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Sample records for heterodimer partner shp

  1. Rifampicin does not significantly affect the expression of Small heterodimer partner (SHP in primary human hepatocytes

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    Petr ePavek

    2012-01-01

    Full Text Available The small/short heterodimer partner (SHP, NR0B2 is a nuclear receptor corepressor lacking a DNA binding domain. SHP is induced by bile acid-activated farnesoid X receptor (FXR resulting in CYP7A1 gene suppression. In contrast, Pregnane X receptor (PXR activation by its ligands was recently suggested to inhibit SHP gene transactivation to maximize the induction of PXR target genes. However, there are also conflicting reports in literature whether PXR or rodent Pxr activation down-regulates SHP/Shp expression. Moreover, the PXR-mediated regulation of the SHP gene has been studied only at the SHP mRNA and transactivation (gene reporter assay levels.In this study, we studied the effect of rifampicin, a prototype PXR ligand, on SHP mRNA and protein expression in three primary human hepatocyte cultures.We found that SHP mRNA is not systematically down-regulated in hepatocyte in culture after 24 h treatment with rifampicin. Consistently, we did not observe down-regulation of SHP protein in primary human hepatocytes after 24 and 48 h of incubation with rifampicin.We can conclude that although we observed slight down-regulation of SHP mRNA and protein in several hepatocyte preparations, the phenomenon is unlikely critical for PXR-mediated induction of its target genes.

  2. Ligand-dependent regulation of the activity of the orphan nuclear receptor, small heterodimer partner (SHP), in the repression of bile acid biosynthetic CYP7A1 and CYP8B1 genes.

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    Miao, Ji; Choi, Sung-E; Seok, Sun Mi; Yang, Linda; Zuercher, William J; Xu, Yong; Willson, Timothy M; Xu, H Eric; Kemper, Jongsook Kim

    2011-07-01

    Small heterodimer partner (SHP) plays important roles in diverse biological processes by directly interacting with transcription factors and inhibiting their activities. SHP has been designated an orphan nuclear receptor, but whether its activity can be modulated by ligands has been a long-standing question. Recently, retinoid-related molecules, including 4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3Cl-AHPC), were shown to bind to SHP and enhance apoptosis. We have examined whether 3Cl-AHPC acts as an agonist and increases SHP activity in the repression of bile acid biosynthetic CYP7A1 and CYP8B1 genes and delineated the underlying mechanisms. Contrary to this expectation, micromolar concentrations of 3Cl-AHPC increased CYP7A1 expression but indirectly via p38 kinase signaling. Nanomolar concentrations, however, repressed CYP7A1 expression and decreased bile acid levels in HepG2 cells, and little repression was observed when SHP was down-regulated by small hairpin RNA. Mechanistic studies revealed that 3Cl-AHPC bound to SHP, increased the interaction of SHP with liver receptor homologue (LRH)-1, a hepatic activator for CYP7A1 and CYP8B1 genes, and with repressive cofactors, Brahma, mammalian Sin3a, and histone deacetylase-1, and, subsequently, increased the occupancy of SHP and these cofactors at the promoters. Mutation of Leu-100, predicted to contact 3Cl-AHPC within the SHP ligand binding pocket by molecular modeling, severely impaired the increased interaction with LRH-1, and repression of LRH-1 activity mediated by 3Cl-AHPC. 3Cl-AHPC repressed SHP metabolic target genes in a gene-specific manner in human primary hepatocytes and HepG2 cells. These data suggest that SHP may act as a ligand-regulated receptor in metabolic pathways. Modulation of SHP activity by synthetic ligands may be a useful therapeutic strategy.

  3. Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

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    Li, Guodong [Department of Surgical Oncology, Cancer Treatment Center, The Fourth Affiliated Hospital of Harbin Medical University, Harbin (China); Kong, Bo [Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Zhu, Yan [Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing (China); Zhan, Le [Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Williams, Jessica A. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Tawfik, Ossama [Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Kassel, Karen M. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Luyendyk, James P. [Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI (United States); Wang, Li [Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT (United States); Guo, Grace L., E-mail: guo@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ (United States)

    2013-10-15

    Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR{sup −/−} and SHP{sup −/−} mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR{sup −/−} mice and therefore, increased SHP expression in FXR{sup −/−} mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR{sup −/−} mice with overexpression of SHP in hepatocytes (FXR{sup −/−}/SHP{sup Tg}) and determined the contribution of SHP in HCC development in FXR{sup −/−} mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR{sup −/−} mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR{sup −/−} mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency.

  4. Nuclear Receptor Small Heterodimer Partner in Apoptosis Signaling and Liver Cancer

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    Zhang, Yuxia; Wang, Li, E-mail: l.wang@hsc.utah.edu [Departments of Medicine and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States)

    2011-01-05

    Small heterodimer partner (SHP, NR0B2) is a unique orphan nuclear receptor that contains the dimerization and a putative ligand-binding domain, but lacks the conserved DNA binding domain. SHP exerts its physiological function as an inhibitor of gene transcription through physical interaction with multiple nuclear receptors and transcriptional factors. SHP is a critical transcriptional regulator affecting diverse biological functions, including bile acid, cholesterol and lipid metabolism, glucose and energy homeostasis, and reproductive biology. Recently, we and others have demonstrated that SHP is an epigenetically regulated transcriptional repressor that suppresses the development of liver cancer. In this review, we summarize recent major findings regarding the role of SHP in cell proliferation, apoptosis, and DNA methylation, and discuss recent progress in understanding the function of SHP as a tumor suppressor in the development of liver cancer. Future study will be focused on identifying SHP associated novel prooncogenes and anti-oncogenes in liver cancer progression and applying the knowledge gained on SHP in liver cancer prevention, diagnosis and treatment.

  5. Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis.

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    Kim, Dong-Hyun; Kwon, Sanghoon; Byun, Sangwon; Xiao, Zhen; Park, Sean; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Kemper, Byron; Kemper, Jongsook Kim

    2016-07-14

    Bile acids (BAs) are recently recognized signalling molecules that profoundly affect metabolism. Because of detergent-like toxicity, BA levels must be tightly regulated. An orphan nuclear receptor, Small Heterodimer Partner (SHP), plays a key role in this regulation, but how SHP senses the BA signal for feedback transcriptional responses is not clearly understood. We show an unexpected function of a nucleoporin, RanBP2, in maintaining BA homoeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 co-localizes with SHP at the nuclear envelope region and mediates SUMO2 modification at K68, which facilitates nuclear transport of SHP and its interaction with repressive histone modifiers to inhibit BA synthetic genes. Mice expressing a SUMO-defective K68R SHP mutant have increased liver BA levels, and upon BA- or drug-induced biliary insults, these mice exhibit exacerbated cholestatic pathologies. These results demonstrate a function of RanBP2-mediated SUMOylation of SHP in maintaining BA homoeostasis and protecting from the BA hepatotoxicity.

  6. A Pleiotropic Role for the Orphan Nuclear Receptor Small Heterodimer Partner in Lipid Homeostasis and Metabolic Pathways

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    Gabriella Garruti

    2012-01-01

    Full Text Available Nuclear receptors (NRs comprise one of the most abundant classes of transcriptional regulators of metabolic diseases and have emerged as promising pharmaceutical targets. Small heterodimer partner (SHP; NR0B2 is a unique orphan NR lacking a DNA-binding domain but contains a putative ligand-binding domain. SHP is a transcriptional regulator affecting multiple key biological functions and metabolic processes including cholesterol, bile acid, and fatty acid metabolism, as well as reproductive biology and glucose-energy homeostasis. About half of all mammalian NRs and several transcriptional coregulators can interact with SHP. The SHP-mediated repression of target transcription factors includes at least three mechanisms including direct interference with the C-terminal activation function 2 (AF2 coactivator domains of NRs, recruitment of corepressors, or direct interaction with the surface of NR/transcription factors. Future research must focus on synthetic ligands acting on SHP as a potential therapeutic target in a series of metabolic abnormalities. Current understanding about the pleiotropic role of SHP is examined in this paper, and principal metabolic aspects connected with SHP function will be also discussed.

  7. Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis

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    Kim, Dong-Hyun; Kwon, Sanghoon; Byun, Sangwon; Xiao, Zhen; Park, Sean; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Kemper, Byron; Kemper, Jongsook Kim

    2016-01-01

    Bile acids (BAs) are recently recognized signalling molecules that profoundly affect metabolism. Because of detergent-like toxicity, BA levels must be tightly regulated. An orphan nuclear receptor, Small Heterodimer Partner (SHP), plays a key role in this regulation, but how SHP senses the BA signal for feedback transcriptional responses is not clearly understood. We show an unexpected function of a nucleoporin, RanBP2, in maintaining BA homoeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 co-localizes with SHP at the nuclear envelope region and mediates SUMO2 modification at K68, which facilitates nuclear transport of SHP and its interaction with repressive histone modifiers to inhibit BA synthetic genes. Mice expressing a SUMO-defective K68R SHP mutant have increased liver BA levels, and upon BA- or drug-induced biliary insults, these mice exhibit exacerbated cholestatic pathologies. These results demonstrate a function of RanBP2-mediated SUMOylation of SHP in maintaining BA homoeostasis and protecting from the BA hepatotoxicity. PMID:27412403

  8. Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1

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    Hwa Young Ahn

    2015-12-01

    Full Text Available BackgroundExpression of hepatic cholesterol 7α-hydroxylase (CYP7A1 is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP. In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1.MethodsWe injected thyroid hormone (triiodothyronine, T3 to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR. Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA were also performed using human hepatoma cell lineResultsInitial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.ConclusionWe found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

  9. Retinoic acid regulates several genes in bile acid and lipid metabolism via upregulation of small heterodimer partner in hepatocytes.

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    Mamoon, Abulkhair; Subauste, Angela; Subauste, Maria C; Subauste, Jose

    2014-10-25

    Retinoic acid (RA) affects multiple aspects of development, embryogenesis and cell differentiation processes. The liver is a major organ that stores RA suggesting that retinoids play an important role in the function of hepatocytes. In our previous studies, we have demonstrated the involvement of small heterodimer partner (SHP) in RA-induced signaling in a non-transformed hepatic cell line AML 12. In the present study, we have identified several critical genes in lipid homeostasis (Apoa1, Apoa2 and ApoF) that are repressed by RA-treatment in a SHP dependent manner, in vitro and also in vivo with the use of the SHP null mice. In a similar manner, RA also represses several critical genes involved in bile acid metabolism (Cyp7a1, Cyp8b1, Mdr2, Bsep, Baat and Ntcp) via upregulation of SHP. Collectively our data suggest that SHP plays a major role in RA-induced potential changes in pathophysiology of metabolic disorders in the liver.

  10. Conicasterol E, a small heterodimer partner sparing farnesoid X receptor modulator endowed with a pregnane X receptor agonistic activity, from the marine sponge Theonella swinhoei.

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    Sepe, Valentina; Ummarino, Raffaella; D'Auria, Maria Valeria; Chini, Maria Giovanna; Bifulco, Giuseppe; Renga, Barbara; D'Amore, Claudio; Debitus, Cécile; Fiorucci, Stefano; Zampella, Angela

    2012-01-12

    We report the isolation and pharmacological characterization of conicasterol E isolated from the marine sponge Theonella swinhoei. Pharmacological characterization of this steroid in comparison to CDCA, a natural FXR ligand, and 6-ECDCA, a synthetic FXR agonist generated by an improved synthetic strategy, and rifaximin, a potent PXR agonist, demonstrated that conicasterol E is an FXR modulator endowed with PXR agonistic activity. Conicasterol E induces the expression of genes involved in bile acids detoxification without effect on the expression of small heterodimer partner (SHP), thus sparing the expression of genes involved in bile acids biosynthesis. The relative positioning in the ligand binding domain of FXR, explored through docking calculations, demonstrated a different spatial arrangement for conicasterol E and pointed to the presence of simultaneous and efficient interactions with the receptor. In summary, conicasterol E represents a FXR modulator and PXR agonist that might hold utility in treatment of liver disorders.

  11. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha activation of CYP7A1 during food restriction and diabetes is still inhibited by small heterodimer partner.

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    Shin, Dong-Ju; Osborne, Timothy F

    2008-05-30

    Cholesterol 7alpha-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the classic pathway of hepatic bile acid biosynthesis from cholesterol. During fasting and in type I diabetes, elevated levels of peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1alpha) induce expression of the Cyp7A1 gene and overexpression of PGC-1alpha in hepatoma cells stimulates bile acid synthesis. Using Ad-PGC-1alpha-RNA interference to induce acute disruption of PGC-1alpha in mice, here we show that PGC-1alpha is necessary for fasting-mediated induction of CYP7A1. Co-immunoprecipitation and promoter activation studies reveal that the induction of CYP7A1 is mediated by direct interaction between PGC-1alpha and the AF2 domain of liver receptor homolog-1 (LRH-1). In contrast, the very similar PGC-1beta could not substitute for PGC-1alpha. We also show that transactivation of PGC-1alpha and LRH-1 is repressed by the small heterodimer partner (SHP). Treatment of mice with GW4064, a synthetic agonist for farnesoid X receptor, induced SHP expression and decreased both the recruitment of PGC-1alpha to the Cyp7A1 promoter and the fasting-induced expression of CYP7A1 mRNA. These data suggest that PGC-1alpha is an important co-activator for LRH-1 and that SHP targets the interaction between LRH-1 and PGC-1alpha to inhibit CYP7A1 expression. Overall, these studies provide further evidence for the important role of PGC-1alpha in bile acid homeostasis and suggest that pharmacological targeting of farnesoid X receptor in vivo can be used to reverse the increase in CYP7A1 associated with adverse metabolic conditions.

  12. Small heterodimer partner 1 directly interacts with NS5A viral protein and has a key role in HCV related liver cell transformation.

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    Conti, Beatrice; Porcu, Cristiana; Viscomi, Carmela; Minutolo, Antonella; Costantini, Susan; Corazzari, Marco; Iannucci, Gino; Barbaro, Barbara; Balsano, Clara

    2016-12-20

    HCV life cycle is strictly correlated with the hepatocyte lipid metabolism; moreover, the progression of HCV chronic hepatitis is accelerated by the presence of liver steatosis. Among the steatogenic genes deregulated during the HCV infection one of the most attractive is the Small Heterodimer Protein 1 (SHP1; NR0B2), that is involved in a remarkable number of metabolic functions. HCV NS5A is an essential and integral component of the HCV membranous-web replicon complex (RC) and plays an essential role to transfer the viral genome from the RCs to the surface of the lipid droplets (LDs) that, in turn, play a key function during HCV life cycle.With the help of a HCV infection model, we demonstrate a functional interaction between SHP1 and HCV NS5A protein. SHP1 silencing (siSHP1) reversed the pro-oncogenic effects of HCV infection, inducing a significant decrease in liver lipid accumulation and in NS5A protein expression. Moreover, siSHP1 causes a strong modulation of some genes involved in HCV-related EMT, such as: HNF4, a central regulators of hepatocyte differentiation, E-Cadherin, SNAILs.Our data suggest that SHP1 results not only to be strictly connected to the pathogenesis of HCV-related liver steatosis, but also to its progression towards the liver transformation.

  13. The orphan nuclear receptor SHP is a positive regulator of osteoblastic bone formation.

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    Jeong, Byung-Chul; Lee, Yong-Soo; Bae, In-Ho; Lee, Chul-Ho; Shin, Hong-In; Ha, Hyun Jung; Franceschi, Renny T; Choi, Hueng-Sik; Koh, Jeong-Tae

    2010-02-01

    The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) interacts with a diverse array of transcription factors and regulates a variety of cellular events such as cell proliferation, differentiation, and metabolism. However, the role of SHP in bone formation has not yet been elucidated. SHP expression is significantly increased during osteoblast differentiation, and its expression is partially regulated by bone morphogenetic protein 2 (BMP-2), which plays an important role in bone formation. In our study, inhibition of SHP expression significantly repressed BMP-2-induced osteoblast differentiation and ectopic bone formation. In accordance with these in vitro and in vivo results, osteoblast differentiation in SHP(-/-) mice primary osteoblasts was significantly repressed, and the mice showed decreased bone mass resulting from decreased numbers of osteoblasts. Finally, SHP physically interacts and forms a complex with runt-related transcription factor 2 (Runx2) on the osteocalcin gene promoter, and overexpression of SHP increased Runx2 transactivity via competition with histone deacetylase 4 (HDAC4), an enzyme that inhibits DNA binding of Runx2 to its target genes. Taken together, these results indicate that SHP acts as a novel positive regulator of bone formation by augmenting osteoblast differentiation through regulation of the transcriptional activity of Runx2.

  14. Small heterodimer partner-interacting leucine zipper protein inhibits adipogenesis by regulating peroxisome proliferator-activated receptor γ activity.

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    Jang, Hoon; Kim, Hyoung-Joo; Kim, Dong-Hwan; Park, Jae-Kyung; Sun, Wu-Sheng; Hwang, Seongsoo; Oh, Keon-Bong; Jang, Won-Gu; Lee, Jeong-Woong

    2015-07-01

    Adipocytes play a critical role in energy balance. Growth of fat tissue is achieved via an increase in adipocyte mass and the formation of newly differentiated adipocytes from precursor cells. Understanding the cellular and molecular mechanisms of adipocyte differentiation is crucial for the study of obesity- and fat-related diseases. The present study was designed to study whether small heterodimer partner-interacting leucine zipper protein (SMILE), a novel co-repressor, could regulate differentiation of adipocyte in 3T3-L1 cells. Treatment of endoplasmic stress inducers, thapsigargin and tunicamycin, inhibited adipocyte differentiation, stimulated Smile mRNA expression, and repressed the expression of adiponectin (Adipoq) in 3T3-L1 pre-adipocyte. Overexpression of SMILE in 3T3-L1 cells decreased the expression of the mRNA encoding Adipoq, a major marker of adipocytes, significantly. Furthermore, knockdown of SMILE recovered the thapsigargin-mediated repression of Adipoq transcription. Co-immunoprecipitation experiments revealed that SMILE interacted physically with PPARγ in 3T3-L1 cells. In addition, chromatin immunoprecipitation experiments revealed that SMILE suppressed the binding affinity of PPARγ for the Adipoq promoter. We demonstrate that SMILE controls adipocyte differentiation by regulating the transactivity of peroxisome proliferator-activated receptor γ (PPARγ). These findings demonstrate that SMILE represses adipocyte differentiation by regulating PPARγ transactivity; hence, SMILE is a potential regulator of PPARγ-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Modulation of expression of the nuclear receptor NR0B2 (small heterodimer partner 1) and its impact on proliferation of renal carcinoma cells.

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    Prestin, Katharina; Olbert, Maria; Hussner, Janine; Isenegger, Tamara L; Gliesche, Daniel G; Böttcher, Kerstin; Zimmermann, Uwe; Meyer Zu Schwabedissen, Henriette E

    2016-01-01

    Mammalian nuclear receptors (NRs) are transcription factors regulating the expression of target genes that play an important role in drug metabolism, transport, and cellular signaling pathways. The orphan and structurally unique receptor small heterodimer partner 1 (syn NR0B2) is not only known for its modulation of drug response, but has also been reported to be involved in hepatocellular carcinogenesis. Indeed, previous studies show that NR0B2 is downregulated in human hepatocellular carcinoma, suggesting that NR0B2 acts as a tumor suppressor via inhibition of cellular growth and activation of apoptosis in this tumor entity. The aim of our study was to elucidate whether NR0B2 may also play a role in other tumor entities. Comparing NR0B2 expression in renal cell carcinoma and adjacent nonmalignant transformed tissue revealed significant downregulation in vivo. Additionally, the impact of heterologous expression of NR0B2 on cell cycle progression and proliferation in cells of renal origin was characterized. Monitoring fluorescence intensity of resazurin turnover in RCC-EW cells revealed no significant differences in metabolic activity in the presence of NR0B2. However, there was a significant decrease of cellular proliferation in cells overexpressing this NR, and NR0B2 was more efficient than currently used antiproliferative agents. Furthermore, flow cytometry analysis showed that heterologous overexpression of NR0B2 significantly reduced the amount of cells passing the G1 phase, while on the other hand, more cells in S/G2 phase were detected. Taken together, our data suggest that downregulation of NR0B2 may also play a role in renal cell carcinoma development and progression.

  16. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis

    NARCIS (Netherlands)

    Bechmann, Lars P.; Kocabayoglu, Peri; Sowa, Jan-Peter; Sydor, Svenja; Best, Jan; Schlattjan, Martin; Beilfuss, Anja; Schmitt, Johannes; Hannivoort, Rebekka A.; Kilicarslan, Alpaslan; Rust, Christian; Berr, Frieder; Tschopp, Oliver; Gerken, Guido; Friedman, Scott L.; Geier, Andreas; Canbay, Ali

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and may proceed to steatohepatitis (NASH). Apoptosis and free fatty acid (FFA)-induced lipotoxicity are important features of NASH pathogenesis. We have shown a hepatoprotective effect of adiponecti

  17. Changes of cholesterol 7alpha-hydroxylase,farnesoid X receptor,and small heterodimer partner expression in liver tissues of rats with obstructive cholestasis%阻塞性胆汁淤积大鼠肝脏胆固醇7α-羟化酶和核受体FXR、SHP表达变化

    Institute of Scientific and Technical Information of China (English)

    吴晓平; 柴进; 陈文生

    2009-01-01

    目的:通过建立梗阻性黄疸动物模型,观察胆固醇7α-羟化酶(cholesterol 7alpha-hydroxylase,CYP7A1)、类法尼醇X受体(farnesoid X receptor,FXR)及小异源二聚体伴侣受体(small heterodimer partner,SHP)的表达变化,并分析CYP7A1和FXR、SHP之问的关系.方法:采用胆总管结扎术制备大鼠梗阻性黄疸模型,分别于术后1、3、14 d麻醉后放血处死.取大鼠肝脏,抽提总RNA,采用实时定量RT-PCR检测CYP7A1 mRNA表达;提取肝细胞核蛋白,采用蛋白质印迹技术检测FXR和SHP蛋白表达.结果:与假手术对照组相比,梗阻性黄疸组大鼠肝细胞CYP7A1 mRNA表达明显增强,FXR和SHP蛋白表达同步降低,差异均有统计学意义(P<0.001,P<0.05).结论:CYP7A1表达增强可能与FXR、SHP表达减弱有关.

  18. Postprandial response and tissue distribution of the bile acid synthesis-related genes, cyp7a1, cyp8b1 and shp, in rainbow trout Oncorhynchus mykiss.

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    Murashita, Koji; Yoshiura, Yasutoshi; Chisada, Shin-ichi; Furuita, Hirofumi; Sugita, Tsuyoshi; Matsunari, Hiroyuki; Yamamoto, Takeshi

    2013-10-01

    In mammals, cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) are rate-limiting enzymes in bile acid synthesis. In addition, a small heterodimer partner (SHP) is also known to inhibit bile acid synthesis via the suppression of CYP7A1 and CYP8B1 expression. However, little information is currently available regarding primary structure of the genes involved in bile acid synthesis in fish. We therefore cloned cyp7a1, cyp8b1 and shp genes from rainbow trout and obtained cDNAs encoding two isoforms each of Cyp7a1 (-1 and -2), Cyp8b1 (-1 and -2) and Shp (-1 and -2). Both cyp7a1-1 and -2 encoded proteins of 512 amino acids. Trout cyp7a1-1 was expressed not only primarily in the kidney, pyloric caecum and mid-gut, but also weakly in the liver, eye, gill and ovary. cyp7a1-2 was highly expressed in the liver, pyloric caecum and mid-gut. cyp8b1-1 and -2, which encoded proteins of 512 and 509 amino acids, respectively, were principally expressed in the liver. Both shp-1 and -2, which encoded proteins of 288 and 290 amino acids, respectively, were strongly expressed in the liver, but shp-2 was also highly expressed in the gallbladder and digestive tract. The temporal changes in the expression of cyp7a1-1/-2, cyp8b1-1/-2 and shp-1/-2 in the liver were assessed after consumption of a single meal. Expression of cyp7a1-1/-2 and cyp8b1-1/-2 increased within 3h post feeding (hpf) when the stomach was still approximately 84% full and the gallbladder was almost completely empty. Although the expression of shp-1 did not change after feeding, the expression pattern of shp-2 was inversely related to the expression patterns of cyp7a1-1/-2 and cyp8b1-1/-2. Specifically, shp-2 expression decreased until 3 hpf before returning to initial levels at 24 hpf. These findings suggest that Cyp7a1s/8b1s and Shp-2 function antagonistically in bile acid synthesis in rainbow trout.

  19. NF-κB p65 recruited SHP regulates PDCD5-mediated apoptosis in cancer cells.

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    Murshed, Farhan; Farhana, Lulu; Dawson, Marcia I; Fontana, Joseph A

    2014-03-01

    Transcription factor NF-κB promotes cell proliferation in response to cell injury. Increasing evidence, however, suggests that NF-κB can also play an apoptotic role depending on the stimulus and cell type. We have previously demonstrated that novel retinoid 4-[3-Cl-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC)-mediated apoptosis in breast carcinoma cells requires activation of canonical and non-canonical NF-κB pathways. The mechanism NF-κB uses to induce apoptosis remains largely unknown. NF-κB subunit p65 (RelA) was identified as one potent transcriptional activator in 3-Cl-AHPC-mediated apoptosis in cells. Here we used ChIP-on-chip to identify NF-κB p65 genes activated in 3-Cl-AHPC mediated apoptosis. This paper focuses on one hit: pro-apoptotic protein programmed cell death 5 (PDCD5). 3-Cl-AHPC mediated apoptosis in MDA-MB-468 had three related effects on PDCD5: NF-κB p65 binding to the PDCD5 gene, enhanced PDCD5 promoter activity, and increased PDCD5 protein expression. Furthermore, 3-Cl-AHPC increased orphan nuclear receptor small heterodimer partner (SHP) mRNA expression, increased SHP protein bound to NF-κB p65, and found the SHP/NF-κB p65 complex attached to the PDCD5 gene. PDCD5 triggered apoptosis through increased Bax protein and release of cytochrome C from mitochondria to cytosol. Lastly, knockdown of PDCD5 protein expression blocked 3-Cl-AHPC mediated apoptosis, while over-expression of PDCD5 enhanced apoptosis, suggesting PDCD5 is necessary and sufficient for NF-κB p65 mediated apoptosis. Our results demonstrate a novel pathway for NF-κB p65 in regulating apoptosis through SHP and PDCD5.

  20. Hypoxic repression of CYP7A1 through a HIF-1α- and SHP-independent mechanism.

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    Moon, Yunwon; Park, Bongju; Park, Hyunsung

    2016-03-01

    Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O2 for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor- 1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O2) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O2, and by decreasing the transcription of CYP7A1. [BMB Reports 2016; 49(3): 173-178].

  1. FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression

    Science.gov (United States)

    Wang, Wei; Zhan, Ming; Li, Qi; Chen, Wei; Chu, Huiling; Huang, Qihong; Hou, Zhaoyuan; Man, Mohan; Wang, Jian

    2016-01-01

    Chemoresistance is common in patients with biliary tract cancer (BTC) including gallbladder cancer (GBC) and cholangiocarcinoma (CC). Therefore, it is necessary to identify effective chemotherapeutic agents for BTC. In the present study, we for the first time tested the effect of farnesoid X receptor (FXR) agonists GW4064 and CDCA (chenodeoxycholic acid) in combination with cisplatin (CDDP) on increasing the chemosensitivity in BTC. Our results show that co-treatment of CDDP with FXR agonists remarkably enhance chemosensitivity of BTC cells. Mechanistically, we found that activation of FXR induced expression of small heterodimer partner (SHP), which in turn inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation and resulted in down-regulation of Bcl-xL expression in BTC cells, leading to increased susceptibility to CDDP. Moreover, the experiments on tumor-bearing mice showed that GW4064/CDDP co-treatment inhibited the tumor growth in vivo by up-regulating SHP expression and down-regulating STAT3 phosphorylation. These results suggest CDDP in combination with FXR agonists could be a potential new therapeutic strategy for BTC. PMID:27127878

  2. Partnering

    Science.gov (United States)

    1991-12-01

    to meet the de- successful despite the site challenges and sign intent, business changes during the project. (Groves was acquired by the Torno ...34 Complete the contract without need for America company during construction- litigation. Torno embraced Partnering and continued the process which was

  3. 2002 Sino-African SHP Training Workshop

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 2002 Sino-African SHP Training Workshop was held from 10 May to 18 June 2002 at Hangzhou Regional Center for Small Hydro Power(HRC). Attended altogether 9 participants from 5 African countries, i.e. Burundi, Nigeria, South African, Tanzania and Tunisia. This is the second training workshop on SHP that HRC conducted for African countries.

  4. Genetic interaction between AINTEGUMENTA (ANT) and the ovule identity genes SEEDSTICK (STK), SHATTERPROOF1 (SHP1) and SHATTERPROOF2 (SHP2).

    Science.gov (United States)

    Losa, Alessia; Colombo, Monica; Brambilla, Vittoria; Colombo, Lucia

    2010-06-01

    AINTEGUMENTA (ANT) promotes initiation and growth of ovule integuments which cell fate is specified by ovule identity factors, such as SEEDSTICK (STK), SHATTERPROOF1 (SHP1) and SHATTERPROOF2 (SHP2). To study the genetic interaction between ANT and the ovule identity genes, we have obtained a stk shp1 shp2 ant quadruple mutant. The molecular and morphological characterization of the quadruple mutant and its comparison with the stk shp1 shp2 triple mutant, the shp1 shp2 ant triple mutant and the stk ant double mutant are here presented.

  5. GABA(B2) is essential for g-protein coupling of the GABA(B) receptor heterodimer.

    Science.gov (United States)

    Robbins, M J; Calver, A R; Filippov, A K; Hirst, W D; Russell, R B; Wood, M D; Nasir, S; Couve, A; Brown, D A; Moss, S J; Pangalos, M N

    2001-10-15

    GABA(B) receptors are unique among G-protein-coupled receptors (GPCRs) in their requirement for heterodimerization between two homologous subunits, GABA(B1) and GABA(B2), for functional expression. Whereas GABA(B1) is capable of binding receptor agonists and antagonists, the role of each GABA(B) subunit in receptor signaling is unknown. Here we identified amino acid residues within the second intracellular domain of GABA(B2) that are critical for the coupling of GABA(B) receptor heterodimers to their downstream effector systems. Our results provide strong evidence for a functional role of the GABA(B2) subunit in G-protein coupling of the GABA(B) receptor heterodimer. In addition, they provide evidence for a novel "sequential" GPCR signaling mechanism in which ligand binding to one heterodimer subunit can induce signal transduction through the second partner of a heteromeric complex.

  6. The formation of heterodimers by vancomycin group antibiotics

    DEFF Research Database (Denmark)

    Staroske, T; O'Brien, DP; Jørgensen, Thomas J. D.;

    2000-01-01

    The formation of heterodimers in mixtures of glycopeptide antibiotics has been detected by electrospray ionization mass spectrometry (ESI-MS), and dimerization constants have been determined. By using NMR spectroscopy, it has been shown that these heterodimers indeed exist in aqueous solution. Th...

  7. Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism

    Science.gov (United States)

    Zhang, Eric E.; Chapeau, Emilie; Hagihara, Kazuki; Feng, Gen-Sheng

    2004-01-01

    Shp2, a Src homology 2-containing tyrosine phosphatase, has been implicated in a variety of growth factor or cytokine signaling pathways. However, it is conceivable that this enzyme acts predominantly in one pathway versus the others in a cell, depending on the cellular context. To determine the putative functions of Shp2 in the adult brain, we selectively deleted Shp2 in postmitotic forebrain neurons by crossing CaMKIIα-Cre transgenic mice with a conditional Shp2 mutant (Shp2flox) strain. Surprisingly, a prominent phenotype of the mutant (CaMKIIα-Cre:Shp2flox/flox or CaSKO) mice was the development of early-onset obesity, with increased serum levels of leptin, insulin, glucose, and triglycerides. The mutant mice were not hyperphagic but developed enlarged and steatotic liver. Consistent with previous in vitro data, we found that Shp2 down-regulates Jak2/Stat3 (signal transducer and activator of transcription 3) activation by leptin in the hypothalamus. However, Jak2/Stat3 down-regulation is offset by a dominant Shp2 promotion of the leptin-stimulated Erk pathway, leading to induction rather than suppression of leptin resistance upon Shp2 deletion in the brain. Collectively, these results suggest that a primary function of Shp2 in postmitotic forebrain neurons is to control energy balance and metabolism, and that this phosphatase is a critical signaling component of leptin receptor ObRb in the hypothalamus. Shp2 shows potential as a neuronal target for pharmaceutical sensitization of obese patients to leptin action. PMID:15520383

  8. Changes in the expression and dynamics of SHP-1 and SHP-2 during cerulein-induced acute pancreatitis in rats

    OpenAIRE

    Sarmiento, Nancy; Sánchez-Bernal, Carmen; Ayra, Manuel; Pérez, Nieves; Hernández-Hernández, Angel; Calvo, José J.; Sánchez-Yagüe, Jesús

    2008-01-01

    Changes in the expression and dynamics of SHP-1 and SHP-2 during cerulein-induced acute pancreatitis in rats correspondance: Corresponding author. Departamento de Bioquimica y Biologia Molecular, Edificio Departamental. Lab. 106, Plaza Doctores de la Reina s/n, 37007 Salamanca, Spain. (Sanchez-Yague, Jesus) (Sanchez-Yague, Jesus) Department of Biochemistry and Molecular Biology--> , University of Salamanca--> -...

  9. Expressions of SHP and CYP7A1 in pregnant rats with intrahepatic cholestasis%小异二聚体伴侣与胆固醇7a-羟化酶在肝内胆汁淤积症孕鼠中的表达

    Institute of Scientific and Technical Information of China (English)

    兰易; 刘建; 程浩; 邹姝丽; 甘晓玲

    2008-01-01

    Objectives To investigate the expressions of small heterodimer partner (SHP) and target gene cholesterol-7-hydroxylase (CYP7A1) in livers of rats with intrahepatic cholestasis of pregnancy (ICP), and to study the mechanism of ICP. Methods Thirty SD rats (pregnant for 15 days) were equally and randomly divided into two groups: an estradiol benzoate (EB) group and a normal saline (NS) group. Two ml blood was drawn from each rat before and on the 5th day after medicine administration to measure the levels of ALT, AST, ALP, TBA, TBIL, and DBIL. After delivery, the histopathological changes of the mother rat livers were studied. The mRNA and protein expressions of SHP and CYP7A1 in the livers were determined by RT-PCR and Western blot. Results (1) In the EB group, the serum levels of ALT, AST, ALE TBA, TBil, and DBil after EB administration increased significantly (P0.05); (2) Intrahepatic cholestasis appeared in the EB group, but not in the NS group; (3) The mRNA expressions of SHP and CYP7A1 were significantly higher in the EB group than in the NS group [(SHPmRNA: NS 0.365±0.0317 vs EB 0.4865±0.0237, P0.05).雌激素组孕鼠肝脏出现肝内胆汁淤积表现,对照组肝脏形态、结构正常.雌激素组和对照组SHP mRNA分别为0.4865±0.0237和0.3657±0.0317, CYP7A1 mRNA分别为0.4311±0.0157和0.3285±0.0123,差异均有统计学意义(P<0.01).雌激素组和对照组SHP蛋白表达分别为0.5033±0.0274和0.3762±0.0284, CYP7A1蛋白表达分别为0.4802±0.0217和0.3570±0.0175,差异均有统计学意义(P<0.01).结论 雌激素诱导的胆汁淤积促进肝脏SHP及其靶基因CYP7A1表达增加,导致胆汁酸合成进一步增加,从而引发胆汁淤积,这可能是妊娠期肝内胆汁淤积症发病机制之一.

  10. Identification of Interactions in the E1E2 Heterodimer of Hepatitis C Virus Important for Cell Entry*

    Science.gov (United States)

    Maurin, Guillemette; Fresquet, Judith; Granio, Ophélia; Wychowski, Czeslaw; Cosset, François-Loïc; Lavillette, Dimitri

    2011-01-01

    Several conserved domains critical for E1E2 assembly and hepatitis C virus entry have been identified in E1 and E2 envelope glycoproteins. However, the role of less conserved domains involved in cross-talk between either glycoprotein must be defined to fully understand how E1E2 undergoes conformational changes during cell entry. To characterize such domains and to identify their functional partners, we analyzed a set of intergenotypic E1E2 heterodimers derived from E1 and E2 of different genotypes. The infectivity of virions indicated that Con1 E1 did not form functional heterodimers when associated with E2 from H77. Biochemical analyses demonstrated that the reduced infectivity was not related to alteration of conformation and incorporation of Con1 E1/H77 E2 heterodimers but rather to cell entry defects. Thus, we generated chimeric E1E2 glycoproteins by exchanging different domains of each protein in order to restore functional heterodimers. We found that both the ectodomain and transmembrane domain of E1 influenced infectivity. Site-directed mutagenesis highlighted the role of amino acids 359, 373, and 375 in transmembrane domain in entry. In addition, we identified one domain involved in entry within the N-terminal part of E1, and we isolated a motif at position 219 that is critical for H77 function. Interestingly, using additional chimeric E1E2 complexes harboring substitutions in this motif, we found that the transmembrane domain of E1 acts as a partner of this motif. Therefore, we characterized domains of E1 and E2 that have co-evolved inside a given genotype to optimize their interactions and allow efficient entry. PMID:21555519

  11. Cross-regulation of protein stability by p53 and nuclear receptor SHP.

    Directory of Open Access Journals (Sweden)

    Zhihong Yang

    Full Text Available We report here a novel interplay between tumor suppressor p53 and nuclear receptor SHP that controls p53 and SHP stability. Overexpression of p53 causes rapid SHP protein degradation, which does not require the presence of Mdm2 and is mediated by the proteosome pathway. Overexpressing SHP alone does not affect p53 stability. However, SHP destabilizes p53 by augmentation of Mdm2 ubiquitin ligase activity toward p53. The single amino acid substitution in the SHP protein SHPK170R increases SHP binding to p53 relative to SHP wild-type, whereas SHPG171A variant shows a diminished p53 binding. As a result of the cross-regulation, the tumor suppressor function of p53 and SHP in inhibition of colon cancer growth is compromised. Our findings reveal a unique scenario for a cross-inhibition between two tumor suppressors to keep their expression and function in check.

  12. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Saori [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Takahashi, Atsushi; Hayashi, Takeru [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Tanuma, Sei-ichi [Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Hatakeyama, Masanori, E-mail: mhata@m.u-tokyo.ac.jp [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

    2016-01-22

    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

  13. A fragile lattice: replacing bacteriophage lambda's head stability gene D with the shp gene of phage 21 generates the Mg2+-dependent virus, lambda shp.

    Science.gov (United States)

    Wendt, Jennifer L; Feiss, Michael

    2004-08-15

    Phage lambda DNA packaging is accompanied by prohead expansion, due to structural changes in gpE, the major capsid protein. Rearrangement of the gpE lattice creates binding sites for trimers of gpD, the head stabilization protein. lambda-Like phage 21's shp gene is homologous to lambda's D gene. gpD and gpShp share 49% amino acid identity. To ask whether gpShp could stabilize the lambda head shell, we replaced lambda's D gene with shp, creating lambda shp. Unlike lambda or 21, lambda shp was strictly dependent on the presence of 10(-2) M Mg2+, and lambda shp virions were very sensitive to chelating agents. Density gradient studies indicated that the lambda gpE lattice was underpopulated with gpShp. gpD's N-terminus has been proposed to contact gpE, and we found that lambda D/shp, which produces a chimeric protein with the N-terminus of gpD and the C-terminus of gpShp, was Mg2+-independent and more stable than lambda shp.

  14. Purification and Characterization of the Catalytic Domain of Protein Tyrosine Phosphatase SHP-1 and the Preparation of Anti-△SHP-1 Antibodies

    Institute of Scientific and Technical Information of China (English)

    LI Wan-nan; ZHUANG Yan; LI He; SUN Ying; FU Yao; WU Xiao-xia; ZHAO Zhi-zhuang; FU Xue-qi

    2008-01-01

    This study is focused on the expression of an SH2 domain-truncated form of protein tyrosine phosphatase SHP-1(designated △SHP-1) and the preparation of its polyelonal antibodies.A cDNA fragment encoding △SHP-1 was amplified by PCR and then cloned into the pT7 expression vector.The recombinant pT7-△SHP-1 plasmid was used to transform Rosetta(DE3) E.coll cells.△SHP-1 was distributed in the exclusion body of E.coll cell extracts and was purified through a two-column chromatographic procedure.The purified enzyme exhibited an expected molecular weight on SDS-gels and HPLC gel filtration columns.It possesses robust tyrosine phosphatase activity and shows typical enzymatic characteristics of classic tyrosine phosphatases.To generate polyclonal anti-△SHP-1 antibodies,purified recombinant △SHP-1 was used to immunize a rabbit.The resultant anti-serum was subjected to purification on △SHP-1 antigen affinity chromatography.The purified polyclonal antibody displayed a high sensitivity and specificity toward △SHP-1.This study thus provides the essential materials for further investigating the biological function and pathological implication of SHP-1 and screening the inhibitors and activators of the enzyme for therapeutic drug development.

  15. Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations

    Directory of Open Access Journals (Sweden)

    Timothy J. Bauler

    2011-03-01

    SHP-2 (encoded by PTPN11 is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF and receptor activator of nuclear factor kappa B ligand (RANKL was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations.

  16. Excitation Dynamics and Relaxation in a Molecular Heterodimer

    CERN Document Server

    Balevicius, V; Abramavicius, D; Mancal, T; Valkunas, L

    2011-01-01

    The exciton dynamics in a molecular heterodimer is studied as a function of differences in excitation and reorganization energies, asymmetry in transition dipole moments and excited state lifetimes. The heterodimer is composed of two molecules modeled as two-level systems coupled by the resonance interaction. The system-bath coupling is taken into account as a modulating factor of the energy gap of the molecular excitation, while the relaxation to the ground state is treated phenomenologically. Comparison of the description of the excitation dynamics modeled using either the Redfield equations (secular and full forms) or the Hierarchical quantum master equation (HQME) is demonstrated and discussed. Possible role of the dimer as an excitation quenching center in photosynthesis self-regulation is discussed. It is concluded that the system-bath interaction rather than the excitonic effect determines the excitation quenching ability of such a dimer.

  17. Resonance coupling in plasmonic nanomatryoshka homo- and heterodimers

    Science.gov (United States)

    Ahmadivand, Arash; Sinha, Raju; Pala, Nezih

    2016-06-01

    Here, we examine the electromagnetic (EM) energy coupling and hybridization of plasmon resonances between closely spaced concentric nanoshells known as "nanomatryoshka" (NM) units in symmetric and antisymmetric compositions using the Finite Difference Time Domain (FDTD) analysis. Utilizing plasmon hybridization model, we calculated the energy level diagrams and verified that, in the symmetric dimer (in-phase mode in a homodimer), plasmonic bonding modes are dominant and tunable within the considered bandwidth. In contrast, in the antisymmetric dimer (out-of-phase mode in a heterodimer), due to the lack of the geometrical symmetry, new antibonding modes appear in the extinction profile, and this condition gives rise to repeal of dipolar field coupling. We also studied the extinction spectra and positions of the antibonding and bonding modes excited due to the energy coupling between silver and gold NM units in a heterodimer structure. Our analysis suggest abnormal shifts in the higher energy modes. We propose a method to analyze the behavior of multilayer concentric nanoshell particles in an antisymmetric orientation employing full dielectric function calculations and the Drude model based on interband transitions in metallic components. This study provides a method to predict the behavior of the higher energy plasmon resonant modes in entirely antisymmetric structures such as compositional heterodimers.

  18. Resonance coupling in plasmonic nanomatryoshka homo- and heterodimers

    Directory of Open Access Journals (Sweden)

    Arash Ahmadivand

    2016-06-01

    Full Text Available Here, we examine the electromagnetic (EM energy coupling and hybridization of plasmon resonances between closely spaced concentric nanoshells known as “nanomatryoshka” (NM units in symmetric and antisymmetric compositions using the Finite Difference Time Domain (FDTD analysis. Utilizing plasmon hybridization model, we calculated the energy level diagrams and verified that, in the symmetric dimer (in-phase mode in a homodimer, plasmonic bonding modes are dominant and tunable within the considered bandwidth. In contrast, in the antisymmetric dimer (out-of-phase mode in a heterodimer, due to the lack of the geometrical symmetry, new antibonding modes appear in the extinction profile, and this condition gives rise to repeal of dipolar field coupling. We also studied the extinction spectra and positions of the antibonding and bonding modes excited due to the energy coupling between silver and gold NM units in a heterodimer structure. Our analysis suggest abnormal shifts in the higher energy modes. We propose a method to analyze the behavior of multilayer concentric nanoshell particles in an antisymmetric orientation employing full dielectric function calculations and the Drude model based on interband transitions in metallic components. This study provides a method to predict the behavior of the higher energy plasmon resonant modes in entirely antisymmetric structures such as compositional heterodimers.

  19. Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells

    Science.gov (United States)

    Sun, Xuan; Zhang, Jie; Wang, Zhiyong; Ji, Wei; Tian, Ran; Zhang, Fei; Niu, Ruifang

    2017-01-01

    Accumulative evidence demonstrates that the protein tyrosine phosphatase Shp2 functions as a powerful tumor promoter in many types of cancers. Abnormal expression of Shp2 has been implicated in many human malignancies. Overexpression of Shp2 in cancer tissues is correlated with cancer metastasis, resistance to targeted therapy, and poor prognosis. The well-known function of Shp2 is its positive role in regulating cellular signaling initiated by growth factors and cytokines, including interleukin-6 (IL-6). Several recent studies have shown that Shp2 is required for epithelial-mesenchymal transition (EMT), triggered by growth factors. However, whether Shp2 is involved in IL-6-signaling-promoted breast cancer EMT and progression, remains undefined. In this study, we showed that exogenous and endogenous IL-6 can enhance breast cancer invasion and migration, through the promotion of EMT. IL-6 also induces the activation of Erk1/2 and the phosphorylation of Shp2. Knockdown of Shp2 attenuated the IL-6-induced downregulation of E-cadherin, as well as IL-6-promoted cell migration and invasion. Moreover, by using Shp2 phosphatase mutants, phosphor-tyrosine mimicking, and deficiency mutants, we provided evidence that the phosphatase activity of Shp2 and its tyrosine phosphorylation, are necessary for the IL-6-induced downregulation of E-cadherin and the phosphorylation of Erk1/2. Our findings uncover an important function that links Shp2 to IL-6-promoted breast cancer progression. PMID:28208810

  20. Putative roles of glutaredoxin-BolA holo-heterodimers in plants.

    Science.gov (United States)

    Dhalleine, Tiphaine; Rouhier, Nicolas; Couturier, Jérémy

    2014-01-01

    Several genomic analyses, high-throughput or targeted interaction studies including the purification of protein complexes indicated a physical and functional link between BolAs and monothiol glutaredoxins (Grxs) that is conserved both in prokaryotes and eukaryotes. In a recent work, we confirmed that several Arabidopsis protein couples, used as plant representatives, also physically interact. More interestingly, we determined that two BolA proteins, BolA2 and SufE1, contain a conserved cysteine that is sensitive to oxidizing treatments, unraveling a possible redox-control of BolA2 and SufE1 by monothiol glutaredoxins. By coexpressing physiological partners in E. coli, Grx-BolA heterodimers binding a labile, oxygen sensitive iron-sulfur cluster were isolated. Altogether, these results illustrate the existence of different modes of interaction between monothiol glutaredoxins and BolA proteins in plants and probably in other organisms. Incidentally, the function of each partner could be differentially modulated depending on the type of interaction.

  1. SHP1 tyrosine phosphatase negatively regulates NPM-ALK tyrosine kinase signaling.

    Science.gov (United States)

    Honorat, Jean-François; Ragab, Ashraf; Lamant, Laurence; Delsol, Georges; Ragab-Thomas, Jeannie

    2006-05-15

    Anaplastic large-cell lymphoma (ALCL) is frequently associated with the 2;5 translocation and expresses the NPM-ALK fusion protein, which possesses a constitutive tyrosine kinase activity. We analyzed SHP1 tyrosine phosphatase expression and activity in 3 ALK-positive ALCL cell lines (Karpas 299, Cost, and SU-DHL1) and in lymph node biopsies (n = 40). We found an inverse correlation between the level of NPM-ALK phosphorylation and SHP1 phosphatase activity. Pull-down and coimmunoprecipitation experiments demonstrated a SHP1/NPM-ALK association. Furthermore, confocal microscopy performed on ALCL cell lines and biopsy specimens showed the colocalization of the 2 proteins in cytoplasmic bodies containing Y664-phosphorylated NPM-ALK. Dephosphorylation of NPM-ALK by SHP1 demonstrated that NPM-ALK was a SHP1 substrate. Downregulation of SHP1 expression by RNAi in Karpas cells led to hyperphosphorylation of NPM-ALK, STAT3 activation, and increase in cell proliferation. Furthermore, SHP1 overexpression in 3T3 fibroblasts stably expressing NPM-ALK led to the decrease of NPM-ALK phosphorylation, lower cell proliferation, and tumor progression in nude mice. These findings show that SHP1 is a negative regulator of NPM-ALK signaling. The use of tissue microarrays revealed that 50% of ALK-positive ALCLs were positive for SHP1. Our results suggest that SHP1 could be a critical enzyme in ALCL biology and a potential therapeutic target.

  2. Excitation dynamics and relaxation in a molecular heterodimer

    Energy Technology Data Exchange (ETDEWEB)

    Balevicius, V.; Gelzinis, A. [Department of Theoretical Physics, Faculty of Physics, Vilnius University, Sauletekio Avenue 9, build. 3, LT-10222 Vilnius (Lithuania); Center for Physical Sciences and Technology, Institute of Physics, Savanoriu Avenue 231, LT-02300 Vilnius (Lithuania); Abramavicius, D. [Department of Theoretical Physics, Faculty of Physics, Vilnius University, Sauletekio Avenue 9, build. 3, LT-10222 Vilnius (Lithuania); State Key Laboratory of Supramolecular Structure and Materials, Jilin University, 2699 Qianjin Street, Changchun 130012 (China); Mancal, T. [Faculty of Mathematics and Physics, Charles University in Prague, Ke Karlovu 5, CZ-121 16 Prague 2 (Czech Republic); Valkunas, L., E-mail: leonas.valkunas@ff.vu.lt [Department of Theoretical Physics, Faculty of Physics, Vilnius University, Sauletekio Avenue 9, build. 3, LT-10222 Vilnius (Lithuania); Center for Physical Sciences and Technology, Institute of Physics, Savanoriu Avenue 231, LT-02300 Vilnius (Lithuania)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Dynamics of excitation within a heterogenous molecular dimer. Black-Right-Pointing-Pointer Excited states can be swapped due to different reorganization energies of monomers. Black-Right-Pointing-Pointer Conventional excitonic basis becomes renormalized due to interaction with the bath. Black-Right-Pointing-Pointer Relaxation is independent of mutual positioning of monomeric excited states. -- Abstract: The exciton dynamics in a molecular heterodimer is studied as a function of differences in excitation and reorganization energies, asymmetry in transition dipole moments and excited state lifetimes. The heterodimer is composed of two molecules modeled as two-level systems coupled by the resonance interaction. The system-bath coupling is taken into account as a modulating factor of the molecular excitation energy gap, while the relaxation to the ground state is treated phenomenologically. Comparison of the description of the excitation dynamics modeled using either the Redfield equations (secular and full forms) or the Hierarchical quantum master equation (HQME) is demonstrated and discussed. Possible role of the dimer as an excitation quenching center in photosynthesis self-regulation is discussed. It is concluded that the system-bath interaction rather than the excitonic effect determines the excitation quenching ability of such a dimer.

  3. RNA recognition by the DNA end-binding Ku heterodimer.

    Science.gov (United States)

    Dalby, Andrew B; Goodrich, Karen J; Pfingsten, Jennifer S; Cech, Thomas R

    2013-06-01

    Most nucleic acid-binding proteins selectively bind either DNA or RNA, but not both nucleic acids. The Saccharomyces cerevisiae Ku heterodimer is unusual in that it has two very different biologically relevant binding modes: (1) Ku is a sequence-nonspecific double-stranded DNA end-binding protein with prominent roles in nonhomologous end-joining and telomeric capping, and (2) Ku associates with a specific stem-loop of TLC1, the RNA subunit of budding yeast telomerase, and is necessary for proper nuclear localization of this ribonucleoprotein enzyme. TLC1 RNA-binding and dsDNA-binding are mutually exclusive, so they may be mediated by the same site on Ku. Although dsDNA binding by Ku is well studied, much less is known about what features of an RNA hairpin enable specific recognition by Ku. To address this question, we localized the Ku-binding site of the TLC1 hairpin with single-nucleotide resolution using phosphorothioate footprinting, used chemical modification to identify an unpredicted motif within the hairpin secondary structure, and carried out mutagenesis of the stem-loop to ascertain the critical elements within the RNA that permit Ku binding. Finally, we provide evidence that the Ku-binding site is present in additional budding yeast telomerase RNAs and discuss the possibility that RNA binding is a conserved function of the Ku heterodimer.

  4. SdAb heterodimer formation using leucine zippers

    Science.gov (United States)

    Goldman, Ellen R.; Anderson, George P.; Brozozog-Lee, P. Audrey; Zabetakis, Dan

    2013-05-01

    Single domain antibodies (sdAb) are variable domains cloned from camel, llama, or shark heavy chain only antibodies, and are among the smallest known naturally derived antigen binding fragments. SdAb derived from immunized llamas are able to bind antigens with high affinity, and most are capable of refolding after heat or chemical denaturation to bind antigen again. We hypothesized that the ability to produce heterodimeric sdAb would enable reagents with the robust characteristics of component sdAb, but with dramatically improved overall affinity through increased avidity. Previously we had constructed multimeric sdAb by genetically linking sdAb that bind non-overlapping epitopes on the toxin, ricin. In this work we explored a more flexible approach; the construction of multivalent binding reagents using multimerization domains. We expressed anti-ricin sdAb that recognize different epitopes on the toxin as fusions with differently charged leucine zippers. When the initially produced homodimers are mixed the leucine zipper domains will pair to produce heterodimers. We used fluorescence resonance energy transfer to confirm heterodimer formation. Surface plasmon resonance, circular dichroism, enzyme linked immunosorbent assays, and fluid array assays were used to characterize the multimer constructs, and evaluate their utility in toxin detection.

  5. SHP-1 phosphatase activity counteracts increased T cell receptor affinity.

    Science.gov (United States)

    Hebeisen, Michael; Baitsch, Lukas; Presotto, Danilo; Baumgaertner, Petra; Romero, Pedro; Michielin, Olivier; Speiser, Daniel E; Rufer, Nathalie

    2013-03-01

    Anti-self/tumor T cell function can be improved by increasing TCR-peptide MHC (pMHC) affinity within physiological limits, but paradoxically further increases (K(d) affinity for the tumor antigen HLA-A2/NY-ESO-1, we investigated the molecular mechanisms underlying this high-affinity-associated loss of function. As compared with cells expressing TCR affinities generating optimal function (K(d) = 5 to 1 μM), those with supraphysiological affinity (K(d) = 1 μM to 15 nM) showed impaired gene expression, signaling, and surface expression of activatory/costimulatory receptors. Preferential expression of the inhibitory receptor programmed cell death-1 (PD-1) was limited to T cells with the highest TCR affinity, correlating with full functional recovery upon PD-1 ligand 1 (PD-L1) blockade. In contrast, upregulation of the Src homology 2 domain-containing phosphatase 1 (SHP-1/PTPN6) was broad, with gradually enhanced expression in CD8(+) T cells with increasing TCR affinities. Consequently, pharmacological inhibition of SHP-1 with sodium stibogluconate augmented the function of all engineered T cells, and this correlated with the TCR affinity-dependent levels of SHP-1. These data highlight an unexpected and global role of SHP-1 in regulating CD8(+) T cell activation and responsiveness and support the development of therapies inhibiting protein tyrosine phosphatases to enhance T cell-mediated immunity.

  6. China's International Cooperation on SHP Strengthened

    Institute of Scientific and Technical Information of China (English)

    D.Pan

    2004-01-01

    The 2004 TCDC (Technical Cooperation among Developing Countries) Training Workshop on SHP Equipment was held from 12 Oct to 22 Nov 2004 by Hangzhou Regional Centrefor Small Hydro Power (HRC). Attended altogether 25 participants from 13 countries, covering Africa, Asia,Eastern Europe and Oceania.

  7. Targeting SHP2 for EGFR inhibitor resistant non-small cell lung carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jie; Zeng, Li-Fan; Shen, Weihua [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States); Turchi, John J. [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States); Department of Medicine, Indiana University School of Medicine, Indianapolis (United States); Zhang, Zhong-Yin, E-mail: zyzhang@iu.edu [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States)

    2013-10-04

    Highlights: •SHP2 is required for EGFR inhibitor resistant NSCLC H1975 cell proliferation. •SHP2 inhibitor blocks EGF-stimulated ERK1/2 activation and proliferation. •SHP2 inhibitor exhibits marked anti-tumor activity in H1975 xenograft mice. •SHP2 inhibitor synergizes with PI3K inhibitor in suppressing cell growth. •Targeting SHP2 represents a novel strategy for EGFR inhibitor resistant NSCLCs. -- Abstract: Targeted therapy with inhibitors of epidermal growth factor receptor (EGFR) has produced a noticeable benefit to non-small cell lung cancer (NSCLC) patients whose tumors carry activating mutations (e.g. L858R) in EGFR. Unfortunately, these patients develop drug resistance after treatment, due to acquired secondary gatekeeper mutations in EGFR (e.g. T790M). Given the critical role of SHP2 in growth factor receptor signaling, we sought to determine whether targeting SHP2 could have therapeutic value for EGFR inhibitor resistant NSCLC. We show that SHP2 is required for EGF-stimulated ERK1/2 phosphorylation and proliferation in EGFR inhibitor resistant NSCLC cell line H1975, which harbors the EGFR T790M/L858R double-mutant. We demonstrate that treatment of H1975 cells with II-B08, a specific SHP2 inhibitor, phenocopies the observed growth inhibition and reduced ERK1/2 activation seen in cells treated with SHP2 siRNA. Importantly, we also find that II-B08 exhibits marked anti-tumor activity in H1975 xenograft mice. Finally, we observe that combined inhibition of SHP2 and PI3K impairs both the ERK1/2 and PI3K/AKT signaling axes and produces significantly greater effects on repressing H1975 cell growth than inhibition of either protein individually. Collectively, these results suggest that targeting SHP2 may represent an effective strategy for treatment of EGFR inhibitor resistant NSCLCs.

  8. Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112.

    Science.gov (United States)

    Chen, Liwei; Pernazza, Daniele; Scott, Latanya M; Lawrence, Harshani R; Ren, Yuan; Luo, Yunting; Wu, Xin; Sung, Shen-Shu; Guida, Wayne C; Sebti, Said M; Lawrence, Nicholas J; Wu, Jie

    2010-09-15

    The protein tyrosine phosphatase (PTP) Shp2 (PTPN11) is an attractive target for anticancer drug discovery because it mediates growth factor signaling and its gain-of-function mutants are causally linked to leukemias. We previously synthesized SPI-112 from a lead compound of Shp2 inhibitor, NSC-117199. In this study, we demonstrated that SPI-112 bound to Shp2 by surface plasmon resonance (SPR) and displayed competitive inhibitor kinetics to Shp2. Like some other compounds in the PTP inhibitor discovery efforts, SPI-112 was not cell permeable, precluding its use in biological studies. To overcome the cell permeation issue, we prepared a methyl ester SPI-112 analog (SPI-112Me) that is predicted to be hydrolyzed to SPI-112 upon entry into cells. Fluorescence uptake assay and confocal imaging suggested that SPI-112Me was taken up by cells. Incubation of cells with SPI-112Me inhibited epidermal growth factor (EGF)-stimulated Shp2 PTP activity and Shp2-mediated paxillin dephosphorylation, Erk1/2 activation, and cell migration. SPI-112Me treatment also inhibited Erk1/2 activation by a Gab1-Shp2 chimera. Treatment of Shp2(E76K) mutant-transformed TF-1 myeloid cells with SPI-112Me resulted in inhibition of Shp2(E76K)-dependent cell survival, which is associated with inhibition of Shp2(E76K) PTP activity, Shp2(E76K)-induced Erk1/2 activation, and Bcl-XL expression. Furthermore, SPI-112Me enhanced interferon-gamma (IFN-gamma)-stimulated STAT1 tyrosine phosphorylation, ISRE-luciferase reporter activity, p21 expression, and the anti-proliferative effect. Thus, the SPI-112 methyl ester analog was able to inhibit cellular Shp2 PTP activity.

  9. The MADS Box Genes ABS, SHP1, and SHP2 Are Essential for the Coordination of Cell Divisions in Ovule and Seed Coat Development and for Endosperm Formation in Arabidopsis thaliana.

    Science.gov (United States)

    Ehlers, Katrin; Bhide, Amey S; Tekleyohans, Dawit G; Wittkop, Benjamin; Snowdon, Rod J; Becker, Annette

    2016-01-01

    Seed formation is a pivotal process in plant reproduction and dispersal. It begins with megagametophyte development in the ovule, followed by fertilization and subsequently coordinated development of embryo, endosperm, and maternal seed coat. Two closely related MADS-box genes, SHATTERPROOF 1 and 2 (SHP1 and SHP2) are involved in specifying ovule integument identity in Arabidopsis thaliana. The MADS box gene ARABIDOPSIS BSISTER (ABS or TT16) is required, together with SEEDSTICK (STK) for the formation of endothelium, part of the seed coat and innermost tissue layer formed by the maternal plant. Little is known about the genetic interaction of SHP1 and SHP2 with ABS and the coordination of endosperm and seed coat development. In this work, mutant and expression analysis shed light on this aspect of concerted development. Triple tt16 shp1 shp2 mutants produce malformed seedlings, seed coat formation defects, fewer seeds, and mucilage reduction. While shp1 shp2 mutants fail to coordinate the timely development of ovules, tt16 mutants show less peripheral endosperm after fertilization. Failure in coordinated division of the innermost integument layer in early ovule stages leads to inner seed coat defects in tt16 and tt16 shp1 shp2 triple mutant seeds. An antagonistic action of ABS and SHP1/SHP2 is observed in inner seed coat layer formation. Expression analysis also indicates that ABS represses SHP1, SHP2, and FRUITFUL expression. Our work shows that the evolutionary conserved Bsister genes are required not only for endothelium but also for endosperm development and genetically interact with SHP1 and SHP2 in a partially antagonistic manner.

  10. The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes.

    Science.gov (United States)

    Wang, Li; Liu, Jun; Saha, Pradip; Huang, Jiansheng; Chan, Lawrence; Spiegelman, Bruce; Moore, David D

    2005-10-01

    Brown adipocytes increase energy production in response to induction of PGC-1alpha, a dominant regulator of energy metabolism. We have found that the orphan nuclear receptor SHP (NR0B2) is a negative regulator of PGC-1alpha expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1alpha, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1alpha expression in SHP null brown adipose tissue is not due to beta-adrenergic activation, since it is also observed in primary cultures of SHP(-/-) brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1alpha expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan nuclear receptor ERRgamma is expressed in BAT and its transactivation of the PGC-1alpha promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT.

  11. SHP2-Deficiency in Chondrocytes Deforms Orofacial Cartilage and Ciliogenesis in Mice.

    Science.gov (United States)

    Kamiya, Nobuhiro; Shen, Jingling; Noda, Kazuo; Kitami, Megumi; Feng, Gen-Sheng; Chen, Di; Komatsu, Yoshihiro

    2015-11-01

    Congenital orofacial abnormalities are clinically seen in human syndromes with SHP2 germline mutations such as LEOPARD and Noonan syndrome. Recent studies demonstrate that SHP2-deficiency leads to skeletal abnormalities including scoliosis and cartilaginous benign tumor metachondromatosis, suggesting that growth plate cartilage is a key tissue regulated by SHP2. The role and cellular mechanism of SHP2 in the orofacial cartilage, however, remains unknown. Here, we investigated the postnatal craniofacial development by inducible disruption of Shp2 in chondrocytes. Shp2 conditional knockout (cKO) mice displayed severe deformity of the mandibular condyle accompanied by disorganized, expanded cartilage in the trabecular bone region, enhanced type X collagen, and reduced Erk production. Interestingly, the length of primary cilia, an antenna like organelle sensing environmental signaling, was significantly shortened, and the number of primary cilia was reduced in the cKO mice. The expression levels of intraflagellar transports (IFTs), essential molecules in the assembly and function of primary cilia, were significantly decreased. Taken together, lack of Shp2 in orofacial cartilage led to severe defects of ciliogenesis through IFT reduction, resulting in mandibular condyle malformation and cartilaginous expansion. Our study provides new insights into the molecular pathogenesis of SHP2-deficiency in cartilage and helps to understand orofacial and skeletal manifestations seen in patients with SHP2 mutations.

  12. A novel screening model for the molecular drug for diabetes and obesity based on tyrosine phosphatase Shp2.

    Science.gov (United States)

    Bu, Yanyan; Shi, Tao; Meng, Minghui; Kong, Guiping; Tian, Yingpu; Chen, Quancheng; Yao, Xinsheng; Feng, Gensheng; Chen, Haifeng; Cheng, Haifeng; Lu, Zhongxian

    2011-01-15

    Tyrosine phosphatase Src-homology phosphotyrosyl phosphatase 2 (Shp2) was identified as a potential molecular target for therapeutic treatment of diabetes and obesity. However, there is still no systematic research on the enhancers for the Shp2 enzyme. The present study established a novel powerful model for the high-throughput screening of Shp2 enhancers and successfully identified a new specific Shp2 enhancer, oleanolic acid, from Chinese herbs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. A new diketopiperazine heterodimer from an endophytic fungus Aspergillus niger.

    Science.gov (United States)

    Li, Xiao-Bin; Li, Yue-Lan; Zhou, Jin-Chuan; Yuan, Hui-Qing; Wang, Xiao-Ning; Lou, Hong-Xiang

    2015-01-01

    One new diketopiperazine heterodimer, asperazine A (1), and eight known compounds, asperazine (2), cyclo(d-Phe-l-Trp) (3), cyclo(l-Trp-l-Trp) (4), 4-(hydroxymethyl)-5,6-dihydro-pyran-2-one (5), walterolactone A (6), and campyrones A-C (7-9), were isolated from an endophytic fungus Aspergillus niger. Their structures were determined unequivocally on the basis of extensive spectroscopic data analysis. This is the first report of the presence of compound 3 as a natural product. Cytotoxicity test against human cancer cell lines PC3, A2780, K562, MBA-MD-231, and NCI-H1688 revealed that compounds 1 and 2 had weak activities.

  14. Structural Basis for LMO2-Driven Recruitment of the SCL:E47bHLH Heterodimer to Hematopoietic-Specific Transcriptional Targets

    Directory of Open Access Journals (Sweden)

    Kamel El Omari

    2013-07-01

    Full Text Available Cell fate is governed by combinatorial actions of transcriptional regulators assembling into multiprotein complexes. However, the molecular details of how these complexes form are poorly understood. One such complex, which contains the basic-helix-loop-helix heterodimer SCL:E47 and bridging proteins LMO2:LDB1, critically regulates hematopoiesis and induces T cell leukemia. Here, we report the crystal structure of (SCL:E47bHLH:LMO2:LDB1LID bound to DNA, providing a molecular account of the network of interactions assembling this complex. This reveals an unexpected role for LMO2. Upon binding to SCL, LMO2 induces new hydrogen bonds in SCL:E47, thereby strengthening heterodimer formation. This imposes a rotation movement onto E47 that weakens the heterodimer:DNA interaction, shifting the main DNA-binding activity onto additional protein partners. Along with biochemical analyses, this illustrates, at an atomic level, how hematopoietic-specific SCL sequesters ubiquitous E47 and associated cofactors and supports SCL’s reported DNA-binding-independent functions. Importantly, this work will drive the design of small molecules inhibiting leukemogenic processes.

  15. Social Partners

    DEFF Research Database (Denmark)

    Tikkanen, Tarja; Hansen, Leif Emil; Guðmundsson, Bernharður

    2012-01-01

    based on a survey carried out in the Nordic countries in the regie of Nordic Council of Ministries the article deals with the role of social partners in senior and older workers policies and practises...

  16. Critical role of SHP2 (PTPN11) signaling in germinal center-derived lymphoma.

    Science.gov (United States)

    Jiang, Xin; Guo, Honggang; Wu, Jianguo; He, Qiang; Li, Yiqiao; Wang, Miao; Pan, Hongyang; Li, Wande; Wang, Jinjie; Wang, Qingqing; Shen, Jing; Ke, Yuehai; Zhou, Ren

    2014-12-01

    Germinal center lymphoma is a heterogeneous human lymphoma entity. Here we report that constitutive activity of SHP2 (PTPN11) and its downstream kinase ERK is essential for the viability of germinal center lymphoma cells and disease progression. Mechanistically, SHP2/ERK inhibition impedes c-Myc transcriptional activity, which results in the repression of proliferative phenotype signatures of germinal center lymphoma. Furthermore, SHP2/ERK signaling is required to maintain the CD19/c-Myc loop, which preferentially promotes survival of a distinct subtype of germinal center lymphoma cells carrying the MYC/IGH translocation. These findings demonstrate a critical function for SHP2/ERK signaling upstream of c-Myc in germinal center lymphoma cells and provide a rationale for targeting SHP2 in the therapy of germinal center lymphoma.

  17. The transition from stem cell to progenitor spermatogonia and male fertility requires the SHP2 protein tyrosine phosphatase.

    Science.gov (United States)

    Puri, Pawan; Phillips, Bart T; Suzuki, Hitomi; Orwig, Kyle E; Rajkovic, Aleksandar; Lapinski, Philip E; King, Philip D; Feng, Gen-Sheng; Walker, William H

    2014-03-01

    SHP2 is a widely expressed protein tyrosine phosphatase required for signal transduction from multiple cell surface receptors. Gain and loss of function SHP2 mutations in humans are known to cause Noonan and LEOPARD syndromes, respectively, that are characterized by numerous pathological conditions including male infertility. Using conditional gene targeting in the mouse, we found that SHP2 is required for maintaining spermatogonial stem cells (SSCs) and the production of germ cells required for male fertility. After deleting SHP2, spermatogenesis was halted at the initial step during which transit-amplifying undifferentiated spermatogonia are produced from SSCs. In the absence of SHP2, proliferation of SSCs and undifferentiated spermatogonia was inhibited, thus germ cells cannot be replenished and SSCs cannot undergo renewal. However, germ cells beyond the undifferentiated spermatogonia stage of development at the time of SHP2 knockout were able to complete their maturation to become sperm. In cultures of SSCs and their progeny, inhibition of SHP2 activity reduced growth factor-mediated intracellular signaling that regulates SSC proliferation and cell fate. Inhibition of SHP2 also decreased the number of SSCs present in culture and caused SSCs to detach from supporting cells. Injection of mice with an SHP2 inhibitor blocked the production of germ cells from SSCs. Together, our studies show that SHP2 is essential for SSCs to maintain fertility and indicates that the pathogenesis of infertility in humans with SHP2 mutations is due to compromised SSC functions that block spermatogenesis. © AlphaMed Press.

  18. Central neuroinvasion and demyelination by inflammatory macrophages after peripheral virus infection is controlled by SHP-1.

    Science.gov (United States)

    Christophi, George P; Massa, Paul T

    2009-12-01

    SHP-1 is a protein tyrosine phosphatase that negatively regulates cytokine signaling and inflammatory gene expression. Mice genetically lacking SHP-1 (me/me) display severe inflammatory demyelinating disease following intracranial inoculation with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) compared to infected wild-type mice. Furthermore, SHP-1-deficient mice show a profound and predominant infiltration of blood-derived macrophages into the CNS following intracerebral injection of TMEV, and these macrophages are concentrated in areas of demyelination in brain and spinal cord. In the present study we investigated the role of SHP-1 in controlling CNS inflammatory demyelination following a peripheral instead of an intracerebral inoculation of TMEV. Surprisingly, we found that while wild-type mice were entirely refractory to intraperitoneal (IP) infection by TMEV, in agreement with previous studies, all SHP-1-deficient mice displayed profound macrophage neuroinvasion and macrophage-mediated inflammatory demyelination. Moreover, SHP-1 deficiency led to increased expression of inflammatory molecules in macrophages, serum, and CNS following IP infection with TMEV. Importantly, pharmacological depletion of peripheral macrophages significantly decreased both paralysis and CNS viral loads in SHP-1-deficient mice. In addition, peripheral MCP-1 neutralization attenuated disease severity, decreased macrophage infiltration into the CNS, and decreased monocyte numbers in the blood of SHP-1-deficient mice, implicating MCP-1 as an important mediator of monocyte migration between multiple tissues. These results demonstrate that peripheral TMEV infection results in a unique evolution of macrophage-mediated demyelination in SHP-1-deficient mice, implicating SHP-1 in the control of neuroinvasion of inflammatory macrophages and neurotropic viruses into the CNS.

  19. PARTNER Project

    CERN Multimedia

    Ballantine, A; Dixon-Altaber, H; Dosanjh, M; Kuchina, L

    2011-01-01

    Hadrontherapy uses particle beams to treat tumours located near critical organs and tumours that respond poorly to conventional radiation therapy. It has become evident that there is an emerging need for reinforcing research in hadrontherapy and it is essential to train professionals in this rapidly developing field. PARTNER is a 4-year Marie Curie Training project funded by the European Commission with 5.6 million Euros aimed at the creation of the next generation of experts. Ten academic institutes and research centres and two leading companies are participating in PARTNER, that is coordinated by CERN, forming a unique multidisciplinary and multinational European network. The project offers research and training opportunities to 25 young biologists, engineers, physicians and physicists and is allowing them to actively develop modern techniques for treating cancer in close collaboration with leading European Institutions. For this purpose PARTNER relies on cutting edge research and technology development, ef...

  20. Protein Tyrosine Phosphatases, TC-PTP, SHP1, and SHP2, Cooperate in Rapid Dephosphorylation of Stat3 in Keratinocytes Following UVB Irradiation

    Science.gov (United States)

    Kim, Dae Joon; Tremblay, Michel L.; DiGiovanni, John

    2010-01-01

    Stat3 is initially dephosphorylated in murine keratinocytes in response to UVB irradiation. Treatment with Na3VO4 desensitized keratinocytes to UVB-induced apoptosis with the recovery of phosphorylated Stat3 protein levels, implying that a protein tyrosine phosphatase (PTP) is involved in this mechanism. In the current work, we report that three PTPs including TC45 (the nuclear form of TC-PTP), SHP1, and SHP2 are involved in this rapid dephosphorylation of Stat3 in keratinocytes induced by UVB irradiation. Dephosphorylation of Stat3 was increased rapidly after UVB irradiation of cultured keratinocytes. Knockdown of TC-PTP, SHP1, or SHP2 using RNAi showed that these PTPs are likely responsible for most of the rapid Stat3 dephosphorylation observed following UVB irradiation. The level of phosphorylated Stat3 was significantly higher in keratinocytes transfected with TC-PTP, SHP1, or SHP2 siRNA in the presence or absence of UVB compared with keratinocytes transfected with control siRNA. TC45 was mainly localized in the cytoplasm of keratinocytes and translocated from cytoplasm to nucleus upon UVB irradiation. Stat3 dephosphorylation was associated with nuclear translocation of TC45. Further studies revealed that knockdown of all three phosphatases, using RNAi, prevented the rapid dephosphorylation of Stat3 following UVB irradiation. In mouse epidermis, the level of phosphorylated Stat3 was initially decreased, followed by a significant increase at later time points after UVB exposure. The levels of Stat3 target genes, such as cyclin D1 and c-Myc, followed the changes in activated Stat3 in response to UVB irradiation. Collectively, these results suggest that three phosphatases, TC45, SHP1, and SHP2, are primarily responsible for UVB-mediated Stat3 dephosphorylation and may serve as part of an initial protective mechanism against UV skin carcinogenesis. PMID:20421975

  1. Shp2 in forebrain neurons regulates synaptic plasticity, locomotion, and memory formation in mice.

    Science.gov (United States)

    Kusakari, Shinya; Saitow, Fumihito; Ago, Yukio; Shibasaki, Koji; Sato-Hashimoto, Miho; Matsuzaki, Yasunori; Kotani, Takenori; Murata, Yoji; Hirai, Hirokazu; Matsuda, Toshio; Suzuki, Hidenori; Matozaki, Takashi; Ohnishi, Hiroshi

    2015-05-01

    Shp2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) regulates neural cell differentiation. It is also expressed in postmitotic neurons, however, and mutations of Shp2 are associated with clinical syndromes characterized by mental retardation. Here we show that conditional-knockout (cKO) mice lacking Shp2 specifically in postmitotic forebrain neurons manifest abnormal behavior, including hyperactivity. Novelty-induced expression of immediate-early genes and activation of extracellular-signal-regulated kinase (Erk) were attenuated in the cerebral cortex and hippocampus of Shp2 cKO mice, suggestive of reduced neuronal activity. In contrast, ablation of Shp2 enhanced high-K(+)-induced Erk activation in both cultured cortical neurons and synaptosomes, whereas it inhibited that induced by brain-derived growth factor in cultured neurons. Posttetanic potentiation and paired-pulse facilitation were attenuated and enhanced, respectively, in hippocampal slices from Shp2 cKO mice. The mutant mice also manifested transient impairment of memory formation in the Morris water maze. Our data suggest that Shp2 contributes to regulation of Erk activation and synaptic plasticity in postmitotic forebrain neurons and thereby controls locomotor activity and memory formation.

  2. Immunization with Streptococcal Heme Binding Protein (Shp) Protects Mice Against Group A Streptococcus Infection.

    Science.gov (United States)

    Zhang, Xiaolan; Song, Yingli; Li, Yuanmeng; Cai, Minghui; Meng, Yuan; Zhu, Hui

    2017-01-01

    Streptococcal heme binding protein (Shp) is a surface protein of the heme acquisition system that is an essential iron nutrient in Group A Streptococcus (GAS). Here, we tested whether Shp immunization protects mice from subcutaneous infection. Mice were immunized subcutaneously with recombinant Shp and then challenged with GAS. The protective effects against GAS challenge were evaluated two weeks after the last immunization. Immunization with Shp elicited a robust IgG response, resulting in high anti-Shp IgG titers in the serum. Immunized mice had a higher survival rate and smaller skin lesions than adjuvant control mice. Furthermore, immunized mice had lower GAS numbers at the skin lesions and in the liver, spleen and lung. Histological analysis with Gram staining showed that GAS invaded the surrounding area of the inoculation sites in the skin in control mice, but not in immunized mice. Thus, Shp immunization enhances GAS clearance and reduces GAS skin invasion and systemic dissemination. These findings indicate that Shp is a protective antigen.

  3. Shp2 Deficiency Impairs the Inflammatory Response Against Haemophilus influenzae by Regulating Macrophage Polarization.

    Science.gov (United States)

    Zhao, Lifang; Xia, Jingyan; Li, Tiantian; Zhou, Hui; Ouyang, Wei; Hong, Zhuping; Ke, Yuehai; Qian, Jing; Xu, Feng

    2016-08-15

    Macrophages can polarize and differentiate to regulate initiation, development, and cessation of inflammation during pulmonary infection with nontypeable Haemophilus influenzae (NTHi). However, the underlying molecular mechanisms driving macrophage phenotypic differentiation are largely unclear. Our study investigated the role of Shp2, a Src homology 2 domain-containing phosphatase, in the regulation of pulmonary inflammation and bacterial clearance. Shp2 levels were increased upon NTHi stimulation. Selective inhibition of Shp2 in mice led to an attenuated inflammatory response by skewing macrophages toward alternatively activated macrophage (M2) polarization. Upon pulmonary NTHi infection, Shp2(-/-) mice, in which the gene encoding Shp2 in monocytes/macrophages was deleted, showed an impaired inflammatory response and decreased antibacterial ability, compared with wild-type controls. In vitro data demonstrated that Shp2 regulated activated macrophage (M1) gene expression via activation of p65-nuclear factor-κB signaling, independent of p38 and extracellular regulated kinase-mitogen-activated proteins kinase signaling pathways. Taken together, our study indicates that Shp2 is required to orchestrate macrophage function and regulate host innate immunity against pulmonary bacterial infection.

  4. Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22.

    Science.gov (United States)

    Blasioli, J; Paust, S; Thomas, M L

    1999-01-22

    CD22 phosphorylation is an early event of B cell antigen receptor engagement and results in the recruitment of the negative regulatory tyrosine phosphatase, SHP-1. Peptides representing the potential phosphorylation sites within the cytoplasmic domain of CD22 have been used to stimulate SHP-1 catalytic activity and to inhibit the binding of SHP-1 to CD22 (Doody, G., Justement, L., Delibrias, C., Matthews, R., Lin, J., Thomas, M., and Fearon, D. (1995) Science 269, 242-244). However, the sites of phosphorylation within the cytoplasmic domain of CD22 and the importance of each for the recruitment and activation of SHP-1 remain unknown. Here we demonstrate that there are multiple sites within the cytoplasmic domain of CD22 that interact with the Src homology 2 domains of SHP-1. Nevertheless, a minimum of two tyrosines in CD22 is required for the association with SHP-1. Furthermore, both Src homology 2 domains of SHP-1 are necessary for efficient binding to CD22.

  5. CD5-mediated inhibition of TCR signaling proceeds normally in the absence of SHP-1

    Science.gov (United States)

    DONG, BAOXIA; SOMANI, ALLY-KHAN; LOVE, PAUL E.; ZHENG, XUAN; CHEN, XIEQUN; ZHANG, JINYI

    2016-01-01

    The CD5 transmembrane glycoprotein functions as a co-receptor in the signaling pathway linking T-cell antigen receptor (TCR) engagement to activation and differentiation. Although CD5 effects on TCR signaling have been shown to be primarily inhibitory, the underlying mechanisms remain unclear. In view of recent data revealing the ability of CD5 to associate with the SHP-1 tyrosine phosphatase, a protein that also downregulates TCR signaling, we examined the role of SHP-1 in modulating CD5 function using thymocytes from SHP-1-deficient viable motheaten (mev) mice. The results revealed the association of SHP-1 with CD5 to be markedly increased following TCR stimulation and indicated that this interaction was enhanced by and was dependent on CD5 tyrosine phosphorylation. However, there was no difference of the tyrosine phosphorylation status of CD5 between resting and TCR-stimulated cells in SHP-1-deficient compared to wild-type thymocytes. Lack of SHP-1 activity did not affect the levels of CD5 surface expression, CD5 co-immunoprecipitable tyrosine phosphatase activity and intracellular calcium increase following co-crosslinking of the TCR and CD5. Similarly, an analysis of T-cell thymocyte populations in mev mice expressing an H-Y transgene as well as a construct mediating T-cell restricted CD5 overexpression, revealed that the reduction in the positive selection conferred by CD5 overexpression was unaffected by SHP-1 deficiency. CD5 is not a SHP-1 substrate and SHP-1 is not required for and possibly not involved in the CD5-mediated modulation of TCR signaling. PMID:27221212

  6. Expression and Clinical Significance of SHP2 in the Tumor Tissues of Smokers with Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xuemei ZHAN

    2010-09-01

    Full Text Available Background and objective It has been proved that protein phosphorylation and dephosphorylation were important mechanisms in lung cancer development, and tobacco smoking is an important risk factor of lung cancer. The aim of this study is to investigate the expression and clinical significance of protein tyrosine phosphatase SHP2 in non-small cell lung cancer (NSCLC and small cell lung cancer (SCLC; the relationship between tobacco smoking and the expression of SHP2 is also studied. Methods Immunohistochemistry (Invision and fluorescence in situ hybridization (FISH were used to detect the expression of SHP2 and the augment of SHP2 mRNA in the 53 lung cancer specimens. Results The weak positive rate of SHP2 was 80% (which was also the total positive rate in normal bronchial epithelium. The weak, moderate and strong positive rates were 35.4%, 43.8% and 6.2% (total positive rate was 85.4% in 48 NSCLC patients, 0%, 80% and 20% (total positve rate was 100% in 5 SCLC patients, 40.7%, 37.4% and 3.7% (total positive rate was 81.5% in the tumor tissues of 27 NSCLC patients who didn’t smoke and 23.8%, 71.4% and 4.7% (total positive rate was 100% in the tumor tissues of 21 NSCLC patients whose smoking indexes were ≥400. Significant differences of SHP2 expression were observed between tumor tissues and normal bronchial epithelium, NSCLC and SCLC, and between different smoking indexes (P < 0.05. Conclusion The enhancement of SHP2 expression in the tumor tissues of NSCLC patients who smoke may be correlated with tobacco smoking; SHP2 may play certain role in the development of lung cancer; SHP2 prospectively provides new ideas for the drug research and development of lung cancer treatment.

  7. UNDERCOVER PARTNER

    Directory of Open Access Journals (Sweden)

    Alexandru MARIAN

    2016-05-01

    Full Text Available The undercover partner takes part in the process of providing the investigating bodies with information. This institution carries out activities similar to undercover investigator. These both represent a proactive investigating instrument used by criminal authorities to obtain better results concerning the fight against criminality. Under the cover another identity, they carefully search for crimes or favorable circumstances for commitment of others new.

  8. UNDERCOVER PARTNER

    Directory of Open Access Journals (Sweden)

    Marian ALEXANDRU

    2016-06-01

    Full Text Available The undercover partner takes part in the process of providing the investigating bodies with information. This institution carries out activities similar to undercover investigator. These both represent a proactive investigating instrument used by criminal authorities to obtain better results concerning the fight against criminality. Under the cover another identity, they carefully search for crimes or favorable circumstances for commitment of others new.

  9. The SHP-2 tyrosine phosphatase: Signaling mechanisms and biological functions

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Cellular biological activities are tightly controlled by intracellular signaling processes initiated by extracellular signals.Protein tyrosine phosphatases, which remove phosphate groups from phosphorylated signaling molecules, play equally important tyrosine roles as protein tyrosine kinases in signal transduction.SHP-2, a cytoplasmic SH2 domain containing protein tyrosine phosphatase, is involved in the signaling pathways of a variety of growth factors and cytokines. Recent studies have clearly demonstrated that this phosphatase plays an important role in transducing signal relay from the cell surface to the nucleus, and is a critical intracellular regulator in mediating cell proliferation and differentiation.

  10. Proto-oncogene Pokemon upregulate the expression of Shp2 in human liver cancer%人肝癌细胞中原癌基因Pokemon上调Shp2的表达

    Institute of Scientific and Technical Information of China (English)

    金秀丽; 孙钦升; 杨红伟; 刘峰; 蒋宇扬; 徐威

    2012-01-01

    目的 研究人肝癌细胞中Pokemon对Shp2表达的影响.方法 通过RT-PCR、Real time PCR和Western blot方法检测人肝癌细胞系QGY-7703和人正常肝细胞系HL-7702中Pokemon和Shp2的mRNA和蛋白表达水平差异;并通过瞬时转染si-Pokemon RNA沉默QGY-7703细胞中Pokemon使其低表达,再检测Shp2的mRNA和蛋白水平变化.结果 Pokemon在人肝癌细胞系QGY7703中的表达水平高于人正常肝细胞系HL-7702,Shp2的表达水平高低与Pokemon表达一致;在QGY-7703细胞中沉默Pokemon表达之后,Shp2的表达也相应降低.结论 原癌基因Pokemon作为一种转录因子,可能调控Shp2的表达.%Objective To investigate the effect of Pokemon on expression of Shp2. Methods Real time PCR and Western blot were performed to measure mRNA level and protein level of Pokemon and Shp2 in QGY-7703 cells and HL-7702 cells, respectively. To de'termine whether reducing Pokemon expression would decrease the level of Shp2, QGY-7703 cells were transfected with si-Pokemon RNA and negative control using Lipofectamine 2000. Results Both real time PCR and Western blot indicate that Pokemon and Shp2 were overexpressed in QGY-7703 cells. More importantly, Shp2 and Pokemon expression is correlated in human liver cancer cell. Conclusions Pokemon might prompt liver cancer progression through upregulating the expression of Shp2.

  11. Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress.

    Science.gov (United States)

    Gupta, Vivek K; You, Yuyi; Klistorner, Alexander; Graham, Stuart L

    2012-11-01

    Tropomyosin-receptor-kinase B (TrkB receptor) activation plays an important role in the survival of retinal ganglion cells (RGCs). This study reports a novel finding that, SH2 domain-containing phosphatase-2 (Shp-2) binds to the TrkB receptor in RGCs and negatively regulates its activity under glaucomatous stress. This enhanced binding of TrkB and Shp2 is mediated through caveolin. Caveolin 1 and 3 undergo hyper-phosphorylation in RGCs under stress and bind to the Shp2 phosphatase. Shp2 undergoes activation under glaucomatous stress conditions in RGCs in vivo with a concurrent loss of TrkB activity. Inhibiting the Shp2 phosphatase restored TrkB activity in cells exposed to excitotoxic and oxidative stress. Collectively, these findings implicate a molecular basis of Shp2 mediated TrkB deactivation leading to RGC degeneration observed in glaucoma. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Protein Tyrosine Phosphatase SHP-2 (PTPN11 in Hematopoiesis and Leukemogenesis

    Directory of Open Access Journals (Sweden)

    Xia Liu

    2011-01-01

    Full Text Available SHP-2 (PTPN11, a ubiquitously expressed protein tyrosine phosphatase, is critical for hematopoietic cell development and function owing to its essential role in growth factor/cytokine signaling. More importantly, germline and somatic mutations in this phosphatase are associated with Noonan syndrome, Leopard syndrome, and childhood hematologic malignancies. The molecular mechanisms by which SHP-2 mutations induce these diseases are not fully understood, as the biochemical bases of SHP-2 functions still remain elusive. Further understanding SHP-2 signaling activities and identification of its interacting proteins/substrates will shed light on the pathogenesis of PTPN11-associated hematologic malignancies, which, in turn, may lead to novel therapeutics for these diseases.

  13. The theory and practice of 100 pilot SHP-based rural electrification counties in China

    Energy Technology Data Exchange (ETDEWEB)

    Luo Gaorong [Organization of the United Nations, Beijing (China). International Centre of Small Hydroelectric Power Plants

    1995-07-01

    This document presents the theory and practice of 100 pilot small hydroelectric power plants (SHP) based rural electrification counties in China. The document reports the research contents, methodology and results, and the pilot benefit analysis and evaluation.

  14. Hydrography, sprzone shp, Published in 2005, 1:24000 (1in=2000ft) scale, Iron County.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Hydrography dataset, published at 1:24000 (1in=2000ft) scale, was produced all or in part from Other information as of 2005. It is described as 'sprzone shp'....

  15. Seeded growth of metal-doped plasmonic oxide heterodimer nanocrystals and their chemical transformation.

    Science.gov (United States)

    Ye, Xingchen; Reifsnyder Hickey, Danielle; Fei, Jiayang; Diroll, Benjamin T; Paik, Taejong; Chen, Jun; Murray, Christopher B

    2014-04-02

    We have developed a generalized seeded-growth methodology for the synthesis of monodisperse metal-doped plasmonic oxide heterodimer nanocrystals (NCs) with a near-unity morphological yield. Using indium-doped cadmium oxide (ICO) as an example, we show that a wide variety of preformed metal NCs (Au, Pt, Pd, FePt, etc.) can serve as the seeds for the tailored synthesis of metal-ICO heterodimers with exquisite size, shape, and composition control, facilitated by the delayed nucleation mechanism of the CdO phase. The metal-ICO heterodimers exhibit broadly tunable near-infrared localized surface plasmon resonances, and dual plasmonic bands are observed for Au-ICO heterodimers. We further demonstrate that the oxide domain of the Au-ICO heterodimers can be selectively and controllably transformed into a series of partially and completely hollow cadmium chalcogenide nanoarchitectures with unprecedented structural complexity, leaving the metal domain intact. Our work not only represents an exciting addition to the rapidly expanding library of chemical reactions that produce colloidal hybrid NCs, but it also provides a general route for the bottom-up chemical design of multicomponent metal-oxide-semiconductor NCs in a rational and sequential manner.

  16. SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes

    DEFF Research Database (Denmark)

    Qi, Weier; Li, Qian; Liew, Chong Wee

    2017-01-01

    expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidised lipids. RESULTS: Mice fed a high-fat diet (HFD) exhibited increased femoral artery intimal hyperplasia...... as Map2k1) and increased DNA methylation of the Shp-1 promoter. VSMCs from Shp-1-Tg mice exhibited impaired platelet-derived growth factor (PDGF)-stimulated tyrosine phosphorylation with a concomitant decrease in PDGF-stimulated VSMC proliferation and migration. Similarly, HFD-fed Shp-1-Tg mice and mice......AIMS/HYPOTHESIS: Accelerated migration and proliferation of vascular smooth muscle cells (VSMCs) enhances arterial restenosis after angioplasty in insulin resistance and diabetes. Elevation of Src homology 2-containing protein tyrosine phosphatase 1 (SHP-1) induces apoptosis in the microvasculature...

  17. The tyrosine phosphatase, SHP-1, is involved in bronchial mucin production during oxidative stress.

    Science.gov (United States)

    Jang, Min Kyoung; Kim, Sae-Hoon; Lee, Ki-Young; Kim, Tae-Bum; Moon, Keun Ae; Park, Chan Sun; Bae, Yun Jeong; Zhu, Zhou; Moon, Hee-Bom; Cho, You Sook

    2010-02-26

    Mucus hypersecretion is a clinically important manifestation of chronic inflammatory airway diseases, such as asthma and Chronic obstructive pulmonary disease (COPD). Mucin production in airway epithelia is increased under conditions of oxidative stress. Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 suppression is related to the development of airway inflammation and increased ROS levels. In this study, we investigated the role of SHP-1 in mucin secretion triggered by oxidative stress. Human lung mucoepidermoid H292 carcinoma cells were transfected with specific siRNA to eliminate SHP-1 gene expression. Cultured cells were treated with hydrogen peroxide (H(2)O(2)), and Mucin 5AC(MUC5AC) gene expression and mucin production were determined. Activation of p38 mitogen activated protein kinase (MAPK) in association with MUC5AC production was evaluated. N-acetylcysteine (NAC) was employed to determine whether antioxidants could block MUC5AC production. To establish the precise role of p38, mucin expression was observed after pre-treatment of SHP-1-depleted H292 cells with the p38 chemical blocker. We investigated the in vivo effects of oxidative stress on airway mucus production in SHP-1-deficient heterozygous (mev/+) mice. MUC5AC expression was enhanced in SHP-1 knockdown H292 cells exposed to H(2)O(2), compared to that in control cells. The ratio between phosphorylated and total p38 was significantly increased in SHP-1-deficient cells under oxidative stress. Pre-treatment with NAC suppressed both MUC5AC production and p38 activation. Blockage of p38 MAPK led to suppression of MUC5AC mRNA expression. Notably, mucin production was enhanced in the airway epithelia of mev/+ mice exposed to oxidative stress. Our results clearly indicate that SHP-1 plays an important role in airway mucin production through regulating oxidative stress.

  18. Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2.

    Directory of Open Access Journals (Sweden)

    Kunihiko Hatanaka

    Full Text Available BACKGROUND: The fibroblast growth factor (FGF system plays a critical role in the maintenance of vascular integrity via enhancing the stability of VE-cadherin at adherens junctions. However, the precise molecular mechanism is not well understood. In the present study, we aimed to investigate the detailed mechanism of FGF regulation of VE-cadherin function that leads to endothelial junction stabilization. METHODS AND FINDINGS: In vitro studies demonstrated that the loss of FGF signaling disrupts the VE-cadherin-catenin complex at adherens junctions by increasing tyrosine phosphorylation levels of VE-cadherin. Among protein tyrosine phosphatases (PTPs known to be involved in the maintenance of the VE-cadherin complex, suppression of FGF signaling reduces SHP2 expression levels and SHP2/VE-cadherin interaction due to accelerated SHP2 protein degradation. Increased endothelial permeability caused by FGF signaling inhibition was rescued by SHP2 overexpression, indicating the critical role of SHP2 in the maintenance of endothelial junction integrity. CONCLUSIONS: These results identify FGF-dependent maintenance of SHP2 as an important new mechanism controlling the extent of VE-cadherin tyrosine phosphorylation, thereby regulating its presence in adherens junctions and endothelial permeability.

  19. SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes.

    Science.gov (United States)

    Qi, Weier; Li, Qian; Liew, Chong Wee; Rask-Madsen, Christian; Lockhart, Samuel M; Rasmussen, Lars Melholt; Xia, Yu; Wang, Xuanchun; Khamaisi, Mogher; Croce, Kevin; King, George L

    2017-03-01

    Accelerated migration and proliferation of vascular smooth muscle cells (VSMCs) enhances arterial restenosis after angioplasty in insulin resistance and diabetes. Elevation of Src homology 2-containing protein tyrosine phosphatase 1 (SHP-1) induces apoptosis in the microvasculature. However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes. Further, we modulated SHP-1 expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidised lipids. Mice fed a high-fat diet (HFD) exhibited increased femoral artery intimal hyperplasia and decreased arterial SHP-1 expression compared with mice fed a regular diet. Arterial SHP-1 expression was also decreased in Zucker fatty rats, Zucker diabetic fatty rats and in patients with type 2 diabetes. In primary cultured VSMCs, oxidised LDL suppressed SHP-1 expression by activating Mek-1 (also known as Map2k1) and increased DNA methylation of the Shp-1 promoter. VSMCs from Shp-1-Tg mice exhibited impaired platelet-derived growth factor (PDGF)-stimulated tyrosine phosphorylation with a concomitant decrease in PDGF-stimulated VSMC proliferation and migration. Similarly, HFD-fed Shp-1-Tg mice and mice treated with the SHP-1 inducer, Icariside II, were protected from the development of intimal hyperplasia following wire injury. Suppression of SHP-1 by oxidised lipids may contribute to the excessive VSMC proliferation, inflammatory cytokine production and intimal hyperplasia observed in arteries from diabetes and insulin resistance. Augmenting SHP-1 levels is a potential therapeutic strategy to maintain stent patency in patients with insulin resistance and diabetes.

  20. PCl3-C6H6 heterodimers: evidence for Pπ phosphorus bonding at low temperatures.

    Science.gov (United States)

    Ramanathan, N; Sankaran, K; Sundararajan, K

    2016-07-28

    A phosphorous trichloride (PCl3)-benzene (C6H6) heterodimer was generated in a low temperature N2 matrix and was characterized using infrared spectroscopy. The structure of the heterodimer produced in the matrix isolation experiment was discerned through ab initio computations. Computations disclosed that the experimentally detected dimer is stabilized through strong non-covalent phosphorus bonded Pπ interaction, considered as a class of pnicogen bonding. This experimentally unmapped Pπ interaction so far has been reconnoitered using atoms in molecules and natural bond orbital and energy decomposition analyses. The influence of substitutions on both the PCl3 and C6H6 monomeric units of the heterodimer was subsequently examined to understand the strength of Pπ interaction as a result of these substitutions.

  1. Synthesis, morphological control, and antibacterial properties of hollow/solid Ag2S/Ag heterodimers

    KAUST Repository

    Pang, Maolin

    2010-08-11

    Ag2S and Ag are important functional materials that have received considerable research interest in recent years. In this work, we develop a solution-based synthetic method to combine these two materials into hollow/solid Ag2S/Ag heterodimers at room temperature. Starting from monodisperse Cu2O solid spheres, CuS hollow spheres can be converted from Cu2O through a modified Kirkendall process, and the obtained CuS can then be used as a solid precursor for preparation of the Ag2S/Ag heterodimers through ion exchange and photo-assisted reduction. We have found that formation of the Ag2S/Ag heterodimers is instantaneous, and the size of Ag nanocrystals on the hollow spheres of Ag2S can be controlled by changing the concentration and power of reducing agents in the synthesis. The growth of Ag nanoparticles on hollow spheres of Ag2S in the dimers is along the [111] direction of the silver crystal; the light absorption properties have also been investigated. Furthermore, coupling or tripling of Ag2S/Ag heterodimers into dumbbell-like trimers ((Ag 2S)2/Ag, linear) and triangular tetramers ((Ag 2S)3/Ag, coplanar) can also be attained at 60°C by adding the bidentate ligand ethylenediamine as a cross-linking agent. To test the applicability of this highly asymmetric dipolar composite, photocatalytic inactivation of Escherichia coli K-12 in the presence of the as-prepared Ag 2S/Ag heterodimers has been carried out under UV irradiation. The added Ag2S/Ag heterodimers show good chemical stability under prolonged UV irradiation, and no appreciable solid dissolution is found. Possible mechanisms regarding the enhanced antibacterial activity have also been addressed. © 2010 American Chemical Society.

  2. Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions

    Science.gov (United States)

    Peng, Jia; Li, Qinglei; Wigglesworth, Karen; Rangarajan, Adithya; Kattamuri, Chandramohan; Peterson, Randall T.; Eppig, John J.; Thompson, Thomas B.; Matzuk, Martin M.

    2013-01-01

    The TGF-β superfamily is the largest family of secreted proteins in mammals, and members of the TGF-β family are involved in most developmental and physiological processes. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), oocyte-secreted paralogs of the TGF-β superfamily, have been shown genetically to control ovarian physiology. Although previous studies found that GDF9 and BMP15 homodimers can modulate ovarian pathways in vitro, the functional species-specific significance of GDF9:BMP15 heterodimers remained unresolved. Therefore, we engineered and produced purified recombinant mouse and human GDF9 and BMP15 homodimers and GDF9:BMP15 heterodimers to compare their molecular characteristics and physiological functions. In mouse granulosa cell and cumulus cell expansion assays, mouse GDF9 and human BMP15 homodimers can up-regulate cumulus expansion-related genes (Ptx3, Has2, and Ptgs2) and promote cumulus expansion in vitro, whereas mouse BMP15 and human GDF9 homodimers are essentially inactive. However, we discovered that mouse GDF9:BMP15 heterodimer is ∼10- to 30-fold more biopotent than mouse GDF9 homodimer, and human GDF9:BMP15 heterodimer is ∼1,000- to 3,000-fold more bioactive than human BMP15 homodimer. We also demonstrate that the heterodimers require the kinase activities of ALK4/5/7 and BMPR2 to activate SMAD2/3 but unexpectedly need ALK6 as a coreceptor in the signaling complex in granulosa cells. Our findings that GDF9:BMP15 heterodimers are the most bioactive ligands in mice and humans compared with homodimers explain many puzzling genetic and physiological data generated during the last two decades and have important implications for improving female fertility in mammals. PMID:23382188

  3. Social Partners

    DEFF Research Database (Denmark)

    Hansen, Leif Emil

    2011-01-01

    The purpose of the paper is to present findings from a new Nordic survey on social partners’ policy and practice in regards older workers. The goal of the survey was to find out to what extent the social partners have developed policies and outlined strategies, which explicitly address...... the demographic change and promote opportunities for lifelong learning and career development among their senior members (45+). Workforce in the Nordic countries tend to be highly organised – especially the older workers. The social partners’ involvement in the discussion of sustainable society...... difficult position” regarding this matter, but also that they should develop clearer strategy in response to demographic change, and communicate it to their members. The OWNsurvey was carried out as a part of the work in the network Older workers in the Nordic countries (OWN) supported by the Nordic Council...

  4. Fluorescence resonance energy transfer imaging reveals that chemokine-binding modulates heterodimers of CXCR4 and CCR5 receptors.

    Directory of Open Access Journals (Sweden)

    Nilgun Isik

    Full Text Available BACKGROUND: Dimerization has emerged as an important feature of chemokine G-protein-coupled receptors. CXCR4 and CCR5 regulate leukocyte chemotaxis and also serve as a co-receptor for HIV entry. Both receptors are recruited to the immunological synapse during T-cell activation. However, it is not clear whether they form heterodimers and whether ligand binding modulates the dimer formation. METHODOLOGY/PRINCIPAL FINDINGS: Using a sensitive Fluorescence Resonance Energy Transfer (FRET imaging method, we investigated the formation of CCR5 and CXCR4 heterodimers on the plasma membrane of live cells. We found that CCR5 and CXCR4 exist as constitutive heterodimers and ligands of CCR5 and CXCR4 promote different conformational changes within these preexisting heterodimers. Ligands of CCR5, in contrast to a ligand of CXCR4, induced a clear increase in FRET efficiency, indicating that selective ligands promote and stabilize a distinct conformation of the heterodimers. We also found that mutations at C-terminus of CCR5 reduced its ability to form heterodimers with CXCR4. In addition, ligands induce different conformational transitions of heterodimers of CXCR4 and CCR5 or CCR5(STA and CCR5(Delta4. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest a model in which CXCR4 and CCR5 spontaneously form heterodimers and ligand-binding to CXCR4 or CCR5 causes different conformational changes affecting heterodimerization, indicating the complexity of regulation of dimerization/function of these chemokine receptors by ligand binding.

  5. The tyrosine phosphatase SHP-1 regulates hypoxia inducible factor-1α (HIF-1α protein levels in endothelial cells under hypoxia.

    Directory of Open Access Journals (Sweden)

    Stefan K Alig

    Full Text Available The tyrosine phosphatase SHP-1 negatively influences endothelial function, such as VEGF signaling and reactive oxygen species (ROS formation, and has been shown to influence angiogenesis during tissue ischemia. In ischemic tissues, hypoxia induced angiogenesis is crucial for restoring oxygen supply. However, the exact mechanism how SHP-1 affects endothelial function during ischemia or hypoxia remains unclear. We performed in vitro endothelial cell culture experiments to characterize the role of SHP-1 during hypoxia.SHP-1 knock-down by specific antisense oligodesoxynucleotides (AS-Odn increased cell growth as well as VEGF synthesis and secretion during 24 hours of hypoxia compared to control AS-Odn. This was prevented by HIF-1α inhibition (echinomycin and apigenin. SHP-1 knock-down as well as overexpression of a catalytically inactive SHP-1 (SHP-1 CS further enhanced HIF-1α protein levels, whereas overexpression of a constitutively active SHP-1 (SHP-1 E74A resulted in decreased HIF-1α levels during hypoxia, compared to wildtype SHP-1. Proteasome inhibition (MG132 returned HIF-1α levels to control or wildtype levels respectively in these cells. SHP-1 silencing did not alter HIF-1α mRNA levels. Finally, under hypoxic conditions SHP-1 knock-down enhanced intracellular endothelial reactive oxygen species (ROS formation, as measured by oxidation of H2-DCF and DHE fluorescence.SHP-1 decreases half-life of HIF-1α under hypoxic conditions resulting in decreased cell growth due to diminished VEGF synthesis and secretion. The regulatory effect of SHP-1 on HIF-1α stability may be mediated by inhibition of endothelial ROS formation stabilizing HIF-1α protein. These findings highlight the importance of SHP-1 in hypoxic signaling and its potential as therapeutic target in ischemic diseases.

  6. Sinapate dehydrodimers and sinapate−ferulate heterodimers in cereal dietary fiber

    Science.gov (United States)

    Mirko Bunzel; John Ralph; Hoon Kim; Fachuang Lu; Sally A. Ralph; Jane M. Marita; Ronald D. Hatfield; Hans Steinhart

    2003-01-01

    Two 8-8-coupled sinapic acid dehydrodimers and at least three sinapate-ferulate heterodimers have been identified as saponification products from different insoluble and soluble cereal grain dietary fibers. The two 8-8-disinapates were authenticated by comparison of their GC retention times and mass spectra with authentic dehydrodimers synthesized from methyl or ethyl...

  7. Spectral Sensitization of TiO2 Substrates by Monolayers of Porphyrin Heterodimers

    NARCIS (Netherlands)

    Koehorst, R.B.M.; Boschloo, G.K.; Savenije, T.J.; Goossens, A.; Schaafsma, T.J.

    2000-01-01

    Photoelectrochemical cells have been constructed by depositing monolayers of oriented covalently linked zinc/free base porphyrin heterodimers onto ~30 nm nonporous layers of TiO2 on ITO, deposited by metal-organic chemical vapor deposition (MO-CVD), and onto ~100 nm porous, nanostructured TiO2

  8. Effect of Candesartan Cilexetil as a Sensitive and Effective Inhibitor of SHP-1 on Insulin Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lei; ZHANG Shi-tao; ZHANG Xiao-ping; SUN Jing; WANG Yong-sen; LIU Yue-long; XUE Miao-miao

    2013-01-01

    The protein tyrosine phosphatases(PTPs) comprise a family of enzymes that specifically dephosphorylate tyrosyl residues.Among them,SHP-1 has been regarded as one of the best validated intracellular tyrosine phosphatases.Downregulation of SHP-1 has shown remarkable efficacy in improving insulin sensitivity in vivo in insulin signaling pathway.In this study,we found the role of Candesartan cilexetil targeting at SHP-1.The results indicate that Candesartan cilexetil was a competitive inhibitor to SHP-1(IC50=85.6 μmol/L and Ki=24 μmol/L).We also found that Candesartan cilexetil was more sensitive towards SHP-1 compared with other PTPs.Through the consequence of Western blotting,it showed that Candesartan cilexetil can strengthen the level of tyrosine phosphorylation of several key cellular proteins[such as insulin receptor(IR),insulin receptor substrate(IRS) and ERK] in insulin signaling pathway in HepG2 cells and improve the insulin sensitivity through inhibiting the protein phosphorylation of SHP-1.These findings showed that Candesartan cilexetil might be an important inhibitor of SHP-1 and had a great application potential in the treatment of diabetes through inhibiting the level of SHP-1 in insulin signaling pathway.

  9. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration

    DEFF Research Database (Denmark)

    Voena, Claudia; Conte, Chiara; Ambrogio, Chiara;

    2007-01-01

    in the activation loop of Src, resulting in impaired ALCL cell proliferation and growth disadvantage. Finally, migration of ALCL cells was reduced by Shp2 shRNA. These findings show a direct involvement of Shp2 in NPM-ALK lymphomagenesis, highlighting its critical role in lymphoma cell proliferation and migration....

  10. Tomato gamma-glutamylhydrolases: expression, characterization, and evidence for heterodimer formation.

    Science.gov (United States)

    Akhtar, Tariq A; McQuinn, Ryan P; Naponelli, Valeria; Gregory, Jesse F; Giovannoni, James J; Hanson, Andrew D

    2008-10-01

    Folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase (GGH). It is known that GGH is active only as a dimer and that plants can have several GGH genes whose homodimeric products differ functionally. However, it is not known whether GGH dimers dissociate under in vivo conditions, whether heterodimers form, or how heterodimerization impacts enzyme activity. These issues were explored using the GGH system of tomato (Solanum lycopersicum). Tomato has three GGH genes that, like those in other eudicots, apparently diverged recently. LeGGH1 and LeGGH2 are expressed in fruit and all other organs, whereas LeGGH3 is expressed mainly in flower buds. LeGGH1 and LeGGH2 homodimers differ in bond cleavage preference; the LeGGH3 homodimer is catalytically inactive. Homodimers did not dissociate in physiological conditions. When coexpressed in Escherichia coli, LeGGH1 and LeGGH2 formed heterodimers with an intermediate bond cleavage preference, whereas LeGGH3 formed heterodimers with LeGGH1 or LeGGH2 that had one-half the activity of the matching homodimer. E. coli cells expressing LeGGH2 showed approximately 85% reduction in folate polyglutamates, but cells expressing LeGGH3 did not, confirming that LeGGH2 can function in vivo and LeGGH3 cannot. The formation of LeGGH1-LeGGH2 heterodimers was demonstrated in planta using bimolecular fluorescence complementation. Plant GGH heterodimers thus appear to form wherever different GGH genes are expressed simultaneously and to have catalytic characteristics midway between those of the corresponding homodimers.

  11. Structural and spectropotentiometric analysis of Blastochloris viridis heterodimer mutant reaction center

    Energy Technology Data Exchange (ETDEWEB)

    Ponomarenko, Nina S.; Li, Liang; Marino, Antony R.; Tereshko, Valentina; Ostafin, Agnes; Popova, Julia A.; Bylina, Edward J.; Ismagilov, Rustem F.; Norris, Jr., James R.; (UC); (Utah)

    2010-07-22

    Heterodimer mutant reaction centers (RCs) of Blastochloris viridis were crystallized using microfluidic technology. In this mutant, a leucine residue replaced the histidine residue which had acted as a fifth ligand to the bacteriochlorophyll (BChl) of the primary electron donor dimer M site (HisM200). With the loss of the histidine-coordinated Mg, one bacteriochlorophyll of the special pair was converted into a bacteriopheophytin (BPhe), and the primary donor became a heterodimer supermolecule. The crystals had dimensions 400 x 100 x 100 {micro}m, belonged to space group P4{sub 3}2{sub 1}2, and were isomorphous to the ones reported earlier for the wild type (WT) strain. The structure was solved to a 2.5 {angstrom} resolution limit. Electron-density maps confirmed the replacement of the histidine residue and the absence of Mg. Structural changes in the heterodimer mutant RC relative to the WT included the absence of the water molecule that is typically positioned between the M side of the primary donor and the accessory BChl, a slight shift in the position of amino acids surrounding the site of the mutation, and the rotation of the M194 phenylalanine. The cytochrome subunit was anchored similarly as in the WT and had no detectable changes in its overall position. The highly conserved tyrosine L162, located between the primary donor and the highest potential heme C{sub 380}, revealed only a minor deviation of its hydroxyl group. Concomitantly to modification of the BChl molecule, the redox potential of the heterodimer primary donor increased relative to that of the WT organism (772 mV vs. 517 mV). The availability of this heterodimer mutant and its crystal structure provides opportunities for investigating changes in light-induced electron transfer that reflect differences in redox cascades.

  12. Expression and clinical significance of tyrosine phosphatase SHP-2 in colon cancer.

    Science.gov (United States)

    Cai, Peifen; Guo, Wenjie; Yuan, Huaqin; Li, Qian; Wang, Weicheng; Sun, Yang; Li, Xiaomin; Gu, Yanhong

    2014-04-01

    Protein-tyrosine phosphatase SHP-2, encoded by gene PTPN11, has been identified as a tumor-promoting factor in several types of leukemia and is hyper-activated by other mechanisms in some solid tumors including gastric cancer, breast cancer, non-small cell lung cancer (NSCLC), etc. But few were reported on the expression and significances of SHP-2 in colon cancer. Here, we detect SHP-2 expression in colon cancer cells, colon cancer-induced by AOM+DSS in mice and 232 human colon cancer specimens, including 58 groups of self-matched adjacent peritumor tissues and normal tissues. We found that compared to the normal colon tissues, SHP-2 significantly decreased in tumor tissues (Pcolon tumor cells as well as mice colon tumors. And in humans samples, low SHP-2 expression showed a significantly correlation with poor tumor differentiation (P<0.05), late TNM stage (P=0.1666) and lymph node metastasis (P<0.05).

  13. Low retinol levels differentially modulate bile salt-induced expression of human and mouse hepatic bile salt transporters

    NARCIS (Netherlands)

    M.O. Hoeke; J.R.M. Plass; J. Heegsma; M. Geuken; D. van Rijsbergen; J.F.W. Baller; F. Kuipers; H. Moshage; P.L.M. Jansen; K.N. Faber

    2009-01-01

    The farnesoid X receptor/retinoid X receptor-alpha (FXR/RXRalpha) complex regulates bile salt homeostasis, in part by modulating transcription of the bile salt export pump (BSEP/ABCB11) and small heterodimer partner (SHP/NR0B2). FXR is activated by bile salts, RXRalpha by the vitamin A derivative 9-

  14. Low Retinol Levels Differentially Modulate Bile Salt-Induced Expression of Human and Mouse Hepatic Bile Salt Transporters

    NARCIS (Netherlands)

    Hoeke, Martijn O.; Plass, Jacqueline R. M.; Heegsma, Janette; Geuken, Mariska; van Rijsbergen, Duncan; Baller, Julius F. W.; Kuipers, Folkert; Moshage, Han; Jansen, Peter L. M.; Faber, Klaas Nico

    2009-01-01

    The farnesoid X receptor/retinoid X receptor-alpha (FXR/RXR alpha) complex regulates bile salt homeostasis, in part by modulating transcription of the bile salt export pump (BSEP/ABCB11 I) and small heterodimer partner (SHP/NR0B2). FXR is activated by bile salts, RXR alpha by the vitamin A derivativ

  15. Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes.

    Science.gov (United States)

    Soong, Joanne; Scott, Glynis

    2013-01-15

    Plexin B1, the receptor for Semaphorin 4D (Sema4D), is expressed by melanocytes in the skin. We recently showed that Sema4D suppresses activation of the hepatocyte growth factor receptor, MET, in melanocytes, and that knockdown of Plexin B1 results in activation of MET. MET signaling mediates proliferation, survival and migration in melanocytes, and its activation is associated with transformation of melanocytes to melanoma. In this report we investigated the mechanism by which Plexin B1 inhibits MET activation. Our results show that Plexin B1 and MET exist as an oligomeric receptor-receptor complex in melanocytes, and that receptor association is increased by Sema4D. MET and Plexin B1 receptor complexes were identified along the cell body of melanocytes, and Sema4D increased receptor association on dendrites, suggesting that Sema4D regulates MET-dependent processes at precise locations on the melanocyte. Despite activation of MET, Plexin B1 knockdowns proliferated slowly and showed increased apoptosis compared with controls. Shp2, a non-receptor protein tyrosine phosphatase, translates growth and survival signals from MET and other receptor tyrosine kinases. Plexin B1 knockdowns had markedly lower levels of Shp2 compared with controls, and Sema4D upregulated Shp2 expression at the protein and message level in normal melanocytes. Functional studies showed that blockade of Shp2 activity abrogated MET-dependent activation of Erk1/Erk2 and Akt in melanocytes. These results suggest a complex role for Sema4D and Plexin B1 in orchestrating signaling from the MET receptor in melanocytes. Because Shp2 is a downstream adaptor protein for multiple receptors, Sema4D may control the effects of several growth factors on melanocytes through regulation of Shp2.

  16. Production in Pichia pastoris of protein-based polymers with small heterodimer-forming blocks.

    Science.gov (United States)

    Domeradzka, Natalia E; Werten, Marc W T; de Vries, Renko; de Wolf, Frits A

    2016-05-01

    Some combinations of leucine zipper peptides are capable of forming α-helical heterodimeric coiled coils with very high affinity. These can be used as physical cross-linkers in the design of protein-based polymers that form supramolecular structures, for example hydrogels, upon mixing solutions containing the complementary blocks. Such two-component physical networks are of interest for many applications in biomedicine, pharmaceutics, and diagnostics. This article describes the efficient secretory production of A and B type leucine zipper peptides fused to protein-based polymers in Pichia pastoris. By adjusting the fermentation conditions, we were able to significantly reduce undesirable proteolytic degradation. The formation of A-B heterodimers in mixtures of the purified products was confirmed by size exclusion chromatography. Our results demonstrate that protein-based polymers incorporating functional heterodimer-forming blocks can be produced with P. pastoris in sufficient quantities for use in future supramolecular self-assembly studies and in various applications.

  17. Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP.

    Science.gov (United States)

    Perederina, Anna; Khanova, Elena; Quan, Chao; Berezin, Igor; Esakova, Olga; Krasilnikov, Andrey S

    2011-10-01

    Ribonuclease (RNase) MRP is a multicomponent ribonucleoprotein complex closely related to RNase P. RNase MRP and eukaryotic RNase P share most of their protein components, as well as multiple features of their catalytic RNA moieties, but have distinct substrate specificities. While RNase P is practically universally found in all three domains of life, RNase MRP is essential in eukaryotes. The structural organizations of eukaryotic RNase P and RNase MRP are poorly understood. Here, we show that Pop5 and Rpp1, protein components found in both RNase P and RNase MRP, form a heterodimer that binds directly to the conserved area of the putative catalytic domain of RNase MRP RNA. The Pop5/Rpp1 binding site corresponds to the protein binding site in bacterial RNase P RNA. Structural and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are discussed.

  18. Fano resonance assisting plasmonic circular dichroism from nanorice heterodimers for extrinsic chirality

    CERN Document Server

    Hu, Li; Fang, Liang; Chen, Guo; Wei, Hua; Fang, Yurui

    2015-01-01

    In this work, the circular dichroisms (CD) of nanorice heterodimers consisting of two parallel arranged nanorices with the same size but different materials are investigated theoretically. Symmetry-breaking is introduced by using different materials and oblique incidence to achieve strong CD at the vicinity of Fano resonance peaks. We demonstrate that all Au-Ag heterodimers exhibit multipolar Fano resonances and strong CD effect. A simple quantitative analysis shows that the structure with larger Fano asymmetry factor has stronger CD. The intensity and peak positions of the CD effect can be flexibly tuned in a large range by changing particle size, shape, the inter-particle distance and surroundings. Furthermore, CD spectra exhibit high sensitivity to ambient medium in visible and near infrared regions. Our results here are beneficial for the design and application of high sensitive CD sensors and other related fields.

  19. Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets

    Energy Technology Data Exchange (ETDEWEB)

    Bellina, Bruno; Merthe, Daniel J.; Kresin, Vitaly V. [Department of Physics and Astronomy, University of Southern California, Los Angeles, California 90089-0484 (United States)

    2015-03-21

    We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N–H ⋅ ⋅ ⋅ N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment.

  20. Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets

    CERN Document Server

    Bellina, Bruno; Kresin, Vitaly V

    2015-01-01

    We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N-H...N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment.

  1. Sorafenib analogue SC-60 induces apoptosis through the SHP-1/STAT3 pathway and enhances docetaxel cytotoxicity in triple-negative breast cancer cells.

    Science.gov (United States)

    Liu, Chun-Yu; Su, Jung-Chen; Huang, Tzu-Ting; Chu, Pei-Yi; Huang, Chun-Teng; Wang, Wan-Lun; Lee, Chia-Han; Lau, Ka-Yi; Tsai, Wen-Chun; Yang, Hsiu-Ping; Shiau, Chung-Wai; Tseng, Ling-Ming; Chen, Kuen-Feng

    2017-03-01

    Recurrent triple-negative breast cancer (TNBC) needs new therapeutic targets. Src homology region 2 domain-containing phosphatase-1 (SHP-1) can act as a tumor suppressor by dephosphorylating oncogenic kinases. One major target of SHP-1 is STAT3, which is highly activated in TNBC. In this study, we tested a sorafenib analogue SC-60, which lacks angiokinase inhibition activity, but acts as a SHP-1 agonist, in TNBC cells. SC-60 inhibited proliferation and induced apoptosis by dephosphorylating STAT3 in both a dose- and time-dependent manner in TNBC cells (MDA-MB-231, MDA-MB-468, and HCC1937). By contrast, ectopic expression of STAT3 rescued the anticancer effect induced by SC-60. SC-60 also increased the SHP-1 activity, but this effect was inhibited when the N-SH2 domain (DN1) was deleted or with SHP-1 point mutation (D61A), implying that SHP-1 is the major target of SC-60 in TNBC. The use of SC-60 in combination with docetaxel synergized the anticancer effect induced by SC-60 through the SHP-1/STAT3 pathway in TNBC cells. Importantly, SC-60 also displayed a significant antitumor effect in an MDA-MB-468 xenograft model by modulating the SHP-1/STAT3 axis, indicating the anticancer potential of SC-60 in TNBC treatment. Targeting SHP-1/p-STAT3 and the potential combination of SHP-1 agonist with chemotherapeutic docetaxel is a feasible therapeutic strategy for TNBC.

  2. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration.

    Science.gov (United States)

    Voena, Claudia; Conte, Chiara; Ambrogio, Chiara; Boeri Erba, Elisabetta; Boccalatte, Francesco; Mohammed, Shabaz; Jensen, Ole N; Palestro, Giorgio; Inghirami, Giorgio; Chiarle, Roberto

    2007-05-01

    Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades, leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry-based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine phosphatase Shp2 as a candidate substrate. We found that NPM-ALK was able to bind Shp2 in coprecipitation experiments and to induce its phosphorylation in the tyrosine residues Y542 and Y580 both in HEK293 cells and ALCL cell lines. In primary lymphomas, antibodies against the phosphorylated tyrosine Y542 of Shp2 mainly stained ALK-positive cells. In ALCL cell lines, Shp2-constitutive phosphorylation was dependent on NPM-ALK, as it significantly decreased after short hairpin RNA (shRNA)-mediated NPM-ALK knock down. In addition, only the constitutively active NPM-ALK, but not the kinase dead NPM-ALK(K210R), formed a complex with Shp2, Gab2, and growth factor receptor binding protein 2 (Grb2), where Grb2 bound to the phosphorylated Shp2 through its SH2 domain. Shp2 knock down by specific shRNA decreased the phosphorylation of extracellular signal-regulated kinase 1/2 and of the tyrosine residue Y416 in the activation loop of Src, resulting in impaired ALCL cell proliferation and growth disadvantage. Finally, migration of ALCL cells was reduced by Shp2 shRNA. These findings show a direct involvement of Shp2 in NPM-ALK lymphomagenesis, highlighting its critical role in lymphoma cell proliferation and migration.

  3. Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

    Science.gov (United States)

    Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

    2015-04-01

    Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

  4. Binary Toxin Subunits of Lysinibacillus sphaericus Are Monomeric and Form Heterodimers after In Vitro Activation.

    Directory of Open Access Journals (Sweden)

    Wahyu Surya

    Full Text Available The binary toxin from Lysinibacillus sphaericus has been successfully used for controlling mosquito-transmitted diseases. An activation step shortens both subunits BinA and BinB before their interaction with membranes and internalization in midgut cells, but the precise role of this activation step is unknown. Herein, we show conclusively using three orthogonal biophysical techniques that protoxin subunits form only monomers in aqueous solution. However, in vitro activated toxins readily form heterodimers. This oligomeric state did not change after incubation of these heterodimers with detergent. These results are consistent with the evidence that maximal toxicity in mosquito larvae is achieved when the two subunits, BinA and BinB, are in a 1:1 molar ratio, and directly link proteolytic activation to heterodimerization. Formation of a heterodimer must thus be necessary for subsequent steps, e.g., interaction with membranes, or with a suitable receptor in susceptible mosquito species. Lastly, despite existing similarities between BinB C-terminal domain with domains 3 and 4 of pore-forming aerolysin, no aerolysin-like SDS-resistant heptameric oligomers were observed when the activated Bin subunits were incubated in the presence of detergents or lipidic membranes.

  5. Five Significant Points of“SHP (Small Hydropower) Replacing Firewood” Ecological Protection Project

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Developing rural hydropower and enforcing “SHP replacing firewood”ecological protection project are deemed very significant to protect and improve ecological environment,promote socioeconomic development of rural areas and rapidly build a wellbeing society in full swing in China,which can be elaborated in the following five aspects:

  6. Speech at opening ceremony of 2002 Sino-African SHP training workshop

    Institute of Scientific and Technical Information of China (English)

    ChenShengshui; DirectorofHRC

    2002-01-01

    I am honored to be with you this morning. You all came far away from Africa to Hangzhou! On behalf of all HRC staff, I'd like to extend my warm welcome to you for attending the 2002 Sino-African SHP Training Workshop.

  7. Partnering and contracting

    DEFF Research Database (Denmark)

    Bohnstedt, Kristian Ditlev

    2014-01-01

    Purpose - Partnering is often, by economists, and construction managerial literature related to more incomplete contracts. This can be explained by seeing partnering as something that neutralizes opportunism. The aim is to uncover whether partnering neutralizes opportunism when there is an incomp......Purpose - Partnering is often, by economists, and construction managerial literature related to more incomplete contracts. This can be explained by seeing partnering as something that neutralizes opportunism. The aim is to uncover whether partnering neutralizes opportunism when...... outcomes with the conception of being repaid later in accordance to reciprocity. Value - Seeing partnering as the willingness to renegotiate complete contracts can reduce the risk for the contractor and lead to lower prices for a given service. Keywords Partnering, Contracting, Pareto efficiency...

  8. Olympic Partner Programme

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ The Olympic Partner Programme (TOP) is an international Olympic marketing programme created by the International Olympic Committee (IOC),which includes the Organising Committees of the Games,the National Olympic Committees and the TOP Partners.

  9. Geographic Place Names, communities.shp, Published in unknown, 1:24000 (1in=2000ft) scale, Door County, Wisconsin.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Geographic Place Names dataset, published at 1:24000 (1in=2000ft) scale as of unknown. It is described as 'communities.shp'. Data by this publisher are often...

  10. Recruitment of SHP-1 protein tyrosine phosphatase and signalling by a chimeric T-cell receptor-killer inhibitory receptor

    DEFF Research Database (Denmark)

    Christensen, M D; Geisler, C

    2000-01-01

    Receptors expressing the immunoreceptor tyrosine-based inhibitory motif (ITIM) in their cytoplasmic tail play an important role in the negative regulation of natural killer and B-cell activation. A subpopulation of T cells expresses the ITIM containing killer cell inhibitory receptor (KIR), which...... recognize MHC class I molecules. Following coligation of KIR with an activating receptor, the tyrosine in the ITIM is phosphorylated and the cytoplasmic protein tyrosine phosphatase SHP-1 is recruited to the ITIM via its SH2 domains. It is still not clear how SHP-1 affects T-cell receptor (TCR) signalling....... In this study, we constructed a chimeric TCR-KIR receptor. We demonstrated that SHP-1 is recruited to the chimeric TCR-KIR receptor following T-cell stimulation with either anti-TCR monoclonal antibody (MoAb) or superantigen. However, in spite of this we could not detect any effect of SHP-1 on TCR signalling...

  11. The Constitution of Partnering

    DEFF Research Database (Denmark)

    Gottlieb, Stefan Christoffer

    The constitution of partnering. Afhandlingen behandler konstitueringen af ledelseskonceptet partnering og dets anvendelse i dansk byggeri. Partnering er et udbredt koncept i byggeriet som betoner samarbejde, tillid og gensidighed mellem de deltagende parter, og konceptet har de senere år har været...

  12. Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-γ

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chia-Ling [Translational Research Center, Taipei Medical University, Taipei 110, Taiwan (China); Chiang, Tzu-Hui; Tseng, Po-Chun [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Wang, Yu-Chih [Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin2014@tmu.edu.tw [Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China)

    2015-10-23

    Src homology-2 domain-containing phosphatase (SHP) 2, an oncogenic phosphatase, inhibits type II immune interferon (IFN)-γ signaling by subverting signal transducers and activators of transcription 1 tyrosine phosphorylation and activation. For cancer immunoediting, this study aimed to investigate the decrease of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor protein, leading to cellular impairment of IFN-γ signaling. In comparison with human lung adenocarcinoma A549 cells, the natural PTEN loss in another human lung adenocarcinoma line, PC14PE6/AS2 cells, presents reduced responsiveness in IFN-γ-induced IFN regulatory factor 1 activation and CD54 expression. Artificially silencing PTEN expression in A549 cells also caused cells to be unresponsive to IFN-γ without affecting IFN-γ receptor expression. IFN-γ-induced inhibition of cell proliferation and cytotoxicity were demonstrated in A549 cells but were defective in PC14PE6/AS2 cells and in PTEN-deficient A549 cells. Aberrant activation of SHP2 by ROS was specifically shown in PC14PE6/AS2 cells and PTEN-deficient A549 cells. Inhibiting ROS and SHP2 rescued cellular responses to IFN-γ-induced cytotoxicity and inhibition of cell proliferation in PC14PE6/AS2 cells. These results demonstrate that a decrease in PTEN facilitates ROS/SHP2 signaling, causing lung cancer cells to become unresponsive to IFN-γ. - Highlights: • This study demonstrates that PTEN decrease causes cellular unresponsive to IFN-γ. • Lung cancer cells with PTEN deficiency show unresponsive to IFN-γ signaling. • PTEN decrease inhibits IFN-γ-induced CD54, cell proliferation inhibition, and cytotoxicity. • ROS-mediated SHP2 activation makes PTEN-deficient cells unresponsive to IFN-γ.

  13. SHP: Smooth Hypocycloidal Paths with Collision-Free and Decoupled Multi-Robot Path Planning

    Directory of Open Access Journals (Sweden)

    Abhijeet Ravankar

    2016-06-01

    Full Text Available Generating smooth and continuous paths for robots with collision avoidance, which avoid sharp turns, is an important problem in the context of autonomous robot navigation. This paper presents novel smooth hypocycloidal paths (SHP for robot motion. It is integrated with collision-free and decoupled multi-robot path planning. An SHP diffuses (i.e., moves points along segments the points of sharp turns in the global path of the map into nodes, which are used to generate smooth hypocycloidal curves that maintain a safe clearance in relation to the obstacles. These nodes are also used as safe points of retreat to avoid collision with other robots. The novel contributions of this work are as follows: (1 The proposed work is the first use of hypocycloid geometry to produce smooth and continuous paths for robot motion. A mathematical analysis of SHP generation in various scenarios is discussed. (2 The proposed work is also the first to consider the case of smooth and collision-free path generation for a load carrying robot. (3 Traditionally, path smoothing and collision avoidance have been addressed as separate problems. This work proposes integrated and decoupled collision-free multi-robot path planning. ‵Node caching‵ is proposed to improve efficiency. A decoupled approach with local communication enables the paths of robots to be dynamically changed. (4 A novel ‵multi-robot map update‵ in case of dynamic obstacles in the map is proposed, such that robots update other robots about the positions of dynamic obstacles in the map. A timestamp feature ensures that all the robots have the most updated map. Comparison between SHP and other path smoothing techniques and experimental results in real environments confirm that SHP can generate smooth paths for robots and avoid collision with other robots through local communication.

  14. An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha.

    Science.gov (United States)

    Shang, Quan; Pan, Luxing; Saumoy, Monica; Chiang, John Y L; Tint, G Stephen; Salen, Gerald; Xu, Guorong

    2007-10-01

    The aim of this study was to explore why in rabbits activation of farnesoid X receptor (FXR) is dominant over activated liver X receptor-alpha (LXRalpha) in the regulation of CYP7A1. We cloned the rabbit CYP7A1 promoter and found a fetoprotein transcription factor (FTF) binding element embedded within the LXRalpha binding site (LXRE). Gel shift assays demonstrated that FTF competes with LXRalpha for binding to LXRE. Short heterodimer partner (SHP) enhances the competitive ability of FTF. Studies in HepG2 cells showed that SHP combined with FTF had more powerful effect to offset the stimulation of CYP7A1 by LXRalpha. Gel shift and chromatin immunoprecipitation assays demonstrated that SHP with FTF diminished LXRalpha binding to the CYP7A1 promoter. In vivo studies in rabbits fed cholesterol for 10 days showed that hepatic expression of SHP but not FTF rose and LXRalpha-bound LXRE decreased. We propose that the SHP/FTF heterodimer occupies LXRE via the embedded FTF binding element and blocks LXRalpha from recruiting to LXRE. Therefore, activation of FXR, which upregulates SHP expression, will eliminate the stimulatory effect of LXRalpha on the CYP7A1 promoter because increased levels of SHP combined with FTF diminish the recruitment of LXRalpha to CYP7A1 promoter.

  15. Sepsis-induced cardiac mitochondrial dysfunction involves altered mitochondrial-localization of tyrosine kinase Src and tyrosine phosphatase SHP2.

    Directory of Open Access Journals (Sweden)

    Qun S Zang

    Full Text Available Our previous research demonstrated that sepsis produces mitochondrial dysfunction with increased mitochondrial oxidative stress in the heart. The present study investigated the role of mitochondria-localized signaling molecules, tyrosine kinase Src and tyrosine phosphatase SHP2, in sepsis-induced cardiac mitochondrial dysfunction using a rat pneumonia-related sepsis model. SD rats were given an intratracheal injection of Streptococcus pneumoniae, 4×10(6 CFU per rat, (or vehicle for shams; heart tissues were then harvested and subcellular fractions were prepared. By Western blot, we detected a gradual and significant decrease in Src and an increase in SHP2 in cardiac mitochondria within 24 hours post-inoculation. Furthermore, at 24 hours post-inoculation, sepsis caused a near 70% reduction in tyrosine phosphorylation of all cardiac mitochondrial proteins. Decreased tyrosine phosphorylation of certain mitochondrial structural proteins (porin, cyclophilin D and cytochrome C and functional proteins (complex II subunit 30kD and complex I subunit NDUFB8 were evident in the hearts of septic rats. In vitro, pre-treatment of mitochondrial fractions with recombinant active Src kinase elevated OXPHOS complex I and II-III activity, whereas the effect of SHP2 phosphatase was opposite. Neither Src nor SHP2 affected complex IV and V activity under the same conditions. By immunoprecipitation, we showed that Src and SHP2 consistently interacted with complex I and III in the heart, suggesting that complex I and III contain putative substrates of Src and SHP2. In addition, in vitro treatment of mitochondrial fractions with active Src suppressed sepsis-associated mtROS production and protected aconitase activity, an indirect marker of mitochondrial oxidative stress. On the contrary, active SHP2 phosphatase overproduced mtROS and deactivated aconitase under the same in vitro conditions. In conclusion, our data suggest that changes in mitochondria

  16. Spinal SIRPα1-SHP2 interaction regulates spinal nerve ligation-induced neuropathic pain via PSD-95-dependent NR2B activation in rats.

    Science.gov (United States)

    Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuang; Hsieh, Ming-Chun; Lin, Tzer-Bin

    2012-05-01

    The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. Nerve ligation induced allodynia, SIRPα1, SHP2, phosphorylated SHP2 (pSHP2), and phosphorylated NR2B (pNR2B) expression, and SHP2-PSD-95, pSHP2-PSD-95, PSD-95-NR2B, and PSD-95-pNR2B coimmunoprecipitation in the ipsilateral dorsal horn. In allodynic rats, injury-induced SHP2 immunoreactivity was localized in the ipsilateral dorsal horn neurons and coincident with PSD-95 and NR2B immunoreactivity. SIRPα1 silencing using small interfering RNA (siRNA; 1, 3, or 5μg/rat for 7days) prevented injury-induced allodynia and the associated changes in protein expression, phosphorylation, and coimmunoprecipitation. Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development

  17. Mutation of the SHP-2 binding site in growth hormone (GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B

    DEFF Research Database (Denmark)

    Stofega, M R; Herrington, J; Billestrup, Nils;

    2000-01-01

    that the SH2 domains of SHP-2 bind directly to tyrosyl phosphorylated GHR from GH-treated cells. Tyrosine-to-phenylalanine mutation of tyrosine 595 of rat GHR greatly diminishes association of the SH2 domains of SHP-2 with GHR, and tyrosine-to-phenylalanine mutation of tyrosine 487 partially reduces...... phosphorylation. Consistent with the effects on STAT5B phosphorylation, tyrosine-to-phenylalanine mutation of tyrosine 595 prolongs the duration of tyrosyl phosphorylation of GHR and JAK2. These data suggest that tyrosine 595 is a major site of interaction of GHR with SHP-2, and that GHR-bound SHP-2 negatively...

  18. Protein tyrosine phosphatase SHP2/PTPN11 mistargeting as a consequence of SH2-domain point mutations associated with Noonan Syndrome and leukemia

    DEFF Research Database (Denmark)

    Müller, Pia J; Rigbolt, Kristoffer T G; Paterok, Dirk

    2013-01-01

    SHP2/PTPN11 is a key regulator of cytokine, growth factor and integrin signaling. SHP2 influences cell survival, proliferation and differentiation by regulating major signaling pathways. Mutations in PTPN11 cause severe diseases like Noonan, LEOPARD syndrome or leukemia. Whereas several of these ......SHP2/PTPN11 is a key regulator of cytokine, growth factor and integrin signaling. SHP2 influences cell survival, proliferation and differentiation by regulating major signaling pathways. Mutations in PTPN11 cause severe diseases like Noonan, LEOPARD syndrome or leukemia. Whereas several...

  19. Engineering of Immunoglobulin Fc Heterodimers Using Yeast Surface-Displayed Combinatorial Fc Library Screening.

    Directory of Open Access Journals (Sweden)

    Hye-Ji Choi

    Full Text Available Immunoglobulin Fc heterodimers, which are useful scaffolds for the generation of bispecific antibodies, have been mostly generated through structure-based rational design methods that introduce asymmetric mutations into the CH3 homodimeric interface to favor heterodimeric Fc formation. Here, we report an approach to generate heterodimeric Fc variants through directed evolution combined with yeast surface display. We developed a combinatorial heterodimeric Fc library display system by mating two haploid yeast cell lines, one haploid cell line displayed an Fc chain library (displayed FcCH3A with mutations in one CH3 domain (CH3A on the yeast cell surface, and the other cell line secreted an Fc chain library (secreted FcCH3B with mutations in the other CH3 domain (CH3B. In the mated cells, secreted FcCH3B is displayed on the cell surface through heterodimerization with the displayed FcCH3A, the detection of which enabled us to screen the library for heterodimeric Fc variants. We constructed combinatorial heterodimeric Fc libraries with simultaneous mutations in the homodimer-favoring electrostatic interaction pairs K370-E357/S364 or D399-K392/K409 at the CH3 domain interface. High-throughput screening of the libraries using flow cytometry yielded heterodimeric Fc variants with heterodimer-favoring CH3 domain interface mutation pairs, some of them showed high heterodimerization yields (~80-90% with previously unidentified CH3 domain interface mutation pairs, such as hydrogen bonds and cation-π interactions. Our study provides a new approach for engineering Fc heterodimers that could be used to engineer other heterodimeric protein-protein interactions through directed evolution combined with yeast surface display.

  20. Engineering of Immunoglobulin Fc Heterodimers Using Yeast Surface-Displayed Combinatorial Fc Library Screening.

    Science.gov (United States)

    Choi, Hye-Ji; Kim, Ye-Jin; Choi, Dong-Ki; Kim, Yong-Sung

    2015-01-01

    Immunoglobulin Fc heterodimers, which are useful scaffolds for the generation of bispecific antibodies, have been mostly generated through structure-based rational design methods that introduce asymmetric mutations into the CH3 homodimeric interface to favor heterodimeric Fc formation. Here, we report an approach to generate heterodimeric Fc variants through directed evolution combined with yeast surface display. We developed a combinatorial heterodimeric Fc library display system by mating two haploid yeast cell lines, one haploid cell line displayed an Fc chain library (displayed FcCH3A) with mutations in one CH3 domain (CH3A) on the yeast cell surface, and the other cell line secreted an Fc chain library (secreted FcCH3B) with mutations in the other CH3 domain (CH3B). In the mated cells, secreted FcCH3B is displayed on the cell surface through heterodimerization with the displayed FcCH3A, the detection of which enabled us to screen the library for heterodimeric Fc variants. We constructed combinatorial heterodimeric Fc libraries with simultaneous mutations in the homodimer-favoring electrostatic interaction pairs K370-E357/S364 or D399-K392/K409 at the CH3 domain interface. High-throughput screening of the libraries using flow cytometry yielded heterodimeric Fc variants with heterodimer-favoring CH3 domain interface mutation pairs, some of them showed high heterodimerization yields (~80-90%) with previously unidentified CH3 domain interface mutation pairs, such as hydrogen bonds and cation-π interactions. Our study provides a new approach for engineering Fc heterodimers that could be used to engineer other heterodimeric protein-protein interactions through directed evolution combined with yeast surface display.

  1. Identification of protein tyrosine phosphatase SHP-2 as a new target of perfluoroalkyl acids in HepG2 cells.

    Science.gov (United States)

    Yang, Yu; Lv, Qi-Yan; Guo, Liang-Hong; Wan, Bin; Ren, Xiao-Min; Shi, Ya-Li; Cai, Ya-Qi

    2016-08-29

    Perfluoroalkyl acids (PFAAs) are widespread environmental contaminants which have been detected in humans and linked to adverse health effects. Previous toxicological studies mostly focused on nuclear receptor-mediated pathways and did not support the observed toxic effects. In this study, we aimed to investigate the molecular mechanisms of PFAA toxicities by identifying their biological targets in cells. Using a novel electrochemical biosensor, 16 PFAAs were evaluated for inhibition of protein tyrosine phosphatase SHP-2 activity. Their potency increased with PFAA chain length, with perfluorooctadecanoic acid (PFODA) showing the strongest inhibition. Three selected PFAAs, 25 μM perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid, and PFODA, also inhibited SHP-2 activity in HepG2 cells and increased paxillin phosphorylation level. PFOA was detected in the immunoprecipitated SHP-2 from the cells exposed to 250 μM PFOA, providing unequivocal evidence for the direct binding of PFOA with SHP-2 in the cell. Molecular docking rationalized the formation of PFAA/SHP-2 complex and chain length-dependent inhibition potency. Our results have established SHP-2 as a new cellular target of PFAAs.

  2. Leishmania-induced IRAK-1 inactivation is mediated by SHP-1 interacting with an evolutionarily conserved KTIM motif.

    Directory of Open Access Journals (Sweden)

    Issa Abu-Dayyeh

    Full Text Available Parasites of the Leishmania genus can rapidly alter several macrophage (MØ signalling pathways in order to tame down the innate immune response and inflammation, therefore favouring their survival and propagation within their mammalian host. Having recently reported that Leishmania and bacterial LPS generate a significantly stronger inflammatory response in animals and phagocytes functionally deficient for the Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1, we hypothesized that Leishmania could exploit SHP-1 to inactivate key kinases involved in Toll-like receptor (TLR signalling and innate immunity such as IL-1 receptor-associated kinase 1 (IRAK-1. Here we show that upon infection, SHP-1 rapidly binds to IRAK-1, completely inactivating its intrinsic kinase activity and any further LPS-mediated activation as well as MØ functions. We also demonstrate that the SHP-1/IRAK-1 interaction occurs via an evolutionarily conserved ITIM-like motif found in the kinase domain of IRAK-1, which we named KTIM (Kinase Tyrosyl-based Inhibitory Motif. This regulatory motif appeared in early vertebrates and is not found in any other IRAK family member. Our study additionally reveals that several other kinases (e.g. Erk1/2, IKKalpha/beta involved in downstream TLR signalling also bear KTIMs in their kinase domains and interact with SHP-1. We thus provide the first demonstration that a pathogen can exploit a host protein tyrosine phosphatase, namely SHP-1, to directly inactivate IRAK-1 through a generally conserved KTIM motif.

  3. Molecular mechanism of the allosteric regulation of the αγ heterodimer of human NAD-dependent isocitrate dehydrogenase

    Science.gov (United States)

    Ma, Tengfei; Peng, Yingjie; Huang, Wei; Ding, Jianping

    2017-01-01

    Human NAD-dependent isocitrate dehydrogenase catalyzes the decarboxylation of isocitrate (ICT) into α-ketoglutarate in the Krebs cycle. It exists as the α2βγ heterotetramer composed of the αβ and αγ heterodimers. Previously, we have demonstrated biochemically that the α2βγ heterotetramer and αγ heterodimer can be allosterically activated by citrate (CIT) and ADP. In this work, we report the crystal structures of the αγ heterodimer with the γ subunit bound without or with different activators. Structural analyses show that CIT, ADP and Mg2+ bind adjacent to each other at the allosteric site. The CIT binding induces conformational changes at the allosteric site, which are transmitted to the active site through the heterodimer interface, leading to stabilization of the ICT binding at the active site and thus activation of the enzyme. The ADP binding induces no further conformational changes but enhances the CIT binding through Mg2+-mediated interactions, yielding a synergistic activation effect. ICT can also bind to the CIT-binding subsite, which induces similar conformational changes but exhibits a weaker activation effect. The functional roles of the key residues are verified by mutagenesis, kinetic and structural studies. Our structural and functional data together reveal the molecular mechanism of the allosteric regulation of the αγ heterodimer. PMID:28098230

  4. The tyrosine 343 residue of nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) is important for its interaction with SHP1, a cytoplasmic tyrosine phosphatase with tumor suppressor functions.

    Science.gov (United States)

    Hegazy, Samar A; Wang, Peng; Anand, Mona; Ingham, Robert J; Gelebart, Pascal; Lai, Raymond

    2010-06-25

    The cytoplasmic tyrosine phosphatase SHP1 has been shown to inhibit the oncogenic fusion protein nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK), and loss of SHP1 contributes to NPM-ALK-mediated tumorigenesis. In this study, we aimed to further understand how SHP1 interacts and regulates NPM-ALK. We employed an in vitro model in which GP293 cells were transfected with various combinations of NPM-ALK (or mutants) and SHP1 (or mutants) expression vectors. We found that SHP1 co-immunoprecipitated with NPM-ALK, but not the enzymatically inactive NPM-ALK(K210R) mutant, or the mutant in which all three functionally important tyrosine residues (namely, Tyr(338), Tyr(342), and Tyr(343)) in the kinase activation loop (KAL) of ALK were mutated. Interestingly, whereas mutation of Tyr(338) or Tyr(342) did not result in any substantial change in the NPM-ALK/SHP1 binding (assessed by co-immunoprecipitation), mutation of Tyr(343) abrogated this interaction. Furthermore, the NPM-ALK/SHP1 binding was readily detectable when each of the remaining 8 tyrosine residues known to be phosphorylated were mutated. Although the expression of SHP1 effectively reduced the level of tyrosine phosphorylation of NPM-ALK, it did not affect that of the NPM-ALK(Y343F) mutant. In soft agar clonogenic assay, SHP1 expression significantly reduced the tumorigenicity of NPM-ALK but not that of NPM-ALK(Y343F). In conclusion, we identified Tyr(343) of NPM-ALK as the crucial site for mediating the NPM-ALK/SHP1 interaction. Our results also support the notion that the tumor suppressor effects of SHP1 on NPM-ALK are dependent on its ability to bind to this oncogenic protein.

  5. Dissociation and trafficking of rat GABAB receptor heterodimer upon chronic capsaicin stimulation.

    Science.gov (United States)

    Laffray, Sophie; Tan, Kelly; Dulluc, Josette; Bouali-Benazzouz, Rabia; Calver, Andrew R; Nagy, Frédéric; Landry, Marc

    2007-03-01

    Gamma-aminobutyric acid type B receptors (GABAB) are G-protein-coupled receptors that mediate GABAergic inhibition in the brain. Their functional expression is dependent upon the formation of heterodimers between GABAB1 and GABAB2 subunits, a process that occurs within the endoplasmic reticulum. However, the mechanisms that regulate GABAB receptor oligomerization at the plasma membrane remain largely unknown. We first characterized the functional cytoarchitecture of an organotypic co-culture model of rat dorsal root ganglia and spinal cord. Subsequently, we studied the interactions between GABAB subunits after chronic stimulation of sensory fibres with capsaicin. Surface labelling of recombinant proteins showed a decrease in subunit co-localization and GABAB2 labelling, after capsaicin treatment. In these conditions, fluorescence lifetime imaging measurements further demonstrated a loss of interactions between green fluorescent protein-GABAB1b and t-dimer discosoma sp red fluorescent protein-GABAB2 subunits. Finally, we established that the GABAB receptor undergoes clathrin-dependent internalization and rapid recycling to the plasma membrane following activation with baclofen, a GABAB agonist. However, in cultures chronically stimulated with capsaicin, the agonist-induced endocytosis was decreased, reflecting changes in the dimeric state of the receptor. Taken together, our results indicate that the chronic stimulation of sensory fibres can dissociate the GABAB heterodimer and alters its responsiveness to the endogenous ligand. Chronic stimulation thus modulates receptor oligomerization, providing additional levels of control of signalling.

  6. Subunits of the Drosophila actin-capping protein heterodimer regulate each other at multiple levels.

    Directory of Open Access Journals (Sweden)

    Ana Rita Amândio

    Full Text Available The actin-Capping Protein heterodimer, composed of the α and β subunits, is a master F-actin regulator. In addition to its role in many cellular processes, Capping Protein acts as a main tumor suppressor module in Drosophila and in humans, in part, by restricting the activity of Yorkie/YAP/TAZ oncogenes. We aimed in this report to understand how both subunits regulate each other in vivo. We show that the levels and capping activities of both subunits must be tightly regulated to control F-actin levels and consequently growth of the Drosophila wing. Overexpressing capping protein α and β decreases both F-actin levels and tissue growth, while expressing forms of Capping Protein that have dominant negative effects on F-actin promote tissue growth. Both subunits regulate each other's protein levels. In addition, overexpressing one of the subunit in tissues knocked-down for the other increases the mRNA and protein levels of the subunit knocked-down and compensates for its loss. We propose that the ability of the α and β subunits to control each other's levels assures that a pool of functional heterodimer is produced in sufficient quantities to restrict the development of tumor but not in excess to sustain normal tissue growth.

  7. Subunits of the Drosophila actin-capping protein heterodimer regulate each other at multiple levels.

    Science.gov (United States)

    Amândio, Ana Rita; Gaspar, Pedro; Whited, Jessica L; Janody, Florence

    2014-01-01

    The actin-Capping Protein heterodimer, composed of the α and β subunits, is a master F-actin regulator. In addition to its role in many cellular processes, Capping Protein acts as a main tumor suppressor module in Drosophila and in humans, in part, by restricting the activity of Yorkie/YAP/TAZ oncogenes. We aimed in this report to understand how both subunits regulate each other in vivo. We show that the levels and capping activities of both subunits must be tightly regulated to control F-actin levels and consequently growth of the Drosophila wing. Overexpressing capping protein α and β decreases both F-actin levels and tissue growth, while expressing forms of Capping Protein that have dominant negative effects on F-actin promote tissue growth. Both subunits regulate each other's protein levels. In addition, overexpressing one of the subunit in tissues knocked-down for the other increases the mRNA and protein levels of the subunit knocked-down and compensates for its loss. We propose that the ability of the α and β subunits to control each other's levels assures that a pool of functional heterodimer is produced in sufficient quantities to restrict the development of tumor but not in excess to sustain normal tissue growth.

  8. High NaCl-induced inhibition of PTG contributes to activation of NFAT5 through attenuation of the negative effect of SHP-1.

    Science.gov (United States)

    Zhou, Xiaoming; Wang, Hong; Burg, Maurice B; Ferraris, Joan D

    2013-08-01

    Activation of the transcription factor NFAT5 by high NaCl involves changes in phosphorylation. By siRNA screening, we previously found that protein targeting to glycogen (PTG), a regulatory subunit of protein phosphatase1 (PP1), contributes to regulation of high NaCl-induced NFAT5 transcriptional activity. The present study addresses the mechanism involved. We find that high NaCl-induced inhibition of PTG elevates NFAT5 activity by increasing NFAT5 transactivating activity, protein abundance, and nuclear localization. PTG acts via a catalytic subunit PP1γ. PTG associates physically with PP1γ, and NaCl reduces both this association and remaining PTG-associated PP1γ activity. High NaCl-induced phosphorylation of p38, ERK, and SHP-1 contributes to activation of NFAT5. Knockdown of PTG does not affect phosphorylation of p38 or ERK. However, PTG and PP1γ bind to SHP-1, and knockdown of either PTG or PP1γ increases high NaCl-induced phosphorylation of SHP-1-S591, which inhibits SHP-1. Mutation of SHP-1-S591 to alanine, which cannot be phosphorylated, increases inhibition of NFAT5 by SHP-1. Thus high NaCl reduces the stimulatory effect of PTG and PP1γ on SHP-1, which in turn reduces the inhibitory effect of SHP-1 on NFAT5. Our findings add to the known functions of PTG, which was previously recognized only for its glycogenic activity.

  9. Strategic Measures and Incentive Policies of SHP in China——Hangzhou Regional Center(Asia-Pacific) for Small Hydro Power

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    At the primary stage of SHP development (1960s—1970s), wooden or iron-wooden turbines manufactured by agricultural machinery works were mainly adopted in China. Before 1949, SHP equipment was generally imported due to lack of domestic manufacturing capability. In 1952, the first turbine-generator unit of 800kW capacity was successfully made in China,

  10. Research and Realization of DWG to SHP Format Conversion Technology%DWG 到 SHP 格式转换技术的研究与实现

    Institute of Scientific and Technical Information of China (English)

    肖锋; 吕宝奇; 林蒙恩

    2013-01-01

    The current surveying and mapping industry is based on topographic map database establishment with the key step of DWG to SHP format lossless conversion , especially property conversion .There is no readily available software which can realize one step conversion.Through the DWG and SHP format data structure , using VC++2005 and ObjectARX SDK development environment , secondary development on AutoCAD platform , graphics data conversion in terms of the point , line and polygon, attribute data, XData XRecord, OData, OProperty conversion , DWG to SHP format conversion is achieved , and requirements of graphics and attributes are satisfied with simple and quick operation and good application in the actual production .%当前测绘行业很多都是基于DWG地形图数据的数据库建设,生产中一个关键的环节就是DWG到SHP格式的无损转换,尤其是属性的转换。目前,没有现成的软件能一步到位地实现转换,通过对DWG和SHP格式数据结构的研究,采用VC++2005和ObjectARX SDK开发环境,在AutoCAD平台上二次开发,图形数据按点、线、面转换,属性数据分扩展数据、扩展记录、对象数据、对象特性转换,完成了DWG到SHP的格式转换,同时满足图形和属性的要求,操作简单快捷,在实际生产中取得较好的应用效果。

  11. A Risk Analysis of Small-Hydro Power (SHP Plants Investments

    Directory of Open Access Journals (Sweden)

    Jorge Cunha

    2014-06-01

    Full Text Available The increase in electricity consumption has led to a sharp increase in energy demand which rose environmental and sustainability concerns. To address this issue, there has been an incentive to resource to renewable energy sources for electricity production. Departing from a real case study, the investment appraisal of a SHP project under the present market conditions is described, followed by a sensitivity analysis in order to identify the main sources of risk. The main results obtained showed that in the context of a regulated tariff the project is worthwhile due to a positive NPV. However, if electricity had to be sold at market prices, the project becomes unprofitable. Theresults put also in evidence the vulnerability of the investment to an adverse change in interest rates. Future SHP plant investments should take into account the need to operate in a free market and to compete with technologies based on fossil fuels or large hydro.

  12. A statistical mechanical model for mass stability in the SHP theory

    Science.gov (United States)

    Horwitz, Lawrence P.

    2017-05-01

    We construct a model for a particle in the framework of the theory of Stueckelberg, Horwitz and Piron (SHP) as an ensemble of events subject to the laws of covariant classical equilibrium statistical mechanics. The canonical and grand canonical ensembles are constructed without an a priori constraint on the total mass of the system. We show that the total mass of the system, corresponding the mass of this particle is determined by a chemical potential. This model has the property that under perturbation, such as collisions in the SHP theory for which the final asymptotic mass of an elementary event is not constrained by the basic theory, the particle returns to its equilibrium mass value. A mechanism similar to the Maxwell construction for more than one equilibrium mass state may result in several possible masses in the final state.

  13. A Statistical Mechanical Model for Mass Stability in the SHP Theory

    CERN Document Server

    Horwitz, Lawrence

    2016-01-01

    We construct a model for a particle in the framework of the theory of Stueckelberg, Horwitz and Piron (SHP) as an ensemble of events subject to the laws of covariant classical equilibrium statistical mechanics. The canonical and grand canonical emsembles are constructed without an a priori constraint on the total mass of the system. We show that the total mass of the system, corresponding to the mass of this particle, is determined by a chemical potential. This model has the property that under perturbation, such as collisions in the SHP theory for which the final asymptotic mass of an elementary event is not constrained by the basic theory, the particle returns to its equilibrium mass value. A mechanism similar to the Maxwell construction for more than one equlibrium mass state may result in several possible masses in the final state.

  14. Biophysical assay for tethered signaling reactions reveals tether-controlled activity for the phosphatase SHP-1

    Science.gov (United States)

    Goyette, Jesse; Salas, Citlali Solis; Coker-Gordon, Nicola; Bridge, Marcus; Isaacson, Samuel A.; Allard, Jun; Dushek, Omer

    2017-01-01

    Tethered enzymatic reactions are ubiquitous in signaling networks but are poorly understood. A previously unreported mathematical analysis is established for tethered signaling reactions in surface plasmon resonance (SPR). Applying the method to the phosphatase SHP-1 interacting with a phosphorylated tether corresponding to an immune receptor cytoplasmic tail provides five biophysical/biochemical constants from a single SPR experiment: two binding rates, two catalytic rates, and a reach parameter. Tether binding increases the activity of SHP-1 by 900-fold through a binding-induced allosteric activation (20-fold) and a more significant increase in local substrate concentration (45-fold). The reach parameter indicates that this local substrate concentration is exquisitely sensitive to receptor clustering. We further show that truncation of the tether leads not only to a lower reach but also to lower binding and catalysis. This work establishes a new framework for studying tethered signaling processes and highlights the tether as a control parameter in clustered receptor signaling.

  15. Characterizing SHP2 as a Novel Therapeutic Target in Breast Cancer

    Science.gov (United States)

    2014-04-01

    signaling and promotes breast cancer tumorigenesis. Because of this, it was hypothesized that SHP2 may be a useful therapeutic target in disease , since it...human insulin, 20 ng/ml EGF (PeproTech), 0.5 μg/ml hydrocortisone, 100 ng/ml  cholera   toxin (Sigma), and 5% horse serum. Other reagents used included

  16. CFD for hydrodynamic efficiency and design optimization of key elements of SHP

    Directory of Open Access Journals (Sweden)

    Ana Pereira, Helena M. Ramos

    2010-11-01

    Full Text Available This paper aims to study how the flow behaves in key elements of small hydropower plants (SHP which should be well designed in order to achieve properly the best hydraulic and energy efficiency. There are some hydrodynamic and structural fundaments that all hydro circuits design has to follow, and there are other aspects that vary from design to the flow behavior. The variables that influence the hydro systems design are related with performance, technical, operational and environmental aspects. For instance, design discharge, produced energy, intakes and outlets geometry are some of the technical variables. The components of SHP design should be characterized by a balance between hydraulic, structural, operational and environment efficiency and economic issues. To improve the hydraulic efficiency is necessary information concerning with hydrodynamic flow behavior. The knowledge in this area is still insufficient since the hydrodynamic flow patterns, in some key elements of hydraulic circuits of SHP are quite complex. Therefore this paper uses an advanced computational fluid dynamic (CFD model for flow simulation, with the aim to improve the behavior comprehension enabling the identification of parameters’ variation which influences the performance efficiency of those components in the design criteria of such SHP. Since the inefficiency and the unsafe operating conditions are normally associated to separated flow zones, vorticity development, macro turbulence intensity, pressure gradients, shear stress increase, this paper intends to analyze causes and consequences of the flow behavior. Among these concerns it is possible to identify induced problems, such as vibrations, resonance effects, ruptures or collapses, cavitation, water column separation, significant friction losses, vortices and regions of reversed flow.

  17. PublisherPartners webshop

    OpenAIRE

    Piferrer Torres, Enric

    2013-01-01

    Projecte realitzat en col·laboració amb Fontys University of Applied Sciences i l'empresa PublisherPartners. The main goal in the project was to build a website where the company PublisherPartners could sell and offer its products online to the customer

  18. Plasiatine, an Unprecedented Indole-Phenylpropanoid Hybrid from Plantago asiatica as a Potent Activator of the Nonreceptor Protein Tyrosine Phosphatase Shp2

    Science.gov (United States)

    Gao, Zhong-Hua; Shi, Yi-Ming; Qiang, Zhe; Wang, Xia; Shang, Shan-Zhai; Yang, Yan; Du, Bao-Wen; Peng, Hui-Pan; Ji, Xu; Li, Honglin; Wang, Fei; Xiao, Wei-Lie

    2016-04-01

    Plasiatine (1), isolated from the seeds of Plantago asiatica, is an unprecedented indole analogue linked to a phenylpropanoid moiety via a carbon bond that builds up a novel heteromeric construction with a C19N2 scaffold. Its structure was determined by spectroscopic data and computational evidence. Notably, experimental assay demonstrated that 1 significantly enhanced the activity of the nonreceptor protein tyrosine phosphatase Shp2 in vitro in a concentration-dependent manner with an EC50 value of 0.97 μM, and activated phosphorylation of ERK, a known target of Shp2. Moreover, plasiatine (1) promoted hepatocellular HepG2 cells migration. Molecular docking suggested that plasiatine (1) binds to the catalytic cleft of Shp2. These results identified plasiatine (1) as the first small molecule Shp2 activator, and it warrants further investigation as a novel pharmaceutical tool to study the function of Shp2 in tumorigenesis.

  19. Regulation of miR-200c by Nuclear Receptors PPARα, LRH-1 and SHP

    Science.gov (United States)

    Zhang, Yuxia; Yang, Zhihong; Whitby, Richard; Wang, Li

    2011-01-01

    We investigated regulation of miR-200c expression by nuclear receptors. Ectopic expression of miR-200c inhibited MHCC97H cell migration, which was abrogated by the synergistic effects of PPARα and LRH-1 siRNAs. The expression of miR-200c was decreased by PPARα/LRH-1 siRNAs and increased by SHP siRNAs, and overexpression of the receptors reversed the effects of their respective siRNAs. SHP siRNAs also drastically enhanced the ability of the LRH-1 agonist RJW100 to induce miR-200c and downregulate ZEB1 and ZEB2 proteins. Co-expression of PPARα and LRH-1 moderately transactivated the miR-200c promoter, which was repressed by SHP co-expression. RJW100 caused strong activation of the miR-200c promoter. This is the first report to demonstrate that miR-200c expression is controlled by nuclear receptors. PMID:22100809

  20. The budding yeast Cdc48(Shp1 complex promotes cell cycle progression by positive regulation of protein phosphatase 1 (Glc7.

    Directory of Open Access Journals (Sweden)

    Stefanie Böhm

    Full Text Available The conserved, ubiquitin-selective AAA ATPase Cdc48 regulates numerous cellular processes including protein quality control, DNA repair and the cell cycle. Cdc48 function is tightly controlled by a multitude of cofactors mediating substrate specificity and processing. The UBX domain protein Shp1 is a bona fide substrate-recruiting cofactor of Cdc48 in the budding yeast S. cerevisiae. Even though Shp1 has been proposed to be a positive regulator of Glc7, the catalytic subunit of protein phosphatase 1 in S. cerevisiae, its cellular functions in complex with Cdc48 remain largely unknown. Here we show that deletion of the SHP1 gene results in severe growth defects and a cell cycle delay at the metaphase to anaphase transition caused by reduced Glc7 activity. Using an engineered Cdc48 binding-deficient variant of Shp1, we establish the Cdc48(Shp1 complex as a critical regulator of mitotic Glc7 activity. We demonstrate that shp1 mutants possess a perturbed balance of Glc7 phosphatase and Ipl1 (Aurora B kinase activities and show that hyper-phosphorylation of the kinetochore protein Dam1, a key mitotic substrate of Glc7 and Ipl1, is a critical defect in shp1. We also show for the first time a physical interaction between Glc7 and Shp1 in vivo. Whereas loss of Shp1 does not significantly affect Glc7 protein levels or localization, it causes reduced binding of the activator protein Glc8 to Glc7. Our data suggest that the Cdc48(Shp1 complex controls Glc7 activity by regulating its interaction with Glc8 and possibly further regulatory subunits.

  1. Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody.

    Science.gov (United States)

    Park, Young-Jun; Pardon, Els; Wu, Meiting; Steyaert, Jan; Hol, Wim G J

    2012-02-01

    The parasite Trypanosoma brucei, the causative agent of sleeping sickness across sub-Saharan Africa, depends on a remarkable U-insertion/deletion RNA editing process in its mitochondrion. A approximately 20 S multi-protein complex, called the editosome, is an essential machinery for editing pre-mRNA molecules encoding the majority of mitochondrial proteins. Editosomes contain a common core of twelve proteins where six OB-fold interaction proteins, called A1-A6, play a crucial role. Here, we report the structure of two single-strand nucleic acid-binding OB-folds from interaction proteins A3 and A6 that surprisingly, form a heterodimer. Crystal growth required the assistance of an anti-A3 nanobody as a crystallization chaperone. Unexpectedly, this anti-A3 nanobody binds to both A3(OB) and A6, despite only ~40% amino acid sequence identity between the OB-folds of A3 and A6. The A3(OB)-A6 heterodimer buries 35% more surface area than the A6 homodimer. This is attributed mainly to the presence of a conserved Pro-rich loop in A3(OB). The implications of the A3(OB)-A6 heterodimer, and of a dimer of heterodimers observed in the crystals, for the architecture of the editosome are profound, resulting in a proposal of a 'five OB-fold center' in the core of the editosome.

  2. Instabilities in the optical response of a semiconductor quantum dot-metal nanoparticle heterodimer : self-oscillations and chaos

    NARCIS (Netherlands)

    Nugroho, Bintoro S.; Iskandar, Alexander A.; Malyshev, Victor A.; Knoester, Jasper

    We theoretically investigate the nonlinear optical response of a heterodimer comprising a semiconductor quantum dot strongly coupled to a metal nanoparticle. The quantum dot is considered as a three-level ladder system with ground, one-exciton, and bi-exction states. As compared to the case of a

  3. Drosophila molting neurohormone bursicon is a heterodimer and the natural agonist of the orphan receptor DLGR2

    DEFF Research Database (Denmark)

    Mendive, Fernando M; Van Loy, Tom; Claeysen, Sylvie;

    2005-01-01

    here Drosophila bioactive bursicon as a heterodimer made of two cystine knot polypeptides. This conclusion was reached in part from the unexpected observation that in the genome of the honey bee, the orthologs of the two Drosophila proteins are predicted to be fused in a single open reading frame...

  4. Collateral Intimate Partner Homicide

    Directory of Open Access Journals (Sweden)

    Emily Meyer

    2013-04-01

    Full Text Available Collateral intimate partner homicide (CIPH is an underinvestigated genre of intimate partner violence (IPV where an individual(s connected to the IPV victim is murdered. We conducted a content analysis of a statewide database of CIPH newspaper articles (1990-2007. Out of 111 collateral murder victims, there were 84 IPV female focal victims and 84 male perpetrators. The most frequently reported CIPH decedent was the focal victim’s new partner (30%; 45% of focal victims were themselves killed. News reports framed CIPH as the unexpected result of interpersonal conflict, despite evidence of a systematic pattern of coercion and violence that capitulated in murder.

  5. A Partner's Guide to Pregnancy

    Science.gov (United States)

    ... For Patients About ACOG A Partner's Guide to Pregnancy Home For Patients Search FAQs A Partner's Guide ... May 2016 PDF Format A Partner's Guide to Pregnancy Pregnancy Why is it important to be supportive ...

  6. Immunoglobulin domain interface exchange as a platform technology for the generation of Fc heterodimers and bispecific antibodies

    Science.gov (United States)

    Skegro, Darko; Stutz, Cian; Ollier, Romain; Svensson, Emelie; Wassmann, Paul; Bourquin, Florence; Monney, Thierry; Gn, Sunitha; Blein, Stanislas

    2017-01-01

    Bispecific antibodies (bsAbs) are of significant importance to the development of novel antibody-based therapies, and heavy chain (Hc) heterodimers represent a major class of bispecific drug candidates. Current technologies for the generation of Hc heterodimers are suboptimal and often suffer from contamination by homodimers posing purification challenges. Here, we introduce a new technology based on biomimicry wherein the protein-protein interfaces of two different immunoglobulin (Ig) constant domain pairs are exchanged in part or fully to design new heterodimeric domains. The method can be applied across Igs to design Fc heterodimers and bsAbs. We investigated interfaces from human IgA CH3, IgD CH3, IgG1 CH3, IgM CH4, T-cell receptor (TCR) α/β, and TCR γ/δ constant domain pairs, and we found that they successfully drive human IgG1 CH3 or IgM CH4 heterodimerization to levels similar to or above those of reference methods. A comprehensive interface exchange between the TCR α/β constant domain pair and the IgG1 CH3 homodimer was evidenced by X-ray crystallography and used to engineer examples of bsAbs for cancer therapy. Parental antibody pairs were rapidly reformatted into scalable bsAbs that were free of homodimer traces by combining interface exchange, asymmetric Protein A binding, and the scFv × Fab format. In summary, we successfully built several new CH3- or CH4-based heterodimers that may prove useful for designing new bsAb-based therapeutics, and we anticipate that our approach could be broadly implemented across the Ig constant domain family. To our knowledge, CH4-based heterodimers have not been previously reported. PMID:28450393

  7. CHP Partnership Partners

    Science.gov (United States)

    Partners of EPA's Combined Heat and Power Partnership include federal, state, and local government agencies and private organizations such as energy users, energy service companies, CHP project developers and consultants, and equipment manufacturers.

  8. The Constitution of Partnering

    DEFF Research Database (Denmark)

    Gottlieb, Stefan Christoffer

    promoveret af branchen og af staten som et væsentligt led i udviklingen af byggeriets arbejdsformer. Med et udgangspunkt i en Foucauldiansk analyse af dispositiver, rum og orden bidrager afhandlingen med en ny differentieret forståelse af mulighederne for at håndtere branchens modsætningsfyldte fornyelse...... om, hvordan partnering som koncept er fremkommet og har udviklet sig og hvilke konstitutive effekter partnering har på byggeriets praksis. Det teoretiske udgangspunkt i Foucault begrundes i behovet for at fastholde en mangefacetteret og historisk analyse af partnering i modsætning til de...... fremherskende endimensionelle og rationelle forståelser, som ikke svarer til den oplevede og observerede praksis i byggebranchen. I afhandlingens første del diskuteres den analytiske anvendelse af et teoretisk nøglebegreb fra Foucault i analysen af partnering; dispositivet. Hermed forstås de bagvedliggende...

  9. Pacific Partners Wargame Analysis

    Science.gov (United States)

    2014-09-01

    such as medical qualifications and malpractice considerations, can be explored as part of interoperability. Partner nations are motivated to...specialized problems. Intellectual exchanges and fora involving experts from government, industry, academic and other institutions could be employed in

  10. Green Power Partner List

    Science.gov (United States)

    The U.S. EPA's Green Power Partnership is a voluntary program designed to reduce the environmental impact of electricity generation by promoting renewable energy. There are thousands of Green Power Partners, all listed on this page.

  11. Collateral Intimate Partner Homicide

    OpenAIRE

    Emily Meyer; Lori Post

    2013-01-01

    Collateral intimate partner homicide (CIPH) is an underinvestigated genre of intimate partner violence (IPV) where an individual(s) connected to the IPV victim is murdered. We conducted a content analysis of a statewide database of CIPH newspaper articles (1990-2007). Out of 111 collateral murder victims, there were 84 IPV female focal victims and 84 male perpetrators. The most frequently reported CIPH decedent was the...

  12. Mathematical modeling of sub-cellular asymmetry of fat-dachsous heterodimer for generation of planar cell polarity.

    Directory of Open Access Journals (Sweden)

    Mohit Kumar Jolly

    Full Text Available Planar Cell Polarity (PCP is an evolutionarily conserved characteristic of animal tissues marked by coordinated polarization of cells or structures in the plane of a tissue. In insect wing epithelium, for instance, PCP is characterized by en masse orientation of hairs orthogonal to its apical-basal axis and pointing along the proximal-distal axis of the organ. Directional cue for PCP has been proposed to be generated by complex sets of interactions amongst three proteins - Fat (Ft, Dachsous (Ds and Four-jointed (Fj. Ft and Ds are two atypical cadherins, which are phosphorylated by Fj, a Golgi kinase. Ft and Ds from adjacent cells bind heterophilically via their tandem cadherin repeats, and their binding affinities are regulated by Fj. Further, in the wing epithelium, sub-cellular levels of Ft-Ds heterodimers are seen to be elevated at the distal edges of individual cells, prefiguring their PCP. Mechanisms generating this sub-cellular asymmetry of Ft-Ds heterodimer in proximal and distal edges of cells, however, have not been resolved yet. Using a mathematical modeling approach, here we provide a framework for generation of this sub-cellular asymmetry of Ft-Ds heterodimer. First, we explain how the known interactions within Ft-Ds-Fj system translate into sub-cellular asymmetry of Ft-Ds heterodimer. Second, we show that this asymmetric localization of Ft-Ds heterodimer is lost when tissue-level gradient of Fj is flattened, or when phosphorylation of Ft by Fj is abolished, but not when tissue-level gradient of Ds is flattened or when phosphorylation of Ds is abrogated. Finally, we show that distal enrichment of Ds also amplifies Ft-Ds asymmetry. These observations reveal that gradient of Fj expression, phosphorylation of Ft by Fj and sub-cellular distal accumulation of Ds are three critical elements required for generating sub-cellular asymmetry of Ft-Ds heterodimer. Our model integrates the known experimental data and presents testable predictions

  13. [Effect of 5-aza-CdR demethylation on expression of SHP-1 and C-kit genes in leukemia HL-60 cells].

    Science.gov (United States)

    Meng, Zhen; Li, Ying-Hua; Wang, Dong-Mei; Luo, Jian-Min

    2014-12-01

    This study was aimed to investigate the expression level of SHP-1 and C-kit genes in acute leukemia HL-60 cells and effect of 5-aza-CdR demethylation on expression of SHP-1 and C-kit genes. RT-PCR was used to detect the mRNA expression level of SHP-1 and C-kit mRNA in HL-60 cells of the drug-treated group and control group.The methylation specific PCR (MSP) was applied to measure the methylation status of SHP-1 and C-kit genes in HL-60 cells.The results showed that after being treated with 5-aza-CdR, the recovery of SHP-1 gene expression was observed in HL-60 cells in which SHP-1 mRNA originally was not expressed. Meanwhile, the high expression level of C-kit mRNA in HL-60 cells was decreased. When HL-60 cells were treated with 0, 0.5, 1.0, 2.0 µmol/L 5-aza-CdR, the demethylation effect was enhanced, the expression of SHP-1 mRNA displayed an ascending tendency, and the expression of C-kit mRNA showed an descending tendency in dose-dependent manner (P HL-60 cells and recovery of expression after treatment with 5-aza-CdR suggest that the hypermethylation of SHP-1 gene relates with pathogenesis of leukemia, and the abnormal increase of C-kit mRNA expression maybe exist in formation of leukemia. The effect of 5-aza-CdR on expression of SHP-1 and C-kit shows dose-dependency, the higher the 5-aza-CdR concentration, the higher the SHP-1 expression and the lower the C-kit expression, moreover, the effect of 5-aza-CdR shows time-dependency in specific concentration.The SHP-1 mRNA expression negatively correlates with C-kit mRNA expression, suggesting that the decrease or absence of SHP-1 expression in leukemia cells weakens the negative regulation on C-kit signaling pathway, thus plays a role in the formation of leukemia.

  14. [Demethylation effect of inhibitor As2O3 on expression of SHP-1 and C-kit genes in leukemia HL-60 cells].

    Science.gov (United States)

    Meng, Zhen; Wang, Dong-Mei; Li, Ying-Hua; Liu, Xiao; Guo, Su-Qing; Luo, Jian-Min

    2013-06-01

    This study was aimed to investigate the expression level of SHP-1 and C-kit genes in acute leukemia HL-60 cells and effect of inhibitor As2O3 demethylation on SHP-1 and C-kit genes expression. RT-PCR was used to detect the expression level of SHP-1 and C-kit mRNA in drug-treated cell group and control group. The methylation specific PCR (MSP) was applied to measure the methylation status of SHP-1 gene in HL-60 cells. The results showed that after being treated with As2O3 the recovery of SHP-1 gene expression was observed in HL-60 cells in which SHP-1 mRNA originally did not expressed, meanwhile the expression level of C-kit mRNA in HL-60 cells with high expression decreased. When HL-60 cells were treated with As2O3 of 1.0, 2.5, 5.0 µmol/L, the demethylation effects was enhanced, the expression of SHP-1 mRNA displayed an ascending tendency, and expression of C-kit mRNA showed an descending tendency in dose-dependent manner (P HL-60 cells and recovery of expression after treatment with As2O3 suggest the hypermethylation of SHP-1 gene related with pathogenesis of leukemia, and the abnormal increase of C-kit mRNA expression maybe exist in formation of leukemia. The effect of As2O3 on expression of SHP-1 and C-kit shows dose-dependency, the higher the As2O3 concentration, the higher the SHP-1 expression and the lower the C-kit expression, moreover, the effect of As2O3 shows time-dependency in specific concentration. The SHP-1 mRNA expression negatively relates with C-kit mRNA expression, suggesting that the decrease or absence of SHP-1 expression in leukemia cells weakens the negative regulation on C-kit signaling pathway, thus plays a role in the formation of leukemia.

  15. MutLα heterodimers modify the molecular phenotype of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Vahid Ezzatizadeh

    Full Text Available BACKGROUND: Friedreich ataxia (FRDA, the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. METHODOLOGY/PRINCIPAL FINDINGS: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. CONCLUSIONS/SIGNIFICANCE: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription.

  16. DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor

    Institute of Scientific and Technical Information of China (English)

    Paola Mazzarelli; Carolina Gravina; Marco Caricato; Maria Luana Poeta; Monica Rinaldi; Sergio Valeri; Roberto Coppola; Vito Michele Fazio; Paola Parrella; Davide Seripa; Emanuela Signori; Giuseppe Perrone; Carla Rabitti; Domenico Borzomati; Armando Gabbrielli; Maria Giovanna Matera

    2005-01-01

    AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis.METHODS: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis.RESULTS: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P<0.00). However,changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity.Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86nuclear expression, as determined by Western blot and immunohistochemical analyses (P<0.001). Cytoplasmic protein expression was found in pathological samples,but not in normal tissues either from tumor patients or from healthy subjects.CONCLUSION: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.

  17. Yeast surface display of a noncovalent MHC class II heterodimer complexed with antigenic peptide.

    Science.gov (United States)

    Boder, Eric T; Bill, Jerome R; Nields, Andrew W; Marrack, Philippa C; Kappler, John W

    2005-11-20

    Microbial protein display technologies have enabled directed molecular evolution of binding and stability properties in numerous protein systems. In particular, dramatic improvements to antibody binding affinity and kinetics have been accomplished using these tools in recent years. Examples of successful application of display technologies to other immunological proteins have been limited to date. Herein, we describe the expression of human class II major histocompatibility complex allele (MHCII) HLA-DR4 on the surface of Saccharomyces cerevisiae as a noncovalently associated heterodimer. The yeast-displayed MHCII is fully native as assessed by binding of conformationally specific monoclonal antibodies; failure of antibodies specific for empty HLA-DR4 to bind yeast-displayed protein indicates antigenic peptide is bound. This report represents the first example of a noncovalent protein dimer displayed on yeast and of successful display of wild-type MHCII. Results further point to the potential for using yeast surface display for engineering and analyzing the antigen binding properties of MHCII.

  18. Predictability of conversation partners

    CERN Document Server

    Takaguchi, Taro; Sato, Nobuo; Yano, Kazuo; Masuda, Naoki

    2011-01-01

    Recent developments in sensing technologies have enabled us to examine the nature of human social behavior in greater detail. By applying an information theoretic method to the spatiotemporal data of cell-phone locations, Song et al. (2010) found that human mobility patterns are remarkably predictable. Inspired by their work, we address a similar predictability question in a different kind of human social activity: conversation events. The predictability in the sequence of one's conversation partners is defined as the degree to which one's next conversation partner can be predicted given the current partner. We quantify this predictability by using the mutual information. We examine the predictability of conversation events for each individual using the longitudinal data of face-to-face interactions collected from two company offices in Japan. Each subject wears a name tag equipped with an infrared sensor node, and conversation events are marked when signals are exchanged between close sensor nodes. We find t...

  19. Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats

    Science.gov (United States)

    Zuo, Hui Ling; Yao, Fen Fen; Ruan, Hui Bing; Xu, Jin; Song, Wei; Zhou, Yi Cheng; Wen, Shi Yao; Dai, Jiang Hua; Zhu, Mei Lan; Luo, Jun

    2016-01-01

    Cortex Eucommiae is used worldwide in traditional medicine, various constituents of Cortex Eucommiae, such as chlorogenic acid (CGA), has been reported to exert anti-osteoporosis activity in China, but the mechanism about their contribution to the overall activity is limited. The aims of this study were to determine whether chlorogenic acid can prevent estrogen deficiency-induced osteoporosis and to analyze the mechanism of CGA bioactivity. The effect of CGA on estrogen deficiency-induced osteoporosis was performed in vivo. Sixty female Sprague-Dawley rats were divided randomly among a sham-operated group and five ovariectomy (OVX) plus treatment subgroups: saline vehicle, 17α-ethinylestradiol (E2), or CGA at 9, 27, or 45 mg/kg/d. The rats’ femoral metaphyses were evaluated by micro-computed tomography (μCT). The mechanism of CGA bioactivity was investigated in vitro. Bone mesenchymal stem cells (BMSCs) were treated with CGA, with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002. BMSCs proliferation and osteoblast differentiation were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and alkaline phosphatase, with or without Shp2 interfering RNA (RNAi). The results display that CGA at 27 and 45 mg/kg/day inhibited the decrease of bone mineral density (BMD) that induced by OVX in femur (p< 0.01), significantly promoted the levels of bone turnover markers, and prevented bone volume fraction (BV/TV), connectivity density (CoonD), trabecular number (Tb.N), trabecular thickness (Tb.Th) (all p< 0.01) to decrease and prevented the trabecular separation (Tb.Sp), structure model index (SMI)(both p< 0.01) to increase. CGA at 1 or 10 μM enhanced BMSC proliferation in a dose-dependent manner. CGA at 0.1 to 10 μM increased phosphorylated Akt (p-Akt) and cyclin D1. These effects were reversed by LY294002. CGA at 1 or 10 μM increased BMSC differentiation to osteoblasts (p< 0.01), Shp2 RNAi suppressed CGA-induced osteoblast

  20. The same periplasmic ExbD residues mediate in vivo interactions between ExbD homodimers and ExbD-TonB heterodimers.

    Science.gov (United States)

    Ollis, Anne A; Postle, Kathleen

    2011-12-01

    The TonB system couples cytoplasmic membrane proton motive force to TonB-gated outer membrane transporters for active transport of nutrients into the periplasm. In Escherichia coli, cytoplasmic membrane proteins ExbB and ExbD promote conformational changes in TonB, which transmits this energy to the transporters. The only known energy-dependent interaction occurs between the periplasmic domains of TonB and ExbD. This study identified sites of in vivo homodimeric interactions within ExbD periplasmic domain residues 92 to 121. ExbD was active as a homodimer (ExbD(2)) but not through all Cys substitution sites, suggesting the existence of conformationally dynamic regions in the ExbD periplasmic domain. A subset of homodimeric interactions could not be modeled on the nuclear magnetic resonance (NMR) structure without significant distortion. Most importantly, the majority of ExbD Cys substitutions that mediated homodimer formation also mediated ExbD-TonB heterodimer formation with TonB A150C. Consistent with the implied competition, ExbD homodimer formation increased in the absence of TonB. Although ExbD D25 was not required for their formation, ExbD dimers interacted in vivo with ExbB. ExbD-TonB interactions required ExbD transmembrane domain residue D25. These results suggested a model where ExbD(2) assembled with ExbB undergoes a transmembrane domain-dependent transition and exchanges partners in localized homodimeric interfaces to form an ExbD(2)-TonB heterotrimer. The findings here were also consistent with our previous hypothesis that ExbD guides the conformation of the TonB periplasmic domain, which itself is conformationally dynamic.

  1. The Same Periplasmic ExbD Residues Mediate In Vivo Interactions between ExbD Homodimers and ExbD-TonB Heterodimers ▿ †

    Science.gov (United States)

    Ollis, Anne A.; Postle, Kathleen

    2011-01-01

    The TonB system couples cytoplasmic membrane proton motive force to TonB-gated outer membrane transporters for active transport of nutrients into the periplasm. In Escherichia coli, cytoplasmic membrane proteins ExbB and ExbD promote conformational changes in TonB, which transmits this energy to the transporters. The only known energy-dependent interaction occurs between the periplasmic domains of TonB and ExbD. This study identified sites of in vivo homodimeric interactions within ExbD periplasmic domain residues 92 to 121. ExbD was active as a homodimer (ExbD2) but not through all Cys substitution sites, suggesting the existence of conformationally dynamic regions in the ExbD periplasmic domain. A subset of homodimeric interactions could not be modeled on the nuclear magnetic resonance (NMR) structure without significant distortion. Most importantly, the majority of ExbD Cys substitutions that mediated homodimer formation also mediated ExbD-TonB heterodimer formation with TonB A150C. Consistent with the implied competition, ExbD homodimer formation increased in the absence of TonB. Although ExbD D25 was not required for their formation, ExbD dimers interacted in vivo with ExbB. ExbD-TonB interactions required ExbD transmembrane domain residue D25. These results suggested a model where ExbD2 assembled with ExbB undergoes a transmembrane domain-dependent transition and exchanges partners in localized homodimeric interfaces to form an ExbD2-TonB heterotrimer. The findings here were also consistent with our previous hypothesis that ExbD guides the conformation of the TonB periplasmic domain, which itself is conformationally dynamic. PMID:21984795

  2. Fluorescence Resonance Energy Transfer Imaging Reveals that Chemokine-Binding Modulates Heterodimers of CXCR4 and CCR5 Receptors

    OpenAIRE

    2008-01-01

    BACKGROUND: Dimerization has emerged as an important feature of chemokine G-protein-coupled receptors. CXCR4 and CCR5 regulate leukocyte chemotaxis and also serve as a co-receptor for HIV entry. Both receptors are recruited to the immunological synapse during T-cell activation. However, it is not clear whether they form heterodimers and whether ligand binding modulates the dimer formation. METHODOLOGY/PRINCIPAL FINDINGS: Using a sensitive Fluorescence Resonance Energy Transfer (FRET) imaging ...

  3. Nanobody-aided structure determination of the EpsI:EpsJ pseudopilin heterodimer from Vibrio vulnificus

    Science.gov (United States)

    Korotkov, Konstantin V.; Hol, Wim G.J.; Steyaert, Jan

    2014-01-01

    Pseudopilins form the central pseudopilus of the sophisticated bacterial type 2 secretion systems. The crystallization of the EpsI:EpsJ pseudopilin heterodimer from Vibrio vulnificus was greatly accelerated by the use of nanobodies, which are the smallest antigen-binding fragments derived from heavy-chain only camelid antibodies. Seven anti-EpsI:EpsJ nanobodies were generated and co-crystallization of EpsI:EpsJ nano-body complexes yielded several crystal forms very rapidly. In the structure solved, the nanobodies are arranged in planes throughout the crystal lattice, linking layers of EpsI:EpsJ heterodimers. The EpsI:EpsJ dimer observed confirms a right-handed architecture of the pseudopilus, but, compared to a previous structure of the EpsI:EpsJ heterodimer, EpsI differs 6° in orientation with respect to EpsJ; one loop of EpsJ is shifted by ~5 Å due to interactions with the nanobody; and a second loop of EpsJ underwent a major change of 17 Å without contacts with the nanobody. Clearly, nanobodies accelerate dramatically the crystallization of recalcitrant protein complexes and can reveal conformational flexibility not observed before. PMID:19118632

  4. 基于SCA的SHP组件部署策略%SHP component strategy deployment based on SCA

    Institute of Scientific and Technical Information of China (English)

    刘青; 曹凯; 徐春林

    2012-01-01

    For making up the deficiency of that the resource mapping mechanism in SCA is not adapted to component deployment on specialized hardware processor(SHP), a deployment model based on symmetry structure is proposed? The software deployment descriptor and the cost function of deployment plan are presented. Based on of all of this, a kind of deployment strategy of SHP component is proposed. This solution offers the automatic mapping between component and specialized hardware processor and enhances the compatibility of SCA for SHP.%针对软件通信体系(SCA)中部署决策机制不能有效解决专用硬件处理器(SHP)上组件部署决策的问题,提出了基于对称结构的部署模型,设计了软件包部署描述文件和部署方案的评价函数,在此基础上给出了完整的SHP组件部署策略,实现了SHP组件到SHP设备的自动映射,增强了SCA对SHP的兼容性.

  5. Regulation of miR-200c by nuclear receptors PPAR{alpha}, LRH-1 and SHP

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuxia; Yang, Zhihong [Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States); Department of Oncological Science, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States); Whitby, Richard [Department of Chemistry, University of Southampton, Southampton, Hants SO17 1BJ (United Kingdom); Wang, Li, E-mail: l.wang@hsc.utah.edu [Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States); Department of Oncological Science, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Knockdown of PPAR{alpha} and LRH-1 abolishes miR-200c inhibition of HCC cell migration. Black-Right-Pointing-Pointer SHP represses miR-200c expression via inhibition of the activity of PPAR{alpha} and LRH-1. Black-Right-Pointing-Pointer RJW100 exhibits strong ability to downregulate ZEB1 and ZEB2 proteins. -- Abstract: We investigated regulation of miR-200c expression by nuclear receptors. Ectopic expression of miR-200c inhibited MHCC97H cell migration, which was abrogated by the synergistic effects of PPAR{alpha} and LRH-1 siRNAs. The expression of miR-200c was decreased by PPAR{alpha}/LRH-1 siRNAs and increased by SHP siRNAs, and overexpression of the receptors reversed the effects of their respective siRNAs. SHP siRNAs also drastically enhanced the ability of the LRH-1 agonist RJW100 to induce miR-200c and downregulate ZEB1 and ZEB2 proteins. Co-expression of PPAR{alpha} and LRH-1 moderately transactivated the miR-200c promoter, which was repressed by SHP co-expression. RJW100 caused strong activation of the miR-200c promoter. This is the first report to demonstrate that miR-200c expression is controlled by nuclear receptors.

  6. Partners in Accomplished Teaching.

    Science.gov (United States)

    National Board for Professional Teaching Standards, Arlington, VA.

    This report describes Partners in Accomplished Teaching, a project of the National Board for Professional Teaching Standards (NBPTS) designed to help increase the number of teachers achieving National Board Certification. It focuses on efforts in St. Paul, Minnesota; Mississippi; North Carolina; and San Antonio, Texas. The St. Paul program is a…

  7. Content for Conversation Partners.

    Science.gov (United States)

    Olson, Kathleen

    2002-01-01

    Suggests that a good strategy for helping English language learners to develop communicative competence in English is by pairing them with native English speakers. In such conversation programs, conversation partners should be provided with topics and activities that incorporate the goals, interests, and experiences of the learners. Recommends…

  8. Partners and Competitors

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ The United States and China are entering an entirely new and complex era in their economic relationship. In a nutshell, China is both partner and competitor, and simplistic efforts to cast the complexity of U.S.-China economic relations as either one of partnership or competition are unhelpful to the development of effective policy.

  9. Partnering i praksis

    DEFF Research Database (Denmark)

    Gottlieb, Stefan Christoffer; Bang, Henrik L.; Larsen, Jacob Norvig

    Publikationen sammenfatter resultater og erfaringer vedrørende brug af partnering i realiseringen af LO's hovedsæde i Havnestaden, København. Forløbet i byggesagen adskiller sig fra traditionelle byggesager på en række områder. Vigtigst af disse er anvendelsen af en række partneringstiltag, der u...

  10. Predictability of Conversation Partners

    Science.gov (United States)

    Takaguchi, Taro; Nakamura, Mitsuhiro; Sato, Nobuo; Yano, Kazuo; Masuda, Naoki

    2011-08-01

    Recent developments in sensing technologies have enabled us to examine the nature of human social behavior in greater detail. By applying an information-theoretic method to the spatiotemporal data of cell-phone locations, [C. Song , ScienceSCIEAS0036-8075 327, 1018 (2010)] found that human mobility patterns are remarkably predictable. Inspired by their work, we address a similar predictability question in a different kind of human social activity: conversation events. The predictability in the sequence of one’s conversation partners is defined as the degree to which one’s next conversation partner can be predicted given the current partner. We quantify this predictability by using the mutual information. We examine the predictability of conversation events for each individual using the longitudinal data of face-to-face interactions collected from two company offices in Japan. Each subject wears a name tag equipped with an infrared sensor node, and conversation events are marked when signals are exchanged between sensor nodes in close proximity. We find that the conversation events are predictable to a certain extent; knowing the current partner decreases the uncertainty about the next partner by 28.4% on average. Much of the predictability is explained by long-tailed distributions of interevent intervals. However, a predictability also exists in the data, apart from the contribution of their long-tailed nature. In addition, an individual’s predictability is correlated with the position of the individual in the static social network derived from the data. Individuals confined in a community—in the sense of an abundance of surrounding triangles—tend to have low predictability, and those bridging different communities tend to have high predictability.

  11. SHP-2 tyrosine phosphatase inhibits p73-dependent apoptosis and expression of a subset of p53 target genes induced by EGCG

    OpenAIRE

    2007-01-01

    Green tea polyphenol, epigallocatechin-3-gallate (EGCG) differentially regulates the cellular growth of cancer cells in a p53-dependent manner through apoptosis and/or cell cycle arrest. In an effort to further elucidate the mechanism of differential growth regulation by EGCG, we have investigated the role of the tyrosine phosphatase, SHP-2. Comparing the responses of mouse embryonic fibroblasts (MEFs), expressing either WT or functionally inactive/truncated SHP-2, we find that inactivation o...

  12. Leishmania infantum-chagasi activates SHP-1 and reduces NFAT5/TonEBP activity in the mouse kidney inner medulla.

    Science.gov (United States)

    Zhou, Xiaoming; Wang, Hong; Koles, Nancy L; Zhang, Aihong; Aronson, Naomi E

    2014-09-01

    Visceral leishmaniasis patients have been reported to have a urine concentration defect. Concentration of urine by the renal inner medulla is essentially dependent on a transcription factor, NFAT5/TonEBP, because it activates expression of osmoprotective genes betaine/glycine transporter 1 (BGT1) and sodium/myo-inositol transporter (SMIT), and water channel aquaporin-2, all of which are imperative for concentrating urine. Leishmania parasites evade macrophage immune defenses by activating protein tyrosine phosphatases, among which SHP-1 is critical. We previously demonstrated that SHP-1 inhibits tonicity-dependent activation of NFAT5/TonEBP in HEK293 cells through screening a genome-wide small interfering (si) RNA library against phosphatases (Zhou X, Gallazzini M, Burg MB, Ferraris JD. Proc Natl Acad Sci USA 107: 7072-7077, 2010). We sought to examine whether Leishmania can activate SHP-1 and inhibit NFAT5/TonEBP activity in the renal inner medulla in a murine model of visceral leishmaniasis by injection of female BALB/c mice with a single intravenous dose of 5 × 10(5) L. chagasi metacyclic promastigotes. We found that SHP-1 is expressed in the kidney inner medulla. L. chagasi activates SHP-1 with an increase in stimulatory phosphorylation of SHP-1-Y536 in the region. L. chagasi reduces expression of NFAT5/TonEBP mRNA and protein as well as expression of its targeted genes: BGT1, SMIT, and aquaporin-2. The culture supernatant from L. chagasi metacyclic promastigotes increases SHP-1 protein abundance and potently inhibits NFAT5 transcriptional activity in mIMCD3 cells. However, L. chagasi in our animal model has no significant effect on urinary concentration. We conclude that L. chagasi, most likely through its secreted virulence factors, activates SHP-1 and reduces NFAT5/TonEBP gene expression, which leads to reduced NFAT5/TonEBP transcriptional activity in the kidney inner medulla.

  13. Molecular insight of isotypes specific β-tubulin interaction of tubulin heterodimer with noscapinoids

    Science.gov (United States)

    Santoshi, Seneha; Naik, Pradeep K.

    2014-07-01

    Noscapine and its derivatives bind stoichiometrically to tubulin, alter its dynamic instability and thus effectively inhibit the cellular proliferation of a wide variety of cancer cells including many drug-resistant variants. The tubulin molecule is composed of α- and β-tubulin, which exist as various isotypes whose distribution and drug-binding properties are significantly different. Although the noscapinoids bind to a site overlapping with colchicine, their interaction is more biased towards β-tubulin. In fact, their precise interaction and binding affinity with specific isotypes of β-tubulin in the αβ-heterodimer has never been addressed. In this study, the binding affinity of a panel of noscapinoids with each type of tubulin was investigated computationally. We found that the binding score of a specific noscapinoid with each type of tubulin isotype is different. Specifically, amino-noscapine has the highest binding score of -6.4, -7.2, -7.4 and -7.3 kcal/mol with αβI, αβII, αβIII and αβIV isotypes, respectively. Similarly 10 showed higher binding affinity of -6.8 kcal/mol with αβV, whereas 8 had the highest binding affinity of -7.2, -7.1 and -7.2 kcal/mol, respectively with αβVI, αβVII and αβVIII isotypes. More importantly, both amino-noscapine and its clinical derivative, bromo-noscapine have the highest binding affinity of -46.2 and -38.1 kcal/mol against αβIII (overexpression of αβIII has been associated with resistance to a wide range of chemotherapeutic drugs for several human malignancies) as measured using MM-PBSA. Knowledge of the isotype specificity of the noscapinoids may allow for development of novel therapeutic agents based on this class of drugs.

  14. Akt and SHP-1 are DC-intrinsic checkpoints for tumor immunity

    Science.gov (United States)

    Prestwood, Tyler R.; Spitzer, Matthew H.; Linde, Ian L.; Chabon, Jonathan; Reticker-Flynn, Nathan E.; Bhattacharya, Nupur; Zhang, Hong; Zhang, Xiangyue; Basto, Pamela A.; Burt, Bryan M.; Alonso, Michael N.; Engleman, Edgar G.

    2016-01-01

    BM-derived DC (BMDC) are powerful antigen-presenting cells. When loaded with immune complexes (IC), consisting of tumor antigens bound to antitumor antibody, BMDC induce powerful antitumor immunity in mice. However, attempts to employ this strategy clinically with either tumor-associated DC (TADC) or monocyte-derived DC (MoDC) have been disappointing. To investigate the basis for this phenomenon, we compared the response of BMDC, TADC, and MoDC to tumor IgG-IC. Our findings revealed, in both mice and humans, that upon exposure to IgG-IC, BMDC internalized the IC, increased costimulatory molecule expression, and stimulated autologous T cells. In contrast, TADC and, surprisingly, MoDC remained inert upon contact with IC due to dysfunctional signaling following engagement of Fcγ receptors. Such dysfunction is associated with elevated levels of the Src homology region 2 domain–containing phosphatase-1 (SHP-1) and phosphatases regulating Akt activation. Indeed, concomitant inhibition of both SHP-1 and phosphatases that regulate Akt activation conferred upon TADC and MoDC the capacity to take up and process IC and induce antitumor immunity in vivo. This work identifies the molecular checkpoints that govern activation of MoDC and TADC and their capacity to elicit T cell immunity. PMID:27812544

  15. Expression of SHP2 and related markers in non-small cell lung cancer: a tissue microarray study of 80 cases.

    Science.gov (United States)

    Tang, Chunlan; Luo, Dan; Yang, Heping; Wang, Qingliang; Zhang, Rong; Liu, Guoxiang; Zhou, Xiangdong

    2013-10-01

    The purpose of this study was to assess the relationships between the expression of SHP2 and VEGF, VEGFR-1, VEGFR-2, MMP-2, MMP-9, TIMP-1, TIMP-2, and microvessel density (MVD), as well as the clinicopathologic parameters of these markers in non-small cell lung cancer (NSCLC). Using a tissue microarray, the expression of these 8 markers in 80 NSCLC cases was detected by immunohistochemistry. The expression of the markers was higher in cancer tissues when compared with the surrounding tissues. The MVD was lower in the CD34-positive cancer tissues than in the surrounding tissues. Significantly higher positive rates of expression for SHP2, MMP-9, and MMP-2 were observed in patients with lymph node metastases. The later the clinical stage was, the higher the expression of MMP-9 and MMP-2. The expression of VEGF in patients with lung squamous cell carcinomas was significantly higher than in patients with lung adenocarcinomas. The positive expression of SHP2 correlated significantly with that of VEGFR-2 and the MVD and a survival disadvantage was noted in the patients with SHP2-positive tumors. Therefore, our data suggest that the expression of SHP2 in NSCLC has high specificity and sensitivity and is closely related to lymph node metastasis and the expression of VEGFR-2 and the MVD in patients with NSCLC. SHP2 expression may promote the invasion and metastasis of NSCLC through angiogenesis and the lymphatic system.

  16. Conditional Deletion of Shp2 in the Mammary Gland Leads to Impaired Lobulo-alveolar Outgrowth and Attenuated Stat5 Activation*

    Science.gov (United States)

    Ke, Yuehai; Lesperance, Jacqueline; Zhang, Eric E.; Bard-Chapeau, Emilie A.; Oshima, Robert G.; Muller, William J.; Feng, Gen-Sheng

    2006-01-01

    Stat5 and Stat3, two members of the Stat (signal transducer and activator of transcription) family, are known to play critical roles in mammopoiesis/lactogenesis and involution, respectively, in the mammary gland. Phosphotyrosine phosphatase Shp2 has been shown to dephosphorylate and thus inactivate both Stat5 and Stat3 in vitro. Paradoxically, cell culture studies also suggest a positive role of Shp2 in promoting prolactin-stimulated Stat5 activation. We have shown here that selective deletion of Shp2 in mouse mammary glands suppresses Stat5 activity during pregnancy and lactation, resulting in significant impairment of lobulo-alveolar outgrowth and lactation. In contrast, Stat3 activity was slightly up-regulated shortly before/at involution, leading to normal epithelial cell apoptosis/involution in Shp2-deficient mammary gland. Thus, Shp2 acts to promote Stat5 activation by the JAK2·prolactin receptor complex, while negatively modulating Stat3 activity before the onset of involution. This is the first demonstration that Shp2 manipulates Stat5 and Stat3 activities reciprocally in mammary epithelial cells, providing novel insight into the complex mechanisms for regulation of various Stat family members by a cytoplasmic tyrosine phosphatase. PMID:16959766

  17. Protein tyrosine phosphatase SHP-1 sensitizes EGFR/HER-2 positive breast cancer cells to trastuzumab through modulating phosphorylation of EGFR and HER-2

    Directory of Open Access Journals (Sweden)

    Wu YF

    2015-09-01

    Full Text Available Yifen Wu,1,2,* Rong Li,3,* Junyi Zhang,4 Gang Wang,5 Bin Liu,6 Xiaofang Huang,7 Tao Zhang,7 Rongcheng Luo8 1Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, 2Department of Oncology, Dongguan People’s Hospital, Dongguan, 3Department of Oncology, Nanfang Hospital, 4Department of Oncology, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, 5Department of Radiology, Dongguan People’s Hospital, Dongguan, 6Second Affiliated Hospital of Guangzhou Medical College, 7College of Traditional Chinese medicine, Southern Medical University, 8Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Background: Trastuzumab resistance in HER-2 positive breast cancer cells is closely related to overexpression of both epidermal growth factor receptor (EGFR and human epidermal receptor (HER-2. SHP-1 has been demonstrated to downregulate tyrosine kinase activity including EGFR via its phosphatase function, but its effect on HER-2 activity is still unknown. Here, we examined the hypothesis that SHP-1 enhances the anticancer efficacy of trastuzumab in EGFR/HER-2 positive breast cancer cells through combining dual inhibition of EGFR and HER-2.Methods: Trastuzumab-resistant breast cancer SKBr-3 cells were generated by long-term in vitro culture of SKBr-3cells in the presence of trastuzumab. The SHP-1 was ectopically expressed by stable transfection. The activity and expression of EGFR, HER-2, and downstream signaling pathways were tested by Western blot. Cell viability was examined by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay, and apoptosis was examined by flow cytometry. The binding between SHP-1 and EGFR/HER-2 was evaluated by immunoprecipitation assay and bimolecular fluorescence complementation. The effects of SHP-1

  18. Heterodimers formed through a partial anionic exchange process: scanning tunneling spectroscopy to monitor bands across the junction vis-à-vis photoinduced charge separation

    Science.gov (United States)

    Bera, Abhijit; Saha, Sudip K.; Pal, Amlan J.

    2015-10-01

    We report controlled formation of heterodimers and their charge separation properties. CdS|CdTe heterodimers were formed through an anionic exchange process of CdS nanostructures. With control over the duration of the anionic exchange process, bulk|dot, bulk|bulk, and then dot|bulk phases of the semiconductors could be observed to have formed. A mapping of density of states as derived from scanning tunneling spectroscopy (STS) brought out conduction and valence band-edges along the nanostructures and heterodimers. The CdS|CdTe heterodimers evidenced a type-II band-alignment between the semiconductors along with the formation of a depletion region at the interface. The width (of the depletion region) and the energy-offset at the interface depended on the size of the semiconductors. We report that the width that is instrumental for photoinduced charge separation in the heterodimers has a direct correlation with the performance of hybrid bulk-heterojunction solar cells based on the nanostructures in a polymer matrix.We report controlled formation of heterodimers and their charge separation properties. CdS|CdTe heterodimers were formed through an anionic exchange process of CdS nanostructures. With control over the duration of the anionic exchange process, bulk|dot, bulk|bulk, and then dot|bulk phases of the semiconductors could be observed to have formed. A mapping of density of states as derived from scanning tunneling spectroscopy (STS) brought out conduction and valence band-edges along the nanostructures and heterodimers. The CdS|CdTe heterodimers evidenced a type-II band-alignment between the semiconductors along with the formation of a depletion region at the interface. The width (of the depletion region) and the energy-offset at the interface depended on the size of the semiconductors. We report that the width that is instrumental for photoinduced charge separation in the heterodimers has a direct correlation with the performance of hybrid bulk

  19. Parents as Writing Partners

    Science.gov (United States)

    Ehrenworth, Mary

    2014-01-01

    Parents know that writing is essential to their children's success, and they're eager to help their children become good writers. But often, they're at a loss about how to help. Instead of leaving them in the dark, schools can make parents into valuable writing partners by giving them a toolkit of guidelines for coaching writers.…

  20. Conicasterol E, a Small Heterodimer Partner Sparing Farnesoid X Receptor Modulator Endowed with a Pregnane X Receptor Agonistic Activity, from the Marine Sponge Theonella swinhoei

    OpenAIRE

    V. Sepe; Ummarino, R.; D'Auria, M. V.; M. G. Chini; Bifulco, G.; Renga, B; D'Amore, C.; Debitus, Cécile; Fiorucci, S.; Zampella, A.

    2012-01-01

    We report the isolation and pharmacological characterization of conicasterol E isolated from the marine sponge Theonella swinhoei. Pharmacological characterization of this steroid in comparison to CDCA, a natural FXR ligand, and 6-ECDCA, a synthetic FXR agonist generated by an improved synthetic strategy, and rifaximin, a potent PXR agonist, demonstrated that conicasterol E is an FXR modulator endowed with PXR agonistic activity. Conicasterol E induces the expression of genes involved in bile...

  1. Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch.

    Directory of Open Access Journals (Sweden)

    Jun Lu

    2006-07-01

    Full Text Available C(2 domains are well characterized as Ca(2+/phospholipid-binding modules, but little is known about how they mediate protein-protein interactions. In neurons, a Munc13-1 C(2A-domain/RIM zinc-finger domain (ZF heterodimer couples synaptic vesicle priming to presynaptic plasticity. We now show that the Munc13-1 C(2A domain homodimerizes, and that homodimerization competes with Munc13-1/RIM heterodimerization. X-ray diffraction studies guided by nuclear magnetic resonance (NMR experiments reveal the crystal structures of the Munc13-1 C(2A-domain homodimer and the Munc13-1 C(2A-domain/RIM ZF heterodimer at 1.44 A and 1.78 A resolution, respectively. The C(2A domain adopts a beta-sandwich structure with a four-stranded concave side that mediates homodimerization, leading to the formation of an eight-stranded beta-barrel. In contrast, heterodimerization involves the bottom tip of the C(2A-domain beta-sandwich and a C-terminal alpha-helical extension, which wrap around the RIM ZF domain. Our results describe the structural basis for a Munc13-1 homodimer-Munc13-1/RIM heterodimer switch that may be crucial for vesicle priming and presynaptic plasticity, uncovering at the same time an unexpected versatility of C(2 domains as protein-protein interaction modules, and illustrating the power of combining NMR spectroscopy and X-ray crystallography to study protein complexes.

  2. Self-assembly of Hydrazide-based Heterodimers Driven by Hydrogen Bonding and Donor-Acceptor Interaction

    Institute of Scientific and Technical Information of China (English)

    FENG,Dai-Jun; WANG,Peng; LI,Xiao-Qiang; LI,Zhan-Ting

    2006-01-01

    A new series of hydrogen bonding-driven heterodimers have been self-assembled in chloroform from hydrazide-based monomers. Additional intermolecular donor-acceptor interaction between the electron-rich bis(p-phenylene)-34-crown-10 unit and the electron-deficient naphthalene diimide unit has been utilized to increase the stability of the dimmers, and pronounced cooperativity of the two discrete non-covalent forces to stabilize the dimer has been revealed by the quantitative 1H (2D) NMR and UV-Vis experiments.

  3. Toxicity evolution of Vipera aspis aspis venom: identification and molecular modeling of a novel phospholipase A(2) heterodimer neurotoxin.

    Science.gov (United States)

    Jan, Virginie; Maroun, R C; Robbe-Vincent, Annie; De Haro, Luc; Choumet, Valérie

    2002-09-11

    We report the simultaneous presence of two phospholipase A(2) (PLA(2)) neurotoxins in the venom of Vipera aspis aspis, the first such observation. One is monomeric and identical to ammodytoxin B of Vipera ammodytes ammodytes. Its presence may result from gene flux after interbreeding between V. aspis aspis and V. ammodytes ammodytes. The second, a novel heterodimer named vaspin, is very similar to vipoxin of Vipera ammodytes meridionalis and to PLA(2)-I of Vipera aspis zinnikeri. It may result from expression of preexisting genes, the acidic subunit evolving from an ancestor common to ammodytin I2 from V. ammodytes ammodytes, which we also found in V. aspis aspis.

  4. Engaging as Equal Partners

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    TRADE volume between China and Africa hit a record last year, sending out positive signals about economic and trade cooperation. China’s robust economic activities,and enhanced cooperation between the two sides,have dragged bilateral trade out of the shadows of the global economic crisis,and helped China emerge as Africa’s largest trading partner in 2009.Professor Mthuli Ncube,Chief Economist and Vice President of the African Development Bank,spoke with ChinAfrica reporter Yu Nan to share his views about the role China has had in Africa’s economic development in recent years. Edited excerpts follow:

  5. New partner - Forestland

    CERN Multimedia

    Staff Association

    2014-01-01

      New partner   Do you need a moment of relaxation and adventure?  Come to Divonne-les-bains and benefit of an immediate discount of 20% on all ropes courses of Forestland http://www.forestland.fr/ upon presentation of your Staff Association membership card. The park is open from 10h00 to 19h00 on Wednesday, Saturday, Sunday during the school period and public holidays (France and Switzerland) or every day during school holidays (France and Switzerland). Different levels of difficulty are available: children, juniors, adults, athletes.

  6. From Neighbors To Partners

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    China and Central Asian nations are both benefiting from closer economic,political and social ties This year marks the 15th anniversary of China’s establishment of diplomatic relations with five Central Asian countries—Uzbekistan,Kazakhstan, Tajikistan, Kyrgyzstan and Turkmenistan. After becoming independent upon the breakup of the Soviet Union, they established and developed stable and sustainable ties with China on a brand new basis. Now, with close cooperation in various fields, China and Central Asian countries have become friendly and cooperative partners.

  7. SHP-Ⅵ: A Shortest Hamiltonian Path-Based POMDP Value Iteration Algorithm%SHP-Ⅵ:一种基于最短哈密顿通路的POMDP值迭代算法

    Institute of Scientific and Technical Information of China (English)

    冯奇; 周雪忠; 黄厚宽; 张小平

    2011-01-01

    Trial-based value iteration is a class of efficient algorithms to solve partially observable Markov decision process (POMDP), among which FSVI is one of the fastest algorithms. But the overhead of computing MDP value function by FSVI is not negligible for large-scale POMDP problems. In this paper, we propose a new value iteration method based on the shortest Hamiltonian path (shortest Hamiltonian path-based value iteration, SHP-VI). This method explores an optimal belief trajectory using the shortest Hamiltonian path resulting from ant colony optimization, and updates value function over the encountered belief states in reversed order. Compared with FSVI, the experimental results show that SHP-VI accelerates the computation of belief trajectory greatly in trial-based algorithms.%基于试探(trial-based)的值迭代算法是求解部分可观察Markov决策过程(partially observable Markov decision process,POMDP)模型的一类有效算法,其中FSVI算法是目前最快的算法之一.然而对于较大规模的POMDP问题,FSVI计算MDP值函数的时间是不容忽视的.提出一种基于最短哈密顿通路(shortest Hamiltonian path)的值迭代算法(shortest Hamiltonian path-based value iteration,SHP-VI).该方法用求解最短哈密顿通路问题的蚁群算法计算一条最优信念状态轨迹,然后在这些信念状态上反向更新值函数.通过与FSVI算法的实验比较,结果表明SHP-VI算法很大程度地提高了基于试探的算法计算信念状态轨迹的效率.

  8. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation.

    Science.gov (United States)

    Chemnitz, Jens M; Parry, Richard V; Nichols, Kim E; June, Carl H; Riley, James L

    2004-07-15

    To study the cis- and trans-acting factors that mediate programmed death 1 (PD-1) signaling in primary human CD4 T cells, we constructed a chimeric molecule consisting of the murine CD28 extracellular domain and human PD-1 cytoplasmic tail. When introduced into CD4 T cells, this construct mimics the activity of endogenous PD-1 in terms of its ability to suppress T cell expansion and cytokine production. The cytoplasmic tail of PD-1 contains two structural motifs, an ITIM and an immunoreceptor tyrosine-based switch motif (ITSM). Mutation of the ITIM had little effect on PD-1 signaling or functional activity. In contrast, mutation of the ITSM abrogated the ability of PD-1 to block cytokine synthesis and to limit T cell expansion. Further biochemical analyses revealed that the ability of PD-1 to block T cell activation correlated with recruitment of Src homology region 2 domain-containing phosphatase-1 (SHP-1) and SHP-2, and not the adaptor Src homology 2 domain-containing molecule 1A, to the ITSM domain. In TCR-stimulated T cells, SHP-2 associated with PD-1, even in the absence of PD-1 engagement. Despite this interaction, the ability of PD-1 to block T cell activation required receptor ligation, suggesting that colocalization of PD-1 with CD3 and/or CD28 may be necessary for inhibition of T cell activation.

  9. Close partner relationships

    Directory of Open Access Journals (Sweden)

    Stefanović-Stanojević Tatjana Z.

    2002-01-01

    Full Text Available According to the theory of emotional attachment, specific emotional relationships are being established at an early age between a child and its parents. On the basis of the quality of these relationships the child creates the so-called internal working model ie the image of itself as well as others. The working model persists throughout one's lifetime, shaping in part the quality of adult relationships. Thus, a dominant adult relationship is a close, partner or love one. Within the indicated theoretical context, we were interested in finding out whether there is a statistically significant link between the emotional ties of parents and their children formed in early childhood. The investigation included 180 grown-ups of the same sex and age. For investigating close partner relationships the test Experience in Close Relationship by the American authors (Brenan K.A., Clark C.L., & Shaver P.R. 1998. was used, while the early emotional relationships were investigated using a test which has been the only one so far to measure this quality in adults - Adult Attachment Interview, (Main M., Casidy J., & Kaplan N., 1985. The results show there is a statistically significant link between the observed variables.

  10. Instabilities in the optical response of a semiconductor quantum dot—metal nanoparticle heterodimer: self-oscillations and chaos

    Science.gov (United States)

    Nugroho, Bintoro S.; Iskandar, Alexander A.; Malyshev, Victor A.; Knoester, Jasper

    2017-01-01

    We theoretically investigate the nonlinear optical response of a heterodimer comprising a semiconductor quantum dot strongly coupled to a metal nanoparticle. The quantum dot is considered as a three-level ladder system with ground, one-exciton, and bi-exction states. As compared to the case of a two-level quantum dot model, adding the third (bi-exciton) state produces fascinating effects in the optical response of the hybrid system. Specifically, we demonstrate that the system may exhibit picosecond and sub-picosecond self-oscillations and quasi-chaotic behaviour under single-frequency continuous wave excitation. An isolated semiconductor quantum dot does not show such features. The effects originate from competing one-exciton and bi-exciton transitions in the semiconductor quantum dot, triggered by the self-action of the quantum dot via the metal nanoparticle. The key parameter that governs the phenomena mentioned is the ratio of the self-action strength and the bi-exciton shift. The self-oscillation regime can be achieved in practice, in particular, in a heterodimer comprised of a closely spaced ZnS/ZnSe core-shell quantum dot and a spherical silver nanoparticle. The results may have applications in nanodevices for generating trains of ultrashort optical pulses.

  11. Regulation of nasal airway homeostasis and inflammation in mice by SHP-1 and Th2/Th1 signaling pathways.

    Directory of Open Access Journals (Sweden)

    Seok Hyun Cho

    Full Text Available Allergic rhinitis is a chronic inflammatory disease orchestrated by Th2 lymphocytes. Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1 is known to be a negative regulator in the IL-4α/STAT-6 signaling pathway of the lung. However, the role of SHP-1 enzyme and its functional relationship with Th2 and Th1 cytokines are not known in the nasal airway. In this study, we aimed to study the nasal inflammation as a result of SHP-1 deficiency in viable motheaten (mev mice and to investigate the molecular mechanisms involved. Cytology, histology, and expression of cytokines and chemokines were analyzed to define the nature of the nasal inflammation. Targeted gene depletion of Th1 (IFN-γ and Th2 (IL-4 and IL-13 cytokines was used to identify the critical pathways involved. Matrix metalloproteinases (MMPs were studied to demonstrate the clearance mechanism of recruited inflammatory cells into the nasal airway. We showed here that mev mice had a spontaneous allergic rhinitis-like inflammation with eosinophilia, mucus metaplasia, up-regulation of Th2 cytokines (IL-4 and IL-13, chemokines (eotaxin, and MMPs. All of these inflammatory mediators were clearly counter-regulated by Th2 and Th1 cytokines. Deletion of IFN-γ gene induced a strong Th2-skewed inflammation with transepithelial migration of the inflammatory cells. These findings suggest that SHP-1 enzyme and Th2/Th1 paradigm may play a critical role in the maintenance of nasal immune homeostasis and in the regulation of allergic rhinitis.

  12. Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice.

    Directory of Open Access Journals (Sweden)

    Shing Hwa Liu

    Full Text Available BACKGROUND: Honokiol, a small-molecular weight natural product, has previously been reported to activate apoptosis and inhibit gastric tumorigenesis. Whether honokiol inhibits the angiogenesis and metastasis of gastric cancer cells remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We tested the effects of honokiol on angiogenic activity and peritoneal dissemination using in vivo, ex vivo and in vitro assay systems. The signaling responses in human gastric cancer cells, human umbilical vascular endothelial cells (HUVECs, and isolated tumors were detected and analyzed. In a xenograft gastric tumor mouse model, honokiol significantly inhibited the peritoneal dissemination detected by PET/CT technique. Honokiol also effectively attenuated the angiogenesis detected by chick chorioallantoic membrane assay, mouse matrigel plug assay, rat aortic ring endothelial cell sprouting assay, and endothelial cell tube formation assay. Furthermore, honokiol effectively enhanced signal transducer and activator of transcription (STAT-3 dephosphorylation and inhibited STAT-3 DNA binding activity in human gastric cancer cells and HUVECs, which was correlated with the up-regulation of the activity and protein expression of Src homology 2 (SH2-containing tyrosine phosphatase-1 (SHP-1. Calpain-II inhibitor and siRNA transfection significantly reversed the honokiol-induced SHP-1 activity. The decreased STAT-3 phosphorylation and increased SHP-1 expression were also shown in isolated peritoneal metastatic tumors. Honokiol was also capable of inhibiting VEGF generation, which could be reversed by SHP-1 siRNA transfection. CONCLUSIONS/SIGNIFICANCE: Honokiol increases expression and activity of SPH-1 that further deactivates STAT3 pathway. These findings also suggest that honokiol is a novel and potent inhibitor of angiogenesis and peritoneal dissemination of gastric cancer cells, providing support for the application potential of honokiol in gastric cancer therapy.

  13. A PTPN11 allele encoding a catalytically impaired SHP2 protein in a patient with a Noonan syndrome phenotype.

    Science.gov (United States)

    Edwards, Jonathan J; Martinelli, Simone; Pannone, Luca; Lo, Ivan Fai-Man; Shi, Lisong; Edelmann, Lisa; Tartaglia, Marco; Luk, Ho-Ming; Gelb, Bruce D

    2014-09-01

    The RASopathies are a relatively common group of phenotypically similar and genetically related autosomal dominant genetic syndromes caused by missense mutations affecting genes participating in the RAS/mitogen-activated protein kinase (MAPK) pathway that include Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML, formerly LEOPARD syndrome). NS and NSML can be difficult to differentiate during infancy, but the presence of multiple lentigines, café au lait spots, and specific cardiac defects facilitate the diagnosis. Furthermore, individual PTPN11 missense mutations are highly specific to each syndrome and engender opposite biochemical alterations on the function of SHP-2, the protein product of that gene. Here, we report on a 5-year-old male with two de novo PTPN11 mutations in cis, c.1471C>T (p.Pro491Ser), and c.1492C>T (p.Arg498Trp), which are associated with NS and NSML, respectively. This boy's phenotype is intermediate between NS and NSML with facial dysmorphism, short stature, mild global developmental delay, pulmonic stenosis, and deafness but absence of café au lait spots or lentigines. The double-mutant SHP-2 was found to be catalytically impaired. This raises the question of whether clinical differences between NS and NSML can be ascribed solely to the relative SHP-2 catalytic activity.

  14. Epstein-Barr virus-encoded latent membrane protein 1 modulates cyclin D1 by c-Jun/Jun B heterodimers

    Institute of Scientific and Technical Information of China (English)

    SONG; Xin; TAO; Yongguang; ZENG; Liang; YANG; Jing; TANG; F

    2005-01-01

    In our recent studies, we found that LMP1 encoded by Epstein-Barr virus could accelerate the formation of active c-Jun/Jun B heterodimer. We studied the regulation of cyclinD1 by c-Jun/Jun B heterodimers by laser scanning confocal influorescence microscopy, Western blot, luciferase activity assay, super-EMSA and flow cytometry in the Tet-on-LMP1 HNE2 cell line, in which LMP1 expression was regulated by Tet-on system. c-Jun/Jun B heterodimers induced by LMP1 could up regulate cyclin D1 promoter activity and expression. Overexpression of cyclinD1 accelerated the progression of cell cycle.

  15. Partnering with NASA: An Overview

    Science.gov (United States)

    Martin, Gary

    2017-01-01

    Partnerships is an important part of doing business at NASA. NASA partners with external organizations to access capabilities under collaborative agreements; enters into agreements for partner access to NASA capabilities; expand overall landscape of space activity; and spurring innovation. NASA partnerships consist of Reimbursable and Non-Reimbursable Space Act Agreements. Partnerships at Ames aligns with Ames' core competencies, and Partners often office in the NASA Research Park, which is an established regional innovation cluster that facilitates commercialization and services as a technology accelerator via onsite collaborations between NASA and its partners.

  16. KARP-1 works as a heterodimer with Ku70, but the function of KARP-1 cannot perfectly replace that of Ku80 in DSB repair.

    Science.gov (United States)

    Koike, Manabu; Yutoku, Yasutomo; Koike, Aki

    2011-10-01

    Ku, the heterodimer of Ku70 and Ku80, plays an essential role in the DNA double-strand break (DSB) repair pathway, i.e., non-homologous end-joining (NHEJ). Two isoforms of Ku80 encoded by the same genes, namely, Ku80 and KARP-1 are expressed and function in primate cells, but not in rodent cells. Ku80 works as a heterodimer with Ku70. However, it is not yet clear whether KARP-1 forms a heterodimer with Ku70 and works as a heterodimer. Although KARP-1 appears to work in NHEJ, its physiological role remains unclear. In this study, we established and characterized EGFP-KARP-1-expressing xrs-6 cell lines, EGFP-KARP-1/xrs-6. We found that nuclear localization signal (NLS) of KARP-1 is localized in the C-terminal region. Our data showed that KARP-1 localizes within the nucleus in NLS-dependent and NLS-independent manner and forms a heterodimer with Ku70, and stabilizes Ku70. On the other hand, EGFP-KARP-1 could not perfectly complement the radiosensitivity and DSB repair activity of Ku80-deficient xrs-6 cells. Furthermore, KARP-1 could not accumulate at DSBs faster than Ku80, although EGFP-KARP-1 accumulates at DSBs. Our data demonstrate that the function of KARP-1 could not perfectly replace that of Ku80 in DSB repair, although KARP-1 has some biochemical properties, which resemble those of Ku80, and works as a heterodimer with Ku70. On the other hand, the number of EGFP-KARP-1-expressing xrs-6 cells showing pan-nuclear γ-H2AX staining significantly increases following X-irradiation, suggesting that KARP-1 may have a novel role in DSB response. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. SDF-1 signaling via the CXCR4-TCR heterodimer requires PLC-β3 and PLC-γ1 for distinct cellular responses 1

    Science.gov (United States)

    Kremer, Kimberly N.; Clift, Ian C.; Miamen, Alexander G.; Bamidele, Adebowale O.; Qian, Nan-Xin; Humphreys, Troy D.; Hedin, Karen E.

    2011-01-01

    The CXCR4 chemokine receptor is a G protein-coupled receptor (GPCR) that signals in T lymphocytes by forming a heterodimer with the T cell antigen receptor (TCR). CXCR4 and TCR functions are consequently highly cross-regulated, affecting T cell immune activation, cytokine secretion, and T cell migration. The CXCR4-TCR heterodimer stimulates T cell migration and activation of the ERK MAP kinase and downstream AP-1-dependent cytokine transcription in response to SDF-1, the sole chemokine ligand of CXCR4. These responses require Gi-type G proteins as well as TCR ITAM domains and the ZAP-70 tyrosine kinase, thus indicating that the CXCR4-TCR heterodimer signals to integrate GPCR-associated and TCR-associated signaling molecules in response to SDF-1. Yet, the phospholipase C (PLC) isozymes responsible for coupling the CXCR4-TCR heterodimer to distinct downstream cellular responses are incompletely characterized. Here, we demonstrate that PLC activity is required for SDF-1 to induce ERK activation, migration, and CXCR4 endocytosis in human T cells. SDF-1 signaling via the CXCR4-TCR heterodimer uses PLC-β3 to activate the Ras-ERK pathway and increase intracellular Ca2+ concentrations, while PLC-γ1 is dispensable for these outcomes. In contrast, PLC-γ1, but not PLC-β3, is required for SDF-1-mediated migration, via a mechanism independent of LAT. These results increase understanding of the signaling mechanisms employed by the CXCR4-TCR heterodimer, characterize new roles for PLC-β3 and PLC-γ1 in T cells, and suggest that multiple PLCs may also be activated downstream of other chemokine receptors in order to distinctly regulate migration versus other signaling functions. PMID:21705626

  18. Novel binding partners and differentially regulated phosphorylation sites clarify Eps8 as a multi-functional adaptor.

    Directory of Open Access Journals (Sweden)

    Debbie L Cunningham

    Full Text Available Eps8 is involved in both cell signalling and receptor trafficking. It is a known phosphorylation substrate for two proteins involved in the fibroblast growth factor receptor (FGFR signalling pathway: the receptor itself and Src. Here we report a differential proteomic analysis of Eps8 aimed to identify specific FGFR and Src family kinase dependent phosphosites and co-associated phosphodependent binding partners. This study reveals a total of 22 Eps8 pTyr and pSer/Thr phosphorylation sites, including those that are dependent on Src family and FGFR kinase activity. Peptide affinity purification of proteins that bind to a selection of the pTyr phosphosites has identified a range of novel Eps8 binding partners including members of the intracellular vesicle trafficking machinery (clathrin and AP-2, proteins which have been shown to regulate activated receptor trafficking (NBR1 and Vav2, and proteins involved in receptor signalling (IRS4 and Shp2. Collectively this study significantly extends the understanding of Eps8 post-translational modification by regulated phosphorylation, identifies novel Eps8 binding partners implicated in receptor trafficking and signalling, and confirms the functions of Eps8 at the nexus of receptor signalling and vesicular trafficking.

  19. Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease.

    Science.gov (United States)

    Xiao, Wenbin; Ando, Tomoaki; Wang, Huan-You; Kawakami, Yuko; Kawakami, Toshiaki

    2010-12-23

    Hyperactivation of the transcription factor Stat5 leads to various leukemias. Stat5 activity is regulated by the protein phosphatase SHP-1 in a phospholipase C (PLC)-β3-dependent manner. Thus, PLC-β3-deficient mice develop myeloproliferative neoplasm, like Lyn (Src family kinase)- deficient mice. Here we show that Lyn/PLC-β3 doubly deficient lyn(-/-);PLC-β3(-/-) mice develop a Stat5-dependent, fatal myelodysplastic/myeloproliferative neoplasm, similar to human chronic myelomonocytic leukemia (CMML). In hematopoietic stem cells of lyn(-/-);PLC-β3(-/-) mice that cause the CMML-like disease, phosphorylation of SHP-1 at Tyr(536) and Tyr(564) is abrogated, resulting in reduced phosphatase activity and constitutive activation of Stat5. Furthermore, SHP-1 phosphorylation at Tyr(564) by Lyn is indispensable for maximal phosphatase activity and for suppression of the CMML-like disease in these mice. On the other hand, Tyr(536) in SHP-1 can be phosphorylated by Lyn and another kinase(s) and is necessary for efficient interaction with Stat5. Therefore, we identify a novel Lyn/PLC-β3-mediated regulatory mechanism of SHP-1 and Stat5 activities.

  20. Lyn- and PLC-β3–dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease

    Science.gov (United States)

    Xiao, Wenbin; Ando, Tomoaki; Wang, Huan-You; Kawakami, Yuko

    2010-01-01

    Hyperactivation of the transcription factor Stat5 leads to various leukemias. Stat5 activity is regulated by the protein phosphatase SHP-1 in a phospholipase C (PLC)–β3-dependent manner. Thus, PLC-β3–deficient mice develop myeloproliferative neoplasm, like Lyn (Src family kinase)– deficient mice. Here we show that Lyn/PLC-β3 doubly deficient lyn−/−;PLC-β3−/− mice develop a Stat5-dependent, fatal myelodysplastic/myeloproliferative neoplasm, similar to human chronic myelomonocytic leukemia (CMML). In hematopoietic stem cells of lyn−/−;PLC-β3−/− mice that cause the CMML-like disease, phosphorylation of SHP-1 at Tyr536 and Tyr564 is abrogated, resulting in reduced phosphatase activity and constitutive activation of Stat5. Furthermore, SHP-1 phosphorylation at Tyr564 by Lyn is indispensable for maximal phosphatase activity and for suppression of the CMML-like disease in these mice. On the other hand, Tyr536 in SHP-1 can be phosphorylated by Lyn and another kinase(s) and is necessary for efficient interaction with Stat5. Therefore, we identify a novel Lyn/PLC-β3–mediated regulatory mechanism of SHP-1 and Stat5 activities. PMID:20858858

  1. KNOWLEDGE SHARING IN PARTNERING

    DEFF Research Database (Denmark)

    Koch, Christian; Thuesen, Christian Langhoff

    This paper adopts practicebased theory for understanding interorganisational knowledge work and extents it with a discussion of the role of redundancy. The paper presents a case study of a project partnership in construction using the partnering concept. The project group responsible...... on arenas (e.g. meetings), brokers (e.g. design manager), and boundary objects (e.g. drawings) . The constellation of firms is interpreted as a multiple configuration of communities of practices, characterised by overlapping practises, multiple memberships and different levels of participation....... The diversity and disjunct feature of the practices is a condition of possibility of knowledge handling as it is a prerequisite for the synthesis of various forms of knowledge in the building construct. Here an orchestrated combination of relationbased interaction with boundary objects and brokers, requisite...

  2. HIV-1 structural proteins serve as PAMPs for TLR2 heterodimers significantly increasing infection and innate immune activation

    Directory of Open Access Journals (Sweden)

    Kenneth Lee Rosenthal

    2015-08-01

    Full Text Available Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2 physically inhibited HIV-induced, NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2. Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41 act as viral PAMPs signalling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to immune activation through TLR2/6. These results were confirmed using TLR2/1 siRNA knock down assays which ablated p17 and gp41-induced cellular activation and through studies of HEK293 cells expressing selected TLRs. Interestingly, our results show in the absence of TLR6, p24 bound to TLR2 and blocked p17 and gp41-induced activation, thus providing a novel mechanism by which HIV-1 can manipulate innate sensing. Taken together, our results identified, for the first time, novel HIV-1 PAMPs that play a role in TLR2-mediated cellular activation and increased proviral DNA. These findings have important implications for our fundamental understanding of HIV-1 immune activation and pathogenesis, as well as HIV-1 vaccine development.

  3. When One Partner Is HIV+

    Science.gov (United States)

    ... Translate Text Size Print When One Partner Is HIV+ What is a “mixed-status” Relationship? A " ... but you can minimize it. Tips for the HIV-negative Partner If you are the HIV-negative ...

  4. Intimate Partner Violence. Prevention Update

    Science.gov (United States)

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2011

    2011-01-01

    The Centers for Disease Control and Prevention (CDC) defines intimate partner violence (IPV) as violence between two people in a close relationship, including current and former spouses and dating partners. IPV occurs on a continuum from a single episode to ongoing battering and can include physical violence, sexual violence, threats, emotional…

  5. Partner selection and Hollywood Films

    DEFF Research Database (Denmark)

    Grodal, Torben Kragh; Kramer, Mette

    2012-01-01

    Based on cognitive, neurological and evolutionary based film theory the article describes the representation of partner selection in Hollywood films. It analyses paradigm scenarios of partner selection and love, It further describes some of those mechanisms that regulate the relation between auto...

  6. Partnering with the NCPV (Brochure)

    Energy Technology Data Exchange (ETDEWEB)

    2013-06-01

    Brochure that explains the basic partnering opportunities that exist within the National Center for Photovoltaics for industry and university groups: non-proprietary partnering opportunities, competitive solicitations, Technology Partnership Agreements, seed fund to develop Technology Partnership Agreements, Hands-On PV Experience Workshop, and NCPV Fellowship Program.

  7. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

    Science.gov (United States)

    Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

    2016-02-01

    Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

  8. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2.

    Science.gov (United States)

    Breitkopf, Susanne B; Yang, Xuemei; Begley, Michael J; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A; Hong, Pengyu; Kontaridis, Maria I; Cantley, Lewis C; Perrimon, Norbert; Asara, John M

    2016-02-03

    Using a series of immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

  9. SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling.

    Science.gov (United States)

    Li, Cong; Li, Hong; Zhang, Peng; Yu, Li-Jun; Huang, Tian-Miao; Song, Xue; Kong, Qing-You; Dong, Jian-Li; Li, Pei-Nan; Liu, Jia

    2016-12-27

    Activated STAT3 signaling is critical for human medulloblastoma cells. SHP2, SOCS3 and PIAS3 are known as the negative regulators of STAT3 signaling, while their relevance to frequent STAT3 activation in medulloblastomas remains unknown. Tissue microarrays were constructed with 17 tumor-surrounding noncancerous brain tissues and 61 cases of the classic medulloblastomas, 44 the large-cell medulloblastomas, and 15 nodular medulloblastomas, which were used for immunohistochemical profiling of STAT3, SHP2, SOCS3 and PIAS3 expression patterns and the frequencies of STAT3 nuclear translocation. Three human medulloblastoma cell lines (Daoy, UW228-2 and UW228-3) were cultured with and without 100 μM resveratrol supplementation. The influences of resveratrol in SHP2, SOCS3 and PIAS3 expression and SOCS3 knockdown in STAT3 activation were analyzed using multiple experimental approaches. SHP2, SOCS3 and PIAS3 levels are reduced in medulloblastomas in vivo and in vitro, of which PIAS3 downregulation is more reversely correlated with STAT3 activation. In resveratrol-suppressed medulloblastoma cells with STAT3 downregulation and decreased incidence of STAT3 nuclear translocation, PIAS3 is upregulated, the SHP2 level remains unchanged and SOCS3 is downregulated. SOCS3 proteins are accumulated in the distal ends of axon-like processes of resveratrol-differentiated medulloblastoma cells. Knockdown of SOCS3 expression by siRNA neither influences cell proliferation nor STAT3 activation or resveratrol sensitivity but inhibits resveratrol-induced axon-like process formation. Our results suggest that (1) the overall reduction of SHP2, SOCS3 and PIAS3 in medulloblastoma tissues and cell lines; (2) the more inverse relevance of PIAS3 expression with STAT3 activation; (3) the favorable prognostic values of PIAS3 for medulloblastomas and (4) the involvement of SOCS3 in resveratrol-promoted axon regeneration of medulloblastoma cells.

  10. Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow.

    Science.gov (United States)

    Rodriguez-Martinez, H; Saravia, F; Wallgren, M; Martinez, E A; Sanz, L; Roca, J; Vazquez, J M; Calvete, J J

    2010-01-01

    Seminal plasma (SP) is a complex fluid which exerts biological actions in the female reproductive tract. In pigs, SP elicits endometrial inflammation and consequent immune changes after mating. This study tested whether heparin-binding spermadhesins (HBPs) and the heterodimer of porcine sperm adhesions I and II (PSP-I/PSP-II) in SP recruit different lymphocyte subsets (CD2(+), CD4(+) and CD8(+) T cells) or polymorphonuclear leukocytes (PMNs) to the superficial endometrium or luminal epithelium and lumen, respectively, of oestrous sows. In Experiment 1, endometrial biopsies were taken between 2 and 120 min after infusion of uterine horns with HBPs, PSP-I/PSP-II or saline and evaluated by immunohistochemistry or histology. In Experiment 2, the uterus of oestrous sows was infused with PSP-I/PSP-II or saline to assess PMN numbers in the uterine lumen 3h later. PSP-I/PSP-II elicited CD2+ T cell recruitment from 10 min, and CD8(+) T cells from 60 min after infusion, while HBPs increased CD4(+) T cell recruitment by 120 min. PSP-I/PSP-II but not HBPs induced PMN migration to the surface epithelium by 10 min. PMN numbers were elevated 5-fold by 30 min and 7-fold from 60 min, with PMNs detectable in the lumen from 30 min after infusion. Six-fold more PMNs were collected from the uterine lumen of PSP-I/PSP-II-infused sows compared to controls at 3h after infusion. These data show that PSP-I/PSP-II heterodimer in seminal plasma has a predominant role in triggering the recruitment of uterine PMNs and T cells after mating, initiating a cascade of transient and long-lasting immunological events.

  11. The phytochrome B/phytochrome C heterodimer is necessary for phytochrome C-mediated responses in rice seedlings.

    Directory of Open Access Journals (Sweden)

    Xianzhi Xie

    Full Text Available BACKGROUND: PhyC levels have been observed to be markedly lower in phyB mutants than in Arabidopsis or rice wild type etiolated seedlings, but the mechanism of this phenomenon has not been fully elucidated. RESULTS: In the present study, we investigated the mechanism by which phyB affects the protein concentration and photo-sensing abilities of phyC and demonstrated that rice phyC exists predominantly as phyB/phyC heterodimers in etiolated seedlings. PHYC-GFP protein was detected when expressed in phyA phyC mutants, but not in phyA phyB mutants, suggesting that phyC requires phyB for its photo-sensing abilities. Interestingly, when a mutant PHYB gene that has no chromophore binding site, PHYB(C364A, was introduced into phyB mutants, the phyC level was restored. Moreover, when PHYB(C364A was introduced into phyA phyB mutants, the seedlings exhibited de-etiolation under both far-red light (FR and red light (R conditions, while the phyA phyB mutants were blind to both FR and R. These results are the first direct evidence that phyC is responsible for regulating seedling de-etiolation under both FR and R. These findings also suggest that phyB is indispensable for the expression and function of phyC, which depends on the formation of phyB/phyC heterodimers. SIGNIFICANCE: The present report clearly demonstrates the similarities and differences in the properties of phyC between Arabidopsis and rice and will advance our understanding of phytochrome functions in monocots and dicots.

  12. BMP2/7 heterodimer can modulate all cellular events of the in vitro rankl-mediated osteoclastogenesis, respectively, in different dose patterns

    NARCIS (Netherlands)

    Zheng, Y.; Wang, L.; Zhang, X.; Gu, Z.; Wu, G.

    2012-01-01

    Bone morphogenetic protein (BMP) heterodimers can trigger and sustain osteoblastic bone regeneration in significantly lower dosages than BMP homodimers. However, their effects on osteoclastic activity—a paramount coupling process with ostoblastic activity—remain undocumented. In this study, we delin

  13. Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation

    NARCIS (Netherlands)

    Wang, J.; Zheng, Y.; Zhao, J.; Liu, T.; Gao, L.; Gu, Z.; Wu, G.

    2012-01-01

    Objectives To delineate the dynamic micro-architectures of bone induced by low-dose bone morphogenetic protein (BMP)-2/7 heterodimer in peri-implant bone defects compared to BMP2 and BMP7 homodimer. Material and Methods Peri-implant bone defects (8 mm in diameter, 4 mm in depth) were created surroun

  14. c-Myc/Max heterodimers bind cooperatively to the E-box sequences located in the first intron of the rat ornithine decarboxylase (ODC) gene

    NARCIS (Netherlands)

    Walhout, A.J.M.; Gubbels, J.M.; Bernards, R.A.; Vliet, P.C. van der; Timmers, H.T.M.

    1997-01-01

    The oncoprotein c-Myc plays an important role in cell proliferation, transformation, inhibition of differentiation and apoptosis. These functions most likely result from the transcription factor activity of c-Myc. As a heterodimer with Max, the c-Myc protein binds to the E-box sequence (CACGTG), whi

  15. Partnering in the Construction Industry

    DEFF Research Database (Denmark)

    Ditlev Bohnstedt, Kristian; Bejder, Erik; Haugbølle, Kim

    2013-01-01

    publications change across this period. It is concluded that trends such as research on developing trust among construction partners to facilitate project success, feasibility of and the barriers to adopting a partnering approach and strategic propositions for overcoming barriers are highly emerging. Finally...... gaps in existing body of knowledge. The objective of this literature-based paper is to explore the current literature by systematically reviewing and summarizing research trends in leading top-tier construction management journals between 2002 and 2012, addressing how the themes in partnering related...

  16. Partnering in the Construction Industry

    DEFF Research Database (Denmark)

    Ditlev Bohnstedt, Kristian; Haugbølle, Kim; Bejder, Erik

    2013-01-01

    gaps in existing body of knowledge. The objective of this literature-based paper is to explore the current literature by systematically reviewing and summarizing research trends in leading top-tier construction management journals between 2002 and 2012, addressing how the themes in partnering related...... publications change across this period. It is concluded that trends such as research on developing trust among construction partners to facilitate project success, feasibility of and the barriers to adopting a partnering approach and strategic propositions for overcoming barriers are highly emerging. Finally...

  17. Same-Sex Partner Bereavement.

    Science.gov (United States)

    Patlamazoglou, Lefteris; Simmonds, Janette G; Snell, Tristan L

    2017-01-01

    The experience of same-sex-attracted people who have lost a partner is neglected in the existing literature on bereavement. Previous research on lesbian, gay, bisexual, transgender, intersex, queer and questioning (LGBTIQ) populations tends to focus on the loss of a partner to HIV-related causes, and there is scant research concerning non-HIV-related bereavement. The purpose of this article is to investigate the non-HIV-related bereavement experiences of same-sex partners and to address the potential complications of disenfranchised grief. Coping with the loss of a same-sex partner and the impact of bereavement on subsequent relationships are also discussed. Implications for counseling of bereaved same-sex-attracted individuals are drawn, and recommendations for future psychological research on the experience of bereavement are made.

  18. 2015 NAIP Partner Availability Map

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — Shows the available NAIP imagery which NAIP Partners can access. Either Quarter Quads (QQs), Compressed County Mosaics (CCMs) or data that has been physically mailed...

  19. A Partner's Guide to Pregnancy

    Science.gov (United States)

    ... growth problems. Women who are well supported during pregnancy may be less anxious and have less stress in the weeks after childbirth. You can be supportive by educating yourself about pregnancy, going with your partner to prenatal care appointments, ...

  20. Partners Against Crime (PAC) Districts

    Data.gov (United States)

    City and County of Durham, North Carolina — The Partners Against Crime (PAC) program promotes collaboration among police officers, Durham residents, and city and county government officials to find...

  1. Managing Your China JV Partner

    Institute of Scientific and Technical Information of China (English)

    CHRIS; DEVONSHIRE-ELLIS

    2008-01-01

    Having critical management tools gives foreign investors the chance to maximize their investment, minimize their risk and develop a mutually profitable business with a Chinese partner. This concludes our series on this topic.

  2. Managing Your China JV Partner

    Institute of Scientific and Technical Information of China (English)

    CHRIS; DEVONSHIRE-ELLIS

    2008-01-01

    Joint ventures (JVs) are a marriage between businesses, and as in any marriage,both partners need to put time and effort intoit. Having conducted your due diligence,negotiated your investments, and agreed to

  3. Partner Ballroom Dance Robot -PBDR-

    Science.gov (United States)

    Kosuge, Kazuhiro; Takeda, Takahiro; Hirata, Yasuhisa; Endo, Mitsuru; Nomura, Minoru; Sakai, Kazuhisa; Koizumi, Mizuo; Oconogi, Tatsuya

    In this research, we have developed a dance partner robot, which has been developed as a platform for realizing the effective human-robot coordination with physical interaction. The robot could estimate the next dance step intended by a human and dance the step with the human. This paper introduce the robot referred to as PBDR (Partner Ballroom Dance Robot), which has performed graceful dancing with the human in EXPO 2005, Aichi, Japan.

  4. Discussion about the number of machines in SHP; Discussao sobre o numero de maquinas em PCH's

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Afonso Henriques Moreira [MS Consultoria Ltda, Itajuba, MG (Brazil); Universidade Federal de Itajuba (UNIFEI), MG (Brazil); Horta, Fabio [IX Consultoria e Representacoes Ltda, Itajuba, MG (Brazil); Batista, Thiago Roberto [IX Consultoria e Representacoes Ltda, Itajuba, MG (Brazil); Universidade Federal de Itajuba (UNIFEI), MG (Brazil)

    2010-07-01

    Given the current economic and regulatory conditions, the axial SHP turbines have spread to the country only recently, with the prevailing culture of Francis turbines. It is often used double Francis, with various groups, to avoid a Kaplan option, expensive and sometimes unavailable. This paper deals with the choice between generating sets Francis and Kaplan, in order to present the basic steps for energy production calculating and operational limitations. Then, it develops a reliability analysis of small hydropower plants inserted into the electrical system, either in terms of forced or scheduled unavailability. (author)

  5. TLR3 drives IRF6-dependent IL-23p19 expression and p19/EBI3 heterodimer formation in keratinocytes.

    Science.gov (United States)

    Ramnath, Divya; Tunny, Kathryn; Hohenhaus, Daniel M; Pitts, Claire M; Bergot, Anne-Sophie; Hogarth, P Mark; Hamilton, John A; Kapetanovic, Ronan; Sturm, Richard A; Scholz, Glen M; Sweet, Matthew J

    2015-10-01

    Interferon regulatory factor (IRF) family members impart cell-type specificity to toll-like receptor (TLR) signalling, and we recently identified a role for IRF6 in TLR2 signalling in epithelial cells. TLR3 has a well-characterized role in wound healing in the skin, and here, we examined TLR3-dependent IRF6 functions in human keratinocytes. Primary keratinocytes responded robustly to the TLR3 agonist poly(IC) with upregulation of mRNAs for interferon-β (IFN-β), the interleukin-12 (IL-12) family member IL-23p19 and the chemokines IL-8 and chemokine (C-C motif) ligand 5 (CCL5). Silencing of IRF6 expression enhanced poly(IC)-inducible IFN-β mRNA levels and inhibited poly(IC)-inducible IL-23p19 mRNA expression in primary keratinocytes. Consistent with these data, co-transfection of IRF6 increased poly(IC)-inducible IL-23p19 promoter activity, but inhibited poly(IC)-inducible IFN-β promoter activity in reporter assays. Surprisingly, poly(IC) did not regulate IL-12p40 expression in keratinocytes, suggesting that TLR3-inducible IL-23p19 may have an IL-23-independent function in these cells. The only other IL-12 family member that was strongly poly(IC) inducible was EBI3, which has not been shown to heterodimerize with IL-23p19. Both co-immunoprecipitation and proximity ligation assays revealed that IL-23p19 and EBI3 interact in cells. Co-expression of IL-23p19 and EBI3, as compared with IL-23p19 alone, resulted in increased levels of secreted IL-23p19, implying a functional role for this heterodimer. In summary, we report that IRF6 regulates a subset of TLR3 responses in human keratinocytes, including the production of a novel IL-12 family heterodimer (p19/EBI3). We propose that the TLR3-IRF6-p19/EBI3 axis may regulate keratinocyte and/or immune cell functions in the context of cell damage and wound healing in the skin.

  6. Interaction of mumps virus V protein variants with STAT1-STAT2 heterodimer: experimental and theoretical studies

    Directory of Open Access Journals (Sweden)

    Reyes-Leyva Julio

    2010-10-01

    Full Text Available Abstract Background Mumps virus V protein has the ability to inhibit the interferon-mediated antiviral response by inducing degradation of STAT proteins. Two virus variants purified from Urabe AM9 mumps virus vaccine differ in their replication and transcription efficiency in cells primed with interferon. Virus susceptibility to IFN was associated with insertion of a non-coded glycine at position 156 in the V protein (VGly of one virus variant, whereas resistance to IFN was associated with preservation of wild-type phenotype in the V protein (VWT of the other variant. Results VWT and VGly variants of mumps virus were cloned and sequenced from Urabe AM9 vaccine strain. VGly differs from VWT protein because it possesses an amino acid change Gln103Pro (Pro103 and the Gly156 insertion. The effect of V protein variants on components of the interferon-stimulated gene factor 3 (ISGF3, STAT1 and STAT2 proteins were experimentally tested in cervical carcinoma cell lines. Expression of VWT protein decreased STAT1 phosphorylation, whereas VGly had no inhibitory effect on either STAT1 or STAT2 phosphorylation. For theoretical analysis of the interaction between V proteins and STAT proteins, 3D structural models of VWT and VGly were predicted by comparing with simian virus 5 (SV5 V protein structure in complex with STAT1-STAT2 heterodimer. In silico analysis showed that VWT-STAT1-STAT2 complex occurs through the V protein Trp-motif (W174, W178, W189 and Glu95 residue close to the Arg409 and Lys415 of the nuclear localization signal (NLS of STAT2, leaving exposed STAT1 Lys residues (K85, K87, K296, K413, K525, K679, K685, which are susceptible to proteasome degradation. In contrast, the interaction between VGly and STAT1-STAT2 heterodimer occurs in a region far from the NLS of STAT2 without blocking of Lys residues in both STAT1 and STAT2. Conclusions Our results suggest that VWT protein of Urabe AM9 strain of mumps virus may be more efficient than VGly to

  7. The stimulatory effect of LXRalpha is blocked by SHP despite the presence of a LXRalpha binding site in the rabbit CYP7A1 promoter.

    Science.gov (United States)

    Shang, Quan; Pan, Luxing; Saumoy, Monica; Chiang, John Y L; Tint, G Stephen; Salen, Gerald; Xu, Guorong

    2006-05-01

    The transcription of the cholesterol 7alpha-hydroxylase gene (CYP7A1) is greatly decreased in cholesterol-fed rabbits. To determine whether the molecular structure of the promoter is responsible for this downregulation, we cloned the rabbit CYP7A1 promoter, identified the binding sites for alpha-fetoprotein transcription factor (FTF) and liver X receptor (LXRalpha), and studied the effects of FTF, LXRalpha, and SHP on its transcription. Adding LXRalpha/retinoid X receptor together with their ligands (L/R) to the promoter/reporter construct transfected into HepG2 cells greatly increased its activity. FTF did not increase promoter activity, nor did it enhance the stimulatory effect of L/R. Mutating the FTF binding site abolished the promoter baseline activity. Increasing amounts of SHP abolished the effect of L/R, and FTF enhanced the ability of SHP to decrease promoter activity below baseline levels. Thus, downregulation of CYP7A1 in cholesterol-fed rabbits is attributable secondarily to the activation of farnesoid X receptor, which increases SHP expression to override the positive effects of LXRalpha. Although FTF is a competent factor for maintaining baseline activity, it does not further enhance and may suppress CYP7A1 transcription.

  8. Tumoral Prostate Shows Different Expression Pattern of Somatostatin Receptor 2 (SSTR2 and Phosphotyrosine Phosphatase SHP-1 (PTPN6 According to Tumor Progression

    Directory of Open Access Journals (Sweden)

    Ariel Ernesto Cariaga-Martinez

    2009-01-01

    Full Text Available Prostate proliferation is dependent of androgens and many peptide hormones. Recent reports suggest that SSTR2 and SHP-1 were two fundamental components on antiproliferative effect of somatostatin. Many studies on SHP-1 revealed that the expression of this protein was diminished or abolished in several of the cancer cell lines and tissues examined. However, it is necessary to confront the cell lines data with real situation in cancer cases. Our studies have shown that epithelial expressions of both proteins, SHP-1 and SSTR2, in normal and benign hyperplasia are localized in the luminal side of duct and acinar cells. Also, SSTR2 is expressed in stromal cells. In malignant prostate tissue, SHP-1 was diminished in 28/45 cases or absent in 12/45 cases, whereas SSTR2 epithelial was diminished in 38/45 cases or lost in only 2/45 cases. The intensity of immunostained was highly negative correlated with Gleason grade for two proteins.

  9. Tumoral Prostate Shows Different Expression Pattern of Somatostatin Receptor 2 (SSTR2) and Phosphotyrosine Phosphatase SHP-1 (PTPN6) According to Tumor Progression

    Science.gov (United States)

    Cariaga-Martinez, Ariel Ernesto; Lorenzati, María Angelica; Riera, Mario Alejandro; Cubilla, Marisa Angelica; De La Rossa, Andrés; Giorgio, Ernesto Martín; Tiscornia, María Mercedes; Gimenez, Esteban Mariano; Rojas, María Eugenia; Chaneton, Bárbara Julieta; Rodríguez, Dora Isabel; Zapata, Pedro Darío

    2009-01-01

    Prostate proliferation is dependent of androgens and many peptide hormones. Recent reports suggest that SSTR2 and SHP-1 were two fundamental components on antiproliferative effect of somatostatin. Many studies on SHP-1 revealed that the expression of this protein was diminished or abolished in several of the cancer cell lines and tissues examined. However, it is necessary to confront the cell lines data with real situation in cancer cases. Our studies have shown that epithelial expressions of both proteins, SHP-1 and SSTR2, in normal and benign hyperplasia are localized in the luminal side of duct and acinar cells. Also, SSTR2 is expressed in stromal cells. In malignant prostate tissue, SHP-1 was diminished in 28/45 cases or absent in 12/45 cases, whereas SSTR2 epithelial was diminished in 38/45 cases or lost in only 2/45 cases. The intensity of immunostained was highly negative correlated with Gleason grade for two proteins. PMID:19365586

  10. Phosphoproteomics of collagen receptor networks reveals SHP-2 phosphorylation downstream of wild-type DDR2 and its lung cancer mutants.

    Science.gov (United States)

    Iwai, Leo K; Payne, Leo S; Luczynski, Maciej T; Chang, Francis; Xu, Huifang; Clinton, Ryan W; Paul, Angela; Esposito, Edward A; Gridley, Scott; Leitinger, Birgit; Naegle, Kristen M; Huang, Paul H

    2013-09-15

    Collagen is an important extracellular matrix component that directs many fundamental cellular processes including differentiation, proliferation and motility. The signalling networks driving these processes are propagated by collagen receptors such as the β1 integrins and the DDRs (discoidin domain receptors). To gain an insight into the molecular mechanisms of collagen receptor signalling, we have performed a quantitative analysis of the phosphorylation networks downstream of collagen activation of integrins and DDR2. Temporal analysis over seven time points identified 424 phosphorylated proteins. Distinct DDR2 tyrosine phosphorylation sites displayed unique temporal activation profiles in agreement with in vitro kinase data. Multiple clustering analysis of the phosphoproteomic data revealed several DDR2 candidate downstream signalling nodes, including SHP-2 (Src homology 2 domain-containing protein tyrosine phosphatase 2), NCK1 (non-catalytic region of tyrosine kinase adaptor protein 1), LYN, SHIP-2 [SH2 (Src homology 2)-domain-containing inositol phosphatase 2], PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2α) and PLCL2 (phospholipase C-like 2). Biochemical validation showed that SHP-2 tyrosine phosphorylation is dependent on DDR2 kinase activity. Targeted proteomic profiling of a panel of lung SCC (squamous cell carcinoma) DDR2 mutants demonstrated that SHP-2 is tyrosine-phosphorylated by the L63V and G505S mutants. In contrast, the I638F kinase domain mutant exhibited diminished DDR2 and SHP-2 tyrosine phosphorylation levels which have an inverse relationship with clonogenic potential. Taken together, the results of the present study indicate that SHP-2 is a key signalling node downstream of the DDR2 receptor which may have therapeutic implications in a subset of DDR2 mutations recently uncovered in genome-wide lung SCC sequencing screens.

  11. Cytosolic BNIP3 Dimer Interacts with Mitochondrial BAX Forming Heterodimers in the Mitochondrial Outer Membrane under Basal Conditions.

    Science.gov (United States)

    Hendgen-Cotta, Ulrike B; Esfeld, Sonja; Rudi, Katharina; Miinalainen, Ilkka; Klare, Johann P; Rassaf, Tienush

    2017-03-23

    The primary function of mitochondria is energy production, a task of particular importance especially for cells with a high energy demand like cardiomyocytes. The B-cell lymphoma (BCL-2) family member BCL-2 adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is linked to mitochondrial targeting after homodimerization, where it functions in inner membrane depolarization and permeabilization of the mitochondrial outer membrane (MOM) mediating cell death. We investigated the basal distribution of cardiac BNIP3 in vivo and its physical interaction with the pro-death protein BCL2 associated X, apoptosis regulator (BAX) and with mitochondria using immunoblot analysis, co-immunoprecipitation, and continuous wave and pulsed electron paramagnetic resonance spectroscopy techniques. We found that BNIP3 is present as a dimer in the cytosol and in the outer membrane of cardiac mitochondria under basal conditions. It forms disulfide-bridged, but mainly non-covalent dimers in the cytosol. Heterodimers with BAX are formed exclusively in the MOM. Furthermore, our results suggest that BNIP3 interacts with the MOM directly via mitochondrial BAX. However, the physical interactions with BAX and the MOM did not affect the membrane potential and cell viability. These findings suggest that another stimulus other than the mere existence of the BNIP3/BAX dimer in the MOM is required to promote BNIP3 cell-death activity; this could be a potential disturbance of the BNIP3 distribution homeostasis, namely in the direction of the mitochondria.

  12. Controlling quantum-beating signals in 2D electronic spectra by packing synthetic heterodimers on single-walled carbon nanotubes

    Science.gov (United States)

    Wang, Lili; Griffin, Graham B.; Zhang, Alice; Zhai, Feng; Williams, Nicholas E.; Jordan, Richard F.; Engel, Gregory S.

    2017-03-01

    In multidimensional spectroscopy, dynamics of coherences between excited states report on the interactions between electronic states and their environment. The prolonged coherence lifetimes revealed through beating signals in the spectra of some systems may result from vibronic coupling between nearly degenerate excited states, and recent observations confirm the existence of such coupling in both model systems and photosynthetic complexes. Understanding the origin of beating signals in the spectra of photosynthetic complexes has been given considerable attention; however, strategies to generate them in artificial systems that would allow us to test the hypotheses in detail are still lacking. Here we demonstrate control over the presence of quantum-beating signals by packing structurally flexible synthetic heterodimers on single-walled carbon nanotubes, and thereby restrict the motions of chromophores. Using two-dimensional electronic spectroscopy, we find that both limiting the relative rotation of chromophores and tuning the energy difference between the two electronic transitions in the dimer to match a vibrational mode of the lower-energy monomer are necessary to enhance the observed quantum-beating signals.

  13. Effects of coating molecules on the magnetic heating properties of Au-Fe3O4 heterodimer nanoparticles

    Science.gov (United States)

    Yamamoto, Y.; Ogasawara, J.; Himukai, H.; Itoh, T.

    2016-10-01

    In this paper, we report the heating properties of gold-magnetite (Au-Fe3O4) heterodimer nanoparticles (NPs) subjected to an alternating magnetic field. The Au-Fe3O4 NPs coated with oleic acid and oleylamine (OA) were synthesized through a method that combines seed mediation and high-temperature decomposition. The coating was replaced with dimercaptosuccinic acid (DMSA) by the ligand-exchange method. The specific absorption rates (SARs) for the OA- and DMSA-coated Au-Fe3O4 NPs coated with OA and DMSA at room temperature were determined through the calorimetric and magnetometric methods. SAR depended on the square of the magnetic field H up to an H value of 4 kA/m. The absolute value of the SAR for DMSA-coated NPs is about fivefold higher than that of the OA-coated NPs. The AC magnetic hysteresis measurements showed the recovery of the magnetic volume and the decrease in the magnetic anisotropy of the DMSA-coated NPs relative to those of the OA-coated NPs. These results suggest that the protective agent influences the magnetic properties of magnetite NPs via gold NPs.

  14. Two-Step Hydrothermal Synthesis of Bifunctional Hematite-Silver Heterodimer Nanoparticles for Potential Antibacterial and Anticancer Applications

    Science.gov (United States)

    Trang, Vu Thi; Tam, Le Thi; Phan, Vu Ngoc; Van Quy, Nguyen; Huy, Tran Quang; Le, Anh-Tuan

    2017-01-01

    In recent years, the development of composite nanostructures containing noble metal and magnetic nanocrystals has attracted much interest because they offer a promising avenue for multifunctional applications in nanomedicine and pharmacotherapy. In this work, we present a facile two-step hydrothermal approach for the synthesis of bifunctional heterodimer nanoparticles (HDNPs) composed of hematite nanocubes (α-Fe2O3 NCs) and silver nanoparticles (Ag-NPs). The formation and magnetic property of α-Fe2O3-Ag HDNPs was analyzed by transmission electron microscopy, x-ray diffraction and vibrating sample magnetometer. Interestingly, the hydrothermal-synthesized α-Fe2O3-Ag HDNPs were found to display significant antibacterial activity against three types of infectious bacteria. The cytotoxicity of α-Fe2O3-Ag nanocomposite against lung cancer A549 cell line was investigated and compared with that of pure α-Fe2O3 NCs and Ag-NPs. The obtained results reveal that the α-Fe2O3-Ag nanocomposite exhibited higher anticancer performance than that of pure Ag-NPs, whereas pure α-Fe2O3 NCs were not cytotoxic to the tested cells. The inhibitory concentration (IC50) of the α-Fe2O3-Ag nanocomposite was found at 20.94 μg/mL. With the aforementioned properties, α-Fe2O3-Ag HDNPs showed a high potential as a multifunctional material for advanced biomedicine and nanotherapy applications.

  15. Inhibition of DNA double-strand break repair by the Ku heterodimer in mrx mutants of Saccharomyces cerevisiae

    Science.gov (United States)

    Wasko, Brian M.; Holland, Cory L.; Resnick, Michael A.; Lewis, L. Kevin

    2009-01-01

    Yeast rad50 and mre11 nuclease mutants are hypersensitive to physical and chemical agents that induce DNA double-strand breaks (DSBs). This sensitivity was suppressed by elevating intracellular levels of TLC1, the RNA subunit of telomerase. Suppression required proteins linked to homologous recombination, including Rad51, Rad52, Rad59 and Exo1, but not genes of the nonhomologous end-joining (NHEJ) repair pathway. Deletion mutagenesis experiments demonstrated that the 5′ end of TLC1 RNA was essential and a segment containing a binding site for the Yku70/Yku80 complex was sufficient for suppression. A mutant TLC1 RNA unable to associate with Yku80 protein did not increase resistance. These and other genetic studies indicated that association of the Ku heterodimer with broken DNA ends inhibits recombination in mrx mutants, but not in repair-proficient cells or in other DNA repair single mutants. In support of this model, DNA damage resistance of mrx cells was enhanced when YKU70 was co-inactivated. Defective recombinational repair of DSBs in mrx cells thus arises from at least two separate processes: loss of Mrx nuclease-associated DNA end-processing and inhibition of the Exo1-mediated secondary recombination pathway by Ku. PMID:18992851

  16. Two-Step Hydrothermal Synthesis of Bifunctional Hematite-Silver Heterodimer Nanoparticles for Potential Antibacterial and Anticancer Applications

    Science.gov (United States)

    Trang, Vu Thi; Tam, Le Thi; Phan, Vu Ngoc; Van Quy, Nguyen; Huy, Tran Quang; Le, Anh-Tuan

    2017-06-01

    In recent years, the development of composite nanostructures containing noble metal and magnetic nanocrystals has attracted much interest because they offer a promising avenue for multifunctional applications in nanomedicine and pharmacotherapy. In this work, we present a facile two-step hydrothermal approach for the synthesis of bifunctional heterodimer nanoparticles (HDNPs) composed of hematite nanocubes (α-Fe2O3 NCs) and silver nanoparticles (Ag-NPs). The formation and magnetic property of α-Fe2O3-Ag HDNPs was analyzed by transmission electron microscopy, x-ray diffraction and vibrating sample magnetometer. Interestingly, the hydrothermal-synthesized α-Fe2O3-Ag HDNPs were found to display significant antibacterial activity against three types of infectious bacteria. The cytotoxicity of α-Fe2O3-Ag nanocomposite against lung cancer A549 cell line was investigated and compared with that of pure α-Fe2O3 NCs and Ag-NPs. The obtained results reveal that the α-Fe2O3-Ag nanocomposite exhibited higher anticancer performance than that of pure Ag-NPs, whereas pure α-Fe2O3 NCs were not cytotoxic to the tested cells. The inhibitory concentration (IC50) of the α-Fe2O3-Ag nanocomposite was found at 20.94 μg/mL. With the aforementioned properties, α-Fe2O3-Ag HDNPs showed a high potential as a multifunctional material for advanced biomedicine and nanotherapy applications.

  17. Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein Barr virus encoded latent membrane protein 1

    Institute of Scientific and Technical Information of China (English)

    SONG Xin; TAO Yongguang; TAN Yunnian; Leo M. Lee; DENG Xiyun; WU Qiao; CAO Ya

    2005-01-01

    Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) may trigger the transcription factor AP-1 including c-Jun and c-fos. In this report, using a Tet-on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated by the Tet-on system, we show that Jun B can efficiently form a new heterodimeric complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser 63, ser 73) and Jun B is involved in the process of the new heterodimeric formation. We also find that this heterodimeric form can bind to the AP-1 consensus sequence. Transfection studies suggest that JNK interaction protein (JIP) could inhibit the heterodimer formation of c-Jun and Jun B through blocking the AP-1 signaling pathway triggered by LMP1. The interaction and function between c-Jun protein and Jun B protein increase the repertoire of possible regulatory complexes by LMP1 that could play an important role in the regulation of transcription of specific cellular genes in the process of genesis of nasopharyngeal carcinoma.

  18. Pharma partnering: other people's science.

    Science.gov (United States)

    Hofmann, Christian

    2017-01-01

    Partnering is an ideal field if someone is seeking to move from a scientific to a more business-oriented discipline. Partnering's goal is to identify and acquire external innovation. These discoveries are then included in a company's pipeline and help bring novel treatments to patients. Advanced scientific training is essential in the identification and evaluation of these external assets. Here I describe how partnering works in a pharmaceutical company and offer advice on how to make a successful transition from a PhD program to a business career. © 2017 Hofmann. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Partnering and integrated supply management

    DEFF Research Database (Denmark)

    Bjarnø, Ole-Christian; Olsen, Anders; Thyssen, Mikael

    2003-01-01

    are common among the actors in the building industry. Partnering is still in its early stages, and a strategic development of the concept to include long-term collaborative relationships appears to be able to offer considerable potential, while there is a pressing need for the development of methods...... for strategic management of collaborative relationships on a line with the purchasing perspectives offered by Supply Chain Management. Based on a study of the literature and an in-depth case study carried out within a large Scandinavian contractor, this article gives a proposal for how Partnering can...... be supported by strategic purchasing, with the aim of achieving strategic Partnering. The contribution of this article is thus the development of a new purchasing perspective within Construction Supply Chain Management....

  20. Lack of SIRPα phosphorylation and concomitantly reduced SHP-2-PI3K-Akt2 signaling decrease osteoblast differentiation.

    Science.gov (United States)

    Holm, Cecilia Koskinen; Engman, Sara; Sulniute, Rima; Matozaki, Takashi; Oldenborg, Per-Arne; Lundberg, Pernilla

    2016-09-09

    Normal differentiation of bone forming osteoblasts is a prerequisite for maintenance of skeletal health and is dependent on intricate cellular signaling pathways, including the essential transcription factor Runx2. The cell surface glycoprotein CD47 and its receptor signal regulatory protein alpha (SIRPα) have both been suggested to regulate bone cell differentiation. Here we investigated osteoblastic differentiation of bone marrow stromal cells from SIRPα mutant mice lacking the cytoplasmic signaling domain of SIRPα. An impaired osteoblastogenesis in SIRPα-mutant cell cultures was demonstrated by lower alkaline phosphatase activity and less mineral formation compared to wild-type cultures. This reduced osteoblastic differentiation potential in SIRPα-mutant stromal cells was associated with a significantly reduced expression of Runx2, osterix, osteocalcin, and alkaline phosphatase mRNA, as well as a reduced phosphorylation of SHP-2 and Akt2, as compared with that in wild-type stromal cells. Addition of a PI3K-inhibitor to wild-type stromal cells could mimic the impaired osteoblastogenesis seen in SIRPα-mutant cells. In conclusion, our data suggest that SIRPα signaling through SHP-2-PI3K-Akt2 strongly influences osteoblast differentiation from bone marrow stromal cells.

  1. Degradation of phycobilisomes in Synechocystis sp. PCC6803: evidence for essential formation of an NblA1/NblA2 heterodimer and its codegradation by A Clp protease complex.

    Science.gov (United States)

    Baier, Antje; Winkler, Wiebke; Korte, Thomas; Lockau, Wolfgang; Karradt, Anne

    2014-04-25

    When cyanobacteria acclimate to nitrogen deficiency, they degrade their large (3-5-MDa), light-harvesting complexes, the phycobilisomes. This massive, yet specific, intracellular degradation of the pigmented phycobiliproteins causes a color change of cyanobacterial cultures from blue-green to yellow-green, a process referred to as chlorosis or bleaching. Phycobilisome degradation is induced by expression of the nblA gene, which encodes a protein of ~7 kDa. NblA most likely acts as an adaptor protein that guides a Clp protease to the phycobiliproteins, thereby initiating the degradation process. Most cyanobacteria and red algae possess just one nblA-homologous gene. As an exception, the widely used "model organism" Synechocystis sp. PCC6803 expresses two such genes, nblA16803 and nblA26803, both of whose products are required for phycobilisome degradation. Here, we demonstrate that the two NblA proteins heterodimerize in vitro and in vivo using pull-down assays and a Förster energy-transfer approach, respectively. We further show that the NblA proteins form a ternary complex with ClpC (the HSP100 chaperone partner of Clp proteases) and phycobiliproteins in vitro. This complex is susceptible to ATP-dependent degradation by a Clp protease, a finding that supports a proposed mechanism of the degradation process. Expression of the single nblA gene encoded by the genome of the N2-fixing, filamentous cyanobacterium Nostoc sp. PCC7120 in the nblA1/nblA2 mutant of Synechocystis sp. PCC6803 induced phycobilisome degradation, suggesting that the function of the NblA heterodimer of Synechocystis sp. PCC6803 is combined in the homodimeric protein of Nostoc sp. PCC7120.

  2. Validation of Fear of Partner Scale.

    Science.gov (United States)

    O'Leary, K Daniel; Foran, Heather; Cohen, Shiri

    2013-10-01

    Therapists have a responsibility to ascertain if psychological aggression, physical aggression, sexual aggression exist, and if there is fear of the partner. A fear of partner measure was evaluated in 100 couples who sought relationship feedback. Fear of partner's psychological, physical, and sexual aggression was related to actual reports of such behavior. For both men and women, fear of speaking in front of partner and fear of being in therapy with partner were related to reports of psychological aggression perpetrated by the partner, dominance, and isolation by the partner, and one's own marital dissatisfaction. Among respondents who were aggressed against, more men than women reported fear of participating in therapy with their partner. The measure herein can be used to determine the extent of fear of aggression by partners and to assist in the decision-making about the appropriateness of marital therapy and divorce mediation.

  3. The Symmetry of Partner Modelling

    Science.gov (United States)

    Dillenbourg, Pierre; Lemaignan, Séverin; Sangin, Mirweis; Nova, Nicolas; Molinari, Gaëlle

    2016-01-01

    Collaborative learning has often been associated with the construction of a shared understanding of the situation at hand. The psycholinguistics mechanisms at work while establishing common grounds are the object of scientific controversy. We postulate that collaborative tasks require some level of mutual modelling, i.e. that each partner needs…

  4. Top couplings and top partners

    OpenAIRE

    2013-01-01

    We review the model-independent description of the couplings of the top quark to the Higgs and gauge bosons in theories beyond the Standard Model. Then we examine these couplings in the case of arbitrary heavy vector-like quarks mixing with the third family. We also discuss the couplings of these top partners, and comment on implications for LHC searches.

  5. CHINA-JANAICA'S VALUABLE PARTNER

    Institute of Scientific and Technical Information of China (English)

    Guo Yan; Yang Wei

    2010-01-01

    @@ Jamaica is China's largest trading partner in the English-speaking Caribbean and bilateral trade has developed rapidly,although last year bilateral trade has been greatly affected because of the economic crisis.However,with continuous development of the two economies,bilateral economic development and trade has great potential.

  6. Beijing 2008 Olympic Games Partners

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ At Olympic times, many business giants try to expand their influence by sponsoring the Games. The Games is an opportunity for them to turn from a national to an international brand. Here are brief introductions to some of the Beijing 2008 Olympic Games partners.

  7. Partnering into the New Century.

    Science.gov (United States)

    Hart, Sharon; And Others

    1995-01-01

    Suggests the need to develop partnerships in this time of rapidly changing technology. Describes the successful partnership between the John Deere Company and Madison (WI) Area Technical College (MATC) that arose because of needs of both partners: John Deere needed well-trained technicians, and MATC was having difficulty attracting students to its…

  8. Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs.

    Directory of Open Access Journals (Sweden)

    Hakryul Jo

    Full Text Available BACKGROUND: Microtubule drugs are effective anti-cancer agents, primarily due to their ability to induce mitotic arrest and subsequent cell death. However, some cancer cells are intrinsically resistant or acquire a resistance. Lack of apoptosis following mitotic arrest is thought to contribute to drug resistance that limits the efficacy of the microtubule-targeting anti-cancer drugs. Genetic or pharmacological agents that selectively facilitate the apoptosis of mitotic arrested cells present opportunities to strengthen the therapeutic efficacy. METHODOLOGY AND PRINCIPAL FINDINGS: We report a natural product Celastrol targets tubulin and facilitates mitotic cell death caused by microtubule drugs. First, in a small molecule screening effort, we identify Celastrol as an inhibitor of neutrophil chemotaxis. Subsequent time-lapse imaging analyses reveal that inhibition of microtubule-mediated cellular processes, including cell migration and mitotic chromosome alignment, is the earliest events affected by Celastrol. Disorganization, not depolymerization, of mitotic spindles appears responsible for mitotic defects. Celastrol directly affects the biochemical properties of tubulin heterodimer in vitro and reduces its protein level in vivo. At the cellular level, Celastrol induces a synergistic apoptosis when combined with conventional microtubule-targeting drugs and manifests an efficacy toward Taxol-resistant cancer cells. Finally, by time-lapse imaging and tracking of microtubule drug-treated cells, we show that Celastrol preferentially induces apoptosis of mitotic arrested cells in a caspase-dependent manner. This selective effect is not due to inhibition of general cell survival pathways or mitotic kinases that have been shown to enhance microtubule drug-induced cell death. CONCLUSIONS AND SIGNIFICANCE: We provide evidence for new cellular pathways that, when perturbed, selectively induce the apoptosis of mitotic arrested cancer cells, identifying a

  9. Regulation of hERG and hEAG channels by Src and by SHP-1 tyrosine phosphatase via an ITIM region in the cyclic nucleotide binding domain.

    Directory of Open Access Journals (Sweden)

    Lyanne C Schlichter

    Full Text Available Members of the EAG K(+ channel superfamily (EAG/Kv10.x, ERG/Kv11.x, ELK/Kv12.x subfamilies are expressed in many cells and tissues. In particular, two prototypes, EAG1/Kv10.1/KCNH1 and ERG1/Kv11.1/KCNH2 contribute to both normal and pathological functions. Proliferation of numerous cancer cells depends on hEAG1, and in some cases, hERG. hERG is best known for contributing to the cardiac action potential, and for numerous channel mutations that underlie 'long-QT syndrome'. Many cells, particularly cancer cells, express Src-family tyrosine kinases and SHP tyrosine phosphatases; and an imbalance in tyrosine phosphorylation can lead to malignancies, autoimmune diseases, and inflammatory disorders. Ion channel contributions to cell functions are governed, to a large degree, by post-translational modulation, especially phosphorylation. However, almost nothing is known about roles of specific tyrosine kinases and phosphatases in regulating K(+ channels in the EAG superfamily. First, we show that tyrosine kinase inhibitor, PP1, and the selective Src inhibitory peptide, Src40-58, reduce the hERG current amplitude, without altering its voltage dependence or kinetics. PP1 similarly reduces the hEAG1 current. Surprisingly, an 'immuno-receptor tyrosine inhibitory motif' (ITIM is present within the cyclic nucleotide binding domain of all EAG-superfamily members, and is conserved in the human, rat and mouse sequences. When tyrosine phosphorylated, this ITIM directly bound to and activated SHP-1 tyrosine phosphatase (PTP-1C/PTPN6/HCP; the first report that a portion of an ion channel is a binding site and activator of a tyrosine phosphatase. Both hERG and hEAG1 currents were decreased by applying active recombinant SHP-1, and increased by the inhibitory substrate-trapping SHP-1 mutant. Thus, hERG and hEAG1 currents are regulated by activated SHP-1, in a manner opposite to their regulation by Src. Given the widespread distribution of these channels, Src and SHP

  10. Tyrosine phosphatases such as SHP-2 act in a balance with Src-family kinases in stabilization of postsynaptic clusters of acetylcholine receptors

    Directory of Open Access Journals (Sweden)

    Rüegg Markus A

    2007-07-01

    Full Text Available Abstract Background Development of neural networks requires that synapses are formed, eliminated and stabilized. At the neuromuscular junction (NMJ, agrin/MuSK signaling, by triggering downstream pathways, causes clustering and phosphorylation of postsynaptic acetylcholine receptors (AChRs. Postnatally, AChR aggregates are stabilized by molecular pathways that are poorly characterized. Gain or loss of function of Src-family kinases (SFKs disassembles AChR clusters at adult NMJs in vivo, whereas AChR aggregates disperse rapidly upon withdrawal of agrin from cultured src-/-;fyn-/- myotubes. This suggests that a balance between protein tyrosine phosphatases (PTPs and protein tyrosine kinases (PTKs such as those of the Src-family may be essential in stabilizing clusters of AChRs. Results We have analyzed the role of PTPs in maintenance of AChR aggregates, by adding and then withdrawing agrin from cultured myotubes in the presence of PTP or PTK inhibitors and quantitating remaining AChR clusters. In wild-type myotubes, blocking PTPs with pervanadate caused enhanced disassembly of AChR clusters after agrin withdrawal. When added at the time of agrin withdrawal, SFK inhibitors destabilized AChR aggregates but concomitant addition of pervanadate rescued cluster stability. Likewise in src-/-;fyn-/- myotubes, in which agrin-induced AChR clusters form normally but rapidly disintegrate after agrin withdrawal, pervanadate addition stabilized AChR clusters. The PTP SHP-2, known to be enriched at the NMJ, associated and colocalized with MuSK, and agrin increased this interaction. Specific SHP-2 knockdown by RNA interference reduced the stability of AChR clusters in wild-type myotubes. Similarly, knockdown of SHP-2 in adult mouse soleus muscle by electroporation of RNA interference constructs caused disassembly of pretzel-shaped AChR-rich areas in vivo. Finally, we found that src-/-;fyn-/- myotubes contained elevated levels of SHP-2 protein. Conclusion Our data

  11. 77 FR 76380 - Partner's Distributive Share

    Science.gov (United States)

    2012-12-28

    ... the type of partner (for example, if the partner is a nonresident alien) and the type of income the partnership earns (for example, if the partnership earns effectively connected income). d. Deemed...

  12. Light 't Hooft Top Partners

    CERN Document Server

    Cacciapaglia, Giacomo

    2015-01-01

    Vector-like quarks, usually dubbed top partners, are a common presence in composite Higgs models. Being composite objects, their mass is expected to be of the order of their inverse size, that is the condensation scale of the new strong interactions. Light top partners, while not being a generic prediction, are however often considered in phenomenological models. We suggest that their lightness may be due to the matching of global 't Hooft anomalies of the underlying theory. We check this mechanism in explicit models showing that, in one case, composite fermions with the quantum numbers of the top quark obtain a mass which is controlled by a soft breaking term and can be made parametrically small.

  13. Actors', partners', and observers' perceptions of sarcasm.

    Science.gov (United States)

    Rockwell, P

    2000-10-01

    This study compared actors', partners', and observers' perceptions of the amount of sarcasm used by participants (n = 80) in videotaped conversations. Significant differences were found among perceptions of actors, partners, and observers. Of the three perspectives, actors perceived themselves as using the greatest amount of sarcasm, followed by partners' perceptions of actors. Observers perceived actors as using the least amount of sarcasm. Correlations conducted to assess whether partners and observers recognized actors' individual attempts at sarcasm during the conversations were generally low.

  14. Privacy against the business partner

    DEFF Research Database (Denmark)

    Jensen, Meiko; Gruschka, Nils

    2009-01-01

    For service-oriented business processes, an important security requirement is confidentiality of transmitted data. Here, existing Web Services security standards provide suitable solutions for single invocations, but fail to cover service composition scenarios properly, especially for securing...... business process data against partners. In this paper, we investigate the issues regarding the realization of process level confidentiality in WS-BPEL-based Web Service compositions....

  15. Positive illusions about one's partner's physical attractiveness

    NARCIS (Netherlands)

    Barelds-Dijkstra, Pieternel; Barelds, Dick P. H.

    2008-01-01

    This study examined couples' ratings of self and partner physical attractiveness. On the basis of the theory of positive illusions, it was expected that individuals would rate their partners as more attractive than their partners would rate themselves. Both members of 93 heterosexual couples, with a

  16. Living with heart failure : Partner perspectives

    NARCIS (Netherlands)

    Luttik, Marie Louise; Blaauwbroek, Arnarins; Dijker, Anton; Jaarsma, Tiny

    2007-01-01

    To preserve the supportive capabilities of partners of heart failure (HF) patients, it is necessary to gain insight in the experiences and potential needs of these partners. Thirteen partners of HF patients participated in semistructured interviews specifically focused on their experiences as a

  17. Positive illusions about one's partner's physical attractiveness

    NARCIS (Netherlands)

    Barelds-Dijkstra, Pieternel; Barelds, Dick P. H.

    2008-01-01

    This study examined couples' ratings of self and partner physical attractiveness. On the basis of the theory of positive illusions, it was expected that individuals would rate their partners as more attractive than their partners would rate themselves. Both members of 93 heterosexual couples, with a

  18. Positive illusions about one's partner's physical attractiveness

    NARCIS (Netherlands)

    Barelds-Dijkstra, Pieternel; Barelds, Dick P. H.

    This study examined couples' ratings of self and partner physical attractiveness. On the basis of the theory of positive illusions, it was expected that individuals would rate their partners as more attractive than their partners would rate themselves. Both members of 93 heterosexual couples, with a

  19. Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation.

    Science.gov (United States)

    Wang, Su Bin; Jang, Ji Yong; Chae, Yun Hee; Min, Ji Hyun; Baek, Jin Young; Kim, Myunghee; Park, Yunjeong; Hwang, Gwi Seo; Ryu, Jae-Sang; Chang, Tong-Shin

    2015-06-01

    Reactive oxygen species (ROS) generated upon collagen stimulation act as second messengers to propagate various platelet-activating events. Among the ROS-generating enzymes, NADPH oxidase (NOX) plays a prominent role in platelet activation. Thus, NOX has been suggested as a novel target for anti-platelet drug development. Although kaempferol has been identified as a NOX inhibitor, the influence of kaempferol on the activation of platelets and the underlying mechanism have never been investigated. Here, we studied the effects of kaempferol on NOX activation, ROS-dependent signaling pathways, and functional responses in collagen-stimulated platelets. Superoxide anion generation stimulated by collagen was significantly inhibited by kaempferol in a concentration-dependent manner. More importantly, kaempferol directly bound p47(phox), a major regulatory subunit of NOX, and significantly inhibited collagen-induced phosphorylation of p47(phox) and NOX activation. In accordance with the inhibition of NOX, ROS-dependent inactivation of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) was potently protected by kaempferol. Subsequently, the specific tyrosine phosphorylation of key components (Syk, Vav1, Btk, and PLCγ2) of collagen receptor signaling pathways was suppressed by kaempferol. Kaempferol also attenuated downstream responses, including cytosolic calcium elevation, P-selectin surface exposure, and integrin-αIIbβ3 activation. Ultimately, kaempferol inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. This study shows that kaempferol impairs collagen-induced platelet activation through inhibition of NOX-derived ROS production and subsequent oxidative inactivation of SHP-2. This effect suggests that kaempferol has therapeutic potential for the prevention and treatment of thrombovascular diseases.

  20. Partner Knowledge Awareness in Knowledge Communication: Learning by Adapting to the Partner

    Science.gov (United States)

    Dehler Zufferey, Jessica; Bodemer, Daniel; Buder, Jurgen; Hesse, Friedrich W.

    2011-01-01

    Awareness of the knowledge of learning partners is not always sufficiently available in collaborative learning scenarios. To compensate, the authors propose to provide collaborators with partner knowledge awareness by means of a visualization tool. Partner knowledge awareness can be used to adapt messages toward the partner. This study…

  1. Adult Attachment as a Risk Factor for Intimate Partner Violence : The "Mispairing" of Partners' Attachment Styles

    Science.gov (United States)

    Doumas, Diana M.; Pearson, Christine L.; Elgin, Jenna E.; McKinley, Lisa L.

    2008-01-01

    This study examined the relationship between intimate partner violence and adult attachment in a sample of 70 couples. The attachment style of each partner and the interaction of the partners' attachment styles were examined as predictors of intimate partner violence. Additional analyses were conducted to examine violence reciprocity and to…

  2. Main Features of the SHP Sector in China——Hangzhou Regional Centre (Asia-Pacific) for Small Hydro Power (HRC), Hangzhou, China.

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    1 An important sector in the hydropower industry Since the founding of the People's Republic of China in 1949, and particularly since the reform and opening up period, rural hydropower has witnessed swift development. Rural hydropower exploitation has been included in the plans for rural electrification development, and has become an important part of the water resources sector. A new SHP industryhas formed, combining social, economic and environmental benefits.

  3. The crystal structure of the AhRR/ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription.

    Science.gov (United States)

    Sakurai, Shunya; Shimizu, Toshiyuki; Ohto, Umeharu

    2017-09-13

    2,3,7,8-Tetrachlorodibenzo-p-dioxin and related compounds (TCDDs) are extraordinarily potent environmental toxic pollutants. Most of the TCDD toxicities are mediated by aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor belonging to the basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) family. Upon ligand binding, AhR forms a heterodimer with AhR nuclear translocator (ARNT) and induces the expression of genes involved in various biological responses. One of the genes induced by AhR encodes AhR repressor (AhRR), which also forms a heterodimer with ARNT and represses the activation of AhR-dependent transcription. The control of AhR activation is critical for managing AhR-mediated diseases, but the mechanisms by which AhRR represses AhR activation remain poorly understood, due to the lack of structural information. Here, we determined the structure of the AhRR/ARNT heterodimer by X-ray crystallography, which revealed an asymmetric intertwined domain organization presenting structural features that are both conserved and distinct among bHLH-PAS family members. The structures of AhRR/ARNT and AhR/ARNT were similar in the bHLH-PAS-A region, while the PAS-B of ARNT in the AhRR/ARNT complex exhibited a different domain arrangement in this family reported so far. The structure clearly disclosed that AhRR competitively represses AhR binding to ARNT and target DNA, and further suggested the existence of an AhRR/ARNT-specific repression mechanism. This study provides a structural basis for understanding the mechanism by which AhRR represses AhR-mediated gene transcription. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  4. Gain-of-function mutations of Ptpn11 (Shp2) cause aberrant mitosis and increase susceptibility to DNA damage-induced malignancies.

    Science.gov (United States)

    Liu, Xia; Zheng, Hong; Li, Xiaobo; Wang, Siying; Meyerson, Howard J; Yang, Wentian; Neel, Benjamin G; Qu, Cheng-Kui

    2016-01-26

    Gain-of-function (GOF) mutations of protein tyrosine phosphatase nonreceptor type 11 Ptpn11 (Shp2), a protein tyrosine phosphatase implicated in multiple cell signaling pathways, are associated with childhood leukemias and solid tumors. The underlying mechanisms are not fully understood. Here, we report that Ptpn11 GOF mutations disturb mitosis and cytokinesis, causing chromosomal instability and greatly increased susceptibility to DNA damage-induced malignancies. We find that Shp2 is distributed to the kinetochore, centrosome, spindle midzone, and midbody, all of which are known to play critical roles in chromosome segregation and cytokinesis. Mouse embryonic fibroblasts with Ptpn11 GOF mutations show a compromised mitotic checkpoint. Centrosome amplification and aberrant mitosis with misaligned or lagging chromosomes are significantly increased in Ptpn11-mutated mouse and patient cells. Abnormal cytokinesis is also markedly increased in these cells. Further mechanistic analyses reveal that GOF mutant Shp2 hyperactivates the Polo-like kinase 1 (Plk1) kinase by enhancing c-Src kinase-mediated tyrosine phosphorylation of Plk1. This study provides novel insights into the tumorigenesis associated with Ptpn11 GOF mutations and cautions that DNA-damaging treatments in Noonan syndrome patients with germ-line Ptpn11 GOF mutations could increase the risk of therapy-induced malignancies.

  5. To punish or to leave: distinct cognitive processes underlie partner control and partner choice behaviors.

    Directory of Open Access Journals (Sweden)

    Justin W Martin

    Full Text Available When a cooperative partner defects, at least two types of response are available: Punishment, aimed at modifying behavior, and ostracism, aimed at avoiding further social interaction with the partner. These options, termed partner control and partner choice, have been distinguished at behavioral and evolutionary levels. However, little work has compared their cognitive bases. Do these disparate behaviors depend on common processes of moral evaluation? Specifically, we assess whether they show identical patterns of dependence on two key dimensions of moral evaluation: A person's intentions, and the outcomes that they cause. We address this issue in a "trembling hand" economic game. In this game, an allocator divides a monetary stake between themselves and a responder based on a stochastic mechanism. This allows for dissociations between the allocator's intent and the actual outcome. Responders were either given the opportunity to punish or reward the allocator (partner control or to switch to a different partner for a subsequent round of play (partner choice. Our results suggest that partner control and partner choice behaviors are supported by distinct underlying cognitive processes: Partner control exhibits greater sensitivity to the outcomes a partner causes, while partner choice is influenced almost exclusively by a partner's intentions. This cognitive dissociation can be understood in light of the unique adaptive functions of partner control and partner choice.

  6. To punish or to leave: distinct cognitive processes underlie partner control and partner choice behaviors.

    Science.gov (United States)

    Martin, Justin W; Cushman, Fiery

    2015-01-01

    When a cooperative partner defects, at least two types of response are available: Punishment, aimed at modifying behavior, and ostracism, aimed at avoiding further social interaction with the partner. These options, termed partner control and partner choice, have been distinguished at behavioral and evolutionary levels. However, little work has compared their cognitive bases. Do these disparate behaviors depend on common processes of moral evaluation? Specifically, we assess whether they show identical patterns of dependence on two key dimensions of moral evaluation: A person's intentions, and the outcomes that they cause. We address this issue in a "trembling hand" economic game. In this game, an allocator divides a monetary stake between themselves and a responder based on a stochastic mechanism. This allows for dissociations between the allocator's intent and the actual outcome. Responders were either given the opportunity to punish or reward the allocator (partner control) or to switch to a different partner for a subsequent round of play (partner choice). Our results suggest that partner control and partner choice behaviors are supported by distinct underlying cognitive processes: Partner control exhibits greater sensitivity to the outcomes a partner causes, while partner choice is influenced almost exclusively by a partner's intentions. This cognitive dissociation can be understood in light of the unique adaptive functions of partner control and partner choice.

  7. Privacy against the business partner

    DEFF Research Database (Denmark)

    Jensen, Meiko; Gruschka, Nils

    2009-01-01

    For service-oriented business processes, an important security requirement is confidentiality of transmitted data. Here, existing Web Services security standards provide suitable solutions for single invocations, but fail to cover service composition scenarios properly, especially for securing bu...... business process data against partners. In this paper, we investigate the issues regarding the realization of process level confidentiality in WS-BPEL-based Web Service compositions. © 2009 IEEE.......For service-oriented business processes, an important security requirement is confidentiality of transmitted data. Here, existing Web Services security standards provide suitable solutions for single invocations, but fail to cover service composition scenarios properly, especially for securing...

  8. Semiconductor foundry, lithography, and partners

    Science.gov (United States)

    Lin, Burn J.

    2002-07-01

    The semiconductor foundry took off in 1990 with an annual capacity of less than 0.1M 8-inch-equivalent wafers at the 2-mm node. In 2000, the annual capacity rose to more than 10M. Initially, the technology practiced at foundries was 1 to 2 generations behind that at integrated device manufacturers (IDMs). Presently, the progress in 0.13-mm manufacturing goes hand-in-hand with any of the IDMs. There is a two-order of magnitude rise in output and the progress of technology development outpaces IDMs. What are the reasons of the success? Is it possible to sustain the pace? This paper shows the quick rise of foundries in capacity, sales, and market share. It discusses the their uniqueness which gives rise to advantages in conjunction with challenges. It also shows the role foundries take with their customer partners and supplier partners, their mutual dependencies, as well as expectations. What role then does lithography play in the foundries? What are the lithographic challenges to sustain the pace of technology? The experience of technology development and transfer, at one of the major foundries, is used to illustrate the difficulties and progresses made. Looking into the future, as semiconductor manufacturing will become even more expensive and capital investment more prohibitive, we will make an attempt to suggest possible solutions.

  9. Collaborative vaccine development: partnering pays.

    Science.gov (United States)

    Ramachandra, Rangappa

    2008-01-01

    Vaccine development, supported by infusions of public and private venture capital, is re-entering a golden age as one of the fastest growing sectors in the life-sciences industry. Demand is driven by great unmet need in underdeveloped countries, increased resistance to current treatments, bioterrorism, and for prevention indications in travelers, pediatric, and adult diseases. Production systems are becoming less reliant on processes such as egg-based manufacturing, while new processes can help to optimize vaccines. Expeditious development hinges on efficient study conduct, which is greatly enhanced through research partnerships with specialized contract research organizations (CROs) that are licensed and knowledgeable in the intricacies of immunology and with the technologic and scientific foundation to support changing timelines and strategies inherent to vaccine development. The CRO often brings a more objective assessment for probability of success and may offer alternative development pathways. Vaccine developers are afforded more flexibility and are free to focus on innovation and internal core competencies. Functions readily outsourced to a competent partner include animal model development, safety and efficacy studies, immunotoxicity and immunogenicity, dose response studies, and stability and potency testing. These functions capitalize on the CRO partner's regulatory and scientific talent and expertise, and reduce infrastructure expenses for the vaccine developer. Successful partnerships result in development efficiencies, elimination or reduced redundancies, and improved time to market. Keys to success include honest communications, transparency, and flexibility.

  10. Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of the yeast RNase MRP and RNase P RNAs.

    Science.gov (United States)

    Perederina, Anna; Esakova, Olga; Koc, Hasan; Schmitt, Mark E; Krasilnikov, Andrey S

    2007-10-01

    Pop6 and Pop7 are protein subunits of Saccharomyces cerevisiae RNase MRP and RNase P. Here we show that bacterially expressed Pop6 and Pop7 form a soluble heterodimer that binds the RNA components of both RNase MRP and RNase P. Footprint analysis of the interaction between the Pop6/7 heterodimer and the RNase MRP RNA, combined with gel mobility assays, demonstrates that the Pop6/7 complex binds to a conserved region of the P3 domain. Binding of these proteins to the MRP RNA leads to local rearrangement in the structure of the P3 loop and suggests that direct interaction of the Pop6/7 complex with the P3 domain of the RNA components of RNases MRP and P may mediate binding of other protein components. These results suggest a role for a key element in the RNase MRP and RNase P RNAs in protein binding, and demonstrate the feasibility of directly studying RNA-protein interactions in the eukaryotic RNases MRP and P complexes.

  11. Effect of NADPH oxidase inhibitor-apocynin on the expression of Src homology-2 domain-containing phosphatase-1 (SHP-1 exposed renal ischemia/reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Zhiming Li

    2015-01-01

    Full Text Available This study was designed to evaluate whether NADPH oxidase inhibitor (apocynin preconditioning induces expression of Src homology-2 domain-containing phosphatase-1 (SHP-1 to protect against renal ischemia/reperfusion (I/R injury (RI/RI in rats. Rats were pretreated with 50 mg/kg apocynin, then subjected to 45 min ischemia and 24 h reperfusion. The results indicated that apocynin preconditioning improved the recovery of renal function and nitroso-redox balance, reduced oxidative stress injury and inflammation damage, and upregulated expression of SHP-1 as compared to RI/RI group. Therefore our study demonstrated that apocynin preconditioning provided a protection to the kidney against I/R injury in rats partially through inducing expression of SHP-1.

  12. Significance study of SHP2 Expression in brain tissue of bacterial meningitis rat%细菌性脑膜炎大鼠脑组织中蛋白络氨酸磷酸酶表达及意义

    Institute of Scientific and Technical Information of China (English)

    王强; 谷席娟

    2015-01-01

    目的:研究细菌性脑膜炎中蛋白络氨酸磷酸酶(SHP2)的表达意义。方法依据随机数字表法将90只大鼠分为脑膜炎组(72只)和健康对照组(18只)两组,用反转录(RT)-PCR、Western印迹法、免疫组织化法对脑膜炎组和健康对照组大鼠不同时间点脑组织SHP2表达进行检测,然后对SHP2蛋白表达和肿瘤坏死因子-α(TNF-α)、白细胞(WBC)计数的关系进行观察分析。结果脑膜炎组大鼠皮层SHP2 mRNA表达(0.035±0.020)、(0.200±0.049)、(0.129±0.032)、(0.057±0.039)均明显比健康对照组(0.031±0.028)高(F=12.74,P<0.05);第三脑室周围 SHP2阳性染色细胞明显比健康对照组多(χ2=5.02,P<0.05);皮层SHP2蛋白表达与脑脊液TNF-α浓度、WBC计数的相关系数分别为0.08(P>0.05)和0.77(t=4.303,P<0.05)。结论细菌性脑膜炎的病理生理过程有中SHP2参与,主要作用可能是抑制炎症、修复炎性反应,可作为病情变化的参考指标。%Objective To study the significance of protein tyrosine phosphatase (SHP2)expression in bac-terial meningitis.Methods 90 rats were divided into meningitis group (72)and healthy controls (18)two groups based on the random number table,The SHP2 expression in rat brain tissue at different time points of meningitis group and healthy control group were tested by reverse transcription (RT)a PCR,Western blotting,immunohistochemical methods,then the relationship between SHP2 protein expression and tumor necrosis factor-α(TNF-α),white blood cell (WBC)counts were observed and analyzed.Results The cortical SHP2 mRNA expression of meningitis rat in-cluding (0.035 ±0.020),(0.200 ±0.049),(0.129 ±0.032)and (0.057 ±0.039),were significantly higher than those of the healthy control group (0.031 ±0.028)(F=12.74,P0.05)and 0.77 (t=4.303,P<0.05).Conclusion SHP2 participates in pathophysiology of

  13. RISK FACTORS FOR INTIMATE PARTNER VIOLENCE

    OpenAIRE

    Ceren Atakay

    2014-01-01

    Intimate partner violence has kept being one of the major societal issues in our country over the past year. It is absolutely necessary to intervene in this substantially psychological issue multi-directionally. In order to intervene in the problem from psychological aspect, it is important to estimate and interpret the risk factors for intimate partner violence. Therefore in the current study, ‘I-cube theory’ which is about the risk factors for intimate partner violence has been explained fi...

  14. Native Folding of a Recombinant gpE1/gpE2 Heterodimer Vaccine Antigen from a Precursor Protein Fused with Fc IgG.

    Science.gov (United States)

    Logan, Michael; Law, John; Wong, Jason Alexander Ji-Xhin; Hockman, Darren; Landi, Amir; Chen, Chao; Crawford, Kevin; Kundu, Juthika; Baldwin, Lesley; Johnson, Janelle; Dahiya, Anita; LaChance, Gerald; Marcotrigiano, Joseph; Law, Mansun; Foung, Steven; Tyrrell, Lorne; Houghton, Michael

    2017-01-01

    A recombinant strain HCV1 (hepatitis C virus [HCV] genotype 1a) gpE1/gpE2 (E1E2) vaccine candidate was previously shown by our group to protect chimpanzees and generate broad cross-neutralizing antibodies in animals and humans. In addition, recent independent studies have highlighted the importance of conserved neutralizing epitopes in HCV vaccine development that map to antigenic clusters in E2 or the E1E2 heterodimer. E1E2 can be purified using Galanthis nivalis lectin agarose (GNA), but this technique is suboptimal for global production. Our goal was to investigate a high-affinity and scalable method for isolating E1E2. We generated an Fc tag-derived (Fc-d) E1E2 that was selectively captured by protein G Sepharose, with the tag being removed subsequently using PreScission protease. Surprisingly, despite the presence of the large Fc tag, Fc-d E1E2 formed heterodimers similar to those formed by GNA-purified wild-type (WT) E1E2 and exhibited nearly identical binding profiles to HCV monoclonal antibodies that target conserved neutralizing epitopes in E2 (HC33.4, HC84.26, and AR3B) and the E1E2 heterodimer (AR4A and AR5A). Antisera from immunized mice showed that Fc-d E1E2 elicited anti-E2 antibody titers and neutralization of HCV pseudotype viruses similar to those with WT E1E2. Competition enzyme-linked immunosorbent assays (ELISAs) showed that antisera from immunized mice inhibited monoclonal antibody binding to neutralizing epitopes. Antisera from Fc-d E1E2-immunized mice exhibited stronger competition for AR3B and AR5A than the WT, whereas the levels of competition for HC84.26 and AR4A were similar. We anticipate that Fc-d E1E2 will provide a scalable purification and manufacturing process using protein A/G-based chromatography.

  15. The isopenicillin N acyltransferases of Aspergillus nidulans and Penicillium chrysogenum differ in their ability to maintain the 40-kDa alphabeta heterodimer in an undissociated form.

    Science.gov (United States)

    Fernández, Francisco J; Cardoza, Rosa E; Montenegro, Eduardo; Velasco, Javier; Gutiérrez, Santiago; Martín, Juan F

    2003-05-01

    The isopenicillin N acyltransferases (IATs) of Aspergillus nidulans and Penicillium chrysogenum differed in their ability to maintain the 40-kDa proacyltransferase alphabeta heterodimer in an undissociated form. The native A. nidulans IAT exhibited a molecular mass of 40 kDa by gel filtration. The P. chrysogenum IAT showed a molecular mass of 29 kDa by gel filtration (corresponding to the beta subunit of the enzyme) but the undissociated 40-kDa heterodimer was never observed even in crude extracts. Heterologous expression experiments showed that the chromatographic behaviour of IAT was determined by the source of the penDE gene used in the expression experiments and not by the host itself. When the penDE gene of A. nidulans was expressed in P. chrysogenum npe6 and npe8 or in Acremonium chrysogenum, the IAT formed had a molecular mass of 40 kDa. On the other hand, when the penDE gene originating from P. chrysogenum was expressed in A. chrysogenum, the active IAT had a molecular mass of 29 kDa. The intronless form of the penDE gene cloned from an A. nidulans cDNA library and overexpressed in Escherichia coli formed the enzymatically active 40-kDa proIAT, which was not self-processed as shown by immunoblotting with antibodies to IAT. This 40-kDa protein remained unprocessed even when treated with A. nidulans crude extract. In contrast, the P. chrysogenum penDE intronless gene cloned from a cDNA library was expressed in E. coli, and the IAT was self-processed efficiently into its alpha (29 kDa) and beta (11 kDa) subunits. It is concluded that P. chrysogenum and A. nidulans differ in their ability to self-process their respective proIAT protein and to maintain the alpha and beta subunits as an undissociated heterodimer, probably because of the amino-acid sequence differences in the proIAT which affect the autocatalytic activity.

  16. Telling Your Partner You Have an STD

    Science.gov (United States)

    ... offer information about the STD and its symptoms. Give your partner time to take in the information. If you and your partner ... your doctor prescribes. You also might need to take medicine if you have an ... A doctor or a health clinic can give advice on how to lower the chance of ...

  17. Increasing HIV testing among male partners

    NARCIS (Netherlands)

    Orne-Gliemann, Joanna; Balestre, Eric; Tchendjou, Patrice; Miric, Marija; Darak, Shrinivas; Butsashvili, Maia; Perez-Then, Eddy; Eboko, Fred; Plazy, Melanie; Kulkarni, Sanjeevani; du Lou, Annabel Desgrees; Dabis, Francois

    2013-01-01

    Objective: Couple-oriented posttest HIV counselling (COC) provides pregnant women with tools and strategies to invite her partner to HIV counselling and testing. We conducted a randomized trial of the efficacy of COC on partner HIV testing in low/medium HIV prevalence settings (Cameroon, Dominican

  18. Increasing HIV testing among male partners

    NARCIS (Netherlands)

    Orne-Gliemann, Joanna; Balestre, Eric; Tchendjou, Patrice; Miric, Marija; Darak, Shrinivas; Butsashvili, Maia; Perez-Then, Eddy; Eboko, Fred; Plazy, Melanie; Kulkarni, Sanjeevani; du Lou, Annabel Desgrees; Dabis, Francois

    2013-01-01

    Objective: Couple-oriented posttest HIV counselling (COC) provides pregnant women with tools and strategies to invite her partner to HIV counselling and testing. We conducted a randomized trial of the efficacy of COC on partner HIV testing in low/medium HIV prevalence settings (Cameroon, Dominican R

  19. Intimate Partner Violence in Older Women

    Science.gov (United States)

    Bonomi, Amy E.; Anderson, Melissa L.; Reid, Robert J.; Carrell, David; Fishman, Paul A.; Rivara, Frederick P.; Thompson, Robert S.

    2007-01-01

    Purpose: We describe the prevalence, types, duration, frequency, and severity of intimate partner violence ("partner violence") in older women. Design and Methods: We randomly sampled a total of 370 English-speaking women (65 years of age and older) from a health care system to participate in a cross-sectional telephone interview. Using 5…

  20. Sexual Experiences of Men with Incontinent Partners

    NARCIS (Netherlands)

    Bekker, Milou D.; Beck, Jacky J. H.; Putter, Hein; van Driel, Mels F.; Pelger, Rob C. M.; Weijmar Schultz, Willibrordus; Nijeholt, Guus A. B. Lycklama A.; Elzevier, Henk W.

    2010-01-01

    Introduction. Several studies show that urinary incontinence (UI) impairs women's sexual functioning and sexual satisfaction. However, there is no scientific knowledge about the effects of UI on sexual functioning of the male partners. Aim. To analyze sexual functioning of the male partners of femal

  1. Facing the partner influences exchanges in force

    Science.gov (United States)

    Takagi, Atsushi; Bagnato, Carlo; Burdet, Etienne

    2016-01-01

    Many studies in psychology have documented how the behaviour of verbally communicating pairs is affected by social factors such as the partner’s gaze. However, few studies have examined whether physically interacting pairs are influenced by social factors. Here, we asked two partners to exchange forces with one another, where the goal was to accurately replicate the force back onto the other. We first measured an individual’s accuracy in reproducing a force from a robot. We then tested pairs who knowingly exchanged forces whilst separated by a curtain. These separated pairs exchanged forces as two independent individuals would, hence the force reproduction accuracy of partners is not affected by knowingly reproducing a force onto a nonvisible partner. On the other hand, pairs who exchanged forces whilst facing one another consistently under-reproduced the partner’s force in comparison to separated partners. Thus, the force reproduction accuracy of subjects is strongly biased by facing a partner. PMID:27739492

  2. Advice from working women with retired partners.

    Science.gov (United States)

    Cooley, Eileen L; Adorno, Gail

    2016-01-01

    in the 21st century, as more women are employed full-time and couples increasingly share egalitarian values, more women continue employment after their partners have voluntarily retired. However, we know very little about the experiences of this growing population of women. We asked working women with retired partners to share their advice for other women who may face this developmental transition. Open-ended responses from 97 women were analyzed to identify pertinent issues and themes. Four primary content areas were identified: time management, division of household labor, financial planning, and communication. Communication between partners was both a topic of concern as well as the solution suggested to resolve conflicts or differences that may arise when women live with a retired partner. It is expected that future changes in the workforce and improvements in the gender balance within relationships will continue to impact experiences for working women with retired partners.

  3. Catastrophizing and perceived partner responses to pain.

    Science.gov (United States)

    Boothby, Jennifer L; Thorn, Beverly E; Overduin, Lorraine Y; Ward, L Charles

    2004-06-01

    This study examined the relationship between catastrophizing and patient-perceived partner responses to pain behaviors. The Catastrophizing subscale of the Cognitive Coping Strategy Inventory and the West Haven-Yale Multidimensional Pain Inventory were completed by 62 adult chronic pain patients. Consistent with past research, catastrophizing and patient-perceived solicitous partner behaviors were positively correlated with negative pain outcomes. The communal coping theory of catastrophizing suggests that catastrophizing might be undertaken to solicit support and empathy from others. However, catastrophizing was not related to perceived solicitous partner behavior in this study. Rather, catastrophizing was associated with perceived punishing partner responses. Implications are that catastrophizing and perceived solicitous partner behaviors are independently associated with pain and that catastrophizing may not be reinforced by empathy from significant others.

  4. Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive PIGF-1/VEGF heterodimers

    DEFF Research Database (Denmark)

    Eriksson, A.; Cao, R.; Pawliuk, R.

    2002-01-01

    , the biological function of its related homolog, placenta growth factor (PlGF), is poorly understood. Here we demonstrate that PlGF-1, an alternatively spliced isoform of the PlGF gene, antagonizes VEGF-induced angiogenesis when both factors are coexpressed in murine fibrosarcoma cells. Overexpression of PlGF-1...... in VEGF-producing tumor cells results in the formation of PlGF-1/VEGF heterodimers and depletion of the majority of mouse VEGF homodimers. The heterodimeric form of PlGF-1/VEGF lacks the ability to induce angiogenesis in vitro and in vivo. Similarly, PlGF-1/VEGF fails to activate the VEGFR-2-mediated...... signaling pathways. Further, PlGF-1 inhibits the growth of a murine fibrosarcoma by approximately 90% when PlGF-1-expressing tumor cells are implanted in syngeneic mice. In contrast, overexpression of human VEGF in murine tumor cells causes accelerated and exponential growth of primary fibrosarcomas...

  5. Synthesis and anti-HIV activity of some [Nucleoside Reverse Transcriptase Inhibitor]-C5'-linker-[Integrase Inhibitor] heterodimers as inhibitors of HIV replication.

    Science.gov (United States)

    Sugeac, Elena; Fossey, Christine; Ladurée, Daniel; Schmidt, Sylvie; Laumond, Geraldine; Aubertin, Anne-Marie

    2004-12-01

    Selected for their expected ability to inhibit HIV replication, a series of eight heterodimers containing a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and an Integrase Inhibitor (INI), bound by a linker, were designed and synthesized. For the NRTIs, d4U, d2U and d4T were chosen. For the INIs, 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid (6) and 4-(3,5-dibenzyloxyphenyl)-2,4-dioxobutyric acid (9) (belonging to the beta-diketo acids class) were chosen. The conjugation of the two different inhibitors (NRTI and INI) was performed using an amino acid (glycine or beta-alanine) as a cleavable linker.

  6. HMO partnering: the provider dilemma.

    Science.gov (United States)

    Ayers, J; Benson, L; Bonhag, R

    1996-10-01

    While the growth of HMOs has slowed patient visits to doctors, it also has created a deluge of press clippings. On July 16, 1996, three articles on the subject appeared in the Wall Street Journal, front section. The headlines painted a vivid picture of the forces acting on HMOs and providers alike (Figure 1). The articles portended more change for healthcare. The "shake-out," a term applied to industries in serious transformation, brings shedding of excess capacity and loss of jobs and income. Providers, in particular, find themselves in a difficult dilemma. They must not only cut costs as reimbursement drops, but also retain patients with good outcomes and high quality service. Patient retention means keeping the individual patient from switching to another provider and keeping the insurer's group of patients as an authorized provider for that insurer. The relationship between provider and HMO lies at the heart of the provider dilemma. The HMO structure, which shifts financial risk for care, is quickly setting the standard, for healthcare pricing, medical standards, and management practices. Understanding and responding to HMO needs are vital to competitive advantage and survival. The article discusses the inherent dilemma of HMO and provider partnering and suggests provider responses.

  7. BMP-2/6 heterodimer is more effective than BMP-2 or BMP-6 homodimers as inductor of differentiation of human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Elvira Valera

    Full Text Available BACKGROUND: Bone Morphogenetic Protein (BMP signaling pathways are involved in differentiation of stem cells into diverse cell types, and thus BMPs can be used as main guidance molecules for in vitro differentiation of human stem cells. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the ability for inducing differentiation of the heterodimer BMP-2/BMP-6 (BMP-2/6 compared to the homodimers BMP-2 or BMP-6, using human embryonic stem (hES cells H9 as model system. When incubated in a medium with high concentration of basic fibroblastic growth factor (FGF2, 100 ng/ml of human recombinant BMPs induced morphological changes and differentiation of hES cells in 24 to 48 hours. After 5 days, expression of differentiation markers was induced and quantified by quantitative PCR (qPCR and flow cytometry. BMP-2/6 exhibited stronger activity for the induction of the expression of trophectodermal (CDX2 and endodermal (SOX17, GATA4, AFP markers than BMP-2 or BMP-6 homodimers. BMP-2/6 also induced the expression of BMPR2 gene more effectively than BMP-2 or BMP-6 when used at the same concentration and time. Moreover, the percentage of cells expressing the surface endodermal marker CXCR4 was also increased for the heterodimer when compared to both homodimers. BMP-2/6 was a more potent activator of Smad-dependent (SMAD1/5 and Smad-independent signaling (mitogen-activated protein kinases ERK and p38 than BMP-2 and BMP-6, and the activation of these pathways might play a role in its increased potency for inducing hES cell differentiation. CONCLUSIONS/SIGNIFICANCE: Therefore, we conclude that BMP-2/6 is more potent than BMP-2 or BMP-6 for inducing differentiation of hES cells, and it can be used as a more powerful substitute of these BMPs in in vitro differentiation guidance.

  8. BMP-2/6 heterodimer is more effective than BMP-2 or BMP-6 homodimers as inductor of differentiation of human embryonic stem cells.

    Science.gov (United States)

    Valera, Elvira; Isaacs, Michael J; Kawakami, Yasuhiko; Izpisúa Belmonte, Juan Carlos; Choe, Senyon

    2010-06-17

    Bone Morphogenetic Protein (BMP) signaling pathways are involved in differentiation of stem cells into diverse cell types, and thus BMPs can be used as main guidance molecules for in vitro differentiation of human stem cells. We have analyzed the ability for inducing differentiation of the heterodimer BMP-2/BMP-6 (BMP-2/6) compared to the homodimers BMP-2 or BMP-6, using human embryonic stem (hES) cells H9 as model system. When incubated in a medium with high concentration of basic fibroblastic growth factor (FGF2), 100 ng/ml of human recombinant BMPs induced morphological changes and differentiation of hES cells in 24 to 48 hours. After 5 days, expression of differentiation markers was induced and quantified by quantitative PCR (qPCR) and flow cytometry. BMP-2/6 exhibited stronger activity for the induction of the expression of trophectodermal (CDX2) and endodermal (SOX17, GATA4, AFP) markers than BMP-2 or BMP-6 homodimers. BMP-2/6 also induced the expression of BMPR2 gene more effectively than BMP-2 or BMP-6 when used at the same concentration and time. Moreover, the percentage of cells expressing the surface endodermal marker CXCR4 was also increased for the heterodimer when compared to both homodimers. BMP-2/6 was a more potent activator of Smad-dependent (SMAD1/5) and Smad-independent signaling (mitogen-activated protein kinases ERK and p38) than BMP-2 and BMP-6, and the activation of these pathways might play a role in its increased potency for inducing hES cell differentiation. Therefore, we conclude that BMP-2/6 is more potent than BMP-2 or BMP-6 for inducing differentiation of hES cells, and it can be used as a more powerful substitute of these BMPs in in vitro differentiation guidance.

  9. Husband/Partner Intoxication and Intimate Partner Violence Against Women in the Philippines.

    Science.gov (United States)

    Kerridge, Bradley T; Tran, Phu

    2016-09-01

    This study examined husband/partner intoxication and experience with physical, sexual, and emotional intimate partner violence against women (IPVAW) using data derived from a nationally representative survey conducted in the Philippines in 2013. Multivariate logistic regression analyses were used to examine the association between intoxication and 3 different types of intimate partner violence against women. Multinomial logistic regression was used to examine intoxication and severity of violence. In this sample, 28.8% of women reported experiencing any form of intimate partner violence and 92.9% of women reported their partner being intoxicated at least sometimes. Intoxication was significantly associated with all 3 types of intimate partner violence, while the odds of experiencing one form of IPVAW versus no form of IPVAW and 2 forms of IPVAW versus 1 form of IPVAW was greater among women reporting frequency of husband/partner intoxication as often.

  10. Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase

    Directory of Open Access Journals (Sweden)

    Seung Ho Baek

    2017-02-01

    Full Text Available Ginkgolic acid C 17:1 (GAC 17:1 extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s through modulation of several molecular targets in tumor cells, however the detailed mechanism(s of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3 is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy. We determined the anti-tumor mechanism of GAC 17:1 with respect to its effect on STAT3 signaling pathway in multiple myeloma cell lines. We found that GAC 17:1 can inhibit constitutive activation of STAT3 through the abrogation of upstream JAK2, Src but not of JAK1 kinases in U266 cells and also found that GAC can suppress IL-6-induced STAT3 phosphorylation in MM.1S cells. Treatment of protein tyrosine phosphatase (PTP inhibitor blocked suppression of STAT3 phosphorylation by GAC 17:1, thereby indicating a critical role for a PTP. We also demonstrate that GAC 17:1 can induce the substantial expression of PTEN and SHP-1 at both protein and mRNA level. Further, deletion of PTEN and SHP-1 genes by siRNA can repress the induction of PTEN and SHP-1, as well as abolished the inhibitory effect of drug on STAT3 phosphorylation. GAC 17:1 down-regulated the expression of STAT3 regulated gene products and induced apoptosis of tumor cells. Overall, GAC 17:1 was found to abrogate STAT3 signaling pathway and thus exert its anticancer effects against multiple myeloma cells.

  11. SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Shu-Jing Yu; Jie-Kai Yu; Wei-Ting Ge; Han-Guang Hu; Ying Yuan; Shu Zheng

    2011-01-01

    AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients.METHODS: One hundred and fifty-six CRC patients were followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was per-formed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers.RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. Ac-cording to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 ex-pression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.

  12. PD-L1 regulates the Tregs’ capacity to repress shock/sepsis induced indirect lung injury (iALI) by recruiting phosphatase SHP-1

    Science.gov (United States)

    Tang, Lunxian; Bai, Jianwen; Chung, Chun-Shiang; Lomas–Neira, Joanne; Chen, Yaping; Huang, Xin; Ayala, Alfred

    2014-01-01

    We recently reported that adoptively transferred (AT) exogenous CD4+CD25+ regulatory T cells (Tregs) to wild type (WT) mice can directly act to repress shock/sepsis induced experimental iALI and this is mediated in part by programmed cell death receptor 1 (PD-1). In this study, we further determine whether recipient mouse lacking PD-L1, one of the primary ligands for PD-1, contributes to the manipulation of the Tregs’ capacity to repress lung injury. To do this, Tregs isolated from the spleen of WT mice were AT into PD-L1−/− mice subjected to hemorrhagic shock [Hem] and subsequent to cecal ligation and puncture (CLP) to induce iALI. Samples were collected for analyses 24 hours after CLP. We found that in PD-L1−/− recipient mice, AT WT-Tregs lost the ability to reverse the development of iALI seen in WT recipient mice (i.e., no reduction of lung injury indices assessed by histology and vascular leakage; failure to decrease the lung neutrophil influx [MPO activity] or the rise in lung apoptosis [caspase 3 activity]). Also a significant increase of interlukin-1β (IL-1β) and keratinocyte-derived chemokine (KC), but no changes in IL-6, IL-10 and IL-17A levels in lung tissues were seen in these mice compared with iALI mice without AT of Tregs. Furthermore, we noted that the lung tissue tyrosine phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP-1), but not SHP-2, was activated with the AT of Tregs in PD-L1−/− iALI mice. Finally, through local depletion of CD4+ T cells or CD25+ (Tregs) in the lung, prior to inducing iALI, we found that SHP-1 activation was associated with the loss of Tregs’ protective effects in vivo. Collectively, our data reveal that PD-L1 is a critical modulator of Treg’s ability to suppress iALI and this appears to involve SHP-1 activation. PMID:25057927

  13. Partners in Leadership for Pearl River

    Science.gov (United States)

    2007-01-01

    Members of the 2007 class of Partners in Leadership toured NASA Stennis Space Center in Hancock County, Miss., on Jan. 11. They visited the center's B Test Stand, part of the center's rocket engine test complex. The Partners in Leadership training program is designed to teach Pearl River County leaders about their county's government, economic development, health and human services, history and arts, environment and education during a 10-month period. The program, sponsored by the Partners for Pearl River County, helps fulfill the mission of the economic and community development agency.

  14. Inferring interaction partners from protein sequences

    CERN Document Server

    Bitbol, Anne-Florence; Colwell, Lucy J; Wingreen, Ned S

    2016-01-01

    Specific protein-protein interactions are crucial in the cell, both to ensure the formation and stability of multi-protein complexes, and to enable signal transduction in various pathways. Functional interactions between proteins result in coevolution between the interaction partners. Hence, the sequences of interacting partners are correlated. Here we exploit these correlations to accurately identify which proteins are specific interaction partners from sequence data alone. Our general approach, which employs a pairwise maximum entropy model to infer direct couplings between residues, has been successfully used to predict the three-dimensional structures of proteins from sequences. Building on this approach, we introduce an iterative algorithm to predict specific interaction partners from among the members of two protein families. We assess the algorithm's performance on histidine kinases and response regulators from bacterial two-component signaling systems. The algorithm proves successful without any a pri...

  15. Gender symmetry, sexism, and intimate partner violence.

    Science.gov (United States)

    Allen, Christopher T; Swan, Suzanne C; Raghavan, Chitra

    2009-11-01

    This study of a predominantly Hispanic sample of 92 male and 140 female college students examines both gender symmetry in intimate partner violence (IPV) and inconsistent relationships found in previous studies between sexist attitudes and IPV. Results indicate that although comparable numbers of men and women perpetrate and are victimized in their relationships with intimate partners, the path models suggest that women's violence tends to be in reaction to male violence, whereas men tend to initiate violence and then their partners respond with violence. Benevolent sexism was shown to have a protective effect against men's violence toward partners. Findings highlight the importance of studying women's violence not only in the context of men's violence but also within a broader sociocultural context.

  16. Whom to Choose as License Partner?

    DEFF Research Database (Denmark)

    Laursen, Keld; Reichstein, Toke; Trombini, Giulia

    2013-01-01

    between technology and market forces: if partners are market distant, the likelihood of technology license contractual partnership decreases with partners’ technological distance. Using data on the formation of license partnerships in the global biopharmaceutical industry over the period 1994...

  17. Featured Partner: Saddle Creek Logistics Services

    Science.gov (United States)

    This EPA fact sheet spotlights Saddle Creek Logistics as a SmartWay partner committed to sustainability in reducing greenhouse gas emissions and air pollution caused by freight transportation, partly by growing its compressed natural gas (CNG) vehicles for

  18. MPS/CAS Partner Group on Cosmology

    Institute of Scientific and Technical Information of China (English)

    Jing Yipeng; Gerhard B(o)rner

    2004-01-01

    @@ The Partner Group does research in cosmology, focussing on the quantitative modeling of the structure and evolution of galaxies and galaxy clusters, the pattern of galaxies and of larger structures.

  19. ORIGINAL ARTICLES Intimate partner violence, health behaviours ...

    African Journals Online (AJOL)

    country study on IPV and women's physical and mental health found a significant association ... heart attack and high blood pressure reached near-significance. Conclusions. Partner ..... These activities were supported by the. United States ...

  20. Inter-ethnic Marriage and Partner Satisfaction

    OpenAIRE

    Sinning, Mathias; Worner, Shane

    2010-01-01

    This paper investigates immigrant assortative mating and relationship satisfaction. Using a modified random effects ordered probit model, the paper demonstrates that spouses of mixed couples are significantly less satisfied with their partner than nativeonly and foreign-only couples. Dieses Papier untersucht die Wahl des Ehepartners und die Zufriedenheit mit dem Partner. Unter Verwendung eines modifizierten Random Effects Ordered Probit-Modells zeigt das Papier, dass Ehepartner gemischter ...

  1. Perceptions of the physical attractiveness of the self, current romantic partners, and former partners.

    Science.gov (United States)

    Swami, Viren; Allum, Lucy

    2012-02-01

    This study examined ratings of physical attractiveness of the self and former and current partners. A total of 304 participants completed measures of attractiveness, relationship satisfaction, love dimensions, self-esteem and sociosexual orientation. Consistent with previous work, results showed that participants rated their current partners as more attractive than themselves and their former partners. However, results also showed that former partners were rated as more attractive than the self on a number of bodily characteristics. Finally, results showed that ratings of former partner physical attractiveness were associated with passion for the former partner, self-esteem, sociosexual orientation, and attributions of relationship termination. These results are discussed in relation to the available literature on positive illusions in intimate relationships.

  2. Partner choice creates fairness in humans.

    Science.gov (United States)

    Debove, Stéphane; André, Jean-Baptiste; Baumard, Nicolas

    2015-06-07

    Many studies demonstrate that partner choice has played an important role in the evolution of human cooperation, but little work has tested its impact on the evolution of human fairness. In experiments involving divisions of money, people become either over-generous or over-selfish when they are in competition to be chosen as cooperative partners. Hence, it is difficult to see how partner choice could result in the evolution of fair, equal divisions. Here, we show that this puzzle can be solved if we consider the outside options on which partner choice operates. We conduct a behavioural experiment, run agent-based simulations and analyse a game-theoretic model to understand how outside options affect partner choice and fairness. All support the conclusion that partner choice leads to fairness only when individuals have equal outside options. We discuss how this condition has been met in our evolutionary history, and the implications of these findings for our understanding of other aspects of fairness less specific than preferences for equal divisions of resources. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  3. Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown

    Science.gov (United States)

    Srikar, R.; Suresh, Dhananjay; Zambre, Ajit; Taylor, Kristen; Chapman, Sarah; Leevy, Matthew; Upendran, Anandhi; Kannan, Raghuraman

    2016-08-01

    A tri-block nanoparticle (TBN) comprising of an enzymatically cleavable porous gelatin nanocore encapsulated with gefitinib (tyrosine kinase inhibitor (TKI)) and surface functionalized with cetuximab-siRNA conjugate has been synthesized. Targeted delivery of siRNA to undruggable KRAS mutated non-small cell lung cancer cells would sensitize the cells to TKI drugs and offers an efficient therapy for treating cancer; however, efficient delivery of siRNA and releasing it in cytoplasm remains a major challenge. We have shown TBN can efficiently deliver siRNA to cytoplasm of KRAS mutant H23 Non-Small Cell Lung Cancer (NSCLC) cells for oncogene knockdown; subsequently, sensitizing it to TKI. In the absence of TKI, the nanoparticle showed minimal toxicity suggesting that the cells adapt a parallel GAB1 mediated survival pathway. In H23 cells, activated ERK results in phosphorylation of GAB1 on serine and threonine residues to form GAB1-p85 PI3K complex. In the absence of TKI, knocking down the oncogene dephosphorylated ERK, and negated the complex formation. This event led to tyrosine phosphorylation at Tyr627 domain of GAB1 that regulated EGFR signaling by recruiting SHP2. In the presence of TKI, GAB1-SHP2 dissociation occurs, leading to cell death. The outcome of this study provides a promising platform for treating NSCLC patients harboring KRAS mutation.

  4. IVIg-mediated amelioration of murine ITP via FcgammaRIIB is independent of SHIP1, SHP-1, and Btk activity.

    Science.gov (United States)

    Crow, Andrew R; Song, Seng; Freedman, John; Helgason, Cheryl D; Humphries, R Keith; Siminovitch, Katherine A; Lazarus, Alan H

    2003-07-15

    It has been established that amelioration of murine immune thrombocytopenia purpura (ITP) by IVIg is dependent on the inhibitory receptor FcgammaRIIB. Co-cross-linking of the FcgammaRIIB with the B-cell receptor complex or with FcepsilonRI in mast cells results in cell inhibition, which is mediated by recruitment of the inositol phosphatase SHIP1 to the cytoplasmic tail of the FcgammaR. The FcgammaRIIB can also associate with protein tyrosine phosphatase SHP-1 as a potential secondary target of the receptor. Alternatively, homoaggregation of FcgammaRIIB can induce a proapoptotic state in B cells that is dependent on the presence of Bruton tyrosine kinase (Btk), a kinase also expressed in monocytes. We sought to determine if these signaling pathways may direct IVIg-mediated FcgammaRIIB-dependent regulation of in vivo monocyte function in a murine model of ITP in which IVIg functions in an FcgammaRIIB-dependent manner. We demonstrate that mice deficient in SHIP1, SHP-1, and Btk respond to the ameliorating effects of IVIg with the same kinetics as control mice. We conclude that IVIgmediated inhibitory pathways operating via monocyte FcgammaRIIB may involve a transmembrane signaling pathway different from that of B cells.

  5. PI3K p110δ uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of JMML.

    Science.gov (United States)

    Goodwin, Charles B; Li, Xing Jun; Mali, Raghuveer S; Chan, Gordon; Kang, Michelle; Liu, Ziyue; Vanhaesebroeck, Bart; Neel, Benjamin G; Loh, Mignon L; Lannutti, Brian J; Kapur, Reuben; Chan, Rebecca J

    2014-05-01

    Although hyperactivation of the Ras-Erk signaling pathway is known to underlie the pathogenesis of juvenile myelomonocytic leukemia (JMML), a fatal childhood disease, the PI3K-Akt signaling pathway is also dysregulated in this disease. Using genetic models, we demonstrate that inactivation of phosphatidylinositol-3-kinase (PI3K) catalytic subunit p110δ, but not PI3K p110α, corrects gain-of-function (GOF) Shp2-induced granulocyte macrophage-colony-stimulating factor (GM-CSF) hypersensitivity, Akt and Erk hyperactivation, and skewed hematopoietic progenitor distribution. Likewise, potent p110δ-specific inhibitors curtail the proliferation of GOF Shp2-expressing hematopoietic cells and cooperate with mitogen-activated or extracellular signal-regulated protein kinase kinase (MEK) inhibition to reduce proliferation further and maximally block Erk and Akt activation. Furthermore, the PI3K p110δ-specific inhibitor, idelalisib, also demonstrates activity against primary leukemia cells from individuals with JMML. These findings suggest that selective inhibition of the PI3K catalytic subunit p110δ could provide an innovative approach for treatment of JMML, with the potential for limiting toxicity resulting from the hematopoietic-restricted expression of p110δ.

  6. Partner preferences among survivors of betrayal trauma.

    Science.gov (United States)

    Gobin, Robyn L

    2012-01-01

    Betrayal trauma theory suggests that social and cognitive development may be affected by early trauma such that individuals develop survival strategies, particularly dissociation and lack of betrayal awareness, that may place them at risk for further victimization. Several experiences of victimization in the context of relationships predicated on trust and dependence may contribute to the development of relational schema whereby abuse is perceived as normal. The current exploratory study investigates interpersonal trauma as an early experience that might impact the traits that are desired in potential romantic partners. Participants in the current study were asked to rate the desirability of several characteristics in potential romantic partners. Although loyalty was desirable to most participants regardless of their trauma history, those who reported experiences of high betrayal trauma rated loyalty less desirable than those who reported experiences of traumas that were low and medium in betrayal. Participants who reported experiences of revictimization (defined as the experience of trauma perpetrated by a close other during 2 different developmental periods) differed from participants who only reported 1 experience of high betrayal trauma in their self-reported desire for a romantic partner who possessed the traits of sincerity and trustworthiness. Preference for a partner who uses the tactic of verbal aggression was also associated with revictimization status. These preliminary findings suggest that victimization perpetrated by close others may affect partner preferences.

  7. Partner Market Opportunities and Relationship Stability

    Directory of Open Access Journals (Sweden)

    Ingmar Rapp

    2015-10-01

    Full Text Available Although partner market opportunities are generally considered to be important for relationship stability, they have never been measured accurately. In order to be able to test the anticipated effects of partner market opportunities, this study conceptualises them as individual opportunities for contact and interaction in concrete social contexts, like the neighbourhood, the workplace, leisure activities, etc. Using data from the German Marriage Market Survey, we first examine the impact of individual partner market opportunities on the risk of separation. Second, we examine to what extend the most frequently studied determinants of divorce and separation depend on partner market opportunities. Our results show that the number of opposite sex contacts increases the probability of separation. Sharing the same contacts with one’s partner decreases the risk of separation. Our results indicate further that reducing opposite sex contacts in the course of the relationship is partly responsible for the higher stability of longer-lasting relationships. Having a migration background is associated with fewer opposite sex contacts. This means that having a migration background would be more destabilising if these individuals did not have less opposite sex contacts than individuals without a migration background. In contrast, joint home ownership, church attendance, higher education and residing in western Germany would generally be more stabilising if these factors were not connected with more opposite sex contacts.

  8. A Community-Academic Partnered Grant Writing Series to Build Infrastructure for Partnered Research.

    Science.gov (United States)

    King, Keyonna M; Pardo, Yvette-Janine; Norris, Keith C; Diaz-Romero, Maria; Morris, D'Ann; Vassar, Stefanie D; Brown, Arleen F

    2015-10-01

    Grant writing is an essential skill necessary to secure financial support for community programs and research projects. Increasingly, funding opportunities for translational biomedical research require studies to engage community partners, patients, or other stakeholders in the research process to address their concerns. However, there is little evidence on strategies to prepare teams of academic and community partners to collaborate on grants. This paper presents the description and formative evaluation of a two-part community-academic partnered grant writing series designed to help community organizations and academic institutions build infrastructure for collaborative research projects using a partnered approach. The first phase of the series was a half-day workshop on grant readiness, which was open to all interested community partners. The second phase, open only to community-academic teams that met eligibility criteria, was a 12-week session that covered partnered grant writing for foundation grants and National Institutes of Health grants. Participants in both phases reported an increase in knowledge and self-efficacy for writing partnered proposals. At 1-year follow-up, participants in Phase 2 had secured approximately $1.87 million in funding. This community-academic partnered grant writing series helped participants obtain proposal development skills and helped community-academic teams successfully compete for funding. © 2015 Wiley Periodicals, Inc.

  9. A Community–Academic Partnered Grant Writing Series to Build Infrastructure for Partnered Research

    Science.gov (United States)

    Pardo, Yvette‐Janine; Norris, Keith C.; Diaz‐Romero, Maria; Morris, D'Ann; Vassar, Stefanie D.; Brown, Arleen F.

    2015-01-01

    Abstract Grant writing is an essential skill necessary to secure financial support for community programs and research projects. Increasingly, funding opportunities for translational biomedical research require studies to engage community partners, patients, or other stakeholders in the research process to address their concerns. However, there is little evidence on strategies to prepare teams of academic and community partners to collaborate on grants. This paper presents the description and formative evaluation of a two‐part community–academic partnered grant writing series designed to help community organizations and academic institutions build infrastructure for collaborative research projects using a partnered approach. The first phase of the series was a half‐day workshop on grant readiness, which was open to all interested community partners. The second phase, open only to community–academic teams that met eligibility criteria, was a 12‐week session that covered partnered grant writing for foundation grants and National Institutes of Health grants. Participants in both phases reported an increase in knowledge and self‐efficacy for writing partnered proposals. At 1‐year follow‐up, participants in Phase 2 had secured approximately $1.87 million in funding. This community–academic partnered grant writing series helped participants obtain proposal development skills and helped community–academic teams successfully compete for funding. PMID:26365589

  10. Interaction of the Ku heterodimer with the DNA ligase IV/Xrcc4 complex and its regulation by DNA-PK.

    Science.gov (United States)

    Costantini, Silvia; Woodbine, Lisa; Andreoli, Lucia; Jeggo, Penny A; Vindigni, Alessandro

    2007-06-01

    DNA non-homologous end-joining (NHEJ) is a major mechanism for repairing DNA double-stranded (ds) breaks in mammalian cells. Here, we characterize the interaction between two key components of the NHEJ machinery, the Ku heterodimer and the DNA ligase IV/Xrcc4 complex. Our results demonstrate that Ku interacts with DNA ligase IV via its tandem BRCT domain and that this interaction is enhanced in the presence of Xrcc4 and dsDNA. Moreover, residues 644-748 of DNA ligase IV encompassing the first BRCT motif are necessary for binding. We show that Ku needs to be in its heterodimeric form to bind DNA ligase IV and that the C-terminal tail of Ku80, which mediates binding to DNA-PKcs, is dispensable for DNA ligase IV recognition. Although the interaction between Ku and DNA ligase IV/Xrcc4 occurs in the absence of DNA-PKcs, the presence of the catalytic subunit of DNA-PK kinase enhances complex formation. Previous studies have shown that DNA-PK kinase activity causes disassembly of DNA-PKcs from Ku at the DNA end. Here, we show that DNA-PK kinase activity also results in disassembly of the Ku/DNA ligase IV/Xrcc4 complex. Collectively, our findings provide novel information on the protein-protein interactions that regulate NHEJ in cells.

  11. Heterodimers of tyrosylprotein sulfotransferases suggest existence of a higher organization level of transferases in the membrane of the trans-Golgi apparatus.

    Science.gov (United States)

    Hartmann-Fatu, Cristina; Trusch, Franziska; Moll, Carina N; Michin, Irina; Hassinen, Antti; Kellokumpu, Sakari; Bayer, Peter

    2015-03-27

    Tyrosine sulfation of proteins is an important post-translational modification shown to play a role in many membrane-associated or extracellular processes such as virus entry, blood clotting, antibody-mediated immune response, inflammation and egg fecundation. The sole two human enzymes that transfer sulfate moieties from 3'-phospho-adenosine-5'-phospho-sulfate onto tyrosine residues, TPST1 and TPST2, are anchored to the membranes of the trans-Golgi compartment with the catalytic domain oriented to the lumen. In contrast to the relatively well studied organization of medial Golgi enzymes, the organization of trans-Golgi transferases remains elusive. Although tyrosylprotein sulfotransferases are known to exist as homodimers in the Golgi membranes, this organization level may represent only a small piece of a puzzle that is linked to the entire picture. Here we report the formation of TPST1/TPST2 heterodimers and a novel interaction between either TPST1 or TPST2 and the α-2,6-sialyltransferase, indicating a higher organization level of tyrosylprotein sulfotransferases that may serve for substrate selectivity and/or effective organization of multiple post-translational modification of proteins.

  12. Time-resolved FRET binding assay to investigate hetero-oligomer binding properties: proof of concept with dopamine D1/D3 heterodimer.

    Science.gov (United States)

    Hounsou, Candide; Margathe, Jean-François; Oueslati, Nadia; Belhocine, Abderazak; Dupuis, Elodie; Thomas, Cécile; Mann, André; Ilien, Brigitte; Rognan, Didier; Trinquet, Eric; Hibert, Marcel; Pin, Jean-Philippe; Bonnet, Dominique; Durroux, Thierry

    2015-02-20

    G protein-coupled receptors (GPCRs) have been described to form hetero-oligomers. The importance of these complexes in physiology and pathology is considered crucial, and heterodimers represent promising new targets to discover innovative therapeutics. However, there is a lack of binding assays to allow the evaluation of ligand affinity for GPCR hetero-oligomers. Using dopamine receptors and more specifically the D1 and D3 receptors as GPCR models, we developed a new time-resolved FRET (TR-FRET) based assay to determine ligand affinity for the D1/D3 heteromer. Based on the high-resolution structure of the dopamine D3 receptor (D3R), six fluorescent probes derived from a known D3R partial agonist (BP 897) were designed, synthesized and evaluated as high affinity and selective ligands for the D3/D2 receptors, and for other dopamine receptor subtypes. The highest affinity ligand 21 was then employed in the development of the D1/D3 heteromer assay. The TR-FRET was monitored between a fluorescent tag donor carried by the D1 receptor (D1R) and a fluorescent acceptor D3R ligand 21. The newly reported assay, easy to implement on other G protein-coupled receptors, constitutes an attractive strategy to screen for heteromer ligands.

  13. Welcoming spouses and partners to CERN

    CERN Multimedia

    Staff Association

    2016-01-01

    The questions related to Diversity were examined in the framework of the Five-yearly Review, which was approved in December 2015. The first themes implemented this year concern helping spouses or partners integrate into the working world, and improving the balance between professional and private life.   To this end, the Social Affairs Service and the CERN Diversity Office organised together on Tuesday, 15 November, a “Welcome Drink” for the spouses and partners of employed members of the personnel of CERN who have recently arrived in the region. This event was an occasion for the spouses and partners to meet and greet with various internal services at CERN, including the Staff Association, as well as local networks that can provide assistance in integrating into the region, in terms of job search for instance. Therefore, several service providers were present, including: the Geneva Welcome Center (CAGI), a welcoming network for newly arrived employees of international organi...

  14. Partner manipulation stabilises a horizontally transmitted mutualism.

    Science.gov (United States)

    Heil, Martin; Barajas-Barron, Alejandro; Orona-Tamayo, Domancar; Wielsch, Natalie; Svatos, Ales

    2014-02-01

    Mutualisms require protection from non-reciprocating exploiters. Pseudomyrmex workers that engage in an obligate defensive mutualism with Acacia hosts feed exclusively on the sucrose-free extrafloral nectar (EFN) that is secreted by their hosts, a behaviour linking ant energy supply directly to host performance and thus favouring reciprocating behaviour. We tested the hypothesis that Acacia hosts manipulate this digestive specialisation of their ant mutualists. Invertase (sucrose hydrolytic) activity in the ant midguts was inhibited by chitinase, a dominant EFN protein. The inhibition occurred quickly in cell-free gut liquids and in native gels and thus likely results from an enzyme-enzyme interaction. Once a freshly eclosed worker ingests EFN as the first diet available, her invertase becomes inhibited and she, thus, continues feeding on host-derived EFN. Partner manipulation acts at the phenotypic level and means that one partner actively controls the phenotype of the other partner to enhance its dependency on host-derived rewards.

  15. Evaluating self and partner physical attractiveness.

    Science.gov (United States)

    Swami, Viren; Furnham, Adrian; Georgiades, Chrissa; Pang, Lily

    2007-03-01

    This study used a novel questionnaire to examine ratings of self and partner physical attractiveness. Seventy-two men and 83 women estimated their own and their opposite-sex partner's overall physical attractiveness and the attractiveness of various body parts and measures. They also answered six simple questions concerning physical attractiveness. Results showed significant gender differences in self-estimates of overall facial attractiveness and upper body features. In general, and regardless of gender, participants rated their opposite-sex partners as being significantly more attractive than themselves. In addition, the results showed that body weight and facial attractiveness were the best predictors of overall physical attractiveness. Implications of these results in terms of social biases are considered.

  16. AIDS, partner notification and gender issues.

    Science.gov (United States)

    Hildesheimer, Galya M

    2002-01-01

    The interplay between public health, human rights, legal obligations and physicians' ethical concerns was revealed dramatically in Israel in recent cases involving reporting of the HIV positive status of patients. This paper reviews and critically analyses the decision-making process of Israeli Ethics Committees regarding HIV partner notification. One aim of this analysis is to suggest principles that may guide the decision in such cases. It is argued that the resolution concerning disclosure to partners be based on the Principle of Proportionality, taking into account the type of relationship between partner and patient, their cultural background and gender issues. The paper demonstrates the advantages of addressing such issues by professional multidisciplinary Ethics Committees, whose decisions can bring to bear the scope of relevant considerations.

  17. Whom to Choose as License Partner?

    DEFF Research Database (Denmark)

    Laursen, Keld; Reichstein, Toke; Trombini, Giulia

    2013-01-01

    This paper investigates the matching of firms on the market for technology. The paper forwards two dimensions along which license formation occurs: technology and product-market. Both sides of the market search for a partner representing potential for high technology synergies to maximize licensing...... benefits and obviate issues related to technology transfer and knowledge recombination. At the same time, firms wish to select a partner operating in a different product market to minimize competitive downside issues and to access other product markets, skills and resources. We contend interdependence...... between technology and market forces: if partners are market distant, the likelihood of technology license contractual partnership decreases with partners’ technological distance. Using data on the formation of license partnerships in the global biopharmaceutical industry over the period 1994...

  18. Partner Selection in Technological Licensing Agreements

    DEFF Research Database (Denmark)

    Laursen, Keld; Trombini, Giulia

    as attractors, and market competition and potential involuntary spillovers act as repellants. Firms seek potential licensing partners by trying to maximize technological synergies while attempting to minimize the competitive downsides. We hypothesize that when licensees engage in matches involving a partner...... that is technologically unrelated, ex ante familiarity with the licensors’ technology is required. We contend also that there is interdependence between technological learning and market competition: if partners are in the same product markets, the likelihood of technology license contractual partnerships decreases...... with partners’ technological relatedness. We use data on the formation of license partnerships in the global biopharmaceutical industry over the period 1994-2004 and find that, on the whole, there is empirical support for our theoretical predictions....

  19. Research on Partner-fly Infrared Decoys

    Institute of Scientific and Technical Information of China (English)

    HONG Yang; LI Yan-jun; WANG Qi

    2006-01-01

    With the rapid development of new generation of infrared-guided missiles, it is very difficult for the traditional point-source infrared decoys to confront them. Therefore it is important to research the jamming mechanism and tactical application of infrared decoys. Through the research on rocket-propelled infrared decoys, a movement model and a radiation pattern of partner-fly infrared decoy are established based on the jamming mechanism of infrared centroid effect, the aerodynamics principle as well as the aeronautical dynamics principle. A dynamic simulation seeking superiority is conducted for its firing range and direction, a tactical application method of partner-fly infrared decoy against infrared-guided missile is explored, and the technical conditions of partner-fly infrared decoys are determined.

  20. Amino Acid 72 of Mouse and Human GDF9 Mature Domain Is Responsible for Altered Homodimer Bioactivities but Has Subtle Effects on GDF9:BMP15 Heterodimer Activities1

    Science.gov (United States)

    Peng, Jia; Wigglesworth, Karen; Rangarajan, Adithya; Eppig, John J.; Thompson, Thomas B.; Matzuk, Martin M.

    2014-01-01

    ABSTRACT Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted paralogs of the transforming growth factor beta (TGFbeta) superfamily. In mammals, these two growth factors play critical roles in folliculogenesis. As previously reported, an arginine in the pre-helix loop of GDF5 defines the high binding specificity to its type 1 receptor. Interestingly, bioactive mouse GDF9 and human BMP15 share the conserved arginine in the pre-helix loop, but their low-activity counterparts (mouse BMP15 and human GDF9) have a glycine or a proline instead. To address the question of whether the arginine residue defines the different activities of GDF9 and BMP15 homodimers and their heterodimers in human and mouse, we used site-directed mutagenesis to change the species-specific residues in human and mouse proteins, and examined their activities in our in vitro assays. Although amino acid 72 of mature GDF9 is responsible for altered homodimer bioactivities, neither the corresponding BMP15 amino acid 62 nor the intact pre-helix loop is indispensable for BMP15 homodimer activity. However, amino acid 72 in GDF9 only has only subtle effects on GDF9:BMP15 heterodimer activity. Based on previous studies and our recent findings, we provide hypothetical models to understand the molecular mechanism to define activities of the homodimeric and heterodimeric ligands. The arginine residue in the pre-helix loop of GDF9 homodimer may prevent the inhibition from its pro-domain or directly alter receptor binding, but this residue in GDF9 does not significantly affect the heterodimer activity, because of suggested conformational changes during heterodimer formation. PMID:25253739

  1. Are human resource professionals strategic business partners?

    DEFF Research Database (Denmark)

    Chiu, Randy; Selmer, Jan

    2011-01-01

    place has been less pervasive. Based on a sample of CEOs, line managers and HR executives, this study applies both a quantitative and a qualitative approach to examine the research question whether HR professionals are strategic business partners. Although the overall quantitative results provided...... a weak support for an affirmative answer to the research question, quantitative analyses and the qualitative findings revealed that while HR executives regarded themselves as strategic business partners, CEOs and line managers were not sure that they played this strategic business role. Plausible...

  2. SHP-1 overexpression increases the radioresistance of NPC cells by enhancing DSB repair, increasing S phase arrest and decreasing cell apoptosis.

    Science.gov (United States)

    Pan, Xiaofen; Mou, Jingjing; Liu, Sha; Sun, Ziyi; Meng, Rui; Zhou, Zhenwei; Wu, Gang; Peng, Gang

    2015-06-01

    The present study aimed to investigate the influence of SHP-1 on the radioresistance of the nasopharyngeal carcinoma (NPC) cell line CNE-2 and the relevant underlying mechanisms. The human NPC cell line CNE-2 was transfected with a lentivirus that contained the SHP-1 gene or a nonsense sequence (referred to as LP-H1802Lv201 and LP-NegLv201 cells, respectively). Cells were irradiated with different ionizing radiation (IR) doses. Cell survival, DNA double-strand breaks (DSBs), apoptosis, cell cycle distribution, and the expression of related proteins were assessed using colony formation assay, immunofluorescent assays (IFAs), flow cytometry (FCM) and western blot analyses, respectively. Compared with the control (CNE-2 cells) and LP-NegLv201 cells, LP-H1802Lv201 cells were more resistant to IR. IFAs showed that IR caused less histone H2AX phosphorylation (γH2AX) and RAD51 foci in the LP-H1802Lv201 cells. Compared with the control and LP-NegLv201 cells, LP-H1802Lv201 cells showed increased S phase arrest. After IR, the apoptotic rate of the LP-H1802Lv201 cells was lower in contrast to the control and LP-NegLv201 cells. Western blot analyses showed that IR increased the phosphorylation of ataxia telangiectasia mutated (ATM) kinase, checkpoint kinase 2 (CHK2), ataxia telangiectasia and Rad3-related (ATR) protein, checkpoint kinase 1 (CHK1) and p53. In LP-H1802Lv201 cells, the phosphorylation levels of ATM and CHK2 were significantly increased while the p53 phosphorylation level was decreased compared to these levels in the control and LP-NegLv201 cells. Phosphorylation of ATR and CHK1 did not show significant differences in the three cell groups. Overexpression of SHP-1 in the CNE-2 cells led to radioresistance and the radioresistance was related to enhanced DNA DSB repair, increased S phase arrest and decreased cell apoptosis.

  3. The X-Ray Crystal Structure of the Keratin 1-Keratin 10 Helix 2B Heterodimer Reveals Molecular Surface Properties and Biochemical Insights into Human Skin Disease.

    Science.gov (United States)

    Bunick, Christopher G; Milstone, Leonard M

    2017-01-01

    Keratins 1 (K1) and 10 (K10) are the primary keratins expressed in differentiated epidermis. Mutations in K1/K10 are associated with human skin diseases. We determined the crystal structure of the complex between the distal (2B) helices of K1 and K10 to better understand how human keratin structure correlates with function. The 3.3 Å resolution structure confirms many features inferred by previous biochemical analyses, but adds unexpected insights. It demonstrates a parallel, coiled-coil heterodimer with a predominantly hydrophobic intermolecular interface; this heterodimer formed a higher order complex with a second K1-K10-2B heterodimer via a Cys401(K10) disulfide link, although the bond angle is unanticipated. The molecular surface analysis of K1-K10-2B identified several pockets, one adjacent to the disulfide linkage and conserved in K5-K14. The solvent accessible surface area of the K1-K10 structure is 20-25% hydrophobic. The 2B region contains mixed acidic and basic patches proximally (N-terminal), whereas it is largely acidic distally (C-terminal). Mapping of conserved and nonconserved residues between K1-K10 and K5-K14 onto the structure demonstrated the majority of unique residues align along the outer helical ridge. Finally, the structure permitted a fresh analysis of the deleterious effects caused by K1/K10 missense mutations found in patients with phenotypic skin disease.

  4. Violence and substance use among female partners of men in treatment for intimate-partner violence.

    Science.gov (United States)

    Wupperman, Peggilee; Amble, Paul; Devine, Susan; Zonana, Howard; Fals-Stewart, William; Easton, Caroline

    2009-01-01

    To improve understanding of the complex dynamics in intimate partner violence (IPV) in heterosexual relationships, we explored violence and substance use among the female partners of men entering treatment for both IPV and substance-related problems. All male participants (n = 75) were alcohol dependent and had at least one domestic-violence arrest. Results showed that female partners were as likely as men to engage in substance use the week before treatment; however, according to reports by the men, the female partners were more likely than men to use substances during the last week of treatment, due to a reported increase in use during the men's treatment. Regarding violence, 59 percent of female IPV victims reported engaging in some form of mild violence against their male partners, and 55 percent reported engaging in some form of severe violence. By contrast, only 23 percent of male batterers reported that their female partners had engaged in mild violence, and only 19 percent reported that their partners had engaged in severe violence. Regardless of whether the violence was defensive in nature, the data suggest that women in relationships involving substance abuse and IPV are in need of treatment. Implications of these findings are discussed.

  5. Cloning, expression, purification, crystallization and preliminary crystallographic analysis of pseudo death-effector domain of HIPPI, a molecular partner of Huntingtin-interacting protein HIP-1

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Manisha; Majumder, Pritha; Bhattacharyya, Nitai P.; Dattagupta, Jiban K.; Sen, Udayaditya, E-mail: udayaditya.sen@saha.ac.in [Structural Genomics Section, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India)

    2006-12-01

    A pseudo death-effector domain (pDED) of HIPPI, a partner of Huntingtin-interacting protein HIP1, has been cloned, overexpressed and crystallized. The crystals of pDED-HIPPI diffracted to 2.2 Å. The formation of a heterodimer between Huntingtin-interacting protein-1 (HIP-1) and its novel partner HIPPI (HIP-1 protein interactor) through their pseudo death-effector domains (pDEDs) is a key step that recruits caspase-8 and initiates apoptosis. This could be one of the pathways by which apoptosis is increased in Huntington’s disease (HD). A construct consisting of the pDED of HIPPI has been cloned and overexpressed as 6NH-tagged protein and purified by Ni–NTA affinity chromatography. Crystals of the pDED of HIPPI were grown in space group P4{sub 1}, with unit-cell parameters a = b = 77.42, c = 33.31 Å and a calculated Matthews coefficient of 1.88 Å{sup 3} Da{sup −1} (33% solvent content) with two molecules per asymmetric unit.

  6. Children Exposed to Intimate Partner Violence: Conduct Problems, Interventions, and Partner Contact With the Child.

    Science.gov (United States)

    Jouriles, Ernest N; Rosenfield, David; McDonald, Renee; Vu, Nicole L; Rancher, Caitlin; Mueller, Victoria

    2016-06-30

    Children's contact with their mother's violent partner is a potentially important variable for understanding conduct problems among children exposed to intimate partner violence (IPV). Within the context of a treatment study evaluating a parenting intervention (Project Support) for families exiting a domestic violence shelter, this study tested four hypotheses regarding children's postshelter contact with their mother's violent partner: (1) participation in Project Support decreases the frequency of children's contact with their mother's violent partner; (2) postshelter contact is positively associated with children's conduct problems and is associated more strongly for girls than boys; (3) frequency of contact mediates Project Support's effects on children's conduct problems; and (4) frequency of contact is positively associated with IPV and partner-child aggression, and these latter associations help explain effects of contact on children's conduct problems. Participants were 66 women (26 White) with a child (32 girls) between 4 and 9 years. Families were assessed every 4 months for 20 months after departure from a domestic violence shelter. Project Support reduced the extent of partner-child contact. In addition, within-subject changes in contact over time were associated with girls', but not boys', conduct problems, and it partially mediated effects of Project Support on girls' conduct problems. Higher average levels of contact over time were also positively associated with further incidents of IPV and partner-child aggression, and partner-child aggression helped explain effects of contact on children's conduct problems. Children's postshelter contact with the mother's violent partner relates positively to several negative family outcomes.

  7. Making the Most of a Teaching Partner

    Science.gov (United States)

    Hamilton, Boni

    2009-01-01

    Teachers often miss opportunities to use their classroom computers as teaching partners because of a lack of knowledge or confidence about how the computers can support learning. Internet-connected computers can enable teachers to access well-designed websites that support literacy instruction and involve students in interactive responses to…

  8. Subtyping Male Perpetrators of Intimate Partner Violence

    Science.gov (United States)

    Fowler, Katherine A.; Westen, Drew

    2011-01-01

    Domestic violence is a serious problem with far-reaching consequences. This study applies a new methodology to derive subtypes of male perpetrators of intimate partner violence. As part of a larger National Institute of Mental Health (NIMH)-funded study, a national sample of randomly selected psychologists and psychiatrists describe 188 adult male…

  9. Risk Recognition and Intimate Partner Violence

    Science.gov (United States)

    Witte, Tricia H.; Kendra, Rachel

    2010-01-01

    The objective of this study was to determine whether female victims of physical forms of intimate partner violence (IPV) displayed deficits in risk recognition, or the ability to detect danger, in physically violent dating encounters. A total of 182 women watched a video depicting a psychologically and physically aggressive encounter between…

  10. Self and partner personality in intimate relationships

    NARCIS (Netherlands)

    Barelds, D.P.H.

    2005-01-01

    Two studies were conducted to examine the relations between both partners' personality and marital quality in married or cohabiting heterosexual couples. In Study 1 (N = 1380, or 690 couples), personality was assessed by means of the Dutch Personality Questionnaire, whereas in Study 2 (N = 564, or 2

  11. Auditory Training with Frequent Communication Partners

    Science.gov (United States)

    Tye-Murray, Nancy; Spehar, Brent; Sommers, Mitchell; Barcroft, Joe

    2016-01-01

    Purpose: Individuals with hearing loss engage in auditory training to improve their speech recognition. They typically practice listening to utterances spoken by unfamiliar talkers but never to utterances spoken by their most frequent communication partner (FCP)--speech they most likely desire to recognize--under the assumption that familiarity…

  12. Yorkie and Scalloped: partners in growth activation.

    Science.gov (United States)

    Bandura, Jennifer L; Edgar, Bruce A

    2008-03-01

    The Hippo (Hpo) signaling pathway limits organ growth in organisms from Drosophila to mammals by suppressing the activity of the transcriptional coactivator Yorkie (Yki)/YAP. The TEAD/TEF factor Scalloped (Sd) has been identified as the first known transcription factor to partner with Yki as a downstream target of Hpo signaling.

  13. Physical Health Effects of Intimate Partner Abuse

    Science.gov (United States)

    Sillito, Carrie LeFevre

    2012-01-01

    Although intimate partner violence has been recognized as both a social problem and health issue, the extent to which it is a health issue for both males and females in the general population is largely unknown. This longitudinal research uses data from the National Survey of Family and Households (1987-2003). Random effects logistic regression…

  14. Intimate Partner Violence Victimization and Associated Factors ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Protective factors. Self-rated health status was assessed by a single ... Life satisfaction was elicited with one question,. “All things ... 95% confidence interval (CI) to determine the associations .... severe depression and 21.1% for PTSD. Regarding .... Table 3: Associations with Intimate Partner Violence among Men. Variables.

  15. Strategy Guideline: Partnering for High Performance Homes

    Energy Technology Data Exchange (ETDEWEB)

    Prahl, D.

    2013-01-01

    High performance houses require a high degree of coordination and have significant interdependencies between various systems in order to perform properly, meet customer expectations, and minimize risks for the builder. Responsibility for the key performance attributes is shared across the project team and can be well coordinated through advanced partnering strategies. For high performance homes, traditional partnerships need to be matured to the next level and be expanded to all members of the project team including trades, suppliers, manufacturers, HERS raters, designers, architects, and building officials as appropriate. In an environment where the builder is the only source of communication between trades and consultants and where relationships are, in general, adversarial as opposed to cooperative, the chances of any one building system to fail are greater. Furthermore, it is much harder for the builder to identify and capitalize on synergistic opportunities. Partnering can help bridge the cross-functional aspects of the systems approach and achieve performance-based criteria. Critical success factors for partnering include support from top management, mutual trust, effective and open communication, effective coordination around common goals, team building, appropriate use of an outside facilitator, a partnering charter progress toward common goals, an effective problem-solving process, long-term commitment, continuous improvement, and a positive experience for all involved.

  16. Librarians as Community Partners: An Outreach Handbook

    Science.gov (United States)

    Smallwood, Carol, Ed.

    2010-01-01

    Including 66 focused snapshots of outreach in action, this resource reflects the creative solutions of librarians searching for new and innovative ways to build programs that meet customer needs while expanding the library's scope into the community. This contributed volume includes: (1) A huge array of program options for partnering with other…

  17. Gender Symmetry, Sexism, and Intimate Partner Violence

    Science.gov (United States)

    Allen, Christopher T.; Swan, Suzanne C.; Raghavan, Chitra

    2009-01-01

    This study of a predominantly Hispanic sample of 92 male and 140 female college students examines both gender symmetry in intimate partner violence (IPV) and inconsistent relationships found in previous studies between sexist attitudes and IPV. Results indicate that although comparable numbers of men and women perpetrate and are victimized in…

  18. Intimate partner violence in orthopaedic trauma patients

    NARCIS (Netherlands)

    Sprague, S.A.

    2013-01-01

    Intimate partner violence (IPV) or domestic violence is a common and serious public health problem around the globe. Victims of IPV frequently present to health care practitioners including orthopaedic surgeons. Substantial research has been conducted on IPV over the past few decades, but very

  19. Inferring interaction partners from protein sequences

    Science.gov (United States)

    Bitbol, Anne-Florence; Dwyer, Robert S.; Colwell, Lucy J.; Wingreen, Ned S.

    2016-01-01

    Specific protein−protein interactions are crucial in the cell, both to ensure the formation and stability of multiprotein complexes and to enable signal transduction in various pathways. Functional interactions between proteins result in coevolution between the interaction partners, causing their sequences to be correlated. Here we exploit these correlations to accurately identify, from sequence data alone, which proteins are specific interaction partners. Our general approach, which employs a pairwise maximum entropy model to infer couplings between residues, has been successfully used to predict the 3D structures of proteins from sequences. Thus inspired, we introduce an iterative algorithm to predict specific interaction partners from two protein families whose members are known to interact. We first assess the algorithm’s performance on histidine kinases and response regulators from bacterial two-component signaling systems. We obtain a striking 0.93 true positive fraction on our complete dataset without any a priori knowledge of interaction partners, and we uncover the origin of this success. We then apply the algorithm to proteins from ATP-binding cassette (ABC) transporter complexes, and obtain accurate predictions in these systems as well. Finally, we present two metrics that accurately distinguish interacting protein families from noninteracting ones, using only sequence data. PMID:27663738

  20. Self and partner personality in intimate relationships

    NARCIS (Netherlands)

    Barelds, D.P.H.

    Two studies were conducted to examine the relations between both partners' personality and marital quality in married or cohabiting heterosexual couples. In Study 1 (N = 1380, or 690 couples), personality was assessed by means of the Dutch Personality Questionnaire, whereas in Study 2 (N = 564, or

  1. Intimate Partner Violence within Law Enforcement Families

    Science.gov (United States)

    Anderson, Anita S.; Lo, Celia C.

    2011-01-01

    Using data from the Baltimore Police Stress and Domestic Violence study, the authors examined how exposure to stressful events on the job affects law enforcement employees' physical aggression toward domestic partners, evaluating the role of negative emotions and authoritarian spillover in mediating the impact of such task-related stress. The…

  2. Perceived neighborhood partner availability, partner selection, and risk for sexually transmitted infections within a cohort of adolescent females.

    Science.gov (United States)

    Matson, Pamela A; Chung, Shang-En; Ellen, Jonathan M

    2014-07-01

    This research examined the association between a novel measure of perceived partner availability and discordance between ideal and actual partner characteristics as well as trajectories of ideal partner preferences and perceptions of partner availability over time. A clinic-recruited cohort of adolescent females (N = 92), aged 1619 years, were interviewed quarterly for 12 months using audio computer-assisted self-interview. Participants ranked the importance of characteristics for their ideal main sex partner and then reported on these characteristics for their current main partner. Participants reported on perceptions of availability of ideal sex partners in their neighborhood. Paired t-tests examined discordance between ideal and actual partner characteristics. Random-intercept regression models examined repeated measures. Actual partner ratings were lower than ideal partner preferences for fidelity, equaled ideal preferences for emotional support and exceeded ideal preferences for social/economic status and physical attractiveness. Discordance on emotional support and social/economic status was associated with sex partner concurrency. Participants perceived low availability of ideal sex partners. Those who perceived more availability were less likely to be ideal/actual discordant on fidelity [OR = .88, 95% CI: .78, 1.0]. Neither ideal partner preferences nor perceptions of partner availability changed over 12 months. Current main sex partners met or exceeded ideal partner preferences in all domains except fidelity. If emotional needs are met, adolescents may tolerate partner concurrency in areas of limited partner pools. Urban adolescent females who perceive low availability may be at increased risk for sexually transmitted infection (STI) because they may be more likely to have nonmonogamous partners. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  3. Alcohol Misuse and Multiple Sexual Partners

    Directory of Open Access Journals (Sweden)

    Shahrzad Bazargan-Hejazi, PhD

    2012-05-01

    Full Text Available Introduction: We examine the association between self-reported alcohol misuse and alcohol usewithin 2 hours of having sex and the number of sexual partners among a sample of African-Americanand Latino emergency department (ED patients.Methods: Cross-sectional data were collected prospectively from a randomized sample of all EDpatients during a 5-week period. In face-to-face interviews, subjects were asked to report their alcoholuse and number of sexual partners in the past 12 months. Data were analyzed using multiple variablenegative binomial regression models, and effect modification was assessed through inclusion ofinteraction terms.Results: The 395 study participants reported an average of 1.4 (standard error¼0.11 sexual partnersin the past 12 months, 23% reported misusing alcohol, and 28% reported consuming alcohol beforesex. There was no statistically significant association between alcohol misuse and the number ofsexual partners; however, alcohol before sex was associated with a larger number of sexual partners inthe past year. Moreover, among those who misused alcohol, participants who reported alcohol beforesex were 3 times more likely to report a higher number of sexual partners (risk ratio¼3.2; confidenceinterval [CI]¼1.9–5.6. The association between alcohol use before sex and number of sexual partnersis dependent upon whether a person has attributes of harmful drinking over the past 12 months.Overall, alcohol use before sex increases the number of sexual partners, but the magnitude of thiseffect is significantly increased among alcohol misusers.Conclusion: Alcohol misusers and those who reported having more than 1 sexual partner were morelikely to cluster in the same group, ie, those who used alcohol before sex. Efforts to reduce the burdenof sexually transmitted diseases, including human immunodeficiency virus, and other consequences ofrisky sexual behavior in the ED population should be cognizant of the interplay of alcohol and

  4. Tanshinone IIA induced cell death via miR30b-p53-PTPN11/SHP2 signaling pathway in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Ren, Xuanqi; Wang, Cui; Xie, Binbin; Hu, Linfeng; Chai, Hui; Ding, Lei; Tang, Lihua; Xia, Yongliang; Dou, Xiaobing

    2017-02-05

    Tanshinone IIA, a multi-pharmaceutical compound from traditional Chinese herb, has been reported to have anti-hepatocarcinomic (HCC) properties through cell death induction. Apart from the typical p53-dependent pathway, mechanisms of the anti-carcinogenic role of Tanshinone remain scarce. In an effort to explore the mechanism behind Tanshinone IIA, we detected the upstream of the p53 and the potential novel pathway. Tanshinone IIA dose-dependently initiated HepG2 cell apoptosis and cell cycle arrest at the G1 checkpoint. In the miR30 family, only the transcription of miR30b was downregulated by Tanshinone IIA, which subsequently upregulated both the genomic and protein levels of p53. Further, we screened that PTPN11 and Tp53 are the two critical genomes involved in the pharmacology of Tanshinone IIA. Building upon LASAGNA-search and kinetics binding assay, p53 was found to be a potential transcription factor for PTPN11. Concomitant with the expression of p53, Tanshinone IIA stimulated both PTPN11 and its encoded protein SHP2. Inhibition miR30b attenuated the Tanshinone IIA-induced cytotoxicity, level of p53 and PTPN11 in HepG2 cells. Finally, the apoptotic molecules such as Bax/Bcl2, cleavage caspase 3 and the cell cycle regulation factors including p21, cyclin D1, and CDK6 were changed by Tanshinone IIA. Several cytotoxic endpoints induced by Tanshinone IIA were also checked in Hep3B cells. This study confirmed that Tanshinone IIA may induce hepatoma cell death through the miR30b-p53- PTPN11/SHP2 pathway. With regard to the complicated tumorigenesis of HCC and the multi-targets of Tanshinone IIA, our results propose developing Tanshinone IIA for clinic therapy and the interference of HCC.

  5. Structure-function analysis of heterodimer formation, oligomerization, and receptor binding of the Staphylococcus aureus bi-component toxin LukGH.

    Science.gov (United States)

    Badarau, Adriana; Rouha, Harald; Malafa, Stefan; Logan, Derek T; Håkansson, Maria; Stulik, Lukas; Dolezilkova, Ivana; Teubenbacher, Astrid; Gross, Karin; Maierhofer, Barbara; Weber, Susanne; Jägerhofer, Michaela; Hoffman, David; Nagy, Eszter

    2015-01-01

    The bi-component leukocidins of Staphylococcus aureus are important virulence factors that lyse human phagocytic cells and contribute to immune evasion. The γ-hemolysins (HlgAB and HlgCB) and Panton-Valentine leukocidin (PVL or LukSF) were shown to assemble from soluble subunits into membrane-bound oligomers on the surface of target cells, creating barrel-like pore structures that lead to cell lysis. LukGH is the most distantly related member of this toxin family, sharing only 30-40% amino acid sequence identity with the others. We observed that, unlike other leukocidin subunits, recombinant LukH and LukG had low solubility and were unable to bind to target cells, unless both components were present. Using biolayer interferometry and intrinsic tryptophan fluorescence we detected binding of LukH to LukG in solution with an affinity in the low nanomolar range and dynamic light scattering measurements confirmed formation of a heterodimer. We elucidated the structure of LukGH by x-ray crystallography at 2.8-Å resolution. This revealed an octameric structure that strongly resembles that reported for HlgAB, but with important structural differences. Structure guided mutagenesis studies demonstrated that three salt bridges, not found in other bi-component leukocidins, are essential for dimer formation in solution and receptor binding. We detected weak binding of LukH, but not LukG, to the cellular receptor CD11b by biolayer interferometry, suggesting that in common with other members of this toxin family, the S-component has the primary contact role with the receptor. These new insights provide the basis for novel strategies to counteract this powerful toxin and Staphylococcus aureus pathogenesis.

  6. Lettuce-produced hepatitis C virus E1E2 heterodimer triggers immune responses in mice and antibody production after oral vaccination.

    Science.gov (United States)

    Clarke, Jihong Liu; Paruch, Lisa; Dobrica, Mihaela-Olivia; Caras, Iuliana; Tucureanu, Catalin; Onu, Adrian; Ciulean, Sonya; Stavaru, Crina; Eerde, Andre; Wang, Yanliang; Steen, Hege; Haugslien, Sissel; Petrareanu, Catalina; Lazar, Catalin; Popescu, Costin-Ioan; Bock, Ralph; Dubuisson, Jean; Branza-Nichita, Norica

    2017-04-17

    The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500 000 die yearly from HCV-related liver pathologies. To date, there is no licensed vaccine available to prevent HCV infection and production of a HCV vaccine remains a major challenge. Here, we report the successful production of the HCV E1E2 heterodimer, an important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using Agrobacterium-mediated transient expression technology. The wild-type dimer (E1E2) and a variant without an N-glycosylation site in the E2 polypeptide (E1E2∆N6) were expressed, and appropriate N-glycosylation pattern and functionality of the E1E2 dimers were demonstrated. The humoral immune response induced by the HCV proteins was investigated in mice following oral administration of lettuce antigens with or without previous intramuscular prime with the mammalian HEK293T cell-expressed HCV dimer. Immunization by oral feeding only resulted in development of weak serum levels of anti-HCV IgM for both antigens; however, the E1E2∆N6 proteins produced higher amounts of secretory IgA, suggesting improved immunogenic properties of the N-glycosylation mutant. The mice group receiving the intramuscular injection followed by two oral boosts with the lettuce E1E2 dimer developed a systemic but also a mucosal immune response, as demonstrated by the presence of anti-HCV secretory IgA in faeces extracts. In summary, our study demonstrates the feasibility of producing complex viral antigens in lettuce, using plant transient expression technology, with great potential for future low-cost oral vaccine development. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and the Association of Applied Biologists and John Wiley & Sons Ltd.

  7. Number of sexual partners and sexual assertiveness predict sexual victimization: do more partners equal more risk?

    Science.gov (United States)

    Walker, Dave P; Messman-Moore, Terri L; Ward, Rose Marie

    2011-01-01

    In previous studies, number of sexual partners and sexual assertiveness were examined as independent risk factors for sexual victimization among college women. Using a sample of 335 college women, this study examined the interaction of number of sexual partners and sexual assertiveness on verbal sexual coercion and rape. Approximately 32% of the sample reported unwanted sexual intercourse, 6.9% (n = 23) experienced verbal sexual coercion, 17.9% (n = 60) experienced rape, and 7.2% (n = 24) experienced both. As number of sexual partners increased, instances of verbal sexual coercion increased for women low in relational sexual assertiveness but not for women high in relational sexual assertiveness. A similar relationship was not found for rape. Among women who experienced both verbal sexual coercion and rape, increases in number of partners in the context of low refusal and relational assertiveness were associated with increases in verbal sexual coercion and rape. Findings suggest sexual assertiveness is related to fewer experiences of sexual coercion.

  8. Partner dependency and intimate partner abuse: A sociocultural grounding of spousal abuse in Ghana

    DEFF Research Database (Denmark)

    Adjei, Stephen Baffour

    2015-01-01

    While sociocultural scholarship has attempted an ecological explanation of intimate partner violence, it has largely been criticized for ignoring dispositional factors of both perpetrators and victims. Dependent personality and attachment-related emotional problems have been implicated in the ext......While sociocultural scholarship has attempted an ecological explanation of intimate partner violence, it has largely been criticized for ignoring dispositional factors of both perpetrators and victims. Dependent personality and attachment-related emotional problems have been implicated...... of dependency and attachment-related spousal violence as a form of a psychopathology. This article discusses partner dependency and jealousy-motivated spousal violence as socioculturally situated, dependent on contextual and relational conditions of meaning embedded in the communal society of Ghana....... It highlights Ghanaian communal personality, gendered socialization and meaning systems of marriage as salient sociocultural features for conceptualizing partner dependency and emotional-related spousal violence....

  9. Ants use partner specific odors to learn to recognize a mutualistic partner.

    Directory of Open Access Journals (Sweden)

    Masaru K Hojo

    Full Text Available Regulation via interspecific communication is an important for the maintenance of many mutualisms. However, mechanisms underlying the evolution of partner communication are poorly understood for many mutualisms. Here we show, in an ant-lycaenid butterfly mutualism, that attendant ants selectively learn to recognize and interact cooperatively with a partner. Workers of the ant Pristomyrmex punctatus learn to associate cuticular hydrocarbons of mutualistic Narathura japonica caterpillars with food rewards and, as a result, are more likely to tend the caterpillars. However, the workers do not learn to associate the cuticular hydrocarbons of caterpillars of a non-ant-associated lycaenid, Lycaena phlaeas, with artificial food rewards. Chemical analysis revealed cuticular hydrocarbon profiles of the mutualistic caterpillars were complex compared with those of non-ant-associated caterpillars. Our results suggest that partner-recognition based on partner-specific chemical signals and cognitive abilities of workers are important mechanisms underlying the evolution and maintenance of mutualism with ants.

  10. Rules about casual sex partners, relationship satisfaction, and HIV risk in partnered gay and bisexual men.

    Science.gov (United States)

    Grov, Christian; Starks, Tyrel J; Rendina, H Jonathon; Parsons, Jeffrey

    2014-01-01

    The authors used latent class analysis to investigate rules guiding nonmonogamy in partnered gay and bisexual men. Data are from a 2010 survey (N = 463) from which those in relationships (n = 191) were analyzed. More than half (56%) were nonmonogamous, and these men responded to 13 rules about sex outside of their relationship. The safe anonymous sex group (34%) included men who indicated that they must use condoms for anal sex and not have sex with people they know. The communication mandate group (19%) included men who indicated that they must talk about outside partners before sex occurs, disclose their relationship status to outside partners, and use condoms for anal sex. The play together group (9%) included men who indicated that they must play with others as a couple, not have anal sex with outside partners, and not spend the night with outside partners. Those in the no salient rule group (37%) were individuals who did not endorse a clear set of rules. These 4 groups (and compared with monogamous men) differed in age, agreement formality and flexibility, relationship satisfaction, and whether anal sex recently occurred with casual partners. This study provides a novel approach for understanding nonmonogamous same-sex relationships and highlights their complexity.

  11. DEF- and GLO-like proteins may have lost most of their interaction partners during angiosperm evolution.

    Science.gov (United States)

    Melzer, Rainer; Härter, Andrea; Rümpler, Florian; Kim, Sangtae; Soltis, Pamela S; Soltis, Douglas E; Theißen, Günter

    2014-11-01

    early-diverging angiosperms may be one reason for the highly diverse flower morphologies observed in these species. The results strengthen the hypothesis that a reduction in the number of interaction partners of DEF- and GLO-like proteins, with DEF-GLO heterodimers remaining the only DNA-binding dimers in core eudicots, contributed to developmental robustness, canalization of flower development and the diversification of angiosperms. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. DEF- and GLO-like proteins may have lost most of their interaction partners during angiosperm evolution

    Science.gov (United States)

    Melzer, Rainer; Härter, Andrea; Rümpler, Florian; Kim, Sangtae; Soltis, Pamela S.; Soltis, Douglas E.; Theißen, Günter

    2014-01-01

    flexibility of DEF- and GLO-like protein interactions in early-diverging angiosperms may be one reason for the highly diverse flower morphologies observed in these species. The results strengthen the hypothesis that a reduction in the number of interaction partners of DEF- and GLO-like proteins, with DEF–GLO heterodimers remaining the only DNA-binding dimers in core eudicots, contributed to developmental robustness, canalization of flower development and the diversification of angiosperms. PMID:24902716

  13. National Intimate Partner and Sexual Violence Survey (NISVS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Intimate Partner and Sexual Violence Survey (NISVS) is an ongoing, nationally representative survey to assess experiences of intimate partner violence,...

  14. Intimate partner violence and mental health in Bolivia

    National Research Council Canada - National Science Library

    Meekers, Dominique; Pallin, Sarah C; Hutchinson, Paul

    2013-01-01

    Latin America has among the highest rates of intimate partner violence. While there is increasing evidence that intimate partner violence is associated with mental health problems, there is little such research for developing countries...

  15. Positive illusions about a partner's personality and relationship quality

    NARCIS (Netherlands)

    Barelds, Dick P. H.; Dijkstra, Pieternel

    2011-01-01

    Previous studies have shown individuals to hold positive biases about their relationships. The present study examined positive illusions about a partner's specific personality characteristics in relation to relationship quality and personality. Both partners of 120 heterosexual couples participated

  16. National Intimate Partner and Sexual Violence Survey: 2010 Highlights

    Science.gov (United States)

    National Intimate Partner and Sexual Violence Survey CDC’s National Intimate Partner and Sexual Violence Survey (NISVS) is an ongoing, nationally-representative telephone survey that collects detailed ...

  17. HIV Treatment Protects Uninfected Partner from The Virus

    Science.gov (United States)

    ... html HIV Treatment Protects Uninfected Partner From the Virus Study of gay couples duplicates findings of earlier ... HealthDay News) -- HIV treatment prevented transmission of the virus in gay couples when only one partner had ...

  18. Positive illusions about a partner's personality and relationship quality

    NARCIS (Netherlands)

    Barelds, Dick P. H.; Dijkstra, Pieternel

    Previous studies have shown individuals to hold positive biases about their relationships. The present study examined positive illusions about a partner's specific personality characteristics in relation to relationship quality and personality. Both partners of 120 heterosexual couples participated

  19. HPV genotypes concordance between sex partners.

    Science.gov (United States)

    Benevolo, M; Mottolese, M; Marandino, F; Carosi, M; Diodoro, M G; Sentinelli, S; Visca, P; Rollo, F; Mariani, L; Vocaturo, G; Sindico, R; Di Giannuario, D; Perrone Donnorso, R; Pellicciotta, M; Vocaturo, A

    2007-12-01

    The HPV genotype concordance in the sexual couples could support the sexual viral transmission of HPV infection. The present study contains a case-report of a stable Italian sex couple harbouring the same five HPV genotypes in their genital samples. The female partner, affected by vulvar condilomatosis, evidenced positivity in her cervicovaginal scraping with high risk HPV DNA Hybrid Capture 2 test and was negative at liquid-based performed Pap Test and at colposcopic examination. The male partner was clinically healthy regarding his external genitalia. In both male and female genital scrapings, the following HPV genotypes were detected by means of a PCR-based assay: 6, 16, 53, 73 and 84. This considerably high genotype concordance does not appear to be casual and supports, in our opinion, the hypothesis that genital HPV types are sexually transmitted agents

  20. Are human resource professionals strategic business partners?

    DEFF Research Database (Denmark)

    Chiu, Randy; Selmer, Jan

    2011-01-01

    Theoretical speculations and prescriptive discussions abound in the literature regarding the strategic importance of human resource management. However, evidence based on rigorous empirical studies that the transformation from an administrative service function to strategic partnership has taken...... place has been less pervasive. Based on a sample of CEOs, line managers and HR executives, this study applies both a quantitative and a qualitative approach to examine the research question whether HR professionals are strategic business partners. Although the overall quantitative results provided...... a weak support for an affirmative answer to the research question, quantitative analyses and the qualitative findings revealed that while HR executives regarded themselves as strategic business partners, CEOs and line managers were not sure that they played this strategic business role. Plausible...

  1. Partners' session spurs progress for Latin women.

    Science.gov (United States)

    1982-02-18

    A workshop sponsored by Partners of the Americas with support from the US Agency for International Development's Women in Development Office held in Christiana, Jamaica, October 1981 was designed to expand the involvement of women in the development process by strengthening leadership capabilities of women in the Caribbean. Sessions were held on project planning, goal identification, and resource evaluation. By the end of the workshop women representing 11 US states and their partners in 17 Latin American and Caribbean countries had initiated several projects. Some projects are: 1) Colombia-Florida: developing literacy training aids about nutrition information, 2) Guatemala-Alabama: home gardening and nutrition education, and 3) Jamaica-western New York: skills training programs for young mothers.

  2. Performance improvement with patient service partners.

    Science.gov (United States)

    Burns, J P

    1998-01-01

    Once the decision is made to use a patient-focused care delivery system, a variety of methods can be used to successfully design the model. The author describes the process used by a multilevel, multidisciplinary team at a community hospital to design and implement a Service Partner role that would meet and exceed customer expectations. Demonstrated performance improvements included increased patient satisfaction, productive labor dollar savings, and improvements in the work environment for staff members.

  3. Unperceived intimate partner violence and women's health.

    Science.gov (United States)

    Sonego, Michela; Gandarillas, Ana; Zorrilla, Belén; Lasheras, Luisa; Pires, Marisa; Anes, Ana; Ordobás, María

    2013-01-01

    Women who experience intimate partner violence (IPV) often do not perceive themselves as abused. This study sought to estimate the health effects of unperceived IPV (uIPV), taking violence-free women as the reference, and to compare the effects of uIPV with those of perceived IPV (pIPV). We performed a cross-sectional population study through telephone interviews of 2835 women aged 18 to 70 years living in the region of Madrid and having an ongoing intimate partner relationship or contact with a former partner in the preceding year. Based on 26 questions from the Conflict Tactics Scale-1 and the Enquête Nacional sur les Violences envers les Femmes en France and the question "Do you feel abused by your partner?" a variable was constructed in three categories, namely, the absence of IPV, uIPV and pIPV. Using logistic regression, we analyzed the association between health problems, medication use, health-service utilization and IPV (perceived and unperceived) vis-à-vis the absence of IPV. There were 247 cases of uIPV and 96 of pIPV (prevalences of 8.8% and 3.4%, respectively). The multivariate analysis showed that a substantial number of the outcomes explored were associated with uIPV, pIPV, or both. The highest odds ratios (ORs) were obtained for depression (Patient Health Questionnaire-9≥10) (uIPV: OR 3.4, 95% CI 2.4-3.8; and pIPV: 4.1, 95%CI 2.5-6.8). In most problems, the ORs did not significantly differ between the two types of IPV. uIPV is 2.6 times more frequent than pIPV and is associated with at least as many health problems as pIPV. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.

  4. Patterns in PARTNERing across Public Health Collaboratives

    Directory of Open Access Journals (Sweden)

    Christine A. Bevc

    2015-10-01

    Full Text Available Inter-organizational networks represent one of the most promising practice-based approaches in public health as a way to attain resources, share knowledge, and, in turn, improve population health outcomes. However, the interdependencies and effectiveness related to the structure, management, and costs of these networks represents a critical item to be addressed. The objective of this research is to identify and determine the extent to which potential partnering patterns influence the structure of collaborative networks. This study examines data collected by PARTNER, specifically public health networks (n = 162, to better understand the structured relationships and interactions among public health organizations and their partners, in relation to collaborative activities. Combined with descriptive analysis, we focus on the composition of public health collaboratives in a series of Exponential Random Graph (ERG models to examine the partnerships between different organization types to identify the attribute-based effects promoting the formation of network ties within and across collaboratives. We found high variation within and between these collaboratives including composition, diversity, and interactions. The findings of this research suggest common and frequent types of partnerships, as well as opportunities to develop new collaborations. The result of this analysis offer additional evidence to inform and strengthen public health practice partnerships.

  5. Intimate partner violence is everyone's problem, but how should we ...

    African Journals Online (AJOL)

    feel fortunate to have a partner, that they would never cope with- out their partner or are ... pelvic pain). • Vague ... Has your partner ever threatened you or forced you to do some- thing you didn't want ... My patient is being abused – now what?

  6. Logistics in Security Force Assistance: Sustainable Partner Development

    Science.gov (United States)

    2014-05-22

    original hypothesis of this paper was that efforts to build partner capacity historically only included sustainment training in a limited fashion . The...LOGISTICS IN SECURITY FORCE ASSISTANCE: SUSTAINABLE PARTNER DEVELOPMENT A Monograph by MAJ J. Troy Fisher United...Logistics in Security Force Assistance: Sustainable Partner Development 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

  7. Trends in Intimate Partner Violence: 1980-2008

    Science.gov (United States)

    Powers, Rachael A.; Kaukinen, Catherine Elizabeth

    2012-01-01

    Research on trends in partner violence has primarily relied on official measures of victimization focusing primarily on women's risk for intimate partner homicide. The current study uses 28 years of data from the National Crime Victimization Survey (NCVS) to examine the trends of intimate partner violence against female victims and identify…

  8. Positive illusions about a partner's physical attractiveness and relationship quality

    NARCIS (Netherlands)

    Barelds, Dick P. H.; Dijkstra, Pieternel

    2009-01-01

    The present research examined the existence of positive illusions about a partner's physical attractiveness and its relations to relationship quality. Positive illusions were assumed to exist when individuals rated their partner as more attractive than their partner rated him or herself. In two Dutc

  9. Positive illusions about a partner's physical attractiveness and relationship quality

    NARCIS (Netherlands)

    Barelds, Dick P. H.; Dijkstra, Pieternel

    The present research examined the existence of positive illusions about a partner's physical attractiveness and its relations to relationship quality. Positive illusions were assumed to exist when individuals rated their partner as more attractive than their partner rated him or herself. In two

  10. Partner's Stake in Conformity and Abused Wives' Psychological Trauma

    Science.gov (United States)

    DeMaris, Alfred; Kaukinen, Catherine

    2008-01-01

    This study investigates the potential buffering effect of help-seeking in the association between intimate partner assault and women's psychological trauma, and how this, in turn, may depend on the partner's stake in conformity. The sample consists of 374 women reporting the experience of domestic violence from a current intimate partner, drawn…

  11. Innovation durch Partnering im deutschen Schlüsselfertigbau

    OpenAIRE

    Schmolke, Daniel

    2008-01-01

    In der angloamerikanischen Baubranche werden bereits seit Jahren innovative Managementkonzepte zur Steuerung partnerschaftlicher Kooperationen nach dem Leitgedanken des Partnering zwischen Haupt- und Nachunternehmern im Schlüsselfertigbau erfolgreich umgesetzt. Hierzulande bleibt der Einsatz derartiger Partnering-Modelle bislang jedoch weitgehend unbeachtet. Das Ziel der Arbeit besteht daher darin, wesentliche Elemente und Erfahrungen des angloamerikanischen Partnering-Konzeptes im Hinb...

  12. Partner Status, Social Support, and Psychological Adjustment during Pregnancy.

    Science.gov (United States)

    Liese, Lawrence H.; And Others

    1989-01-01

    Studied partner status, social support, and psychological adjustment of pregnant women. Administered Brief Symptom Inventory to predominantly minority and lower-income pregnant women (N=157) categorized as married, single/partnered, or single/unpartnered. Found single/partnered women were at least risk for emotional disequilibrium and suggested…

  13. 45 CFR 162.915 - Trading partner agreements.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Trading partner agreements. 162.915 Section 162... REQUIREMENTS ADMINISTRATIVE REQUIREMENTS General Provisions for Transactions § 162.915 Trading partner agreements. A covered entity must not enter into a trading partner agreement that would do any of...

  14. Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

    Science.gov (United States)

    Palmisano, Brian T; Le, Thao D; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M

    2016-08-01

    Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  15. Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes.

    Directory of Open Access Journals (Sweden)

    Yunwon Moon

    Full Text Available This study evaluated HIF-1α inhibitors under different hypoxic conditions, physiological hypoxia (5% O2 and severe hypoxia (0.1% O2. We found that chenodeoxy cholic acid (CDCA reduced the amount of HIF-1α protein only under physiological hypoxia but not under severe hypoxia without decreasing its mRNA level. By using a proteasome inhibitor MG132 and a translation inhibitor cyclohexamide, we showed that CDCA reduced HIF-1α protein by decreasing its translation but not by enhancing its degradation. The following findings indicated that farnesoid X receptor (FXR, a CDCA receptor and its target gene, Small heterodimer partner (SHP are not involved in this effect of CDCA. Distinctly from CDCA, MG132 prevented SHP and an exogenous FXR agonist, GW4064 from reducing HIF-1α protein. Furthermore a FXR antagonist, guggulsterone failed to prevent CDCA from decreasing HIF-1α protein. Furthermore, guggulsterone by itself reduced HIF-1α protein even in the presence of MG132. These findings suggested that CDCA and guggulsterone reduced the translation of HIF-1α in a mechanism which FXR and SHP are not involved. This study reveals novel therapeutic functions of traditional nontoxic drugs, CDCA and guggulsterone, as inhibitors of HIF-1α protein.

  16. Partner notification for sexually transmitted infections and perception of notified partners

    Directory of Open Access Journals (Sweden)

    Elani Graça Ferreira Cavalcante

    2016-06-01

    Full Text Available Abstract OBJECTIVE Learn the perceptions of patients with sexually transmitted infections and sexual partners who are notified of the infection. METHOD A descriptive and qualitative study, based on the collective subject discourse technique, was conducted in four healthcare centers of reference in Fortaleza, Ceará, from March to July 2014. The sample comprised 21 subjects (11 index patients and 10 notified partners. RESULTS The index patients reported complicity, concern about the partner's health and revelation of diagnosis aiming to preserve the relationship. The partners showed antagonistic perceptions: tranquility-betrayal, fear of death, of incurability and the diagnosis, especially of HIV. The reasons for coming to a healthcare center were: fear of being sick, attenuation of guilt of infection transmission, need for diagnosis, early start of treatment. CONCLUSION Fear of losing trust, insecurities when dealing with a sexual infection and being responsible or co-responsible for the transmission were the predominant feelings. Various types of partner notification were reported (verbal, telephone, notification card, according to individual convenience. This study suggests the use of alternative methods of notification and an integrated system of notification.

  17. The influences of partner accuracy and partner memory ability on social false memories.

    Science.gov (United States)

    Numbers, Katya T; Meade, Michelle L; Perga, Vladimir A

    2014-11-01

    In this study, we examined whether increasing the proportion of false information suggested by a confederate would influence the magnitude of socially introduced false memories in the social contagion paradigm Roediger, Meade, & Bergman (Psychonomic Bulletin & Review 8:365-371, 2001). One participant and one confederate collaboratively recalled items from previously studied household scenes. During collaboration, the confederate interjected 0 %, 33 %, 66 %, or 100 % false items. On subsequent individual-recall tests across three experiments, participants were just as likely to incorporate misleading suggestions from a partner who was mostly accurate (33 % incorrect) as they were from a partner who was not at all accurate (100 % incorrect). Even when participants witnessed firsthand that their partner had a very poor memory on a related memory task, they were still as likely to incorporate the confederate's entirely misleading suggestions on subsequent recall and recognition tests (Exp. 2). Only when participants witnessed firsthand that their partner had a very poor memory on a practice test of the experimental task itself were they able to reduce false memory, and this reduction occurred selectively on a subsequent individual recognition test (Exp. 3). These data demonstrate that participants do not always consider their partners' memory ability when working on collaborative memory tasks.

  18. Romantic Partners, Friends, Friends with Benefits, and Casual Acquaintances As Sexual Partners

    Science.gov (United States)

    Furman, Wyndol; Shaffer, Laura

    2011-01-01

    The purpose of the present study was to provide a detailed examination of sexual behavior with different types of partners. A sample of 163 young adults reported on their light nongenital, heavy nongenital, and genital sexual activity with romantic partners, friends, and casual acquaintances. They described their sexual activity with “friends with benefits” as well as with friends in general. Young adults were most likely to engage in sexual behavior with romantic partners, but sexual behavior also often occurred with some type of nonromantic partner. More young adults engaged in some form of sexual behavior with casual acquaintances than with friends with benefits. The frequencies of sexual behavior, however, were greater with friends with benefits than with friends or casual acquaintances. Interview and questionnaire data revealed that friends with benefits were typically friends, but not necessarily. Nonsexual activities were also less common with friends with benefits than other friends. Taken together, the findings illustrate the value of differentiating among different types of nonromantic partners and different levels of sexual behavior. PMID:21128155

  19. Intimate Partner Violence: The Lived Experience of Single Women.

    Science.gov (United States)

    Thomas, Laura; Scott-Tilley, Donna

    2017-03-01

    Research in intimate partner violence has focused on married, cohabiting, adolescents, or college aged women. The experience of intimate partner violence by single women has not been studied separately from other groups of women. An interpretive phenomenological approach was used with feminist inquiry to gain insight into the experience of intimate partner violence by single women. The overarching theme was control and manipulation by the abuser. Subthemes included not feeling safe, poor communication skills, and caretaking. Nurses need to be aware of the occurrence of intimate partner violence in male and female partnered relationships to provide comprehensive and nonjudgmental care.

  20. Identification of the critical sequence elements in the cytoplasmic domain of leptin receptor isoforms required for Janus kinase/signal transducer and activator of transcription activation by receptor heterodimers.

    Science.gov (United States)

    Bahrenberg, Gregor; Behrmann, Iris; Barthel, Andreas; Hekerman, Paul; Heinrich, Peter Claus; Joost, Hans-Georg; Becker, Walter

    2002-04-01

    Two predominant splice variants of the leptin receptor (LEPR) are coexpressed in leptin-responsive tissues: the long form, LEPRb, characterized as the signal-transducing receptor, and the signaling-defective short form, LEPRa. It is unknown whether heterodimers of these isoforms are capable of signal transduction via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. To address this question, chimeric receptors were constructed consisting of the transmembrane and intracellular parts of LEPRb and LEPRa fused with the extracellular domains of either the alpha- or beta-subunit of the IL-5 receptor. This strategy allows the directed heterodimerization of different LEPR cytoplasmic tails and excludes homodimerization. In COS-7 and HEPG2 cells, chimeric receptor heterodimers of LEPRa and LEPRb failed to activate the JAK/STAT pathway, whereas receptor dimers of LEPRb gave rise to the expected ligand-dependent activation of JAK2, phosphorylation of STAT3, and STAT3-dependent promoter activity. Markedly lower amounts of JAK2 were found to be associated with immunoprecipitated LEPRa chimeras than with LEPRb chimeras. Analysis of a series of deletion constructs indicated that a segment of 15 amino acids in addition to the 29 amino acids common to LEPRa and LEPRb was required for partial restoration of JAK/STAT activation. Site-directed mutagenesis of the critical sequence indicated that two hydrophobic residues (Leu896, Phe897) not present in LEPRa were indispensable for receptor signaling. These findings show that LEPRa/LEPRb heterodimers cannot activate STAT3 and identify sequence elements within the LEPR that are critical for the activation of JAK2 and STAT3.

  1. Partner switching can favour cooperation in a biological market.

    Science.gov (United States)

    Schwagmeyer, P L

    2014-09-01

    Intraspecific cooperation and interspecific mutualisms can be promoted by mechanisms that reduce the frequency with which cooperative organisms are exploited by unhelpful partners. One such mechanism consists of changing partners after interacting with an uncooperative individual. I used McNamara et al.'s (Nature, 451, 2008, 189) partner switching model as a framework to examine whether this mechanism can select for increased cooperative investment by house sparrows (Passer domesticus) collaborating to rear offspring; previous research on this species has shown that substantial cooperative investments by both pair members are required to achieve high pay-offs from collaborating. I found that the poorer the outcome of a breeding attempt relative to the number of eggs the female invested, the greater the likelihood of partner switching. The incidence of partner switching changed seasonally, with peak switching coinciding with an increase in the number of alternative partners available to females. After females switched partners, their breeding outcomes rose to match those of females that remained with the same partner; this was not the case for males that switched partners. Consistent with the model's prediction, males in stable partnerships achieved over 25% higher than average reproductive success, which was attributable to both persistently good breeding outcomes and their older partners' high fecundity. These results provide empirical support for the hypothesis that partner switching favours increased cooperative investment levels, and they demonstrate that variation in the relative value of by-product benefits can enhance that process.

  2. Mutagenesis of Varicella-Zoster Virus Glycoprotein I (gI) Identifies a Cysteine Residue Critical for gE/gI Heterodimer Formation, gI Structure, and Virulence in Skin Cells▿

    Science.gov (United States)

    Oliver, Stefan L.; Sommer, Marvin H.; Reichelt, Mike; Rajamani, Jaya; Vlaycheva-Beisheim, Leonssia; Stamatis, Shaye; Cheng, Jason; Jones, Carol; Zehnder, James; Arvin, Ann M.

    2011-01-01

    Varicella-zoster virus (VZV) is the alphaherpesvirus that causes chicken pox (varicella) and shingles (zoster). The two VZV glycoproteins gE and gI form a heterodimer that mediates efficient cell-to-cell spread. Deletion of gI yields a small-plaque-phenotype virus, ΔgI virus, which is avirulent in human skin using the xenograft model of VZV pathogenesis. In the present study, 10 mutant viruses were generated to determine which residues were required for the typical function of gI. Three phosphorylation sites in the cytoplasmic domain of gI were not required for VZV virulence in vivo. Two deletion mutants mapped a gE binding region in gI to residues 105 to 125. A glycosylation site, N116, in this region did not affect virulence. Substitution of four cysteine residues highly conserved in the Alphaherpesvirinae established that C95 is required for gE/gI heterodimer formation. The C95A and Δ105–125 (with residues 105 to 125 deleted) viruses had small-plaque phenotypes with reduced replication kinetics in vitro similar to those of the ΔgI virus. The Δ105–125 virus was avirulent for human skin in vivo. In contrast, the C95A mutant replicated in vivo but with significantly reduced kinetics compared to those of the wild-type virus. In addition to abolished gE/gI heterodimer formation, gI from the C95A or the Δ105–125 mutant was not recognized by monoclonal antibodies that detect the canonical conformation of gI, demonstrating structural disruption of gI in these viruses. This alteration prevented gI incorporation into virus particles. Thus, residues C95 and 105 to 125 are critical for gI structure required for gE/gI heterodimer formation, virion incorporation, and ultimately, effective viral spread in human skin. PMID:21345964

  3. The inhibition of the human cholesterol 7α-hydroxylase gene (CYP7A1) promoter by fibrates in cultured cells is mediated via the liver x receptor α and peroxisome proliferator-activated receptor α heterodimer

    OpenAIRE

    Gbaguidi, G. Franck; Agellon, Luis B.

    2004-01-01

    In previous work, we showed that the binding of the liver x receptor α:peroxisome proliferator-activated receptor α (LXRα:PPARα) heterodimer to the murine Cyp7a1 gene promoter antagonizes the stimulatory effect of their respective ligands. In this study, we determined if LXRα:PPARα can also regulate human CYP7A1 gene promoter activity. Co-expression of LXRα and PPARα in McArdle RH7777 hepatoma cells decreased the activity of the human CYP7A1 gene promoter in response to fibrates and 25-hydrox...

  4. Associations of Partner Age Gap at Sexual Debut with Teenage Parenthood and Lifetime Number of Partners.

    Science.gov (United States)

    Masho, Saba W; Chambers, Gregory J; Wallenborn, Jordyn T; Ferrance, Jacquelyn L

    2017-06-01

    Age at sexual debut and age gap between partners at debut are modifiable characteristics that may be related to risky sexual behaviors. Understanding any such relationships is a necessary first step toward strengthening risk interventions. Age at sexual debut and partner age gap were examined for 3,154 female and 2,713 male respondents to the 2011-2013 National Survey of Family Growth who first had intercourse before age 18. Multivariable logistic regression was used to assess associations between these measures and teenage parenthood and reporting a high lifetime number of partners (i.e., a number above the sample median). Females' odds of teenage parenthood were elevated if sexual debut occurred at ages 15-17 and involved a partner age gap of 3-4 years (odds ratio, 1.8) or more (2.0); they were reduced if debut occurred before age 15 and the gap was 3-4 years (0.8). Females' likelihood of reporting a high lifetime number of partners was negatively associated with age gap (0.4-0.7, depending on age at debut and length of age gap). Males' likelihood of reporting a large number of partners was positively associated with age gap if sexual debut was before age 15 and the gap was five or more years (1.7) or if debut was at ages 15-17 and involved a 3-4-year gap (2.0). Identifying the mechanisms underlying these associations could inform program design and implementation. Copyright © 2017 by the Guttmacher Institute.

  5. Community Partners for Healthy Farming Intervention Research.

    Science.gov (United States)

    Ehlers, J; Palermo, T

    2005-05-01

    The purpose of the Community Partners for Healthy Farming Intervention Research (CPHF-IR) program is to implement and evaluate existing or new interventions for reduction of agriculture-related injuries, hazards, and illnesses. Objectives include the development of active partnerships between experienced researchers, communities, workers, managers, agricultural organizations, agribusinesses, and other stakeholders. Specific intervention projects were selected by the competitive review process in response to a request for proposals. The second series of projects (funded 2000-2003) targeted: improved ergonomics for handling grapes (CA) and for small-scale berry growers (WI, IA, MI, MN), engineering controls (KY, VA, SC) and training (IN) related to tractors, private-sector financial incentives for safety (IA, NE), and reducing eye injuries in Latino farmworkers (IL, MI, FL). Partners have provided their unique resources for accessing the target population, planning, implementation, dissemination, and evaluation. They have produced useful engineering controls, educational and motivational tools, and helped build infrastructure for promoting agricultural health as essential to sustainable agriculture. Additional outcomes have included: increased interest among participants in collaborating in further research, the feasibility of Latino lay health advisors as active partners in research, and the value of process evaluation of a partnership to enhance intervention sustainability. NIOSH is utilizing the model created for Simple Solutions: Ergonomics for Farm Workers, a document related to earlier CPHF-IR projects, for a comparable document for construction in both English and Spanish. This program has confirmed that such partnerships can produce not only sustainable interventions but also products and models with the potential to expand farther geographically than originally anticipated and even into other sectors, e.g., for primary prevention among healthcare workers and

  6. TEP Power Partners Project [Tucson Electric Power

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2014-02-06

    The Arizona Governor’s Office of Energy Policy, in partnership with Tucson Electric Power (TEP), Tendril, and Next Phase Energy (NPE), formed the TEP Power Partners pilot project to demonstrate how residential customers could access their energy usage data and third party applications using data obtained from an Automatic Meter Reading (AMR) network. The project applied for and was awarded a Smart Grid Data Access grant through the U.S. Department of Energy. The project participants’ goal for Phase I is to actively engage 1,700 residential customers to demonstrate sustained participation, reduction in energy usage (kWh) and cost ($), and measure related aspects of customer satisfaction. This Demonstration report presents a summary of the findings, effectiveness, and customer satisfaction with the 15-month TEP Power Partners pilot project. The objective of the program is to provide residential customers with energy consumption data from AMR metering and empower these participants to better manage their electricity use. The pilot recruitment goals included migrating 700 existing customers from the completed Power Partners Demand Response Load Control Project (DRLC), and enrolling 1,000 new participants. Upon conclusion of the project on November 19, 2013; 1,390 Home Area Networks (HANs) were registered; 797 new participants installed a HAN; Survey respondents’ are satisfied with the program and found value with a variety of specific program components; Survey respondents report feeling greater control over their energy usage and report taking energy savings actions in their homes after participating in the program; On average, 43 % of the participants returned to the web portal monthly and 15% returned weekly; and An impact evaluation was completed by Opinion Dynamics and found average participant savings for the treatment period1 to be 2.3% of their household use during this period.2 In total, the program saved 163 MWh in the treatment period of 2013.

  7. Coordinating the United States Interagency Partnering Effort

    Science.gov (United States)

    2013-03-01

    stage over the last 6 years.7 The DoD is on the cutting edge of partnering and there have been valuable lessons learned at the tactical and...global stage . “3D are the three pillars that provide the foundation for promoting and protecting U.S. national security interests abroad.”33 DoD, DoS...operations now will mean throwing 18 away hard-fought gains, and expose the United States to new risks from across the globalising

  8. Intimate Partner Violence Against Women in Zimbabwe.

    Science.gov (United States)

    Fidan, Ahmet; Bui, Hoan N

    2016-08-01

    The present study examines intimate partner violence (IPV) reported by a sample of women in Zimbabwe to explore factors associated with the problem. Findings from the study indicate an important role of gender relationships in violence against women. The effects of gender inequalities on the likelihood of IPV vary with types of violence, but husband's patriarchal behaviors increase the likelihood of all forms of violence. The study suggests the importance of improving gender equality through public education on gender relationships, increasing women's education and economic opportunities, and eliminating customary laws that sustain gender inequality as necessary steps to combat IPV against women in Zimbabwe. © The Author(s) 2015.

  9. Jacobi photonic lattices and their SUSY partners.

    Science.gov (United States)

    Zúñiga-Segundo, A; Rodríguez-Lara, B M; Fernández C, David J; Moya-Cessa, H M

    2014-01-13

    We present a classical analog of quantum optical deformed oscillators in arrays of waveguides. The normal modes of these one-dimensional photonic crystals are given in terms of Jacobi polynomials. We show that it is possible to attack the problem via factorization by exploiting the corresponding quantum optical model. This allows us to provide an unbroken supersymmetric partner of the proposed Jacobi lattices. Thanks to the underlying SU(1, 1) group symmetry of the lattices, we present the analytic propagators and impulse functions for these one-dimensional photonic crystals.

  10. Hiring your next partner: AOA critical issues.

    Science.gov (United States)

    Blasier, R Dale; Gagnon, Michael R; Iannotti, Joseph P; Jarvis-Selinger, Sandra

    2014-09-01

    Hiring a new partner into an orthopaedic department or group can be a daunting task. A recent American Orthopedic Association symposium sought to address three major aspects of hiring that affect orthopaedic leaders: (1) when to hire-the chairperson's role; (2) generational issues that affect hiring; and (3) the development of an initial compensation package.How does the chairperson recruit new physicians? Hiring a new partner into the academic setting requires a good deal of foresight. There must be an established game plan. Advertising and interviews need to be orchestrated. Chairpersons can find information about candidates from many unique sources. Fit within the department and community is important and must be cultivated. Spouses and families need special attention. Research candidates have individual needs. Perhaps the most important aspect of recruitment is the development of a realistic business plan. This paper provides an overview of factors to consider in managing a new hire.Generational issues are intriguing. Should they affect our hiring practices? It seems clear to established physicians that the new generation of graduates is different from their predecessors. Is this really true? Most everyone is familiar with the terms "Silent Generation," "Baby Boomers," "Generation X," and "Generation Y." Is there anything to be gained by categorizing an applicant? Is it important to hire a replica of one's self? This paper provides a thoughtful overview of generational issues as they apply to hiring new partners.Most department chairpersons are not trained as negotiators. Some preparation and experience are helpful in guiding the process of making an initial offer to a candidate. It is not all about pay. The package includes the guarantee period, expectations for the new hire, mentorship, and resources. How much should new orthopaedic academic hires be paid? Recent benchmark data from the Academic Orthopaedic Consortium suggest a mean income of $282,667 for

  11. Touch increases autonomic coupling between romantic partners

    Directory of Open Access Journals (Sweden)

    Jonas eChatel-Goldman

    2014-03-01

    Full Text Available Interpersonal touch is of paramount importance in human social bonding and close relationships, allowing a unique channel for affect communication. So far the effect of touch on human physiology has been studied at an individual level. The present study aims at extending the study of affective touch from isolated individuals to truly interacting dyads. We have designed an ecological paradigm where romantic partners interact only via touch and we manipulate their empathic states. Simultaneously, we collected their autonomic activity (skin conductance, pulse, respiration. 14 couples participated to the experiment. We found that interpersonal touch increased coupling of electrodermal activity between the interacting partners, regardless the intensity and valence of the emotion felt. In addition, physical touch induced strong and reliable changes in physiological states within individuals. These results support an instrumental role of interpersonal touch for affective support in close relationships. Furthermore, they suggest that touch alone allows the emergence of a somatovisceral resonance between interacting individuals, which in turn is likely to form the prerequisites for emotional contagion and empathy.

  12. An approach to non-traditional partners

    Directory of Open Access Journals (Sweden)

    Ornela Fabani

    2015-11-01

    Full Text Available The aim of this paper is to describe and analyse the evolution of the political-diplomatic and the economic and trade links between Argentina and the Gulf monarchies, as well as the factors that explain this evolution, during the administrations of Cristina Fernandez (2007-2015. Meanwhile, the premise that informs it is that that during Fernandez's governments the political and diplomatic relations between Argentina and the UAE, Saudi Arabia, Kuwait and Qatar became more dynamic as a result of the Argentine interest in strengthening economic and trade ties with those States. The deepening of these ties is explained in terms of some of the main areas of Argentina's foreign trade policy, which focus on the following: to diversify trade partners, attract investment and increase the volume of trade. Moreover, the aforementioned actors are perceived as potential partners in that the Gulf monarchies need to ensure food security and advance technological cooperation, in a context marked by the international financial crisis.

  13. Designing Comprehensive Partnering Agreements : An Introduction to the Partnering Agreement Scorecard

    NARCIS (Netherlands)

    S.M. Pfisterer (Stella); N. Payandeh (Nasim); S. Reid

    2014-01-01

    textabstractAgreements are a key mechanism of partnerships because their role is to govern interactions. They help partnerships become more effective by allowing partners to cope with relational, performance and situational risks that characterise inter-organisational relationships. The Partnerships

  14. Actor and Partner Effects of Adolescents' Romantic Working Models and Styles on Interactions with Romantic Partners

    Science.gov (United States)

    Furman, Wyndol; Simon, Valerie A.

    2006-01-01

    The present study examined how adolescents' and their romantic partners' romantic working models and relational styles were related to their interactions with each other. Sixty-five couples (M age=18.1 years) were observed interacting. Romantic working models were assessed in interviews about their romantic experiences; romantic styles were…

  15. Violence in childhood, attitudes about partner violence, and partner violence perpetration among men in Vietnam

    NARCIS (Netherlands)

    Yount, K.M.; Huyen, T.P.; Tran, H.M.; Krause, K.H.; Schuler, S.R.; Hoang, T.A.; VanderEnde, K.; Kramer, M.R.

    2014-01-01

    Purpose: We assess the association of men’s exposure to violence in childhood—witnessing physical violence against one’s mother and being hit or beaten by a parent or adult relative—with their attitudes about intimate partner violence (IPV) against women. We explore whether men’s perpetration of IPV

  16. Nothing is more important than my partner's health: Turkish men's perspectives on partner's appearance after mastectomy and alopecia.

    Science.gov (United States)

    Gürsoy, Ayla; Koçan, Sema; Aktuğ, Cemile

    2017-08-01

    The aim of this study was to acquire a deeper understanding of male experiences on the emotional and social impact of their partners' mastectomy and chemotherapy-induced alopecia. A purposive sample of 16 males whose partners had undergone mastectomy and alopecia due to chemotherapy was chosen. The data were collected through a semi-structured interview method. Interpretative Phenomenological Analysis of tape-recorded interviews was employed. Two main themes emerged from the data: facing the changes and my wife and I at present. Male partners were affected differently by the change in the physical appearance of their female partners. Our study participants said it was a difficult experience to see their partners for the first time after the surgery, but they emphasized that it was more important that their partners were healthy than the fact that they did not have a breast and hair. They also said they did not know how to behave towards their partners after surgery and/or chemotherapy. Nevertheless, they felt that the disease process of their partners had strengthened their bond and had not negatively influenced their relationship with others. The changes in the partners' physical appearance after mastectomy and chemotherapy affected males differently in psychological, emotional and social terms. Since nurses working in this field are in contact with patients during all phases of treatment and care, it would be positive and beneficial to plan nursing interventions that give emotional support for male partners of patients with breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Intimate partner violence and maternal educational practice.

    Science.gov (United States)

    Silva, Josianne Maria Mattos da; Lima, Marília de Carvalho; Ludermir, Ana Bernarda

    2017-04-10

    The objective of this study is to analyze the association between intimate partner violence against women and maternal educational practice directed to children at the beginning of formal education. This is a cross-sectional study, carried out between 2013 and 2014, with 631 mother/child pairs, registered in the Family Health Strategy of the Health District II of the city of Recife, State of Pernambuco, Brazil. It integrates a prospective cohort study designed to investigate the consequences of exposure to intimate partner violence in relation to the child who was born between 2005 and 2006. The maternal educational practice has been assessed by the Parent-Child Conflict Tactics Scale and the intimate partner violence by a questionnaire adapted from the Multi-Country Study on Women's Health and Domestic Violence of the World Health Organization. Intimate partner violence referred to the last 12 months and was defined by specific acts of psychological, physical, and sexual violence inflicted to women by the partner. The crude and adjusted prevalence ratios were estimated for the association studied, using log-binomial regression. The prevalence of intimate partner violence was 24.4%, and violent maternal educational practice was 93.8%. The use of non-violent discipline was mentioned by 97.6% of the women, coexisting with violent strategies of discipline. Children whose mothers reported intimate partner violence presented a higher chance of suffering psychological aggression (PR = 2.2; 95%CI 1.0-4.7). The violence suffered by the mother interferes in the parental education. The findings show high prevalence of violent maternal educational practice, pointing to the need for interventions that minimize the damage of violence in women and children. Analisar a associação entre a violência pelo parceiro íntimo contra a mulher e a prática educativa materna direcionada às crianças no início da escolaridade formal. Estudo transversal, realizado entre 2013 e 2014, com

  18. Preferential partner selection in an evolutionary study of prisoner's dilemma

    CERN Document Server

    Ashlock, D; Stanley, E A; Tesfatsion, L; Ashlock, Dan; Smucker, Mark D; Stanley, E Ann; Tesfatsion, Leigh

    1994-01-01

    Partner selection is an important process in many social interactions, permitting individuals to decrease the risks associated with cooperation. In large populations, defectors may escape punishment by roving from partner to partner, but defectors in smaller populations risk social isolation. We investigate these possibilities for an evolutionary prisoner's dilemma in which agents use expected payoffs to choose and refuse partners. In comparison to random or round-robin partner matching, we find that the average payoffs attained with preferential partner selection tend to be more narrowly confined to a few isolated payoff regions. Most ecologies evolve to essentially full cooperative behavior, but when agents are intolerant of defections, or when the costs of refusal and social isolation are small, we also see the emergence of wallflower ecologies in which all agents are socially isolated. In between these two extremes, we see the emergence of ecologies whose agents tend to engage in a small number of defecti...

  19. Infrastructure for Personalized Medicine at Partners HealthCare

    Directory of Open Access Journals (Sweden)

    Scott T. Weiss

    2016-02-01

    Full Text Available Partners HealthCare Personalized Medicine (PPM is a center within the Partners HealthCare system (founded by Massachusetts General Hospital and Brigham and Women’s Hospital whose mission is to utilize genetics and genomics to improve the care of patients in a cost effective manner. PPM consists of five interconnected components: (1 Laboratory for Molecular Medicine (LMM, a CLIA laboratory performing genetic testing for patients world-wide; (2 Translational Genomics Core (TGC, a core laboratory providing genomic platforms for Partners investigators; (3 Partners Biobank, a biobank of samples (DNA, plasma and serum for 50,000 Consented Partners patients; (4 Biobank Portal, an IT infrastructure and viewer to bring together genotypes, samples, phenotypes (validated diagnoses, radiology, and clinical chemistry from the electronic medical record to Partners investigators. These components are united by (5 a common IT system that brings researchers, clinicians, and patients together for optimal research and patient care.

  20. Partner Selection Optimization Model of Agricultural Enterprises in Supply Chain

    Directory of Open Access Journals (Sweden)

    Feipeng Guo

    2013-10-01

    Full Text Available With more and more importance of correctly selecting partners in supply chain of agricultural enterprises, a large number of partner evaluation techniques are widely used in the field of agricultural science research. This study established a partner selection model to optimize the issue of agricultural supply chain partner selection. Firstly, it constructed a comprehensive evaluation index system after analyzing the real characteristics of agricultural supply chain. Secondly, a heuristic method for attributes reduction based on rough set theory and principal component analysis was proposed which can reduce multiple attributes into some principal components, yet retaining effective evaluation information. Finally, it used improved BP neural network which has self-learning function to select partners. The empirical analysis on an agricultural enterprise shows that this model is effective and feasible for practical partner selection.

  1. Partner Power: A study of two distance education consortia

    Directory of Open Access Journals (Sweden)

    Anne Banks Pidduck

    2006-12-01

    Full Text Available This research reports findings from a study which explored the process and criteria of partner selection – how and why partners are chosen – for two distance education consortia. The researchers reviewed recent literature on partnerships and partner selection. Two Canada-wide distance education consortia were identified as large-scale case studies for investigation of the research theory. A total of 34 informants were contacted. Written business plans, contracts, documents, partner network diagrams, and 231 archival emails from 36 correspondents were collected and analyzed for the two consortia. The research identified four criteria that influence why specific partners are chosen: requirements, resource availability, social network, and reputation. These findings suggest that the formation of partnerships and the process of partner selection are both very complex.

  2. The psychopathic intimate partner batterer: a non-psychopathological profile

    Directory of Open Access Journals (Sweden)

    José M. Pozueco-Romero

    2014-01-01

    Full Text Available This theoretical study reviews two of the most cited profiles of intimate partner batterers in the scientific literature, paying special attention to the most notable differences between them, as well as to their common criteria. The study also discusses one of the longest standing controversies in various research studies, including the particular overview with respect to Spain: it being the constant yet erroneous reference to the equivalence of psychopathy and antisocial personality disorder. Similarly, special attention is paid to the implications of considering intimate partner batterers as having either a psychopathological or psychopathic profile, while also stressing the specific role played by psychopathy in the intimate partner batterer and, concerning psychopathic intimate partner batterers, such aspects as their specific motives for perpetrating intimate partner violence and the evaluation instruments of this particular profile. Finally, a series of future directives for research concerning psychopathic intimate partner batterers are also pointed out.

  3. Perpetration and Victimization of Intimate Partner Aggression Among Rural Mothers

    OpenAIRE

    Schwab Reese, Laura M.; Harland, Karisa; Smithart, Kelsey; Ramirez, Marizen

    2015-01-01

    Intimate partner aggression is a leading cause of injury among women of child-bearing age. Research suggests that pregnancy and the postpartum period are times of increased vulnerability to aggression. Since rural women are at an increased risk of intimate partner aggression, research is needed to examine the role of pregnancy and the presence of children on intimate partner aggression among this vulnerable population. The purpose of this study is to examine the association between young chil...

  4. Ovulatory shifts in women's attractions to primary partners and other men: further evidence of the importance of primary partner sexual attractiveness

    National Research Council Canada - National Science Library

    Larson, Christina M; Pillsworth, Elizabeth G; Haselton, Martie G

    2012-01-01

    Previous research has documented shifts in women's attractions to their romantic partner and to men other than their partner across the ovulation cycle, contingent on the degree to which her partner...

  5. High Rate of Partner Treatment Among Chlamydia trachomatis-Infected Pregnant Women in Lima, Peru.

    Science.gov (United States)

    Nguyen, Minh; Cabeza, Jeanne; Segura, Eddy; García, Patricia J; Klausner, Jeffrey D

    2016-05-01

    This was a substudy of 60 Chlamydia trachomatis-infected women from a larger study of pregnant women in Lima, Peru. Participants were encouraged to bring their partners in for concurrent patient-partner treatment. The alternative partner treatment was expedited partner therapy. Partner treatment uptake was 91.7%. Twenty-one partners (38.2%) received treatment through concurrent patient-partner treatment, and 34 (61.8%) through expedited partner therapy. Living with the partner was significantly associated with having the partner treated (P=0.0028).

  6. Current evidence on perinatal home visiting and intimate partner violence.

    Science.gov (United States)

    Sharps, Phyllis W; Campbell, Jacquelyn; Baty, Marguerite L; Walker, Keisha S; Bair-Merritt, Megan H

    2008-01-01

    To describe current evidence on home visiting interventions for pregnant or postpartum women with specific intimate partner violence assessment and content. Online bibliographic databases including PubMed, CINAHL Plus, and Web of Science and a hand search of bibliographies of relevant articles. Original research and intervention studies were included that contained (a) a well-described prenatal and/or postpartum home visitation; (b) an assessment of perinatal intimate partner violence; and (c) quantitative data describing health outcomes for the women and their infants. The search yielded 128 articles, and 8 relevant articles met all of the inclusion criteria. Nonresearch, nonintervention, and international articles were excluded. No perinatal home visiting interventions were designed to address intimate partner violence. Programs that screened for intimate partner violence found high rates, and the presence of intimate partner violence limited the ability of the intervention to improve maternal and child outcomes. Perinatal home visitation programs likely improve pregnancy and infant outcomes. Home visiting interventions addressing intimate partner violence in nonperinatal population groups have been effective in minimizing intimate partner violence and improving outcomes. This suggests that perinatal home visiting programs adding specific intimate partner violence interventions may reduce intimate partner violence and improve maternal and infant health. Continued rigorous research is needed.

  7. Partner Selection for Interfirm Collaboration: The Context of Ship Design

    Science.gov (United States)

    Solesvik, Marina Z.; Encheva, Sylvia

    There is a growing body of research devoted to the issues of cooperative design. However, there are still gaps in the existing knowledge on partner selection for cooperation. This paper intends to explore partner selection issues in the context of collaborative ship design. The study aims to fill a gap in the partner selection literature by proposing a quantitative technique based on formal concept analysis. An illustrative example of the selection of a partner for a project-based alliance in a naval architect firm is presented. The study has implications for practitioners and researchers.

  8. Partner change among Norwegian teenage girls attending youth health clinics.

    Science.gov (United States)

    Egil Skjeldestad, Finn; Nilsen, Stine

    2008-01-01

    To examine incidence and risk factors of partner change among Norwegian teenage girls attending youth health clinics. Prospective cohort study. Setting. Study subjects were 691 girls, aged 16 to 19 years, who participated in a study on prescription of oral contraceptives at three youth health clinics in the city of Trondheim, Norway. Eligible for analysis were participants who were sexually active, and who returned for at least one follow-up visit more than 120 days after study start. All demographic and behavior data were collected through interview by public health nurses. All analyses were performed with SPSS for Windows (version 15.0) using chi-square test, survival analyses and logistic regression. New sexual male partners. Four out of five girls (80%) did not have any new partner during the study period of 12 months. From survival analyses the 12-month incidence rate were 29.8 (95% CI: 25.3-34.1) and 10.6 per 100-women months (95% CI: 7.3-13.9) for one or two or more partners, respectively. Predictors of partner change were partner change during the last six month prior study start, being single and sexual debut within three years after menarche. CONCLUSION. Being in a regular relationship with a boyfriend reduce considerably the risk of having a new sexual partner. Recent history of partner change is the strongest predictor of future partner change.

  9. Prominent 85-kDa oligomannosidic glycoproteins of rat brain are signal regulatory proteins and include the SHP substrate-1 for tyrosine phosphatases.

    Science.gov (United States)

    Bartoszewicz, Z P; Jaffe, H; Sasaki, M; Möller, J R; Stebbins, J W; Gebrekristos, H; Quarles, R H

    1999-04-01

    The glycoprotein component in rat brain reacting most strongly with Galanthus nivalis agglutinin (GNA) on western blots migrates as an 85-kDa band. GNA identifies mannose-rich oligosaccharides because it is highly specific for terminal alpha-mannose residues. After purification of this 85-kDa glycoprotein band by chromatography on GNA-agarose and preparative gel electrophoresis, binding of other lectins demonstrated the presence of fucose and a trace of galactose, but no sialic acid. Treatment with N-Glycanase or endoglycosidase H produced a 65-kDa band, indicating that it consisted of about one-fourth N-linked oligomannosidic carbohydrate moieties. High-performance anion-exchange chromatography and fluorescence-assisted carbohydrate electrophoresis indicated that the major carbohydrate moiety is a heptasaccharide with the structure Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4Glc-NAcbeta1-4GlcNAc (Man5GlcNAc2). Determination of amino acid sequences of peptides produced by endoproteinase digestion demonstrated that this 85-kDa mannose-rich glycoprotein component contained the SHP substrate-1 for phosphotyrosine phosphatases and at least one other member of the signal-regulatory protein (SIRP) family. The unusually high content of oligomannosidic carbohydrate moieties on these receptor-like members of the immunoglobulin superfamily in neural tissue could be of functional significance for intercellular adhesion or signaling.

  10. Simplified matrix for assessment to environmental impacts on small hydroelectric power plants (SHP); Matriz simplificada para avaliar impactos ambientais em pequenas centrais hidreletricas (PCH)

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Tania A.P. de Souza; Dupas, Francisco Antonio [Universidade Federal de Itajuba, MG (Brazil). Inst. de Recursos Naturais]. E-mails: taniabarbosa@unifei.edu.br; dupas@unifei.edu.br

    2006-07-01

    This work intends to study the methodologies used by EIA and proposes the adaptation of a simplified matrix for the assessment of environmental impacts regarding small hydropower plants. A case study of Ninho da Aguia SHP, located in the city of Delfim Moreira, MG, was used for elaborating the matrix. The methodology used the analysis of all the negative impacts and they were given combined weight based on a pre-established impact scale. The weights that were given to each impact were distributed according to the combination of features presented in the referred EIA. The results attained show that the environmental damage is reduced by 45% when the mitigating measures suggested by the EIA and by the analysis carried out by this study are applied. Besides, this preliminary proposal will make it possible for the process of getting an environmental license to be accelerated. Today, this process is considered as an investment inhibitor because of its slowness caused by the environmental organs that analyze these studies. Also, it may be used as initial guidelines regarding the environmental cost of the implementation of the enterprise. The proposed matrix shows itself as efficient because it is easy to be used and it is a useful tool for the analysis of projects that will be implemented.

  11. Uncertainty in Partner Selection for Virtual Enterprises

    Science.gov (United States)

    Crispim, José; de Sousa, Jorge Pinho

    A virtual enterprise (VE) is a temporary organization that pools the core competencies of its member enterprises and exploits fast changing market opportunities. The success of such an organization is strongly dependent on its composition, and the selection of partners becomes therefore a crucial issue. This problem is particularly difficult because of the uncertainties related to information, market dynamics, customer expectations and technology speed up. In this paper we propose an integrated approach to rank alternative VE configurations in business environments with uncertainty, using an extension of the TOPSIS method for fuzzy data, improved through the use of a stochastic multiobjective tabu search meta-heuristic. Preliminary computational results clearly demonstrate the potential of this approach for practical application.

  12. Physical intimate partner violence in northern India.

    Science.gov (United States)

    Ragavan, Maya I; Iyengar, Kirti; Wurtz, Rebecca M

    2014-04-01

    In this article, we examine perceptions about the definition of physical intimate partner violence (IPV) in northern India utilizing feminist perspectives as a framework. We interviewed 56 women and 52 men affiliated with a health services nongovernmental organization in the Udaipur district of Rajasthan. We transcribed, coded, and analyzed the interviews utilizing grounded theory. We found that perceptions regarding physical IPV were associated with both structural and ideological patriarchal beliefs and microlevel constructs such as alcohol use. We discovered multiple types of physical IPV in the study region, including rationalized violence (socially condoned violence perpetrated by a husband against his wife), unjustified violence (socially prohibited violence perpetrated by a husband against his wife), and majboori violence (violence perpetrated by a wife against her husband). Our results add to the breadth of research available about IPV in India and create a framework for future research and IPV prevention initiatives.

  13. Top Partners Searches and Composite Higgs Models

    CERN Document Server

    Matsedonskyi, Oleksii; Wulzer, Andrea

    2015-01-01

    Colored fermionic partners of the top quark are well-known signatures of the Composite Higgs scenario and for this reason they have been and will be subject of an intensive experimental study at the LHC. Performing an assessment of the theoretical implications of this experimental effort is the goal of the present paper. We proceed by analyzing a set of simple benchmark models, characterized by simple two-dimensional parameter spaces where the results of the searches are conveniently visualized and their impact quantified. We only draw exclusion contours, in the hypothesis of no signal, but of course our formalism could equally well be used to report discoveries in a theoretically useful format.

  14. Top partners searches and composite Higgs models

    Science.gov (United States)

    Matsedonskyi, Oleksii; Panico, Giuliano; Wulzer, Andrea

    2016-04-01

    Colored fermionic partners of the top quark are well-known signatures of the Composite Higgs scenario and for this reason they have been and will be subject of an intensive experimental study at the LHC. Performing an assessment of the theoretical implications of this experimental effort is the goal of the present paper. We proceed by analyzing a set of simple benchmark models, characterized by simple two-dimensional parameter spaces where the results of the searches are conveniently visualized and their impact quantified. We only draw exclusion contours, in the hypothesis of no signal, but of course our formalism could equally well be used to report discoveries in a theoretically useful format.

  15. The clinical studies to developing BV Partner

    Directory of Open Access Journals (Sweden)

    Kwon Gi-Rok

    2001-12-01

    Full Text Available Objective: This study was performed to examine the Herbal Acupuncture decrease the side effect of Bee Venom. Methods: We treated Bee Venom and various Herbal Acupuncture mixed Bee Venom using double blind test to 70th health youth, and checked pain, edema size, CBC, Serum biochemistry and Thermography. Results:1. Herbal Acupuncture made by Morus bombycis Koidzumi showed good results to decrease the side effect of Bee Venom than any other Herbal Acupuncture. 2. We examined CBC, ESR and Serum biochemistry before and after treated. Special change was not showed. 3. We observed the pain and edema after treated Bee Venom and Morus bombycis Koidzumi Herbal Acupuncture mixed Bee Venom. We knew that Morus bombycis Koidzumi Herbal Acupuncture was decrease the pain and edema due to Bee Venom. 4. According to these clinical studies, Morus bombycis Koidzumi Herbal Acupuncture has a possibility to be a good partner of Bee Venom.

  16. New partners of TKS4 scaffold protein

    Directory of Open Access Journals (Sweden)

    Kropyvko S. V.

    2015-10-01

    Full Text Available TKS4 scaffold protein is involved in the formation of invadopodia, the production of reactive oxygen species (ROS by tumor cells and other cellular processes. Aim. To identify new TKS4 partners involved in the actin cytoskeleton rearrangements and endo-/exocytosis. Methods. The GST pull-down assay was used to identify the interaction. Results. We revealed that TKS4 SH3 domains interact with the actin cytoskeleton reorganization proteins N-WASP and CR16, as well as with DNM2, SYNJ1 and OPHN1 which are involved in endo-/exocytosis. We also tested the WIP, WIRE, SHIP2, RhoU, RhoV and NUMB proteins, but their interaction with the SH3 domains of TKS4 was not found. Conclusions. The SH3 domains of TKS4 interact with N-WASP, DNM2, SYNJ1, OPHN1 and weakly with CR16 in vitro.

  17. Strategy Guideline. Partnering for High Performance Homes

    Energy Technology Data Exchange (ETDEWEB)

    Prahl, Duncan [IBACOS, Inc., Pittsburgh, PA (United States)

    2013-01-01

    High performance houses require a high degree of coordination and have significant interdependencies between various systems in order to perform properly, meet customer expectations, and minimize risks for the builder. Responsibility for the key performance attributes is shared across the project team and can be well coordinated through advanced partnering strategies. For high performance homes, traditional partnerships need to be matured to the next level and be expanded to all members of the project team including trades, suppliers, manufacturers, HERS raters, designers, architects, and building officials as appropriate. This guide is intended for use by all parties associated in the design and construction of high performance homes. It serves as a starting point and features initial tools and resources for teams to collaborate to continually improve the energy efficiency and durability of new houses.

  18. Effects of partner violence in migrant women

    Directory of Open Access Journals (Sweden)

    Leonor Guadalupe Delgadillo Guzmán

    2013-06-01

    Full Text Available This study analyzes the relationship between partner violence, depression and maternal self-efficacy in migrant women. It is thought that this type of violence brings about sinking morale and a hindrance for their development as mothers. It is a quantitative study of an explanatory correlational type, worked with 40 immigrant women with a residence of two to 25 years, with at least one reported episode of violation and at least one son in preschool. Three instruments were employed: “The Parental Involvement and Efficacy”, “The Survey-Depression Scale” and“The Revised Conflict Tactic Scale”. The results showed important relationships between the variables, namely, the more violence women suffer, the greater the depression is, and the greater the depression is, the lesser the maternal self-efficacy becomes.

  19. Top partner searches and Composite Higgs models

    Energy Technology Data Exchange (ETDEWEB)

    Matsedonskyi, Oleksii [DESY Hamburg (Germany); Panico, Giuliano [Barcelona Univ. Autonoma (Spain). IFAE; Wulyer, Andrea [Padova Univ. (Italy). Dipt. di Fisica e Astronomia; INFN, Padova (Italy)

    2015-12-15

    Colored fermionic partners of the top quark are well-known signatures of the Composite Higgs scenario and for this reason they have been and will be subject of an intensive experimental study at the LHC. Performing an assessment of the theoretical implications of this experimental effort is the goal of the present paper. We proceed by analyzing a set of simple benchmark models, characterized by simple two-dimensional parameter spaces where the results of the searches are conveniently visualized and their impact quantified. We only draw exclusion contours, in the hypothesis of no signal, but of course our formalism could equally well be used to report discoveries in a theoretically useful format.

  20. With or without you: does partner satisfaction and partner-directed violence influence the presence of a partner on women's Facebook cover profile photographs?

    Directory of Open Access Journals (Sweden)

    Pavol Prokop

    Full Text Available Social network sites (SNSs provide new opportunities for online self-presentation of millions of users. The cover profile photograph (CPP along with written information regarding relationship status is a central component of online self-presentation, although their associations with actual romantic relationships are not clear. We investigated relationships between the presence of a current romantic partner on the CPP and the displayed relationship status and partner satisfaction, partner-directed violence and women's intrasexual competition with peers. A total of 28 % of the 158 women with a Facebook profile and being involved in a romantic relationship had their romantic partners on their CPP. As predicted, women with their partners on the CPP were more satisfied with their romantic relationship than others. Furthermore, women who did not have their partner on the CPP tended to conceal or lie in their displayed mating status suggesting that this may be a strategy how to attract another potential mate. The partner-directed violence and intrasexual competition hypotheses were not supported. Overall, the CPP and an honestly displayed relationship status is an expression of relationship satisfaction amongst women.

  1. Virtual conversation partner for adults with autism.

    Science.gov (United States)

    Trepagnier, Cheryl Y; Olsen, Dale E; Boteler, Laura; Bell, Corinne A

    2011-01-01

    Autistic Spectrum Disorder (ASD) is notable for severely impaired reciprocal social interaction skills relative to language and intellectual abilities, presenting a major barrier to social integration and vocational success. Evidence-based interventions to address these needs are lacking. We report on the development of a small, prototype conversation simulation to teach conversational skills to adolescents and adults with ASD and average to superior intellectual abilities. We also report on a test of the feasibility and acceptability of the simulation approach with a sample of the target population. The simulation engages the user in a virtual conversation with an on-screen partner whose reactions provide naturalistic feedback geared to the appropriateness of the learner's response choices. The prototype simulation, which provides for up to 12 potentially unique multi-turn conversations, was used over a period of 2 weeks by 16 adolescents and adults who then rated statements about the system on a linear scale of 1 (disagreement) to 5 (high agreement). The participants highly endorsed the majority of positive statements about the quality and credibility of the interaction and the virtual conversation partner. In contrast, agreement with positive statements about instructional features external to the conversation was moderate. Unexpectedly, most participants strongly agreed that using the simulation had been helpful to them. Further development and testing in the context of a controlled study with randomized assignment to control and experimental groups are needed to determine whether this approach is effective in improving real-world pragmatic language behavior of high-functioning adults with ASD.

  2. Global methylation and promoter-specific methylation of the P16, SOCS-1, E-cadherin, P73 and SHP-1 genes and their expression in patients with multiple myeloma during active disease and remission.

    Science.gov (United States)

    Martínez-Baños, Déborah; Sánchez-Hernández, Beatríz; Jiménez, Guadalupe; Barrera-Lumbreras, Georgina; Barrales-Benítez, Olga

    2017-05-01

    Tumor suppressor gene promoter CpG island methylation is a well-recognized mechanism in cancer pathogenesis, but its role in multiple myeloma (MM) is controversial. The present study investigated the methylation status and expression of P16, suppressor of cytokine signaling 1 (SOCS-1), P73, E-cadherin and Src homology region 2 domain-containing phosphatase 1 (SHP-1), as well as global methylation in patients with MM during active disease and remission. Bone marrow samples were obtained from 43 patients at the Multiple Myeloma Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (Mexico City, Mexico) during active disease and remission. Methylation-specific polymerase chain reaction and ELISA were performed on bisulfite-treated or untreated DNA to determine promoter-specific or genomic methylation, respectively. Gene expression was measured using reverse-transcription polymerase chain reaction. The results indicated that SOCS-1 methylation occurred more frequently during active disease than remission [29 vs. 3.2% (P=0.021)] and was associated with more advanced forms of the disease [international staging system (ISS) 3, 16.67% vs. ISS 1, 8.3% (P=0.037)]. SHP-1 methylation during active disease was associated with a lower probability of survival at 39-month follow up (median), 52.5 vs. 87.5% (P=0.025). The percentage of methylation was associated with active disease at remission, but this was not significant. Global hypomethylation at remission was a negative predictor factor for overall survival (OS). The results indicated that methylated P16, SOCS-1 and SHP-1 were associated with clinical variables of poor prognosis in MM, likewise the persistence of global hypomethylation at remission. The negative impact on OS of global hypomethylation at remission must be confirmed in a larger sample. Future studies are necessary to investigate whether patients with global hypermethylation at remission should receive more aggressive treatments to

  3. A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth.

    Science.gov (United States)

    Patel, Yogin; Shah, Nirav; Lee, Ji Shin; Markoutsa, Eleni; Jie, Chunfa; Liu, Shou; Botbyl, Rachel; Reisman, David; Xu, Peisheng; Chen, Hexin

    2016-04-05

    Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several microRNAs (miRNAs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRNAs dysregualted in HER2-positive breast cancer cells. Our molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially through the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenecity and tumor growth in xenograft mice. Mechanistically, we found that overexpression of miR-489 led to the decreased levels of HER2 and SHP2 and thus attenuated HER2-downstream signaling. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2-SHP2-MAPK and miR-489 signaling pathways form a mutually inhibitory loop. Using quantitative real-time PCR analysis and Fluorescent in situ hybridization technique (FISH), we found that miR-489 was expressed at significantly lower level in tumor tissues compared to the adjacent normal tissues. Downregulation of miR-489 in breast cancers was associated with aggressive tumor phenotypes. Overall, our results define a double-negative feedback loop involving miR-489 and the HER2-SHP2-MAPK signaling axis that can regulate breast cancer cell proliferation and tumor progression and might have therapeutic relevance for HER2-positive breast cancer.

  4. Gab2 is phosphorylated on tyrosine upon interleukin-2/interleukin-15 stimulation in mycosis-fungoides-derived tumor T cells and associates inducibly with SHP-2 and Stat5a

    DEFF Research Database (Denmark)

    Brockdorff, J L; Gu, H; Mustelin, T

    2001-01-01

    Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2) receptor signaling. In this study, we investigated the role of Gab2, a recently identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show that Gab2 was transiently phosphorylated by tyrosine in human...... mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor beta-chain is important for IL-2-induced Gab2 phosphorylation. Preincubation...

  5. Psychosocial adjustment and marital intimacy among partners of patients with breast cancer: a comparison study with partners of healthy women.

    Science.gov (United States)

    Moreira, Helena; Canavarro, Maria Cristina

    2013-01-01

    This cross-sectional study investigated the psychosocial adjustment of 70 partners of patients with breast cancer by comparing their emotional adjustment and quality of life (QoL) with 70 partners of women without cancer. The role of marital intimacy in their adjustment and the moderating effect of group type were analyzed. The partners of patients with breast cancer presented higher levels of anxious and depressive symptomatology; poor social, psychological, general and physical QoL; and higher levels of intimacy. The moderation analysis showed that higher levels of intimacy predicted lower levels of depression and anxiety and greater QoL only among the partners of cancer patients.

  6. Romantic partners in a market perspective: expectations about what ensures a highly desirable partner.

    Science.gov (United States)

    Castro, Felipe N; Hattori, Wallisen T; Yamamoto, Maria Emília; Lopes, Fívia A

    2013-10-01

    This study used the biological market perspective and influential statistical models from the marketing field to investigate males' and females' expectations regarding which combination of characteristics are most relevant in ensuring desirable partnerships for same-sex individuals. Thus, 358 Brazilian undergraduates assessed eight descriptions of same-gender stimulus targets (formulated with different levels of physical attractiveness, social skills, and current or prospective social status) and evaluated the overall desirability of the targets' expected or probable partners. From the possible combinations, three groups emerged: for one group, mainly composed of men, status characteristics were the most important attributes; for the others, mostly composed of women, social skills or physical characteristics were identified as most important in appealing to a desirable partner. This work expands the understanding of variability in male and female romantic expectations, and its implications are discussed from an evolutionary perspective.

  7. Between rigidity and chaos: worldviews of partners experiencing intimate partner violence.

    Science.gov (United States)

    Enosh, Guy; Eisikovits, Zvi; Gross, Chen

    2013-09-01

    The goal of this article was to examine the worldviews of cohabiting or married men and women who experienced domestic violence in their relationships. The study was based on content analysis of in-depth interviews with 48 men and women (24 couples), who were living together after experiencing at least one violent event in their relationships over the previous 12 months. Using constructivist grounded theory, the authors examined the deep structure of the ways by which partners living with intimate partner violence constructed their world. The men and women under study constructed heuristic models in two major life domains-psychological processes and how the world works overall. The analysis has revealed two axes resulting in four worldviews. The two axes were the construction of the world and the construction of the mind. Constructions of the mind ranged from chaotic to deterministic. Constructions of external reality ranged from static to fluid and uncontrollable. The theoretical model developed suggested four different types of basic worldviews. The suggested typology was examined in relation to existing typologies in the field of intimate partner violence and in relation to future research and interventions.

  8. Discussing partner abuse: Does doctor's gender really matter?

    NARCIS (Netherlands)

    Wong, S.H.; Jonge, A. de; Wester, F.P.J.; Mol, S.S.L.; Römkens, R.R.; Lagro-Janssen, A.L.M.

    2006-01-01

    BACKGROUND: There are conflicting findings on the influence of gender on responding to partner abuse. OBJECTIVES: We aimed to explore gender differences in family doctors' views, attitudes, experiences and practices regarding intimate partner abuse against women. METHODS: We used the focus-group

  9. Discussing partner abuse : Does doctor's gender really matter?

    NARCIS (Netherlands)

    Lo Fo Wong, S.; de Jonge, A.; Wester, F.; Mol, S.; Römkens, R.; Lagro-Janssen, T.

    2006-01-01

    Background. There are conflicting findings on the influence of gender on responding to partner abuse. Objectives. We aimed to explore gender differences in family doctors' views, attitudes, experiences and practices regarding intimate partner abuse against women. Methods. We used the focus-group

  10. 76 FR 68745 - Seneca Power Partners, L.P.

    Science.gov (United States)

    2011-11-07

    ...] Seneca Power Partners, L.P. v. New York Independent System Operator, Inc.; Notice of Complaint Take... and Procedures, 18 CFR 385.206, Seneca Power Partners, L.P. (Complainant) filed a complaint against... TTY, call (202) 502-8659. Comment Date: 5 p.m. Eastern Time on November 28, 2011. Dated: October...

  11. The crossover of burnout and its relation to partner health

    NARCIS (Netherlands)

    A.B. Bakker (Arnold)

    2009-01-01

    textabstractTwo studies among medical residents and teachers in the Netherlands and Greece tested the hypothesis that burnout may transfer from employees to their intimate partners at home and indirectly influence the partner's health. Study 1 included a general index of self-rated health, whereas,

  12. Female Intimate Partner Violence Survivors' Experiences with Accessing Resources

    Science.gov (United States)

    McLeod, Amy L.; Hays, Danica G.; Chang, Catherine Y.

    2010-01-01

    This phenomenological study investigates the types of personal and community resources that female intimate partner violence (IPV) survivors used when leaving an abusive male partner. Three African American and 2 European American IPV survivors, ages 24 to 38 years, described positive and negative experiences with social support, personal…

  13. Intimate Partner Violence and Belief Systems in Liberia

    Science.gov (United States)

    Allen, Mary; Devitt, Catherine

    2012-01-01

    Intimate partner violence is endemic in parts of the African continent. A small scale survey (n = 229) was conducted in 2009 in Northern Liberia, West Africa, to determine the prevalence and nature of intimate partner violence, and the cultural beliefs and gender norms that underpin respondent experiences and views towards intimate partner…

  14. Attitudes toward Intimate Partner Violence in Dating Relationships

    Science.gov (United States)

    Fincham, Frank D.; Cui, Ming; Braithwaite, Scott; Pasley, Kay

    2008-01-01

    Prevention of intimate partner violence on college campuses includes programs designed to change attitudes, and hence, a scale that assesses such attitudes is needed. Study 1 (N = 859) cross validates the factor structure of the Intimate Partner Violence Attitude Scale-Revised using exploratory factor analysis and presents initial validity data on…

  15. Trauma Symptoms among Infants Exposed to Intimate Partner Violence

    Science.gov (United States)

    Bogat, G. Anne; DeJonghe, Erika; Levendosky, Alytia A.; Davidson, William S.; von Eye, Alexander

    2006-01-01

    Objective: To determine whether infants have a traumatic response to intimate partner violence (male violence toward their female partner; IPV) experienced by their mothers, two questions were explored: (1) Is the number of infant trauma symptoms related to the infant's temperament and the mother's mental health? (2) Does severity of violence…

  16. 76 FR 50715 - Briefing on Partner Vetting System Pilot Program

    Science.gov (United States)

    2011-08-16

    ...; ] DEPARTMENT OF STATE Agency for International Development Briefing on Partner Vetting System Pilot Program... briefing. SUMMARY: Notice is hereby given of a briefing on the Partner Vetting System (PVS) pilot program. The objective of the briefing is to provide information about the PVS pilot program. Members of the...

  17. Interaction Design Patterns for ePartners : Method and Example

    NARCIS (Netherlands)

    Paulissen, R.T.; Neerincx, M.A.; Cremers, A.H.M.; Kranenborg, K.

    2013-01-01

    An ePartner is a personal computer application that helps its user to achieve personal goals such as managing his or her health related behaviors concerning nutrition, exercise and medication. The aim of the first phase of the ‘ePartners that Care’ project is to achieve a general method and framewor

  18. Betriebliche Bildungsmanager als Business Partner: Professionalisierung und Kompetenzen

    OpenAIRE

    Breßler, Julia; Gehde, Karla

    2015-01-01

    Das Paper ist motiviert durch die Arbeiten von Hasanbegovic, die Bildungsmanagement einbetten in Beratungsforschung und in Managementkonzepte sowie die Arbeit von Diesner, die den Typ 3 Bildungsmanagement als Business Partner einführt. Aufgrund dieser Vorarbeiten analysieren wir betriebliche Bildungsmanager als Business Partner und erarbeiten ein spezifisches Kompetenzprofil. Darauf aufbauend synthetisieren wir die Ergebnisse im Hinblick auf die Professionalisierungstheorie nach Freidson. ...

  19. Parenting and Women Arrested for Intimate Partner Violence

    Science.gov (United States)

    Simmons, Catherine A.; Lehmann, Peter; Dia, David A.

    2010-01-01

    Exploring the relationship between parenting and women's use of violence the current study surveyed 106 mothers arrested for intimate partner violence (IPV) related crimes on parenting styles and attitudes toward when using violence against their partner is justified. Findings indicate parenting styles indicative of low belief in using physical…

  20. Intimate Partner Violence: Building Resilience with Families and Children

    Science.gov (United States)

    Wortham, Thomasine T.

    2014-01-01

    Intimate partner violence includes physical, emotional, or sexual maltreatment from an intimate partner that may include name-calling, hitting, controlling behaviors, use of weapons, rape, intimidation, and a plethora of other physical and emotional tactics (Kress, Protivnak, & Sadlak, 2008; United States Department of Justice, 2013). Such…

  1. Self and partner personality and responses to relationship threats

    NARCIS (Netherlands)

    Dijkstra, Pieternel; Barelds, Dick P. H.

    2008-01-01

    Two studies examined the relations between three different types of jealousy and personality characteristics of self and partner in two large heterogeneous community samples of heterosexual couples (459 and 230 couples, respectively). It was expected that partners would resemble each other to some e

  2. Associating Pregnancy with Partner Violence against Chinese Women

    Science.gov (United States)

    Chan, Ko Ling; Brownridge, Douglas A.; Tiwari, Agnes; Fong, Daniel Y. T.; Leung, Wing Cheong; Ho, Pak Chung

    2011-01-01

    The present study discusses if pregnancy is a risk factor for intimate partner violence using a large, representative sample containing detailed information on partner violence including physical and sexual abuse as well as perpetrator-related risk factors. Data from a representative sample of 2,225 men were analyzed. The self-reported prevalence…

  3. Differences between Partners from Heterosexual, Gay, and Lesbian Cohabiting Couples

    Science.gov (United States)

    Kurdek, Lawrence A.

    2006-01-01

    Partners from four types of couples without children (gay unmarried, lesbian unmarried, heterosexual unmarried, and heterosexual married, Ns=1,412, 1,310, 1,036, and 1,728, respectively) were compared to partners from heterosexual married couples with children ("N"= 3,116) on mean levels of variables from a model of relationship adjustment as well…

  4. Sex Partner with No Zika Symptoms Transmits Virus: CDC

    Science.gov (United States)

    ... news/fullstory_160643.html Sex Partner With No Zika Symptoms Transmits Virus: CDC New report also highlights ties between Zika ... HealthDay News) -- U.S. health officials report that the Zika virus can be spread sexually even when a partner ...

  5. Colorful Twisted Top Partners and Partnerium at the LHC

    Science.gov (United States)

    Kats, Yevgeny; McCullough, Matthew; Perez, Gilad; Soreq, Yotam; Thaler, Jesse

    2017-06-01

    In scenarios that stabilize the electroweak scale, the top quark is typically accompanied by partner particles. In this work, we demonstrate how extended stabilizing symmetries can yield scalar or fermionic top partners that transform as ordinary color triplets but carry exotic electric charges. We refer to these scenarios as "hypertwisted" since they involve modifications to hypercharge in the top sector. As proofs of principle, we construct two hypertwisted scenarios: a supersymmetric construction with spin-0 top partners, and a composite Higgs construction with spin-1/2 top partners. In both cases, the top partners are still phenomenologically compatible with the mass range motivated by weak-scale naturalness. The phenomenology of hypertwisted scenarios is diverse, since the lifetimes and decay modes of the top partners are model dependent. The novel coupling structure opens up search channels that do not typically arise in top-partner scenarios, such as pair production of top-plus-jet resonances. Furthermore, hypertwisted top partners are typically sufficiently long lived to form "top-partnerium" bound states that decay predominantly via annihilation, motivating searches for rare narrow resonances with diboson decay modes.

  6. Gender Differences in Expectations of Self and Future Partner.

    Science.gov (United States)

    Ganong, Lawrence H.; Coleman, Marilyn

    1992-01-01

    Investigated expectations that 131 single female and 103 male college students had for themselves and their future marital partners. Genders did not differ on expectations for personal success but did differ on expectations for success of future marital partner. Women expected more success for future husbands than men expected for wives.…

  7. Examining the Interface Between Substance Misuse and Intimate Partner Violence

    Directory of Open Access Journals (Sweden)

    Peter M. Monti

    2009-01-01

    Full Text Available There is considerable theoretical and empirical support for a link between substance misuse and perpetration and victimization of intimate partner violence. This review briefly summarizes this literature and highlights current research that addresses the interface between treatment for substance abuse and intimate partner violence. Suggestions for future research and clinical implications are provided.

  8. Interaction Design Patterns for ePartners : Method and Example

    NARCIS (Netherlands)

    Paulissen, R.T.; Neerincx, M.A.; Cremers, A.H.M.; Kranenborg, K.

    2013-01-01

    An ePartner is a personal computer application that helps its user to achieve personal goals such as managing his or her health related behaviors concerning nutrition, exercise and medication. The aim of the first phase of the ‘ePartners that Care’ project is to achieve a general method and framewor

  9. Institutional Distance and Partner Selection in International Technological Alliances

    NARCIS (Netherlands)

    Krammer, Marius

    2013-01-01

    This study posits that institutional distance has a negative influence on partner selection in international technological alliances. Empirical results based on a dataset of firms in the global tire industry confirm that firms prefer technological partners from closer cognitive, normative and regula

  10. Partner's stake in conformity and abused wives' psychological trauma.

    Science.gov (United States)

    Demaris, Alfred; Kaukinen, Catherine

    2008-10-01

    This study investigates the potential buffering effect of help-seeking in the association between intimate partner assault and women's psychological trauma, and how this, in turn, may depend on the partner's stake in conformity. The sample consists of 374 women reporting the experience of domestic violence from a current intimate partner, drawn from the larger survey Violence and Threats of Violence Against Women and Men in the United States, 1994-1996. Help-seeking did not appear to buffer the impact of assault severity, contrary to expectation. However, the partner's stake in conformity did condition the effect of his or her having been arrested. Victims had higher levels of posttraumatic stress disorder (PTSD) when police arrested partners of average or below-average stake in conformity. But victims of partners characterized by higher than average stake in conformity did not show elevated PTSD due to their partners having been arrested. On the other hand, PTSD was higher among women experiencing more emotional abuse from the partner.

  11. Care Partner Responses to the Onset of Mild Cognitive Impairment

    Science.gov (United States)

    Blieszner, Rosemary; Roberto, Karen A.

    2010-01-01

    Purpose: We examined characteristics, responses, and psychological well-being of care partners who support and assist older adults recently diagnosed with mild cognitive impairment (MCI). Design and Methods: Based on a sample of 106 care partners of community residents diagnosed with MCI at memory clinics, we conducted face-to-face interviews…

  12. Differences between Partners from Heterosexual, Gay, and Lesbian Cohabiting Couples

    Science.gov (United States)

    Kurdek, Lawrence A.

    2006-01-01

    Partners from four types of couples without children (gay unmarried, lesbian unmarried, heterosexual unmarried, and heterosexual married, Ns=1,412, 1,310, 1,036, and 1,728, respectively) were compared to partners from heterosexual married couples with children ("N"= 3,116) on mean levels of variables from a model of relationship adjustment as well…

  13. Partnering with Big Pharma-What Academics Need to Know.

    Science.gov (United States)

    Lipton, Stuart A; Nordstedt, Christer

    2016-04-21

    Knowledge of the parameters of drug development can greatly aid academic scientists hoping to partner with pharmaceutical companies. Here, we discuss the three major pillars of drug development-pharmacodynamics, pharmacokinetics, and toxicity studies-which, in addition to pre-clinical efficacy, are critical for partnering with Big Pharma to produce novel therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Gender Differences in Expectations of Self and Future Partner.

    Science.gov (United States)

    Ganong, Lawrence H.; Coleman, Marilyn

    1992-01-01

    Investigated expectations that 131 single female and 103 male college students had for themselves and their future marital partners. Genders did not differ on expectations for personal success but did differ on expectations for success of future marital partner. Women expected more success for future husbands than men expected for wives.…

  15. The crossover of burnout and its relation to partner health

    NARCIS (Netherlands)

    A.B. Bakker (Arnold)

    2009-01-01

    textabstractTwo studies among medical residents and teachers in the Netherlands and Greece tested the hypothesis that burnout may transfer from employees to their intimate partners at home and indirectly influence the partner's health. Study 1 included a general index of self-rated health, whereas,

  16. PARTNER: A Marie Curie Initial Training Network for hadron therapy

    CERN Document Server

    CERN BULLETIN; Nathalie Hospital; Manuela Cirilli

    2011-01-01

    PARTNER is a 4-year Marie Curie Training project funded by the European Commission with 5.6 million Euros aimed at the creation of the next generation of experts. Ten academic institutes and research centres and two leading companies are participating in PARTNER, that is coordinated by CERN, forming a unique multidisciplinary and multinational European network.

  17. Self and partner personality and responses to relationship threats

    NARCIS (Netherlands)

    Dijkstra, Pieternel; Barelds, Dick P. H.

    2008-01-01

    Two studies examined the relations between three different types of jealousy and personality characteristics of self and partner in two large heterogeneous community samples of heterosexual couples (459 and 230 couples, respectively). It was expected that partners would resemble each other to some

  18. Alignment of Partnering with Construction IT

    Directory of Open Access Journals (Sweden)

    Eleni Papadonikolaki

    2016-10-01

    Full Text Available Supply Chain Management (SCM and Building Information Modelling (BIM are seen as innovations that can manage complexities in construction by focusing on integrating processes and products respectively. Whereas these two innovations have been considered compatible, their practical combination has been mainly anecdotal. The Netherlands was the locale of this study, where both SCM and BIM have been popular approaches. The research objective is to explore their real-world combination and propose strategies for the alignment of SCM and BIM, by viewing Supply Chain (SC partnering as the inter-organisational proxy of SCM. The main question is: “How to align the SCM philosophy with BIM technologies to achieve integration in the construction industry? What aspects contribute to this alignment?”. The methodology was mixed and both qualitative and quantitative data were analysed. The overarching method was case study research and the unit of analysis was the firm, also referred to as ‘actor’.After a semi-chronological review of the relevant literature, the two constructs of SCM and BIM were found interdependent in product-, process-, and actor-related (P/P/A dimensions. The study consisted of four other consecutive studies. First, empirical insights into the practical implementation of SC partnering and BIM were obtained via the exploration of five cases. Second, a conceptual model for the quantitative analysis of the product-, process-, and actor-related dimensions was designed. Third, this model and mixed methods were applied to two polar (extreme cases to analyse the contractual (typically SC-related, digital (typically BIM-related, and informal interactions among the involved actors. Fourth, an additional theoretical exploration of the BIM-enabled SC partnerships took place with focusing also on intra-organisational relations within the involved firms. After the four studies, the findings were systematically combined to create the theoretical

  19. The impact of partner coping in couples experiencing infertility

    DEFF Research Database (Denmark)

    Peterson, B D; Pirritano, M; Christensen, Ulla

    2008-01-01

    as the unit of analysis. RESULTS: A partner's use of active-avoidance coping was related to the increased personal, marital and social distress for men and women. A woman's use of active-confronting coping was related to increased male marital distress. And a partner's use of meaning-based coping...... is particularly relevant. METHODS: Data were based on a questionnaire in a consecutive sample of 1169 women and 1081 Danish men prior to beginning assisted reproduction treatment. Multilevel modeling using the Actor Partner Interdependence Model and follow-up analysis of variance were used to examine the couple...... was associated with decreased marital distress in men and increased social distress in women. CONCLUSIONS: Although understudied, partner coping patterns play a key role in a partner's ability to cope with the infertility experience. Physicians and mental health providers can help couples to understand...

  20. Intimate partner violence: what do movies have to teach us?

    Science.gov (United States)

    Lenahan, Patricia M

    2009-06-01

    Intimate partner violence is one of the most pervasive global public health problems affecting women. It results in untold costs to the healthcare system and is positively linked to eight out of ten leading indicators for Healthy People 2010. Intimate partner violence also is one of the factors associated with adverse childhood experiences that result in negative healthcare behaviours. Intimate partner violence has been the subject of film, made for television movies and music videos. The use of film as an innovative tool to teach about common health and mental health disorders is well-documented. Film also has been used as an adjunctive therapeutic tool in counselling. This paper will provide an overview of intimate partner violence, its portrayal in popular film and ways in which educators may use film to teach intimate partner violence-related topics.

  1. Telling partners about chlamydia: how acceptable are the new technologies?

    Directory of Open Access Journals (Sweden)

    Parker Rhian M

    2010-03-01

    Full Text Available Abstract Background Partner notification is accepted as a vital component in the control of chlamydia. However, in reality, many sexual partners of individuals diagnosed with chlamydia are never informed of their risk. The newer technologies of email and SMS have been used as a means of improving partner notification rates. This study explored the use and acceptability of different partner notification methods to help inform the development of strategies and resources to increase the number of partners notified. Methods Semi-structured telephone interviews were conducted with 40 people who were recently diagnosed with chlamydia from three sexual health centres and two general practices across three Australian jurisdictions. Results Most participants chose to contact their partners either in person (56% or by phone (44%. Only 17% chose email or SMS. Participants viewed face-to-face as the "gold standard" in partner notification because it demonstrated caring, respect and courage. Telephone contact, while considered insensitive by some, was often valued because it was quick, convenient and less confronting. Email was often seen as less personal while SMS was generally considered the least acceptable method for telling partners. There was also concern that emails and SMS could be misunderstood, not taken seriously or shown to others. Despite these, email and SMS were seen to be appropriate and useful in some circumstances. Letters, both from the patients or from their doctor, were viewed more favourably but were seldom used. Conclusion These findings suggest that many people diagnosed with chlamydia are reluctant to use the new technologies for partner notification, except in specific circumstances, and our efforts in developing partner notification resources may best be focused on giving patients the skills and confidence for personal interaction.

  2. Lack of evidence for AT1R/B2R heterodimerization in COS-7, HEK293, and NIH3T3 cells: how common is the AT1R/B2R heterodimer?

    DEFF Research Database (Denmark)

    Hansen, Jakob L; Hansen, Jonas T; Speerschneider, Tobias

    2008-01-01

    It has been suggested previously ( AbdAlla, S., Lother, H., and Quitterer, U. (2000) Nature 407, 94-98 ) that the angiotensin II type 1 receptor (AT1R) and the bradykinin B2 receptor (B2R) form constitutive heterodimers. Furthermore they demonstrate that AT1R signaling significantly increases...... in the presence of the B2R. These findings suggest that heterodimerization and potentiation of AT1R signaling is a universal phenomenon that occurs as a natural consequence of simultaneous expression of the two receptors. Hence this potential interaction is of great pharmacological and biological interest...... by or physical interaction between the two receptor proteins. In contrast to the previous observations, our data collectively suggest that AT1R/B2R heterodimerization does not occur as a natural consequence of their simultaneous expression in the same cell nor does the B2R influence the AT1R signaling....

  3. PARTNER INVOLVEMENT: NEGOTIATING THE PRESENCE OF PARTNERS IN PSYCHOSOCIAL ASSESSMENT AS CONDUCTED BY MIDWIVES AND CHILD AND FAMILY HEALTH NURSES.

    Science.gov (United States)

    Rollans, Mellanie; Kohlhoff, Jane; Meade, Tanya; Kemp, Lynn; Schmied, Virginia

    2016-05-01

    Universal screening for maternal depression and assessment of psychosocial risks has been integrated into the routine perinatal care provided in many Australian hospitals, but to date, partners/fathers have been largely excluded from the process. This study explored the ways in which clinicians in health service settings include partners who attend antenatal and postnatal visits with women. Qualitative data were collected using observations (n = 54), interviews (n = 60), and discussion groups (n = 7) with midwives and child and family health nurses who conducted the appointments. Transcripts from observations, interviews, and discussion groups underwent qualitative analysis, and key themes were identified. Results showed partners to have little or no involvement in psychosocial assessment and depression screening. Thematic analysis revealed four key themes: negotiating partner exclusion, partial inclusion, women's business or a couple concern? and they know anyway. Partner involvement appeared to be challenged particularly by mandatory interpersonal violence screening, which, according to health service policy, is to be conducted confidentially. Overall, results highlighted partner involvement in perinatal depression screening and psychosocial assessment processes and identified some of the benefits such as partner disclosure, but also the challenges and complexities of inclusion of partners. Clinical implications and directions for further education and research are discussed. © 2016 Michigan Association for Infant Mental Health.

  4. 26 CFR 1.736-1 - Payments to a retiring partner or a deceased partner's successor in interest.

    Science.gov (United States)

    2010-04-01

    ... time of his death or retirement of the withdrawing partner's interest in all the assets of the... shall not be considered to have terminated upon the death of the partner but shall terminate as to both... interest in partnership property in an arm's length agreement will be regarded as correct. If...

  5. An Initial Test of Inconsistent Nurturing as Control Theory: How Partners of Drug Abusers Assist Their Partners' Sobriety.

    Science.gov (United States)

    Le Poire, Beth A.; Hallett, Jennifer S.; Erlandson, Karen T.

    2000-01-01

    Discusses how inconsistent nurturing as control theory asserts that because of competing goals of nurturing and controlling, partners of drug-dependent individuals will unintentionally encourage the very behavior they are trying to extinguish through inconsistent manifestations of reinforcement and punishment. Finds that partners of substance…

  6. Trajectories of Intimate Partner Violence Victimization

    Directory of Open Access Journals (Sweden)

    Kevin M. Swartout

    2012-08-01

    Full Text Available Introduction: The purposes of this study were to assess the extent to which latent trajectories of female intimate partner violence (IPV victimization exist; and, if so, use negative childhood experiences to predict trajectory membership.Methods: We collected data from 1,575 women at 5 time-points regarding experiences during adolescence and their 4 years of college. We used latent class growth analysis to fit a series of personcentered, longitudinal models ranging from 1 to 5 trajectories. Once the best-fitting model was selected, we used negative childhood experience variables—sexual abuse, physical abuse, and witnessing domestic violence—to predict most-likely trajectory membership via multinomial logistic regression.Results: A 5-trajectory model best fit the data both statistically and in terms of interpretability. The trajectories across time were interpreted as low or no IPV, low to moderate IPV, moderate to low IPV, high to moderate IPV, and high and increasing IPV, respectively. Negative childhood experiences differentiated trajectory membership, somewhat, with childhood sexual abuse as a consistent predictor of membership in elevated IPV trajectories.Conclusion: Our analyses show how IPV risk changes over time and in different ways. These differential patterns of IPV suggest the need for prevention strategies tailored for women that consider victimization experiences in childhood and early adulthood. [West J Emerg Med. 2012;13(3:272–277.

  7. Survivors of Intimate Partner Violence Speak Out

    Science.gov (United States)

    Battaglia, Tracy A; Finley, Erin; Liebschutz, Jane M

    2003-01-01

    OBJECTIVE To identify characteristics that facilitate trust in the patient-provider relationship among survivors of intimate partner violence (IPV). DESIGN Semistructured, open-ended interviews were conducted to elicit participants' beliefs and attitudes about trust in interactions with health care providers. Using grounded theory methods, the transcripts were analyzed for common themes. A community advisory group, composed of advocates, counselors and IPV survivors, helped interpret themes and interview exerpts. Together, key components of trust were identified. SETTING Eastern Massachusetts. PARTICIPANTS Twenty-seven female survivors of IPV recruited from community-based IPV organizations. MAIN RESULTS Participants' ages ranged from 18 to 56 years, 36% were African American, 32% Hispanic, and 18% white. We identified 5 dimensions of provider behavior that were uniquely important to the development of trust for these IPV survivors: 1) communication about abuse: provider was willing to openly discuss abuse; 2) professional competency: provider asked about abuse when appropriate and was familiar with medical and social histories; 3) practice style: provider was consistently accessible, respected confidentiality, and shared decision making; 4) caring: provider demonstrated personal concern beyond biomedical role through nonjudgmental and compassionate gestures, empowering statements, and persistent, committed behaviors; 5) emotional equality: provider shared personal information and feelings and was perceived by the participant as a friend. CONCLUSIONS These IPV survivors identified dimensions of provider behavior that facilitate trust in their clinical relationship. Strengthening these provider behaviors may increase trust with patients and thus improve disclosure of and referral for IPV. PMID:12911643

  8. Marital dysfunction and personality characteristics of partners

    Directory of Open Access Journals (Sweden)

    Draganić-Gajić Saveta

    2005-01-01

    Full Text Available Introduction A number of studies indicate that an early trauma is of extreme importance (most often experienced in the family of origin in developing personality disorders. Researches on correlations between family dysfunction and individual psychopathology have been rare and controversial. The reason for this stems from an attempt to establish links between traditional medical models and systemic family therapy. The aim of this research was to explore specific personality structures of married couples and the way they relate to the type of dysfunction within the partner relationship. Material and methods The sample consisted of 25 families in the middle of divorce. The examinees were aged 25-45. Specific interactional behavioral patterns were examined by Dyadic Adjustment Scale (DAS, while personality profile data were obtained using Millon Clinical Multiaxial Inventory (MCMI. Results and conclusions In both groups dependency and obsessivness were marked, while males also presented with marked narcissism. Related to structural personality disorders, we have found only a group of men with significantly increased paranoid dimension. Concerning clinical syndromes, the obtained results revealed anxiety and depressive disorder in both genders and a tendency towards alcohol abuse among men. Results indicated to correlation of communication-interactive family patterns on one hand, and certain personality traits on the other. .

  9. Partners in quality: managing your suppliers.

    Science.gov (United States)

    Conway, B A

    1991-05-01

    Just expecting more from your supplier is not what partnership is about. We have had the experience where the quality improvement and partnership banner has been waved but the tone and spirit of the meeting did not encourage or support a joint quality improvement effort. Benefits will not be achieved until the wall truly begins to come apart and the relationship is built on mutual respect and trust. Data collection and open answers to questions often reveal embarrassing errors and obvious needs for improvements. As stated before, blame and finger-pointing must be replaced with a mutual commitment to asking and answering the question, "How can we improve?" As Dr. W. Edwards Deming has stated, "End the practice of awarding business on the basis of price tag. Instead, minimize total cost. Move toward a single supplier for any one item on a long-term relationship of loyalty and trust." The structured approach of a quality improvement process and the application of quality methods and techniques has proven useful in removing emotion and helping the team focus on the process rather than the people and the issues involved. Quality improvement methods are focused on achieving both customer and supplier goals--customer satisfaction, employee satisfaction, and operational efficiency and effectiveness. Our experience with Partners in Quality as well as our experience with the quality leadership process supports a recent quote in the Harvard Business Review: "Quality is not just a slogan...(it is) the most profitable way to run a business."

  10. Problem gambling and intimate partner violence.

    Science.gov (United States)

    Korman, Lorne M; Collins, Jane; Dutton, Don; Dhayananthan, Bramilee; Littman-Sharp, Nina; Skinner, Wayne

    2008-03-01

    This study examined the prevalence and severity of intimate partner violence (IPV) among 248 problem gamblers (43 women, 205 men) recruited from newspaper advertisements. The main outcome measures used were the Canadian Problem Gambling Index, the Conflicts Tactics Scale-2, the State Trait Anger Expression Inventory-2, the drug and alcohol section of the Addiction Severity Index and the substance use section of the Structured Clinical Interview for the DSM-IV. In this sample, 62.9% of participants reported perpetrating and/or being the victims of IPV in the past year, with 25.4% reporting perpetrating severe IPV. The majority of the sample (64.5%) also had clinically significant anger problems, which was associated with an increased risk of being both the perpetrator and victim of IPV. The presence of a lifetime substance use disorder among participants who had clinically significant anger problems further increased the likelihood of both IPV perpetration and victimization. These findings underscore the importance of routinely screening gambling clients for anger and IPV, and the need to develop public policy, prevention and treatment programs to address IPV among problem gamblers. Future research to examine IPV among problem gamblers is recommended.

  11. 26 CFR 301.6223(h)-1 - Responsibilities of pass-thru partner.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Responsibilities of pass-thru partner. 301.6223... Responsibilities of pass-thru partner. (a) In general. The pass-thru partner shall, within 30 days of receiving... tax matters partner, or another pass-thru partner, forward a copy of that notice or information to...

  12. The inhibition of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) promoter by fibrates in cultured cells is mediated via the liver x receptor alpha and peroxisome proliferator-activated receptor alpha heterodimer.

    Science.gov (United States)

    Gbaguidi, G Franck; Agellon, Luis B

    2004-01-01

    In previous work, we showed that the binding of the liver x receptor alpha:peroxisome proliferator-activated receptor alpha (LXRalpha:PPARalpha) heterodimer to the murine Cyp7a1 gene promoter antagonizes the stimulatory effect of their respective ligands. In this study, we determined if LXRalpha:PPARalpha can also regulate human CYP7A1 gene promoter activity. Co-expression of LXRalpha and PPARalpha in McArdle RH7777 hepatoma cells decreased the activity of the human CYP7A1 gene promoter in response to fibrates and 25-hydroxycholesterol. In vitro, the human CYP7A1 Site I bound LXRalpha:PPARalpha, although with substantially less affinity compared with the murine Cyp7a1 Site I. The binding of LXRalpha:PPARalpha to human CYP7A1 Site I was increased in the presence of either LXRalpha or PPARalpha ligands. In HepG2 hepatoblastoma cells, fibrates and 25-hydroxycholesterol inhibited the expression of the endogenous CYP7A1 gene as well as the human CYP7A1 gene promoter when co-transfected with plasmids encoding LXRalpha and PPARalpha. However, a derivative of the human CYP7A1 gene promoter that contains a mutant form of Site I that does not bind LXRalpha:PPARalpha was not inhibited by WY 14,643 or 25-hydroxycholesterol in both McArdle RH7777 and HepG2 cells. The ligand-dependent recruitment of LXRalpha:PPARalpha heterodimer onto the human CYP7A1 Site I can explain the inhibition of the human CYP7A1 gene promoter in response to fibrates and 25-hydroxycholesterol.

  13. Better than nothing? Patient-delivered partner therapy and partner notification for chlamydia: the views of Australian general practitioners

    Directory of Open Access Journals (Sweden)

    Bowden Francis J

    2010-09-01

    Full Text Available Abstract Background Genital chlamydia is the most commonly notified sexually transmissible infection (STI in Australia and worldwide and can have serious reproductive health outcomes. Partner notification, testing and treatment are important facets of chlamydia control. Traditional methods of partner notification are not reaching enough partners to effectively control transmission of chlamydia. Patient-delivered partner therapy (PDPT has been shown to improve the treatment of sexual partners. In Australia, General Practitioners (GPs are responsible for the bulk of chlamydia testing, diagnosis, treatment and follow up. This study aimed to determine the views and practices of Australian general practitioners (GPs in relation to partner notification and PDPT for chlamydia and explored GPs' perceptions of their patients' barriers to notifying partners of a chlamydia diagnosis. Methods In-depth, semi-structured telephone interviews were conducted with 40 general practitioners (GPs from rural, regional and urban Australia from November 2006 to March 2007. Topics covered: GPs' current practice and views about partner notification, perceived barriers and useful supports, previous use of and views regarding PDPT. Transcripts were imported into NVivo7 and subjected to thematic analysis. Data saturation was reached after 32 interviews had been completed. Results Perceived barriers to patients telling partners (patient referral included: stigma; age and cultural background; casual or long-term relationship, ongoing relationship or not. Barriers to GPs undertaking partner notification (provider referral included: lack of time and staff; lack of contact details; uncertainty about the legality of contacting partners and whether this constitutes breach of patient confidentiality; and feeling both personally uncomfortable and inadequately trained to contact someone who is not their patient. GPs were divided on the use of PDPT - many felt concerned that it is not

  14. Partner Services in STD Prevention Programs: A Review

    Science.gov (United States)

    Hogben, Matthew; Collins, Dayne; Hoots, Brooke; O’Connor, Kevin

    2015-01-01

    Background Partner services have been a mainstay of public health sexually transmitted disease (STD) prevention programs for decades. The principal goals are to interrupt transmission and reduce STD morbidity and sequelae. In this paper, we review current literature with the goal of informing STD prevention programs. Methods We searched the literature for systematic reviews. We found nine reviews published between 2005 and 2014 (covering 108 studies). The reviews varied by study inclusion criteria (e.g., study methods, geographic location, infections). We abstracted major conclusions and recommendations from the reviews. Results Conclusions and recommendations were divided into patient referral interventions and provider referral interventions. For patient referral, there was evidence supporting the use of expedited partner therapy and interactive counseling, but not purely didactic instruction. Provider referral through Disease Intervention Specialists was efficacious and particularly well-supported for HIV. For other studies, modeling data and testing outcomes showed that partner notification in general reached high-prevalence populations. Reviews also suggested more focus on using technology and population-level implementation strategies. However, partner services may not be the most efficient means to reach infected persons. Conclusions Partner services programs constitute a large proportion of program STD prevention activities. Value is maximized by balancing a portfolio of patient and provider referral interventions and by blending partner notification interventions with other STD prevention interventions in overall partner services program structure. STD prevention needs program-level research and development to generate this portfolio. PMID:26779688

  15. Heteronormativity and sexual partnering among bisexual Latino men.

    Science.gov (United States)

    Muñoz-Laboy, Miguel; Garcia, Jonathan; Wilson, Patrick A; Parker, Richard G; Severson, Nicolette

    2015-05-01

    Our analyses address the question of how bisexual Latino men organize their sexual partnerships. Heteronormativity can be understood as the set of social norms and normative structures that guide sexual partnering among men and women. We provide descriptive statistics to describe bisexual Latino men's sexual partnerships. Logistic and linear regression modeling were used to explore bivariate and multivariate relationships. Of our total sample (N = 142), 41.6 % had unprotected vaginal intercourse 2 months prior to the interview; 21.8 % had unprotected anal intercourse with female partners; 37.5 % had unprotected insertive anal intercourse with male partners; and 22.5 % had unprotected receptive anal intercourse with male partners. In our multivariate model, machismo was directly associated with meeting female partners through formal spaces (workplace, school, and/or church), but inversely associated with meeting male partners in formal spaces. Machismo was positively associated with meeting male sex partners through social networks (i.e., friendship and kinship networks). The more comfortable men were with homosexuality the less likely they were to meet men online and the more likely they were to meet men through social networks of friends and kinship. Interventions to reduce sexually transmitted diseases that target bisexual behavior as an epidemiological "bridge" of transmission from homosexual to heterosexual networks might very well benefit from a more complex understanding of how Latino bisexuality is patterned. Thus, this exploratory analysis might lead to a rethinking of how to address risk and vulnerability among Latino bisexual men and their sexual networks.

  16. The moderating role of partner support among smokers and abstainers

    Directory of Open Access Journals (Sweden)

    Maria da Graça Pereira

    2014-05-01

    Full Text Available Objective: To analyze the moderating effect of partner support in the relationship between psychological morbidity and quality of life among smokers and abstainers. Methods: This observational cross-sectional study assessed “partner support”, “psychological morbidity” (depression, anxiety and stress and “quality of life” in a convenience sample of 224 smokers and 169 abstainers through questionnaires that were validated and analyzed using regression and simple slopes. Results: Partner support (positive and negative among smokers appeared as a moderator in the relationship between psychological morbidity and physical quality of life. As for mental quality of life, the partner support did not have a moderating effect. The results among abstainers are similar to those found among smokers. When positive partner support is strong, there is an opposite relationship between psychological morbidity and quality of life. However, this relationship is stronger when negative partner support is strong and, in this case, the relationship between psychological morbidity and quality of life is negative. Conclusion: Partner support, whether positive or negative, was an important moderator concerning quality of life and psychological morbidity of smokers and abstainers. doi:10.5020/18061230.2013.p349

  17. Women's experience of intimate partner violence in Haiti.

    Science.gov (United States)

    Gage, Anastasia J

    2005-07-01

    This study examined individual, partner, and community characteristics associated with the occurrence of intimate partner violence among ever-married women of reproductive age, using data from the 2000 Haiti Demographic and Health Survey. Separate logistic regressions were analyzed to assess women's risks of experiencing emotional, physical and sexual violence and multiple forms of intimate partner violence in the past 12 months. Twenty-nine percent of women in the sample experienced some form of intimate partner violence in the past 12 months, with 13 percent having experienced at least two different forms of violence. Significant positive associations with all forms of violence were found for lack of completion of primary school, history of violence exposure in women's families of origin either through witnessing violence between parents while growing up or direct experience of physical violence perpetrated by family members, partner's jealousy, partner's need for control, partner's history of drunkenness, and female-dominated financial decision-making. Significant positive associations were found between men's physical abuse of children at the community level and women's risk of experiencing emotional and physical violence. Neighborhood poverty and male unemployment, number of children living at home, women's attitudinal acceptance of wife beating, and male-dominated financial decision-making were additional risk factors for sexual violence. Women's economic independence was a protective factor for emotional and physical violence, while relationship quality was protective for all forms of violence and multiple victimizations.

  18. Intimate partner violence and breastfeeding in Africa.

    Science.gov (United States)

    Misch, Emily S; Yount, Kathryn M

    2014-04-01

    We examined the associations of maternal intimate partner violence (IPV) victimization with early initiation and exclusive breastfeeding in eight African countries. For mothers 15-49 years with an infant aged less than 6 months from national Demographic and Health Surveys since 2007 for Ghana (n = 173), Kenya (n = 449), Liberia (n = 313), Malawi (n = 397), Nigeria (n = 2007), Tanzania (n = 549), Zambia (n = 454), and Zimbabwe (n = 480), logistic regression was used to estimate the unadjusted and adjusted associations of lifetime maternal emotional, physical, and sexual IPV victimization with early initiation (less than 1 hour of birth) and exclusive breastfeeding in the prior 24 hours. Maternal lifetime IPV victimization often was adversely associated with optimal breastfeeding practices. Physical IPV in Zimbabwe (aOR 0.40, p = 0.002), sexual IPV in Zambia (aOR 0.42, p = 0.017), and emotional IPV in Kenya (aOR 0.54, p = 0.050) and Tanzania (aOR 0.57, p = 0.088) were associated with lower adjusted odds of early initiation. Sexual IPV in Liberia (aOR 0.09, p = 0.026), Ghana (aOR 0.17, p = 0.033), and Kenya (aOR 0.34, p = 0.085) were associated with lower adjusted odds of exclusive breastfeeding. Atypically, physical IPV in Tanzania (aOR 2.11, p = 0.042) and sexual IPV in Zambia (aOR 2.49, p = 0.025) were associated with higher adjusted odds of early initiation and exclusive breastfeeding, respectively. Across several settings, maternal IPV victimization may adversely influence breastfeeding practices. Longitudinal research of these relationships is warranted. Screening for IPV victimization and breastfeeding counseling in prenatal and postpartum care may mitigate the potential intergenerational effects of IPV.

  19. Understanding intimate partner violence and its correlates

    Directory of Open Access Journals (Sweden)

    Shashikumar Ramadugu

    2015-01-01

    Full Text Available Objectives: This study assessed intimate partner violence (IPV and alcohol use in an urban population in Pune, India. The prevalence of IPV and alcohol use was assessed along with the correlation of IPV with alcohol and other variables. Materials and Methods: The study was cross-sectional, questionnaire-based. The materials used were the hurt insult threaten scream (HITS scale, the alcohol use disorders identification test, and a brief psychosocial questionnaire. Systematic random sampling was done on the target population. Regression analysis of various factors in relation to HITS score was done. Results: Sample size (n was 318 individuals. Prevalence of IPV was found to be 16% and the victims were mostly women. Prevalence of alcohol use was 44%, of which 8.9% were harmful users. No female subjects consumed alcohol, but 94% were aware of their husband's alcohol consumption. No significant correlation was found between IPV and education (P = 0.220 or income of women (P = 0.250. Alcohol consumption by males was a significant risk factor for women experiencing IPV (σ = +0.524; P< 0.001. Regression analysis also revealed that increasing marital age (P = 0.019 and financial support from in-laws (P = 0.040 were significantly protective. Conclusion: IPV prevalence was less than the national average for India, but the majority of victims was women. The most common type of IPV was verbal. Alcohol use prevalence was higher than the national average, but harmful use was lower. Alcohol use is a significant risk factor for IPV. Education and income of women were not significantly protective against IPV but increased age at marriage and support from in-laws were.

  20. Intimate partner violence and housing instability.

    Science.gov (United States)

    Pavao, Joanne; Alvarez, Jennifer; Baumrind, Nikki; Induni, Marta; Kimerling, Rachel

    2007-02-01

    The mental and physical health consequences of intimate partner violence (IPV) have been well established, yet little is known about the impact of violence on a woman's ability to obtain and maintain housing. This cross-sectional study examines the relationship between recent IPV and housing instability among a representative sample of California women. It is expected that women who have experienced IPV will be at increased risk for housing instability as evidenced by: (1) late rent or mortgage, (2) frequent moves because of difficulty obtaining affordable housing, and/or (3) without their own housing. Data were taken from the 2003 California Women's Health Survey, a population-based, random-digit-dial, annual probability survey of adult California women (N=3619). Logistic regressions were used to predict housing instability in the past 12 months, adjusting for the following covariates; age, race/ethnicity, education, poverty status, marital status, children in the household, and past year IPV. In the multivariate model, age, race/ethnicity, marital status, poverty, and IPV were significant predictors of housing instability. After adjusting for all covariates, women who experienced IPV in the last year had almost four times the odds of reporting housing instability than women who did not experience IPV (adjusted odds ratio=3.98, 95% confidence interval: 2.94-5.39). This study found that IPV was associated with housing instability among California women. Future prospective studies are needed to learn more about the nature and direction of the relationship between IPV and housing instability and the possible associated negative health consequences.

  1. [Health status and intimate partner violence].

    Science.gov (United States)

    Sanz-Barbero, Belén; Rey, Lourdes; Otero-García, Laura

    2014-01-01

    To describe the prevalence of intimate partner violence (IPV) in Spain in the last year and at some point during the lifetime, to determine health status in women according to whether they had experienced IPV or not, and to analyze the individual variables associated with IPV in Spain. A cross-sectional study was performed of the database, Macrosurvey on Gender Violence in Spain 2011. This database includes data on 7,898 women older than 18 years old. The dependent variables were IPV-last year, IPV-ever in life. Covariates consisted of sociodemographic characteristics, socioeconomic status, maternal experience of IPV, social support, and self-care. The measure of association used was the OR with its 95% confidence interval (95% CI). A total of 3.6% of women had experienced IPV-last year and 12.2% ever in life. Female victims of IPV had poorer health than women who had not experienced IPV. Immigrant women living in Spain for 6 years or more were more likely to experience IPV-ever in life than Spanish women [OR (95% CI): 1.95 (1.50, 2.53)]. An interaction was found between nationality and the existence of children under 18 years old. Among women with children under 18 years old, immigrant women were more likely to experience IPV-last year than Spanish women [OR (95% CI): 1.99 (1.25, 3.17)]. Other variables associated with IPV were age, low socioeconomic status, low social support and having a mother who had experienced IPV. In Spain, some women have a higher probability of experiencing IPV. The variables associated with greater vulnerability to IPV should be taken into account when implementing measures to prevent or alleviate IPV. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  2. Partner Selection for Strategic Alliance in Networked Manufacturing

    Institute of Scientific and Technical Information of China (English)

    CHENYou-ping; YINYong; ZHOUZu-de

    2004-01-01

    Networked Manufacturing is the trend evolution for manufacture enterprise to gain core competence in the networked economy environment. In this paper, the definition of the strategic alliance is introduced and its life cycle is described. As the selection of suitable partners is of vital importance to the success for strategic alliance in Networked Manufacturing environment, also in this paper, the definition, criteria and process for partner selection are introduced. Then the fuzzy-AHP (Analytic Hierarchy Process) method, as a fuzzy extension of analytic hierarchical approach for partner selection, is given. In the end, a case study is provided.

  3. Partners selection of VE based on the organizational field

    Institute of Scientific and Technical Information of China (English)

    GUO Chang-yu; SHOU Jian-min

    2007-01-01

    VE organizational field is a management meaning field formed by the mutual action of resources element. It studies leader and partners in VE as a system, and founds the affiliation among them by the relation of resources. It describes candidate partner enterprise's inner trait and exterior trait by quality parameter and exterior parameter, then analyzes and evaluates them. It combines the qualitative variable and quantitative variable to evaluate the candidate enterprises. It integrates static and dynamic method to help the VE leader to choose partner, which is good for the whole alliance.

  4. College students' perceptions of intimate partner cyber harassment.

    Science.gov (United States)

    Melander, Lisa A

    2010-06-01

    Little is known about cyber harassment in general, and in order to understand more about online harassment among intimate partners, it is important to examine people's perceptions of this new form of aggression. Using Johnson's typology of relationship violence as a guiding framework, the role of technology in partner violence was explored using data from five focus group interviews. Six themes emerged from the analyses, four of which revealed that this partner violence typology accounted for the aggressive use of technology in dating relationships. The remaining themes centered on the ways in which online harassment differs from offline violence. These findings have important theoretical implications and may inform future prevention and intervention efforts.

  5. What were they thinking? Men who murder an intimate partner.

    Science.gov (United States)

    Dobash, R Emerson; Dobash, Russell P

    2011-01-01

    The focus is on cognitions of men who murder an intimate partner and includes thinking prior to and after the murder. Based on the Murder in Britain Study, the qualitative accounts of various professionals included in the case-files of 104 men convicted of murdering a woman partner are used to examine beliefs about intimate relationships, orientations toward violence and previous violence to the victim, as well as subsequent denials, rationalizations, and justifications. We conclude that these and other cognitions are important elements of intimate partner murder and must be challenged and changed in efforts to eliminate nonlethal abuse and murder.

  6. Spinal-Cord-Injured Individual's Experiences of Having a Partner

    DEFF Research Database (Denmark)

    Angel, Sanne

    2015-01-01

    Having a partner is a strong factor in adaptation to the new life situation with a spinal cord injury (SCI). Still, more knowledge in detail about the partner's influences according to the experiences of individuals with SCI could contribute to the understanding of the situation after an injury...... and allowed SCI individuals the ability to self-realize. This promoted feelings of profound gratitude but also dependency. Thus, the SCI individual benefitted from the partner's support mentally and physically, which enabled a life that would not otherwise be possible....

  7. Intimate partner violence among rural South African men: alcohol use, sexual decision-making, and partner communication.

    Science.gov (United States)

    Hatcher, Abigail M; Colvin, Christopher J; Ndlovu, Nkuli; Dworkin, Shari L

    2014-01-01

    Nearly one-third of South African men report enacting intimate partner violence. Beyond the direct health consequences for women, intimate partner violence is also linked to varied risk behaviours among men who enact it, including alcohol abuse, risky sex, and poor healthcare uptake. Little is known about how to reduce violence perpetration among men. We conducted retrospective, in-depth interviews with men (n = 53) who participated in a rural South African programme that targeted masculinities, HIV risk, and intimate partner violence. We conducted computer-assisted thematic qualitative coding alongside a simple rubric to understand how the programme may lead to changes in men's use of intimate partner violence. Many men described new patterns of reduced alcohol intake and improved partner communication, allowing them to respond in ways that did not lead to the escalation of violence. Sexual decision-making changed via reduced sexual entitlement and increased mutuality about whether to have sex. Men articulated the intertwined nature of each of these topics, suggesting that a syndemic lens may be useful for understanding intimate partner violence. These data suggest that alcohol and sexual relationship skills may be useful levers for future violence prevention efforts, and that intimate partner violence may be a tractable issue as men learn new skills for enacting masculinities in their household and in intimate relationships.

  8. Urban adolescent girls' perspectives on multiple partners in the context of the sexual double standard and intimate partner violence.

    Science.gov (United States)

    Teitelman, Anne M; Tennille, Julie; Bohinski, Julia; Jemmott, Loretta S; Jemmott, John B

    2013-01-01

    This article describes the influence of abusive and nonabusive relationship dynamics on the number of sex partners among urban adolescent girls. Focus groups were conducted with 64 sexually active adolescent girls ages 14 to 17 years. General coding and content analyses identified patterns, themes, and salient beliefs. More than one third (37.5%) reported having experienced physical, intimate partner violence; 32.8% had two or more recent sex partners, and 37.5% had ever had a sexually transmitted infection (STI) or HIV. Although some girls in abusive relationships feared retribution if they had more than one partner, others sought additional partners for solace or as an act of resistance. Adolescent HIV/STI prevention programs need to address the influence of gender norms such as the sexual double standard, as well as partner pressure and partner abuse on adolescent decision-making about safer sex, and also promote healthy relationships as integral to advancing HIV/STI risk reduction. Copyright © 2013 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  9. Using Ecological Momentary Assessment to investigate associations between ejaculatory latency and control in partnered and non-partnered sexual activities.

    Science.gov (United States)

    Jern, Patrick; Gunst, Annika; Sandqvist, Felicia; Sandnabba, N Kenneth; Santtila, Pekka

    2011-07-01

    Ecological Momentary Assessment (EMA) was used to investigate associations between, and variations in, ejaculatory control and ejaculation latency time (ELT) over repeated measurements of sexual activities. Differences between measures recorded in partnered or non-partnered settings were also investigated. The sample consisted of 21 male Finns aged 18 years or above, contributing a total of 158 reports of partnered and non-partnered sexual activities over a six-week period. In the context of non-partnered sexual activities, after controlling for within-subjects dependence, ELTs between events were predictive of one another, but ELT did not predict ejaculatory control when measured simultaneously, nor at subsequent events. Also, ejaculatory control could not predict simultaneously measured ELT or ejaculatory control at subsequent events. During partnered sexual activities, both ejaculatory control and ELT could be accurately predicted by observing ejaculatory control at prior events. In this context, ejaculatory control could also reliably predict simultaneously measured ELT. ELT or ejaculatory control during partnered sexual activity could not be predicted by observing ELT at prior events. Between-event correlations were generally low, indicating considerable variation in ejaculatory functioning over time. EMA is a thrifty assessment method for studying variations in ejaculatory function, and is likely suitable for studying sexual dysfunctions in general.

  10. Effects of potential partners' physical attractiveness and socioeconomic status on sexuality and partner selection.

    Science.gov (United States)

    Townsend, J M; Levy, G D

    1990-04-01

    Male (n = 170) and female (n = 212) college students viewed photographs, which had been prerated for physical attractiveness, of three opposite-sex individuals. These photographs were paired with three levels of occupational status and income. Subjects indicated their willingness to engage in relationships of varying levels of sexual intimacy and marital potential with the portrayed individuals. Analyses of variance, correlations, and trend analyses supported the hypotheses. Compared to men, women are more likely to prefer or insist that sexual intercourse occur in relationships that involve affection and marital potential, and women place more emphasis than men do on partners' SES in such relationships. Consequently, men's SES and their willingness and ability to invest affection and resources in relationships may often outweigh the effects of their physical attractiveness in women's actual selection of partners. These results and the literature reviewed are more consistent with parental investment theory than with the view that these sex differences are solely the result of differential access to resources and differential socialization.

  11. Knowledge, Perception and Level of Male Partner Involvement in ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Choice of Delivery Site among Couples at Coast Level Five Hospital,. Mombasa County .... conditions of sexual relations, family size and whether their .... Meaning, awareness and importance of male partner involvement. (N=207). Women.

  12. When Loved One Has Breast Cancer, Partner Suffers, Too

    Science.gov (United States)

    ... health care professionals need to do a better job reaching out to partners early on and identifying ... to help them cope," added Markham, an associate professor of medicine at the University of Florida. "When ...

  13. Isovector and hidden-beauty partners of the X(3872)

    Energy Technology Data Exchange (ETDEWEB)

    Høgaasen, Hallstein, E-mail: hallstein.hogasen@fys.uio.no [Department of Physics, University of Oslo, Box 1048, NO-0316 Oslo (Norway); Kou, Emi, E-mail: kou@lal.in2p3.fr [Laboratoire de l' Accélérateur Linéaire, Université Paris-Sud, IN2P3-CNRS, Centre Scientifique d' Orsay, 91898 Orsay Cedex (France); Richard, Jean-Marc, E-mail: j-m.richard@ipnl.in2p3.fr [Université de Lyon, Institut de Physique Nucléaire de Lyon, UCBL–IN2P3-CNRS, 4, rue Enrico Fermi, 69622 Villeurbanne Cedex (France); Sorba, Paul, E-mail: paul.sorba@lapth.cnrs.fr [LAPTh, Laboratoire d' Annecy-le-Vieux de Physique Théorique, CNRS, Université de Savoie, BP 110, 74941 Annecy-le-Vieux Cedex (France)

    2014-05-01

    The isovector partners of the X(3872), recently found at BES III, Belle and CLEO-c were predicted in a simple model based on the chromomagnetic interaction among quarks. The extension to the hidden-beauty sector is discussed.

  14. Parents as partners: building collaborations to support the ...

    African Journals Online (AJOL)

    Parents as partners: building collaborations to support the development of school ... South African Journal of Education ... children to develop the abilities underlying vital school-readiness skills during whole-class, therapeutic group sessions.

  15. PARTNER project: Trained to battle cancer with particles

    CERN Multimedia

    2009-01-01

    The four CERN students participating in the PARTNER project. From left to right: Daniel Abler (Germany), Faustin Laurentiu Roman (Romania), Vassiliki Kanellopoulos (Greece/Germany) and Till Tobias Boehlen (Germany).

  16. Sexual partners and condom use of migrant workers in Thailand.

    Science.gov (United States)

    Ford, Kathleen; Chamrathrithirong, Aphichat

    2007-11-01

    The objectives of this paper were to identify the types of sexual partners and condom use of migrant workers. Data for the study were drawn from a survey of 3,426 migrant workers in southern coastal and northern areas of Thailand conducted in 2004. Among sexually active men, 25% reported visiting a sex worker, 57% reported a regular partner, and 6% reported another non-regular partner in the last year. Reported condom use was high with sex workers (79% reported always use), but low with regular partners (4% ever use). Factors related to visiting sex workers included marital status (more visits if not married), longer residence in Thailand, occupation of seafarer or seafood production worker, Cambodian origin, and perceived AIDS risk. Condom use with sex workers was higher for younger men, married men, men who had been in Thailand longer, men with lower perceived AIDS risk, and men who drank alcohol less frequently.

  17. Residence in Switzerland of partners of members of the personnel

    CERN Multimedia

    2012-01-01

    1. Definitions a) CERN Staff Rules and Regulations Article S IV 1.02 of the Staff Rules defines a "partner", irrespective of gender, as "any person linked to an employed member of the personnel by a partnership officially registered in a Member State". Partners are regarded as family members for the purposes of protection against the financial consequences of illness and accidents. b) Swiss Federal Law Under Swiss federal law, to which the text below essentially refers, the following definitions apply: "partners": a couple of the same sex (linked by a registered partnership), "common-law spouses": a couple of the opposite sex (unmarried). Provided that they are aged 18 or more and are not blood relatives, two people of the same sex ("partners") may officially register their partnership with the competent registry office in order to give it a legal framework (a civil partnership commonly known as the Federal PACS...

  18. The Process of Partnering; Gluing Contracts, Organising and Financing together

    DEFF Research Database (Denmark)

    Koch, Christian; Thuesen, Christian; Gottlieb, Stefan

    2005-01-01

    This paper discusses management of partnering projects where construction companies and clients cooperate in developing buildings and services. Taking a practice based theory and political process approach, partnering is seen as an example of a complex project operation, characterised by processual...... interactions between an emergent conceptual frame and the project's operational activities. Drawing on two case studies, it is analyzed how the governance frame of partnering projects is constituted by a combination of partnering elements, traditional contracts and financial arrangements. On the operational...... level these elements is continuously mobilized, negotiated and stabilized in their intersection with the practices and skill basis for the project. It is thus shown how incentives becomes especially problematic for the architects due to tensions between new and old contractual forms, and that project...

  19. socio-economic status and preferences in marriage partner ...

    African Journals Online (AJOL)

    Engr E. Egbochukwu

    evolve preferences for males who had good financial prospects, were older than themselves, had ... of love and sex find that women value more than men, marriage partners who possess status ..... Marriage Choices and Social Reproduction:.

  20. Public-Private Partnerships: NASA as Your Business Partner

    Science.gov (United States)

    Martin, Gary

    2017-01-01

    Partnerships is an important part of doing business at NASA. NASA partners with external organizations to access capabilities under collaborative agreements; enters into agreements for partner access to NASA capabilities; expand overall landscape of space activity; and spurring innovation. The U.S. national policy on commercial space is to develop a robust and competitive U.S. commercial space sector and to energize competitive domestic industries to participate in global markets. Commercial space must be competitive, while the government has other priorities such as safety, jobs, etc. NASA partnerships consist of Reimbursable and Non-Reimbursable Space Act Agreements. Partnerships at Ames aligns with Ames' core competencies, and Partners often office in the NASA Research Park, which is an established regional innovation cluster that facilitates commercialization and services as a technology accelerator via onsite collaborations between NASA and its partners.