas and symptomatic myeloma (mean ± SD, 0.84±0.36 vs. 0.60±0.23 and 0.62±0.51; P<0.01). Moreover, the median progression-free survival was significantly longer in symptomatic myeloma patients with high expression of Dicer (not reached vs. 23.6 months; P=0.02). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of monoclonal gammopathies. (Clinicaltrials.gov identifier: NCT00461747 for MM patients under 65 years of age and NCT00443235 for MM patients over 65 years of age) PMID:21160068

  17. Identification of a member of the catalase multigene family on wheat chromosome 7A associated with flour b* colour and biological significance of allelic variation.

    PubMed

    Li, Dora A; Walker, Esther; Francki, Michael G

    2015-12-01

    Carotenoids (especially lutein) are known to be the pigment source for flour b* colour in bread wheat. Flour b* colour variation is controlled by a quantitative trait locus (QTL) on wheat chromosome 7AL and one gene from the carotenoid pathway, phytoene synthase, was functionally associated with the QTL on 7AL in some, but not all, wheat genotypes. A SNP marker within a sequence similar to catalase (Cat3-A1snp) derived from full-length (FL) cDNA (AK332460), however, was consistently associated with the QTL on 7AL and implicated in regulating hydrogen peroxide (H2O2) to control carotenoid accumulation affecting flour b* colour. The number of catalase genes on chromosome 7AL was investigated in this study to identify which gene may be implicated in flour b* variation and two were identified through interrogation of the draft wheat genome survey sequence consisting of five exons and a further two members having eight exons identified through comparative analysis with the single catalase gene on rice chromosome 6, PCR amplification and sequencing. It was evident that the catalase genes on chromosome 7A had duplicated and diverged during evolution relative to its counterpart on rice chromosome 6. The detection of transcripts in seeds, the co-location with Cat3-A1snp marker and maximised alignment of FL-cDNA (AK332460) with cognate genomic sequence indicated that TaCat3-A1 was the member of the catalase gene family associated with flour b* colour variation. Re-sequencing identified three alleles from three wheat varieties, TaCat3-A1a, TaCat3-A1b and TaCat3-A1c, and their predicted protein identified differences in peroxisomal targeting signal tri-peptide domain in the carboxyl terminal end providing new insights into their potential role in regulating cellular H2O2 that contribute to flour b* colour variation.

  18. Including xpc® feed additive in the diet of inoculated broilers during grow-out helps control salmonella associated with their carcasses after processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to test XPC® feed additive for control of Salmonella in poultry meat products. Day of hatch broiler chicks were gavaged with 106 cells of a nalidixic acid resistant marker strain of Salmonella Typhimurium and placed on clean pine shavings in 9 separate floor pens (25 ...

  19. Permo-Triassic hypabyssal mafic intrusions and associated tholeiitic basalts of the Kolyuchinskaya Guba, Chukotka (NE Russia): Significance for interregional correlations

    NASA Astrophysics Data System (ADS)

    Ledneva, G. V.; Pease, V. L.; Sokolov, S. D.

    2008-12-01

    In order to test tectonic hypotheses regarding the evolution of the Arctic Alaska-Chukotka microplate prior to the opening of the Amerasian basin, we investigated rocks exposed near Kolyuchinskaya Guba, eastern Chukotka. Hypabyssal mafic rocks and associated basaltic flows enclose terrigenous sediments, minor cherts and limestones in pillow interstices. The hypabyssal mafic rock yields a U-Pb zircon age of 252+/-4 Ma and indicates intrusion of basic magma at the Permo-Triassic boundary, contemporaneous with voluminous magmatism of the Siberian large igneous province (LIP). The lava flows and hypabyssal mafic rocks of the Kolyuchinskaya Guba region have major and trace element compositions identical the tholeiitic flood basalts of the main plateau stage of the Siberian LIP. They are strongly differentiated, the result of high-pressure equilibrium crystallization of a low-Ti/Y tholeiitic melt, and contaminated. The compositional variations in these rocks, however, neither proves nor disproves a correlation between the Permo-Triassic tholeiitic flood basalts of eastern Chukotka and the Siberian LIP. Thus, two alternative geodynamic interpretations are possible: 1) The hypabyssal mafic rocks and associated tholeiitic flows crystallized from a plume-derived melt; 2) The rocks are not related to plume activity, consequently eastern Chukotka was probably part of a passive rifted or extensional continental margin in the Permo-Triassic. Nonetheless, we prefer the first of these two possibilities. Funding for this work is gratefully acknowledged from the Swedish Polar Research Secretariat ("Beringia-2005"), the Swedish Research Council, the Russian Foundation for Basic Research (grant No 08-05-00547), Leading Scientific School (NSH-3172.2008.5) and ONZ RAS. Thanks are also extended to M.J. Whitehouse and the Nordsim facility - the Nordsim facility is funded by the research councils of Denmark, Norway, Sweden, the Geological Survey of Finland, and the Swedish Museum of

  20. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    PubMed

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; de Oliveira, Ana Paula Ligeiro

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

  1. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke–Induced COPD in C57BL/6 mice

    PubMed Central

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; Ligeiro de Oliveira, Ana Paula

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J—660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

  2. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    PubMed

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; de Oliveira, Ana Paula Ligeiro

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

  3. Frequent inactivation of MCC/CTNNBIP1 and overexpression of phospho-beta-catenin(Y654) are associated with breast carcinoma: Clinical and prognostic significance.

    PubMed

    Mukherjee, Nupur; Dasgupta, Hemantika; Bhattacharya, Rittwika; Pal, Debolina; Roy, Rituparna; Islam, Saimul; Alam, Neyaz; Biswas, Jaydip; Roy, Anup; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2016-09-01

    Transcriptional activation of β-catenin is a hallmark of Wnt/β-catenin pathway activation. The MCC (Mutated in colorectal cancers) and CTNNBIP1 (catenin, beta interacting protein 1) are two candidate genes which inhibit the transcriptional activity of nuclear β-catenin. The importance of MCC and CTNNBIP1 in breast cancer (BC) development has not yet been studied in detail. For this reason, in present study, the alterations (deletion/methylation/mutation/expression) of MCC and CTNNBIP1 were analyzed in BC of Indian patients (N=120) followed by expression/mutation analysis of β-catenin. Then transcriptional activity of β-catenin was checked by expression analysis of its target genes (EGFR, C-MYC and CCND1) in the same set of samples. Frequent methylation (44-45%) than deletion (20-32%) with overall alterations of 52-55% was observed in MCC/CTNNBIP1 in the BC samples. The alterations of MCC/CTNNBIP1 showed significant correlation with increased nuclear β-catenin/p-β-catenin(Y654) expression. Also, a significant correlation was seen between nuclear β-catenin expression and overexpression of its target genes like EGFR, MYC and CCND1 in the BC samples (P<0.0001). An upregulation of MCC and CTNNBIP1 expression by 5-Aza-2'-deoxycytidine treatment of MCF7 and MDA-MB-231 cell lines lead to downregulation of β-catenin and its target genes. The expression of nuclear p-β-catenin(Y654), EGFR, MYC and CCND1 were significantly high in TNBC (Triple negative BC) and Her2+ compared to Luminal A/B+ subtypes. The TNBC patients in stage III/IV having reduced expression of MCC in the tumors showed poor prognosis. Thus, our data suggests that inactivation of MCC/CTNNBIP1 could be an important event in activation of β-catenin mediated transcription of target genes in BC. PMID:27208794

  4. Metallogenetic systems associated with granitoid magmatism in the Amazonian Craton: An overview of the present level of understanding and exploration significance

    NASA Astrophysics Data System (ADS)

    Bettencourt, Jorge Silva; Juliani, Caetano; Xavier, Roberto P.; Monteiro, Lena V. S.; Bastos Neto, Artur C.; Klein, Evandro L.; Assis, Rafael R.; Leite, Washington Barbosa, Jr.; Moreto, Carolina P. N.; Fernandes, Carlos Marcello Dias; Pereira, Vitor Paulo

    2016-07-01

    The Amazonian Craton hosts world-class metallogenic provinces with a wide range of styles of primary precious, rare, base metal, and placer deposits. This paper provides a synthesis of the geological database with regard to granitoid magmatic suites, spatio temporal distribution, tectonic settings, and the nature of selected mineral deposits. The Archean Carajás Mineral Province comprises greenstone belts (3.04-2.97 Ga), metavolcanic-sedimentary units (2.76-2.74 Ga), granitoids (3.07-2.84 Ga) formed in a magmatic arc and syn-collisional setting, post-orogenic A2-type granites as well as gabbros (ca. 2.74 Ga), and anorogenic granites (1.88 Ga). Archean iron oxide-Cu-Au (IOCG) deposits were synchronous or later than bimodal magmatism (2.74-2.70 Ga). Paleoproterozoic IOCG deposits, emplaced at shallow-crustal levels, are enriched with Nb-Y-Sn-Be-U. The latter, as well as Sn-W and Au-EGP deposits are coeval with ca. 1.88 Ga A2-type granites. The Tapajós Mineral Province includes a low-grade meta-volcano-sedimentary sequence (2.01 Ga), tonalites to granites (2.0-1.87 Ga), two calc-alkaline volcanic sequences (2.0-1.95 Ga to 1.89-1.87 Ga) and A-type rhyolites and granites (1.88 Ga). The calc-alkaline volcanic rocks host epithermal Au and base metal mineralization, whereas Cu-Au and Cu-Mo ± Au porphyry-type mineralization is associated with sub-volcanic felsic rocks, formed in two continental magmatic arcs related to an accretionary event, resulting from an Andean-type northwards subduction. The Alta Floresta Gold Province consists of Paleoproterozoic plutono-volcanic sequences (1.98-1.75 Ga), generated in ocean-ocean orogenies. Disseminated and vein-type Au ± Cu and Au + base metal deposits are hosted by calc-alkaline I-type granitic intrusions (1.98 Ga, 1.90 Ga, and 1.87 Ga) and quartz-feldspar porphyries (ca. 1.77 Ga). Timing of the gold deposits has been constrained between 1.78 Ga and 1.77 Ga and linked to post-collisional Juruena arc felsic magmatism (e.g., Col

  5. Temporal Variability of Zooplankton (2000-2013) in the Levantine Sea: Significant Changes Associated to the 2005-2010 EMT-like Event?

    PubMed

    Ouba, Anthony; Abboud-Abi Saab, Marie; Stemmann, Lars

    2016-01-01

    In this study, we investigated, for the first time, the potential impact of environmental changes on zooplankton abundance over a fourteen year period (2000-2013) at an offshore station in the Eastern Mediterranean Sea (the Levantine basin, offshore Lebanon). Samples were collected monthly and analyzed using the semi-automated system ZooScan. Salinity, temperature and phytoplankton abundance (nano and microphytoplankton) were also measured. Results show no significant temporal trend in sea surface temperature over the years. Between 2005-2010, salinity in the upper layer (0-80 m) of the Levantine basin increased (~0.3°C). During this 5 year period, total zooplankton abundance significantly increased. These modifications were concomitant to the activation of Aegean Sea as a source of dense water formation as part of the "Eastern Mediterranean Transient-like" event. The results of the present study suggested that zooplankton benefited from enhanced phytoplankton production during the mixing years of the event. Changes in the phenology of some taxa were observed accordingly with a predominantly advanced peak of zooplankton abundance. In conclusion, long-term changes in zooplankton abundance were related to the Levantine thermohaline circulation rather than sea surface warming. Sampling must be maintained to assess the impact of long-term climate change on zooplankton communities.

  6. Temporal Variability of Zooplankton (2000-2013) in the Levantine Sea: Significant Changes Associated to the 2005-2010 EMT-like Event?

    PubMed

    Ouba, Anthony; Abboud-Abi Saab, Marie; Stemmann, Lars

    2016-01-01

    In this study, we investigated, for the first time, the potential impact of environmental changes on zooplankton abundance over a fourteen year period (2000-2013) at an offshore station in the Eastern Mediterranean Sea (the Levantine basin, offshore Lebanon). Samples were collected monthly and analyzed using the semi-automated system ZooScan. Salinity, temperature and phytoplankton abundance (nano and microphytoplankton) were also measured. Results show no significant temporal trend in sea surface temperature over the years. Between 2005-2010, salinity in the upper layer (0-80 m) of the Levantine basin increased (~0.3°C). During this 5 year period, total zooplankton abundance significantly increased. These modifications were concomitant to the activation of Aegean Sea as a source of dense water formation as part of the "Eastern Mediterranean Transient-like" event. The results of the present study suggested that zooplankton benefited from enhanced phytoplankton production during the mixing years of the event. Changes in the phenology of some taxa were observed accordingly with a predominantly advanced peak of zooplankton abundance. In conclusion, long-term changes in zooplankton abundance were related to the Levantine thermohaline circulation rather than sea surface warming. Sampling must be maintained to assess the impact of long-term climate change on zooplankton communities. PMID:27459093

  7. The clinical significance of HRCT in evaluation of patients with rheumatoid arthritis-associated interstitial lung disease: a report from China.

    PubMed

    Zou, Yu-Qiong; Li, Ya-Song; Ding, Xiao-Nan; Ying, Zhen-Hua

    2012-03-01

    The objective of this study is to describe the interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients of China, and to study clinical significance of high-resolution computed tomography (HRCT) in evaluation and treatment. One hundred and ten Chinese patients (79 women and 31 man) diagnosed with RA between December 2008 to November 2009 were analyzed. According to the HRCT, 47 (42.73%) RA patients were diagnosed as ILD. Old age, smoking and pulmonary rales were closely related to ILD (P < 0.05). The main appearances of ILD were ground-glass (39.09%), honeycombing (4.55%), reticular patterns and consolidation (1.82%). Patients with reticular patterns and honeycombing were more likely to show the respiratory symptoms. It was also common to find other abnormal changes, such as fiber cord shadow (22.73%), lung markings fuzzy disorder (30%), pulmonary nodules (11.82%), emphysema (9.09%), bronchiectasis (3.64%), subpleural nodules (11.82%) and pleural thickening (24.55%). In treatment, honeycombing and subpleural nodules were more common in patients with methotrexate (MTX) and/or leflunomide treatment than without (P < 0.05). Other abnormal changes were no statistical significance (P > 0.05). Pulmonary involvement is common in RA patients, and it is suggested that HRCT could be a sensitive and useful way in evaluating the lung of RA patients.

  8. Temporal Variability of Zooplankton (2000-2013) in the Levantine Sea: Significant Changes Associated to the 2005-2010 EMT-like Event?

    PubMed Central

    Ouba, Anthony; Abboud-Abi Saab, Marie; Stemmann, Lars

    2016-01-01

    In this study, we investigated, for the first time, the potential impact of environmental changes on zooplankton abundance over a fourteen year period (2000–2013) at an offshore station in the Eastern Mediterranean Sea (the Levantine basin, offshore Lebanon). Samples were collected monthly and analyzed using the semi-automated system ZooScan. Salinity, temperature and phytoplankton abundance (nano and microphytoplankton) were also measured. Results show no significant temporal trend in sea surface temperature over the years. Between 2005–2010, salinity in the upper layer (0–80 m) of the Levantine basin increased (~0.3°C). During this 5 year period, total zooplankton abundance significantly increased. These modifications were concomitant to the activation of Aegean Sea as a source of dense water formation as part of the “Eastern Mediterranean Transient-like” event. The results of the present study suggested that zooplankton benefited from enhanced phytoplankton production during the mixing years of the event. Changes in the phenology of some taxa were observed accordingly with a predominantly advanced peak of zooplankton abundance. In conclusion, long-term changes in zooplankton abundance were related to the Levantine thermohaline circulation rather than sea surface warming. Sampling must be maintained to assess the impact of long-term climate change on zooplankton communities. PMID:27459093

  9. Diverse and High Prevalence of Human Papillomavirus Associated with a Significant High Rate of Cervical Dysplasia in Human Immunodeficiency Virus–Infected Women in Johannesburg, South Africa

    PubMed Central

    Firnhaber, Cynthia; Zungu, Khumbuzile; Levin, Simon; Michelow, Pam; Montaner, Luis J.; McPhail, Patrick; Williamson, Anna-Lise; Allan, Bruce R.; Van der Horst, Charlie; Rinas, Allen; Sanne, Ian

    2010-01-01

    Objective To evaluate the epidemiology of the human papillomavirus (HPV) type and correlate it with the Papanicolaou smears in human immunodeficiency virus–seropositive women in Johannesburg, South Africa. Study Design In a cohort of 148 women, HPV DNA testing was performed with the Roche HPV genotyping test (Branchburg, New Jersey, U.S.A.). Papanicolaou smears were performed by standard cytology utilizing 2001 Bethesda reporting guidelines. Results The average age and CD4 count of the participants was 35 years and 255 cells per mm3, respectively. Fifty-four percent had abnormal Papanicolaou smears; 66% of the abnormal cytology was low grade changes, with 33% assessed as having high grade changes. HPV DNA was found in 95% of the 148 subjects assessed, with 83% having 1 or more HPV oncogenic types. Common oncogenic types were 16, 35, 53 and 18. When HPV results were stratified by CD4, there was a significant risk of an oncogenic HPV type in women with CD4 <200. Significant odds ratios for high grade lesions were seen in HPV types 16, 35, 51, 66, 69 and 73. Conclusion The results of HPV typing illustrate the diverse range of oncogenic HPV and high prevalence of oncogenic type. These results highlight the need for improved access to Papanicolaou smear screening for this population. PMID:19248549

  10. Functional Diversity of Cytomegalovirus–Specific T Cells Is Maintained in Older People and Significantly Associated With Protein Specificity and Response Size

    PubMed Central

    Bajwa, Martha; Vita, Serena; Vescovini, Rosanna; Larsen, Martin; Sansoni, Paolo; Terrazzini, Nadia; Caserta, Stefano; Thomas, David; Davies, Kevin A.; Smith, Helen; Kern, Florian

    2016-01-01

    Background. Parallel upregulation of several T-cell effector functions (ie, polyfunctionality) is believed to be critical for the protection against viruses but thought to decrease in large T-cell expansions, in particular at older ages. The factors determining T-cell polyfunctionality are incompletely understood. Here we revisit the question of cytomegalovirus (CMV)–specific T-cell polyfunctionality, including a wide range of T-cell target proteins, response sizes, and participant ages. Methods. Polychromatic flow cytometry was used to analyze the functional diversity (ie, CD107, CD154, interleukin 2, tumor necrosis factor, and interferon γ expression) of CD4+ and CD8+ T-cell responses to 19 CMV proteins in a large group of young and older United Kingdom participants. A group of oldest old people (age >85 years) was included to explore these parameters in exceptional survivors. Polyfunctionality was assessed for each protein-specific response subset, by subset and in aggregate, across all proteins by using the novel polyfunctionality index. Results. Polyfunctionality was not reduced in healthy older people as compared to young people. However, it was significantly related to target protein specificity. For each protein, it increased with response size. In the oldest old group, overall T-cell polyfunctionality was significantly lower. Discussion. Our results give a new perspective on T-cell polyfunctionality and raise the question of whether maintaining polyfunctionality of CMV-specific T cells at older ages is necessarily beneficial. PMID:27521364

  11. High prevalence of asthma symptoms in Warao Amerindian children in Venezuela is significantly associated with open-fire cooking: a cross-sectional observational study

    PubMed Central

    2013-01-01

    Background The International Study on Asthma and Allergies in Childhood (ISAAC) reported a prevalence of asthma symptoms in 17 centers in nine Latin American countries that was similar to prevalence rates reported in non-tropical countries. It has been proposed that the continuous exposure to infectious diseases in rural populations residing in tropical areas leads to a relatively low prevalence of asthma symptoms. As almost a quarter of Latin American people live in rural tropical areas, the encountered high prevalence of asthma symptoms is remarkable. Wood smoke exposure and environmental tobacco smoke have been identified as possible risk factors for having asthma symptoms. Methods We performed a cross-sectional observational study from June 1, 2012 to September 30, 2012 in which we interviewed parents and guardians of Warao Amerindian children from Venezuela. Asthma symptoms were defined according to the ISAAC definition as self-reported wheezing in the last 12 months. The associations between wood smoke exposure and environmental tobacco smoke and the prevalence of asthma symptoms were calculated by means of univariate and multivariable logistic regression analyses. Results We included 630 children between two and ten years of age. Asthma symptoms were recorded in 164 of these children (26%). The prevalence of asthma symptoms was associated with the cooking method. Children exposed to the smoke produced by cooking on open wood fires were at higher risk of having asthma symptoms compared to children exposed to cooking with gas (AOR 2.12, 95% CI 1.18 - 3.84). Four percent of the children lived in a household where more than ten cigarettes were smoked per day and they had a higher risk of having asthma symptoms compared to children who were not exposed to cigarette smoke (AOR 2.69, 95% CI 1.11 - 6.48). Conclusion Our findings suggest that children living in rural settings in a household where wood is used for cooking or where more than ten cigarettes are smoked

  12. Combined action of time-delay and colored cross-associated multiplicative and additive noises on stability and stochastic resonance for a stochastic metapopulation system

    NASA Astrophysics Data System (ADS)

    Wang, Kang-Kang; Zong, De-Cai; Wang, Ya-Jun; Li, Sheng-Hong

    2016-05-01

    In this paper, the transition between the stable state of a big density and the extinction state and stochastic resonance (SR) for a time-delayed metapopulation system disturbed by colored cross-correlated noises are investigated. By applying the fast descent method, the small time-delay approximation and McNamara and Wiesenfeld's SR theory, we investigate the impacts of time-delay, the multiplicative, additive noises and colored cross-correlated noise on the SNR and the shift between the two states of the system. Numerical results show that the multiplicative, additive noises and time-delay can all speed up the transition from the stable state to the extinction state, while the correlation noise and its correlation time can slow down the extinction process of the population system. With respect to SNR, the multiplicative noise always weakens the SR effect, while noise correlation time plays a dual role in motivating the SR phenomenon. Meanwhile, time-delay mainly plays a negative role in stimulating the SR phenomenon. Conversely, it could motivate the SR effect to increase the strength of the cross-correlation noise in the SNR-β plot, while the increase of additive noise intensity will firstly excite SR, and then suppress the SR effect.

  13. Role of the HSP90-associated cochaperone p23 in enhancing activity of the androgen receptor and significance for prostate cancer.

    PubMed

    Reebye, Vikash; Querol Cano, Laia; Lavery, Derek N; Brooke, Greg N; Powell, Sue M; Chotai, Deepa; Walker, Marjorie M; Whitaker, Hayley C; Wait, Robin; Hurst, Helen C; Bevan, Charlotte L

    2012-10-01

    Prostate tumor growth initially depends on androgens, which act via the androgen receptor (AR). Despite androgen ablation therapy, tumors eventually progress to a castrate-resistant stage in which the AR remains active. The mechanisms are poorly understood but it may be that changes in levels or activity of AR coregulators affect trafficking and activation of the receptor. A key stage in AR signaling occurs in the cytoplasm, where unliganded receptor is associated with the heat shock protein (HSP)90 foldosome complex. p23, a key component of this complex, is best characterized as a cochaperone for HSP90 but also has HSP90-independent activity and has been reported as having differential effects on the activity of different steroid receptors. Here we report that p23 increases activity of the AR, and this appears to involve steps both in the cytoplasm (increasing ligand-binding capacity, possibly via direct interaction with AR) and the nucleus (enhancing AR occupancy at target promoters). We show, for the first time, that AR and p23 can interact, perhaps directly, when HSP90 is not present in the same complex. The effects of p23 on AR activity are at least partly HSP90 independent because a mutant form of p23, unable to bind HSP90, nevertheless increases AR activity. In human prostate tumors, nuclear p23 was higher in malignant prostate cells compared with benign/normal cells, supporting the utility of p23 as a therapeutic target in prostate cancer.

  14. Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina

    SciTech Connect

    Leach, Natalie R.; Roller, Richard J.

    2010-10-10

    The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid. Disruption of the lamina accompanied by phosphorylation of lamina proteins is a conserved feature of herpesvirus infection. In HSV-1-infected cells, protein kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested two critical hypotheses about the mechanism and significance of lamina disruption. First, we show that chemical inhibition of all PKC isoforms reduced viral growth five-fold and inhibited capsid egress from the nucleus. However, specific inhibition of either conventional PKCs or PKC delta does not inhibit viral growth. Second, we show hyperphosphorylation of emerin by viral and cellular kinases is required for its disassociation from the lamina. These data support hypothesis that phosphorylation of lamina components mediates lamina disruption during HSV nuclear egress.

  15. Variation in prescribing of lipid-lowering medication in primary care is associated with incidence of cardiovascular disease and all-cause mortality in people with screen-detected diabetes: findings from the ADDITION-Denmark trial

    PubMed Central

    Simmons, R K; Carlsen, A H; Griffin, S J; Charles, M; Christiansen, J S; Borch-Johnsen, K; Sandbæk, A; Lauritzen, T

    2014-01-01

    Aims To examine variation between general practices in the prescription of lipid-lowering treatment to people with screen-detected Type 2 diabetes, and associations with practice and participant characteristics and risk of cardiovascular events and all-cause mortality. Methods Observational cohort analysis of data from 1533 people with screen-detected Type 2 diabetes aged 40–69 years from the ADDITION-Denmark study. One hundred and seventy-four general practices were cluster randomized to receive: (1) routine diabetes care according to national guidelines (623 individuals), or (2) intensive multifactorial target-driven management (910 individuals). Multivariable logistic regression was used to quantify the association between the proportion of individuals in each practice who redeemed prescriptions for lipid-lowering medication in the two years following diabetes diagnosis and a composite cardiovascular disease (CVD) outcome, adjusting for age, sex, prevalent chronic disease, baseline CVD risk factors, smoking and lipid-lowering medication, and follow-up time. Results The proportion of individuals treated with lipid-lowering medication varied widely between practices (0–100%). There were 118 CVD events over 9431 person-years of follow-up. For the whole trial cohort, the risk of CVD was significantly higher in practices in the lowest compared with the highest quartile for prescribing lipid-lowering medication [adjusted odds ratio (OR) 3.4, 95% confidence interval (CI) 1.6–7.3]. Similar trends were found for all-cause mortality. Conclusions More frequent prescription of lipid-lowering treatment was associated with a lower incidence of CVD and all-cause mortality. Improved understanding of factors underlying practice variation in prescribing may enable more frequent use of lipid-lowering treatment. The results highlight the benefits of intensive treatment of people with screen-detected diabetes (Clinical Trials Registry No; NCT 00237549). What's new Despite

  16. Synkinematic high-K calc-alkaline plutons associated with the Pan-African Central Cameroon shear zone (W-Tibati area): Petrology and geodynamic significance

    NASA Astrophysics Data System (ADS)

    Njanko, Théophile; Nédélec, Anne; Affaton, Pascal

    2006-04-01

    Four plutons from the W-Tibati area of central Cameroon crop out in close relationships with the Pan-African Adamawa ductile shear zone (Central Cameroon Shear Zone: CCSZ). These plutons include diorites, tonalites, granodiorites and granites, and most of them are porphyritic due to the abundance of pink K-feldspar megacrysts. Syn-kinematic magma emplacement is demonstrated by the elongate shape of the plutons and by magmatic and ductile (gneissic) foliations that strike parallel to or at a low angle with the CCSZ; the foliation obliquity is consistent with dextral transcurrent tectonics. Whole-rock geochemistry points to high-K calc-alkaline to shoshonitic magmatism. Mixing-mingling features can be observed in the field. However, fractional crystallization of plagioclase, amphibole, biotite (+ K-feldspar in the more felsic compositions) appears to have played a dominant role in the magmatic differentiation processes, as confirmed by mass balance calculations based on major elements. Isotopic signatures suggest that the magmas may have originated from different sources, i.e. either from a young mafic underplate for most magmas with ɛNdi(600 Ma) around -1 to -2 and Sri (600 Ma) around 0.705, or from an enriched lithospheric mantle for some diorites with ɛNdi(600 Ma) at -6 and Sri (600 Ma) at 0.7065; mixing with young crustal component is likely. The plutonic rocks of W-Tibati are similar to other Pan-African high-K calk-alkaline syn-kinematic plutons in western Cameroon. They also display striking similarities with high-K calk-alkaline plutons associated with the Patos and Pernambuco shear zones of the Borborema province in NE Brazil.

  17. Drug Resistance in Cortical and Hippocampal Slices from Resected Tissue of Epilepsy Patients: No Significant Impact of P-Glycoprotein and Multidrug Resistance-Associated Proteins

    PubMed Central

    Sandow, Nora; Kim, Simon; Raue, Claudia; Päsler, Dennis; Klaft, Zin-Juan; Antonio, Leandro Leite; Hollnagel, Jan Oliver; Kovacs, Richard; Kann, Oliver; Horn, Peter; Vajkoczy, Peter; Holtkamp, Martin; Meencke, Heinz-Joachim; Cavalheiro, Esper A.; Pragst, Fritz; Gabriel, Siegrun; Lehmann, Thomas-Nicolas; Heinemann, Uwe

    2015-01-01

    Drug resistant patients undergoing epilepsy surgery have a good chance to become sensitive to anticonvulsant medication, suggesting that the resected brain tissue is responsible for drug resistance. Here, we address the question whether P-glycoprotein (Pgp) and multidrug resistance-associated proteins (MRPs) expressed in the resected tissue contribute to drug resistance in vitro. Effects of anti-epileptic drugs [carbamazepine (CBZ), sodium valproate, phenytoin] and two unspecific inhibitors of Pgp and MRPs [verapamil (VPM) and probenecid (PBN)] on seizure-like events (SLEs) induced in slices from 35 hippocampal and 35 temporal cortex specimens of altogether 51 patients (161 slices) were studied. Although in slice preparations the blood brain barrier is not functional, we found that SLEs predominantly persisted in the presence of anticonvulsant drugs (90%) and also in the presence of VPM and PBN (86%). Following subsequent co-administration of anti-epileptic drugs and drug transport inhibitors, SLEs continued in 63% of 143 slices. Drug sensitivity in slices was recognized either as transition to recurrent epileptiform transients (30%) or as suppression (7%), particularly by perfusion with CBZ in PBN containing solutions (43, 9%). Summarizing responses to co-administration from more than one slice per patient revealed that suppression of seizure-like activity in all slices was only observed in 7% of patients. Patients whose tissue was completely or partially sensitive (65%) presented with higher seizure frequencies than those with resistant tissue (35%). However, corresponding subgroups of patients do not differ with respect to expression rates of drug transporters. Our results imply that parenchymal MRPs and Pgp are not responsible for drug resistance in resected tissue. PMID:25741317

  18. Pre-transplant phospholipase A2 receptor autoantibody concentration is associated with clinically significant recurrence of membranous nephropathy post-kidney transplantation.

    PubMed

    Gupta, Gaurav; Fattah, Hasan; Ayalon, Rivka; Kidd, Jason; Gehr, Todd; Quintana, Luis F; Kimball, Pamela; Sadruddin, Salima; Massey, H Davis; Kumar, Dhiren; King, Anne L; Beck, Laurence H

    2016-04-01

    Previous studies that have assessed the association of pre-transplant antiphospholipase A2 receptor autoantibody (PLA2R-Ab) concentration with a recurrence of membranous nephropathy (rMN) post-kidney transplant have yielded variable results. We tested 16 consecutive transplant patients with a history of iMN for pre-transplant PLA2R-Ab. Enzyme-linked immunosorbent assay titers (Euroimmun, NJ, USA) >14 RU/mL were considered positive. A receiver operating characteristic (ROC) analysis was performed after combining data from Quintana et al. (n = 21; Transplantation February 2015) to determine a PLA2R-Ab concentration which could predict rMN. Six of 16 (37%) patients had biopsy-proven rMN at a median of 3.2 yr post-transplant. Of these, five of six (83%) had a positive PLA2R-Ab pre-transplant with a median of 82 RU/mL (range = 31-1500). The only patient who had rMN with negative PLA2R-Ab was later diagnosed with B-cell lymphoma. One hundred percent (n = 10) of patients with no evidence of rMN (median follow-up = five yr) had negative pre-transplant PLA2R-Ab. In a combined ROC analysis (n = 37), a pre-transplant PLA2R-Ab > 29 RU/mL predicted rMN with a sensitivity of 85% and a specificity of 92%. Pre-transplant PLA2R-Ab could be a useful tool for the prediction of rMN. Patients with rMN in the absence of PLA2R-Ab should be screened for occult malignancy and/or alternate antigens.

  19. Nature and regional significance of unconformities associated with the Middle Ordovician Hagan K-bentonite complex in the North American midcontinent

    USGS Publications Warehouse

    Kolata, Dennis R.; Huff, W.D.; Bergstrom, Stig M.

    1998-01-01

    Stratal patterns of the Middle Ordovician Hagan K-bentonite complex and associated rocks show that the Black River-Trenton unconformity in the North American midcontinent formed through the complex interplay of eustasy, sediment accumulation rates, siliciclastic influx, bathymetry, seawater chemistry, and perhaps local tectonic uplift. The unconformity is diachronous and is an amalgamated surface that resulted from local late Turinian lowstand exposure followed by regional early Chatfieldian transgressive drowning and sediment starvation. The duration of the unconformity is greatest in southern Wisconsin, northern Illinois, and northern Indiana, where the Deicke and Millbrig K-bentonite Beds converge at the unconformity. On the basis of published isotopic ages for the Deicke and Millbrig beds, it is possible that in these regions erosion and non-deposition spanned a period of as much as 3.2 m.y. Two broad coeval depositional settings are recognized within the North American midcontinent during early Chatfieldian time. 1) An inner shelf, subtidal facies of fossiliferous shale (Spechts Ferry Shale Member and Ion Shale Member of the Decorah Formation) and argillaceous lime mudstone and skeletal wackestone (Guttenberg and Kings Lake Limestone Members) extended from the Canadian shield and Transcontinental arch southeastward through Minnesota, Wisconsin, Iowa, and Missouri. 2) A seaward, relatively deep subtidal, sediment-starved, middle shelf extended eastward from the Mississippi Valley region to the Taconian foreland basins in the central and southern Appalachians and southward through the pericratonic Arkoma and Black Warrior basins. In the inner shelf region, the Black River-Trenton unconformity is a composite of at least two prominent hardground omission surfaces, one at the top of the Castlewood and Carimona Limestone Members and the other at the top of the Guttenberg and Kings Lake Limestone Members, both merging to a single surface in the middle shelf region

  20. Rare allele of OsPPKL1 associated with grain length causes extra-large grain and a significant yield increase in rice

    PubMed Central

    Zhang, Xiaojun; Wang, Jianfei; Huang, Ji; Lan, Hongxia; Wang, Cailin; Yin, Congfei; Wu, Yunyu; Tang, Haijuan; Qian, Qian; Li, Jiayang; Zhang, Hongsheng

    2012-01-01

    Grain size and shape are important components determining rice grain yield, and they are controlled by quantitative trait loci (QTLs). Here, we report the cloning and functional characterization of a major grain length QTL, qGL3, which encodes a putative protein phosphatase with Kelch-like repeat domain (OsPPKL1). We found a rare allele qgl3 that leads to a long grain phenotype by an aspartate-to-glutamate transition in a conserved AVLDT motif of the second Kelch domain in OsPPKL1. The rice genome has other two OsPPKL1 homologs, OsPPKL2 and OsPPKL3. Transgenic studies showed that OsPPKL1 and OsPPKL3 function as negative regulators of grain length, whereas OsPPKL2 as a positive regulator. The Kelch domains are essential for the OsPPKL1 biological function. Field trials showed that the application of the qgl3 allele could significantly increase grain yield in both inbred and hybrid rice varieties, due to its favorable effect on grain length, filling, and weight. PMID:23236132

  1. How significant is submarine groundwater discharge and its associated dissolved inorganic carbon in a river-dominated shelf system-the northern South China Sea?

    NASA Astrophysics Data System (ADS)

    Liu, Q.; Dai, M.; Chen, W.; Huh, C.-A.; Wang, G.; Li, Q.; Charette, M. A.

    2011-12-01

    In order to assess the role of submarine groundwater discharge (SGD) and its impact on the carbonate system on the northern South China Sea (NSCS) shelf, we measured seawater concentrations of four radium isotopes 223,224,226,228Ra along with carbon dioxide parameters in June-July, 2008. Complementary groundwater sampling was conducted in coastal areas in December 2008 and October 2010 to constrain the groundwater end-members. The distribution of Ra isotopes in the NSCS was largely controlled by the Pearl River plume and coastal upwelling. Long-lived Ra isotopes (228Ra and 226Ra) were enriched in the river plume but low in the offshore surface water and subsurface water/upwelling zone. In contrast, short-lived Ra isotopes (224Ra and 223Ra) were elevated in the subsurface water/upwelling zone as well as the river plume but depleted in the offshore surface water. In order to quantify SGD, we adopted two independent mathematical approaches. Using a three end-member mixing model with total alkalinity (TAlk) and Ra isotopes, we derived a SGD flux into the NSCS shelf of 2.3-3.7 ×108 m3 d-1. Our second approach involved a simple mass balance of 228Ra and 226Ra and resulted in a first order but consistent SGD rate estimate of 2.8-4.5 × 108 m3 d-1. These fluxes were equivalent to 13-25 % of the Pearl River discharge, but the source of the SGD is mostly recirculated seawater. Despite the relatively small SGD volume flow compared to the river, the associated material fluxes were substantial given the elevated concentrations of dissolved inorganic solutes. In this case, dissolved inorganic carbon (DIC) flux through SGD was 266-520 × 109 mol yr-1, which was ~44-73 % of the riverine DIC export flux. Given our estimates of the groundwater-derived phosphate flux, SGD may be responsible for new production on the shelf up to 3-6 mmol C m-2 d-1. This rate of new production would at most consume 18 % of the DIC contribution delivered by SGD. Hence, SGD may play an important role in

  2. Lichenoid Reactions in Association with Tumor Necrosis Factor Alpha Inhibitors: A Review of the Literature and Addition of a Fourth Lichenoid Reaction.

    PubMed

    McCarty, Morgan; Basile, Amy; Bair, Brooke; Fivenson, David

    2015-06-01

    In this manuscript, a clinical case of a patient treated with adalimumab for Behcet's disease develops lichen planopilaris. A variety of mucocutaneous lichenoid eruptions have recently been described in association with tumor necrosis factor alpha inhibitors. The authors briefly discuss the clinical and pathological presentation of lichen planopilaris as well as a potential pathogenesis of cutaneous adverse effects seen as the result of tumor necrosis factor alpha inhibitor therapy. They review all case reports of lichen planopilaris occurring on tumor necrosis factor alpha inhibitors and suggest its classification as a fourth recognized pattern on this therapy.

  3. High-pressure metamorphic age and significance of eclogite-facies continental fragments associated with oceanic lithosphere in the Western Alps (Etirol-Levaz Slice, Valtournenche, Italy)

    NASA Astrophysics Data System (ADS)

    Fassmer, Kathrin; Obermüller, Gerrit; Nagel, Thorsten J.; Kirst, Frederik; Froitzheim, Nikolaus; Sandmann, Sascha; Miladinova, Irena; Fonseca, Raúl O. C.; Münker, Carsten

    2016-05-01

    The Etirol-Levaz Slice in the Penninic Alps (Valtournenche, Italy) is a piece of eclogite-facies continental basement sandwiched between two oceanic units, the blueschist-facies Combin Zone in the hanging wall and the eclogite-facies Zermatt-Saas Zone in the footwall. It has been interpreted as an extensional allochthon from the continental margin of Adria, emplaced onto ultramafic and mafic basement of the future Zermatt-Saas Zone by Jurassic, rifting-related detachment faulting, and later subducted together with the future Zermatt-Saas Zone. Alternatively, the Etirol-Levaz Slice could be derived from a different paleogeographic domain and be separated from the Zermatt-Saas Zone by an Alpine shear zone. We present Lu-Hf whole rock-garnet ages of two eclogite samples, one from the center of the unit and one from the border to the Zermatt-Saas Zone below. These data are accompanied by a new geological map of the Etirol-Levaz Slice and the surrounding area, as well as detailed petrology of these two samples. Assemblages, mineral compositions and garnet zoning in both samples indicate a clockwise PT-path and peak-metamorphic conditions of about 550-600 °C/20-25 kbar, similar to conditions proposed for the underlying Zermatt-Saas Zone. Prograde garnet ages of the two samples are 61.8 ± 1.8 Ma and 52.4 ± 2.1 Ma and reflect different timing of subduction. One of these is significantly older than published ages of eclogite-facies metamorphism in the Zermatt-Saas Zone and thus contradicts the hypothesis of Mesozoic emplacement. The occurrence of serpentinite and metagabbro bodies possibly derived from the Zermatt-Saas Zone inside the Etirol-Levaz Slice suggests that the latter is a tectonic composite. The basement slivers forming the Etirol-Levaz Slice and other continental fragments were subducted earlier than the Zermatt-Saas Zone, but nonetheless experienced similar pressure-temperature histories. Our results support the hypothesis that the Zermatt-Saas Zone and the

  4. Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin.

    PubMed

    Diep, Binh An; Le, Vien T M; Visram, Zehra C; Rouha, Harald; Stulik, Lukas; Dip, Etyene Castro; Nagy, Gábor; Nagy, Eszter

    2016-10-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), especially the USA300 pulsotype, is a frequent cause of skin and soft tissue infections and severe pneumonia. Despite appropriate antibiotic treatment, complications are common and pneumonia is associated with high mortality. S. aureus strains express multiple cytotoxins, including alpha-hemolysin (Hla) and up to five bicomponent leukocidins that specifically target phagocytic cells for lysis. CA-MRSA USA300 strains carry the genes for all six cytotoxins. Species specificity of the leukocidins greatly contributes to the ambiguity regarding their role in S. aureus pathogenesis. We performed a comparative analysis of the leukocidin susceptibility of human, rabbit, and mouse polymorphonuclear leukocytes (PMNs) to assess the translational value of mouse and rabbit S. aureus models. We found that mouse PMNs were largely resistant to LukSF-PV, HlgAB, and HlgCB and susceptible only to LukED, whereas rabbit and human PMNs were highly sensitive to all these cytotoxins. In the rabbit pneumonia model with a USA300 CA-MRSA strain, passive immunization with a previously identified human monoclonal antibody (MAb), Hla-F#5, which cross-neutralizes Hla, LukSF-PV, HlgAB, HlgCB, and LukED, provided full protection, whereas an Hla-specific MAb was only partially protective. In the mouse USA300 CA-MRSA pneumonia model, both types of antibodies demonstrated full protection, suggesting that Hla, but not leukocidin(s), is the principal virulence determinant in mice. As the rabbit recapitulates the high susceptibility to leukocidins characteristic of humans, this species represents a valuable model for assessing novel, cytotoxin-targeting anti-S. aureus therapeutic approaches.

  5. Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: Application of the additive model for cancer

    PubMed Central

    Pérez-Morales, Rebeca; Méndez-Ramírez, Ignacio; Castro-Hernández, Clementina; Martínez-Ramírez, Ollin C.; Gonsebatt, María Eugenia; Rubio, Julieta

    2011-01-01

    Lung cancer is the leading cause of cancer mortality in Mexico and worldwide. In the past decade, there has been an increase in the number of lung cancer cases in young people, which suggests an important role for genetic background in the etiology of this disease. In this study, we genetically characterized 16 polymorphisms in 12 low penetrance genes (AhR, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTPI, XRCC1, ERCC2, MGMT, CCND1 and TP53) in 382 healthy Mexican Mestizos as the first step in elucidating the genetic structure of this population and identifying high risk individuals. All of the genotypes analyzed were in Hardy-Weinberg equilibrium, but different degrees of linkage were observed for polymorphisms in the CYP1A1 and EPHX1 genes. The genetic variability of this population was distributed in six clusters that were defined based on their genetic characteristics. The use of a polygenic model to assess the additive effect of low penetrance risk alleles identified combinations of risk genotypes that could be useful in predicting a predisposition to lung cancer. Estimation of the level of genetic susceptibility showed that the individual calculated risk value (iCRV) ranged from 1 to 16, with a higher iCRV indicating a greater genetic susceptibility to lung cancer. PMID:22215955

  6. Additive Manufacturing Infrared Inspection

    NASA Technical Reports Server (NTRS)

    Gaddy, Darrell

    2014-01-01

    Additive manufacturing is a rapid prototyping technology that allows parts to be built in a series of thin layers from plastic, ceramics, and metallics. Metallic additive manufacturing is an emerging form of rapid prototyping that allows complex structures to be built using various metallic powders. Significant time and cost savings have also been observed using the metallic additive manufacturing compared with traditional techniques. Development of the metallic additive manufacturing technology has advanced significantly over the last decade, although many of the techniques to inspect parts made from these processes have not advanced significantly or have limitations. Several external geometry inspection techniques exist such as Coordinate Measurement Machines (CMM), Laser Scanners, Structured Light Scanning Systems, or even traditional calipers and gages. All of the aforementioned techniques are limited to external geometry and contours or must use a contact probe to inspect limited internal dimensions. This presentation will document the development of a process for real-time dimensional inspection technique and digital quality record of the additive manufacturing process using Infrared camera imaging and processing techniques.

  7. Social and Demographic Factors Associated with Morbidities in Young Children in Egypt: A Bayesian Geo-Additive Semi-Parametric Multinomial Model

    PubMed Central

    Khatab, Khaled; Adegboye, Oyelola; Mohammed, Taofeeq Ibn

    2016-01-01

    Background Globally, the burden of mortality in children, especially in poor developing countries, is alarming and has precipitated concern and calls for concerted efforts in combating such health problems. Examples of diseases that contribute to this burden of mortality include diarrhoea, cough, fever, and the overlap between these illnesses, causing childhood morbidity and mortality. Methods To gain insight into these health issues, we employed the 2008 Demographic and Health Survey Data of Egypt, which recorded details from 10,872 children under five. This data focused on the demographic and socio-economic characteristics of household members. We applied a Bayesian multinomial model to assess the area-specific spatial effects and risk factors of co-morbidity of fever, diarrhoea and cough for children under the age of five. Results The results showed that children under 20 months of age were more likely to have the three diseases (OR: 6.8; 95% CI: 4.6–10.2) than children between 20 and 40 months (OR: 2.14; 95% CI: 1.38–3.3). In multivariate Bayesian geo-additive models, the children of mothers who were over 20 years of age were more likely to have only cough (OR: 1.2; 95% CI: 0.9–1.5) and only fever (OR: 1.2; 95% CI: 0.91–1.51) compared with their counterparts. Spatial results showed that the North-eastern region of Egypt has a higher incidence than most of other regions. Conclusions This study showed geographic patterns of Egyptian governorates in the combined prevalence of morbidity among Egyptian children. It is obvious that the Nile Delta, Upper Egypt, and south-eastern Egypt have high rates of diseases and are more affected. Therefore, more attention is needed in these areas. PMID:27442018

  8. EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2+, basal-like, and HER2 intrinsic subtypes of breast cancer

    PubMed Central

    Soysal, S D; Muenst, S; Barbie, T; Fleming, T; Gao, F; Spizzo, G; Oertli, D; Viehl, C T; Obermann, E C; Gillanders, W E

    2013-01-01

    Background: Epithelial cell adhesion molecule (EpCAM) is frequently expressed in breast cancer, and its expression has been associated with poor prognosis. Breast cancer can be subdivided into intrinsic subtypes, differing in prognosis and response to therapy. Methods: To investigate the association between EpCAM expression and prognosis in the intrinsic subtypes of breast cancer, we performed immunohistochemical studies on a tissue microarray encompassing a total of 1365 breast cancers with detailed clinicopathological annotation and outcomes data. Results: We observed EpCAM expression in 660 out of 1365 (48%) cases. EpCAM expression varied significantly in the different intrinsic subtypes. In univariate analyses of all cases, EpCAM expression was associated with a significantly worse overall survival. In the intrinsic subtypes, EpCAM expression was associated with an unfavourable prognosis in the basal-like and luminal B HER2+ subtypes but associated with a favourable prognosis in the HER2 subtype. Consistently, specific ablation of EpCAM resulted in increased cell viability in the breast cancer cell line SKBR3 (ER−, PR−, and HER2+) but decreased viability in the breast cancer cell line MDA-MB-231 (ER−, PR−, and HER2− ). Conclusion: The differential association of EpCAM expression with prognosis in intrinsic subtypes has important implications for the development of EpCAM-targeted therapies in breast cancer. PMID:23519058

  9. HIF-1α 1772 C/T and 1790 G/A Polymorphisms Are Significantly Associated with Higher Cancer Risk: An Updated Meta-Analysis from 34 Case-Control Studies

    PubMed Central

    Zhang, Chi; Qin, Qin; Liu, Jia; Xu, Li-Ping; Zhao, Lian-Jun; Zhang, Qu; Cai, Jing; Ma, Jian-Xin; Cheng, Hong-Yan; Sun, Xin-Chen

    2013-01-01

    Background HIF-1 activates various genes in cancer progression and metastasis. HIF-1α 1772 C/T and 1790 G/A polymorphisms are reportedly associated with cancer risk; however, the results are inconclusive. Methodology/Principal Findings A meta-analysis of 34 studies that involved 7522 cases and 9847 controls for 1772 C/T and 24 studies that involved 4884 cases and 8154 controls for 1790 G/A was conducted to identify the association of C/T and G/A polymorphisms with cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. HIF-1α 1772 C/T and 1790 G/A polymorphisms were associated with higher cancer risk in homozygote comparison (1772C/T: TT vs. CC: OR = 2.45, 95% CI: 1.52, 3.96; Pheterogeneity = 0.028; 1790G/A: AA vs. GG: OR=4.74, 95% CI: 1.78, 12.6; Pheterogeneity < 0.01), dominant model (1772C/T: TT/CT vs. CC: OR = 1.27, 95% CI: 1.04, 1.55; Pheterogeneity < 0.01, 1790G/A: AA/GA vs. GG: OR = 1.65, 95% CI: 1.05, 2.60; Pheterogeneity < 0.01), T allele versus C allele (T vs. C: OR = 1.42, 95% CI: 1.18, 1.70; Pheterogeneity < 0.01), and A allele versus G allele (A vs. G: OR = 1.83, 95% CI: 1.13, 2.96; Pheterogeneity < 0.01). On a subgroup analysis, the 1772 C/T polymorphism was significantly linked to higher risks for breast cancer, lung cancer, prostate cancer, and cervical cancer, whereas the 1790 G/A polymorphism was significantly linked to higher risks for lung cancer and prostate cancer. A significantly increased cancer risk was found in both Asians and Caucasians for 1772C/T polymorphism, whereas a significantly increased cancer risk was found in Caucasians in the heterozygote comparison and recessive model for 1790G/A polymorphism. Conclusions HIF-1α 1772 C/T and 1790 G/A polymorphisms are significantly associated with higher cancer risk. PMID:24260383

  10. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group.

    PubMed

    Forstpointner, Roswitha; Dreyling, Martin; Repp, Roland; Hermann, Sandra; Hänel, Annette; Metzner, Bernd; Pott, Christiane; Hartmann, Frank; Rothmann, Frank; Rohrberg, Robert; Böck, Hans-Peter; Wandt, Hannes; Unterhalt, Michael; Hiddemann, Wolfgang

    2004-11-15

    In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab may improve the prognosis when combined with chemotherapy. This was investigated in a prospective randomized study in patients with relapsed disease. A total of 147 patients were randomized to receive 4 courses of chemotherapy with 25 mg/m(2) fludarabine on days 1 to 3, 200 mg/m(2) cyclophosphamide on days 1 to 3, and 8 mg/m(2) mitoxantrone on day 1 (FCM), alone or combined with rituximab (375 mg/m(2); R-FCM). Of 128 evaluable patients, 62 were randomized for FCM and 66 for R-FCM. R-FCM revealed an overall response rate of 79% (33% complete remission [CR], 45% partial remission [PR]) as compared with 58% for FCM alone (13% CR, 45% PR; P = .01), with similar results in a subgroup analysis of FL (94% vs 70%) and MCL (58% vs 46%). In the total group, the R-FCM arm was significantly superior concerning progression-free survival (PFS; P = .0381) and overall survival (OS; P = .0030). In FL PFS was significantly longer in the R-FCM arm (P = .0139) whereas in MCL a significantly longer OS was observed (P = .0042). There were no differences in clinically relevant side effects in both study arms. Hence, the addition of rituximab to FCM chemotherapy significantly improves the outcome of relapsed or refractory FL and MCL.

  11. [Patch-testing methods: additional specialised or additional series].

    PubMed

    Cleenewerck, M-B

    2009-01-01

    The tests in the European standard battery must occasionally be supplemented by specialised or additional batteries, particularly where the contact allergy is thought to be of occupational origin. These additional batteries cover all allergens associated with various professional activities (hairdressing, baking, dentistry, printing, etc.) and with different classes of materials and chemical products (glue, plastic, rubber...). These additional tests may also include personal items used by patients on a daily basis such as cosmetics, shoes, plants, textiles and so on.

  12. [Malassezia yeasts and their significance in dermatology].

    PubMed

    Hort, W; Nilles, M; Mayser, P

    2006-07-01

    Yeasts of the genus Malassezia belong to the normal microflora of the human skin. In addition they are known to cause a variety of skin diseases; the most frequent of which is pityriasis versicolor. Malassezia yeasts are also thought to be associated with seborrheic dermatitis, dandruff and Malassezia folliculitis. Recently the significance of Malassezia yeasts as a trigger factor for atopic dermatitis of the head and neck region has been pointed out. The role of the Malassezia yeasts in these different diseases has been controversial in the past and remains an issue because of difficulties in isolation, culture and differentiation of the organism. Thanks to molecular techniques, 10 species can actually be differentiated. The article presents the different Malassezia-associated diseases, their clinical picture, diagnosis and appropriate therapy. In addition the speciation of Malassezia is reviewed. PMID:16758222

  13. Functional Generalized Additive Models.

    PubMed

    McLean, Mathew W; Hooker, Giles; Staicu, Ana-Maria; Scheipl, Fabian; Ruppert, David

    2014-01-01

    We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to t of F{X(t), t} where F(·,·) is an unknown regression function and X(t) is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models. We estimate F(·,·) using tensor-product B-splines with roughness penalties. A pointwise quantile transformation of the functional predictor is also considered to ensure each tensor-product B-spline has observed data on its support. The methods are evaluated using simulated data and their predictive performance is compared with other competing scalar-on-function regression alternatives. We illustrate the usefulness of our approach through an application to brain tractography, where X(t) is a signal from diffusion tensor imaging at position, t, along a tract in the brain. In one example, the response is disease-status (case or control) and in a second example, it is the score on a cognitive test. R code for performing the simulations and fitting the FGAM can be found in supplemental materials available online.

  14. Significant Tsunami Events

    NASA Astrophysics Data System (ADS)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  15. Microbial biosurfactants as additives for food industries.

    PubMed

    Campos, Jenyffer Medeiros; Stamford, Tânia Lúcia Montenegro; Sarubbo, Leonie Asfora; de Luna, Juliana Moura; Rufino, Raquel Diniz; Banat, Ibrahim M

    2013-01-01

    Microbial biosurfactants with high ability to reduce surface and interfacial surface tension and conferring important properties such as emulsification, detergency, solubilization, lubrication and phase dispersion have a wide range of potential applications in many industries. Significant interest in these compounds has been demonstrated by environmental, bioremediation, oil, petroleum, food, beverage, cosmetic and pharmaceutical industries attracted by their low toxicity, biodegradability and sustainable production technologies. Despite having significant potentials associated with emulsion formation, stabilization, antiadhesive and antimicrobial activities, significantly less output and applications have been reported in food industry. This has been exacerbated by uneconomical or uncompetitive costing issues for their production when compared to plant or chemical counterparts. In this review, biosurfactants properties, present uses and potential future applications as food additives acting as thickening, emulsifying, dispersing or stabilising agents in addition to the use of sustainable economic processes utilising agro-industrial wastes as alternative substrates for their production are discussed.

  16. Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study.

    PubMed

    Poirel, H A; Cairo, M S; Heerema, N A; Swansbury, J; Aupérin, A; Launay, E; Sanger, W G; Talley, P; Perkins, S L; Raphaël, M; McCarthy, K; Sposto, R; Gerrard, M; Bernheim, A; Patte, C

    2009-02-01

    Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event-free survival (EFS) in pediatric mature B-cell non-Hodgkin's lymphoma (B-NHL) treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24-associated chromosomal aberrations were +1q (29%), +7q and del(13q) (14% each). The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 (34%) was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS (hazard ratio: 6.1 (P=0.030), 2.5 (P=0.015) and 4.0 (P=0.0003), respectively). The adverse prognosis of R8q24 was observed only in DLBCL, whereas del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk-adapted therapy in childhood mature B-NHL.

  17. Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 international study

    PubMed Central

    Poirel, HA; Cairo, MS; Heerema, NA; Swansbury, J; Aupérin, A; Launay, E; Sanger, WG; Talley, P; Perkins, SL; Raphaël, M; McCarthy, K; Sposto, R; Gerrard, M; Bernheim, A; Patte, C

    2010-01-01

    Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event free survival (EFS) in pediatric mature B-NHL treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt Lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature-B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24 associated chromosomal aberrations were +1q [29%], +7q and del(13q) [14% each]. The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 [34%] was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS [HR: 6.1 (p=0.030), 2.5 (p=0.015), 4.0 (p=0.0003), respectively]. The adverse prognosis of R8q24 was observed only in DLBCL while del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk adapted therapy in childhood mature-B-NHL. PMID:19020548

  18. Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia): A Preliminary Clinical Study.

    PubMed

    Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev

    2016-06-01

    Hypothesis Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies. PMID:27154182

  19. Prevalence of defined ultrasound findings of unknown significance at the second trimester fetal anomaly scan and their association with adverse pregnancy outcomes: the Welsh study of mothers and babies population‐based cohort

    PubMed Central

    Hurt, Lisa; Wright, Melissa; Dunstan, Frank; Thomas, Susan; Brook, Fiona; Morris, Susan; Tucker, David; Wills, Marilyn Ann; Davies, Colin; John, Gareth; Fone, David

    2015-01-01

    Abstract Objective The aim of this article was to estimate the population prevalence of seven defined ultrasound findings of uncertain significance (‘markers’) in the second trimester and the associated risk of adverse pregnancy outcomes. Method A prospective record‐linked cohort study of 30 078 pregnant women who had second trimester anomaly scans between July 2008 and March 2011 in Wales was conducted. Results The prevalence of markers ranged from 43.7 per 1000 singleton pregnancies for cardiac echogenic foci [95% confidence interval (CI): 38.8, 51.1] to 0.6 for mild‐to‐moderate ventriculomegaly (95% CI: 0.3, 1.0). Isolated echogenic bowel was associated with an increased risk of congenital anomalies [risk ratio (RR) 4.54, 95% CI: 2.12, 9.73] and preterm birth (RR 2.30, 95% CI: 1.08, 4.90). Isolated pelvicalyceal dilatation was associated with an increased risk of congenital anomalies (RR 3.82, 95% CI: 2.16, 6.77). Multiple markers were associated with an increased risk of congenital anomalies (RR 5.00, 95% CI: 1.35, 18.40) and preterm birth (RR 3.38, 95% CI 1.20, 9.53). Conclusions These data are useful for counselling families and developing clinical guidance and care pathways following the detection of markers in clinical practice, particularly the need for follow‐up scans to monitor placental function and growth in pregnancies with isolated echogenic bowel, and further investigation for multiple markers. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:26475362

  20. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer

    PubMed Central

    Strickland, Kyle C.; Howitt, Brooke E.; Shukla, Sachet A.; Rodig, Scott; Ritterhouse, Lauren L.; Liu, Joyce F.; Garber, Judy E.; Chowdhury, Dipanjan; Wu, Catherine J.; D'Andrea, Alan D.; Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.

    2016-01-01

    Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2-mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2-mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs. PMID

  1. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer.

    PubMed

    Strickland, Kyle C; Howitt, Brooke E; Shukla, Sachet A; Rodig, Scott; Ritterhouse, Lauren L; Liu, Joyce F; Garber, Judy E; Chowdhury, Dipanjan; Wu, Catherine J; D'Andrea, Alan D; Matulonis, Ursula A; Konstantinopoulos, Panagiotis A

    2016-03-22

    Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2-mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2-mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs.

  2. Work organization is significantly associated with upper extremities musculoskeletal disorders among employees engaged in interactive computer-telephone tasks of an international bank subsidiary in São Paulo, Brazil.

    PubMed

    Ferreira Júnior, M; Conceição, G M; Saldiva, P H

    1997-04-01

    This study was designed to verify the risk factors for developing upper extremities musculoskeletal disorders (UEMD) among workers engaged in customer service tasks performed by telephone at a private banking corporation in São Paulo, Brazil. The monthly incidence of UEMD in hands and/or wrists in this group was studied retrospectively from January 1993 to June 1995. The statistical analysis was done by using multiple linear regression with the monthly incidence of UEMD considered as dependent variable in models controlled for age, seniority, mean daily regular worktime and overtime per operator, time pressure at work, rest/work schedule, management status, personnel training on postural and muscle stretching, and ergonomic hazards. The variables associated with UEMD were the following: time pressure at work (coefficient = 0.049; p = 0.008) and rest/work schedule (coefficient = -0.047; p = 0.02). The results indicate that working conditions are significantly associated with UEMD, and changes in the working schedule may decrease the incidence of this problem in workers assigned to tasks related to the interactive use of computer-accessible databases during telephone contacts. PMID:9093663

  3. Metformin may function as anti-cancer agent via targeting cancer stem cells: the potential biological significance of tumor-associated miRNAs in breast and pancreatic cancers.

    PubMed

    Bao, Bin; Azmi, Asfar S; Ali, Shadan; Zaiem, Feras; Sarkar, Fazlul H

    2014-06-01

    Metformin is one of the most used diabetic drugs for the management of type II diabetes mellitus (DM) in the world. Increased numbers of epidemiological and clinical studies have provided convincing evidence supporting the role of metformin in the development and progression of a variety of human tumors including breast and pancreatic cancer. Substantial pre-clinical evidence from in vitro and in vivo experimental studies strongly suggests that metformin has an anti-cancer activity mediated through the regulation of several cell signaling pathways including activation of AMP kinase (AMPK), and other direct and indirect mechanisms; however, the detailed mechanism(s) has not yet been fully understood. The concept of cancer stem cells (CSCs) has gained significant attention in recent years due its identification and defining its clinical implications in many different tumors including breast cancer and pancreatic cancer. In this review, we will discuss the protective role of metformin in the development of breast and pancreatic cancers. We will further discuss the role of metformin as an anti-cancer agent, which is in part mediated through targeting CSCs. Finally, we will discuss the potential role of metformin in the modulation of tumor-associated or CSC-associated microRNAs (miRNAs) as part of the novel mechanism of action of metformin in the development and progression of breast and pancreatic cancers. PMID:25333034

  4. Metformin may function as anti-cancer agent via targeting cancer stem cells: the potential biological significance of tumor-associated miRNAs in breast and pancreatic cancers

    PubMed Central

    Bao, Bin; Azmi, Asfar S.; Ali, Shadan; Zaiem, Feras

    2014-01-01

    Metformin is one of the most used diabetic drugs for the management of type II diabetes mellitus (DM) in the world. Increased numbers of epidemiological and clinical studies have provided convincing evidence supporting the role of metformin in the development and progression of a variety of human tumors including breast and pancreatic cancer. Substantial pre-clinical evidence from in vitro and in vivo experimental studies strongly suggests that metformin has an anti-cancer activity mediated through the regulation of several cell signaling pathways including activation of AMP kinase (AMPK), and other direct and indirect mechanisms; however, the detailed mechanism(s) has not yet been fully understood. The concept of cancer stem cells (CSCs) has gained significant attention in recent years due its identification and defining its clinical implications in many different tumors including breast cancer and pancreatic cancer. In this review, we will discuss the protective role of metformin in the development of breast and pancreatic cancers. We will further discuss the role of metformin as an anti-cancer agent, which is in part mediated through targeting CSCs. Finally, we will discuss the potential role of metformin in the modulation of tumor-associated or CSC-associated microRNAs (miRNAs) as part of the novel mechanism of action of metformin in the development and progression of breast and pancreatic cancers. PMID:25333034

  5. Amelioration of the typical cognitive phenotype in a patient with the 5pter deletion associated with Cri-du-chat syndrome in addition to a partial duplication of CTNND2.

    PubMed

    Sardina, Jennifer M; Walters, Allyson R; Singh, Kathryn E; Owen, Renius X; Kimonis, Virginia E

    2014-07-01

    Cri-du-chat is a rare congenital syndrome characterized by intellectual disability, severe speech/developmental delay, dysmorphic features, and additional syndromic findings. The etiology of this disorder is well known, and is attributed to a large deletion on chromosome 5 that typically ranges from band 5p15.2 to the short arm terminus. This region contains CTNND2, a gene encoding a neuronal-specific protein, delta-catenin, which plays a critical role in cellular motility and brain function. The exact involvement of CTNND2 in the cognitive functionality of individuals with Cri-du-chat has not been fully deciphered, but it is thought to be significant. This report describes an 8-year-old African-American female with a complex chromosome 5 abnormality and a relatively mild case of cri-du-chat syndrome. Because of the surprisingly mild cognitive phenotype, although a karyotype had confirmed the 5p deletion at birth, an oligo-SNP microarray was obtained to further characterize her deletion. The array revealed a complex rearrangement, including a breakpoint in the middle of CTNND2, which resulted in a partial deletion and partial duplication of that gene. The array also verified the expected 5p terminal deletion. Although the patient has a significant deletion in CTNND2, half of the gene (including the promoter region) is not only preserved, but is duplicated. The patient's milder cognitive and behavioral presentation, in conjunction with her atypical 5p alteration, provides additional evidence for the role of CTNND2 in the cognitive phenotype of individuals with Cri-du-chat. PMID:24677774

  6. Glacial marine sedimentation: Paleoclimatic significance

    SciTech Connect

    Anderson, J.B.; Ashley, G.M.

    1991-01-01

    This publication resulted from a symposium held during the 1988 Annual Meeting of the Geological Society of America. Many, but not all, contributors to the symposium have papers in this volume. This Special Paper consists of 14 chapters and a Subject/Geographic index. Each chapter has is own list of references. The papers cover a wide range of modem climate/ ocean environments, including papers on glacial marine sediments from Antarctica, the fiords of Alaska, and sediments from the Canadian High Arctic. In addition, three papers discuss [open quote]old[close quotes] glacial marine records (i.e., pre-Tertiary), and one paper discusses the Yakataga Formation of the Gulf of Alaska which is a Miocene-to-late-Pleistocene sequence. The last chapter in the book includes a survey and summary of the evidence for the paleoclimatic significance of glacial marine sediments by the two editors, John Anderson and Gail Ashley. It is worth noting that Anderson and Domack state in the Foreword that there is a considerable variation in terminology; hence they employ a series of definitions which they urge the other authors to employ. They define and explain what they mean by [open quotes]polar ice cap,[close quotes] [open quote]polar tundra (subpolar),[close quotes] and [open quotes]temperate oceanic and boreal[close quotes] in terms of the dominant glacial and glacial marine processes. Although one might quarrel with the terminology, the broad differences between these three glaciological regimes are indeed fundamental and need to be sought in the geological record. The flavor of the volume can be judged by some of the chapter titles. Contributions on Antarctica include a paper by Anderson and other entitled [open quote]Sedimentary facies associated with Antarctica's floating ice masses[close quotes] and a companion paper by Anderson and Domack which deals with the extremely complex glacial marine facies (13 facies are delimited) in McMurdo Sound, Antarctica.

  7. MDS/AML-associated cytogenetic abnormalities in multiple myeloma and monoclonal gammopathy of undetermined significance: evidence for frequent de novo occurrence and multipotent stem cell involvement of del(20q).

    PubMed

    Nilsson, Therese; Nilsson, Lars; Lenhoff, Stig; Rylander, Lars; Astrand-Grundström, Ingbritt; Strömbeck, Bodil; Höglund, Mattias; Turesson, Ingemar; Westin, Jan; Mitelman, Felix; Jacobsen, Sten E W; Johansson, Bertil

    2004-11-01

    Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are characterized cytogenetically by 14q32 rearrangements, -13/13q-, and various trisomies. Occasionally, karyotypic patterns characteristic of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) occur in MM, often signifying therapy-related (t)-MDS/t-AML. Comparison of cytogenetic features in all published MMs (n = 993) and t-MDS/t-AML post-MM (n = 117) revealed significant differences in complexity and ploidy levels and in most genomic changes. Thus, these features often can be used to distinguish between MM and t-MDS/t-AML. Rarely, myeloid-associated aberrations are detected in MM without any signs of MDS/AML. To characterize such abnormalities in MM/MGUS, we ascertained all 122 MM and 26 MGUS/smoldering MM (SMM) cases analyzed in our department. Sixty-six (54%) MMs and 8 (31%) MGUS/SMMs were karyotypically abnormal, of which 6 (9%) MMs and 3 (38%) MGUS/SMMs displayed myeloid abnormalities, that is, +8 (1 case) and 20q- (8 cases) as the sole anomalies, without any evidence of MDS/AML. One patient developed AML, whereas no MDS/AML occurred in the remaining 8 patients. In one MGUS with del(20q), fluorescence in situ hybridization analyses revealed its presence in CD34+CD38- (hematopoietic stem cells), CD34+CD38+ (progenitors), CD19+ (B cells), and CD15+ (myeloid cells). The present data indicate that 20q- occurs in 10% of karyotypically abnormal MM/MGUS cases and that it might arise at a multipotent progenitor/stem cell level. PMID:15334545

  8. Are changes in glycaemic control associated with diabetes-specific quality of life and health status in screen-detected type 2 diabetes patients? Four-year follow up of the ADDITION-Cambridge cohort

    PubMed Central

    Kuznetsov, L; Long, G H; Griffin, S J; Simmons, R K

    2015-01-01

    Background Interventions that improve HbA1c levels do not necessarily improve health-related quality of life (QoL). This issue may be particularly relevant in asymptomatic diabetes patients detected earlier in the course of the disease. Methods HbA1c, diabetes-specific QoL (ADDQoL) and health status were measured in 510 screen-detected diabetes patients from the ADDITION-Cambridge trial at 1 and 5 years post diagnosis. Multivariable logistic/linear regression was used to quantify the longitudinal association between change in HbA1c from 1 to 5 years and ADDQoL and health status at 5 years, adjusting for age, sex, education and trial group; alcohol consumption, smoking, physical activity, plasma vitamin C, HbA1c, ADDQoL or health status at 1 year, and glucose-lowering medication at 5 years. Results From 1 to 5 years, median HbA1c interquartile range increased from 6.3% (5.9–6.8) to 6.8% (6.4–7.4); the median ADDQoL score and mean health status physical health summary score decreased from -0.4 (-1 to -0.08) to -0.5 (-1.08 to -0.09) (suggesting an adverse impact of diabetes on QoL) and by -0.79 (8.94) points, respectively. Increases in HbA1c were independently associated with reporting a negative impact of diabetes on QoL (OR = 1.38, 95% CI: 1.03 to 1.85) but not with the health status summary scores. Conclusions Increases in HbA1c from 1 to 5 years post-diagnosis were independently associated with increased odds of reporting a negative impact of diabetes on QoL. While our results suggest that efforts to reduce HbA1c do not adversely affect health-related QoL, large numbers of participants still report a negative impact of diabetes on their QoL 5 years post-diagnosis. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd. PMID:24817063

  9. [Food additives and healthiness].

    PubMed

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects.

  10. Elevation of neuron specific enolase and brain iron deposition on susceptibility-weighted imaging as diagnostic clues for beta-propeller protein-associated neurodegeneration in early childhood: Additional case report and review of the literature.

    PubMed

    Takano, Kyoko; Shiba, Naoko; Wakui, Keiko; Yamaguchi, Tomomi; Aida, Noriko; Inaba, Yuji; Fukushima, Yoshimitsu; Kosho, Tomoki

    2016-02-01

    Beta-propeller protein-associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a subtype of neurodegeneration with brain iron accumulation (NBIA). BPAN is caused by mutations in an X-linked gene WDR45 that is involved in autophagy. BPAN is characterized by developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. Brain magnetic resonance imaging (MRI) shows iron deposition in the bilateral globus pallidus (GP) and substantia nigra (SN). Clinical manifestations and laboratory findings in early childhood are limited. We report a 3-year-old girl with BPAN who presented with severe developmental delay and characteristic facial features. In addition to chronic elevation of serum aspartate transaminase, lactate dehydrogenase, creatine kinase, and soluble interleukin-2 receptor, she had persistent elevation of neuron specific enolase (NSE) in serum and cerebrospinal fluid. MRI using susceptibility-weighted imaging (SWI) demonstrated iron accumulation in the GP and SN bilaterally. Targeted next-generation sequencing identified a de novo splice-site mutation, c.831-1G>C in WDR45, which resulted in aberrant splicing evidenced by reverse transcriptase-PCR. Persistent elevation of NSE and iron deposition on SWI may provide clues for diagnosis of BPAN in early childhood.

  11. Pre- and/or Intra-Operative Prescription of Diuretics, but Not Renin-Angiotensin-System Inhibitors, Is Significantly Associated with Acute Kidney Injury after Non-Cardiac Surgery: A Retrospective Cohort Study

    PubMed Central

    Tagawa, Miho; Ogata, Ai; Hamano, Takayuki

    2015-01-01

    Background and Objectives Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. Design, Setting, Participants, and Measurements This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output < 0.5 ml/kg/hour for > 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. Results There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1). Conclusions Prescription of diuretics, but not ACE-I/ARB, was independently associated with

  12. Clinical significance of chimerism.

    PubMed

    Abuelo, Dianne

    2009-05-15

    Twins have been previously classified as either monozygotic or dizygotic. In recent years, fascinating, non-traditional mechanisms of twinning have been uncovered. We define chimerism versus mosaicism, touch on chimerism in the animal world, and explain timing of chimerism in humans. In addition, we discuss when to suspect chimerism in patients, and how to proceed with diagnostic evaluation and confirmation.

  13. The significance of research

    NASA Astrophysics Data System (ADS)

    2014-02-01

    When promoting the value of their research or procuring funding, researchers often need to explain the significance of their work to the community -- something that can be just as tricky as the research itself.

  14. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Fletcher, James C. (Inventor); Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1992-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  15. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1993-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of the additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  16. Correlation between the expression of DNMT1, and GSTP1 and APC, and the methylation status of GSTP1 and APC in association with their clinical significance in prostate cancer

    PubMed Central

    ZHANG, WEIJIE; JIAO, HONGLIANG; ZHANG, XUDONG; ZHAO, RUIHUA; WANG, FENG; HE, WEI; ZONG, HONG; FAN, QINGXIA; WANG, LIUXING

    2015-01-01

    The aim of the present study was to investigate the correlation between the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1), glutathione S-transferase-P1 (GSTP1) and adenomatous polyposis coli (APC), and the methylation status of GSTP1 and APC in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), and to examine its clinical significance. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of DNMT1, GSTP1 and APC in 56 samples of PCa tissue and 10 samples of BPH tissue. Methylation-specific-PCR was used to detect the methylation status of the CpG island promoters of GSTP1 and APC. The positive rate of expression of DNMT1 in poorly-differentiated PCa, moderately-differentiated PCa, well-differentiated PCa and BPH was 86.7%, 70.6%, 55.6% and 30.0%, respectively (P<0.05); for GSTP1, the positive rate was 13.3%, 29.4%, 44.4% and 90.0%, respectively (P<0.05); and for APC, the positive rate was 23.3%, 47.6%, 55.6% and 70.0%, respectively (P<0.05). The correlation coefficient for the association between the expression of DNMT1 and GSTP1 was −0.891 (P<0.05). Between the expression of DNMT1 and APC, the correlation coefficient was −0.721 (P<0.05). GSTP1 and APC were hypermethylated in the majority of PCa tissue samples. The positive rate of methylation of these genes in poorly-differentiated PCa was 83.3% and 73.3%, respectively. By contrast, hypomethylation (or demethylation) was observed in BPH samples, in which the positive rate of methylation was 10.0% and 20.0%, respectively (P<0.05). The increased expression of DNMT1, and the reduced expression of GSTP1 and APC have an important role in the development of PCa. Due to the high expression of DNMT1 mRNA, it is likely that the hypermethylation of CpG islands contributed to the silencing of GSTP1 and APC in PCa tissues. PMID:25738352

  17. Significant lexical relationships

    SciTech Connect

    Pedersen, T.; Kayaalp, M.; Bruce, R.

    1996-12-31

    Statistical NLP inevitably deals with a large number of rare events. As a consequence, NLP data often violates the assumptions implicit in traditional statistical procedures such as significance testing. We describe a significance test, an exact conditional test, that is appropriate for NLP data and can be performed using freely available software. We apply this test to the study of lexical relationships and demonstrate that the results obtained using this test are both theoretically more reliable and different from the results obtained using previously applied tests.

  18. Food additives and preschool children.

    PubMed

    Martyn, Danika M; McNulty, Breige A; Nugent, Anne P; Gibney, Michael J

    2013-02-01

    Food additives have been used throughout history to perform specific functions in foods. A comprehensive framework of legislation is in place within Europe to control the use of additives in the food supply and ensure they pose no risk to human health. Further to this, exposure assessments are regularly carried out to monitor population intakes and verify that intakes are not above acceptable levels (acceptable daily intakes). Young children may have a higher dietary exposure to chemicals than adults due to a combination of rapid growth rates and distinct food intake patterns. For this reason, exposure assessments are particularly important in this age group. The paper will review the use of additives and exposure assessment methods and examine factors that affect dietary exposure by young children. One of the most widely investigated unfavourable health effects associated with food additive intake in preschool-aged children are suggested adverse behavioural effects. Research that has examined this relationship has reported a variety of responses, with many noting an increase in hyperactivity as reported by parents but not when assessed using objective examiners. This review has examined the experimental approaches used in such studies and suggests that efforts are needed to standardise objective methods of measuring behaviour in preschool children. Further to this, a more holistic approach to examining food additive intakes by preschool children is advisable, where overall exposure is considered rather than focusing solely on behavioural effects and possibly examining intakes of food additives other than food colours.

  19. TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection

    PubMed Central

    Cavalla, Franco; Biguetti, Claudia Cristina; Colavite, Priscila Maria; Silveira, Elcia Varise; Martins, Walter; Letra, Ariadne; Trombone, Ana Paula Favaro; Silva, Renato Menezes; Garlet, Gustavo Pompermaier

    2015-01-01

    Th1-polarized host response, mediated by IFN-γ, has been associated with increased severity of periodontal disease as well as control of periodontal infection. The functional polymorphism TBX21-1993T/C (rs4794067) increases the transcriptional activity of the TBX21 gene (essential for Th1 polarization) resulting in a predisposition to a Th-1 biased immune response. Thus, we conducted a case-control study, including a population of healthy controls (H, n = 218), chronic periodontitis (CP, n = 197), and chronic gingivitis patients (CG, n = 193), to investigate if genetic variations in TBX21 could impact the development of Th1 responses, and consequently influence the pattern of bacterial infection and periodontitis outcome. We observed that the polymorphic allele T was significantly enriched in the CP patients compared to CG subjects, while the H controls demonstrated and intermediate genotype. Also, investigating the putative functionality TBX21-1993T/C in the modulation of local response, we observed that the transcripts levels of T-bet, but not of IFN-γ, were upregulated in homozygote and heterozygote polymorphic subjects. In addition, TBX21-1993T/C did not influence the pattern of bacterial infection or the clinical parameters of disease severity, being the presence/absence of red complex bacteria the main factor associated with the disease status and the subrogate variable probing depth (PD) in the logistic regression analysis. PMID:25832120

  20. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

  1. Smog control fuel additives

    SciTech Connect

    Lundby, W.

    1993-06-29

    A method is described of controlling, reducing or eliminating, ozone and related smog resulting from photochemical reactions between ozone and automotive or industrial gases comprising the addition of iodine or compounds of iodine to hydrocarbon-base fuels prior to or during combustion in an amount of about 1 part iodine per 240 to 10,000,000 parts fuel, by weight, to be accomplished by: (a) the addition of these inhibitors during or after the refining or manufacturing process of liquid fuels; (b) the production of these inhibitors for addition into fuel tanks, such as automotive or industrial tanks; or (c) the addition of these inhibitors into combustion chambers of equipment utilizing solid fuels for the purpose of reducing ozone.

  2. Significance of brown dwarfs

    NASA Technical Reports Server (NTRS)

    Black, D. C.

    1986-01-01

    The significance of brown dwarfs for resolving some major problems in astronomy is discussed. The importance of brown dwarfs for models of star formation by fragmentation of molecular clouds and for obtaining independent measurements of the ages of stars in binary systems is addressed. The relationship of brown dwarfs to planets is considered.

  3. Statistical Significance Testing.

    ERIC Educational Resources Information Center

    McLean, James E., Ed.; Kaufman, Alan S., Ed.

    1998-01-01

    The controversy about the use or misuse of statistical significance testing has become the major methodological issue in educational research. This special issue contains three articles that explore the controversy, three commentaries on these articles, an overall response, and three rejoinders by the first three authors. They are: (1)…

  4. [Significant events in Polish psychiatry in 2003?].

    PubMed

    Bomba, Jacek

    2004-01-01

    The aim of this paper was a reflection on the most significant events in Polish psychiatry in 2003. Reform in health care financing and its realisation in 2003 introduced a risk of inhibiting further development of mental health care. The endangerment is a result of allocation of resources, which is inadequate to real costs and promotes in-patient treatment. An additional risk is seen in a project of privatisation of health care institutions. Increasing orientation towards methodology of molecular biology, which is similar to a general global tendency, influences research in psychiatry. Nevertheless the low number of publications resulting from government sponsored studies is disturbing. The situation in forensic psychiatry calls for involvement and studies. Psychiatria Polska published a report indicating low standard of psychiatric expertise for courts and high probability of corruption. The same was reflected in mass media publications later on. Polish Psychiatric Association Board had appointed a special commission to study this problem.

  5. Tougher Addition Polyimides Containing Siloxane

    NASA Technical Reports Server (NTRS)

    St. Clair, T. L.; Maudgal, S.

    1986-01-01

    Laminates show increased impact resistances and other desirable mechanical properties. Bismaleamic acid extended by reaction of diaminosiloxane with maleic anhydride in 1:1 molar ratio, followed by reaction with half this molar ratio of aromatic dianhydride. Bismaleamic acid also extended by reaction of diaminosiloxane with maleic anhydride in 1:2 molar ratio, followed by reaction with half this molar ratio of aromatic diamine (Michael-addition reaction). Impact resistances improved over those of unmodified bismaleimide, showing significant increase in toughness. Aromatic addition polyimides developed as both matrix and adhesive resins for applications on future aircraft and spacecraft.

  6. Phenylethynyl Containing Reactive Additives

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor); Hergenrother, Paul M. (Inventor)

    2002-01-01

    Phenylethynyl containing reactive additives were prepared from aromatic diamine, containing phenylethvnvl groups and various ratios of phthalic anhydride and 4-phenylethynviphthalic anhydride in glacial acetic acid to form the imide in one step or in N-methyl-2-pvrrolidinone to form the amide acid intermediate. The reactive additives were mixed in various amounts (10% to 90%) with oligomers containing either terminal or pendent phenylethynyl groups (or both) to reduce the melt viscosity and thereby enhance processability. Upon thermal cure, the additives react and become chemically incorporated into the matrix and effect an increase in crosslink density relative to that of the host resin. This resultant increase in crosslink density has advantageous consequences on the cured resin properties such as higher glass transition temperature and higher modulus as compared to that of the host resin.

  7. Tales of significance.

    PubMed

    Bell, Graham

    2016-01-01

    In this experiment, the authors were interested in testing the effect of a small molecule inhibitor on the ratio of males and females in the offspring of their model Dipteran species. The authors report that in a wild-type population, ~50 % of offspring are male. They then test the effect of treating females with the chemical, which they think might affect the male:female ratio compared with the untreated group. They claim that there is a statistically significant increase in the percentage of males produced and conclude that the drug affects sex ratios. PMID:27338560

  8. Multifunctional fuel additives

    SciTech Connect

    Baillargeon, D.J.; Cardis, A.B.; Heck, D.B.

    1991-03-26

    This paper discusses a composition comprising a major amount of a liquid hydrocarbyl fuel and a minor low-temperature flow properties improving amount of an additive product of the reaction of a suitable diol and product of a benzophenone tetracarboxylic dianhydride and a long-chain hydrocarbyl aminoalcohol.

  9. Biobased lubricant additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fully biobased lubricants are those formulated using all biobased ingredients, i.e. biobased base oils and biobased additives. Such formulations provide the maximum environmental, safety, and economic benefits expected from a biobased product. Currently, there are a number of biobased base oils that...

  10. The glycemic index: physiological significance.

    PubMed

    Esfahani, Amin; Wong, Julia M W; Mirrahimi, Arash; Srichaikul, Korbua; Jenkins, David J A; Kendall, Cyril W C

    2009-08-01

    The glycemic index (GI) is a physiological assessment of a food's carbohydrate content through its effect on postprandial blood glucose concentrations. Evidence from trials and observational studies suggests that this physiological classification may have relevance to those chronic Western diseases associated with overconsumption and inactivity leading to central obesity and insulin resistance. The glycemic index classification of foods has been used as a tool to assess potential prevention and treatment strategies for diseases where glycemic control is of importance, such as diabetes. Low GI diets have also been reported to improve the serum lipid profile, reduce C-reactive protein (CRP) concentrations, and aid in weight control. In cross-sectional studies, low GI or glycemic load diets (mean GI multiplied by total carbohydrate) have been associated with higher levels of high-density lipoprotein cholesterol (HDL-C), with reduced CRP concentrations, and, in cohort studies, with decreased risk of developing diabetes and cardiovascular disease. In addition, some case-control and cohort studies have found positive associations between dietary GI and risk of various cancers, including those of the colon, breast, and prostate. Although inconsistencies in the current findings still need to be resolved, sufficient positive evidence, especially with respect to renewed interest in postprandial events, suggests that the glycemic index may have a role to play in the treatment and prevention of chronic diseases.

  11. Statistical or biological significance?

    PubMed

    Saxon, Emma

    2015-01-01

    Oat plants grown at an agricultural research facility produce higher yields in Field 1 than in Field 2, under well fertilised conditions and with similar weather exposure; all oat plants in both fields are healthy and show no sign of disease. In this study, the authors hypothesised that the soil microbial community might be different in each field, and these differences might explain the difference in oat plant growth. They carried out a metagenomic analysis of the 16 s ribosomal 'signature' sequences from bacteria in 50 randomly located soil samples in each field to determine the composition of the bacterial community. The study identified >1000 species, most of which were present in both fields. The authors identified two plant growth-promoting species that were significantly reduced in soil from Field 2 (Student's t-test P < 0.05), and concluded that these species might have contributed to reduced yield. PMID:26541972

  12. Anthropological significance of phenylketonuria.

    PubMed

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations.

  13. Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain.

    PubMed

    Duarte, Rodrigo R R; Troakes, Claire; Nolan, Matthew; Srivastava, Deepak P; Murray, Robin M; Bray, Nicholas J

    2016-09-01

    Chromosome 10q24.32-q24.33 is one of the most robustly supported risk loci to emerge from genome-wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele-specific expression to assess cis-regulatory effects associated with the two best-supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis-effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

  14. Genome‐wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis‐regulation of BORCS7, AS3MT, and NT5C2 in the human brain

    PubMed Central

    Duarte, Rodrigo R. R.; Troakes, Claire; Nolan, Matthew; Srivastava, Deepak P.; Murray, Robin M.

    2016-01-01

    Chromosome 10q24.32‐q24.33 is one of the most robustly supported risk loci to emerge from genome‐wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele‐specific expression to assess cis‐regulatory effects associated with the two best‐supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis‐effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27004590

  15. Yawning and its physiological significance

    PubMed Central

    Gupta, Sharat; Mittal, Shallu

    2013-01-01

    Although yawning is a commonly witnessed human behavior, yet it has not been taught in much detail in medical schools because, until the date, no particular physiological significance has been associated with it. It is characterized by opening up of mouth which is accompanied by a long inspiration, with a brief interruption of ventilation and followed by a short expiration. Since time immemorial, yawning has been associated with drowsiness and boredom. However, this age old belief is all set to change as the results of some newer studies have pointed out that yawning might be a way by which our body is trying to accomplish some more meaningful goals. In this review, we have tried to put together some of the important functions that have been proposed by a few authors, with the hope that this article will stimulate the interest of newer researchers in this hitherto unexplored field. PMID:23776833

  16. Vinyl capped addition polyimides

    NASA Technical Reports Server (NTRS)

    Vannucci, Raymond D. (Inventor); Malarik, Diane C. (Inventor); Delvigs, Peter (Inventor)

    1991-01-01

    Polyimide resins (PMR) are generally useful where high strength and temperature capabilities are required (at temperatures up to about 700 F). Polyimide resins are particularly useful in applications such as jet engine compressor components, for example, blades, vanes, air seals, air splitters, and engine casing parts. Aromatic vinyl capped addition polyimides are obtained by reacting a diamine, an ester of tetracarboxylic acid, and an aromatic vinyl compound. Low void materials with improved oxidative stability when exposed to 700 F air may be fabricated as fiber reinforced high molecular weight capped polyimide composites. The aromatic vinyl capped polyimides are provided with a more aromatic nature and are more thermally stable than highly aliphatic, norbornenyl-type end-capped polyimides employed in PMR resins. The substitution of aromatic vinyl end-caps for norbornenyl end-caps in addition polyimides results in polymers with improved oxidative stability.

  17. Tackifier for addition polyimides

    NASA Technical Reports Server (NTRS)

    Butler, J. M.; St.clair, T. L.

    1980-01-01

    A modification to the addition polyimide, LaRC-160, was prepared to improve tack and drape and increase prepeg out-time. The essentially solventless, high viscosity laminating resin is synthesized from low cost liquid monomers. The modified version takes advantage of a reactive, liquid plasticizer which is used in place of solvent and helps solve a major problem of maintaining good prepeg tack and drape, or the ability of the prepeg to adhere to adjacent plies and conform to a desired shape during the lay up process. This alternate solventless approach allows both longer life of the polymer prepeg and the processing of low void laminates. This approach appears to be applicable to all addition polyimide systems.

  18. Electrophilic addition of astatine

    SciTech Connect

    Norseev, Yu.V.; Vasaros, L.; Nhan, D.D.; Huan, N.K.

    1988-03-01

    It has been shown for the first time that astatine is capable of undergoing addition reactions to unsaturated hydrocarbons. A new compound of astatine, viz., ethylene astatohydrin, has been obtained, and its retention numbers of squalane, Apiezon, and tricresyl phosphate have been found. The influence of various factors on the formation of ethylene astatohydrin has been studied. It has been concluded on the basis of the results obtained that the univalent cations of astatine in an acidic medium is protonated hypoastatous acid.

  19. Septic tank additive impacts on microbial populations.

    PubMed

    Pradhan, S; Hoover, M T; Clark, G H; Gumpertz, M; Wollum, A G; Cobb, C; Strock, J

    2008-01-01

    Environmental health specialists, other onsite wastewater professionals, scientists, and homeowners have questioned the effectiveness of septic tank additives. This paper describes an independent, third-party, field scale, research study of the effects of three liquid bacterial septic tank additives and a control (no additive) on septic tank microbial populations. Microbial populations were measured quarterly in a field study for 12 months in 48 full-size, functioning septic tanks. Bacterial populations in the 48 septic tanks were statistically analyzed with a mixed linear model. Additive effects were assessed for three septic tank maintenance levels (low, intermediate, and high). Dunnett's t-test for tank bacteria (alpha = .05) indicated that none of the treatments were significantly different, overall, from the control at the statistical level tested. In addition, the additives had no significant effects on septic tank bacterial populations at any of the septic tank maintenance levels. Additional controlled, field-based research iswarranted, however, to address additional additives and experimental conditions.

  20. [Submitting studies without significant results].

    PubMed

    Texier, Gaëtan; Meynard, Jean-Baptiste; Michel, Rémy; Migliani, René; Boutin, Jean-Paul

    2007-03-01

    When a study finds that no exposure factor or therapy is significantly related to a given effect, researchers legitimately wonder if the results should be submitted for publication and to what journal. Clinical trials that report significant associations have a higher probability of publication, a phenomenon known as selective publication. The principal reasons of this selective publication include author self-censorship, peer-reviewing, trials not intended for publication, interpretation of the p value, cost of journal subscriptions, and policies. Subsequent reviews and meta-analyses are biased by the unavailability of nonsignificant results. Suggestions for preventing this risk include university training, trial registries, an international standard randomised controlled trial number (ISRCTN), Cochrane collaboration, and the gray literature. Journals (including electronic journals) interested in studies with nonsignificant results are listed. New technologies are changing the relations between publishers, libraries, authors and readers. PMID:17287106

  1. Fungi producing significant mycotoxins.

    PubMed

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  2. Metal Additive Manufacturing: A Review

    NASA Astrophysics Data System (ADS)

    Frazier, William E.

    2014-06-01

    This paper reviews the state-of-the-art of an important, rapidly emerging, manufacturing technology that is alternatively called additive manufacturing (AM), direct digital manufacturing, free form fabrication, or 3D printing, etc. A broad contextual overview of metallic AM is provided. AM has the potential to revolutionize the global parts manufacturing and logistics landscape. It enables distributed manufacturing and the productions of parts-on-demand while offering the potential to reduce cost, energy consumption, and carbon footprint. This paper explores the material science, processes, and business consideration associated with achieving these performance gains. It is concluded that a paradigm shift is required in order to fully exploit AM potential.

  3. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

    There are thousands of agents that are intentionally added to the food that we consume. These include preservatives, stabilizers, conditioners, thickeners, colorings, flavorings, sweeteners, antioxidants, etc. etc. Yet only a surprisingly small number have been associated with hypersensitivity reactions. Amongst all the additives, FD&C dyes have been most frequently associated with adverse reactions. Tartrazine is the most notorious of them all; however, critical review of the medical literature and current Scripps Clinic studies would indicate that tartrazine has been confirmed to be at best only occasionally associated with flares of urticaria or asthma. There is no convincing evidence in the literature of reactivity to the other azo or nonazo dyes. This can also be said of BHA/BHT, nitrites/nitrates and sorbates. Parabens have been shown to elicit IgE mediated hypersensitivity reactions when used as pharmaceutical preservatives; however, as with the other additives noted above, ingested parabens have only occasionally been associated with adverse reactions. MSG, the cause of the 'Chinese restaurant syndrome' has only been linked to asthma in one report. Sulfiting agents used primarily as food fresheners and to control microbial growth in fermented beverages have been established as the cause of any where from mild to severe and even fatal reactions in at least 5% of the asthmatic population. Other reactions reported to follow sulfite ingestion include anaphylaxis, gastro intestinal complaints and dermatological eruptions. The prevalence of these non asthmatic reactions is unknown. The mechanism of sulfite sensitive asthma is also unknown but most likely involves hyperreactivity to inhale SO2 in the great majority of cases; however, there are reports of IgE mediated reactions and other sulfite sensitive asthmatics have been found with low levels of sulfite oxidase; necessary to oxidize endogenous sulfite to sulfate.

  4. Obesity and Metabolic Phenotypes (Metabolically Healthy and Unhealthy Variants) Are Significantly Associated with Prevalence of Elevated C-Reactive Protein and Hepatic Steatosis in a Large Healthy Brazilian Population

    PubMed Central

    Shaharyar, Sameer; Roberson, Lara L.; Jamal, Omar; Younus, Adnan; Blaha, Michael J.; Ali, Shozab S.; Zide, Kenneth; Agatston, Arthur A.; Blumenthal, Roger S.; Conceição, Raquel D.; Santos, Raul D.; Nasir, Khurram

    2015-01-01

    Background. Among the obese, the so-called metabolically healthy obese (MHO) phenotype is thought to confer a lower CVD risk as compared to obesity with typical associated metabolic changes. The present study aims to determine the relationship of different subtypes of obesity with inflammatory-cardiometabolic abnormalities. Methods. We evaluated 5,519 healthy, Brazilian subjects (43 ± 10 years, 78% males), free of known cardiovascular disease. Those with <2 metabolic risk factors (MRF) were considered metabolically healthy, and those with BMI ≥ 25 kg/m2 and/or waist circumference meeting NCEP criteria for metabolic syndrome as overweight/obese (OW). High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and hepatic steatosis (HS) was determined via abdominal ultrasound. Results. Overall, 40% of OW individuals were metabolically healthy, and 12% normal-weight had ≥2 MRF. The prevalence of elevated CRP (≥3 mg/dL) and HS in MHO versus normal weight metabolically healthy group was 22% versus 12%, and 40% versus 8% respectively (P < 0.001). Both MHO individuals and metabolically unhealthy normal weight (MUNW) phenotypes were associated with elevated hsCRP and HS. Conclusion. Our study suggests that MHO and MUNW phenotypes may not be benign and physicians should strive to treat individuals in these subgroups to reverse these conditions. PMID:25838943

  5. 76 FR 55882 - Procurement List; Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... INFORMATION: Additions On 6/17/2011 (76 FR 35415-35417), the Committee for Purchase From People Who Are Blind...--Detergent, Laundry, Biobased with Bleach, Powdered/7930-01-490-7301 NPA: Association for the Blind...

  6. Performance Boosting Additive

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Mainstream Engineering Corporation was awarded Phase I and Phase II contracts from Goddard Space Flight Center's Small Business Innovation Research (SBIR) program in early 1990. With support from the SBIR program, Mainstream Engineering Corporation has developed a unique low cost additive, QwikBoost (TM), that increases the performance of air conditioners, heat pumps, refrigerators, and freezers. Because of the energy and environmental benefits of QwikBoost, Mainstream received the Tibbetts Award at a White House Ceremony on October 16, 1997. QwikBoost was introduced at the 1998 International Air Conditioning, Heating, and Refrigeration Exposition. QwikBoost is packaged in a handy 3-ounce can (pressurized with R-134a) and will be available for automotive air conditioning systems in summer 1998.

  7. Sewage sludge additive

    NASA Technical Reports Server (NTRS)

    Kalvinskas, J. J.; Mueller, W. A.; Ingham, J. D. (Inventor)

    1980-01-01

    The additive is for a raw sewage treatment process of the type where settling tanks are used for the purpose of permitting the suspended matter in the raw sewage to be settled as well as to permit adsorption of the dissolved contaminants in the water of the sewage. The sludge, which settles down to the bottom of the settling tank is extracted, pyrolyzed and activated to form activated carbon and ash which is mixed with the sewage prior to its introduction into the settling tank. The sludge does not provide all of the activated carbon and ash required for adequate treatment of the raw sewage. It is necessary to add carbon to the process and instead of expensive commercial carbon, coal is used to provide the carbon supplement.

  8. Perspectives on Additive Manufacturing

    NASA Astrophysics Data System (ADS)

    Bourell, David L.

    2016-07-01

    Additive manufacturing (AM) has skyrocketed in visibility commercially and in the public sector. This article describes the development of this field from early layered manufacturing approaches of photosculpture, topography, and material deposition. Certain precursors to modern AM processes are also briefly described. The growth of the field over the last 30 years is presented. Included is the standard delineation of AM technologies into seven broad categories. The economics of AM part generation is considered, and the impacts of the economics on application sectors are described. On the basis of current trends, the future outlook will include a convergence of AM fabricators, mass-produced AM fabricators, enabling of topology optimization designs, and specialization in the AM legal arena. Long-term developments with huge impact are organ printing and volume-based printing.

  9. Sarks as additional fermions

    NASA Astrophysics Data System (ADS)

    Agrawal, Jyoti; Frampton, Paul H.; Jack Ng, Y.; Nishino, Hitoshi; Yasuda, Osamu

    1991-03-01

    An extension of the standard model is proposed. The gauge group is SU(2) X ⊗ SU(3) C ⊗ SU(2) S ⊗ U(1) Q, where all gauge symmetries are unbroken. The colour and electric charge are combined with SU(2) S which becomes strongly coupled at approximately 500 GeV and binds preons to form fermionic and vector bound states. The usual quarks and leptons are singlets under SU(2) X but additional fermions, called sarks. transform under it and the electroweak group. The present model explains why no more than three light quark-lepton families can exist. Neutral sark baryons, called narks, are candidates for the cosmological dark matter having the characteristics designed for WIMPS. Further phenomenological implications of sarks are analyzed i including electron-positron annihilation. Z 0 decay, flavor-changing neutral currents. baryon-number non-conservation, sarkonium and the neutron electric dipole moment.

  10. Supplier Selection Using Weighted Utility Additive Method

    NASA Astrophysics Data System (ADS)

    Karande, Prasad; Chakraborty, Shankar

    2015-10-01

    Supplier selection is a multi-criteria decision-making (MCDM) problem which mainly involves evaluating a number of available suppliers according to a set of common criteria for choosing the best one to meet the organizational needs. For any manufacturing or service organization, selecting the right upstream suppliers is a key success factor that will significantly reduce purchasing cost, increase downstream customer satisfaction and improve competitive ability. The past researchers have attempted to solve the supplier selection problem employing different MCDM techniques which involve active participation of the decision makers in the decision-making process. This paper deals with the application of weighted utility additive (WUTA) method for solving supplier selection problems. The WUTA method, an extension of utility additive approach, is based on ordinal regression and consists of building a piece-wise linear additive decision model from a preference structure using linear programming (LP). It adopts preference disaggregation principle and addresses the decision-making activities through operational models which need implicit preferences in the form of a preorder of reference alternatives or a subset of these alternatives present in the process. The preferential preorder provided by the decision maker is used as a restriction of a LP problem, which has its own objective function, minimization of the sum of the errors associated with the ranking of each alternative. Based on a given reference ranking of alternatives, one or more additive utility functions are derived. Using these utility functions, the weighted utilities for individual criterion values are combined into an overall weighted utility for a given alternative. It is observed that WUTA method, having a sound mathematical background, can provide accurate ranking to the candidate suppliers and choose the best one to fulfill the organizational requirements. Two real time examples are illustrated to prove

  11. The oxidation capacity of Mn3O4 nanoparticles is significantly enhanced by anchoring them onto reduced graphene oxide to facilitate regeneration of surface-associated Mn(III).

    PubMed

    Duan, Lin; Wang, Zhongyuan; Hou, Yan; Wang, Zepeng; Gao, Guandao; Chen, Wei; Alvarez, Pedro J J

    2016-10-15

    Metal oxides are often anchored to graphene materials to achieve greater contaminant removal efficiency. To date, the enhanced performance has mainly been attributed to the role of graphene materials as a conductor for electron transfer. Herein, we report a new mechanism via which graphene materials enhance oxidation of organic contaminants by metal oxides. Specifically, Mn3O4-rGO nanocomposites (Mn3O4 nanoparticles anchored to reduced graphene oxide (rGO) nanosheets) enhanced oxidation of 1-naphthylamine (used here as a reaction probe) compared to bare Mn3O4. Spectroscopic analyses (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) show that the rGO component of Mn3O4-rGO was further reduced during the oxidation of 1-naphthylamine, although rGO reduction was not the result of direct interaction with 1-naphthylamine. We postulate that rGO improved the oxidation efficiency of anchored Mn3O4 by re-oxidizing Mn(II) formed from the reaction between Mn3O4 and 1-naphthylamine, thereby regenerating the surface-associated oxidant Mn(III). The proposed role of rGO was verified by separate experiments demonstrating its ability to oxidize dissolved Mn(II) to Mn(III), which subsequently can oxidize 1-naphthylamine. The role of dissolved oxygen in re-oxidizing Mn(II) was ruled out by anoxic (N2-purged) control experiments showing similar results as O2-sparged tests. Opposite pH effects on the oxidation efficiency of Mn3O4-rGO versus bare Mn3O4 were also observed, corroborating the proposed mechanism because higher pH facilitates oxidation of surface-associated Mn(II) even though it lowers the oxidation potential of Mn3O4. Overall, these findings may guide the development of novel metal oxide-graphene nanocomposites for contaminant removal. PMID:27448035

  12. The oxidation capacity of Mn3O4 nanoparticles is significantly enhanced by anchoring them onto reduced graphene oxide to facilitate regeneration of surface-associated Mn(III).

    PubMed

    Duan, Lin; Wang, Zhongyuan; Hou, Yan; Wang, Zepeng; Gao, Guandao; Chen, Wei; Alvarez, Pedro J J

    2016-10-15

    Metal oxides are often anchored to graphene materials to achieve greater contaminant removal efficiency. To date, the enhanced performance has mainly been attributed to the role of graphene materials as a conductor for electron transfer. Herein, we report a new mechanism via which graphene materials enhance oxidation of organic contaminants by metal oxides. Specifically, Mn3O4-rGO nanocomposites (Mn3O4 nanoparticles anchored to reduced graphene oxide (rGO) nanosheets) enhanced oxidation of 1-naphthylamine (used here as a reaction probe) compared to bare Mn3O4. Spectroscopic analyses (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) show that the rGO component of Mn3O4-rGO was further reduced during the oxidation of 1-naphthylamine, although rGO reduction was not the result of direct interaction with 1-naphthylamine. We postulate that rGO improved the oxidation efficiency of anchored Mn3O4 by re-oxidizing Mn(II) formed from the reaction between Mn3O4 and 1-naphthylamine, thereby regenerating the surface-associated oxidant Mn(III). The proposed role of rGO was verified by separate experiments demonstrating its ability to oxidize dissolved Mn(II) to Mn(III), which subsequently can oxidize 1-naphthylamine. The role of dissolved oxygen in re-oxidizing Mn(II) was ruled out by anoxic (N2-purged) control experiments showing similar results as O2-sparged tests. Opposite pH effects on the oxidation efficiency of Mn3O4-rGO versus bare Mn3O4 were also observed, corroborating the proposed mechanism because higher pH facilitates oxidation of surface-associated Mn(II) even though it lowers the oxidation potential of Mn3O4. Overall, these findings may guide the development of novel metal oxide-graphene nanocomposites for contaminant removal.

  13. Impact significance determination-Back to basics

    SciTech Connect

    Lawrence, David P.

    2007-11-15

    Impact significance determination is widely recognized as a vital and critical EIA activity. But impact significance related concepts are poorly understood. And the quality of approaches for impact significance determination in EIA practice remains highly variable. This article seeks to help establish a sound and practical conceptual foundation for formulating and evaluating impact significance determination approaches. It addresses the nature (what is impact significance?), the core characteristics (what are the major properties of significance determination?), the rationale (why are impact significance determinations necessary?), the procedural and substantive objectives (what do impact significance determinations seek to achieve?), and the process for making impact significance judgments (how is impact significance determination conducted?). By identifying fundamental attributes and key distinctions associated with impact significance determinations, a basis is provided for designing and evaluating impact significance determination procedures at both the regulatory and applied levels.

  14. Individualized additional instruction for calculus

    NASA Astrophysics Data System (ADS)

    Takata, Ken

    2010-10-01

    College students enrolling in the calculus sequence have a wide variance in their preparation and abilities, yet they are usually taught from the same lecture. We describe another pedagogical model of Individualized Additional Instruction (IAI) that assesses each student frequently and prescribes further instruction and homework based on the student's performance. Our study compares two calculus classes, one taught with mandatory remedial IAI and the other without. The class with mandatory remedial IAI did significantly better on comprehensive multiple-choice exams, participated more frequently in classroom discussion and showed greater interest in theorem-proving and other advanced topics.

  15. The Mozart Effect: Additional Data.

    PubMed

    Hughes, John R.

    2002-04-01

    After the review of the Mozart effect was published in this journal (Hughes JR. Epilepsy Behav 2001;2:369-417), additional data from the music of Haydn and Liszt have been analyzed that may account for the decrease in seizure activity originally reported during Mozart music. Even with these added data Mozart music continued to score significantly higher than the selections from the other six composers in one of the important characteristics of this music, namely, the repetition of the melody. However Haydn's values were second highest among Mozart, J. S. Bach, Wagner, Beethoven, Chopin, and Liszt.

  16. Additive lattice kirigami

    PubMed Central

    Castle, Toen; Sussman, Daniel M.; Tanis, Michael; Kamien, Randall D.

    2016-01-01

    Kirigami uses bending, folding, cutting, and pasting to create complex three-dimensional (3D) structures from a flat sheet. In the case of lattice kirigami, this cutting and rejoining introduces defects into an underlying 2D lattice in the form of points of nonzero Gaussian curvature. A set of simple rules was previously used to generate a wide variety of stepped structures; we now pare back these rules to their minimum. This allows us to describe a set of techniques that unify a wide variety of cut-and-paste actions under the rubric of lattice kirigami, including adding new material and rejoining material across arbitrary cuts in the sheet. We also explore the use of more complex lattices and the different structures that consequently arise. Regardless of the choice of lattice, creating complex structures may require multiple overlapping kirigami cuts, where subsequent cuts are not performed on a locally flat lattice. Our additive kirigami method describes such cuts, providing a simple methodology and a set of techniques to build a huge variety of complex 3D shapes. PMID:27679822

  17. Additive lattice kirigami

    PubMed Central

    Castle, Toen; Sussman, Daniel M.; Tanis, Michael; Kamien, Randall D.

    2016-01-01

    Kirigami uses bending, folding, cutting, and pasting to create complex three-dimensional (3D) structures from a flat sheet. In the case of lattice kirigami, this cutting and rejoining introduces defects into an underlying 2D lattice in the form of points of nonzero Gaussian curvature. A set of simple rules was previously used to generate a wide variety of stepped structures; we now pare back these rules to their minimum. This allows us to describe a set of techniques that unify a wide variety of cut-and-paste actions under the rubric of lattice kirigami, including adding new material and rejoining material across arbitrary cuts in the sheet. We also explore the use of more complex lattices and the different structures that consequently arise. Regardless of the choice of lattice, creating complex structures may require multiple overlapping kirigami cuts, where subsequent cuts are not performed on a locally flat lattice. Our additive kirigami method describes such cuts, providing a simple methodology and a set of techniques to build a huge variety of complex 3D shapes.

  18. 31 CFR 354.10 - Additional provisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT REGULATIONS GOVERNING BOOK-ENTRY SECURITIES OF THE STUDENT LOAN MARKETING ASSOCIATION (SALLIE MAE) § 354.10 Additional provisions. (a) Additional... Securities in Book-entry System. The interest of a debtor in a Security Entitlement may be reached by...

  19. PARTICLE-ASSOCIATED MICROORGANISMS IN STORMWATER RUNOFF

    EPA Science Inventory

    This research investigated the effects of blending and chemical addition before analysis of the concentration of microorganisms in stormwater runoff to determine whether clumped or particle-associated organisms play a significant role. All organisms, except for Escherichia coli, ...

  20. Some additional considerations in modelling the dynamic traits and genome-wide association studies. Comments on "Mapping complex traits as a dynamic system" by L. Sun and R. Wu

    NASA Astrophysics Data System (ADS)

    Das, Kiranmoy

    2015-06-01

    The revolution in the genetic research in our time is mainly due to (i) the successful completion of human genome project (2003) and its derivative hapmap project (2005), (ii) advanced statistical methodologies for analyzing ultrahigh dimensional data and (iii) the availability of statistical softwares (R, SAS etc.) to analyze large datasets. When complex traits are to be modeled as dynamic systems, the statistical issues regarding the complexity in the model, predictive power of the model, computational cost etc. are to be addressed adequately for powerful inferences. I will mention two additional considerations (statistical) which make dynamic models more meaningful and the results from GWAS more reliable.

  1. Kinetic studies and structural models of the association of E. coli sigma(70) RNA polymerase with the lambdaP(R) promoter: large scale conformational changes in forming the kinetically significant intermediates.

    PubMed

    Saecker, Ruth M; Tsodikov, Oleg V; McQuade, Kristi L; Schlax, Peter E; Capp, Michael W; Record, M Thomas

    2002-06-01

    The kinetics of interaction of Esigma(70) RNA polymerase (R) with the lambdaP(R) promoter (P) were investigated by filter binding over a broad range of temperatures (7.3-42 degrees C) and concentrations of RNA polymerase (1-123 nM) in large excess over promoter DNA. Under all conditions examined, the kinetics of formation of competitor-resistant complexes (I(2), RP(o)) are single-exponential with first order rate constant beta(CR). Interpretation of the polymerase concentration dependence of beta(CR) in terms of the three step mechanism of open complex formation yields the equilibrium constant K(1) for formation of the first kinetically significant intermediate (I(1)) and the forward rate constant (k(2)) for the conformational change converting I(1) to the second kinetically significant intermediate I(2): R + P-->(K(1))<--I(1)(k(2))-->I(2). Use of rapid quench mixing allows K(1) and k(2) to be individually determined over the entire temperature range investigated, previously not possible at this promoter using manual mixing. Given the large (>60 bp) interface formed in I(1), its relatively small binding constant K(1) at 37 degrees C at this [salt] (approximately 6 x 10(6) M(-1)) strongly argues that binding free energy is used to drive large-scale structural changes in polymerase and/or promoter DNA or other coupled processes. Evidence for coupling of protein folding is provided by the large and negative activation heat capacity of k(a)[DeltaC(o,++)(a)= -1.5(+/-0.2)kcal K(-1)], now shown to originate directly from formation of I(1) [DeltaC(o)(1)= -1.4(+/-0.3)kcal K(-1)] rather than from the formation of I(2) as previously proposed. The isomerization I(1)-->I(2) exhibits relatively slow kinetics and has a very large temperature-independent Arrhenius activation energy [E(act)(2)= 34(+/-2)kcal]. This kinetic signature suggests that formation of the transition state (I(1)-I(2)++ involves large conformational changes dominated by changes in the exposure of polar and

  2. MAGNETOMETRY, SELF-POTENTIAL, AND SEISMIC - ADDITIONAL GEOPHYSICAL METHODS HAVING POTENTIALLY SIGNIFICANT FUTURE UTILIZATION IN AGRICULTURE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Geophysical methods can provide important information in agricultural settings, and the use of these techniques are becoming more and more widespread. Magnetrometry, self-potential, and seismic are three geophysical methods, all of which have the potential for substantial future use in agriculture, ...

  3. Significance of Ferritin in Recurrent Oral Ulceration

    PubMed Central

    K., Sumathi; B., Shanthi; Palaneeswari M., Subha; Devi A.J., Manjula

    2014-01-01

    Background: Ferritin is the storage form of iron. Hence, the sensitive test which can be used for diagnosing iron deficiency anaemia is estimation of ferritin in serum. One of the causative factors of oral ulceration is nutritional deficiency, which includes iron also. Aim: To study the meaningful association between recurrent oral ulcer and ferritin. Materials and Methods: Fifty oral ulcer cases which were diagnosed clinically in the ENT Department of Sree Balaji Medical College and Hospital and Twenty Five controls were included in this study. Serum ferritin was estimated by doing a particle enhanced turbidimetric immunoassay for both cases and controls. Results: 66% of cases had decreased ferritin values and 34% had normal values, which was significant. Conclusion: From this study, it can be concluded that it is mandatory to screen oral ulcer patients for iron deficiency anaemia by estimating serum ferritin and it is also advisable for the patients to have iron supplementation on regular basis, along with diet rich in iron in addition to vitamins. PMID:24783067

  4. Astrobiological Significance of Chemolithoautotrophic Acidophiles

    NASA Technical Reports Server (NTRS)

    Pikuta, Elena V.; Hoover, Richard B.

    2003-01-01

    For more than a century (since Winogradsky discovered lithoautotrophic bacteria) a dilemma in microbiology has concerned life that first inhabited the Earth. Which types of life forms first appeared in the primordial oceans during the earliest geological period on Earth as the primary ancestors of modem biological diversity? How did a metabolism of ancestors evolve: from lithoautotrophic to lithohetherotrophic and organoheterotrophic or from organoheterotrophic to organoautotrophic and lithomixotrophic types? At the present time, it is