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Sample records for elevated pin1 expression

  1. PIN1 gene overexpression and beta-catenin gene mutation/expression in hepatocellular carcinoma and their significance.

    Science.gov (United States)

    Wang, Hui; Zhang, Jinxiang; Feng, Wei; Zhang, Shu; Liang, Huifang; Wang, Yang; Zheng, Qichang; Li, Zhuoya

    2007-02-01

    The evolution of hepatocellular carcinoma (HCC) is a compound process which involves many kinds of genes and transductional pathways. The expression of the peptidyl-proplyl-isomerase PIN1 gene, the mutation in exon 3 of beta-catenin and its correspondent abnormal expression and their roles in the hepatocellular carcinogeneisis were investigated. Among 29 pair cases of HCC and non-carcinoma tissues, the expression of PIN1 gene was detected by immunochemical staining. Mutations in exon 3 of beta-catenin gene and differential expression of beta-catenin gene were investigated by the methods of PCR-SSCP, direct sequencing and immunohistochemical technique as well. The results indicated: (1) 44.8% (13/29) cases of HCC presented higher level of PIN1 gene expression than non-cancerous tissues (chi2=32.63, Pexpression in non-cancerous tissues; (2) 58.6% (17/29) HCC tissues showed beta-catenin protein accumulation in cytoplasm and nucleus. 46.2% (6/13) HCC tissues indicated beta-catenin protein accumulation with higher level of PIN1 expression, while 53.8% (7/13) HCC tissues indicated beta-catenin protein accumulation with lower level or trace of PIN1 expression (chi2=0.00, P>0.05); (3) 24.1% (7/29) of primary tumor lesions carried gene mutations in exon 3 of beta-catenin, and accompanied by beta-catenin protein accumulation. There was no mutation in non-cancerous tissues. All the mutation presented in tissues with low level of PIN1 expression. There was no mutation of beta-catenin gene in tissues with high PIN1 expression level (chi2=58.12, Pexpression could promote hepatocellular carcinogenesis via a way different from beta-catenin gene mutation.

  2. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

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    Lu Kun

    2008-12-01

    Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

  3. The prolyl isomerase Pin1 increases β-cell proliferation and enhances insulin secretion.

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    Nakatsu, Yusuke; Mori, Keiichi; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mitsuzaki-Miyoshi, Keiko; Sakoda, Hideyuki; Fujishiro, Midori; Yamaguchi, Suguru; Kushiyama, Akifumi; Ono, Hiraku; Ishihara, Hisamitsu; Asano, Tomoichiro

    2017-07-14

    The prolyl isomerase Pin1 binds to the phosphorylated Ser/Thr-Pro motif of target proteins and enhances their cis-trans conversion. This report is the first to show that Pin1 expression in pancreatic β cells is markedly elevated by high-fat diet feeding and in ob/ob mice. To elucidate the role of Pin1 in pancreatic β cells, we generated β-cell-specific Pin1 KO (βPin1 KO) mice. These mutant mice showed exacerbation of glucose intolerance but had normal insulin sensitivity. We identified two independent factors underlying impaired insulin secretion in the βPin1 KO mice. Pin1 enhanced pancreatic β-cell proliferation, as indicated by a reduced β-cell mass in βPin1 KO mice compared with control mice. Moreover, a diet high in fat and sucrose failed to increase pancreatic β-cell growth in the βPin1 KO mice, an observation to which up-regulation of the cell cycle protein cyclin D appeared to contribute. The other role of Pin1 was to activate the insulin-secretory step: Pin1 KO β cells showed impairments in glucose- and KCl-induced elevation of the intracellular Ca 2+ concentration and insulin secretion. We also identified salt-inducible kinase 2 (SIK2) as a Pin1-binding protein that affected the regulation of Ca 2+ influx and found Pin1 to enhance SIK2 kinase activity, resulting in a decrease in p35 protein, a negative regulator of Ca 2+ influx. Taken together, our observations demonstrate critical roles of Pin1 in pancreatic β cells and that Pin1 both promotes β-cell proliferation and activates insulin secretion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Investigation of gene expression and serum levels of PIN1 and eNOS with high blood pressure in patients with Alzheimer disease.

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    Azimi, Mina; Nikanfar, Masoud; Khakikhatibi, Fatemeh; Rahbarghazi, Reza; Nourazarian, Seyed Manuchehr; Biray Avci, Cigir; Nourazarian, Alireza

    2017-09-01

    According to evidence, Alzheimer's disease is known as one of the most serious neurodegenerative diseases, for which hypertension has been observed to be a key risk factor. Therefore, this study aims to examine the relationship between the PIN1 and eNOS genes expression, as well as serum levels and hypertension in Alzheimer's disease sufferers. Blood samples were obtained from subjects who were divided into four groups: the control group, normotensive Alzheimer's patients, the Alzheimer's sufferers group with hypertension, and the healthy group with only hypertension, considering the inhibition of confounding factors. Thereafter, eNOS and PIN1 genes expression along with serum levels were studied. Based on the obtained results, a statistically significant correlation didn't exist between serum level of PIN1 and the systolic and diastolic blood pressure, between serum level of eNOS and diastolic blood pressure in the norm tension Alzheimer's disease patients, between serum levels of PIN1, eNOS and systolic blood pressure, and between serum eNOS and systolic and diastolic blood pressure in the patients with hypertension (pdiseases in Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Negative Regulation of the Stability and Tumor Suppressor Function of Fbw7 by the Pin1 Prolyl Isomerase

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    Min, Sang-Hyun; Lau, Alan W.; Lee, Tae Ho; Inuzuka, Hiroyuki; Wei, Shuo; Huang, Pengyu; Shaik, Shavali; Lee, Daniel Yenhong; Finn, Greg; Balastik, Martin; Chen, Chun-Hau; Luo, Manli; Tron, Adriana E.; DeCaprio, James A.; Zhou, Xiao Zhen; Wei, Wenyi; Lu, Kun Ping

    2012-01-01

    SUMMARY Fbw7 is the substrate recognition component of the SCF (Skp1-Cullin-F-box)-type E3 ligase complex and a well-characterized tumor suppressor that targets numerous oncoproteins for destruction. Genomic deletion or mutation of FBW7 has been frequently found in various types of human cancers, however, little is known about the upstream signaling pathway(s) governing Fbw7 stability and cellular functions. Here we report that Fbw7 protein destruction and tumor suppressor function are negatively regulated by the prolyl isomerase Pin1. Pin1 interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. Consequently, over-expressing Pin1 reduces Fbw7 abundance and suppresses Fbw7’s ability to inhibit proliferation and transformation. By contrast, depletion of Pin1 in cancer cells leads to elevated Fbw7 expression, which subsequently reduces Mcl-1 abundance, sensitizing cancer cells to Taxol. Thus, Pin1-mediated inhibition of Fbw7 contributes to oncogenesis and Pin1 may be a promising drug target for anti-cancer therapy. PMID:22608923

  6. Overexpression of PvPin1, a Bamboo Homolog of PIN1-Type Parvulin 1, Delays Flowering Time in Transgenic Arabidopsis and Rice

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    Zhigang Zheng

    2017-09-01

    Full Text Available Because of the long and unpredictable flowering period in bamboo, the molecular mechanism of bamboo flowering is unclear. Recent study showed that Arabidopsis PIN1-type parvulin 1 (Pin1At is an important floral activator and regulates floral transition by facilitating the cis/trans isomerization of the phosphorylated Ser/Thr residues preceding proline motifs in suppressor of overexpression of CO 1 (SOC1 and agamous-like 24 (AGL24. Whether bamboo has a Pin1 homolog and whether it works in bamboo flowering are still unknown. In this study, we cloned PvPin1, a homolog of Pin1At, from Phyllostachys violascens (Bambusoideae. Bioinformatics analysis showed that PvPin1 is closely related to Pin1-like proteins in monocots. PvPin1 was widely expressed in all tested bamboo tissues, with the highest expression in young leaf and lowest in floral bud. Moreover, PvPin1 expression was high in leaves before bamboo flowering then declined during flower development. Overexpression of PvPin1 significantly delayed flowering time by downregulating SOC1 and AGL24 expression in Arabidopsis under greenhouse conditions and conferred a significantly late flowering phenotype by upregulating OsMADS56 in rice under field conditions. PvPin1 showed subcellular localization in both the nucleus and cytolemma. The 1500-bp sequence of the PvPin1 promoter was cloned, and cis-acting element prediction showed that ABRE and TGACG-motif elements, which responded to abscisic acid (ABA and methyl jasmonate (MeJA, respectively, were characteristic of P. violascens in comparison with Arabidopsis. On promoter activity analysis, exogenous ABA and MeJA could significantly inhibit PvPin1 expression. These findings suggested that PvPin1 may be a repressor in flowering, and its delay of flowering time could be regulated by ABA and MeJA in bamboo.

  7. Pin1 promotes production of Alzheimer's amyloid β from β-cleaved amyloid precursor protein

    International Nuclear Information System (INIS)

    Akiyama, Hirotada; Shin, Ryong-Woon; Uchida, Chiyoko; Kitamoto, Tetsuyuki; Uchida, Takafumi

    2005-01-01

    Here we show that prolyl isomerase Pin1 is involved in the Aβ production central to the pathogenesis of Alzheimer's disease. Enzyme immunoassay of brains of the Pin1-deficient mice revealed that production of Aβ40 and Aβ42 was lower than that of the wild-type mice, indicating that Pin1 promotes Aβ production in the brain. GST-Pin1 pull-down and immunoprecipitation assay revealed that Pin1 binds phosphorylated Thr668-Pro of C99. In the Pin1 -/- MEF transfected with C99, Pin1 co-transfection enhanced the levels of Aβ40 and Aβ42 compared to that without Pin1 co-transfection. In COS7 cells transfected with C99, Pin1 co-transfection enhanced the generation of Aβ40 and Aβ42, and reduced the expression level of C99, facilitating the C99 turnover. Thus, Pin1 interacts with C99 and promotes its γ-cleavage, generating Aβ40 and Aβ42. Further, GSK3 inhibitor lithium blocked Pin1 binding to C99 by decreasing Thr668 phosphorylation and attenuated Aβ generation, explaining the inhibitory effect of lithium on Aβ generation

  8. Peptidyl Prolyl Isomerase PIN1 Directly Binds to and Stabilizes Hypoxia-Inducible Factor-1α.

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    Hyeong-Jun Han

    Full Text Available Peptidyl prolyl isomerase (PIN1 regulates the functional activity of a subset of phosphoproteins through binding to phosphorylated Ser/Thr-Pro motifs and subsequently isomerization of the phosphorylated bonds. Interestingly, PIN1 is overexpressed in many types of malignancies including breast, prostate, lung and colon cancers. However, its oncogenic functions have not been fully elucidated. Here, we report that PIN1 directly interacts with hypoxia-inducible factor (HIF-1α in human colon cancer (HCT116 cells. PIN1 binding to HIF-1α occurred in a phosphorylation-dependent manner. We also found that PIN1 interacted with HIF-1α at both exogenous and endogenous levels. Notably, PIN1 binding stabilized the HIF-1α protein, given that their levels were significantly increased under hypoxic conditions. The stabilization of HIF-1α resulted in increased transcriptional activity, consequently upregulating expression of vascular endothelial growth factor, a major contributor to angiogenesis. Silencing of PIN1 or pharmacologic inhibition of its activity abrogated the angiogenesis. By utilizing a bioluminescence imaging technique, we were able to demonstrate that PIN1 inhibition dramatically reduced the tumor volume in a subcutaneous mouse xenograft model and angiogenesis as well as hypoxia-induced transcriptional activity of HIF-1α. These results suggest that PIN1 interacting with HIF-1α is a potential cancer chemopreventive and therapeutic target.

  9. Pin1 and secondary hyperparathyroidism of chronic kidney disease: gene polymorphisms and protein levels.

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    Zhao, Yu; Zhang, Li-Li; Ding, Fa-Xian; Cao, Ping; Qi, Yuan-Yuan; Wang, Jing

    2017-11-01

    Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a key regulator of PTH mRNA stability. Secondary hyperparathyroidism (SHPT), which is characterized by elevated serum PTH levels, is a common complication of CKD. We investigated the possible associations between CKD with SHPT (CKD SHPT) and single-nucleotide polymorphisms of the Pin1 gene and compared the levels of the Pin1 protein in the CKD SHPT patients with those of the controls. The study group included 251 CKD SHPT patients and 61 controls. One putative functional SNP (single nucleotide polymorphism) in the Pin1 promoter (rs2233679C > T: c.-667C > T) is the main object. Genotyping was performed on purified DNA using polymerase chain reaction-restriction (PCR) and restriction fragment length polymorphisms (RFLP). The levels of Pin1 were measured in serum using an enzyme-linked immunosorbent assay. Genotyping showed that CT + TT in the Pin1 promoter was significantly more common in the CKD SHPT group than in the control group (p<.05). The correlation analysis demonstrated that a significant difference in the C to T transition in the Pin1 promoter contributed to CKD SHPT (χ 2 =12.47, p<.05; Odds ratios (OR) = 1.26, 95% confidence (CI) intervals =1.06-1.49). The multivariate logistic regression analysis reported that the OR and 95%CI were 12.693 and 2.029-75.819 (p<.05), respectively, in the Pin1 gene promoter -667T variant genotypes (CT + TT) after adjusting for other factors, and those values in Pin1 were 0.310 and 0.122-0.792 (p<.05). The -667T genetic variants in the Pin1 promoter contribute to an increased risk of CKD SHPT and may be biomarkers of susceptibility to CKD SHPT.

  10. Regulation of AR and (beta)-Catenin Signaling by Pin 1 in Prostate Cancer

    National Research Council Canada - National Science Library

    Chen, Shaoyong

    2006-01-01

    .... The mechanisms include that Pin1 can enhance beta-catenin nuclear localization, TCF/beta-catenin dependent Topflash activity, and c-Myc and Cyclin D1 expression, and disrupt AR-mediated suppression...

  11. Role of Pin1 in UVA-induced cell proliferation and malignant transformation in epidermal cells

    International Nuclear Information System (INIS)

    Han, Chang Yeob; Hien, Tran Thi; Lim, Sung Chul; Kang, Keon Wook

    2011-01-01

    Highlights: → Pin1 expression is enhanced by low energy UVA irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. → UVA irradiation increases activator protein-1 activity and cyclin D1 in a Pin1-dependent manner. → UVA potentiates EGF-inducible, anchorage-independent growth of epidermal cells, and this is suppressed by Pin1 inhibition or by anti-oxidant. -- Abstract: Ultraviolet A (UVA) radiation (λ = 320-400 nm) is considered a major cause of human skin cancer. Pin1, a peptidyl prolyl isomerase, is overexpressed in most types of cancer tissues and plays an important role in cell proliferation and transformation. Here, we demonstrated that Pin1 expression was enhanced by low energy UVA (300-900 mJ/cm 2 ) irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. Exposure of epidermal cells to UVA radiation increased cell proliferation and cyclin D1 expression, and these changes were blocked by Pin1 inhibition. UVA irradiation also increased activator protein-1 (AP-1) minimal reporter activity and nuclear levels of c-Jun, but not c-Fos, in a Pin1-dependent manner. The increases in Pin1 expression and in AP-1 reporter activity in response to UVA were abolished by N-acetylcysteine (NAC) treatment. Finally, we found that pre-exposure of JB6 C141 cells to UVA potentiated EGF-inducible, anchorage-independent growth, and this effect was significantly suppressed by Pin1inhibition or by NAC.

  12. Targeting Pin1 by inhibitor API-1 regulates microRNA biogenesis and suppresses hepatocellular carcinoma development.

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    Pu, Wenchen; Li, Jiao; Zheng, Yuanyuan; Shen, Xianyan; Fan, Xin; Zhou, Jian-Kang; He, Juan; Deng, Yulan; Liu, Xuesha; Wang, Chun; Yang, Shengyong; Chen, Qiang; Liu, Lunxu; Zhang, Guolin; Wei, Yu-Quan; Peng, Yong

    2018-01-30

    Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, but there are few effective treatments. Aberrant microRNA (miRNA) biogenesis is correlated with HCC development. We previously demonstrated that prolyl isomerase Pin1 participates in miRNA biogenesis and is a potential HCC treatment target. However, how Pin1 modulates miRNA biogenesis remains obscure. Here, we present in vivo evidence that Pin1 overexpression is directly linked to the development of HCC. Administration with Pin1 inhibitor API-1, a novel and specific small molecule targeting Pin1 PPIase domain and inhibiting Pin1 cis-trans isomerizing activity, suppresses in vitro cell proliferation and migration of HCC cells. But API-1-induced Pin1 inhibition is insensitive to HCC cells with low Pin1 expression and/or low XPO5 phosphorylation. Mechanistically, Pin1 recognizes and isomerizes the phosphorylated Serine-Proline (pS-P) motif of pXPO5 and passivates pXPO5. Pin1 inhibition by API-1 maintains the active conformation of pXPO5, restores XPO5-driven precursor miRNA nuclear-to-cytoplasm export, activating anticancer miRNA biogenesis, and leading to both in vitro HCC suppression and HCC suppression in xenograft mice. Experimental evidence suggests Pin1 inhibition by API-1 upregulates miRNA biogenesis via retaining active XPO5 conformation and suppresses HCC development, revealing the mechanism of Pin1-mediated miRNA biogenesis and unequivocally supports API-1 as a novel drug candidate for HCC therapy, especially for Pin1-overexpressing, ERK-activated HCC. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  13. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations

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    Yusuke Nakatsu

    2016-09-01

    Full Text Available Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14. Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  14. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations.

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    Nakatsu, Yusuke; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mori, Keiichi; Sakoda, Hideyuki; Fujishiro, Midori; Ono, Hiraku; Kushiyama, Akifumi; Asano, Tomoichiro

    2016-09-07

    Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer's disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  15. Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: insights in patients with diabetes.

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    Paneni, Francesco; Costantino, Sarah; Castello, Lorenzo; Battista, Rodolfo; Capretti, Giuliana; Chiandotto, Sergio; D'Amario, Domenico; Scavone, Giuseppe; Villano, Angelo; Rustighi, Alessandra; Crea, Filippo; Pitocco, Dario; Lanza, Gaetano; Volpe, Massimo; Del Sal, Giannino; Lüscher, Thomas F; Cosentino, Francesco

    2015-04-01

    Diabetes is a major driver of cardiovascular disease, but the underlying mechanisms remain elusive. Prolyl-isomerase Pin1 recognizes specific peptide bonds and modulates function of proteins altering cellular homoeostasis. The present study investigates Pin1 role in diabetes-induced vascular disease. In human aortic endothelial cells (HAECs) exposed to high glucose, up-regulation of Pin1-induced mitochondrial translocation of pro-oxidant adaptor p66(Shc) and subsequent organelle disruption. In this setting, Pin1 recognizes Ser-116 inhibitory phosphorylation of endothelial nitric oxide synthase (eNOS) leading to eNOS-caveolin-1 interaction and reduced NO availability. Pin1 also mediates hyperglycaemia-induced nuclear translocation of NF-κB p65, triggering VCAM-1, ICAM-1, and MCP-1 expression. Indeed, gene silencing of Pin1 in HAECs suppressed p66(Shc)-dependent ROS production, restored NO release and blunted NF-kB p65 nuclear translocation. Consistently, diabetic Pin1(-/-) mice were protected against mitochondrial oxidative stress, endothelial dysfunction, and vascular inflammation. Increased expression and activity of Pin1 were also found in peripheral blood monocytes isolated from diabetic patients when compared with age-matched healthy controls. Interestingly, enough, Pin1 up-regulation was associated with impaired flow-mediated dilation, increased urinary 8-iso-prostaglandin F2α and plasma levels of adhesion molecules. Pin1 drives diabetic vascular disease by causing mitochondrial oxidative stress, eNOS dysregulation as well as NF-kB-induced inflammation. These findings provide molecular insights for novel mechanism-based therapeutic strategies in patients with diabetes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  16. Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the γ subunit.

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    Nakatsu, Yusuke; Iwashita, Misaki; Sakoda, Hideyuki; Ono, Hiraku; Nagata, Kengo; Matsunaga, Yasuka; Fukushima, Toshiaki; Fujishiro, Midori; Kushiyama, Akifumi; Kamata, Hideaki; Takahashi, Shin-Ichiro; Katagiri, Hideki; Honda, Hiroaki; Kiyonari, Hiroshi; Uchida, Takafumi; Asano, Tomoichiro

    2015-10-02

    AMP-activated protein kinase (AMPK) plays a critical role in metabolic regulation. In this study, first, it was revealed that Pin1 associates with any isoform of γ, but not with either the α or the β subunit, of AMPK. The association between Pin1 and the AMPK γ1 subunit is mediated by the WW domain of Pin1 and the Thr(211)-Pro-containing motif located in the CBS domain of the γ1 subunit. Importantly, overexpression of Pin1 suppressed AMPK phosphorylation in response to either 2-deoxyglucose or biguanide stimulation, whereas Pin1 knockdown by siRNAs or treatment with Pin1 inhibitors enhanced it. The experiments using recombinant Pin1, AMPK, LKB1, and PP2C proteins revealed that the protective effect of AMP against PP2C-induced AMPKα subunit dephosphorylation was markedly suppressed by the addition of Pin1. In good agreement with the in vitro data, the level of AMPK phosphorylation as well as the expressions of mitochondria-related genes, such as PGC-1α, which are known to be positively regulated by AMPK, were markedly higher with reduced triglyceride accumulation in the muscles of Pin1 KO mice as compared with controls. These findings suggest that Pin1 plays an important role in the pathogenic mechanisms underlying impaired glucose and lipid metabolism, functioning as a negative regulator of AMPK. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Loss of Pin1 Suppresses Hedgehog-Driven Medulloblastoma Tumorigenesis

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    Tao Xu

    2017-03-01

    Full Text Available Medulloblastoma is the most common malignant brain tumor in children. Therapeutic approaches to medulloblastoma (combination of surgery, radiotherapy, and chemotherapy have led to significant improvements, but these are achieved at a high cost to quality of life. Alternative therapeutic approaches are needed. Genetic mutations leading to the activation of the Hedgehog pathway drive tumorigenesis in ~30% of medulloblastoma. In a yeast two-hybrid proteomic screen, we discovered a novel interaction between GLI1, a key transcription factor for the mediation of Hedgehog signals, and PIN1, a peptidylprolyl cis/trans isomerase that regulates the postphosphorylation fate of its targets. The GLI1/PIN1 interaction was validated by reciprocal pulldowns using epitope-tagged proteins in HEK293T cells as well as by co-immunoprecipiations of the endogenous proteins in a medulloblastoma cell line. Our results support a molecular model in which PIN1 promotes GLI1 protein abundance, thus contributing to the positive regulation of Hedgehog signals. Most importantly, in vivo functional analyses of Pin1 in the GFAP-tTA;TRE-SmoA1 mouse model of Hedgehog-driven medulloblastoma demonstrate that the loss of Pin1 impairs tumor development and dramatically increases survival. In summary, the discovery of the GLI1/PIN1 interaction uncovers PIN1 as a novel therapeutic target in Hedgehog-driven medulloblastoma tumorigenesis.

  18. Inhibition of histone deacetylation alters Arabidopsis root growth in response to auxin via PIN1 degradation.

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    Nguyen, Hoai Nguyen; Kim, Jun Hyeok; Jeong, Chan Young; Hong, Suk-Whan; Lee, Hojoung

    2013-10-01

    Our results showed the histone deacetylase inhibitors (HDIs) control root development in Arabidopsis via regulation of PIN1 degradation. Epigenetic regulation plays a crucial role in the expression of many genes in response to exogenous or endogenous signals in plants as well as other organisms. One of epigenetic mechanisms is modifications of histone, such as acetylation and deacetylation, are catalyzed by histone acetyltransferase (HAT) and histone deacetylase (HDAC), respectively. The Arabidopsis HDACs, HDA6, and HDA19, were reported to function in physiological processes, including embryo development, abiotic stress response, and flowering. In this study, we demonstrated that histone deacetylase inhibitors (HDIs) inhibit primary root elongation and lateral root emergence. In response to HDIs treatment, the PIN1 protein was almost abolished in the root tip. However, the PIN1 gene did not show decreased expression in the presence of HDIs, whereas IAA genes exhibited increases in transcript levels. In contrast, we observed a stable level of gene expression of stress markers (KIN1 and COR15A) and a cell division marker (CYCB1). Taken together, these results suggest that epigenetic regulation may control auxin-mediated root development through the 26S proteasome-mediated degradation of PIN1 protein.

  19. Pin1 and neurodegeneration: a new player for prion disorders?

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    Elisa Isopi

    2015-07-01

    Full Text Available Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders.

  20. Discovery of novel selenium derivatives as Pin1 inhibitors by high-throughput screening

    Energy Technology Data Exchange (ETDEWEB)

    Subedi, Amit [Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, Saitama, 338-8570 (Japan); Shimizu, Takeshi [Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198 (Japan); Ryo, Akihide [Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa, 236-0004 (Japan); Sanada, Emiko [Bio-Active Compounds Discovery Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198 (Japan); Watanabe, Nobumoto [Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198 (Japan); Bio-Active Compounds Discovery Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198 (Japan); Osada, Hiroyuki, E-mail: hisyo@riken.jp [Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, Saitama, 338-8570 (Japan)

    2016-06-03

    Peptidyl prolyl cis/trans isomerization by Pin1 regulates various oncogenic signals during cancer progression, and its inhibition through multiple approaches has established Pin1 as a therapeutic target. However, lack of simplified screening systems has limited the discovery of potent Pin1 inhibitors. We utilized phosphorylation-dependent binding of Pin1 to its specific substrate to develop a screening system for Pin1 inhibitors. Using this system, we screened a chemical library, and identified a novel selenium derivative as Pin1 inhibitor. Based on structure-activity guided chemical synthesis, we developed more potent Pin1 inhibitors that inhibited cancer cell proliferation. -- Highlights: •Novel screening for Pin1 inhibitors based on Pin1 binding is developed. •A novel selenium compound is discovered as Pin1 inhibitor. •Activity guided chemical synthesis of selenium derivatives resulted potent Pin1 inhibitors.

  1. The peptidyl-prolyl isomerase Pin1 determines parathyroid hormone mRNA levels and stability in rat models of secondary hyperparathyroidism.

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    Nechama, Morris; Uchida, Takafumi; Mor Yosef-Levi, Irit; Silver, Justin; Naveh-Many, Tally

    2009-10-01

    Secondary hyperparathyroidism is a major complication of chronic kidney disease (CKD). In experimental models of secondary hyperparathyroidism induced by hypocalcemia or CKD, parathyroid hormone (PTH) mRNA levels increase due to increased PTH mRNA stability. K-homology splicing regulator protein (KSRP) decreases the stability of PTH mRNA upon binding a cis-acting element in the PTH mRNA 3' UTR region. As the peptidyl-prolyl isomerase (PPIase) Pin1 has recently been shown to regulate the turnover of multiple cytokine mRNAs, we investigated the role of Pin1 in regulating PTH mRNA stability in rat parathyroids and transfected cells. The data generated were consistent with Pin1 being a PTH mRNA destabilizing protein. Initial analysis indicated that Pin1 activity was decreased in parathyroid protein extracts from both hypocalcemic and CKD rats and that pharmacologic inhibition of Pin1 increased PTH mRNA levels posttranscriptionally in rat parathyroid and in transfected cells. Pin1 mediated its effects via interaction with KSRP, which led to KSRP dephosphorylation and activation. In the rat parathyroid, Pin1 inhibition decreased KSRP-PTH mRNA interactions, increasing PTH mRNA levels. Furthermore, Pin1-/- mice displayed increased serum PTH and PTH mRNA levels, suggesting that Pin1 determines basal PTH expression in vivo. These results demonstrate that Pin1 is a key mediator of PTH mRNA stability and indicate a role for Pin1 in the pathogenesis of secondary hyperparathyroidism in individuals with CKD.

  2. G Protein-coupled Receptor Kinase 2 (GRK2 Promotes Breast Tumorigenesis Through a HDAC6-Pin1 Axis

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    Laura Nogués

    2016-11-01

    Full Text Available In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2 as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6 leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators. Interestingly, a correlation between GRK2 expression and Pin1 levels and de-acetylation status is detected in breast cancer patients. Activation of the HDAC6-Pin1 axis underlies the positive effects of GRK2 on promoting growth factor signaling, cellular proliferation and anchorage-independent growth in both luminal and basal breast cancer cells. Enhanced GRK2 levels promote tumor growth in mice, whereas GRK2 down-modulation sensitizes cells to therapeutic drugs and abrogates tumor formation. Our data suggest that GRK2 acts as an important onco-modulator by strengthening the functionality of key players in breast tumorigenesis such as HDAC6 and Pin1.

  3. The peptidyl prolyl cis/trans isomerase Pin1/Ess1 inhibits phosphorylation and toxicity of tau in a yeast model for Alzheimer’s disease

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    Ann De Vos

    2015-04-01

    Full Text Available Since hyperphosphorylation of protein tau is a crucial event in Alzheimer’s disease, additional mechanisms besides the interplay of kinase and phosphatase activities are investigated, such as the effect of the peptidyl prolyl cis/trans isomerase Pin1. This isomerase was shown to bind and isomerize phosphorylated protein tau, thereby restoring the microtubule associated protein function of tau as well as promoting the dephosphorylation of the protein by the trans-dependent phosphatase PP2A. In this study we used models based on Saccharomyces cerevisiae to further elucidate the influence of Pin1 and its yeast ortholog Ess1 on tau phosphorylation and self-assembly. We could demonstrate that in yeast, a lack of Pin1 isomerase activity leads to an increase in phosphorylation of tau at Thr231, comparable to AD brain and consistent with earlier findings in other model organisms. However, we could also distinguish an effect by Pin1 on other residues of tau, i.e. Ser235 and Ser198/199/202. Furthermore, depletion of Pin1 isomerase activity results in reduced growth of the yeast cells, which is enhanced upon expression of tau. This suggests that the accumulation of hyperphosphorylated and aggregation-prone tau causes cytotoxicity in yeast. This study introduces yeast as a valuable model organism to characterize in detail the effect of Pin1 on the biochemical characteristics of protein tau, more specifically its phosphorylation and aggregation.

  4. The PIN1 family gene PvPIN1 is involved in auxin-dependent root emergence and tillering in switchgrass

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    Kaijie Xu

    2016-03-01

    Full Text Available Abstract Switchgrass (Panicum virgatum L.; family Poaceae is a warm-season C4 perennial grass. Tillering plays an important role in determining the morphology of aboveground parts and the final biomass yield of switchgrass. Auxin distribution in plants can affect a variety of important growth and developmental processes, including the regulation of shoot and root branching, plant resistance and biological yield. Auxin transport and gradients in plants are mediated by influx and efflux carriers. PvPIN1, a switchgrass PIN1-like gene that is involved in regulating polar transport, is a putative auxin efflux carrier. Neighbor-joining analysis using sequences deposited in NCBI databases showed that the PvPIN1gene belongs to the PIN1 family and is evolutionarily closer to the Oryza sativa japonica group. Tiller emergence and development was significantly promoted in plants subjected toPvPIN1 RNA interference (RNAi, which yielded a phenotype similar to that of wild-type plants treated with the auxin transport inhibitor TIBA (2,3,5-triiodobenzoic acid. A transgenic approach that inducedPvPIN1 gene overexpression or suppression altered tiller number and the shoot/root ratio. These data suggest that PvPIN1plays an important role in auxin-dependent adventitious root emergence and tillering.

  5. Effects of Pin1 loss in HdhQ111 knock-in mice

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    Elena eAgostoni

    2016-05-01

    Full Text Available Huntington’s disease (HD is a fatal, dominantly inherited, neurodegenerative disorder due to a pathological expansion of the CAG repeat in the coding region of the HTT gene. In the quest for understanding the molecular basis of neurodegeneration, we have previously demonstrated that the prolyl isomerase Pin1 plays a crucial role in mediating p53-dependent apoptosis triggered by mutant huntingtin (mHtt in vitro. To assess the effects of the lack of Pin1 in vivo, we have bred Pin1 knock-out mice with HdhQ111 knock-in mice, a genetically precise model of HD. We show that Pin1 genetic ablation modifies a portion of HdhQ111 phenotypes in a time-dependent fashion. As an early event, Pin1 activity reduces the DNA damage response. In midlife mice, by taking advantage of next-generation sequencing technology, we show that Pin1 activity modulates a portion of the alterations triggered by mHtt, extending the role of Pin1 to two additional HdhQ111 phenotypes: the unbalance in the synthesis/concentration of hormones, as well as the alteration of Wnt/β-catenin signaling. In aging animals, Pin1 significantly increases the number of mHtt-positive nuclear inclusions while it reduces gliosis. In summary, this work provides further support for a role of Pin1 in HD pathogenesis.

  6. Pin1, a new player in the fate of HIF-1α degradation: an hypothetical mechanism inside vascular damage as Alzheimer’s disease risk factor.

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    Elena eLonati

    2014-01-01

    Full Text Available Aetiology of neurodegenerative mechanisms underlying Alzheimer's disease (AD are still under elucidation. The contribution of cerebrovascular deficiencies (such as cerebral ischemia/stroke has been strongly endorsed in recent years. Reduction of blood supply leading to hypoxic condition is known to activate cellular responses mainly controlled by hypoxia-inducible transcription factor-1 (HIF-1. Thus alterations of oxygen responsive HIF-1α subunit in the central nervous system may contribute to the cognitive decline, especially influencing mechanisms associated to APP (amyloid precursor protein amyloidogenic metabolism. Although HIF-1α protein level is known to be regulated by von Hippel-Lindau (VHL ubiquitin-proteasome system, it has been recently suggested that Gsk-3β (glycogen synthase kinase-3β promotes a VHL-independent HIF-1α degradation. Here we provide evidences that in rat primary hippocampal cell cultures, HIF-1α degradation might be mediated by a synergic action of Gsk-3β and Pin1 (peptidyl-prolyl cis/trans isomerase. In post-ischemic conditions, such as those mimicked with oxygen glucose deprivation (OGD, HIF-1α protein level increases remaining unexpectedly high for long time after normal condition restoration jointly with the increase of LDH (lactate dehydrogenase and BACE1 (β-secretase 1 protein expression (70% and 140% respectively. Interestingly the Pin1 activity decreases about 40%-60% and Pin1S16 inhibitory phosphorylation significantly increases, indicating that Pin1 binding to its substrate and enzymatic activity are reduced by treatment. Co-immunoprecipitation experiments demonstrate that HIF-1α/Pin1 in normoxia are associated, and that in presence of specific Pin1 and Gsk-3β inhibitors their interaction is reduced in parallel to an increase of HIF-1α protein level. Thus we suggest that in post-OGD neurons the high level of HIF-1α might be due to Pin1 binding ability and activity reduction which affects HIF-1

  7. Nerve growth factor stimulates interaction of Cayman ataxia protein BNIP-H/Caytaxin with peptidyl-prolyl isomerase Pin1 in differentiating neurons.

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    Jan Paul Buschdorf

    Full Text Available Mutations in ATCAY that encodes the brain-specific protein BNIP-H (or Caytaxin lead to Cayman cerebellar ataxia. BNIP-H binds to glutaminase, a neurotransmitter-producing enzyme, and affects its activity and intracellular localization. Here we describe the identification and characterization of the binding between BNIP-H and Pin1, a peptidyl-prolyl cis/trans isomerase. BNIP-H interacted with Pin1 after nerve growth factor-stimulation and they co-localized in the neurites and cytosol of differentiating pheochromocytoma PC12 cells and the embryonic carcinoma P19 cells. Deletional mutagenesis revealed two cryptic binding sites within the C-terminus of BNIP-H such that single point mutants affecting the WW domain of Pin1 completely abolished their binding. Although these two sites do not contain any of the canonical Pin1-binding motifs they showed differential binding profiles to Pin1 WW domain mutants S16E, S16A and W34A, and the catalytically inert C113A of its isomerase domain. Furthermore, their direct interaction would occur only upon disrupting the ability of BNIP-H to form an intramolecular interaction by two similar regions. Furthermore, expression of Pin1 disrupted the BNIP-H/glutaminase complex formation in PC12 cells under nerve growth factor-stimulation. These results indicate that nerve growth factor may stimulate the interaction of BNIP-H with Pin1 by releasing its intramolecular inhibition. Such a mechanism could provide a post-translational regulation on the cellular activity of BNIP-H during neuronal differentiation.

  8. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action

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    Campaner, Elena; Rustighi, Alessandra; Zannini, Alessandro; Cristiani, Alberto; Piazza, Silvano; Ciani, Yari; Kalid, Ori; Golan, Gali; Baloglu, Erkan; Shacham, Sharon; Valsasina, Barbara; Cucchi, Ulisse; Pippione, Agnese Chiara; Lolli, Marco Lucio; Giabbai, Barbara; Storici, Paola; Carloni, Paolo; Rossetti, Giulia; Benvenuti, Federica; Bello, Ezia; D'Incalci, Maurizio; Cappuzzello, Elisa; Rosato, Antonio; Del Sal, Giannino

    2017-06-01

    The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority of cancers and its activity strongly contributes to tumour initiation and progression. Inactivation of PIN1 function conversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks metastatic spread, thus providing the rationale for a therapeutic strategy based on PIN1 inhibition. Notwithstanding, potent PIN1 inhibitors are still missing from the arsenal of anti-cancer drugs. By a mechanism-based screening, we have identified a novel covalent PIN1 inhibitor, KPT-6566, able to selectively inhibit PIN1 and target it for degradation. We demonstrate that KPT-6566 covalently binds to the catalytic site of PIN1. This interaction results in the release of a quinone-mimicking drug that generates reactive oxygen species and DNA damage, inducing cell death specifically in cancer cells. Accordingly, KPT-6566 treatment impairs PIN1-dependent cancer phenotypes in vitro and growth of lung metastasis in vivo.

  9. Non-Catalytic Participation of the Pin1 Peptidyl-Prolyl Isomerase Domain in Target Binding

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    Brendan Tooke Innes

    2013-02-01

    Full Text Available Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase that has the potential to add an additional level of regulation within protein kinase mediated signaling pathways. Furthermore, there is a mounting body of evidence implicating Pin1 in the emergence of pathological phenotypes in neurodegeneration and cancer through the isomerization of a wide variety of substrates at peptidyl-prolyl bonds where the residue preceding proline is a phosphorylated serine or threonine residue (ie. pS/T-P motifs. A key step in this regulatory process is the interaction of Pin-1 with its substrates. This is a complex process since Pin1 is composed of two domains, the catalytic PPIase domain, and a type IV WW domain, both of which recognize pS/T-P motifs. The observation that the WW domain exhibits considerably higher binding affinity for pS/T-P motifs has led to predictions that the two domains may have distinct roles in mediating the actions of Pin1 on its substrates. To evaluate the participation of its individual domains in target binding, we performed GST pulldowns to monitor interactions between various forms of Pin1 and mitotic phospho-proteins that revealed two classes of Pin-1 interacting proteins, differing in their requirement for residues within the PPIase domain. From these observations, we consider models for Pin1-substrate interactions and the potential functions of the different classes of Pin1 interacting proteins. We also compare sequences that are recognized by Pin1 within its individual interaction partners to investigate the underlying basis for its different types of interactions.

  10. Cyclohexyl ketone inhibitors of Pin1 dock in a trans-diaxial cyclohexane conformation.

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    Guoyan G Xu

    Full Text Available Cyclohexyl ketone substrate analogue inhibitors (Ac-pSer-Ψ[C = OCH]-Pip-tryptamine of Pin1, the cell cycle regulatory peptidyl-prolyl isomerase (PPIase, were designed and synthesized as potential electrophilic acceptors for the Pin1 active site Cys113 nucleophile to test a proposed nucleophilic addition-isomerization mechanism. Because they were weak inhibitors, models of all three stereoisomers were docked into the active site of Pin1. Each isomer consistently minimized to a trans-diaxial cyclohexane conformation. From this, we hypothesize that Pin1 stretches substrates into a trans-pyrrolidine conformation to lower the barrier to isomerization. Our reduced amide inhibitor of Pin1 adopted a similar trans-pyrrolidine conformation in the crystal structure. The molecular model of 1, which mimics the l-Ser-l-Pro stereochemistry, in the Pin1 active site showed a distance of 4.4 Å, and an angle of 31° between Cys113-S and the ketone carbon. The computational models suggest that the mechanism of Pin1 PPIase is not likely to proceed through nucleophilic addition.

  11. The role of PIN1 on odontogenic and adipogenic differentiation in human dental pulp stem cells.

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    Lee, Young-Man; Shin, Seung-Yun; Jue, Seong-Suk; Kwon, Il-Keun; Cho, Eun-Hee; Cho, Eui-Sic; Park, Sang-Hyuk; Kim, Eun-Cheol

    2014-03-15

    Recently, the involvement of PIN1, a peptidyl-prolyl cis/trans isomerase, has been reported in age-related bone homeostasis and adipogenesis. However, the role of PIN1 during odontogenic and adipogenic differentiation remains to be fully understood, particularly regarding human dental pulp stem cells (HDPSCs). Thus, in the present study, we have investigated the role of PIN1 in odontogenic and adipogenic differentiation of HDPSCs and signaling pathways possibly involved. PIN1 mRNA and protein level were upregulated in a time-dependent manner during adipogenic differentiation, increasing until 1 day of odontogenic induction and then steadily declined during odontogenic differentiation. Treatment of a known PIN1 inhibitor, juglone, significantly increased odontogenic differentiation as confirmed by alkaline phosphatase (ALP) activity, calcium deposition, and mRNAs induction of odontogenic markers [ALP, osteopontin (OPN), osteocalcin (OCN), dentin sialophosphoprotein (DSPP), and dentin matrix protein 1 (DMP-1)]. On the contrary, adipogenic differentiation was dramatically reduced upon juglone treatment, with concomitant downregulation of lipid droplet accumulation and adipogenic marker genes [peroxisome proliferation-activated receptor gamma (PPARγ), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (AP2)]. In contrast to PIN1 inhibition, the overexpression of PIN1 via adenoviral infection (Ad-PIN1) in HDPSCs inhibited odontogenic differentiation but increased adipogenic differentiation, in which stem cell property markers such as stage-specific embryonic antigen-4 (SSEA-4) and STRO-1 were upregulated during odontogenic differentiation but downregulated in adiopogenic differentiation. Consistently, juglone-mediated inhibition of PIN1 augmented the osteogenic medium (OM)-induced activation of bone morphogenetic protein (BMP), Wnt/β-catenin, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF

  12. The Role of PIN1 on Odontogenic and Adipogenic Differentiation in Human Dental Pulp Stem Cells

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    Lee, Young-Man; Shin, Seung-Yun; Jue, Seong-Suk; Kwon, Il-Keun; Cho, Eun-Hee; Cho, Eui-Sic

    2014-01-01

    Recently, the involvement of PIN1, a peptidyl-prolyl cis/trans isomerase, has been reported in age-related bone homeostasis and adipogenesis. However, the role of PIN1 during odontogenic and adipogenic differentiation remains to be fully understood, particularly regarding human dental pulp stem cells (HDPSCs). Thus, in the present study, we have investigated the role of PIN1 in odontogenic and adipogenic differentiation of HDPSCs and signaling pathways possibly involved. PIN1 mRNA and protein level were upregulated in a time-dependent manner during adipogenic differentiation, increasing until 1 day of odontogenic induction and then steadily declined during odontogenic differentiation. Treatment of a known PIN1 inhibitor, juglone, significantly increased odontogenic differentiation as confirmed by alkaline phosphatase (ALP) activity, calcium deposition, and mRNAs induction of odontogenic markers [ALP, osteopontin (OPN), osteocalcin (OCN), dentin sialophosphoprotein (DSPP), and dentin matrix protein 1 (DMP-1)]. On the contrary, adipogenic differentiation was dramatically reduced upon juglone treatment, with concomitant downregulation of lipid droplet accumulation and adipogenic marker genes [peroxisome proliferation-activated receptor gamma (PPARγ), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (AP2)]. In contrast to PIN1 inhibition, the overexpression of PIN1 via adenoviral infection (Ad-PIN1) in HDPSCs inhibited odontogenic differentiation but increased adipogenic differentiation, in which stem cell property markers such as stage-specific embryonic antigen-4 (SSEA-4) and STRO-1 were upregulated during odontogenic differentiation but downregulated in adiopogenic differentiation. Consistently, juglone-mediated inhibition of PIN1 augmented the osteogenic medium (OM)-induced activation of bone morphogenetic protein (BMP), Wnt/β-catenin, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF

  13. PATELLINS are regulators of auxin-mediated PIN1 relocation and plant development in Arabidopsis thaliana.

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    Tejos, Ricardo; Rodriguez-Furlán, Cecilia; Adamowski, Maciej; Sauer, Michael; Norambuena, Lorena; Friml, Jiří

    2018-01-29

    Coordinated cell polarization in developing tissues is a recurrent theme in multicellular organisms. In plants, a directional distribution of the plant hormone auxin is at the core of many developmental programs. A feedback regulation of auxin on the polarized localization of PIN auxin transporters in individual cells has been proposed as a self-organizing mechanism for coordinated tissue polarization, but the molecular mechanisms linking auxin signalling to PIN-dependent auxin transport remain unknown. We used a microarray-based approach to find regulators of the auxin-induced PIN relocation in Arabidopsis thaliana root, and identified a subset of a family of phosphatidylinositol transfer proteins (PITPs), the PATELLINs (PATLs). Here, we show that PATLs are expressed in partially overlapping cell types in different tissues going through mitosis or initiating differentiation programs. PATLs are plasma membrane-associated proteins accumulated in Arabidopsis embryos, primary roots, lateral root primordia and developing stomata. Higher order patl mutants display reduced PIN1 repolarization in response to auxin, shorter root apical meristem, and drastic defects in embryo and seedling development. This suggests that PATLs play a redundant and crucial role in polarity and patterning in Arabidopsis . © 2018. Published by The Company of Biologists Ltd.

  14. Sorting Motifs Involved in the Trafficking and Localization of the PIN1 Auxin Efflux Carrier.

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    Sancho-Andrés, Gloria; Soriano-Ortega, Esther; Gao, Caiji; Bernabé-Orts, Joan Miquel; Narasimhan, Madhumitha; Müller, Anna Ophelia; Tejos, Ricardo; Jiang, Liwen; Friml, Jiří; Aniento, Fernando; Marcote, María Jesús

    2016-07-01

    In contrast with the wealth of recent reports about the function of μ-adaptins and clathrin adaptor protein (AP) complexes, there is very little information about the motifs that determine the sorting of membrane proteins within clathrin-coated vesicles in plants. Here, we investigated putative sorting signals in the large cytosolic loop of the Arabidopsis (Arabidopsis thaliana) PIN-FORMED1 (PIN1) auxin transporter, which are involved in binding μ-adaptins and thus in PIN1 trafficking and localization. We found that Phe-165 and Tyr-280, Tyr-328, and Tyr-394 are involved in the binding of different μ-adaptins in vitro. However, only Phe-165, which binds μA(μ2)- and μD(μ3)-adaptin, was found to be essential for PIN1 trafficking and localization in vivo. The PIN1:GFP-F165A mutant showed reduced endocytosis but also localized to intracellular structures containing several layers of membranes and endoplasmic reticulum (ER) markers, suggesting that they correspond to ER or ER-derived membranes. While PIN1:GFP localized normally in a μA (μ2)-adaptin mutant, it accumulated in big intracellular structures containing LysoTracker in a μD (μ3)-adaptin mutant, consistent with previous results obtained with mutants of other subunits of the AP-3 complex. Our data suggest that Phe-165, through the binding of μA (μ2)- and μD (μ3)-adaptin, is important for PIN1 endocytosis and for PIN1 trafficking along the secretory pathway, respectively. © 2016 American Society of Plant Biologists. All Rights Reserved.

  15. Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity.

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    Helander, Sara; Montecchio, Meri; Pilstål, Robert; Su, Yulong; Kuruvilla, Jacob; Elvén, Malin; Ziauddin, Javed M E; Anandapadamanaban, Madhanagopal; Cristobal, Susana; Lundström, Patrik; Sears, Rosalie C; Wallner, Björn; Sunnerhagen, Maria

    2015-12-01

    Hierarchic phosphorylation and concomitant Pin1-mediated proline isomerization of the oncoprotein c-Myc controls its cellular stability and activity. However, the molecular basis for Pin1 recognition and catalysis of c-Myc and other multisite, disordered substrates in cell regulation and disease is unclear. By nuclear magnetic resonance, surface plasmon resonance, and molecular modeling, we show that Pin1 subdomains jointly pre-anchor unphosphorylated c-Myc1-88 in the Pin1 interdomain cleft in a disordered, or "fuzzy", complex at the herein named Myc Box 0 (MB0) conserved region N-terminal to the highly conserved Myc Box I (MBI). Ser62 phosphorylation in MBI intensifies previously transient MBI-Pin1 interactions in c-Myc1-88 binding, and increasingly engages Pin1PPIase and its catalytic region with maintained MB0 interactions. In cellular assays, MB0 mutated c-Myc shows decreased Pin1 interaction, increased protein half-life, but lowered rates of Myc-driven transcription and cell proliferation. We propose that dynamic Pin1 recognition of MB0 contributes to the regulation of c-Myc activity in cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A multifunctional ELISA to measure oxidised proteins: oxPin1 in Alzheimer's brain as an example

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    Herbert, Megan K.; Verbeek, Marcel M.; Küsters, Benno; Kuiperij, H. Bea

    2015-01-01

    Background Oxidative stress occurs in many neurodegenerative diseases including Alzheimer's disease (AD) and evidence suggests that specific proteins are oxidised in individual diseases. Thus measures of oxidised proteins such as in human biological samples could represent potential disease-specific biomarkers. Protein carbonylation is considered to be an important marker of oxidative stress. In AD in particular, the peptidyl prolyl isomerase, Pin1, has been shown to be sensitive to metal-catalysed oxidation with the addition of carbonyl side-chains. Methods Based on this protein modification we developed a novel, enzyme-linked sandwich immunoassay for the quantification of oxidised Pin1 (oxPin1) in human brain tissue samples. Results We successfully developed an ELISA for the measurement of oxidised Pin1 in biological samples and measured oxPin1 in hippocampal tissue extracts from controls and AD, which showed an increased ratio of oxPin1 to total Pin1 in patients with early AD pathology compared with controls. Conclusions We show that oxidised proteins, in this case oxPin1, can be measured using the developed ELISA. In addition, our results support the presence of increased oxidative stress in the early stages of AD pathology and show that the oxPin1/Pin1 ratio could indicate early stage pathology. This warrants further investigation in other biological fluids. General significance Importantly, further development and adaption of the assay design will enable multi-functional use for the quantification of oxidised proteins in tissues and biological fluids that may be used in investigating the role of oxidised proteins in a range of neurodegenerative diseases, particularly in which disease-specific protein oxidation has been implicated. PMID:26673529

  17. Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons

    Czech Academy of Sciences Publication Activity Database

    Balaštík, Martin; Zhou, X.Z.; Alberich-Jorda, Meritxell; Weissová, Romana; Žiak, Jakub; Pazyra-Murphy, M.F.; Cosker, K.E.; Machoňová, Olga; Kozmiková, Iryna; Chen, CH.; Pastorino, L.; Asara, J.M.; Cole, A.; Sutherland, C.; Segal, R. A.; Lu, K.P.

    2015-01-01

    Roč. 13, č. 4 (2015), s. 812-828 ISSN 2211-1247 R&D Projects: GA MŠk(CZ) LK11213; GA MŠk LK21307; GA ČR GA15-03796S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : Pin1 * axon guidance * Semaphorin 3A Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.870, year: 2015

  18. Brown Algae Polyphenol, a Prolyl Isomerase Pin1 Inhibitor, Prevents Obesity by Inhibiting the Differentiation of Stem Cells into Adipocytes.

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    Suzuki, Atsuko; Saeki, Toshiyuki; Ikuji, Hiroko; Uchida, Chiyoko; Uchida, Takafumi

    2016-01-01

    While screening for an inhibitor of the peptidyl prolyl cis/trans isomerase, Pin1, we came across a brown algae polyphenol that blocks the differentiation of fibroblasts into adipocytes. However, its effectiveness on the accumulation of fat in the body has never been studied. Oral administration of brown algae polyphenol to mice fed with a high fat diet, suppressed the increase in fat volume to a level observed in mice fed with a normal diet. We speculate that Pin1 might be required for the differentiation of stem cell to adipocytes. We established wild type (WT) and Pin1-/- (Pin1-KO) adipose-derived mesenchymal stem cell (ASC) lines and found that WT ASCs differentiate to adipocytes but Pin1-KO ASCs do not. Oral administration of brown algae polyphenol, a Pin1 inhibitor, reduced fat buildup in mice. We showed that Pin1 is required for the differentiation of stem cells into adipocytes. We propose that oral intake of brown algae polyphenol is useful for the treatment of obesity.

  19. Brown Algae Polyphenol, a Prolyl Isomerase Pin1 Inhibitor, Prevents Obesity by Inhibiting the Differentiation of Stem Cells into Adipocytes.

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    Atsuko Suzuki

    Full Text Available While screening for an inhibitor of the peptidyl prolyl cis/trans isomerase, Pin1, we came across a brown algae polyphenol that blocks the differentiation of fibroblasts into adipocytes. However, its effectiveness on the accumulation of fat in the body has never been studied.Oral administration of brown algae polyphenol to mice fed with a high fat diet, suppressed the increase in fat volume to a level observed in mice fed with a normal diet. We speculate that Pin1 might be required for the differentiation of stem cell to adipocytes. We established wild type (WT and Pin1-/- (Pin1-KO adipose-derived mesenchymal stem cell (ASC lines and found that WT ASCs differentiate to adipocytes but Pin1-KO ASCs do not.Oral administration of brown algae polyphenol, a Pin1 inhibitor, reduced fat buildup in mice. We showed that Pin1 is required for the differentiation of stem cells into adipocytes. We propose that oral intake of brown algae polyphenol is useful for the treatment of obesity.

  20. Mutants of Agrobacterium tumefaciens with elevated vir gene expression

    International Nuclear Information System (INIS)

    Pazour, G.J.; Ta, C.N.; Das, A.

    1991-01-01

    Expression of Agrobacterium tumefaciens virulence (vir) genes requires virA, virG, and a plant-derived inducing compound such as acetosyringone. To identify the critical functional domains of virA and virG, a mutational approach was used. Agrobacterium A136 harboring plasmid pGP159, which contains virA, virG, and a reporter virB:lacZ gene fusion, was mutagenized with UV light or nitrosoguanidine. Survivors that formed blue colonies on a plate containing 5-bromo-4-chloro-3-indolyl beta-D-galactoside were isolated and analyzed. Quantification of beta-galactosidase activity in liquid assays identified nine mutant strains. By plasmid reconstruction and other procedures, all mutations mapped to the virA locus. These mutations caused an 11- to 560-fold increase in the vegetative level of virB:lacZ reporter gene expression. DNA sequence analysis showed that the mutations are located in four regions of VirA: transmembrane domain one, the active site, a glycine-rich region with homology to ATP-binding sites, and a region at the C terminus that has homology to the N terminus of VirG

  1. Solution structure of the single-domain prolyl cis/trans isomerase PIN1At from Arabidopsis thaliana.

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    Landrieu, Isabelle; Wieruszeski, Jean-Michel; Wintjens, René; Inzé, Dirk; Lippens, Guy

    2002-07-05

    The 119-amino acid residue prolyl cis/trans isomerase from Arabidopsis thaliana (PIN1At) is similar to the catalytic domain of the human hPIN1. However, PIN1At lacks the N-terminal WW domain that appears to be essential for the hPIN1 function. Here, the solution structure of PIN1At was determined by three-dimensional nuclear magnetic resonance spectroscopy. The PIN1At fold could be superimposed on that of the catalytic domain of hPIN1 and had a 19 residue flexible loop located between strand beta1 and helix alpha1. The dynamical features of this beta1/alpha1-loop, which are characteristic for a region involved in protein-protein interactions, led to exchange broadening in the NMR spectra. When sodium sulfate salt was added to the protein sample, the beta1/alpha1 loop was stabilized and, hence, a complete backbone resonance assignment was obtained. Previously, with a phospho-Cdc25 peptide as substrate, PIN1At had been shown to catalyze the phosphoserine/phosphothreonine prolyl cis/trans isomerization specifically. To map the catalytic site of PIN1At, the phospho-Cdc25 peptide or sodium sulfate salt was added in excess to the protein and chemical shift changes in the backbone amide protons were monitored in the (1)H(N)-(15)N heteronuclear single quantum coherence spectrum. The peptide caused perturbations in the loops between helix alpha4 and strand beta3, between strands beta3 and beta4, in the alpha3 helix, and in the beta1/alpha1 loop. The amide groups of the residues Arg21 and Arg22 showed large chemical shift perturbations upon phospho-Cdc25 peptide or sulfate addition. We conclude that this basic cluster formed by Arg21 and Arg22, both located in the beta1/alpha1 loop, is homologous to that found in the hPIN1 crystal structure (Arg68 and Arg69), which also is involved in sulfate ion binding. We showed that the sulfate group competed for the interaction between PIN1At and the phospho-Cdc25 peptide. In the absence of the WW domain, three hydrophobic residues (Ile

  2. Proline isomerase Pin1 represses terminal differentiation and myocyte enhancer factor 2C function in skeletal muscle cells.

    Science.gov (United States)

    Magli, Alessandro; Angelelli, Cecilia; Ganassi, Massimo; Baruffaldi, Fiorenza; Matafora, Vittoria; Battini, Renata; Bachi, Angela; Messina, Graziella; Rustighi, Alessandra; Del Sal, Giannino; Ferrari, Stefano; Molinari, Susanna

    2010-11-05

    Reversible proline-directed phosphorylation at Ser/Thr-Pro motifs has an essential role in myogenesis, a multistep process strictly regulated by several signaling pathways that impinge on two families of myogenic effectors, the basic helix-loop-helix myogenic transcription factors and the MEF2 (myocyte enhancer factor 2) proteins. The question of how these signals are deciphered by the myogenic effectors remains largely unaddressed. In this study, we show that the peptidyl-prolyl isomerase Pin1, which catalyzes the isomerization of phosphorylated Ser/Thr-Pro peptide bonds to induce conformational changes of its target proteins, acts as an inhibitor of muscle differentiation because its knockdown in myoblasts promotes myotube formation. With the aim of clarifying the mechanism of Pin1 function in skeletal myogenesis, we investigated whether MEF2C, a critical regulator of the myogenic program that is the end point of several signaling pathways, might serve as a/the target for the inhibitory effects of Pin1 on muscle differentiation. We show that Pin1 interacts selectively with phosphorylated MEF2C in skeletal muscle cells, both in vitro and in vivo. The interaction with Pin1 requires two novel critical phospho-Ser/Thr-Pro motifs in MEF2C, Ser(98) and Ser(110), which are phosphorylated in vivo. Overexpression of Pin1 decreases MEF2C stability and activity and its ability to cooperate with MyoD to activate myogenic conversion. Collectively, these findings reveal a novel role for Pin1 as a regulator of muscle terminal differentiation and suggest that Pin1-mediated repression of MEF2C function could contribute to this function.

  3. Modeling conformational ensembles of slow functional motions in Pin1-WW.

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    Faruck Morcos

    2010-12-01

    Full Text Available Protein-protein interactions are often mediated by flexible loops that experience conformational dynamics on the microsecond to millisecond time scales. NMR relaxation studies can map these dynamics. However, defining the network of inter-converting conformers that underlie the relaxation data remains generally challenging. Here, we combine NMR relaxation experiments with simulation to visualize networks of inter-converting conformers. We demonstrate our approach with the apo Pin1-WW domain, for which NMR has revealed conformational dynamics of a flexible loop in the millisecond range. We sample and cluster the free energy landscape using Markov State Models (MSM with major and minor exchange states with high correlation with the NMR relaxation data and low NOE violations. These MSM are hierarchical ensembles of slowly interconverting, metastable macrostates and rapidly interconverting microstates. We found a low population state that consists primarily of holo-like conformations and is a "hub" visited by most pathways between macrostates. These results suggest that conformational equilibria between holo-like and alternative conformers pre-exist in the intrinsic dynamics of apo Pin1-WW. Analysis using MutInf, a mutual information method for quantifying correlated motions, reveals that WW dynamics not only play a role in substrate recognition, but also may help couple the substrate binding site on the WW domain to the one on the catalytic domain. Our work represents an important step towards building networks of inter-converting conformational states and is generally applicable.

  4. DLX5, FGF8 and the Pin1 isomerase control ΔNp63α protein stability during limb development: a regulatory loop at the basis of the SHFM and EEC congenital malformations.

    Science.gov (United States)

    Restelli, Michela; Lopardo, Teresa; Lo Iacono, Nadia; Garaffo, Giulia; Conte, Daniele; Rustighi, Alessandra; Napoli, Marco; Del Sal, Giannino; Perez-Morga, David; Costanzo, Antonio; Merlo, Giorgio Roberto; Guerrini, Luisa

    2014-07-15

    Ectrodactyly, or Split-Hand/Foot Malformation (SHFM), is a congenital condition characterized by the loss of central rays of hands and feet. The p63 and the DLX5;DLX6 transcription factors, expressed in the embryonic limb buds and ectoderm, are disease genes for these conditions. Mutations of p63 also cause the ectodermal dysplasia-ectrodactyly-cleft lip/palate (EEC) syndrome, comprising SHFM. Ectrodactyly is linked to defects of the apical ectodermal ridge (AER) of the developing limb buds. FGF8 is the key signaling molecule in this process, able to direct proximo-distal growth and patterning of the skeletal primordial of the limbs. In the limb buds of both p63 and Dlx5;Dlx6 murine models of SHFM, the AER is poorly stratified and FGF8 expression is severely reduced. We show here that the FGF8 locus is a downstream target of DLX5 and that FGF8 counteracts Pin1-ΔNp63α interaction. In vivo, lack of Pin1 leads to accumulation of the p63 protein in the embryonic limbs and ectoderm. We show also that ΔNp63α protein stability is negatively regulated by the interaction with the prolyl-isomerase Pin1, via proteasome-mediated degradation; p63 mutant proteins associated with SHFM or EEC syndromes are resistant to Pin1 action. Thus, DLX5, p63, Pin1 and FGF8 participate to the same time- and location-restricted regulatory loop essential for AER stratification, hence for normal patterning and skeletal morphogenesis of the limb buds. These results shed new light on the molecular mechanisms at the basis of the SHFM and EEC limb malformations. © The Author 2014. Published by Oxford University Press.

  5. Elevated TATA-binding protein expression drives vascular endothelial growth factor expression in colon cancer.

    Science.gov (United States)

    Johnson, Sandra A S; Lin, Justin J; Walkey, Christopher J; Leathers, Michael P; Coarfa, Cristian; Johnson, Deborah L

    2017-07-25

    The TATA-binding protein (TBP) plays a central role in eukaryotic gene transcription. Given its key function in transcription initiation, TBP was initially thought to be an invariant protein. However, studies showed that TBP expression is upregulated by oncogenic signaling pathways. Furthermore, depending on the cell type, small increases in cellular TBP amounts can induce changes in cellular growth properties towards a transformed phenotype. Here we sought to identify the specific TBP-regulated gene targets that drive its ability to induce tumorigenesis. Using microarray analysis, our results reveal that increases in cellular TBP concentrations produce selective alterations in gene expression that include an enrichment for genes involved in angiogenesis. Accordingly, we find that TBP levels modulate VEGFA expression, the master regulator of angiogenesis. Increases in cellular TBP amounts induce VEGFA expression and secretion to enhance cell migration and tumor vascularization. TBP mediates changes in VEGFA transcription requiring its recruitment at a hypoxia-insensitive proximal TSS, revealing a mechanism for VEGF regulation under non-stress conditions. The results are clinically relevant as TBP expression is significantly increased in both colon adenocarcinomas as well as adenomas relative to normal tissue. Furthermore, TBP expression is positively correlated with VEGFA expression. Collectively, these studies support the idea that increases in TBP expression contribute to enhanced VEGFA transcription early in colorectal cancer development to drive tumorigenesis.

  6. Peptidyl prolyl isomerase Pin1-inhibitory activity of D-glutamic and D-aspartic acid derivatives bearing a cyclic aliphatic amine moiety.

    Science.gov (United States)

    Nakagawa, Hidehiko; Seike, Suguru; Sugimoto, Masatoshi; Ieda, Naoya; Kawaguchi, Mitsuyasu; Suzuki, Takayoshi; Miyata, Naoki

    2015-12-01

    Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic aliphatic amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Elevated COX2 expression and PGE2 production by downregulation of RXRα in senescent macrophages

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    Chen, Huimin, E-mail: huiminchen.jq@gmail.com [Department of Geratology, Liaoning Jinqiu Hospital, Shenyang 110015 (China); Ma, Feng [Institute of Immunology, Zhejiang University of Medicine, Hangzhou 310058 (China); Hu, Xiaona; Jin, Ting; Xiong, Chuhui [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China); Teng, Xiaochun, E-mail: tengxiaochun@126.com [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China)

    2013-10-11

    Highlights: •Downregulation of RXRα in senescent macrophage. •RXRα suppresses NF-κB activity and COX2 expression. •Increased PGE2 production due to downregulation of RXRα. -- Abstract: Increased systemic level of inflammatory cytokines leads to numerous age-related diseases. In senescent macrophages, elevated prostaglandin E2 (PGE2) production contributes to the suppression of T cell function with aging, which increases the susceptibility to infections. However, the regulation of these inflammatory cytokines and PGE2 with aging still remains unclear. We have verified that cyclooxygenase (COX)-2 expression and PGE2 production are higher in LPS-stimulated macrophages from old mice than that from young mice. Downregulation of RXRα, a nuclear receptor that can suppress NF-κB activity, mediates the elevation of COX2 expression and PGE2 production in senescent macrophages. We also have found less induction of ABCA1 and ABCG1 by RXRα agonist in senescent macrophages, which partially accounts for high risk of atherosclerosis in aged population. Systemic treatment with RXRα antagonist HX531 in young mice increases COX2, TNF-α, and IL-6 expression in splenocytes. Our study not only has outlined a mechanism of elevated NF-κB activity and PGE2 production in senescent macrophages, but also provides RXRα as a potential therapeutic target for treating the age-related diseases.

  8. Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer

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    Liu, Chenchen; Yue, Ben; Yuan, Chenwei; Zhao, Senlin; Fang, Changyi; Yu, Yang; Yan, Dongwang, E-mail: yandw70@163.com

    2015-12-04

    The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

  9. Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer

    International Nuclear Information System (INIS)

    Liu, Chenchen; Yue, Ben; Yuan, Chenwei; Zhao, Senlin; Fang, Changyi; Yu, Yang; Yan, Dongwang

    2015-01-01

    The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

  10. Evidence for small-molecule-mediated loop stabilization in the structure of the isolated Pin1 WW domain.

    Science.gov (United States)

    Mortenson, David E; Kreitler, Dale F; Yun, Hyun Gi; Gellman, Samuel H; Forest, Katrina T

    2013-12-01

    The human Pin1 WW domain is a small autonomously folding protein that has been useful as a model system for biophysical studies of β-sheet folding. This domain has resisted previous attempts at crystallization for X-ray diffraction studies, perhaps because of intrinsic conformational flexibility that interferes with the formation of a crystal lattice. Here, the crystal structure of the human Pin1 WW domain has been obtained via racemic crystallization in the presence of small-molecule additives. Both enantiomers of a 36-residue variant of the Pin1 WW domain were synthesized chemically, and the L- and D-polypeptides were combined to afford diffracting crystals. The structural data revealed packing interactions of small carboxylic acids, either achiral citrate or a D,L mixture of malic acid, with a mobile loop region of the WW-domain fold. These interactions with solution additives may explain our success in crystallization of this protein racemate. Molecular-dynamics simulations starting from the structure of the Pin1 WW domain suggest that the crystal structure closely resembles the conformation of this domain in solution. The structural data presented here should provide a basis for further studies of this important model system.

  11. Seawater acidification and elevated temperature affect gene expression patterns of the pearl oyster Pinctada fucata.

    Directory of Open Access Journals (Sweden)

    Wenguang Liu

    Full Text Available Oceanic uptake of anthropogenic carbon dioxide results in decrease in seawater pH and increase in temperature. In this study, we demonstrated the synergistic effects of elevated seawater temperature and declined seawater pH on gene expression patterns of aspein, calmodulin, nacrein, she-7-F10 and hsp70 in the pearl oyster Pinctada fucata. Under 'business-as-usual' scenarios, four treatments were examined: (1 ambient pH (8.10 and ambient temperature (27 °C (control condition, (2 ambient pH and elevated temperature (+3 °C, (3 declined pH (7.70 and ambient temperature, (4 declined pH and elevated temperature. The results showed that under warming and acidic seawater conditions, expression of aspein and calmodulin showed no significant differences among different time point in condition 8.10 T. But the levels of aspein and calmodulin in conditions 8.10 T+3, 7.70 T and 7.70 T+3, and levels of nacrein, she-7-F10 in all the four treatments changed significantly. Low pH and pH × temperature interaction influenced the expression of aspein and calmodulin significantly after hours 48 and 96. Significant effects of low pH and pH × temperature interaction on the expression of nacrein were observed at hour 96. The expression level of she-7-F10 was affected significantly by pH after hours 48 and 96. The expression of hsp70 was significantly affected by temperature, pH, temperature × pH interaction at hour 6, and by temperature × pH interaction at hour 24. This study suggested that declined pH and pH × temperature interaction induced down regulation of calcification related genes, and the interaction between declined seawater pH and elevated temperature caused up regulation of hsp70 in P. facata. These results demonstrate that the declined seawater pH and elevated temperature will impact the physiological process, and potentially the adaptability of P. fucata to future warming and acidified ocean.

  12. Inflammatory gene expression signatures in idiopathic intracranial hypertension: possible implications in microgravity-induced ICP elevation.

    Science.gov (United States)

    Zanello, Susana B; Tadigotla, Vasisht; Hurley, James; Skog, Johan; Stevens, Brian; Calvillo, Eusebia; Bershad, Eric

    2018-01-01

    The visual impairment and intracranial pressure (VIIP) syndrome is a neuro-ophthalmologic condition described in astronauts returning from long duration space missions. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is characterized by a chronic elevation of intracranial pressure (ICP) in the absence of an intracranial mass lesion. Because VIIP and IIH share some neurologic and ophthalmologic manifestations, the latter might be used as a model to study some of the processes underlying VIIP. This work constitutes a preliminary investigation of the molecular pathways associated with the elevation of ICP in IIH. Gene expression signatures were obtained from exosomes collected from CSF and plasma in patients with possible signs of IIH. The gene expression targets focused on inflammatory genes and miRNAs. The results suggest that inflammatory cytokine-driven processes and immune cell migration are activated when ICP is elevated in IIH patients, either as a cause or effect of the ICP increase. Several miRNAs appear to be involved in this response, among which miR-9 and miR-16 are upregulated in CSF and plasma of higher ICP subjects. This study provides evidence in support of neurophysiological alterations and neuro-immunomodulation in this condition. If similar changes are seen in astronauts manifesting with the VIIP syndrome, an underlying pathophysiological basis may be discovered.

  13. Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells.

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    Yun-Ju Chen

    Full Text Available The sensitivity of non-small cell lung cancer (NSCLC patients to EGFR tyrosine kinase inhibitors (TKIs is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2, which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR.

  14. Elevated expression of CD93 promotes angiogenesis and tumor growth in nasopharyngeal carcinoma

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    Bao, Lili [Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province (China); Tang, Mingming [Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu (China); Zhang, Qicheng; You, Bo; Shan, Ying; Shi, Si; Li, Li [Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province (China); Hu, Songqun, E-mail: hsq@ntu.edu.cn [Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province (China); You, Yiwen, E-mail: youyiwen_nantong@163.com [Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province (China)

    2016-08-05

    CD93, also known as the complement component C1q receptor (C1qRp), has been reported to promote the progression of some cancer types. However, the expression and physiological significance of CD93 in nasopharyngeal carcinoma (NPC) remain largely elusive. In this study, we first examined the expression of CD93 in NPC and experimentally manipulated its expression. We observed that vascular CD93 expression is elevated in NPC and is correlated with T classification, N classification, distant metastasis, clinical stage and poor prognosis (all P < 0.05). In addition, overexpression of CD93 promoted angiogenesis in vitro. What’s more, we found that CD93 was highly expressed in NPC tissues and cells, and the regulation of CD93 on cell proliferation was determined by cell counting kit (CCK)-8 assay and cell cycle analyses. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as CD93 to improve NPC treatment. -- Highlights: •This is the first research about the relationship between CD93 and nasopharyngeal carcinoma. •We explored the prognostic significance of vascular CD93 expression in nasopharyngeal carcinoma. •We researched on angiogenesis and cell proliferation of nasopharyngeal carcinoma and how CD93 affected them.

  15. Subtype specific elevated expression of hyaluronidase-1 (HYAL-1 in epithelial ovarian cancer.

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    Paule Héléna Yoffou

    Full Text Available BACKGROUND: Epithelial ovarian cancer (EOC is morphologically heterogeneous being classified as serous, endometrioid, clear cell, or mucinous. Molecular genetic analysis has suggested a role for tumor suppressor genes located at chromosome 3p in serous EOC pathogenesis. Our objective was to evaluate the expression of HYAL1, located at chromosome 3p21.3, in these EOC subtypes, and to investigate its correlation with the expression of steroid hormone receptors. METHODOLOGY/PRINCIPAL FINDINGS: We determined the mRNA expression of HYAL1, estrogen receptor (ER-α, ERβ and progesterone receptor (PR in EOC tumor samples and cell lines using quantitative RT-PCR. We also examined the expression of these genes in a publicly available microarray dataset. HYAL-1 enzyme activity was measured in EOC cell lines and in plasma samples from patients. We found that HYAL1 mRNA expression was elevated in clear cell and mucinous EOC tissue samples, but not in serous and endometrioid samples, normal ovaries or benign tumors. Similar results were obtained by two different techniques and with tissue sample cohorts from two independent institutions. Concordantly, HYAL1 mRNA levels and enzymatic activity were elevated only in EOC cell lines derived from clear cell and mucinous subtypes. We also showed that HYAL1 mRNA was inversely correlated to that of ERα specifically in clear cell and mucinous EOCs. Additionally, ectopic expression of ERα in a clear cell EOC cell line (ER- and PR-negative induced 50% reduction of HYAL1 mRNA expression, supporting a role of ERα in HYAL1 gene regulation. Significantly, HYAL-1 activity was also high in the plasma of patients with these EOC subtypes. CONCLUSIONS/SIGNIFICANCE: This is the first report showing high HYAL-1 levels in EOC and demonstrating HYAL1 gene repression by ERα. Our results identify Hyaluronidase-1 as a potential target/biomarker for clear cell and mucinous EOCs and especially in tumors with low ERα levels.

  16. Response of marine bacterioplankton pH homeostasis gene expression to elevated CO2

    Science.gov (United States)

    Bunse, Carina; Lundin, Daniel; Karlsson, Christofer M. G.; Akram, Neelam; Vila-Costa, Maria; Palovaara, Joakim; Svensson, Lovisa; Holmfeldt, Karin; González, José M.; Calvo, Eva; Pelejero, Carles; Marrasé, Cèlia; Dopson, Mark; Gasol, Josep M.; Pinhassi, Jarone

    2016-05-01

    Human-induced ocean acidification impacts marine life. Marine bacteria are major drivers of biogeochemical nutrient cycles and energy fluxes; hence, understanding their performance under projected climate change scenarios is crucial for assessing ecosystem functioning. Whereas genetic and physiological responses of phytoplankton to ocean acidification are being disentangled, corresponding functional responses of bacterioplankton to pH reduction from elevated CO2 are essentially unknown. Here we show, from metatranscriptome analyses of a phytoplankton bloom mesocosm experiment, that marine bacteria responded to lowered pH by enhancing the expression of genes encoding proton pumps, such as respiration complexes, proteorhodopsin and membrane transporters. Moreover, taxonomic transcript analysis showed that distinct bacterial groups expressed different pH homeostasis genes in response to elevated CO2. These responses were substantial for numerous pH homeostasis genes under low-chlorophyll conditions (chlorophyll a 20 μg l-1) were low. Given that proton expulsion through pH homeostasis mechanisms is energetically costly, these findings suggest that bacterioplankton adaptation to ocean acidification could have long-term effects on the economy of ocean ecosystems.

  17. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells.

    Science.gov (United States)

    Ramsuran, Veron; Naranbhai, Vivek; Horowitz, Amir; Qi, Ying; Martin, Maureen P; Yuki, Yuko; Gao, Xiaojiang; Walker-Sperling, Victoria; Del Prete, Gregory Q; Schneider, Douglas K; Lifson, Jeffrey D; Fellay, Jacques; Deeks, Steven G; Martin, Jeffrey N; Goedert, James J; Wolinsky, Steven M; Michael, Nelson L; Kirk, Gregory D; Buchbinder, Susan; Haas, David; Ndung'u, Thumbi; Goulder, Philip; Parham, Peter; Walker, Bruce D; Carlson, Jonathan M; Carrington, Mary

    2018-01-05

    The highly polymorphic human leukocyte antigen ( HLA ) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease. Copyright © 2017, American Association for the Advancement of Science.

  18. Elevated expression of squamous cell carcinoma antigen (SCCA is associated with human breast carcinoma.

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    Joseph M Catanzaro

    2011-04-01

    Full Text Available Squamous cell carcinoma antigen (SCCA belongs to the serine protease inhibitor (Serpin family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360 and normal breast epithelium (n = 124. SCCA expression was scored on a tiered scale (0-3 independently by two evaluators blind to the patient's clinical status. SCCA expression was observed in Grade I (0.3%, Grade II (2.5%, and Grade III (9.4% breast cancers (p<0.0001. Comparing tissues categorized into the three non-metastatic TNM stages, I-III, SCCA positivity was seen in 2.4% of Stage I cancers, 3.1% of Stage II cancers, and 8.6% of Stage III breast cancers (p = 0.0005. No positive staining was observed in normal/non-neoplastic breast tissue (0 out of 124. SCCA expression also correlated to estrogen receptor/progesterone receptor (ER/PR double-negative tumors (p = 0.0009. Compared to SCCA-negative patients, SCCA-positive patients had both a worse overall survival and recurrence-free survival (p<0.0001 and p<0.0001, respectively. This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma, and suggests the necessity to further explore the role of SCCA in breast cancer development and treatment.

  19. Andrographolide reversed 5-FU resistance in human colorectal cancer by elevating BAX expression.

    Science.gov (United States)

    Wang, Weicheng; Guo, Wenjie; Li, Lele; Fu, Zan; Liu, Wen; Gao, Jian; Shu, Yongqian; Xu, Qiang; Sun, Yang; Gu, Yanhong

    2016-12-01

    5-FU is the first line therapy for colorectal cancer, however, treatment effect is often hampered by the development of drug resistance or toxicity at high doses. Andrographolide is a natural diterpenoid from Andrographis paniculata which has anti-bacterial, anti-antiviral and anti-inflammation activities. In the current study, we test the hypothesis that Andrographolide reverses 5-FU resistance in colorectal cancer and examine the underlying mechanism. In vitro and vivo studies indicated that Andrographolide treatment significantly re-sensitizes HCT116/5-FUR cells (HCT116 cells which are 5-FU resistant) to cytotoxicity of 5-FU. Mechanism analysis showed that Andrographolide/5-FU co-treatment elevated apoptosis level of HCT116/5-FUR cells with highly increased level of BAX. By using biotin-Andrographolide pull down and cellular thermal shift assay, we found out that Andrographolide can directly target to BAX. Andrographolide-BAX interaction prevented BAX degradation, enhancing mitochondria-mediated apoptosis thus reversed 5-FU resistance while BAX silence diminished this effect. Further, by analyzing patient samples who received 5-FU involved chemotherapy, we found that expression level of BAX is correlated with PFS. Our results here provide a novel combination treatment strategy, especially for patients with 5-FU-resistant tumors expressing low level of BAX. Meanwhile, we also proposed that BAX expression may be a predicted and prognosis marker of 5-FU involved chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Improving xylitol production at elevated temperature with engineered Kluyveromyces marxianus through over-expressing transporters.

    Science.gov (United States)

    Zhang, Jia; Zhang, Biao; Wang, Dongmei; Gao, Xiaolian; Hong, Jiong

    2015-01-01

    Three transporter genes including Kluyveromyces marxianus aquaglyceroporin gene (KmFPS1), Candida intermedia glucose/xylose facilitator gene (CiGXF1) or glucose/xylose symporter gene (CiGXS1) were over-expressed in K. marxianus YZJ017 to improve xylitol production at elevated temperatures. The xylitol production of YZJ074 that harbored CiGXF1 was improved to 147.62g/L in Erlenmeyer flask at 42°C. In fermenter, 99.29 and 149.60g/L xylitol were produced from 99.55 and 151.91g/L xylose with productivity of 4.14 and 3.40g/L/h respectively at 42°C. Even at 45°C, YZJ074 could produce 101.30g/L xylitol from 101.41g/L xylose with productivity of 2.81g/L/h. Using fed-batch fermentation through repeatedly adding non-sterilized substrate directly, YZJ074 could produce 312.05g/L xylitol which is the highest yield reported to date. The engineered strains YZJ074 which can produce xylitol at elevated temperatures is an excellent foundation for xylitol bioconversion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Elevated expression of SLC34A2 inhibits the viability and invasion of A549 cells

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    YANG, WEIHAN; WANG, YU; PU, QIANG; YE, SUJUAN; MA, QINGPING; REN, JIANG; ZHONG, GUOXING; LIU, LUNXU; ZHU, WEN

    2014-01-01

    Abnormal expression of solute carrier family 34 (sodium phosphate), member 2 (SLC34A2) in the lung may induce abnormal alveolar type II (AT II) cells to transform into lung adenocarcinoma cells, and may also be important in biological process of lung adenocarcinoma. However, at present, the effects and molecular mechanisms of SLC34A2 in the initiation and progression of lung cancer remain to be elucidated. To the best of our knowledge, the present study revealed for the first time that the expression levels of SLC34A2 were downregulated in the A549 and H1299 lung adenocarcinoma cell lines. Further investigation demonstrated that the elevated expression of SLC34A2 in A549 cells was able to significantly inhibit cell viability and invasion in vitro. In addition, 10 upregulated genes between the A549-P-S cell line stably expressing SLC34A2 and the control cell line A549-P were identified by microarray analysis and quantitative polymerase chain reaction, including seven tumor suppressor genes and three complement genes. Furthermore, the upregulation of complement gene C3 and complement 4B preproprotein (C4b) in A549-P-S cells was confirmed by ELISA analysis and was identified to be correlated with recovering Pi absorption in A549 cells by the phosphomolybdic acid method by enhancing the expression of SLC34A2. Therefore, it was hypothesized that the mechanisms underlying the effect of SLC34A2 on A549 cells might be associated with the activation of the complement alternative pathway (C3 and C4b) and upregulation of the expression of selenium binding protein 1, thioredoxin-interacting protein, PDZK1-interacting protein 1 and dual specificity protein phosphatase 6. Downregulation of SLC34A2 may primarily cause abnormal AT II cells to escape from complement-associated immunosurveillance and abnormally express certain tumor-suppressor genes inducing AT II cells to develop into lung adenocarcinoma. The present study further elucidated the effects and mechanisms of SLC34A2 in

  2. Elevated catalase expression in a fungal pathogen is a double-edged sword of iron.

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    Arnab Pradhan

    2017-05-01

    Full Text Available Most fungal pathogens of humans display robust protective oxidative stress responses that contribute to their pathogenicity. The induction of enzymes that detoxify reactive oxygen species (ROS is an essential component of these responses. We showed previously that ectopic expression of the heme-containing catalase enzyme in Candida albicans enhances resistance to oxidative stress, combinatorial oxidative plus cationic stress, and phagocytic killing. Clearly ectopic catalase expression confers fitness advantages in the presence of stress, and therefore in this study we tested whether it enhances fitness in the absence of stress. We addressed this using a set of congenic barcoded C. albicans strains that include doxycycline-conditional tetON-CAT1 expressors. We show that high basal catalase levels, rather than CAT1 induction following stress imposition, reduce ROS accumulation and cell death, thereby promoting resistance to acute peroxide or combinatorial stress. This conclusion is reinforced by our analyses of phenotypically diverse clinical isolates and the impact of stochastic variation in catalase expression upon stress resistance in genetically homogeneous C. albicans populations. Accordingly, cat1Δ cells are more sensitive to neutrophil killing. However, we find that catalase inactivation does not attenuate C. albicans virulence in mouse or invertebrate models of systemic candidiasis. Furthermore, our direct comparisons of fitness in vitro using isogenic barcoded CAT1, cat1Δ and tetON-CAT1 strains show that, while ectopic catalase expression confers a fitness advantage during peroxide stress, it confers a fitness defect in the absence of stress. This fitness defect is suppressed by iron supplementation. Also high basal catalase levels induce key iron assimilatory functions (CFL5, FET3, FRP1, FTR1. We conclude that while high basal catalase levels enhance peroxide stress resistance, they place pressure on iron homeostasis through an

  3. Elevated catalase expression in a fungal pathogen is a double-edged sword of iron.

    Science.gov (United States)

    Pradhan, Arnab; Herrero-de-Dios, Carmen; Belmonte, Rodrigo; Budge, Susan; Lopez Garcia, Angela; Kolmogorova, Aljona; Lee, Keunsook K; Martin, Brennan D; Ribeiro, Antonio; Bebes, Attila; Yuecel, Raif; Gow, Neil A R; Munro, Carol A; MacCallum, Donna M; Quinn, Janet; Brown, Alistair J P

    2017-05-01

    Most fungal pathogens of humans display robust protective oxidative stress responses that contribute to their pathogenicity. The induction of enzymes that detoxify reactive oxygen species (ROS) is an essential component of these responses. We showed previously that ectopic expression of the heme-containing catalase enzyme in Candida albicans enhances resistance to oxidative stress, combinatorial oxidative plus cationic stress, and phagocytic killing. Clearly ectopic catalase expression confers fitness advantages in the presence of stress, and therefore in this study we tested whether it enhances fitness in the absence of stress. We addressed this using a set of congenic barcoded C. albicans strains that include doxycycline-conditional tetON-CAT1 expressors. We show that high basal catalase levels, rather than CAT1 induction following stress imposition, reduce ROS accumulation and cell death, thereby promoting resistance to acute peroxide or combinatorial stress. This conclusion is reinforced by our analyses of phenotypically diverse clinical isolates and the impact of stochastic variation in catalase expression upon stress resistance in genetically homogeneous C. albicans populations. Accordingly, cat1Δ cells are more sensitive to neutrophil killing. However, we find that catalase inactivation does not attenuate C. albicans virulence in mouse or invertebrate models of systemic candidiasis. Furthermore, our direct comparisons of fitness in vitro using isogenic barcoded CAT1, cat1Δ and tetON-CAT1 strains show that, while ectopic catalase expression confers a fitness advantage during peroxide stress, it confers a fitness defect in the absence of stress. This fitness defect is suppressed by iron supplementation. Also high basal catalase levels induce key iron assimilatory functions (CFL5, FET3, FRP1, FTR1). We conclude that while high basal catalase levels enhance peroxide stress resistance, they place pressure on iron homeostasis through an elevated cellular demand

  4. ShaPINg cell fate upon DNA damage:role of Pin1 isomerase in DNA damage-induced cell death and repair

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    Thomas G Hofmann

    2014-06-01

    Full Text Available The peptidyl-prolyl cis/trans isomerase Pin1 acts as a molecular timer in proline-directed Ser/Thr kinase signaling and shapes cellular responses based on recognition of phosphorylation marks and implementing conformational changes in its substrates. Accordingly, Pin1 has been linked to numerous phosphorylation-controlled signaling pathways and cellular processes such as cell cycle progression, proliferation and differentiation. In addition, Pin1 plays a pivotal role in DNA damage-triggered cell fate decisions. Whereas moderate DNA damage is balanced by DNA repair, cells confronted with massive genotoxic stress are eliminated by the induction of programmed cell death or cellular senescence. In this review we summarize and discuss the current knowledge on how Pin1 specifies cell fate through regulating key players of the apoptotic and the repair branch of the DNA damage response.

  5. Unraveling a phosphorylation event in a folded protein by NMR spectroscopy: phosphorylation of the Pin1 WW domain by PKA

    International Nuclear Information System (INIS)

    Smet-Nocca, Caroline; Launay, Hélène; Wieruszeski, Jean-Michel; Lippens, Guy; Landrieu, Isabelle

    2013-01-01

    The Pin1 protein plays a critical role in the functional regulation of the hyperphosphorylated neuronal Tau protein in Alzheimer’s disease and is by itself regulated by phosphorylation. We have used Nuclear Magnetic Resonance (NMR) spectroscopy to both identify the PKA phosphorylation site in the Pin1 WW domain and investigate the functional consequences of this phosphorylation. Detection and identification of phosphorylation on serine/threonine residues in a globular protein, while mostly occurring in solvent-exposed flexible loops, does not lead to chemical shift changes as obvious as in disordered proteins and hence does not necessarily shift the resonances outside the spectrum of the folded protein. Other complications were encountered to characterize the extent of the phosphorylation, as part of the 1 H, 15 N amide resonances around the phosphorylation site are specifically broadened in the unphosphorylated state. Despite these obstacles, NMR spectroscopy was an efficient tool to confirm phosphorylation on S16 of the WW domain and to quantify the level of phosphorylation. Based on this analytical characterization, we show that WW phosphorylation on S16 abolishes its binding capacity to a phosphorylated Tau peptide. A reduced conformational heterogeneity and flexibility of the phospho-binding loop upon S16 phosphorylation could account for part of the decreased affinity for its phosphorylated partner. Additionally, a structural model of the phospho-WW obtained by molecular dynamics simulation and energy minimization suggests that the phosphate moiety of phospho-S16 could compete with the phospho-substrate.

  6. Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells.

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    Shan Wan

    Full Text Available Low doses of anticancer drugs have been shown to enhance antitumor immune response and increase the efficacy of immunotherapy. The molecular basis for such effects remains elusive, although selective depletion of T regulatory cells has been demonstrated. In the current studies, we demonstrate that topotecan (TPT, a topoisomerase I-targeting drug with a well-defined mechanism of action, stimulates major histocompatibility complex class I (MHC I expression in breast cancer cells through elevated expression/secretion of interferon-β (IFN-β and activation of type I IFN signaling. First, we show that TPT treatment elevates the expression of both total and cell-surface MHC I in breast cancer cells. Second, conditioned media from TPT-treated breast cancer ZR-75-1 cells induce elevated expression of cell-surface MHC I in drug-naïve recipient cells, suggesting the involvement of cytokines and/or other secreted molecules. Consistently, TPT-treated cells exhibit elevated expression of multiple cytokines such as IFN-β, TNF-α, IL-6 and IL-8. Third, either knocking down the type I interferon receptor subunit 1 (IFNAR1 or addition of neutralizing antibody against IFN-β results in reduced MHC I expression in TPT-treated cells. Together, these results suggest that TPT induces increased IFN-β autocrine/paracrine signaling through type I IFN receptor, resulting in the elevated MHC I expression in tumor cells. Studies have also demonstrated that other chemotherapeutic agents (e.g. etoposide, cisplatin, paclitaxel and vinblastine similarly induce increased IFN-β secretion and elevated MHC I expression. In addition, conditioned media from γ-irradiated donor cells are shown to induce IFN-β-dependent MHC I expression in unirradiated recipient cells. In the aggregate, our results suggest that many cancer therapeutics induce elevated tumor antigen presentation through MHC I, which could represent a common mechanism for enhanced antitumor immune response through

  7. Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment.

    Science.gov (United States)

    Jukić, M M; Opel, N; Ström, J; Carrillo-Roa, T; Miksys, S; Novalen, M; Renblom, A; Sim, S C; Peñas-Lledó, E M; Courtet, P; Llerena, A; Baune, B T; de Quervain, D J; Papassotiropoulos, A; Tyndale, R F; Binder, E B; Dannlowski, U; Ingelman-Sundberg, M

    2017-08-01

    The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype. In humans, we found that the absence of CYP2C19 was associated with a bilateral hippocampal volume increase in two independent healthy cohorts (N=386 and 1032) and a lower prevalence of major depressive disorder and depression severity in African-Americans (N=3848). Moreover, genetically determined high CYP2C19 enzymatic capacity was associated with higher suicidality in depressed suicide attempters (N=209). 2C19TG mice showed high stress sensitivity, impaired hippocampal Bdnf homeostasis in stress, and more despair-like behavior in the forced swim test (FST). After the treatment with citalopram and 5-HT 1A receptor agonist 8OH-DPAT, the reduction in immobility time in the FST was more pronounced in 2C19TG mice compared with WTs. Conversely, in the 2C19TG hippocampus, metabolic turnover of serotonin was reduced, whereas ERK1/2 and GSK3β phosphorylation was increased. Altogether, this study indicates that elevated CYP2C19 expression is associated with depressive symptoms, reduced hippocampal volume and impairment of hippocampal serotonin and BDNF homeostasis.

  8. [The expression of p53, MDM2 and Ref1 gene in cultured retina neurons of SD rats treated with vitamin B1 and/or elevated pressure].

    Science.gov (United States)

    Yang, Zhikuan; Ge, Jian; Yin, Wei; Shen, Huangxuan; Liu, Haiquan; Guo, Yan

    2004-12-01

    To investigate the expression of p53, MDM2 and Ref1 gene in cultured retina neurons of SD rats treated with Vitamin B1 and (or) elevated pressure. The retinal neuron of postnatal SD rats were cultured in vivo, the elevated pressure was produced after 7 days, and the total RNA was extracted after another 2 days, expression of p53, MDM2 and Ref1 gene were analyzed with RT-PCR. The expression level of p53 and MDM2 gene were increased in elevated pressure group, normal with Ref1 gene expression. But the expression of p53 and MDM2 gene were decreased significantly in elevated pressure group treated with vitamine B1 compare to the elevated group. Apoptosis seem to be a mechanism of cell death in retinal neurons of SD rats with elevated pressure.Vitamine B1 have protect effects against elevated pressure.

  9. Elevated cyclooxygenase-2 expression is associated with altered expression of p53 and SMAD4, amplification of HER-2/neu, and poor outcome in serous ovarian carcinoma.

    Science.gov (United States)

    Erkinheimo, Tiina-Liisa; Lassus, Heini; Finne, Patrik; van Rees, Bastiaan P; Leminen, Arto; Ylikorkala, Olavi; Haglund, Caj; Butzow, Ralf; Ristimäki, Ari

    2004-01-15

    Cyclooxygenase-2 (COX-2) is frequently expressed in human adenocarcinomas and inhibition of COX-2 suppresses tumor formation in various animal models of carcinogenesis. We analyzed expression of COX-2 protein in human serous ovarian carcinomas by immunohistochemistry (n = 442) and by Western blotting (n = 12) and COX-2 mRNA by reverse transcriptase PCR (n = 12). COX-2 immunoreactivity was correlated to clinicopathological variables and to expression of p53 and SMAD4 as detected by immunohistochemistry and to amplification of HER-2/neu as detected by in situ hybridization. COX-2 mRNA expression was detected in 75% (9 of 12) and COX-2 protein in 42% (5 of 12) of the serous ovarian adenocarcinoma specimens as detected by reverse transcriptase-PCR and Western blot analysis, respectively. Moderate to strong (elevated) immunoreactivity for COX-2 was detected in 70% (310 of 442) of the tumors. Elevated COX-2 expression associated with reduced disease-specific survival (P = 0.0011), high histological grade (P 1 cm (P = 0.0111), and age > 57 years (P = 0.0099). Tumors with altered immunostaining pattern for p53 or SMAD4 expressed more frequently elevated levels of COX-2 when compared with the tumors with normal staining pattern of these tumor suppressor genes (P ovarian carcinomas and that expression of COX-2 may be induced in these tumors by loss of tumor suppressor genes such as p53 and SMAD4 and by amplification of HER-2/neuoncogene.

  10. Histone deacetylase turnover and recovery in sulforaphane-treated colon cancer cells: competing actions of 14-3-3 and Pin1 in HDAC3/SMRT corepressor complex dissociation/reassembly

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    Williams David E

    2011-05-01

    Full Text Available Abstract Background Histone deacetylase (HDAC inhibitors are currently undergoing clinical evaluation as anti-cancer agents. Dietary constituents share certain properties of HDAC inhibitor drugs, including the ability to induce global histone acetylation, turn-on epigenetically-silenced genes, and trigger cell cycle arrest, apoptosis, or differentiation in cancer cells. One such example is sulforaphane (SFN, an isothiocyanate derived from the glucosinolate precursor glucoraphanin, which is abundant in broccoli. Here, we examined the time-course and reversibility of SFN-induced HDAC changes in human colon cancer cells. Results Cells underwent progressive G2/M arrest over the period 6-72 h after SFN treatment, during which time HDAC activity increased in the vehicle-treated controls but not in SFN-treated cells. There was a time-dependent loss of class I and selected class II HDAC proteins, with HDAC3 depletion detected ahead of other HDACs. Mechanism studies revealed no apparent effect of calpain, proteasome, protease or caspase inhibitors, but HDAC3 was rescued by cycloheximide or actinomycin D treatment. Among the protein partners implicated in the HDAC3 turnover mechanism, silencing mediator for retinoid and thyroid hormone receptors (SMRT was phosphorylated in the nucleus within 6 h of SFN treatment, as was HDAC3 itself. Co-immunoprecipitation assays revealed SFN-induced dissociation of HDAC3/SMRT complexes coinciding with increased binding of HDAC3 to 14-3-3 and peptidyl-prolyl cis/trans isomerase 1 (Pin1. Pin1 knockdown blocked the SFN-induced loss of HDAC3. Finally, SFN treatment for 6 or 24 h followed by SFN removal from the culture media led to complete recovery of HDAC activity and HDAC protein expression, during which time cells were released from G2/M arrest. Conclusion The current investigation supports a model in which protein kinase CK2 phosphorylates SMRT and HDAC3 in the nucleus, resulting in dissociation of the corepressor

  11. Elevated procoagulant endothelial and tissue factor expressing microparticles in women with recurrent pregnancy loss.

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    Rucha Patil

    Full Text Available BACKGROUND: 15% of reproducing couples suffer from pregnancy loss(PL and recurs in 2-3%. One of the most frequently hypothesized causes of unexplained PL refers to a defective maternal haemostatic response leading to uteroplacental thrombosis. Hereditary thrombophilia and antiphospholipid antibodies have been extensively described as risk factors for PL in women with unknown aetiology. Recently, a new marker has emerged: the cell-derived procoagulant circulating microparticles(MPs which have been reported to have a major role in many thrombosis complicated diseases. This study aims to analyze the significance of procoagulant MPs in women suffering from unexplained recurrent pregnancy loss(RPL, and characterize their cellular origin. METHOD AND FINDINGS: 115 women with RPL were analyzed for common thrombophilia markers and different cell derived MPs-total annexinV, platelet(CD41a, endothelial(CD146,CD62e, leukocyte(CD45, erythrocyte(CD235a and tissue factor(CD142(TF expressing MPs and were compared with 20 healthy non-pregnant women. Methodology for MP analysis was standardized by participating in the "Vascular Biology Scientific and Standardization Committee workshop". RESULTS: Total annexinV, TF and endothelial MPs were found significantly increased(p<0.05, 95% confidence interval in women with RPL. The procoagulant activity of MPs measured by STA-PPL clotting time assay was found in correspondence with annexinV MP levels, wherein the clot time was shortened in samples with increased MP levels. Differences in platelet, leukocyte and erythrocyte derived MPs were not significant. Thirty seven of 115 women were found to carry any of the acquired or hereditary thrombophilia markers. No significant differences were seen in the MP profile of women with and without thrombophilia marker. CONCLUSION: The presence of elevated endothelial, TF and phosphatidylserine expressing MPs at a distance (at least 3 months from the PL suggests a continued chronic

  12. Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer

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    Ellen L. Jones

    2008-01-01

    Full Text Available Tumor hypoxia is associated with adverse outcome in many malignancies. The goal of this study was to determine if elevated expression of carbonic anhydrase IX (CAIX, a biomarker of hypoxia, predicts for recurrence in early-stage cervical cancer. The charts of all patients with early-stage cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988–2001 were reviewed. Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remained disease-free were stained for CAIX. An immunohistochemical score (IHC was generated from the extent/intensity of staining. Outcome, as measured by freedom from recurrence (FFR, distant metastases (FFDM and local recurrence (FFLR, was analyzed as a function of age, IHC, lymph node status (LN and histology.Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastases as first site of failure (5-year FFDM 50% than patients with only +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004. In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p = 0.0015 though there was a strong trend with elevated CAIX expression (p = 0.069. Elevated CAIX expression is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

  13. Molecular implication of PP2A and Pin1 in the Alzheimer's disease specific hyperphosphorylation of Tau.

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    Isabelle Landrieu

    Full Text Available Tau phosphorylation and dephosphorylation regulate in a poorly understood manner its physiological role of microtubule stabilization, and equally its integration in Alzheimer disease (AD related fibrils. A specific phospho-pattern will result from the balance between kinases and phosphatases. The heterotrimeric Protein Phosphatase type 2A encompassing regulatory subunit PR55/Bα (PP2A(T55α is a major Tau phosphatase in vivo, which contributes to its final phosphorylation state. We use NMR spectroscopy to determine the dephosphorylation rates of phospho-Tau by this major brain phosphatase, and present site-specific and kinetic data for the individual sites including the pS202/pT205 AT8 and pT231 AT180 phospho-epitopes.We demonstrate the importance of the PR55/Bα regulatory subunit of PP2A within this enzymatic process, and show that, unexpectedly, phosphorylation at the pT231 AT180 site negatively interferes with the dephosphorylation of the pS202/pT205 AT8 site. This inhibitory effect can be released by the phosphorylation dependent prolyl cis/trans isomerase Pin1. Because the stimulatory effect is lost with the dimeric PP2A core enzyme (PP2A(D or with a phospho-Tau T231A mutant, we propose that Pin1 regulates the interaction between the PR55/Bα subunit and the AT180 phospho-epitope on Tau.Our results show that phosphorylation of T231 (AT180 can negatively influence the dephosphorylation of the pS202/pT205 AT8 epitope, even without an altered PP2A pool. Thus, a priming dephosphorylation of pT231 AT180 is required for efficient PP2A(T55α-mediated dephosphorylation of pS202/pT205 AT8. The sophisticated interplay between priming mechanisms reported for certain Tau kinases and the one described here for Tau phosphatase PP2A(T55α may contribute to the hyperphosphorylation of Tau observed in AD neurons.

  14. The prolyl isomerase Pin1 acts synergistically with CDK2 to regulate the basal activity of estrogen receptor α in breast cancer.

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    Chiara Lucchetti

    Full Text Available In hormone receptor-positive breast cancers, most tumors in the early stages of development depend on the activity of the estrogen receptor and its ligand, estradiol. Anti-estrogens, such as tamoxifen, have been used as the first line of therapy for over three decades due to the fact that they elicit cell cycle arrest. Unfortunately, after an initial period, most cells become resistant to hormonal therapy. Peptidylprolyl isomerase 1 (Pin1, a protein overexpressed in many tumor types including breast, has been demonstrated to modulate ERalpha activity and is involved in resistance to hormonal therapy. Here we show a new mechanism through which CDK2 drives an ERalpha-Pin1 interaction under hormone- and growth factor-free conditions. The PI3K/AKT pathway is necessary to activate CDK2, which phosphorylates ERalphaSer294, and mediates the binding between Pin1 and ERalpha. Site-directed mutagenesis demonstrated that ERalphaSer294 is essential for Pin1-ERalpha interaction and modulates ERalpha phosphorylation on Ser118 and Ser167, dimerization and activity. These results open up new drug treatment opportunities for breast cancer patients who are resistant to anti-estrogen therapy.

  15. Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators

    Science.gov (United States)

    Birt, Julie A.; Nabli, Henda; Stilley, Julie A.; Windham, Emma A.; Frazier, Shellaine R.

    2013-01-01

    Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis. PMID:23427178

  16. Elevated HERV-K Expression in Soft Tissue Sarcoma Is Associated with Worsened Relapse-Free Survival.

    Science.gov (United States)

    Giebler, Maria; Staege, Martin S; Blauschmidt, Sindy; Ohm, Lea I; Kraus, Matthias; Würl, Peter; Taubert, Helge; Greither, Thomas

    2018-01-01

    A wide variety of endogenous retroviral sequences has been demonstrated in the human genome so far, divided into several different families according to the sequence homology to viral strains. While increased expression of human endogenous retrovirus (HERV) elements has already been linked to unfavorable prognosis in hepatocellular carcinoma, breast cancer, and ovarian carcinoma yet less is known about the impact of the expression of different HERV elements on sarcomagenesis in general as well as the outcome of soft tissue sarcoma (STS) patients. Therefore, in this study the association between expression of HERV-K and HERV-F and the clinicopathological characteristics in a cohort of STSs as well as the patients' prognosis was evaluated. HERV-K and HERV-F expression was assessed by quantitative real-time PCR in 120 patient specimens. HERV-K and HERV-F expression was significantly correlated ( r S = 0.5; p = 6.4 × 10 -9 ; Spearman's rank bivariate correlation). Also, tumor diameter exhibited a significant negative association to HERV-K and HERV-F expression. Levels of several hypoxia-related RNAs like HIF-1α and miR-210 showed a significant positive correlation with both HERV-K and HERV-F expression. Although in survival analyses no impact of HERV expression on disease-specific survival could be detected, patients with elevated HERV-K expression had a significantly shorter relapse-free survival ( p = 0.014, log-rank analysis). In conclusion, we provide evidence for the first time that the increased expression of HERV-K in tumors is associated with STS patients' prognosis.

  17. Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status

    International Nuclear Information System (INIS)

    Wang-Rodriguez, Jessica; Urquidi, Virginia; Rivard, Amber; Goodison, Steve

    2003-01-01

    Our previous characterization of a human breast tumor metastasis model identified several candidate metastasis genes. The expression of osteopontin (OPN) correlated with the metastatic phenotype, whereas thrombospondin-1 (TSP-1) and tyrosinase-related protein-1 (TYRP-1) correlated with the nonmetastatic phenotype of independent MDA-MB-435 cell lines implanted orthotopically into athymic mice. The aim of the present study was to examine the cellular distribution of these molecules in human breast tissue and to determine whether the relative expression level of these three genes is associated with human breast tumor metastasis. Sixty-eight fresh, frozen specimens including 31 primary infiltrating ductal carcinomas, 22 nodal metastases, 10 fibroadenomas, and five normal breast tissues were evaluated for OPN expression, TSP-1 expression and TYRP-1 expression. Immunohistochemistry was performed to monitor the cellular distribution and to qualitatively assess expression. Quantitative analysis was achieved by enrichment of breast epithelial cells using laser-capture microdissection and subsequent real-time, quantitative PCR. The epithelial components of the breast tissue were the source of OPN and TSP-1 expression, whereas TYRP-1 was present in both the epithelial and stromal components. Both OPN and TSP-1 expression were significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels was evident between primary tumors with or without metastases, nor between primary and metastatic carcinomas. Elevated expression of OPN and TSP-1 may play a role in the pathogenesis of breast cancer. The multiplex analysis of these molecules may enhance our ability to diagnose and/or prognosticate human breast malignancy

  18. Elevated c-Src and c-Yes expression in malignant skin cancers

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    Lee Jang

    2010-08-01

    Full Text Available Abstracts Background Src family kinases (SFKs play an important role in cancer proliferation, survival, motility, invasiveness, metastasis, and angiogenesis. Among the SFKs, c-Src and c-Yes are particularly over-expressed or hyper-activated in many human epithelial cancers. However, only a few studies have attempted to define the expression and role of c-Src and c-Yes in cutaneous carcinomas. Objectives To investigate the expression of c-Src and c-Yes in cutaneous carcinomas to include malignant melanoma (MM, squamous cell carcinoma (SCC and basal cell carcinoma (BCC. Methods We examined 6 normal skin tissues and 18 malignant skin tumor tissues using western blotting for the expression of c-Src and c-Yes. In another set, 16 specimens of MM, 16 SCCs and 16 BCCs were analyzed for the expression of c-Src and c-Yes using immunohistochemical staining. Results Western blotting showed that c-Src was expressed in all malignant skin tumors, but not in normal skin, while c-Yes was expressed in MM and SCC, but not in BCC and normal skin. Immunohistochemical staining results of c-Src and c-Yes in MM, SCC, and BCC mirrored those of the western blot analysis. Conclusions c-Src, rather than c-Yes, plays a key role in the proliferation and progression of malignant skin cancers.

  19. Elevated Adenylyl Cyclase 9 Expression Is a Potential Prognostic Biomarker for Patients with Colon Cancer.

    Science.gov (United States)

    Yi, Hua; Wang, Kun; Jin, Jun-Feng; Jin, He; Yang, Lihua; Zou, Yidan; Du, Biaoyan; Liu, Xiaodong

    2018-01-02

    BACKGROUND Adenylyl cyclase 9 (ADCY9) is an enzyme that modulates signal transduction by producing the second messenger, cyclic adenosine monophosphate (cAMP). The aim of the present study was to investigate the association of ADCY9 expression with clinicopathological features and disease-free survival of colon cancer patients. MATERIAL AND METHODS Immunohistochemistry staining with ADCY9 antibody was performed on a tissue microarray. Immunoreactivity scores (IRS) were recorded and applied for association analysis. ADCY9 mRNA expression and clinicopathogical information were also extracted from TCGA colon cancer dataset and analyzed using univariate and multivariate Cox proportional hazards models.  RESULTS ADCY9 IRS was significantly higher (P=0.002) in tumor tissues (6.40±1.26, n=200) than in adjacent normal samples (4.13±0.83, n=8). The IRS and mRNA expression of ADCY9 were correlated to colon cancer TNM staging. Longer disease-free survival was observed in patients with lower ADCY9 expression (P=0.001). In the multivariate models, ADCY9 expression level (hazard ratio [HR] 5.495, 95% confidence interval [CI] 1.753-17.227, P=0.003), and distant metastasis (HR 4.329, 95% CI 1.374-13.636, P=0.012) were still associated with disease-free survival. CONCLUSIONS High ADCY9 expression is a poor prognostic factor for disease-free survival in colon cancer.

  20. Changes in gene expression, cell physiology and toxicity of the harmful cyanobacterium Microcystis aeruginosa at elevated CO2

    Directory of Open Access Journals (Sweden)

    Giovanni eSandrini

    2015-05-01

    Full Text Available Rising CO2 concentrations may have large effects on aquatic microorganisms. In this study, we investigated how elevated pCO2 affects the harmful freshwater cyanobacterium Microcystis aeruginosa. This species is capable of producing dense blooms and hepatotoxins called microcystins. Strain PCC 7806 was cultured in chemostats that were shifted from low to high pCO2 conditions. This resulted in a transition from a C-limited to a light-limited steady state, with a ~2.7 fold increase of the cyanobacterial biomass and ~2.5 fold more microcystin per cell. Cells increased their chlorophyll a and phycocyanin content, and raised their PSI/PSII ratio at high pCO2. Surprisingly, cells had a lower dry weight and contained less carbohydrates, which might be an adaptation to improve the buoyancy of Microcystis when light becomes more limiting at high pCO2. Only 234 of the 4,691 genes responded to elevated pCO2. For instance, expression of the carboxysome, RuBisCO, photosystem and C metabolism genes did not change significantly, and only a few N assimilation genes were expressed differently. The lack of large-scale changes in the transcriptome could suit a buoyant species that lives in eutrophic lakes with strong CO2 fluctuations very well. However, we found major responses in inorganic carbon uptake. At low pCO2, cells were mainly dependent on bicarbonate uptake, whereas at high pCO2 gene expression of the bicarbonate uptake systems was down-regulated and cells shifted to CO2 and low-affinity bicarbonate uptake. These results show that the need for high-affinity bicarbonate uptake systems ceases at elevated CO2. Moreover, the combination of an increased cyanobacterial abundance, improved buoyancy, and higher toxin content per cell indicates that rising atmospheric CO2 levels may increase the problems associated with the harmful cyanobacterium Microcystis in eutrophic lakes.

  1. Elevated D8/17 expression on B lymphocytes, a marker of rheumatic fever, measured with flow cytometry in tic disorder patients

    NARCIS (Netherlands)

    Hoekstra, PJ; Bijzet, J; Limburg, PC; Steenhuis, MP; Troost, PW; Oosterhoff, MD; Korf, J; Kallenberg, CGM; Minderaa, RB

    Objective: Elevated D8/17 expression on B lymphocytes is a known susceptibility marker of rheumatic fever. Previous studies have reported higher than usual D8/ 17 expression on B lymphocytes of patients with tic disorders. The purpose of this study was to assess D8/17 expression on B lymphocytes of

  2. Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

    International Nuclear Information System (INIS)

    Wu, Hsu-Pin; Hsu, Shu-Yuan; Wu, Wen-Ai; Hu, Ji-Wei; Ouyang, Pin

    2014-01-01

    Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB +/− mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity

  3. Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hsu-Pin; Hsu, Shu-Yuan [Department of Anatomy, Chang Gung University Medical College, Taiwan (China); Wu, Wen-Ai; Hu, Ji-Wei [Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan (China); Ouyang, Pin, E-mail: ouyang@mail.cgu.edu.tw [Department of Anatomy, Chang Gung University Medical College, Taiwan (China); Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Taiwan (China)

    2014-01-03

    Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB{sup +/−} mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity.

  4. Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus).

    Science.gov (United States)

    Fedorov, Vadim B; Goropashnaya, Anna V; Tøien, Øivind; Stewart, Nathan C; Gracey, Andrew Y; Chang, Celia; Qin, Shizhen; Pertea, Geo; Quackenbush, John; Showe, Louise C; Showe, Michael K; Boyer, Bert B; Barnes, Brian M

    2009-04-10

    We conducted a large-scale gene expression screen using the 3,200 cDNA probe microarray developed specifically for Ursus americanus to detect expression differences in liver and skeletal muscle that occur during winter hibernation compared with animals sampled during summer. The expression of 12 genes, including RNA binding protein motif 3 (Rbm3), that are mostly involved in protein biosynthesis, was induced during hibernation in both liver and muscle. The Gene Ontology and Gene Set Enrichment analysis consistently showed a highly significant enrichment of the protein biosynthesis category by overexpressed genes in both liver and skeletal muscle during hibernation. Coordinated induction in transcriptional level of genes involved in protein biosynthesis is a distinctive feature of the transcriptome in hibernating black bears. This finding implies induction of translation and suggests an adaptive mechanism that contributes to a unique ability to reduce muscle atrophy over prolonged periods of immobility during hibernation. Comparing expression profiles in bears to small mammalian hibernators shows a general trend during hibernation of transcriptional changes that include induction of genes involved in lipid metabolism and carbohydrate synthesis as well as depression of genes involved in the urea cycle and detoxification function in liver.

  5. Degradation of elastic fiber and elevated elastase expression in long head of biceps tendinopathy.

    Science.gov (United States)

    Wu, Yen-Ting; Su, Wei-Ren; Wu, Po-Ting; Shen, Po-Chuan; Jou, I-Ming

    2017-09-01

    Tendinopathy of the long head of the biceps (TLHB) involves various types of extracellular matrix degeneration, but previous studies have not evaluated elastic fibers. The purpose of this study was to investigate elastic fiber distribution in long head of the biceps (LHB). The TLHB tendons of 16 consecutive patients (eight men and eight women; average age of 55.75 years; age range of 40-71 years) were transected and harvested. Three cadaveric LHB tendons were used as the control group. The expression of collagen type I was decreased, but type III was increased in TLHB. Disruption of elastic fibers was particularly observed in grade II specimens where the level of elastase-positive staining was significantly higher than in grade I specimens. Elastic fibers were not observed in the grade III area, implying a higher expression of elastase than in the grade I area. Results of Western blotting showed that the expression of elastin was higher in the control group and the levels of elastin significantly decreased in grades II and III of TLHB. Levels of osteopontin and elastase were increased in primary culture of human tenocytes after experiencing elastic derived peptide treatment. These results suggested that elastase may be caused by the disruption of elastic fibers in the development of chronic tendinopathy and that elastic derived peptide may enhance elastase and osteopontin expression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1919-1926, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Expression of the gene for large subunit of m-calpain is elevated in ...

    Indian Academy of Sciences (India)

    cerebral ischemia. J. Neurochem. 66, 421±424. Sambrook J., Fritsch E. F. and Maniatis T. 1989 Molecular cloning: a laboratory manual (2nd edition). Cold spring Harbor. Laboratory Press, Cold Spring Harbor. Samis J. A., Back D. W., Graham E. J., DeLuca C. L. and Elce J. S.. 1991 Constitutive expression of calpain II in the ...

  7. Elevated BSC-1 and ROMK expression in Dahl salt-sensitive rat kidneys.

    Science.gov (United States)

    Hoagland, Kimberly M; Flasch, Averia K; Dahly-Vernon, Annette J; dos Santos, Elisabete Alcantara; Knepper, Mark A; Roman, Richard J

    2004-04-01

    This study compared the expression of enzymes and transport and channel proteins involved in the regulation of sodium reabsorption in the kidney of Dahl salt-sensitive (DS) and salt-resistant Brown-Norway (BN) and consomic rats (SS.BN13), in which chromosome 13 from the BN rat has been introgressed into the DS genetic background. The expression of the Na+/K+/2Cl- (BSC-1) cotransporter, Na+/H+ exchanger (NHE3), and Na+-K+-ATPase proteins were similar in the renal cortex of DS, BN, and SS.BN13 rats fed either a low-salt (0.1% NaCl) or a high-salt (8% NaCl) diet. The expression of the BSC-1 and the renal outer medullary K+ channel (ROMK) were higher, whereas the expression of the cytochrome P4504A proteins responsible for the formation of 20-hydroxyeicosatetraenoic (20-HETE) was lower in the outer medulla of the kidney of DS than in BN or SS.BN13 rats fed either a low-salt or a high-salt diet. In addition, the renal formation and excretion of 20-HETE was lower in DS than in BN and SS.BN13 rats. These results suggest that overexpression of ROMK and BSC-1 in the thick ascending limb combined with a deficiency in renal formation of 20-HETE may predispose Dahl S rats fed a high-salt diet to Na+ retention and hypertension.

  8. Preservation of bone mass and structure in hibernating black bears (Ursus americanus) through elevated expression of anabolic genes.

    Science.gov (United States)

    Fedorov, Vadim B; Goropashnaya, Anna V; Tøien, Øivind; Stewart, Nathan C; Chang, Celia; Wang, Haifang; Yan, Jun; Showe, Louise C; Showe, Michael K; Donahue, Seth W; Barnes, Brian M

    2012-06-01

    Physical inactivity reduces mechanical load on the skeleton, which leads to losses of bone mass and strength in non-hibernating mammalian species. Although bears are largely inactive during hibernation, they show no loss in bone mass and strength. To obtain insight into molecular mechanisms preventing disuse bone loss, we conducted a large-scale screen of transcriptional changes in trabecular bone comparing winter hibernating and summer non-hibernating black bears using a custom 12,800 probe cDNA microarray. A total of 241 genes were differentially expressed (P 1.4) in the ilium bone of bears between winter and summer. The Gene Ontology and Gene Set Enrichment Analysis showed an elevated proportion in hibernating bears of overexpressed genes in six functional sets of genes involved in anabolic processes of tissue morphogenesis and development including skeletal development, cartilage development, and bone biosynthesis. Apoptosis genes demonstrated a tendency for downregulation during hibernation. No coordinated directional changes were detected for genes involved in bone resorption, although some genes responsible for osteoclast formation and differentiation (Ostf1, Rab9a, and c-Fos) were significantly underexpressed in bone of hibernating bears. Elevated expression of multiple anabolic genes without induction of bone resorption genes, and the down regulation of apoptosis-related genes, likely contribute to the adaptive mechanism that preserves bone mass and structure through prolonged periods of immobility during hibernation.

  9. The hepatic Raldh1 expression is elevated in Zucker fatty rats and its over-expression introduced the retinal-induced Srebp-1c expression in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available The roles of vitamin A (VA in the development of metabolic diseases remain unanswered. We have reported that retinoids synergized with insulin to induce the expression of sterol-regulatory element-binding protein 1c gene (Srebp-1c expression in primary rat hepatocytes. Additionally, the hepatic Srebp-1c expression is elevated in Zucker fatty (ZF rats, and reduced in those fed a VA deficient diet. VA is metabolized to retinoic acid (RA for regulating gene expression. We hypothesized that the expression of RA production enzymes contributes to the regulation of the hepatic Srebp-1c expression. Therefore, we analyzed their expression levels in Zucker lean (ZL and ZF rats. The mRNA levels of retinaldehyde dehydrogenase family 1 gene (Raldh1 were found to be higher in the isolated and cultured primary hepatocytes from ZF rats than that from ZL rats. The RALDH1 protein level was elevated in the liver of ZF rats. Retinol and retinal dose- and time-dependently induced the expression of RA responsive Cyp26a1 gene in hepatocytes and hepatoma cells. INS-1 cells were identified as an ideal tool to study the effects of RA production on the regulation of gene expression because only RA, but not retinal, induced Srebp-1c mRNA expression in them. Recombinant adenovirus containing rat Raldh1 cDNA was made and used to infect INS-1 cells. The over-expression of RALDH1 introduced the retinal-mediated induction of Srebp-1c expression in INS-1 cells. We conclude that the expression levels of the enzymes for RA production may contribute to the regulation of RA responsive genes, and determine the responses of the cells to retinoid treatments. The elevated hepatic expression of Raldh1 in ZF rats may cause the excessive RA production from retinol, and in turn, result in higher Srebp-1c expression. This excessive RA production may be one of the factors contributing to the elevated lipogenesis in the liver of ZF rats.

  10. Elevated expression and potential roles of human Sp5, a member of Sp transcription factor family, in human cancers

    International Nuclear Information System (INIS)

    Chen Yongxin; Guo Yingqiu; Ge Xijin; Itoh, Hirotaka; Watanabe, Akira; Fujiwara, Takeshi; Kodama, Tatsuhiko; Aburatani, Hiroyuki

    2006-01-01

    In this report, we describe the expression and function of human Sp5, a member of the Sp family of zinc finger transcription factors. Like other family members, the Sp5 protein contains a Cys2His2 zinc finger DNA binding domain at the C-terminus. Our experiments employing Gal4-Sp5 fusion proteins reveal multiple transcriptional domains, including a N-terminal activity domain, an intrinsic repressive element, and a C-terminal synergistic domain. Elevated expression of Sp5 was noted in several human tumors including hepatocellular carcinoma, gastric cancer, and colon cancer. To study the effects of the Sp5 protein on growth properties of human cancer cells and facilitate the identification of its downstream genes, we combined an inducible gene expression system with microarray analysis to screen for its transcriptional targets. Transfer of Sp5 into MCF-7 cells that expressed no detectable endogenous Sp5 protein elicited significant growth promotion activity. Several of the constitutively deregulated genes have been associated with tumorigenesis (CDC25C, CEACAM6, TMPRSS2, XBP1, MYBL1, ABHD2, and CXCL12) and Wnt/β-Catenin signaling pathways (BAMBI, SIX1, IGFBP5, AES, and p21 WAF1 ). This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against human cancers

  11. The study on highly expressed proteins as a function of an elevated ultraviolet radiation in the copepod, Tigriopus japonicus

    Science.gov (United States)

    Zubrzycki, Igor Z.; Lee, Seunghan; Lee, Kanghyun; Wiacek, Magdalena; Lee, Wonchoel

    2012-06-01

    The objective of the study was to analyze constantlyhighly expressed proteins as a function of elevated midultraviolet (UVB, 280-315 nm) radiation in Tigriopus japonicus sensu lato ( T. japonicus s.l). We also analyzed associations between kinetics of radiation avoidance, measured as a covered distance per time unit, and highly expressed proteins. The obtained results indicate an increase in T. japonicus s.l. mobility between the control (no radiation) and mild UV radiation levels (15 kJ·m-2). Two-dimensional gel electrophoresis combined with MALDI-MS-MS resulted in 2D protein map comprising of 686 protein spots, of which 19 were identified as highly expressed proteins across all experimental conditions. Obtained results indicate that calpain, vitellogenin, and collagenase are housekeeping protein that are expressed at a constant level independently of environmental changes and that adoption of a locomotive system for the avoidance of a UV source may be, at least partially, supported by hepatopancreas-driven metabolism.

  12. Chronic stress is associated with pain precipitation and elevation in DeltaFosb expression

    OpenAIRE

    Hang eWang; Xinrong eTao; Si-Ting eHuang; Liang eWu; Hui-Li eTang; Ying eSong; Gongliang eZhang; Yong-Mei eZhang

    2016-01-01

    A number of acute or repeated stimuli can induce expression of DeltaFosB (ΔFosB), a transcription factor derived from the fosB gene (an osteosarcoma viral oncogene) via alternative splicing. ΔFosB protein is currently viewed as a 'molecular switch' to repeated stimuli that gradually converts acute responses into relatively stable adaptations underlying long-term neural and behavioral plasticity. ΔFosB has received extensive attention in drug addition, depression and stress adaptation, but cha...

  13. Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue.

    Science.gov (United States)

    Koban, Michael; Swinson, Kevin L

    2005-07-01

    A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing approximately 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.

  14. Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis.

    Science.gov (United States)

    Greaves, Erin; Grieve, Kelsey; Horne, Andrew W; Saunders, Philippa T K

    2014-09-01

    Ovarian suppression is a common treatment for endometriosis-associated pelvic pain. Its exact mechanism of action is poorly understood, although it is assumed to reflect reduced production/action of estrogens. The objective of the study was to measure the expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis and to investigate whether estrogens alter nociceptive gene expression in human sensory neurons. The study was performed using human tissue analysis and cell culture. The study was conducted at a university research institute. Peritoneal biopsies were obtained from women with CPP and endometriosis (n = 12), CPP and no endometriosis (n = 10), and no pain or endometriosis (n = 5). Endometriosis lesions were obtained from women with endometriosis (n = 18). mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in human tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens. TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P endometriosis lesions (P endometriosis (P endometriosis-associated pain. Strategies directly targeting ion channels may offer an alternative option for the management of CPP.

  15. Doxorubicin Activates Hepatitis B Virus Replication by Elevation of p21 (Waf1/Cip1 and C/EBPα Expression.

    Directory of Open Access Journals (Sweden)

    Yu-Fang Chen

    Full Text Available Hepatitis B virus reactivation is an important medical issue in cancer patients who undergo systemic chemotherapy. Up to half of CHB carriers receiving chemotherapy develop hepatitis and among these cases a notable proportion are associated with HBV reactivation. However, the molecular mechanism(s through which various chemotherapeutic agents induce HBV reactivation is not yet fully understood. In this study, we investigated the role of the cell cycle regulator p21 (Waf1/Cip1 in the modulation of HBV replication when a common chemotherapeutic agent, doxorubicin, is present. We showed that p21 expression was increased by doxorubicin treatment. This elevation in p21 expression enhanced the expression of CCAAT/enhancer-binding protein α (C/EBPα; such an increase is likely to promote the binding of C/EBPα to the HBV promoter, which will contribute to the activation of HBV replication. Our current study thus reveals the mechanism underlying doxorubicin modulation of HBV replication and provides an increased understanding of HBV reactivation in CHB patients who are receiving systemic chemotherapy.

  16. Elevated Immune Gene Expression Is Associated with Poor Reproductive Success of Urban Blue Tits

    Directory of Open Access Journals (Sweden)

    Pablo Capilla-Lasheras

    2017-06-01

    Full Text Available Urban and forest habitats differ in many aspects that can lead to modifications of the immune system of wild animals. Altered parasite communities, pollution, and artificial light at night in cities have been associated with exacerbated inflammatory responses, with possibly negative fitness consequences, but few data are available from free-living animals. Here, we investigate how urbanization affects major immune pathways and experimentally test potentially contributing factors in blue tits (Cyanistes caeruleus from an urban and forest site. We first compared breeding adults by quantifying the mRNA transcript levels of proteins associated with anti-bacterial, anti-malarial (TLR4, LY86 and anti-helminthic (Type 2 transcription factor GATA3 immune responses. Adult urban and forest blue tits differed in gene expression, with significantly increased TLR4 and GATA3, but not LY86, in the city. We then experimentally tested whether these differences were environmentally induced by cross-fostering eggs between the sites and measuring mRNA transcripts in nestlings. The populations differed in reduced reproductive success, with a lower fledging success and lower fledgling weight recorded at the urban site. This mirrors the findings of our twin study reporting that the urban site was severely resource limited when compared to the forest. Because of low urban survival, robust gene expression data were only obtained from nestlings reared in the forest. Transcript levels in these nestlings showed no (TLR4, LY86, or weak (GATA3, differences according to their origin from forest or city nests, suggesting little genetic or maternal contribution to nestling immune transcript levels. Lastly, to investigate differences in parasite pressure between urban and forest sites, we measured the prevalence of malaria in adult and nestling blood. Prevalence was invariably high across environments and not associated with the transcript levels of the studied immune genes. Our

  17. Elevated production of melatonin in transgenic rice seeds expressing rice tryptophan decarboxylase.

    Science.gov (United States)

    Byeon, Yeong; Park, Sangkyu; Lee, Hyoung Yool; Kim, Young-Soon; Back, Kyoungwhan

    2014-04-01

    A major goal of plant biotechnology is to improve the nutritional qualities of crop plants through metabolic engineering. Melatonin is a well-known bioactive molecule with an array of health-promoting properties, including potent antioxidant capability. To generate melatonin-rich rice plants, we first independently overexpressed three tryptophan decarboxylase isogenes in the rice genome. Melatonin levels were altered in the transgenic lines through overexpression of TDC1, TDC2, and TDC3; TDC3 transgenic seed (TDC3-1) had melatonin concentrations 31-fold higher than those of wild-type seeds. In TDC3 transgenic seedlings, however, only a doubling of melatonin content occurred over wild-type levels. Thus, a seed-specific accumulation of melatonin appears to occur in TDC3 transgenic lines. In addition to increased melatonin content, TDC3 transgenic lines also had enhanced levels of melatonin intermediates including 5-hydroxytryptophan, tryptamine, serotonin, and N-acetylserotonin. In contrast, expression levels of melatonin biosynthetic mRNA did not increase in TDC3 transgenic lines, indicating that increases in melatonin and its intermediates in these lines are attributable exclusively to overexpression of the TDC3 gene. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Elevated expression of Ki-67 identifies aggressive prostate cancers but does not distinguish BRCA1 or BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Mitra, A V; Jameson, C; Barbachano, Y

    2010-01-01

    Prostate cancers in men with germline BRCA1 and BRCA2 mutations are more aggressive than morphologically similar cancers in men without these mutations. This study was performed to test the hypothesis that enhanced expression of Ki-67, as a surrogate of cell proliferation, is a characteristic...... feature of prostate cancers occurring in BRCA1 or BRCA2 mutation carriers. The study cohort comprised 20 cases of prostate cancer in mutation carriers and 126 control sporadic prostate cancers. Of the combined sample cohort, 65.7% stained only within malignant tissues while 0.7% stained in both malignant...... a background of BRCA1 or BRCA2 mutations or as sporadic disease. The data suggest that, since elevated Ki-67 does not distinguish prostate cancers occurring in BRCA1 or BRCA2 mutation carriers from sporadic prostatic malignancies, the effects of these genetic mutations are probably independent. While all...

  19. Doublecortin-like kinase 1 is elevated serologically in pancreatic ductal adenocarcinoma and widely expressed on circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Dongfeng Qu

    Full Text Available Doublecortin-like kinase 1 (DCLK1 is a putative pancreatic stem cell marker and is upregulated in pancreatic cancer, colorectal cancer, and many other solid tumors. It marks tumor stem cells in mouse models of intestinal neoplasia. Here we sought to determine whether DCLK1 protein can be detected in the bloodstream and if its levels in archived serum samples could be quantitatively assessed in pancreatic cancer patients. DCLK1 specific ELISA, western blotting, and immunohistochemical analyses were used to determine expression levels in the serum and staining intensity in archived tumor tissues of pancreatic ductal adenocarcinoma (PDAC patients and in pancreatic cancer mouse models. DCLK1 levels in the serum were elevated in early stages of PDAC (stages I and II compared to healthy volunteers (normal controls. No differences were observed between stages III/IV and normal controls. In resected surgical tissues, DCLK1 expression intensity in the stromal cells was significantly higher than that observed in tumor epithelial cells. Circulating tumor cells were isolated from KPCY mice and approximately 52% of these cells were positive for Dclk1 staining. Dclk1 levels in the serum of KPC mice were also elevated. We have previously demonstrated that DCLK1 plays a potential role in regulating epithelial mesenchymal transition (EMT. Given the increasingly recognized role of EMT derived stem cells in cancer progression and metastasis, we hypothesize that DCLK1 may contribute to the metastatic process. Taken together, our results suggest that DCLK1 serum levels and DCLK1 positive circulating tumor cells should be further assessed for their potential diagnostic and prognostic significance.

  20. Elevation of HLA-G-expressing DC-10 cells in patients with gastric cancer.

    Science.gov (United States)

    Xu, Dan-Ping; Shi, Wei-Wu; Zhang, Tong-Tong; Lv, Hai-Yan; Li, Jing-Bo; Lin, Aifen; Yan, Wei-Hua

    2016-09-01

    DC-10 is a distinct subset of human tolerogenic dendritic cells (DCs) which express high levels of human leukocyte antigen-G (HLA-G). DC-10 could induce adaptive type 1 regulatory T cells through the IL-10 dependent ILT4/HLA-G signaling pathway. However, the significance of DC-10 in malignancies remains unclear. In this study, the frequency and mean fluorescence intensity (MFI) of HLA-G+ DC-10 in the peripheral blood of 124 patients with gastric cancer (GC) and 130 normal controls was analyzed with flow cytometry. Plasma sHLA-G was analyzed with ELISA. Results showed both the percentages of peripheral HLA-G+ DC-10 (median: 0.13% vs 0.01%; pHLA-G on these cells (median: 310.0 vs 91.5; pHLA-G+ DC-10 in GC patients was strongly relative to the tumor grade (p=0.021). sHLA-G levels in GC patients were significantly higher than in healthy controls (median: 85.80U/ml vs 61.20U/ml; p0.05). However, the increased HLA-G+ DC-10, HLA-G MFI and plasma sHLA-G in patients with gastric cancer could be a diagnostic factor with the area under the ROC curve with 0.947 (pcancer, while more studies are necessary to illustrate the clinical relevance of DC-10 in cancer patients. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  1. Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

    International Nuclear Information System (INIS)

    Fang, Zhong-Ze; Zhang, Dunfang; Cao, Yun-Feng; Xie, Cen; Lu, Dan; Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao; Chen, Qianming; Chen, Yu; Wang, Haina; Gonzalez, Frank J.

    2016-01-01

    Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4 + naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4 + naive T cells.

  2. Cytokines Elevated in HIV Elite Controllers Reduce HIV ReplicationIn Vitroand Modulate HIV Restriction Factor Expression.

    Science.gov (United States)

    Jacobs, Evan S; Keating, Sheila M; Abdel-Mohsen, Mohamed; Gibb, Stuart L; Heitman, John W; Inglis, Heather C; Martin, Jeffrey N; Zhang, Jinbing; Kaidarova, Zhanna; Deng, Xutao; Wu, Shiquan; Anastos, Kathryn; Crystal, Howard; Villacres, Maria C; Young, Mary; Greenblatt, Ruth M; Landay, Alan L; Gange, Stephen J; Deeks, Steven G; Golub, Elizabeth T; Pillai, Satish K; Norris, Philip J

    2017-03-15

    A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4 + T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects. Four cytokines were elevated in ECs but not NCs or ART subjects: CCL14, CCL21, CCL27, and XCL1. In addition, median stromal cell-derived factor-1 (SDF-1) levels were 43% higher in ECs than in NCs. The combination of the five cytokines suppressed R5 and X4 virus replication in resting CD4 + T cells, and individually SDF-1β, CCL14, and CCL27 suppressed R5 virus replication, while SDF-1β, CCL21, and CCL14 suppressed X4 virus replication. Functional studies revealed that the combination of the five cytokines upregulated CD69 and CCR5 and downregulated CXCR4 and CCR7 on CD4 + T cells. The CD69 and CXCR4 effects were driven by SDF-1, while CCL21 downregulated CCR7. The combination of the EC-associated cytokines induced expression of the anti-HIV host restriction factors IFITM1 and IFITM2 and suppressed expression of RNase L and SAMHD1. These results identify a set of cytokines that are elevated in ECs and define their effects on cellular activation, HIV coreceptor expression, and innate restriction factor expression. This cytokine pattern may be a signature characteristic of HIV-1 elite control, potentially important for HIV therapeutic and curative strategies. IMPORTANCE Approximately 1% of people infected with HIV control virus replication without taking antiviral medications. These subjects, termed elite controllers (ECs), are known to have stronger immune responses targeting HIV than the typical HIV-infected subject, but the

  3. Elevated expression levels of lysyl oxidases protect against aortic aneurysm progression in Marfan syndrome.

    Science.gov (United States)

    Busnadiego, O; Gorbenko Del Blanco, D; González-Santamaría, J; Habashi, J P; Calderon, J F; Sandoval, P; Bedja, D; Guinea-Viniegra, J; Lopez-Cabrera, M; Rosell-Garcia, T; Snabel, J M; Hanemaaijer, R; Forteza, A; Dietz, H C; Egea, G; Rodriguez-Pascual, F

    2015-08-01

    Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic dissections. The condition is caused by mutations in the gene encoding fibrillin-1, an essential component in the formation of elastic fibers. While experimental findings in animal models of the disease have shown the involvement of transforming growth factor-β (TGF-β)- and angiotensin II-dependent pathways, alterations in the vascular extracellular matrix (ECM) may also play a role in the onset and progression of the aortic disease. Lysyl oxidases (LOX) are extracellular enzymes, which initiates the formation of covalent cross-linking of collagens and elastin, thereby contributing to the maturation of the ECM. Here we have explored the role of LOX in the formation of aortic aneurysms in MFS. We show that aortic tissue from MFS patients and MFS mouse model (Fbn1(C1039G/+)) displayed enhanced expression of the members of the LOX family, LOX and LOX-like 1 (LOXL1), and this is associated with the formation of mature collagen fibers. Administration of a LOX inhibitor for 8weeks blocked collagen accumulation and aggravated elastic fiber impairment, and these effects correlated with the induction of a strong and rapidly progressing aortic dilatation, and with premature death in the more severe MFS mouse model, Fbn1(mgR/mgR), without any significant effect on wild type animals. This detrimental effect occurred preferentially in the ascending portion of the aorta, with little or no involvement of the aortic root, and was associated to an overactivation of both canonical and non-canonical TGF-β signaling pathways. The blockade of angiotensin II type I receptor with losartan restored TGF-β signaling activation, normalized elastic fiber impairment and prevented the aortic dilatation induced by LOX inhibition in Fbn1(C1039G/+) mice. Our data indicate that LOX enzymes and LOX-mediated collagen accumulation play a critical protective role in aneurysm formation in MFS. Copyright © 2015 Elsevier

  4. Elevated Expression of Dkk-1 by Glucocorticoid Treatment Impairs Bone Regenerative Capacity of Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Kato, Toshiki; Khanh, Vuong Cat; Sato, Kazutoshi; Kimura, Kenichi; Yamashita, Toshiharu; Sugaya, Hisashi; Yoshioka, Tomokazu; Mishima, Hajime; Ohneda, Osamu

    2018-01-15

    Glucocorticoids are steroid hormones used as anti-inflammatory treatments. However, this strong immunomodulation causes undesirable side effects that impair bones, such as osteoporosis. Glucocorticoid therapy is a major risk factor for developing steroid-induced osteonecrosis of the femur head (ONFH). Since ONFH is incurable, therapy with mesenchymal stem cells (MSCs) that can differentiate into osteoblasts are a first-line choice. Bone marrow-derived MSCs (BM-MSCs) are often used as a source of stem cell therapy for ONFH, but their proliferative activity is impaired after steroid treatment. Adipose tissue-derived MSCs (AT-MSCs) may be an attractive alternative source; however, it is unknown whether AT-MSCs from steroid-induced ONFH (sAT-MSCs) have the same differentiation ability as BM-MSCs or normal AT-MSCs (nAT-MSCs). In this study, we demonstrate that nAT-MSCs chronically exposed to glucocorticoids show lower alkaline phosphatase activity leading to reduced osteogenic differentiation ability. This impaired osteogenesis is mediated by high expression of Dickkopf1 (Dkk-1) that inhibits wnt/β-catenin signaling. Increased Dkk-1 also causes impaired osteogenesis along with reductions in bone regenerative capacity in sAT-MSCs. Of note, plasma Dkk-1 levels are elevated in steroid-induced ONFH patients. Collectively, our findings suggest that glucocorticoid-induced expression of Dkk-1 could be a key factor in modulating the differentiation ability of MSCs used for ONFH and other stem cell therapies.

  5. The polymorphism and haplotypes of PIN1 gene are associated with the risk of lung cancer in Southern and Eastern Chinese populations.

    Science.gov (United States)

    Lu, Jiachun; Yang, Lei; Zhao, Hongjun; Liu, Bin; Li, Yinyan; Wu, Hongxia; Li, Qingchu; Zeng, Bohang; Wang, Yunnan; Ji, Weidong; Zhou, Yifeng

    2011-11-01

    Peptidyl-prolyl cis/trans isomerase (PPIase), PIN1, has been found to be a critical catalyst that involves in multiple oncogenic signaling pathways. Recently, several putative functional polymorphisms of the PIN1 gene have been identified to be associated with cancer risk. In this study, we tested the hypothesis that two common polymorphisms, c.-842G>C (rs2233678) and c.-667C>T (rs2233679), in the PIN1 promoter are associated with risk of lung cancer. In two independent case-control studies of 1,559 lung cancer cases and 1,679 controls conducted in Southern and Eastern Chinese population, we found that compared with the most common c.-842GG genotype, the carriers of c.-842C variant genotypes (GC + CC) had a decreased risk of lung cancer (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.51-0.78, p = 1.13 × 10(-5) ). Although no association was observed between the c.-667C>T polymorphism and cancer risk, we found that the haplotype "C-C" had a greater protective effect (OR = 0.39, 95% CI = 0.23-0.67, p = 5.03 × 10(-4) ). The stratification analysis showed that the protective role of c.-842C variants was more pronounced in current smokers (p = 4.45 × 10(-5) ), especially in male smokers (p = 6.71 × 10(-6) ) and in those who smoked more than 20 pack-years (p = 2.30 × 10(-5) ) and the c.-842C variant genotypes interacted with smoking status (P(interaction) = 0.019) or pack-years smoked (P(interaction) = 0.008) on reducing cancer risk. Further functional assay revealed that the c.-842C variant allele had a lower transcription activity in luciferase assay and a lower DNA-binding ability with nuclear proteins, and low transcription activity in western blot assay. In conclusions, our data suggest that functional c.-842C variants and haplotype "C-C" in the PIN1 promoter contribute to decreased risk of lung cancer by diminishing the promoter activity, which may be susceptibility biomarkers for lung cancer. © 2011 Wiley Periodicals, Inc.

  6. Elevating your elevator talk

    Science.gov (United States)

    An important and often overlooked item that every early career researcher needs to do is compose an elevator talk. The elevator talk, named because the talk should not last longer than an average elevator ride (30 to 60 seconds), is an effective method to present your research and yourself in a clea...

  7. Differential effects of Pseudomonas mendocina and Glomus intraradices on lettuce plants physiological response and aquaporin PIP2 gene expression under elevated atmospheric CO2 and drought.

    Science.gov (United States)

    Alguacil, Maria Del Mar; Kohler, Josef; Caravaca, Fuensanta; Roldán, Antonio

    2009-11-01

    Arbuscular mycorrhizal (AM) symbiosis and plant-growth-promoting rhizobacterium (PGPR) can alleviate the effects of water stress in plants, but it is unknown whether these benefits can be maintained at elevated CO2. Therefore, we carried out a study where seedlings of Lactuca sativa were inoculated with the AM fungus (AMF) Glomus intraradices N.C. Schenk & G.S. Sm. or the PGPR Pseudomonas mendocina Palleroni and subjected to two levels of watering and two levels of atmospheric CO2 to ascertain their effects on plant physiological parameters and gene expression of one PIP aquaporin in roots. The inoculation with PGPR produced the greatest growth in lettuce plants under all assayed treatments as well as the highest foliar potassium concentration and leaf relative water content under elevated [CO2] and drought. However, under such conditions, the PIP2 gene expression remained almost unchanged. G. intraradices increased significantly the AMF colonization, foliar phosphorus concentration and leaf relative water content in plants grown under drought and elevated [CO2]. Under drought and elevated [CO2], the plants inoculated with G. intraradices showed enhanced expression of the PIP2 gene as compared to P. mendocina or control plants. Our results suggest that both microbial inoculation treatments could help to alleviate drought at elevated [CO2]. However, the PIP2 gene expression was increased only by the AMF but not by the PGPR under these conditions.

  8. Auxin modulates the enhanced development of root hairs in Arabidopsis thaliana (L.) Heynh. under elevated CO(2).

    Science.gov (United States)

    Niu, Yaofang; Jin, Chongwei; Jin, Gulei; Zhou, Qingyan; Lin, Xianyong; Tang, Caixian; Zhang, Yongsong

    2011-08-01

    Root hairs may play a critical role in nutrient acquisition of plants grown under elevated CO(2) . This study investigated how elevated CO(2) enhanced the development of root hairs in Arabidopsis thaliana (L.) Heynh. The plants under elevated CO(2) (800 µL L(-1)) had denser and longer root hairs, and more H-positioned cells in root epidermis than those under ambient CO(2) (350 µL L(-1)). The elevated CO(2) increased auxin production in roots. Under elevated CO(2) , application of either 1-naphthoxyacetic acid (1-NOA) or N-1-naphthylphthalamic acid (NPA) blocked the enhanced development of root hairs. The opposite was true when the plants under ambient CO(2) were treated with 1-naphthylacetic acid (NAA), an auxin analogue. Furthermore, the elevated CO(2) did not enhance the development of root hairs in auxin-response mutants, axr1-3, and auxin-transporter mutants, axr4-1, aux1-7 and pin1-1. Both elevated CO(2) and NAA application increased expressions of caprice, triptychon and rho-related protein from plants 2, and decreased expressions of werewolf, GLABRA2, GLABRA3 and the transparent testa glabra 1, genes related to root-hair development, while 1-NOA and NPA application had an opposite effect. Our study suggests that elevated CO(2) enhanced the development of root hairs in Arabidopsis via the well-characterized auxin signalling and transport that modulate the initiation of root hairs and the expression of its specific genes. © 2011 Blackwell Publishing Ltd.

  9. Elevation of WNT5A expression in polyp formation in Lkb1+/- mice and Peutz-Jeghers syndrome.

    Science.gov (United States)

    Lai, Cecilia; Robinson, James; Clark, Sue; Stamp, Gordon; Poulsom, Richard; Silver, Andrew

    2011-04-01

    Peutz-Jeghers syndrome (PJS) is a rare, inherited disease caused by germline mutation of the LKB1 gene. Patients with PJS develop characteristic polyps in the digestive tract and carry an elevated risk of cancers in multiple organs, including the intestinal tract. While LKB1 is capable of phosphorylating AMPK and regulates the mTOR pathway, it is also known to be a multitasking protein that can influence other cellular processes, including cell polarity. We hypothesized that there may be other biological pathways directly or indirectly affected by the loss of LKB1 in PJS and aimed to investigate this possibility through transcriptional profiling of polyps harvested from an Lkb1(+/-) mouse model of PJS and from PJS patients. We identified alterations in the mRNA level of a wide range of genes, including some that are involved in Wnt signalling (Wnt5a, Wif1, Dixdc1, Wnt11, Ccnd1, and Ccnd2), although we did not observe nuclear localization of β-catenin in over 93 human PJS intestinal polyps or in 24 gastric polyps from Lkb1(+/-) mice. Among these genes, WNT5A, a non-canonical and non-transforming Wnt, is consistently up-regulated in both Lkb1(+/-) mice and human PJS polyps at a high level. We performed in situ hybridization to further define the spatial expression pattern of WNT5A and observed a strong signal in the stroma of mouse and human polyps compared to no or very low expression in the mucosa. Our findings indicate that WNT5A plays an important role in PJS polyposis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  10. Antidepressants elevate GDNF expression and release from C₆ glioma cells in a β-arrestin1-dependent, CREB interactive pathway.

    Science.gov (United States)

    Golan, Moran; Schreiber, Gabriel; Avissar, Sofia

    2011-11-01

    Glial cell line-derived neurotrophic factor (GDNF), essential for neuronal survival, plasticity and development, has been implicated in the mechanism of action of antidepressant drugs (ADs). β-arrestin1, a member of the arrestin protein family, was found to play a role in AD mechanism of action. The present study aimed at evaluating whether the effect of ADs on GDNF in C6 rat glioma cells is exerted through a β-arrestin1-dependent, CREB-interactive pathway. For chronic treatment, C6 rat glioma cells were treated for 3 d with different classes of ADs: imipramine - a non-selective monoamine reuptake inhibitor, citalopram - a serotonin selective reuptake inhibitor (SSRI) or desipramine - a norepinephrine selective reuptake inhibitor (NSRI) and compared to mood stabilizers (lithium and valproic acid) or to the antipsychotic haloperidol. Only ADs significantly elevated β-arrestin1 levels in the cytosol, while reducing phospho-β-arrestin1 levels in the cell nuclear fraction. ADs significantly increased both GDNF expression and release from the cells, but were unable to induce such effects in β-arrestin1 knock-down cells. Chronic AD treatment significantly increased CREB phosphorylation without altering the level of total CREB in the nuclear fraction of the cells. Moreover, treatment with ADs significantly increased β-arrestin1/CREB interaction. These findings support the involvement of β-arrestin1 in the mechanism of action of ADs. We suggest that following AD treatment, β-arrestin1 generates a transcription complex involving CREB essential for GDNF expression and release, thus enhancing GDNF's neuroprotective action that promotes cellular survival and plasticity when the survival and function of neurons is compromised as occurs in major depression.

  11. Interactive Effects of Elevated [CO2] and Water Stress on Physiological Traits and Gene Expression during Vegetative Growth in Four Durum Wheat Genotypes

    Directory of Open Access Journals (Sweden)

    Susan Medina

    2016-11-01

    Full Text Available The interaction of elevated [CO2] and water stress will have an effect on the adaptation of durum wheat to future climate scenarios. For the Mediterranean basin these scenarios include the rising occurrence of water stress during the first part of the crop cycle. In this study, we evaluated the interactive effects of elevated [CO2] and moderate to severe water stress during the first part of the growth cycle on physiological traits and gene expression in four modern durum wheat genotypes. Physiological data showed that elevated [CO2] promoted plant growth but reduced N content. This was related to a down-regulation of Rubisco and N assimilation genes and up-regulation of genes that take part in C-N remobilization, which might suggest a higher N efficiency. Water restriction limited the stimulation of plant biomass under elevated [CO2], especially at severe water stress, while stomatal conductance and carbon isotope signature revealed a water saving strategy. Transcript profiles under water stress suggested an inhibition of primary C fixation and N assimilation. Nevertheless, the interactive effects of elevated [CO2] and water stress depended on the genotype and the severity of the water stress, especially for the expression of drought stress-responsive genes such as dehydrins, catalase and superoxide dismutase. The network analysis of physiological traits and transcript levels showed coordinated shifts between both categories of parameters and between C and N metabolism at the transcript level, indicating potential genes and traits that could be used as markers for early vigor in durum wheat under future climate change scenarios. Overall the results showed that greater plant growth was linked to an increase in N content and expression of N metabolism-related genes and down-regulation of genes related to the antioxidant system. The combination of elevated [CO2] and severe water stress was highly dependent on the genotypic variability, suggesting

  12. Interactive Effects of Elevated [CO2] and Water Stress on Physiological Traits and Gene Expression during Vegetative Growth in Four Durum Wheat Genotypes.

    Science.gov (United States)

    Medina, Susan; Vicente, Rubén; Amador, Amaya; Araus, José Luis

    2016-01-01

    The interaction of elevated [CO 2 ] and water stress will have an effect on the adaptation of durum wheat to future climate scenarios. For the Mediterranean basin these scenarios include the rising occurrence of water stress during the first part of the crop cycle. In this study, we evaluated the interactive effects of elevated [CO 2 ] and moderate to severe water stress during the first part of the growth cycle on physiological traits and gene expression in four modern durum wheat genotypes. Physiological data showed that elevated [CO 2 ] promoted plant growth but reduced N content. This was related to a down-regulation of Rubisco and N assimilation genes and up-regulation of genes that take part in C-N remobilization, which might suggest a higher N efficiency. Water restriction limited the stimulation of plant biomass under elevated [CO 2 ], especially at severe water stress, while stomatal conductance and carbon isotope signature revealed a water saving strategy. Transcript profiles under water stress suggested an inhibition of primary C fixation and N assimilation. Nevertheless, the interactive effects of elevated [CO 2 ] and water stress depended on the genotype and the severity of the water stress, especially for the expression of drought stress-responsive genes such as dehydrins, catalase, and superoxide dismutase. The network analysis of physiological traits and transcript levels showed coordinated shifts between both categories of parameters and between C and N metabolism at the transcript level, indicating potential genes and traits that could be used as markers for early vigor in durum wheat under future climate change scenarios. Overall the results showed that greater plant growth was linked to an increase in N content and expression of N metabolism-related genes and down-regulation of genes related to the antioxidant system. The combination of elevated [CO 2 ] and severe water stress was highly dependent on the genotypic variability, suggesting

  13. Elevation of HO-1 Expression Mitigates Intestinal Ischemia-Reperfusion Injury and Restores Tight Junction Function in a Rat Liver Transplantation Model

    Directory of Open Access Journals (Sweden)

    Xinjin Chi

    2015-01-01

    Full Text Available Aims. This study was aimed at investigating whether elevation of heme oxygenase-1 (HO-1 expression could lead to restoring intestinal tight junction (TJ function in a rat liver transplantation model. Methods. Intestinal mucosa injury was induced by orthotopic autologous liver transplantation (OALT on male Sprague-Dawley rats. Hemin (a potent HO-1 activator and zinc-protoporphyrin (ZnPP, a HO-1 competitive inhibitor, were separately administered in selected groups before OALT. The serum and intestinal mucosa samples were collected at 8 hours after the operation for analysis. Results. Hemin pretreatment significantly reduced the inflammation and oxidative stress in the mucosal tissue after OALT by elevating HO-1 protein expression, while ZnPP pretreatment aggravated the OALT mucosa injury. Meanwhile, the restriction on the expression of tight junction proteins zonula occludens-1 and occludin was removed after hemin pretreatment. These molecular events led to significant improvement on intestinal barrier function, which was proved to be through increasing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2 and reducing nuclear translocation of nuclear factor kappa-B (NF-κB in intestinal injured mucosa. Summary. Our study demonstrated that elevation of HO-1 expression reduced the OALT-induced intestinal mucosa injury and TJ dysfunction. The HO-1 protective function was likely mediated through its effects of anti-inflammation and antioxidative stress.

  14. Elevation of HO-1 Expression Mitigates Intestinal Ischemia-Reperfusion Injury and Restores Tight Junction Function in a Rat Liver Transplantation Model

    Science.gov (United States)

    Chi, Xinjin; Yao, Weifeng; Xia, Hua; Jin, Yi; Li, Xi; Cai, Jun; Hei, Ziqing

    2015-01-01

    Aims. This study was aimed at investigating whether elevation of heme oxygenase-1 (HO-1) expression could lead to restoring intestinal tight junction (TJ) function in a rat liver transplantation model. Methods. Intestinal mucosa injury was induced by orthotopic autologous liver transplantation (OALT) on male Sprague-Dawley rats. Hemin (a potent HO-1 activator) and zinc-protoporphyrin (ZnPP, a HO-1 competitive inhibitor), were separately administered in selected groups before OALT. The serum and intestinal mucosa samples were collected at 8 hours after the operation for analysis. Results. Hemin pretreatment significantly reduced the inflammation and oxidative stress in the mucosal tissue after OALT by elevating HO-1 protein expression, while ZnPP pretreatment aggravated the OALT mucosa injury. Meanwhile, the restriction on the expression of tight junction proteins zonula occludens-1 and occludin was removed after hemin pretreatment. These molecular events led to significant improvement on intestinal barrier function, which was proved to be through increasing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and reducing nuclear translocation of nuclear factor kappa-B (NF-κB) in intestinal injured mucosa. Summary. Our study demonstrated that elevation of HO-1 expression reduced the OALT-induced intestinal mucosa injury and TJ dysfunction. The HO-1 protective function was likely mediated through its effects of anti-inflammation and antioxidative stress. PMID:26064429

  15. Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells

    Science.gov (United States)

    Zhuang, Yan; Nguyen, Hong T.; Burow, Matthew E.; Zhuo, Ying; El-Dahr, Samir S.; Yao, Xiao; Cao, Subing; Flemington, Erik K.; Nephew, Kenneth P.; Fang, Fang; Collins-Burow, Bridgette; Rhodes, Lyndsay V.; Yu, Qiang; Jayawickramarajah, Janarthanan; Shan, Bin

    2015-01-01

    Epigenetic regulation of gene expression is critical to phenotypic maintenance and transition of human breast cancer cells. HOX antisense intergenic RNA (HOTAIR) is a long intergenic non-coding RNA that epigenetically represses gene expression via recruitment of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase. Elevated expression of HOTAIR promotes progression of breast cancer. In the current study we examined the expression and function of HOTAIR in MCF-7-TNR cells, a derivative of the luminal-like breast cancer cell line MCF-7 that acquired resistance to TNF-α-induced cell death. The expression of HOTAIR, markers of the luminal-like and basal-like subtypes, and growth were compared between MCF-7 and MCF-7-TNR cells. These variables were further assessed upon inhibition of HOTAIR, EZH2, p38 MAPK, and SRC kinase in MCF-7-TNR cells. When compared with MCF-7 cells, MCF-7-TNR cells exhibited an increase in the expression of HOTAIR, which correlated with characteristics of a luminal-like to basal-like transition as evidenced by dysregulated gene expression and accelerated growth. MCF-7-TNR cells exhibited reduced suppressive histone H3 lysine27 trimethylation on the HOTAIR promoter. Inhibition of HOTAIR and EZH2 attenuated the luminal-like to basal-like transition in terms of gene expression and growth in MCF-7-TNR cells. Inhibition of p38 and SRC diminished HOTAIR expression and the basal-like phenotype in MCF-7-TNR cells. HOTAIR was robustly expressed in the native basal-like breast cancer cells and inhibition of HOTAIR reduced the basal-like gene expression and growth. Our findings suggest HOTAIR-mediated regulation of gene expression and growth associated with the basal-like phenotype of breast cancer cells. PMID:25328122

  16. Impact of elevated H2S on metabolite levels, activity of enzymes and expression of genes involved in cysteine metabolism

    NARCIS (Netherlands)

    Riemenschneider, A; Nikiforova, V.; Hoefgen, R; De Kok, LJ; Papenbrock, J

    The effects of elevated atmospheric hydrogen sulfide (H2S) levels (0.25, 0.5, and 0.75 mu l l(-1)) have been investigated in a short-term exposure experiment (3-48 h) on the model plant Arabidopsis thaliana (L.) Heynh. in comparison to untreated control plants. The most pronounced effects of H2S

  17. Elevated Expression of Ox2R in Cervical Cancers and Placentas of Uyghur Women in Xinjiang, China

    OpenAIRE

    Taximaimaiti, Reyisha; Abuliken, Xiekelai; Maihemuti, Muzhapaer; Abudujilile, Dilinuer; Abudulimu, Haimiti

    2016-01-01

    Objective: Cervical cancer is one of the major causes of mortality of Uyghur women in Xinjiang, China. Although increased expression of orexin receptor (OxR), known to be strongly expressed in human placenta, has a proven relation to some cancers, there have been few studies of cervical cancer. Thus, we explored this question by evaluating the expression of orexin receptor as a biomarker for screening early stage of cervical cancer in Uyghur women with highest occurrence rate of cervical canc...

  18. Nitrogen-efficient and nitrogen-inefficient Indian mustard cultivars show differential protein expression in response to elevated CO2 and low nitrogen

    Directory of Open Access Journals (Sweden)

    Peerjada Yasir Yousof

    2016-07-01

    Full Text Available Carbon (C and nitrogen (N are two essential elements that influence plant growth and development. The C and N metabolic pathways influence each other to affect gene expression, but little is known about which genes are regulated by interaction between C and N or the mechanisms by which the pathways interact. In the present investigation, proteome analysis of N-efficient and N-inefficient Indian mustard, grown under varied combinations of low-N, sufficient-N, ambient [CO2] and elevated [CO2] was carried out to identify proteins and the encoding genes of the interactions between C and N. Two-dimensional gel electrophoresis (2-DE revealed 158 candidate protein spots. Among these, 72 spots were identified by matrix-assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF. The identified proteins are related to various molecular processes including photosynthesis, energy metabolism, protein synthesis, transport and degradation, signal transduction, nitrogen metabolism and defense to oxidative, water and heat stresses. Identification of proteins like PII-like protein, cyclophilin, elongation factor-TU, oxygen-evolving enhancer protein and rubisco activase offers a peculiar overview of changes elicited by elevated [CO2], providing clues about how N-efficient cultivar of Indian mustard adapt to low N supply under elevated [CO2] conditions. This study provides new insights and novel information for a better understanding of adaptive responses to elevated [CO2] under N deficiency in Indian mustard.

  19. The human megakaryocytic cell line UT-7/TPO responds to platelet agonists with intracellular Ca2+ elevation and P-selectin expression.

    Science.gov (United States)

    Kawaguchi, Tatsuya; Hashimoto, Ryuji; Nawa, Katsuhiko; Yokota, Hiroshi

    2011-05-01

    Megakaryocytes have several signal transduction cascades that are similar, but not identical to platelet activation signals. In order to understand platelet signals in detail, it is useful to compare the similarities and/or differences between platelets and megakaryocytes. We evaluated platelet activation signals related to three kinds of Gq protein-coupled receptors using the megakaryocytic cell line UT-7/TPO. It was found that UT-7/TPO responded to thrombin, resulting in a continuous elevation of the [Ca2+]i (intracellular Ca2+) and P-selectin expression on the surface of the cells. Activation of integrin αIIbβ3 and thromboxane generation was not detected by any of the three stimulations. Taken together, although strong [Ca2+]i elevation by thrombin stimulation caused further P-selection expression, we could detect [Ca2+]i elevation, which is thought to be the individual signals through the thrombin, thromboxane A2 or ADP receptor, without considering the secondary signalling caused by αIIbβ3 activation and the arachidonic acid cascade using UT-7/TPO.

  20. Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer

    International Nuclear Information System (INIS)

    Zhang, Chunhui; Hao, Li; Wang, Liang; Xiao, Yichuan; Ge, Hailiang; Zhu, Zhenya; Luo, Yunbao; Zhang, Yi; Zhang, Yanyun

    2010-01-01

    Insulin-like growth factor-I receptor (IGFIR) has been shown to regulate the tumor development. The objective of the current study is to determine the association of IGFIR with lymph node metastasis and to explore the related mechanism in human colorectal cancer in clinic. In a random series of 98 colorectal cancer patients, the expressions of IGFIR, vascular endothelial growth factor (VEGF) and VEGF-C were investigated by immunohistochemistry, and the association of these expressions with lymph node metastasis was statistically analyzed. The expressions of VEGF and VEGF-C in colorectal cancer cells stimulated with IGF-I were also examined by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Higher rates of IGFIR (46%), VEGF (53%), and VEGF-C (46%) expression were found in colorectal cancer tissues than in normal and colorectal adenoma tissues. These expressions were significantly associated with clinicopathologic factors and lymph node status. We also found the concomitant high expressions of IGFIR/VEGF (P < 0.001) and IGFIR/VEGF-C (P = 0.001) had a stronger correlation with lymph node metastasis than did each alone or both low expressions. In addition, IGF-I could effectively induce the VEGF and VEGF-C mRNA expression and protein secretion in colorectal cancer cells expressing IGFIR molecules. Moreover, Patients who had strong staining for IGFIR, VEGF and VEGF-C showed significantly less favorable survival rates compared with patients who had low staining for these molecules (P < 0.001). The survival rates of patients who were both high expression of IGFIR/VEGF and IGFIR/VEGF-C also were significantly lower compared with patients who were negative or one of high expression of these molecules (P < 0.001). Together the findings indicated for the first time that simultaneous examination of the expressions of IGFIR, VEGF and VEGF-C will benefit the diagnosis of lymph node metastasis in order to assay the

  1. Elevated atherosclerosis-related gene expression, monocyte activation and microparticle-release are related to increased lipoprotein-associated oxidative stress in familial hypercholesterolemia.

    Science.gov (United States)

    Hjuler Nielsen, Morten; Irvine, Helle; Vedel, Simon; Raungaard, Bent; Beck-Nielsen, Henning; Handberg, Aase

    2015-01-01

    Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypothesis that elevated oxLDL-C induce proinflammatory monocytes and increased release of monocyte-derived microparticles (MMPs), as well as up-regulation of CD36, chemokine receptors and proinflammatory factors through CD36-dependent pathways and that this is associated with accelerated atherosclerosis in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX). We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT) thickness were measured by ultrasonography. Monocyte classification and MMP analysis were performed by flow cytometry. Monocyte expression of genes involved in atherosclerosis was determined by quantitative PCR. IMT and oxLDL-C were increased in FH subjects, especially in the presence of ATX. In addition, FH subjects had elevated proportions of intermediate CD14++CD16+ monocytes and higher circulating MMP levels. Stepwise linear regression identified oxLDL-C, gender and intermediate monocytes as predictors of MMPs. Monocyte expression of pro-atherogenic and pro-inflammatory genes regulated by oxLDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT. Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly in the presence of ATX, by inducing pro-inflammatory monocytes and increased release of MMPs along with elevated monocyte expression of oxLDL-C-induced atherosclerosis-related genes.

  2. Elevated atherosclerosis-related gene expression, monocyte activation and microparticle-release are related to increased lipoprotein-associated oxidative stress in familial hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Morten Hjuler Nielsen

    Full Text Available Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C through a CD36-dependent mechanism. The aim of this study was to investigate the hypothesis that elevated oxLDL-C induce proinflammatory monocytes and increased release of monocyte-derived microparticles (MMPs, as well as up-regulation of CD36, chemokine receptors and proinflammatory factors through CD36-dependent pathways and that this is associated with accelerated atherosclerosis in subjects with heterozygous familial hypercholesterolemia (FH, in particular in the presence of Achilles tendon xanthomas (ATX.We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT and Achilles tendon (AT thickness were measured by ultrasonography. Monocyte classification and MMP analysis were performed by flow cytometry. Monocyte expression of genes involved in atherosclerosis was determined by quantitative PCR. IMT and oxLDL-C were increased in FH subjects, especially in the presence of ATX. In addition, FH subjects had elevated proportions of intermediate CD14++CD16+ monocytes and higher circulating MMP levels. Stepwise linear regression identified oxLDL-C, gender and intermediate monocytes as predictors of MMPs. Monocyte expression of pro-atherogenic and pro-inflammatory genes regulated by oxLDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT.Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly in the presence of ATX, by inducing pro-inflammatory monocytes and increased release of MMPs along with elevated monocyte expression of oxLDL-C-induced atherosclerosis-related genes.

  3. Elevated Atherosclerosis-Related Gene Expression, Monocyte Activation and Microparticle-Release Are Related to Increased Lipoprotein-Associated Oxidative Stress in Familial Hypercholesterolemia

    Science.gov (United States)

    Hjuler Nielsen, Morten; Irvine, Helle; Vedel, Simon; Raungaard, Bent; Beck-Nielsen, Henning; Handberg, Aase

    2015-01-01

    Objective Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypothesis that elevated oxLDL-C induce proinflammatory monocytes and increased release of monocyte-derived microparticles (MMPs), as well as up-regulation of CD36, chemokine receptors and proinflammatory factors through CD36-dependent pathways and that this is associated with accelerated atherosclerosis in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX). Approach and Results We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT) thickness were measured by ultrasonography. Monocyte classification and MMP analysis were performed by flow cytometry. Monocyte expression of genes involved in atherosclerosis was determined by quantitative PCR. IMT and oxLDL-C were increased in FH subjects, especially in the presence of ATX. In addition, FH subjects had elevated proportions of intermediate CD14++CD16+ monocytes and higher circulating MMP levels. Stepwise linear regression identified oxLDL-C, gender and intermediate monocytes as predictors of MMPs. Monocyte expression of pro-atherogenic and pro-inflammatory genes regulated by oxLDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT. Conclusions Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly in the presence of ATX, by inducing pro-inflammatory monocytes and increased release of MMPs along with elevated monocyte expression of oxLDL-C-induced atherosclerosis-related genes. PMID:25875611

  4. Significant immunohistochemical expression of human chorionic gonadotropin in high-grade osteosarcoma is rare, but may be associated with clinically elevated serum levels.

    Science.gov (United States)

    Lee, Anna F; Pawel, Bruce R; Sullivan, Lisa M

    2014-01-01

    Survival rates have plateaued at 70% for osteosarcoma. Proteins ectopically produced by malignant tumors may provide insight into new therapeutic targets. Osteosarcomas secreting human chorionic gonadotropin (hCG) have been suggested to have a worse prognosis. We examined the frequency of expression of β-subunit of hCG (β-hCG) in pretreatment osteosarcoma biopsies, and asked if it was associated with various clinical prognostic parameters, and the development of metastases. We subjected 51 pretreatment biopsies of high-grade osteosarcoma, from 51 patients, to β-hCG immunohistochemistry. In 19 of these patients, postchemotherapy metastatic biopsies also were examined for β-hCG expression. Clinical information (patient age, sex, survival status, and serum hCG in females only), and tumor characteristics (site, size, and presence of metastases) were recorded. The β-hCG positive and negative biopsies were separated and compared. Of 49 interpretable pretreatment biopsies, 28 (57%) showed positive cytoplasmic β-hCG expression: 27 with sparse positivity (1% of tumor cells) and 1 with frequent positivity (10% of tumor cells). The patient with frequent β-hCG positivity in her pretreatment biopsy had elevated serum hCG (88.2 mIU/mL) at diagnosis, decreasing to undetectable following chemotherapy and definitive resection. There was no difference in clinical parameters or rate of metastasis between β-hCG positive versus negative groups. Expression of β-hCG may be seen in high-grade osteosarcoma, but frequent β-hCG immunohistochemical expression by tumor cells, associated with clinically elevated serum β-hCG, is rare. Recognition that some nongerm cell tumors may produce β-hCG can prevent confusion with malignancies containing neoplastic syncytiotrophoblast cells, including germ cell and trophoblastic tumors.

  5. Expression Profile of Antioxidant Enzymes in Hemocytes from Freshwater Prawn Macrobrachium rosenbergii Exposed to an Elevated Level of Copper.

    Science.gov (United States)

    Guo, Hui; Miao, Yu-Tao; Xian, Jian-An; Qian, Kun; Wang, An-Li

    2015-10-01

    This study evaluated the expression level of antioxidant enzymes Cu, Zn-superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) in hemocytes of Macrobrachium rosenbergii exposed to copper by real-time PCR (qRT-PCR). Results showed that the mRNA expression of Cu, Zn-SOD increased to reach a peak at 6 h, then recovered to its normal level at 48 h. CAT expression level was significantly increased at 12 h and reached a peak at 24 h, but recovered to its normal level later. GPx expression level was significantly increased at 6 h and reached the peak at 12 h. GST expression level was significantly induced from 12 to 24 h and then dropped to its normal level at 48 h. These results indicated that antioxidant enzymes were inducible, possibly for removing excessive reactive oxygen species to protect prawn from oxidative stress.

  6. Elevated FOXC2 Expression Promotes Invasion of HCC Cell Lines and is Associated with Poor Prognosis in Hepatocellular Carcinoma.

    Science.gov (United States)

    Yang, Fang; Lv, Lizhi; Zhang, Kun; Cai, Qiucheng; Liu, Jianyong; Jiang, Yi

    2017-01-01

    Increasing evidence has indicated that Forkhead box protein C2 (FOXC2) plays an important role in carcinogenesis. However, the expression and the role of FOXC2 in hepatocellular carcinoma (HCC) have not been extensively studied. FOXC2 expression was analyzed by quantitative real-time polymerase chain reaction, Western blot analysis and immunohistochemistry in HCC tissue and cells. The relationship between FOXC2 expression and patient clinical significance and survival were assessed by Pearson's correlation and Kaplan-Meier analysis, respectively. Cell proliferation assays, colony formation assays, flow cytometric analysis and Transwell assays were employed to measure the effects of FOXC2 on HCC cells in vitro. The expression of FOXC2 was increased in HCC tissue, and high FOXC2 expression was associated with worse patient survival. Knockdown of FOXC2 inhibited HCC cell growth, migration, and invasion in vitro, as well as tumor growth. Furthermore, we found that activation of AKT-mediated MMP-2 and MMP-9 was involved in FOXC2 promoting an aggressive phenotype. Taken together, these findings demonstrate that FOXC2 is upregulated in HCC tissue and is associated with tumor size, vascular invasion and advanced TNM stage. Further investigation suggested that FOXC2 may play a vital role in promoting proliferation and invasion in HCC and serves as a novel therapeutic target in HCC. © 2017 The Author(s). Published by S. Karger AG, Basel.

  7. Thrombin induces Egr-1 expression in fibroblasts involving elevation of the intracellular Ca2+ concentration, phosphorylation of ERK and activation of ternary complex factor

    Directory of Open Access Journals (Sweden)

    Thiel Gerald

    2009-05-01

    Full Text Available Abstract Background The serine protease thrombin catalyzes fibrin clot formation by converting fibrinogen into fibrin. Additionally, thrombin stimulation leads to an activation of stimulus-responsive transcription factors in different cell types, indicating that the gene expression pattern is changed in thrombin-stimulated cells. The objective of this study was to analyze the signaling cascade leading to the expression of the zinc finger transcription factor Egr-1 in thrombin-stimulated lung fibroblasts. Results Stimulation of 39M1-81 fibroblasts with thrombin induced a robust and transient biosynthesis of Egr-1. Reporter gene analysis revealed that the newly synthesized Egr-1 was biologically active. The signaling cascade connecting thrombin stimulation with Egr-1 gene expression required elevated levels of cytosolic Ca2+, the activation of diacylgycerol-dependent protein kinase C isoenzymes, and the activation of extracellular signal-regulated protein kinase (ERK. Stimulation of the cells with thrombin triggered the phosphorylation of the transcription factor Elk-1. Expression of a dominant-negative mutant of Elk-1 completely prevented Egr-1 expression in stimulated 39M1-81 cells, indicating that Elk-1 or related ternary complex factors connect the intracellular signaling cascade elicited by activation of protease-activated receptors with transcription of the Egr-1 gene. Lentiviral-mediated expression of MAP kinase phosphatase-1, a dual-specific phosphatase that dephosphorylates and inactivates ERK in the nucleus, prevented Elk-1 phosphorylation and Egr-1 biosynthesis in thrombin stimulated 39M1-81 cells, confirming the importance of nuclear ERK and Elk-1 for the upregulation of Egr-1 expression in thrombin-stimulated lung fibroblasts. 39M1-81 cells additionally express M1 muscarinic acetylcholine receptors. A comparison between the signaling cascades induced by thrombin or carbachol showed no differences, except that signal transduction via M

  8. Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

    Science.gov (United States)

    2011-01-01

    Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi

  9. Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs

    International Nuclear Information System (INIS)

    Erdmann, Kati; Kaulke, Knut; Thomae, Cathleen; Huebner, Doreen; Sergon, Mildred; Froehner, Michael; Wirth, Manfred P; Fuessel, Susanne

    2014-01-01

    Recent evidence suggests that the prostate cancer (PCa)-specific up-regulation of certain genes such as AMACR, EZH2, PSGR, PSMA and TRPM8 could be associated with an aberrant expression of non-coding microRNAs (miRNA). In silico analyses were used to search for miRNAs being putative regulators of PCa-associated genes. The expression of nine selected miRNAs (hsa-miR-101, -138, -186, -224, -26a, -26b, -374a, -410, -660) as well as of the aforementioned PCa-associated genes was analyzed by quantitative PCR using 50 malignant (Tu) and matched non-malignant (Tf) tissue samples from prostatectomy specimens as well as 30 samples from patients with benign prostatic hyperplasia (BPH). Then, correlations between paired miRNA and target gene expression levels were analyzed. Furthermore, the effect of exogenously administered miR-26a on selected target genes was determined by quantitative PCR and Western Blot in various PCa cell lines. A luciferase reporter assay was used for target validation. The expression of all selected miRNAs was decreased in PCa tissue samples compared to either control group (Tu vs Tf: -1.35 to -5.61-fold; Tu vs BPH: -1.17 to -5.49-fold). The down-regulation of most miRNAs inversely correlated with an up-regulation of their putative target genes with Spearman correlation coefficients ranging from -0.107 to -0.551. MiR-186 showed a significantly diminished expression in patients with non-organ confined PCa and initial metastases. Furthermore, over-expression of miR-26a reduced the mRNA and protein expression of its potential target gene AMACR in vitro. Using the luciferase reporter assay AMACR was validated as new target for miR-26a. The findings of this study indicate that the expression of specific miRNAs is decreased in PCa and inversely correlates with the up-regulation of their putative target genes. Consequently, miRNAs could contribute to oncogenesis and progression of PCa via an altered miRNA-target gene-interaction

  10. Contraction-induced muscle fiber damage is increased in soleus muscle of streptozotocin-diabetic rats and is associated with elevated expression of brain-derived neurotrophic factor mRNA in muscle fibers and activated satellite cells

    NARCIS (Netherlands)

    Copray, S; Liem, R; Brouwer, N; Greenhaff, P; Habens, F; Fernyhough, P

    The expression of brain-derived neurotrophic factor (BDNF) is elevated in the soleus muscle of streptozotocin-diabetic rats. To determine whether this diabetes-induced elevation was associated with or enhanced by muscle activity we have induced high-intensity muscle contraction by electrically

  11. Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis.

    Science.gov (United States)

    Liu, Yanhua; Wang, Xinjing; Jiang, Jing; Cao, Zhihong; Yang, Bingfen; Cheng, Xiaoxing

    2011-05-01

    microRNAs have a critical role in regulating innate and adaptive immunity. To understand whether microRNAs play roles in regulating immune responses to Mycobacterium tuberculosis infection in humans, microRNA expression profiling was performed in PBMCs from pulmonary tuberculosis patients and healthy controls. Analysis of expression profiles showed that expression of 30 microRNAs was significantly altered during active TB as compared with healthy controls, 28 microRNAs were up-regulated and 2 microRNAs down-regulated. miR-144* was one of the microRNAs that were overexpressed in active TB patients. Real-time RT-PCR analysis showed that miR-144* was mainly expressed in T cells. Transfection of T cells with miR-144* precursor demonstrated that miR-144* could inhibit TNF-α and IFN-γ production and T cell proliferation. It is concluded that miR-144* might involve in regulation of anti-TB immunity through modification of cytokine production and cell proliferation of T cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Elevated ERCC-1 Gene Expression in blood cells associated with exposure to arsenic from drinking water in Inner Mongolia

    Science.gov (United States)

    Background: Chronic arsenic exposure has been associated with human cancers. The objective of this study was to investigate arsenic effects on a DNA nucleotide excision repair gene, ERCC1, expression in human blood cells. Material and Methods: Water and toe nail samples were coll...

  13. Elevated eukaryotic elongation factor 2 expression is involved in proliferation and invasion of lung squamous cell carcinoma.

    Science.gov (United States)

    Song, Yang; Sun, Bing; Hao, LiHong; Hu, Jun; Du, Sha; Zhou, Xin; Zhang, LiYuan; Liu, Lu; Gong, LinLin; Chi, XinMing; Liu, Qiang; Shao, ShuJuan

    2016-09-06

    Eukaryotic elongation factor 2 (EF2), is a critical enzyme solely responsible for catalyzing the translocation of the elongated peptidyl-tRNA from the A to P sites of the ribosome during the process of protein synthesis. EF2 is found to be highly expressed in a variety of malignant tumors and is correlated with cancer cell progression and recurrence. The present study was designed to uncover the function of EF2 on lung squamous cell carcinoma (LSCC) cancer cell growth and progression. Our results from clinical tissue studies showed that EF2 protein was significantly overexpressed in LSCC tissues, compared with the adjacent normal lung tissues, which was confirmed by western blotting and tissue microarray. Forced expression of EF2 resulted in the enhancement of lung squamous carcinoma NCI-H520 cells growth through promotion of G2/M progression in cell cycle, activating Akt and Cdc2/Cyclin B1. In nude mice cancer xenograft model, overexpression of EF2 significantly facilitated cell proliferation in vivo. Furthermore, forced expression of EF2 in the cells increased the capabilities of migration and invasion by changing the expressions of EMT-related proteins and genes. These results provided novel insights into the role of EF2 in tumorigenesis and progression in LSCC. EF2-targeted therapy could become a good strategy for the clinical treatment of LSCC.

  14. Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients.

    Science.gov (United States)

    Giaginis, Constantinos; Sampani, Anastasia; Kotta-Loizou, Iolly; Giannopoulou, Ioanna; Danas, Eugene; Politi, Ekaterini; Tsourouflis, Gerasimos; Kouraklis, Gregorios; Patsouris, Efstratios; Keramopoulos, Antonios; Nakopoulou, Lydia; Theocharis, Stamatios

    2017-08-14

    Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 expression was negatively associated with histological (p Cox-regression analysis, p = 0.0223 and p = 0.0004, respectively) level. On the other hand, high COX-2 expression was associated with favorable overall and disease-free patients' survival merely at univariate level (log-rank test, p = 0.0389 and p = 0.0154, respectively). HuR expression was not associated with COX-2 expression (Spearman R = 0.1489, p = 0.1032). The present data support evidence that HuR is associated with tumor aggressiveness and poor prognosis in breast carcinoma, reinforcing its potential as promising therapeutic target in this type of neoplasia.

  15. Histological change and heat shock protein 70 expression in different tissues of Japanese flounder Paralichthys olivaceus in response to elevated temperature

    Science.gov (United States)

    Liu, Yifan; Ma, Daoyuan; Xiao, Zhizhong; Xu, Shihong; Wang, Yanfeng; Wang, Yufu; Xiao, Yongshuang; Song, Zongcheng; Teng, Zhaojun; Liu, Qinghua; Li, Jun

    2015-01-01

    High temperature influences the homeostasis of fish. We investigated the effects of elevated temperature on tissues of Japanese flounder ( Paralichthys olivaceus) by analyzing the histology and heat shock protein 70 ( hsp70) expression of fish reared in warm conditions. In this study, temperature was increased at 1±0.5°C/day starting at 24±0.5°C, and was kept at that temperature for 5 days before the next rise. After raising temperature at the rate up to 32±0.5°C, tissue samples from midgut, spleen, stomach, liver, muscle, gill, heart, trunk kidney and brain were collected for histological analysis and mRNA assay. Almost all the tissues showed changes in morphological structure and hsp70 level at 32±0.5°C. Histological assessment of the tissues indicated that the gill had the most serious damage, including highly severe epithelial lifting and edema, curved tips and hyperemia at the ending of the lamellars, desquamation and necrosis. The next most severe damage was found in liver and kidney. The hsp70 levels in all the tissues first increased and then decreased. The gut, stomach, muscle, heart, and brain had the highest expressions in 6 h, whereas the spleen, liver, gill and kidney had the highest expressions in 2 h. Therefore, tissues with the most significant lesions (especially gill and liver) responded much earlier (2 h) in hsp70 expression than other tissues, and these tissues demonstrated the most marked histological disruption and elevated mRNA levels, making them ideal candidates for further studies on the thermal physiology of this species.

  16. Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions

    Science.gov (United States)

    Kurabayashi, Kumiko; Tanimoto, Koichi; Fueki, Shinobu; Tomita, Haruyoshi

    2015-01-01

    Because a shortage of new antimicrobial agents is a critical issue at present, and with the spread of multidrug-resistant (MDR) pathogens, the use of fosfomycin to treat infections is being revisited as a “last-resort option.” This drug offers a particular benefit in that it is more effective against bacteria growing under oxygen-limited conditions, unlike other commonly used antimicrobials, such as fluoroquinolones and aminoglycosides. In this study, we showed that Escherichia coli strains, including enterohemorrhagic E. coli (EHEC), were more susceptible to fosfomycin when grown anaerobically than when grown aerobically, and we investigated how the activity of this drug was enhanced during anaerobic growth of E. coli. Our quantitative PCR analysis and a transport assay showed that E. coli cells grown under anaerobic conditions had higher levels of expression of glpT and uhpT, encoding proteins that transport fosfomycin into cells with their native substrates, i.e., glycerol-3-phosphate and glucose-6-phosphate, and led to increased intracellular accumulation of the drug. Elevation of expression of these genes during anaerobic growth requires FNR, a global transcriptional regulator that is activated under anaerobic conditions. Purified FNR bound to DNA fragments from regions upstream of glpT and uhpT, suggesting that it is an activator of expression of glpT and uhpT during anaerobic growth. We concluded that the increased antibacterial activity of fosfomycin toward E. coli under anaerobic conditions can be attributed to elevated expression of GlpT and UhpT following activation of FNR, leading to increased uptake of the drug. PMID:26248376

  17. Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A.

    Science.gov (United States)

    Kaur, Manminder; Holden, Neil S; Wilson, Sylvia M; Sukkar, Maria B; Chung, Kian Fan; Barnes, Peter J; Newton, Robert; Giembycz, Mark A

    2008-09-01

    In diseases such as asthma, airway smooth muscle (ASM) cells play a synthetic role by secreting inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, or IL-8 and by expressing surface adhesion molecules, including ICAM-1. In the present study, PGE(2), forskolin, and short-acting (salbutamol) and long-acting (salmeterol and formoterol) beta(2)-adrenoceptor agonists reduced the expression of ICAM-1 and the release of GM-CSF evoked by IL-1beta in ASM cells. IL-1beta-induced IL-8 release was also repressed by PGE(2) and forskolin, whereas the beta(2)-adrenoceptor agonists were ineffective. In each case, repression of these inflammatory indexes was prevented by adenoviral overexpression of PKIalpha, a highly selective PKA inhibitor. These data indicate a PKA-dependent mechanism of repression and suggest that agents that elevate intracellular cAMP, and thereby activate PKA, may have a widespread anti-inflammatory effect in ASM cells. Since ICAM-1 and GM-CSF are highly NF-kappaB-dependent genes, we used an adenoviral-delivered NF-kappaB-dependent luciferase reporter to examine the effects of forskolin and the beta(2)-adrenoceptor agonists on NF-kappaB activation. There was no effect on luciferase activity measured in the presence of forskolin or beta(2)-adrenoceptor agonists. This finding is consistent with the observation that IL-1beta-induced expression of IL-6, a known NF-kappaB-dependent gene in ASM, was also unaffected by beta(2)-adrenoceptor agonists, forskolin, PGE(2), 8-bromo-cAMP, or rolipram. Collectively, these results indicate that repression of IL-1beta-induced ICAM-1 expression and GM-CSF release by cAMP-elevating agents, including beta(2)-adrenoceptor agonists, may not occur through a generic effect on NF-kappaB.

  18. Expression of a gymnosperm PIN homologous gene correlates with auxin immunolocalization pattern at cotyledon formation and in demarcation of the procambium during Picea abies somatic embryo development and in seedling tissues.

    Science.gov (United States)

    Palovaara, Joakim; Hallberg, Henrik; Stasolla, Claudio; Luit, Bert; Hakman, Inger

    2010-04-01

    In seed plants, the body organization is established during embryogenesis and is uniform across gymnosperms and angiosperms, despite differences during early embryogeny. Evidence from angiosperms implicates the plant hormone auxin and its polar transport, mainly established by the PIN family of auxin efflux transporters, in the patterning of embryos. Here, PaPIN1 from Norway spruce (Picea abies [L.] Karst.), a gene widely expressed in conifer tissues and organs, was characterized and its expression and localization patterns were determined with reverse transcription polymerase chain reaction and in situ hybridization during somatic embryo development and in seedlings. PaPIN1 shares the predicted structure of other PIN proteins, but its central hydrophilic loop is longer than most PINs. In phylogenetic analyses, PaPIN1 clusters with Arabidopsis thaliana (L.) Heynh. PIN3, PIN4 and PIN7, but its expression pattern also suggests similarity to PIN1. The PaPIN1 expression signal was high in the protoderm of pre-cotyledonary embryos, but not if embryos were pre-treated with the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). This, together with a high auxin immunolocalization signal in this cell layer, suggests a role of PaPIN1 during cotyledon formation. At later stages, high PaPIN1 expression was observed in differentiating procambium, running from the tip of incipient cotyledons down through the embryo axis and to the root apical meristem (RAM), although the mode of RAM specification in conifer embryos differs from that of most angiosperms. Also, the PaPIN1 in situ signal was high in seedling root tips including root cap columella cells. The results thus suggest that PaPIN1 provides an ancient function associated with auxin transport and embryo pattern formation prior to the separation of angiosperms and gymnosperms, in spite of some morphological differences.

  19. Cardiac CRFR1 Expression Is Elevated in Human Heart Failure and Modulated by Genetic Variation and Alternative Splicing

    Science.gov (United States)

    Lewis, Kathy A.; Perrin, Marilyn H.; Sweet, Wendy E.; Moravec, Christine S.; Tang, W. H. Wilson; Huising, Mark O.; Troughton, Richard W.; Cameron, Vicky A.

    2016-01-01

    Corticotropin-releasing factor (CRF) and the CRF-related peptides, urocortin (Ucn)-1, Ucn2, and Ucn3 signal through receptors CRFR1 and CRFR2 to restore homeostasis in response to stress. The Ucns exert potent cardioprotective effects and may have clinical utility in heart failure. To explore the activity of this system in the heart, we measured the levels of myocardial gene expression of the CRF/Ucn family of ligands/receptors and investigated genetic variation and alternative splicing of CRFR1 in 110 heart failure patients and 108 heart donors. Using quantitative real-time PCR, we detected CRFR1, CRFR2, CRF, Ucn1, Ucn2, and Ucn3 in all samples. CRFR2α was the most abundant receptor and Ucn3 the most abundant ligand, both in patients and donors. Compared with donors, cardiac expression of CRFR1, CRF, and Ucn3 was higher (P heart failure and may contribute to the activation of the CRF/Ucn system in these patients. A common variant within the CRFR1 gene and a novel CRFR1 splice variant may modulate CRFR1 expression and signaling. PMID:27754786

  20. Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine.

    Science.gov (United States)

    Kopra, Jaakko; Villarta-Aguilera, Marian; Savolainen, Mari; Weingerl, Samo; Myöhänen, Timo T; Rannanpää, Saara; Salvatore, Michael F; Andressoo, Jaan-Olle; Piepponen, T Petteri

    2018-01-01

    Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Cardiac CRFR1 Expression Is Elevated in Human Heart Failure and Modulated by Genetic Variation and Alternative Splicing.

    Science.gov (United States)

    Pilbrow, Anna P; Lewis, Kathy A; Perrin, Marilyn H; Sweet, Wendy E; Moravec, Christine S; Tang, W H Wilson; Huising, Mark O; Troughton, Richard W; Cameron, Vicky A

    2016-12-01

    Corticotropin-releasing factor (CRF) and the CRF-related peptides, urocortin (Ucn)-1, Ucn2, and Ucn3 signal through receptors CRFR1 and CRFR2 to restore homeostasis in response to stress. The Ucns exert potent cardioprotective effects and may have clinical utility in heart failure. To explore the activity of this system in the heart, we measured the levels of myocardial gene expression of the CRF/Ucn family of ligands/receptors and investigated genetic variation and alternative splicing of CRFR1 in 110 heart failure patients and 108 heart donors. Using quantitative real-time PCR, we detected CRFR1, CRFR2, CRF, Ucn1, Ucn2, and Ucn3 in all samples. CRFR2α was the most abundant receptor and Ucn3 the most abundant ligand, both in patients and donors. Compared with donors, cardiac expression of CRFR1, CRF, and Ucn3 was higher (P heart failure and may contribute to the activation of the CRF/Ucn system in these patients. A common variant within the CRFR1 gene and a novel CRFR1 splice variant may modulate CRFR1 expression and signaling.

  2. Hyperproduction of Alpha-Hemolysin in a sigB Mutant Is Associated with Elevated SarA Expression in Staphylococcus aureus

    Science.gov (United States)

    Cheung, Ambrose L.; Chien, Yueh-tyng; Bayer, Arnold S.

    1999-01-01

    To evaluate the role of SigB in modulating the expression of virulence determinants in Staphylococcus aureus, we constructed a sigB mutant of RN6390, a prototypic S. aureus strain. The mutation in the sigB gene was confirmed by the absence of the SigB protein in the mutant on an immunoblot as well as the failure of the mutant to activate ςB-dependent promoters (e.g., the sarC promoter) of S. aureus. Phenotypic analysis indicated that both alpha-hemolysin level and fibrinogen-binding capacity were up-regulated in the mutant strain compared with the parental strain. The increase in fibrinogen-binding capacity correlated with enhanced expression of clumping factor and coagulase on immunoblots. The effect of the sigB mutation on the enhanced expression of the alpha-hemolysin gene (hla) was primarily transcriptional. Upon complementation with a plasmid containing the sigB gene, hla expression returned to near parental levels in the mutant. Detailed immunoblot analysis as well as a competitive enzyme-linked immunosorbent assay of the cell extract of the sigB mutant with anti-SarA monoclonal antibody 1D1 revealed that the expression of SarA was higher in the mutant than in the parental control. Despite an elevated SarA level, the transcription of RNAII and RNAIII of the agr locus remained unaltered in the sigB mutant. Because of a lack of perturbation in agr, we hypothesize that inactivation of sigB leads to increased expression of SarA which, in turn, modulates target genes via an agr-independent but SarA-dependent pathway. PMID:10024579

  3. Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.

    Directory of Open Access Journals (Sweden)

    Melissa S Monsey

    Full Text Available Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs in the lateral nucleus of the amygdala (LA. Rats received chronic exposure to CORT (50 μg/ml in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM is not affected, while long-term memory (LTM is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.

  4. Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.

    Science.gov (United States)

    Monsey, Melissa S; Boyle, Lara M; Zhang, Melinda L; Nguyen, Caroline P; Kronman, Hope G; Ota, Kristie T; Duman, Ronald S; Taylor, Jane R; Schafe, Glenn E

    2014-01-01

    Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT) on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs) in the lateral nucleus of the amygdala (LA). Rats received chronic exposure to CORT (50 μg/ml) in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM) is not affected, while long-term memory (LTM) is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.

  5. Loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer.

    Science.gov (United States)

    Ettl, T; Baader, K; Stiegler, C; Müller, M; Agaimy, A; Zenk, J; Kühnel, T; Gosau, M; Zeitler, K; Schwarz, S; Brockhoff, G

    2012-02-14

    Activity of the tumour-suppressor gene PTEN is reduced in different types of cancer and implicates non-responsiveness to targeted therapy. This study evaluates the gene and protein status of PTEN in salivary gland carcinomas. A total of 287 carcinomas of the major and minor salivary glands were investigated for phosphatase and tensin homologue located on chromosome 10 (PTEN) deletion and loss of PTEN expression using fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively. Results were correlated to clinicopathological parameters, long-term survival, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (IHC and FISH) status of the tumours. Hemizygous deletions of PTEN were found in 35 out of 232 (15.1%) carcinomas, while homozygous deletions were observed in 17 out of 232 (7.3%) tumours. Phosphatase and tensin homologue located on chromosome 10 deletion was common in certain histological subtypes and especially homozygous deletion was associated with high-grade malignancy, lymph node metastases and unfavourable long-term prognosis (P<0.001). Loss of PTEN expression was present in 59 out of 273 (21.6%) carcinomas and was significantly correlated to genomic PTEN deletion, high-grade malignancy (P<0.001), increased tumour size (P=0.036), lymph node metastases (P=0.007) and worse disease-specific survival (P=0.002). Genomic PTEN deletion, in particular homogenous deletion (P<0.001) predominantly occurred in tumours with increased gene copy number of EGFR (60.0%) and/or amplification of HER2 (63.6%). Loss of PTEN expression was frequently found in tumours overexpressing EGFR (28.6%) and/or HER2 (52.6%). PTEN function is reduced in different types of salivary gland cancer indicating unfavourable prognosis. Its association with EGFR and HER2 signalling might affect targeted therapy.

  6. Golden bananas in the field: elevated fruit pro-vitamin A from the expression of a single banana transgene.

    Science.gov (United States)

    Paul, Jean-Yves; Khanna, Harjeet; Kleidon, Jennifer; Hoang, Phuong; Geijskes, Jason; Daniells, Jeff; Zaplin, Ella; Rosenberg, Yvonne; James, Anthony; Mlalazi, Bulukani; Deo, Pradeep; Arinaitwe, Geofrey; Namanya, Priver; Becker, Douglas; Tindamanyire, James; Tushemereirwe, Wilberforce; Harding, Robert; Dale, James

    2017-04-01

    Vitamin A deficiency remains one of the world's major public health problems despite food fortification and supplements strategies. Biofortification of staple crops with enhanced levels of pro-vitamin A (PVA) offers a sustainable alternative strategy to both food fortification and supplementation. As a proof of concept, PVA-biofortified transgenic Cavendish bananas were generated and field trialed in Australia with the aim of achieving a target level of 20 μg/g of dry weight (dw) β-carotene equivalent (β-CE) in the fruit. Expression of a Fe'i banana-derived phytoene synthase 2a (MtPsy2a) gene resulted in the generation of lines with PVA levels exceeding the target level with one line reaching 55 μg/g dw β-CE. Expression of the maize phytoene synthase 1 (ZmPsy1) gene, used to develop 'Golden Rice 2', also resulted in increased fruit PVA levels although many lines displayed undesirable phenotypes. Constitutive expression of either transgene with the maize polyubiquitin promoter increased PVA accumulation from the earliest stage of fruit development. In contrast, PVA accumulation was restricted to the late stages of fruit development when either the banana 1-aminocyclopropane-1-carboxylate oxidase or the expansin 1 promoters were used to drive the same transgenes. Wild-type plants with the longest fruit development time had also the highest fruit PVA concentrations. The results from this study suggest that early activation of the rate-limiting enzyme in the carotenoid biosynthetic pathway and extended fruit maturation time are essential factors to achieve optimal PVA concentrations in banana fruit. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  7. Increased Epithelial Expression of CTGF and S100A7 with Elevated Subepithelial Expression of IL-1β in Trachomatous Trichiasis.

    Directory of Open Access Journals (Sweden)

    Tamsyn Derrick

    2016-06-01

    Full Text Available To characterize the histological appearance and expression of pro-inflammatory mediators, growth factors, matrix metalloproteinases and biomarkers of epithelial-mesenchymal transition (EMT in healthy control and trachomatous trichiasis (TT conjunctival tissue.Conjunctival biopsies were taken from 20 individuals with TT and from 16 individuals with healthy conjunctiva, which served as controls. Study participants were of varying ethnicity and were living in a trachoma-endemic region of northern Tanzania. Formalin-fixed paraffin-embedded tissue sections were stained using hematoxylin and eosin or by immunohistochemistry using antibodies against: IL-1β, IL-6, IL-17A, IL-22, CXCL5, S100A7, cleaved caspase 1 (CC1, PDGF, CTGF, TGFβ2, MMP7, MMP9, E-cadherin, vimentin, and αSMA.Tissue from TT cases had a greater inflammatory cell infiltrate relative to controls and greater disruption of collagen structure. CTGF and S100A7 were more highly expressed in the epithelium and IL-1β was more highly expressed in the substantia propria of TT cases relative to controls. Latent TGFβ2 was slightly more abundant in the substantia propria of control tissue. No differences were detected between TT cases and controls in the degree of epithelial atrophy, the number of myofibroblasts or expression of EMT biomarkers.These data indicate that the innate immune system is active in the immunopathology of trachoma, even in the absence of clinical inflammation. CTGF might provide a direct link between inflammation and fibrosis and could be a suitable target for therapeutic treatment to halt the progression of trachomatous scarring.

  8. Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes.

    Science.gov (United States)

    Sárvári, Miklós; Hrabovszky, Erik; Kalló, Imre; Solymosi, Norbert; Likó, István; Berchtold, Nicole; Cotman, Carl; Liposits, Zsolt

    2012-12-03

    The intricate interactions between the immune, endocrine and central nervous systems shape the innate immune response of the brain. We have previously shown that estradiol suppresses expression of immune genes in the frontal cortex of middle-aged ovariectomized rats, but not in young ones reflecting elevated expression of these genes in middle-aged, ovarian hormone deficient animals. Here, we explored the impact of menopause on the microglia phenotype capitalizing on the differential expression of macrophage-associated genes in quiescent and activated microglia. We selected twenty-three genes encoding phagocytic and recognition receptors expressed primarily in microglia, and eleven proinflammatory genes and followed their expression in the rat frontal cortex by real-time PCR. We used young, middle-aged and middle-aged ovariectomized rats to reveal age- and ovariectomy-related alterations. We analyzed the expression of the same set of genes in the postcentral and superior frontal gyrus of pre- and postmenopausal women using raw microarray data from our previous study. Ovariectomy caused up-regulation of four classic microglia reactivity marker genes including Cd11b, Cd18, Cd45 and Cd86. The change was reversible since estradiol attenuated transcriptional activation of the four marker genes. Expression of genes encoding phagocytic and toll-like receptors such as Cd11b, Cd18, C3, Cd32, Msr2 and Tlr4 increased, whereas scavenger receptor Cd36 decreased following ovariectomy. Ovarian hormone deprivation altered the expression of major components of estrogen and neuronal inhibitory signaling which are involved in the control of microglia reactivity. Strikingly similar changes took place in the postcentral and superior frontal gyrus of postmenopausal women. Based on the overlapping results of rat and human studies we propose that the microglia phenotype shifts from the resting toward the reactive state which can be characterized by up-regulation of CD11b, CD14, CD18, CD45

  9. Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes

    Directory of Open Access Journals (Sweden)

    Sárvári Miklós

    2012-12-01

    Full Text Available Abstract Background The intricate interactions between the immune, endocrine and central nervous systems shape the innate immune response of the brain. We have previously shown that estradiol suppresses expression of immune genes in the frontal cortex of middle-aged ovariectomized rats, but not in young ones reflecting elevated expression of these genes in middle-aged, ovarian hormone deficient animals. Here, we explored the impact of menopause on the microglia phenotype capitalizing on the differential expression of macrophage-associated genes in quiescent and activated microglia. Methods We selected twenty-three genes encoding phagocytic and recognition receptors expressed primarily in microglia, and eleven proinflammatory genes and followed their expression in the rat frontal cortex by real-time PCR. We used young, middle-aged and middle-aged ovariectomized rats to reveal age- and ovariectomy-related alterations. We analyzed the expression of the same set of genes in the postcentral and superior frontal gyrus of pre- and postmenopausal women using raw microarray data from our previous study. Results Ovariectomy caused up-regulation of four classic microglia reactivity marker genes including Cd11b, Cd18, Cd45 and Cd86. The change was reversible since estradiol attenuated transcriptional activation of the four marker genes. Expression of genes encoding phagocytic and toll-like receptors such as Cd11b, Cd18, C3, Cd32, Msr2 and Tlr4 increased, whereas scavenger receptor Cd36 decreased following ovariectomy. Ovarian hormone deprivation altered the expression of major components of estrogen and neuronal inhibitory signaling which are involved in the control of microglia reactivity. Strikingly similar changes took place in the postcentral and superior frontal gyrus of postmenopausal women. Conclusions Based on the overlapping results of rat and human studies we propose that the microglia phenotype shifts from the resting toward the reactive state

  10. Hawthorn Fruit Extract Elevates Expression of Nrf2/HO-1 and Improves Lipid Profiles in Ovariectomized Rats

    Science.gov (United States)

    Yoo, Jeong-Hyun; Liu, Yanan; Kim, Hyun-Sook

    2016-01-01

    The purpose of this study was to investigate the effects of hawthorn (Crataegus pinnatifida Bunge) extract on the lipid profiles and antioxidant properties in ovariectomized (OVX) rats. After ovariectomy, the rats were randomly divided into four groups: the non-OVX control (Sham), the OVX-control (OVX), the OVX + 100 mg/kg b.w. of hawthorn extract (OL), and the OVX + 200 mg/kg b.w. of hawthorn extract (OH). The final body weights of the OVX group were significantly increased, but the increment was significantly decreased in hawthorn groups (p hawthorn groups showed a significant decrease in these levels (p hawthorn groups compared with the OVX group (p hawthorn groups exhibited a significant increase in expression (p hawthorn extract reversed the suppression of protein levels. These results suggest that hawthorn extract could have protective effects in OVX rats by improving lipid profiles, decreasing oxidative stress, and improving the antioxidant defense system. PMID:27187458

  11. Nanoformulated alpha-mangostin ameliorates Alzheimer's disease neuropathology by elevating LDLR expression and accelerating amyloid-beta clearance.

    Science.gov (United States)

    Yao, Lei; Gu, Xiao; Song, Qingxiang; Wang, Xiaolin; Huang, Meng; Hu, Meng; Hou, Lina; Kang, Ting; Chen, Jun; Chen, Hongzhuan; Gao, Xiaoling

    2016-03-28

    Alzheimer's disease (AD), the most common form of dementia, is now representing one of the largest global healthcare challenges. However, an effective therapy is still lacking. Accumulation of amyloid-beta (Aβ) in the brain is supposed to trigger pathogenic cascades that eventually lead to AD. Therefore, Aβ clearance strategy is being actively pursued as a promising disease modifying therapy. Here, we found that α-mangostin (α-M), a polyphenolic xanthone derivative from mangosteen, up-regulated low density lipoprotein receptor (LDLR) expression in microglia and liver cells, and efficiently facilitated Aβ clearance. However, the in vivo application of α-M is limited due to its hydrophobic nature, poor aqueous solubility and stability, and thus low bioavailability and accumulation in the target organs. To overcome this limitation, α-M was encapsulated into the core of poly(ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles [NP(α-M)]. Such nanoencapsulation improved the biodistribution of α-M in both the brain and liver, enhanced the brain clearance of (125)I-radiolabeled Aβ1-42 in an LDLR-dependent manner, reduced Aβ deposition, attenuated neuroinflammatory responses, ameliorated neurologic changes and reversed behavioral deficits in AD model mice. These findings justified the concept that polyphenol-mediated modulation of LDLR expression might serve as a safe and efficient disease-modifying therapy for AD by accelerating Aβ clearance. It also demonstrated the powerful capacity of nanotechnology in modulating the biodistribution behavior of drug to improve its therapeutic efficacy in AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Neuroserpin up-regulation in the Alzheimer’s disease brain is associated with elevated thyroid hormone receptor-β1 and HuD expression

    Science.gov (United States)

    Subhadra, Bobban; Schaller, Kristin; Seeds, Nicholas W.

    2013-01-01

    Neuroserpin, the major inhibitor of tissue plasminogen activator (tPA) in brain, has been shown to be up-regulated in Alzheimer’s disease (AD). Inhibition of tPA activity leads to reduced brain levels of plasmin, one of the main enzymes responsible for the degradation and clearance of amyloid-beta and its plaques from the brain. Thyroid hormone is one of the few factors known to enhance expression of neuroserpin in neurons. Thyroid hormone acts on neurons by binding to its receptors THR1α and THR1β, which then function in the nucleus to up-regulate the expression of numerous genes including the RNA-binding protein HuD. HuD acts post-transcriptionally to enhance expression of numerous proteins including neuroserpin by stabilizing their mRNAs. A series of Alzheimer’s disease brain tissues were compared to age-matched control brains for their expression of neuroserpin, THRβ1 and HuD by western blotting. Alzheimer’s disease brain tissues with elevated neuroserpin protein also showed increased expression of THRβ1 and HuD. Pair-wise analyses showed significant correlation p-values between neuroserpin, THRβ1 and HuD levels; suggesting that the up-regulation of neuroserpin in Alzheimer’s disease brain may result from an activation of the thyroid hormone response system in these individuals. These findings provide evidence for a potential relationship between thyroid hormone disorders and Alzheimer’s disease. PMID:24036060

  13. Profound elevation of CD8+ T cells expressing the intraepithelial lymphocyte marker CD103 (alphaE/beta7 Integrin) in high-grade serous ovarian cancer.

    Science.gov (United States)

    Webb, John R; Wick, Darin A; Nielsen, Julie S; Tran, Eric; Milne, Katy; McMurtrie, Elissa; Nelson, Brad H

    2010-09-01

    Tumor-infiltrating CD8(+) T cells are strongly associated with survival in high-grade serous ovarian cancer, but their functional phenotype remains poorly defined. The mucosal integrin CD103 (alpha(E)/beta(7)) facilitates the infiltration of T cells into epithelial tissues, including gut and lung mucosa, solid organ allografts, and various epithelial cancers. We reasoned that CD103 might also be expressed by tumor-reactive T cells in ovarian cancer. Flow cytometry was used to assess the frequency and phenotype of CD103-expressing T cells in primary ascites fluid from 13 patients with high-grade serous ovarian cancer and 2 patients with recurrent disease. We report that a subset of patients with advanced serous ovarian cancer have profoundly elevated frequencies of CD103-expressing CD8(+) cells in ascites (between 20% and 70% of CD8(+) cells in ascites were CD103(+)) and that CD103 expression correlated with levels of TGF-beta in ascitic fluid. Conversely, CD103 was not expressed on CD4(+) cells, even in those patients with very high frequencies of CD8(+)CD103(+) cells. CD8(+)CD103(+) cells were antigen-experienced (CD45RA(-)CD45RO(+)CD62L(lo)CCR7(-)) and of an intermediate (EM2) effector memory phenotype (CD27(+)CD28(-)). TCR repertoire analysis indicated significant skewing between CD8(+)CD103(-) and CD8(+)CD103(+) T cell subsets, suggesting the two populations contain distinct antigenic specificities. Lastly, HLA pentamer analysis revealed that one patient in the cohort harbored a high frequency of CD8(+) T cells in ascites that were specific for the tumor antigen NY-ESO-1, and that approximately 75% of these NY-ESO-1 specific CD8(+) T cells were CD103(+). CD103(+) may be a marker of activated and tumor-reactive CD8(+) T cells in high-grade serous ovarian cancer. Copyright 2010 Elsevier Inc. All rights reserved.

  14. Elevated gene expression in chalcone synthase enzyme suggests an increased production of flavonoids in skin and synchronized red cell cultures of North American native grape berries.

    Science.gov (United States)

    Davis, Gina; Ananga, Anthony; Krastanova, Stoyanka; Sutton, Safira; Ochieng, Joel W; Leong, Stephen; Tsolova, Violetka

    2012-06-01

    Anthocyanins are antioxidants and are among the natural products synthesized via the flavonoid biosynthesis pathway. Anthocyanins have been recommended for dietary intake in the prevention of cardiovascular diseases, cancer, and age-related conditions such as Alzheimer's disease or dementia. With an increasingly aging population in many parts of the world, strategies for the commercial production of in vitro synchronized red cell cultures as natural antioxidants will be a significant contribution to human medicine. Red pigmented fruits such as grapes (Vitis sp.) are a major source of bioavailable anthocyanins and other polyphenols. Since the level of antioxidants varies among cultivars, this study is the first one that phytochemically and genetically characterizes native grape cultivars of North America to determine the optimal cultivar and berry cells for the production of anthocyanins as antioxidants. Using real-time PCR and bioinformatics approaches, we tested for the transcript expression of the chalcone synthase (CHS) gene, an enzyme involved in the flavonoid and anthocyanin biosynthesis pathway, in different parts of physiologically mature grape berries and in vitro synchronized red cells. A low level of expression was recorded in berry flesh, compared with an elevated expression in berry skins and in vitro synchronized red cells, suggesting increased production of flavonoids in skin and cell cultures. This preliminary study demonstrates the potential of functional genomics in natural products research as well as in systematic studies of North American native grapes, specifically in muscadine (Vitis rotundifolia).

  15. Kynurenic Acid Inhibits the Electrical Stimulation Induced Elevated Pituitary Adenylate Cyclase-Activating Polypeptide Expression in the TNC

    Directory of Open Access Journals (Sweden)

    Tamás Körtési

    2018-01-01

    Full Text Available BackgroundMigraine is a primary headache of imprecisely known mechanism, but activation of the trigeminovascular system (TS appears to be essential during the attack. Intensive research has recently focused on pituitary adenylate cyclase-activating polypeptide (PACAP and the kynurenine systems as potential pathogenic factors.AimWe investigated the link between these important mediators and the effects of kynurenic acid (KYNA and its synthetic analog (KYNA-a on PACAP expression in the rat trigeminal nucleus caudalis (TNC in a TS stimulation model related to migraine mechanisms.MethodsAdult male Sprague-Dawley rats were pretreated with KYNA, KYNA-a, the NMDA receptor antagonist MK-801, or saline (vehicle. Next, the trigeminal ganglion (TRG was electrically stimulated, the animals were transcardially perfused following 180 min, and the TNC was removed. In the TNC samples, 38 amino acid form of PACAP (PACAP1–38-like radioimmunoactivity was measured by radioimmunoassay, the relative optical density of preproPACAP was assessed by Western blot analysis, and PACAP1–38 mRNA was detected by real-time PCR.Results and conclusionElectrical TRG stimulation resulted in significant increases of PACAP1–38-LI, preproPACAP, and PACAP1–38 mRNA in the TNC. These increases were prevented by the pretreatments with KYNA, KYNA-a, and MK-801. This is the first study to provide evidence for a direct link between PACAP and the kynurenine system during TS activation.

  16. Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progressioan

    International Nuclear Information System (INIS)

    Dozmorov, Mikhail G; Lin, Hsueh-Kung; Azzarello, Joseph T; Wren, Jonathan D; Fung, Kar-Ming; Yang, Qing; Davis, Jeffrey S; Hurst, Robert E; Culkin, Daniel J; Penning, Trevor M

    2010-01-01

    Aldo-keto reductase (AKR) 1C family member 3 (AKR1C3), one of four identified human AKR1C enzymes, catalyzes steroid, prostaglandin, and xenobiotic metabolism. In the prostate, AKR1C3 is up-regulated in localized and advanced prostate adenocarcinoma, and is associated with prostate cancer (PCa) aggressiveness. Here we propose a novel pathological function of AKR1C3 in tumor angiogenesis and its potential role in promoting PCa progression. To recapitulate elevated AKR1C3 expression in cancerous prostate, the human PCa PC-3 cell line was stably transfected with an AKR1C3 expression construct to establish PC3-AKR1C3 transfectants. Microarray and bioinformatics analysis were performed to identify AKR1C3-mediated pathways of activation and their potential biological consequences in PC-3 cells. Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and an in vitro Matrigel angiogenesis assays were applied to validate the pro-angiogenic activity of PC3-AKR1C3 transfectants identified by bioinformatics analysis. Microarray and bioinformatics analysis suggested that overexpression of AKR1C3 in PC-3 cells modulates estrogen and androgen metabolism, activates insulin-like growth factor (IGF)-1 and Akt signaling pathways, as well as promotes tumor angiogenesis and aggressiveness. Levels of IGF-1 receptor (IGF-1R) and Akt activation as well as vascular endothelial growth factor (VEGF) expression and secretion were significantly elevated in PC3-AKR1C3 transfectants in comparison to PC3-mock transfectants. PC3-AKR1C3 transfectants also promoted endothelial cell (EC) tube formation on Matrigel as compared to the AKR1C3-negative parental PC-3 cells and PC3-mock transfectants. Pre-treatment of PC3-AKR1C3 transfectants with a selective IGF-1R kinase inhibitor (AG1024) or a non-selective phosphoinositide 3-kinases (PI3K) inhibitor (LY294002) abolished ability of the cells to promote EC tube formation. Bioinformatics

  17. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Hiroyuki [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Nemoto, Eiji, E-mail: e-nemoto@umin.ac.jp [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Kanaya, Sousuke; Hamaji, Nozomu; Sato, Hisae; Shimauchi, Hidetoshi [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)

    2010-04-16

    Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca{sup 2+}Ca{sub o}{sup 2+} has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Ca{sub o}{sup 2+} signaling in odontogenesis remains unclear. We found that elevated Ca{sub o}{sup 2+} increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca{sup 2+} increased the stability of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca{sup 2+} channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca{sup 2+}, suggesting that the Ca{sup 2+} influx from Ca{sup 2+} channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca{sup 2+}-sensing receptors (CaSR) and only respond slightly to other cations such as Sr{sup 2+} and spermine, suggesting that dental pulp cells respond to Ca{sub o}{sup 2+} to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Ca{sub o}{sup 2+} among cations.

  18. Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progressioan

    Directory of Open Access Journals (Sweden)

    Davis Jeffrey S

    2010-12-01

    Full Text Available Abstract Background Aldo-keto reductase (AKR 1C family member 3 (AKR1C3, one of four identified human AKR1C enzymes, catalyzes steroid, prostaglandin, and xenobiotic metabolism. In the prostate, AKR1C3 is up-regulated in localized and advanced prostate adenocarcinoma, and is associated with prostate cancer (PCa aggressiveness. Here we propose a novel pathological function of AKR1C3 in tumor angiogenesis and its potential role in promoting PCa progression. Methods To recapitulate elevated AKR1C3 expression in cancerous prostate, the human PCa PC-3 cell line was stably transfected with an AKR1C3 expression construct to establish PC3-AKR1C3 transfectants. Microarray and bioinformatics analysis were performed to identify AKR1C3-mediated pathways of activation and their potential biological consequences in PC-3 cells. Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR, enzyme-linked immunosorbent assay (ELISA, and an in vitro Matrigel angiogenesis assays were applied to validate the pro-angiogenic activity of PC3-AKR1C3 transfectants identified by bioinformatics analysis. Results Microarray and bioinformatics analysis suggested that overexpression of AKR1C3 in PC-3 cells modulates estrogen and androgen metabolism, activates insulin-like growth factor (IGF-1 and Akt signaling pathways, as well as promotes tumor angiogenesis and aggressiveness. Levels of IGF-1 receptor (IGF-1R and Akt activation as well as vascular endothelial growth factor (VEGF expression and secretion were significantly elevated in PC3-AKR1C3 transfectants in comparison to PC3-mock transfectants. PC3-AKR1C3 transfectants also promoted endothelial cell (EC tube formation on Matrigel as compared to the AKR1C3-negative parental PC-3 cells and PC3-mock transfectants. Pre-treatment of PC3-AKR1C3 transfectants with a selective IGF-1R kinase inhibitor (AG1024 or a non-selective phosphoinositide 3-kinases (PI3K inhibitor (LY294002 abolished ability of the cells

  19. Knockdown of astrocyte elevated gene-1 inhibits tumor growth and modifies microRNAs expression profiles in human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Sujun [East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080 (China); Southern Medical University, Guangzhou, Guangdong 510515 (China); Wu, Binwen, E-mail: wubinwengd@aliyun.com [East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080 (China); Li, Dongfeng; Zhou, Weihong; Deng, Gang; Zhang, Kaijun; Li, Youjia [East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080 (China)

    2014-02-14

    Highlights: • AEG-1 expression in CRC cell lines and down-regulation or upregulation of AEG-1 in vitro. • Knockdown of AEG-1 inhibits cell proliferation, colony formation and invasion. • Upregulation of AEG-1 enhances proliferation, invasion and colony formation. • Knockdown of AEG-1 accumulates G0/G1-phase cells and promotes apoptosis in CRC cells. • AEG-1 knockdown increases 5-FU cytotoxicity. - Abstract: Astrocyte elevated gene-1 (AEG-1), upregulated in various types of malignancies including colorectal cancer (CRC), has been reported to be associated with the carcinogenesis. MicroRNAs (miRNAs) are widely involved in the initiation and progression of cancer. However, the functional significance of AEG-1 and the relationship between AEG-1 and microRNAs in human CRC remains unclear. The aim of this study was to investigate whether AEG-1 could serve as a potential therapeutic target of human CRC and its possible mechanism. We adopted a strategy of ectopic overexpression or RNA interference to upregulate or downregulate expression of AEG-1 in CRC models. Their phenotypic changes were analyzed by Western blot, MTT and transwell matrix penetration assays. MicroRNAs expression profiles were performed using microarray analysis followed by validation using qRT-PCR. Knockdown of AEG-1 could significantly inhibit colon cancer cell proliferation, colony formation, invasion and promotes apoptosis. Conversely, upregulation of AEG-1 could significantly enhance cell proliferation, invasion and reduced apoptisis. AEG-1 directly contributes to resistance to chemotherapeutic drug. Targeted downregulation of AEG-1 might improve the expression of miR-181a-2{sup ∗}, -193b and -193a, and inversely inhibit miR-31 and -9{sup ∗}. Targeted inhibition of AEG-1 can lead to modification of key elemental characteristics, such as miRNAs, which may become a potential effective therapeutic strategy for CRC.

  20. Knockdown of astrocyte elevated gene-1 inhibits tumor growth and modifies microRNAs expression profiles in human colorectal cancer cells

    International Nuclear Information System (INIS)

    Huang, Sujun; Wu, Binwen; Li, Dongfeng; Zhou, Weihong; Deng, Gang; Zhang, Kaijun; Li, Youjia

    2014-01-01

    Highlights: • AEG-1 expression in CRC cell lines and down-regulation or upregulation of AEG-1 in vitro. • Knockdown of AEG-1 inhibits cell proliferation, colony formation and invasion. • Upregulation of AEG-1 enhances proliferation, invasion and colony formation. • Knockdown of AEG-1 accumulates G0/G1-phase cells and promotes apoptosis in CRC cells. • AEG-1 knockdown increases 5-FU cytotoxicity. - Abstract: Astrocyte elevated gene-1 (AEG-1), upregulated in various types of malignancies including colorectal cancer (CRC), has been reported to be associated with the carcinogenesis. MicroRNAs (miRNAs) are widely involved in the initiation and progression of cancer. However, the functional significance of AEG-1 and the relationship between AEG-1 and microRNAs in human CRC remains unclear. The aim of this study was to investigate whether AEG-1 could serve as a potential therapeutic target of human CRC and its possible mechanism. We adopted a strategy of ectopic overexpression or RNA interference to upregulate or downregulate expression of AEG-1 in CRC models. Their phenotypic changes were analyzed by Western blot, MTT and transwell matrix penetration assays. MicroRNAs expression profiles were performed using microarray analysis followed by validation using qRT-PCR. Knockdown of AEG-1 could significantly inhibit colon cancer cell proliferation, colony formation, invasion and promotes apoptosis. Conversely, upregulation of AEG-1 could significantly enhance cell proliferation, invasion and reduced apoptisis. AEG-1 directly contributes to resistance to chemotherapeutic drug. Targeted downregulation of AEG-1 might improve the expression of miR-181a-2 ∗ , -193b and -193a, and inversely inhibit miR-31 and -9 ∗ . Targeted inhibition of AEG-1 can lead to modification of key elemental characteristics, such as miRNAs, which may become a potential effective therapeutic strategy for CRC

  1. Rats with differential self-grooming expression in the elevated plus-maze do not differ in anxiety-related behaviors.

    Science.gov (United States)

    Reimer, Adriano Edgar; de Oliveira, Amanda Ribeiro; Diniz, Juliana Belo; Hoexter, Marcelo Queiroz; Chiavegatto, Silvana; Brandão, Marcus Lira

    2015-10-01

    Individual differences are important biological predictors for reactivity to stressful stimulation. The extent to which trait differences underlie animal's reactions to conditioned and unconditioned fear stimuli, for example, is still to be clarified. Although grooming behavior has been associated with some aspects of the obsessive-compulsive disorder in humans, its relation with other anxiety disorders is still unknown. Given that grooming behavior could be a component of the whole spectrum of these disorders, in the present study we allocated male Wistar rats in low, intermediate and high self-grooming groups according to the duration of such behavior in the elevated plus-maze (EPM). These groups were then evaluated in unconditioned fear tests, such as the EPM and the open-field, and in conditioned fear tests, such as fear-potentiated startle and fear extinction retention. Additionally, we studied the expression of unconditioned behaviors in marble burying test and the sensorimotor gate function with prepulse inhibition test. Neurochemicals and neuroendocrine parameters were also evaluated, with the quantification of basal corticosterone in the plasma, and dopamine, serotonin and their metabolites in brain structures involved with fear processing. In general, rats classified according to grooming expression showed similar performance in all behavioral tests. Accordingly, corticosterone and monoamine concentrations were similar among groups. Thus, despite grooming expression elicited by different approaches--especially pharmacological ones--has been related with some aspects of anxiety disorders, rats with different expression of spontaneous self-grooming in the EPM do not differ in anxiety-like behaviors nor in neurochemical and neuroendocrine parameters generally associated with anxiety disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Increased severity of inflammation correlates with elevated expression of TRPV1 nerve fibers and nerve growth factor on interstitial cystitis/bladder pain syndrome.

    Science.gov (United States)

    Liu, Bo-long; Yang, Fei; Zhan, Hai-lun; Feng, Zhi-ying; Zhang, Zhi-gang; Li, Wen-biao; Zhou, Xiang-fu

    2014-01-01

    Although evidence supports a role for inflammation in interstitial cystitis/bladder pain syndrome (IC/BPS), the mechanism remains unknown. We determined whether inflammation causes an elevated expression of nerve growth factor (NGF) and transient receptor potential vanilloid receptor subtype 1 (TRPV1) and correlated them with the symptoms. Bladder biopsies were obtained from 53 IC/BPS patients and 27 controls, and hematoxylin and eosin staining, immunostaining and Western blotting were performed to detect inflammation, TRPV1-immunoreactive and PGP9.5-immunoreactive nerve fibers, and NGF, respectively. Symptoms were assessed using the Pelvic Pain/Urgency/Frequency (PUF) questionnaire and pain visual analogue scale scores. Suburothelial nerve fiber density was quantified and correlated with PUF scores. Increased severity of inflammation was correlated with a higher TRPV1-immunoreactive nerve fiber density (r = 0.4113, p = 0.0024) and higher NGF levels (r = 0.3775, p = 0.0052). Suburothelial TRPV1-immunoreactive nerve fiber density was significantly correlated with pain scores and urgency scores (r = 0.3320, p = 0.0145 and r = 0.3823, p = 0.0039, respectively). PGP9.5-immunoreactive nerve fibers were significantly increased in IC/BPS (p = 0.0193) and had a positive relationship with inflammation severity (r = 0.6138, p inflammation correlated with a higher expression of TRPV1-immunoreactive nerve fibers and NGF in IC/BPS and correlated with clinical symptoms. 2014 S. Karger AG, Basel.

  3. Elevated C1orf63 expression is correlated with CDK10 and predicts better outcome for advanced breast cancers: a retrospective study

    International Nuclear Information System (INIS)

    Hong, Chao-Qun; Zhang, Fan; You, Yan-Jie; Qiu, Wei-Li; Giuliano, Armando E.; Cui, Xiao-Jiang; Zhang, Guo-Jun; Cui, Yu-Kun

    2015-01-01

    independent prognostic factor predicting better clinical outcome (HR: 0.41; 95 % CI: 0.17 ~ 0.97; P = 0.042). Additionally, we found that CDK10 mRNA expression was positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10 (r s = 0.391; P < 0.001). Compared to adjacent non-cancerous tissues, C1orf63 expression was elevated in tumor tissues. However, C1orf63 predicts better prognosis for breast cancers with advanced TNM stage, and the underlying mechanism is unknown. In addition, C1orf63 is correlated with the cell cycle related gene, CDK10

  4. Two Paralogous Genes Encoding Auxin Efflux Carrier Differentially Expressed in Bitter Gourd (Momordica charantia

    Directory of Open Access Journals (Sweden)

    Yi-Li Li

    2017-11-01

    Full Text Available The phytohormone auxin regulates various developmental programs in plants, including cell growth, cell division and cell differentiation. The auxin efflux carriers are essential for the auxin transport. To show an involvement of auxin transporters in the coordination of fruit development in bitter gourd, a juicy fruit, we isolated novel cDNAs (referred as McPIN encoding putative auxin efflux carriers, including McPIN1, McPIN2 (allele of McPIN1 and McPIN3, from developing fruits of bitter gourd. Both McPIN1 and McPIN3 genes possess six exons and five introns. Hydropathy analysis revealed that both polypeptides have two hydrophobic regions with five transmembrane segments and a predominantly hydrophilic core. Phylogenetic analyses revealed that McPIN1 shared the highest homology to the group of Arabidopsis, cucumber and tomato PIN1, while McPIN3 belonged to another group, including Arabidopsis and tomato PIN3 as well as PIN4. This suggests different roles for McPIN1 and McPIN3 in auxin transport involved in the fruit development of bitter gourd. Maximum mRNA levels for both genes were detected in staminate and pistillate flowers. McPIN1 is expressed in a particular period of early fruit development but McPIN3 continues to be expressed until the last stage of fruit ripening. Moreover, these two genes are auxin-inducible and qualified as early auxin-response genes. Their expression patterns suggest that these two auxin transporter genes play a pivotal role in fruit setting and development.

  5. Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors

    Directory of Open Access Journals (Sweden)

    Campbell Craig I

    2011-11-01

    Full Text Available Abstract Background Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor. Results MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRα and PDGFRβ. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB-IGFIR mice, it was demonstrated that PDGFRα and to a lesser extent PDGFRβ was important for cell migration and invasion as RNAi knockdown of PDGFRα alone or PDGFRα and PDGFRβ in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRα and PDGFRβ resulted in a modest increase in cell proliferation and a decrease in apoptosis. Conclusion During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion.

  6. TGF-β1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-β1/Smad pathway

    International Nuclear Information System (INIS)

    Fang, Ling; Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Ma, Taotao; Liu, Xuejiao; Zhu, Qian; Zhan, Shuxiang; Li, Jun

    2014-01-01

    Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-β1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7 protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-β1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-β1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-β1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-β1-induced expression of myofibroblast markers, as measured by the induction of α-SMA and Col1α1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-β1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 protein in human fibrotic livers • Upregulation of TRPM7 by TGF-β1 elicited Smad signaling in HSC-T6 cells

  7. TGF-β1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-β1/Smad pathway

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Ling, E-mail: fangling_1984@126.com [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); The First Affiliated Hospital of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Ma, Taotao; Liu, Xuejiao; Zhu, Qian [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); Zhan, Shuxiang [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); The First Affiliated Hospital of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Li, Jun, E-mail: lj@ahmu.edu.cn [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China)

    2014-10-15

    Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-β1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7 protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-β1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-β1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-β1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-β1-induced expression of myofibroblast markers, as measured by the induction of α-SMA and Col1α1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-β1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 protein in human fibrotic livers • Upregulation of TRPM7 by TGF-β1 elicited Smad signaling in HSC-T6 cells

  8. Formaldehyde-Induced Aggravation of Pruritus and Dermatitis Is Associated with the Elevated Expression of Th1 Cytokines in a Rat Model of Atopic Dermatitis.

    Directory of Open Access Journals (Sweden)

    Rafael Taeho Han

    suggested that 1.2 ppm of FA penetrated the injured skin barrier, and exacerbated Th1 responses and serum IgE level in the AD rats so that dermatitis and pruritus were aggravated, while the elevated expression of Th2 cytokines by 1.2 ppm of FA in naive rats was probably insufficient for clinical manifestation. In conclusion, in a rat model of atopic dermatitis, exposure to 1.2 ppm of FA aggravated pruritus and skin inflammation, which was associated with the elevated expression of Th1 cytokines.

  9. Formaldehyde-Induced Aggravation of Pruritus and Dermatitis Is Associated with the Elevated Expression of Th1 Cytokines in a Rat Model of Atopic Dermatitis.

    Science.gov (United States)

    Han, Rafael Taeho; Back, Seung Keun; Lee, Hyunkyoung; Lee, JaeHee; Kim, Hye Young; Kim, Hee Jin; Na, Heung Sik

    2016-01-01

    .2 ppm of FA penetrated the injured skin barrier, and exacerbated Th1 responses and serum IgE level in the AD rats so that dermatitis and pruritus were aggravated, while the elevated expression of Th2 cytokines by 1.2 ppm of FA in naive rats was probably insufficient for clinical manifestation. In conclusion, in a rat model of atopic dermatitis, exposure to 1.2 ppm of FA aggravated pruritus and skin inflammation, which was associated with the elevated expression of Th1 cytokines.

  10. Data Elevator

    Energy Technology Data Exchange (ETDEWEB)

    2017-04-29

    Data Elevator: Efficient Asynchronous Data Movement in Hierarchical Storage Systems Multi-layer storage subsystems, including SSD-based burst buffers and disk-based parallel file systems (PFS), are becoming part of HPC systems. However, software for this storage hierarchy is still in its infancy. Applications may have to explicitly move data among the storage layers. We propose Data Elevator for transparently and efficiently moving data between a burst buffer and a PFS. Users specify the final destination for their data, typically on PFS, Data Elevator intercepts the I/O calls, stages data on burst buffer, and then asynchronously transfers the data to their final destination in the background. This system allows extensive optimizations, such as overlapping read and write operations, choosing I/O modes, and aligning buffer boundaries. In tests with large-scale scientific applications, Data Elevator is as much as 4.2X faster than Cray DataWarp, the start-of-art software for burst buffer, and 4X faster than directly writing to PFS. The Data Elevator library uses HDF5's Virtual Object Layer (VOL) for intercepting parallel I/O calls that write data to PFS. The intercepted calls are redirected to the Data Elevator, which provides a handle to write the file in a faster and intermediate burst buffer system. Once the application finishes writing the data to the burst buffer, the Data Elevator job uses HDF5 to move the data to final destination in an asynchronous manner. Hence, using the Data Elevator library is currently useful for applications that call HDF5 for writing data files. Also, the Data Elevator depends on the HDF5 VOL functionality.

  11. The Ca2+/calmodulin2-binding transcription factor TGA3 elevates LCD expression and H2S production to bolster Cr6+tolerance in Arabidopsis.

    Science.gov (United States)

    Fang, Huihui; Liu, Zhiqiang; Long, Yanping; Liang, Yali; Jin, Zhuping; Zhang, Liping; Liu, Danmei; Li, Hua; Zhai, Jixian; Pei, Yanxi

    2017-09-01

    Heavy metal (HM) contamination on agricultural land not only reduces crop yield but also causes human health concerns. As a plant gasotransmitter, hydrogen sulfide (H 2 S) can trigger various defense responses and help reduce accumulation of HMs in plants; however, little is known about the regulatory mechanisms of H 2 S signaling. Here, we provide evidence to answer the long-standing question about how H 2 S production is elevated in the defense of plants against HM stress. During the response of Arabidopsis to chromium (Cr 6+ ) stress, the transcription of L-cysteine desulfhydrase (LCD), the key enzyme for H 2 S production, was enhanced through a calcium (Ca 2+ )/calmodulin2 (CaM2)-mediated pathway. Biochemistry and molecular biology studies demonstrated that Ca 2+ /CaM2 physically interacts with the bZIP transcription factor TGA3, a member of the 'TGACG'-binding factor family, to enhance binding of TGA3 to the LCD promoter and increase LCD transcription, which then promotes the generation of H 2 S. Consistent with the roles of TGA3 and CaM2 in activating LCD expression, both cam2 and tga3 loss-of-function mutants have reduced LCD abundance and exhibit increased sensitivity to Cr 6+ stress. Accordingly, this study proposes a regulatory pathway for endogenous H 2 S generation, indicating that plants respond to Cr 6+ stress by adjusting the binding affinity of TGA3 to the LCD promoter, which increases LCD expression and promotes H 2 S production. This suggests that manipulation of the endogenous H 2 S level through genetic engineering could improve the tolerance of grains to HM stress and increase agricultural production on soil contaminated with HMs. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  12. Ferulic Acid Improves Functional Recovery after Acute Spinal Cord Injury in Rats by Inducing Hypoxia to Inhibit microRNA-590 and Elevate Vascular Endothelial Growth Factor Expressions.

    Science.gov (United States)

    Li, Zhenjie; Wang, Shengyun; Li, Wenfang; Yuan, Hongbin

    2017-01-01

    Spinal cord injury (SCI) is the leading cause of paralysis, disability and even death in severe cases, and neural stem cells (NSCs) transplant has been employed for repairing SCI. Ferulic acid (FA) is able to promote neurogenesis in various stem cell therapies. We aimed to investigate the effect of FA on NSC transplant therapy, and the underlying mechanism, in improving functional recovery in SCI rat model. A rat model of SCI was established, which then received transplant of NSCs with or without FA pre-treatment. Functional recovery of the SCI rats was then evaluated, in terms of spinal cord water content, myeloperoxidase activity and behavioral assessments. Effect of FA in inducing hypoxia in NSCs was also assessed, followed by identifying the hypoxic regulated microRNA and the subsequent target gene. Transplant of FA pre-treated NSCs improved functional recovery of SCI rats to a more significant extent than NSCs without FA pre-treatment. The beneficial effects of FA in repairing SCI was mediated by inducing hypoxia in NSCs, which in turn inhibited microRNA-590 to elevate vascular endothelial growth factor expression. Our findings support the clinical potential of FA in improving efficacy of NSC transplant therapy for treatment of SCI.

  13. Consolidated ethanol production from Jerusalem artichoke tubers at elevated temperature by Saccharomyces cerevisiae engineered with inulinase expression through cell surface display.

    Science.gov (United States)

    Khatun, M Mahfuza; Liu, Chen-Guang; Zhao, Xin-Qing; Yuan, Wen-Jie; Bai, Feng-Wu

    2017-02-01

    Ethanol fermentation from Jerusalem artichoke tubers was performed at elevated temperatures by the consolidated bioprocessing strategy using Saccharomyces cerevisiae MK01 expressing inulinase through cell surface display. No significant difference was observed in yeast growth when temperature was controlled at 38 and 40 °C, respectively, but inulinase activity with yeast cells was substantially enhanced at 40 °C. As a result, enzymatic hydrolysis of inulin was facilitated and ethanol production was improved with 89.3 g/L ethanol produced within 72 h from 198.2 g/L total inulin sugars consumed. Similar results were also observed in ethanol production from Jerusalem artichoke tubers with 85.2 g/L ethanol produced within 72 h from 185.7 g/L total sugars consumed. On the other hand, capital investment on cooling facilities and energy consumption for running the facilities would be saved, since regular cooling water instead of chill water could be used to cool down the fermentation system.

  14. Transgenic tobacco plants with improved cyanobacterial Rubisco expression but no extra assembly factors grow at near wild-type rates if provided with elevated CO2.

    Science.gov (United States)

    Occhialini, Alessandro; Lin, Myat T; Andralojc, P John; Hanson, Maureen R; Parry, Martin A J

    2016-01-01

    Introducing a carbon-concentrating mechanism and a faster Rubisco enzyme from cyanobacteria into higher plant chloroplasts may improve photosynthetic performance by increasing the rate of CO2 fixation while decreasing losses caused by photorespiration. We previously demonstrated that tobacco plants grow photoautotrophically using Rubisco from Synechococcus elongatus, although the plants exhibited considerably slower growth than wild-type and required supplementary CO2 . Because of concerns that vascular plant assembly factors may not be adequate for assembly of a cyanobacterial Rubisco, prior transgenic plants included the cyanobacterial chaperone RbcX or the carboxysomal protein CcmM35. Here we show that neither RbcX nor CcmM35 is needed for assembly of active cyanobacterial Rubisco. Furthermore, by altering the gene regulatory sequences on the Rubisco transgenes, cyanobacterial Rubisco expression was enhanced and the transgenic plants grew at near wild-type growth rates, although still requiring elevated CO2 . We performed detailed kinetic characterization of the enzymes produced with and without the RbcX and CcmM35 cyanobacterial proteins. These transgenic plants exhibit photosynthetic characteristics that confirm the predicted benefits of introduction of non-native forms of Rubisco with higher carboxylation rate constants in vascular plants and the potential nitrogen-use efficiency that may be achieved provided that adequate CO2 is available near the enzyme. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  15. Repression of miR-17-5p with elevated expression of E2F-1 and c-MYC in non-metastatic hepatocellular carcinoma and enhancement of cell growth upon reversing this expression pattern

    Energy Technology Data Exchange (ETDEWEB)

    El Tayebi, H.M.; Omar, K.; Hegy, S.; El Maghrabi, M.; El Brolosy, M. [The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo (Egypt); Hosny, K.A. [Department of General Surgery, Faculty of Medicine, Cairo University, Cairo (Egypt); Esmat, G. [Department of Endemic Medicine and Hepatology, Cairo University, Cairo (Egypt); Abdelaziz, A.I., E-mail: ahmed.abdel-aziz@guc.edu.eg [The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo (Egypt)

    2013-05-10

    Highlights: •The oncogenic miR-17-5p is downregulated in non-metastatic hepatocellular carcinoma patients. •E2F-1 and c-MYC transcripts are upregulated in non-metastatic HCC patients. •miR-17-5p forced overexpression inhibited E2F-1 and c-MYC expression in HuH-7 cells. •miR-17-5p mimicking increased HuH-7 cell growth, proliferation, migration and colony formation. •miR-17-5p is responsible for HCC progression among the c-MYC/E2F-1/miR-17-5p triad members. -- Abstract: E2F-1, c-MYC, and miR-17-5p is a triad of two regulatory loops: a negative and a positive loop, where c-MYC induces the expression of E2F-1 that induces the expression of miR-17-5p which in turn reverses the expression of E2F-1 to close the loop. In this study, we investigated this triad for the first time in hepatocellular carcinoma (HCC), where miR-17-5p showed a significant down-regulation in 23 non-metastatic HCC biopsies compared to 10 healthy tissues; however, E2F-1 and c-MYC transcripts were markedly elevated. Forced over-expression of miR-17-5p in HuH-7 cells resulted in enhanced cell proliferation, growth, migration and clonogenicity with concomitant inhibition of E2F-1 and c-MYC transcripts expressions, while antagomirs of miR-17-5p reversed these events. In conclusion, this study revealed a unique pattern of expression for miR-17-5p in non-metastatic HCC patients in contrast to metastatic HCC patients. In addition we show that miR-17-5p is the key player among the triad that tumor growth and spread.

  16. Repression of miR-17-5p with elevated expression of E2F-1 and c-MYC in non-metastatic hepatocellular carcinoma and enhancement of cell growth upon reversing this expression pattern

    International Nuclear Information System (INIS)

    El Tayebi, H.M.; Omar, K.; Hegy, S.; El Maghrabi, M.; El Brolosy, M.; Hosny, K.A.; Esmat, G.; Abdelaziz, A.I.

    2013-01-01

    Highlights: •The oncogenic miR-17-5p is downregulated in non-metastatic hepatocellular carcinoma patients. •E2F-1 and c-MYC transcripts are upregulated in non-metastatic HCC patients. •miR-17-5p forced overexpression inhibited E2F-1 and c-MYC expression in HuH-7 cells. •miR-17-5p mimicking increased HuH-7 cell growth, proliferation, migration and colony formation. •miR-17-5p is responsible for HCC progression among the c-MYC/E2F-1/miR-17-5p triad members. -- Abstract: E2F-1, c-MYC, and miR-17-5p is a triad of two regulatory loops: a negative and a positive loop, where c-MYC induces the expression of E2F-1 that induces the expression of miR-17-5p which in turn reverses the expression of E2F-1 to close the loop. In this study, we investigated this triad for the first time in hepatocellular carcinoma (HCC), where miR-17-5p showed a significant down-regulation in 23 non-metastatic HCC biopsies compared to 10 healthy tissues; however, E2F-1 and c-MYC transcripts were markedly elevated. Forced over-expression of miR-17-5p in HuH-7 cells resulted in enhanced cell proliferation, growth, migration and clonogenicity with concomitant inhibition of E2F-1 and c-MYC transcripts expressions, while antagomirs of miR-17-5p reversed these events. In conclusion, this study revealed a unique pattern of expression for miR-17-5p in non-metastatic HCC patients in contrast to metastatic HCC patients. In addition we show that miR-17-5p is the key player among the triad that tumor growth and spread

  17. Monocular Elevation Deficiency - Double Elevator Palsy

    Science.gov (United States)

    ... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

  18. NADPH oxidase inhibitor diphenyleneiodonium and reduced glutathione mitigate ethephon-mediated leaf senescence, H2O2 elevation and senescence-associated gene expression in sweet potato (Ipomoea batatas).

    Science.gov (United States)

    Chen, Hsien-Jung; Huang, Chin-Shu; Huang, Guan-Jhong; Chow, Te-Jin; Lin, Yaw-Huei

    2013-11-15

    Ethephon, an ethylene releasing compound, promoted leaf senescence, H2O2 elevation, and senescence-associated gene expression in sweet potato. It also affected the glutathione and ascorbate levels, which in turn perturbed H2O2 homeostasis. The decrease of reduced glutathione and the accumulation of dehydroascorbate correlated with leaf senescence and H2O2 elevation at 72h in ethephon-treated leaves. Exogenous application of reduced glutathione caused quicker and significant increase of its intracellular level and resulted in the attenuation of leaf senescence and H2O2 elevation. A small H2O2 peak produced within the first 4h after ethephon application was also eliminated by reduced glutathione. Diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, delayed leaf senescence and H2O2 elevation at 72h, and its influence was effective only within the first 4h after ethephon treatment. Ethephon-induced senescence-associated gene expression was repressed by DPI and reduced glutathione at 72h in pretreated leaves. Leaves treated with l-buthionine sulfoximine, an endogenous glutathione synthetase inhibitor, did enhance senescence-associated gene expression, and the activation was strongly repressed by reduced glutathione. In conclusion, ethephon-mediated leaf senescence, H2O2 elevation and senescence-associated gene expression are all alleviated by reduced glutathione and NADPH oxidase inhibitor DPI. The speed and the amount of intracellular reduced glutathione accumulation influence its effectiveness of protection against ethephon-mediated effects. Reactive oxygen species generated from NADPH oxidase likely serves as an oxidative stress signal and participates in ethephon signaling. The possible roles of NADPH oxidase and reduced glutathione in the regulation of oxidative stress signal in ethephon are discussed. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. The RNA helicase/transcriptional co-regulator, p68 (DDX5), stimulates expression of oncogenic protein kinase, Polo-like kinase-1 (PLK1), and is associated with elevated PLK1 levels in human breast cancers

    Science.gov (United States)

    Iyer, R Sumanth; Nicol, Samantha M; Quinlan, Philip R; Thompson, Alastair M; Meek, David W; Fuller-Pace, Frances V

    2014-01-01

    p68 (DDX5) acts both as an ATP-dependent RNA helicase and as a transcriptional co-activator of several cancer-associated transcription factors, including the p53 tumor suppressor. p68 is aberrantly expressed in a high proportion of cancers, but the oncogenic drive for, or the consequences of, these expression changes remain unclear. Here we show that elevated p68 expression in a cohort of human breast cancers is associated significantly with elevated levels of the oncogenic protein kinase, Polo-like kinase-1 (PLK1). Patients expressing detectable levels of both p68 and PLK1 have a poor prognosis, but only if they also have mutation in the TP53 gene (encoding p53), suggesting that p68 can regulate PLK1 levels in a manner that is suppressed by p53. In support of this hypothesis, we show that p68 stimulates expression from the PLK1 promoter, and that silencing of endogenous p68 expression downregulates endogenous PLK1 gene expression. In the absence of functional p53, p68 stimulates the expression of PLK1 both at basal levels and in response to the clinically relevant drug, etoposide. In keeping with a role as a transcriptional activator/co-activator, chromatin immuno-precipitation analysis shows that p68 is associated with the PLK1 promoter, irrespective of the p53 status. However, its recruitment is stimulated by etoposide in cells lacking p53, suggesting that p53 can oppose association of p68 with the PLK1 promoter. These data provide a model in which p68 and p53 interplay regulates PLK1 expression, and which describes the behavior of these molecules, and the outcome of their interaction, in human breast cancer. PMID:24626184

  20. An elevator

    Energy Technology Data Exchange (ETDEWEB)

    Rastorguyev, M.A.; Maloyarovslavtesv, D.A.; Prokopov, O.I.; Tukayev, Sh.V.; Zanilov, I.F.

    1983-01-01

    An elevator is proposed which includes a body with a turning collar locking device and a rod with longitudinal grooves, which are flexibly linked with jaws positioned in grooves in the body. To increase safety through ensuring automatic locking of the jaws in the closed position, the locking device is made in the form of head on wedges, spring loaded relative to the collar and made with cams and positioned with the capability of interacting with the grooves of the rod and through the cams with the collar.

  1. Bucket elevator

    OpenAIRE

    Chromek, Jiří

    2013-01-01

    Cílem této bakalářské práce je návrh svislého korečkového elevátoru, který má sloužit k dopravě obilovin s dopravní výškou 19 m a dopravovaným množstvím 100 t/hod. Práce se skládá z popisu korečkového elevátoru a jeho hlavních částí, zmiňující se v úvodní rešerši. Tato práce je zaměřena na funkční a kapacitní výpočet, určení pohonu a napínacího zařízení. Další výpočet je kontrolní, skládající se z pevnostní kontroly hnacího hřídele, výpočtu pera, životnosti ložisek a výpočtu napínacího zaříze...

  2. Roles of Prolyl Isomerases in RNA-Mediated Gene Expression

    Directory of Open Access Journals (Sweden)

    Roopa Thapar

    2015-05-01

    Full Text Available The peptidyl-prolyl cis-trans isomerases (PPIases that include immunophilins (cyclophilins and FKBPs and parvulins (Pin1, Par14, Par17 participate in cell signaling, transcription, pre-mRNA processing and mRNA decay. The human genome encodes 19 cyclophilins, 18 FKBPs and three parvulins. Immunophilins are receptors for the immunosuppressive drugs cyclosporin A, FK506, and rapamycin that are used in organ transplantation. Pin1 has also been targeted in the treatment of Alzheimer’s disease, asthma, and a number of cancers. While these PPIases are characterized as molecular chaperones, they also act in a nonchaperone manner to promote protein-protein interactions using surfaces outside their active sites. The immunosuppressive drugs act by a gain-of-function mechanism by promoting protein-protein interactions in vivo. Several immunophilins have been identified as components of the spliceosome and are essential for alternative splicing. Pin1 plays roles in transcription and RNA processing by catalyzing conformational changes in the RNA Pol II C-terminal domain. Pin1 also binds several RNA binding proteins such as AUF1, KSRP, HuR, and SLBP that regulate mRNA decay by remodeling mRNP complexes. The functions of ribonucleoprotein associated PPIases are largely unknown. This review highlights PPIases that play roles in RNA-mediated gene expression, providing insight into their structures, functions and mechanisms of action in mRNP remodeling in vivo.

  3. Elevated expression of LSD1 (Lysine-specific demethylase 1 during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Serce Nuran

    2012-08-01

    Full Text Available Abstract Background Lysine-specific demethylase1 (LSD1 is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS in comparison to invasive ductal breast cancer (IDC. Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27, intermediate grade DCIS (n = 30, high grade DCIS (n = 31 and in invasive ductal breast cancer (n = 32. SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

  4. Elevated mammaglobin (h-MAM) expression in breast cancer is associated with clinical and biological features defining a less aggressive tumour phenotype

    International Nuclear Information System (INIS)

    Núñez-Villar, MJ; Martínez-Arribas, F; Pollán, M; Lucas, AR; Sánchez, J; Tejerina, A; Schneider, J

    2003-01-01

    Mammaglobin (h-MAM) is expressed mainly by breast epithelial cells, and this feature has been used to detect circulating breast cancer cells and occult metastases in sentinel axillary lymph nodes of breast cancer patients. However, the biological role of mammaglobin is completely unknown. We studied 128 fresh-frozen breast cancer specimens by means of reverse transcriptase–polymerase chain reaction and quantified their h-MAM mRNA expression. This was then correlated with histological and nuclear grade, oestrogen and progesterone receptor expression, c-erb-B2 and mutant p53 expression, as well as with cellular proliferation measured by means of the Ki67 labelling index, DNA ploidy and S-phase, and finally with the presence or not of invaded axillary nodes in the mastectomy specimen. In the univariate analysis, high h-MAM expression (above the median for the whole group) correlated significantly (P < 0.05) with oestrogen and progesterone receptor expression, diploid DNA content, low Ki67 labelling index, low nuclear grade and almost significantly (P = 0.058) with the absence of axillary nodal invasion in the mastectomy specimen. In a final, multivariate model, only progesterone receptor expression, diploid DNA content and absence of nodal invasion were found to be independently associated with high h-MAM expression. All of the features associated with mammaglobin expression reflect, without exception, a less aggressive tumour phenotype. Further studies are needed to clarify whether this is attributable to h-MAM expression itself, or to another mechanism of which mammaglobin expression forms part

  5. Elevated Atherosclerosis-Related Gene Expression, Monocyte Activation and Microparticle-Release Are Related to Increased Lipoprotein-Associated Oxidative Stress in Familial Hypercholesterolemia

    OpenAIRE

    Hjuler Nielsen, Morten; Irvine, Helle; Vedel, Simon; Raungaard, Bent; Beck-Nielsen, Henning; Handberg, Aase

    2015-01-01

    Objective Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypothesis that elevated oxLDL-C induce proinflammatory monocytes and increased release of monocyte-derived microparticles (MMPs), as well as up-regulation of CD36, chemokine receptors and proinflammatory fa...

  6. Expression

    Directory of Open Access Journals (Sweden)

    Wang-Xia Wang

    2014-02-01

    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  7. Yoghurt fermentation at elevated temperatures by strains of Streptococcus thermophilus expressing a small heat-shock protein: application of a two-plasmid system for constructing food-grade strains of Streptococcus thermophilus.

    Science.gov (United States)

    El Demerdash, Hassan A; Oxmann, Julian; Heller, Knut J; Geis, Arnold

    2006-04-01

    Streptococcus thermophilus S4 expressing a small heat-shock protein from the plasmid pSt04-encoded copy of shsp, is able to carry out fermentation at elevated temperature, i.e., at 50 degrees C. In yoghurt culture together with Lactobacillus delbrueckii subsp. bulgaricus, fermentation at elevated temperature results in a mild yoghurt with low post-acidification and improved stability of the starter bacteria during storage at 4 degrees C. To transfer pSt04 into commercial S. thermophilus yoghurt starter strains, a two-plasmid system was constructed. A helper plasmid providing a selectable antibiotic marker, but relying on the repA gene of pSt04, was transformed together with pSt04. After isolation of transformants, the helper plasmid was readily lost upon incubation of transformants in antibiotic-free medium, thus yielding food-grade strains carrying pSt04 only. Successful application of the system was demonstrated.

  8. Experimental Autoimmune Encephalomyelitis (EAE-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1: Implications in Multiple Sclerosis (MS-Induced Neurological Disability and Associated Myelin Damage

    Directory of Open Access Journals (Sweden)

    Tina Khorshid Ahmad

    2017-06-01

    Full Text Available Multiple sclerosis (MS is a chronic neurological disease characterized by the destruction of central nervous system (CNS myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2 called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC and active control (AC animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC. The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG. Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC

  9. Elevated responses to constant facial emotions in different faces in the human amygdala: an fMRI study of facial identity and expression

    Directory of Open Access Journals (Sweden)

    Weiller Cornelius

    2004-11-01

    Full Text Available Abstract Background Human faces provide important signals in social interactions by inferring two main types of information, individual identity and emotional expression. The ability to readily assess both, the variability and consistency among emotional expressions in different individuals, is central to one's own interpretation of the imminent environment. A factorial design was used to systematically test the interaction of either constant or variable emotional expressions with constant or variable facial identities in areas involved in face processing using functional magnetic resonance imaging. Results Previous studies suggest a predominant role of the amygdala in the assessment of emotional variability. Here we extend this view by showing that this structure activated to faces with changing identities that display constant emotional expressions. Within this condition, amygdala activation was dependent on the type and intensity of displayed emotion, with significant responses to fearful expressions and, to a lesser extent so to neutral and happy expressions. In contrast, the lateral fusiform gyrus showed a binary pattern of increased activation to changing stimulus features while it was also differentially responsive to the intensity of displayed emotion when processing different facial identities. Conclusions These results suggest that the amygdala might serve to detect constant facial emotions in different individuals, complementing its established role for detecting emotional variability.

  10. Simultaneous pancreas-kidney transplantation in patients with type 1 diabetes reverses elevated MBL levels in association with MBL2 genotype and VEGF expression.

    Science.gov (United States)

    Bijkerk, Roel; van der Pol, Pieter; Khairoun, Meriem; van Gijlswijk-Jansen, Danielle J; Lievers, Ellen; de Vries, Aiko P J; de Koning, Eelco J; de Fijter, Hans W; Roelen, Dave L; Vossen, Rolf H A M; van Zonneveld, Anton Jan; van Kooten, Cees; Reinders, Marlies E J

    2016-04-01

    High levels of circulating mannan-binding lectin (MBL) are associated with the development of diabetic nephropathy and hyperglycaemia-induced vasculopathy. Here, we aimed to assess the effect of glycaemic control on circulating levels of MBL and the relationship of these levels with vascular damage. We assessed MBL levels and corresponding MBL2 genotype, together with vascular endothelial growth factor (VEGF) levels as a marker of vascular damage, in type 1 diabetes patients with diabetic nephropathy before and after simultaneous pancreas-kidney (SPK) transplantation. We included diabetic nephropathy patients (n = 21), SPK patients (n = 37), healthy controls (n = 19), type 1 diabetes patients (n = 15) and diabetic nephropathy patients receiving only a kidney transplant (n = 15). Fourteen diabetic nephropathy patients were followed up for 12 months after SPK. We found elevated circulating MBL levels in diabetic nephropathy patients, and a trend towards elevated circulating MBL levels in type 1 diabetes patients, compared with healthy control individuals. MBL levels in SPK patients completely normalised and our data indicate that this predominantly occurs in patients with a polymorphism in the MBL2 gene. By contrast, MBL levels in kidney transplant only patients remained elevated, suggesting that glycaemic control but not reversal of renal failure is associated with decreased MBL levels. In line, levels of glucose and HbA1c, but not creatinine levels and estimated GFR, were correlated with MBL levels. VEGF levels were associated with levels of MBL and HbA1c in an MBL-polymorphism-dependent manner. Taken together, circulating MBL levels are associated with diabetic nephropathy and are dependent on glycaemic control, possibly in an MBL2-genotype-dependent manner.

  11. MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13

    OpenAIRE

    Sankaran, Vijay G.; Menne, Tobias F.; Šćepanović, Danilo; Vergilio, Jo-Anne; Ji, Peng; Kim, Jinkuk; Thiru, Prathapan; Orkin, Stuart H.; Lander, Eric S.; Lodish, Harvey F.

    2011-01-01

    Many human aneuploidy syndromes have unique phenotypic consequences, but in most instances it is unclear whether these phenotypes are attributable to alterations in the dosage of specific genes. In human trisomy 13, there is delayed switching and persistence of fetal hemoglobin (HbF) and elevation of embryonic hemoglobin in newborns. Using partial trisomy cases, we mapped this trait to chromosomal band 13q14; by examining the genes in this region, two microRNAs, miR-15a and -16-1, appear as t...

  12. Gene expression of hematoregulatory cytokines is elevated endogenously after sublethal gamma irradiation and is differentially enhanced by therapeutic administration of biologic response modifiers

    International Nuclear Information System (INIS)

    Peterson, V.M.; Adamovicz, J.J.; Madonna, G.S.; Gause, W.C.; Elliott, T.B.; Moore, M.M.; Ledney, G.D.; Jackson, W.E. III

    1994-01-01

    Prompt, cytokine-mediated restoration of hematopoiesis is a prerequisite for survival after irradiation. Therapy with biologic response modifiers (BRMs), such as LPS, 3D monophosphoryl lipid A (MPL), and synthetic trehalose dicrynomycolate (S-TDCM) presumably accelerates hematopoietic recovery after irradiation are poorly defined. One hour after sublethal (7.0 Gy) 60 Co gamma irradiation, B6D2F1/J female mice received a single i.p. injection of LPS, MPL, S-TDCM, an extract from Serratia marcescens (Sm-BRM), or Tween 80 in saline (TS). Five hours later, a quantitative reverse transcription-PCR assay demonstrated marked splenic gene expression for IL-1β, IL-3, IL-6, and granulocyte-CSF (G-CSF). Enhanced gene expression for TNF-α, macrophage-CSF (M-CSF), and stem cell factor (SCF) was not detected. Injection of any BRM further enhanced cytokine gene expression and plasma levels of CSF activity within 24 h after irradiation and hastened bone marrow recovery. Mice injected with S-TDCM or Sm-BRM sustained expression of the IL-6 gene for at least 24 h after irradiation. Sm-BRM-treated mice exhibited greater gene expression for IL-1β, IL-3, TNF-α, and G-CSF at day 1 than any other BRM. When challenged with 2 LD 50/30 of Klebsiella pneumoniae 4 days after irradiation, 100% of Sm-BRM-treated mice and 70% of S-TDCM-treated mice survived, whereas ≤30% of mice treated with LPS, MPL, or TS survived. Thus, sublethal irradiation induces transient, splenic cytokine gene expression that can be differentially amplified and prolonged by BRMs. BRMs that sustained and/or enhanced irradiation-induced expression of specific cytokine genes improved survival after experimental infection. 67 refs., 7 figs., 1 tab

  13. Mechanical strain stimulates vasculogenesis and expression of angiogenesis guidance molecules of embryonic stem cells through elevation of intracellular calcium, reactive oxygen species and nitric oxide generation.

    Science.gov (United States)

    Sharifpanah, Fatemeh; Behr, Sascha; Wartenberg, Maria; Sauer, Heinrich

    2016-12-01

    Differentiation of embryonic stem (ES) cells may be regulated by mechanical strain. Herein, signaling molecules underlying mechanical stimulation of vasculogenesis and expression of angiogenesis guidance cues were investigated in ES cell-derived embryoid bodies. Treatment of embryoid bodies with 10% static mechanical strain using a Flexercell strain system significantly increased CD31-positive vascular structures and the angiogenesis guidance molecules plexinB1, ephrin B2, neuropilin1 (NRP1), semaphorin 4D (sem4D) and robo4 as well as vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-BB (PDGF-BB) as evaluated by Western blot and real time RT-PCR. In contrast ephrin type 4 receptor B (EphB4) expression was down-regulated upon mechanical strain, indicating an arterial-type differentiation. Robo1 protein expression was modestly increased with no change in mRNA expression. Mechanical strain increased intracellular calcium as well as reactive oxygen species (ROS) and nitric oxide (NO). Mechanical strain-induced vasculogenesis was abolished by the NOS inhibitor L-NAME, the NADPH oxidase inhibitor VAS2870, upon chelation of intracellular calcium by BAPTA as well as upon siRNA inactivation of ephrin B2, NRP1 and robo4. BAPTA blunted the strain-induced expression of angiogenic growth factors, the increase in NO and ROS as well as the expression of NRP1, sem4D and plexinB1, whereas ephrin B2, EphB4 as well as robo1 and robo4 expression were not impaired. Mechanical strain stimulates vasculogenesis of ES cells by the intracellular messengers ROS, NO and calcium as well as by upregulation of angiogenesis guidance molecules and the angiogenic growth factors VEGF, FGF-2 and PDGF-BB. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. ADAMTS-7 Exhibits Elevated Expression in Cartilage of Osteonecrosis of Femoral Head and Has a Positive Correlation with TNF-α and NF-κB P65

    Directory of Open Access Journals (Sweden)

    Jing-kun Li

    2015-01-01

    Full Text Available ADAMTS-7 has been reported to exaggerate cartilage degeneration and to be associated with TNF-α and NF-κB signaling pathway. In this study we compared the expression of ADAMTS-7, TNF-α, and Phospho-NF-κB in patients with femoral neck fracture (FNF and osteonecrosis of femoral head (ONFH at different stages. We found that expression of ADAMTS-7, TNF-α, and Phospho-NF-κB was significantly upregulated in ONFH patients’ articular cartilage and related to the pathogenesis of ONFH. Thus we conclude that ADAMTS-7 level appears to be positively associated with expression of TNF-α and Phospho-NF-κB P65 in cartilage, which may imply its association with cartilage destruction of ONFH.

  15. Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

    Science.gov (United States)

    Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

    2017-12-01

    The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

  16. Elevated microRNA-126 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Andersen, Claus Lindbjerg; Nielsen, Boye Schnack

    2011-01-01

    was to analyse the possible relationship between miRNA-126, VEGFR-2 and angiogenesis in tumour tissue from patients with colorectal cancer (CRC). Tumour tissue was obtained from 81 patients. The miRNA-126 and VEGFR-2 gene expression levels were analysed by PCR and the protein concentrations of VEGFR-2 were...... analysed by ELISA. Angiogenesis, visualised by the endothelial cell marker CD105 combined with caldesmon, was assessed by immunohistochemistry and the microvessel density (MVD) technique. In situ hybridisation was performed for miRNA-126. Tumours were classified as low or high miRNA-126-expressing using...

  17. Reduced miR-512 and the Elevated Expression of Its Targets cFLIP and MCL1 Localize to Neurons With Hyperphosphorylated Tau Protein in Alzheimer Disease.

    Science.gov (United States)

    Mezache, Louisa; Mikhail, Madison; Garofalo, Michela; Nuovo, Gerard J

    2015-10-01

    The cause for the neurofibrillary tangles and plaques in Alzheimer disease likely relates to an abnormal accumulation of their key components, which include β-amyloid and hyperphosphorylated tau protein. We segregated Alzheimer brain sections from people with end-stage disease into those with abundant hyperphosphorylated tau protein and those without and compared each to normal brains for global microRNA patterns. A significant reduced expression of several microRNAs, including miR-512, was evident in the Alzheimer brain sections with abundant hyperphosphorylated tau. Immunohistochemistry documented that 2 known targets of microRNA-512, cFLIP and MCL1, were significantly over expressed and each colocalized to neurons with the abnormal tau protein. Analysis for apoptosis including activated caspase-3, increased caspase-4 and caspase-8, apoptosis initiating factor, APAF-1 activity, and the TUNEL assay was negative in the areas where neurons showed hyperphosphorylated tau. MCM2 expression, a marker of neuroprogenitor cells, was significantly reduced in the Alzheimer sections that contained the hyperphosphorylated tau. These results suggest that a basic defect in Alzheimer disease may be the reduced microRNA-driven increased expression of proteins that may alter the apoptotic/antiapoptotic balance of neurons. This, in turn, could lead to the accumulation of key Alzheimer proteins such as hyperphosphorylated tau that ultimately prevent normal neuronal function and lead to disease symptomatology.

  18. Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival.

    Science.gov (United States)

    Kang, M K; Kim, R H; Kim, S J; Yip, F K; Shin, K-H; Dimri, G P; Christensen, R; Han, T; Park, N-H

    2007-01-15

    Bmi-1 is a polycomb group protein that was identified as c-myc cooperating oncogene in murine lymphomagenesis. The current study was undertaken to determine the role of Bmi-1 in human oral carcinogenesis. Bmi-1 protein and RNA expression levels were markedly enhanced in the cells of oral squamous cell carcinomas (OSCC) compared with that of normal human oral keratinocytes (NHOK). Enhanced-Bmi-1 expression was also detected in situ in the archived oral mucosal tissues with cancerous and precancerous histopathology, including that of mild epithelial dysplasia. Thus, Bmi-1 expression occurs at a very early stage in oral carcinogenesis. To determine the biological role of Bmi-1 in cell proliferation, endogenous Bmi-1 was knocked down in actively proliferating SCC4 cells and NHOK by RNA interference. After Bmi-1 knockdown, cell replication was severely retarded. However, the expression of p16(INK4A), a known cellular target of Bmi-1, was not changed in cells with or without Bmi-1 knockdown. Furthermore, Bmi-1 knockdown in HOK-16B-BaP-T cells, in which the p16(INK4A)/pRb pathway was abrogated, led to immediate arrest of replication and loss of viable cells. Thus, our data suggest that Bmi-1 may act through p16(INK4A)-independent pathways to regulate cellular proliferation during oral cancer progression.

  19. In female rats, ethylene glycol treatment elevates protein expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) without inducing hyperoxaluria.

    Science.gov (United States)

    Breljak, Davorka; Brzica, Hrvoje; Vrhovac, Ivana; Micek, Vedran; Karaica, Dean; Ljubojević, Marija; Sekovanić, Ankica; Jurasović, Jasna; Rašić, Dubravka; Peraica, Maja; Lovrić, Mila; Schnedler, Nina; Henjakovic, Maja; Wegner, Waja; Burckhardt, Gerhard; Burckhardt, Birgitta C; Sabolić, Ivan

    2015-10-01

    To investigate whether the sex-dependent expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) changes in a rat model of ethylene glycol (EG)-induced hyperoxaluria. Rats were given tap water (12 males and 12 females; controls) or EG (12 males and 12 females; 0.75% v/v in tap water) for one month. Oxaluric state was confirmed by biochemical parameters in blood plasma, urine, and tissues. Expression of sat-1 and rate-limiting enzymes of oxalate synthesis, alcohol dehydrogenase 1 (Adh1) and hydroxy-acid oxidase 1 (Hao1), was determined by immunocytochemistry (protein) and/or real time reverse transcription polymerase chain reaction (mRNA). EG-treated males had significantly higher (in μmol/L; mean±standard deviation) plasma (59.7±27.2 vs 12.9±4.1, Psat-1 protein and mRNA expression did not differ significantly between these groups. EG-treated females, in comparison with controls had significantly higher (in μmol/L) serum oxalate levels (18.8±2.9 vs 11.6±4.9, Psat-1 protein, but not mRNA. The mRNA expression of Adh1 was female-dominant and that of Hao1 male-dominant, but both were unaffected by EG treatment. An increased expression of hepatic and renal oxalate transporting protein sat-1 in EG-treated female rats could protect from hyperoxaluria and oxalate urolithiasis.

  20. Elevated p16ink4a Expression in Human Labial Salivary Glands as a Potential Correlate of Cognitive Aging in Late Midlife.

    Directory of Open Access Journals (Sweden)

    Christiane Elisabeth Sørensen

    Full Text Available The cell-cycle inhibitor and tumor suppressor cyclin dependent kinase inhibitor, p16ink4a, is one of the two gene products of the ink4a/ARF (cdkn2a locus on chromosome 9q21. Up-regulation of p16ink4a has been linked to cellular senescence, and findings from studies on different mammalian tissues suggest that p16ink4a may be a biomarker of organismal versus chronological age.The aim of this study was to examine the immunolocalization pattern of p16ink4a in human labial salivary gland (LSG tissue, and to analyze whether its expression level in LSGs is a peripheral correlate of cognitive decline in late midlife.The present study was a part of a study of causes and predictors of cognitive decline in middle-aged men in a Danish birth cohort. It is based on data from 181 male participants from the Danish Metropolit birth cohort, born in 1953, who were examined for age-associated alterations in cognition, dental health, and morphological and autonomic innervation characteristics of the LSGs. The participants were allocated to two groups based on the relative change in cognitive performance from young adulthood to late midlife. LSG biopsies were analyzed by qRT-PCR for the expression level of p16ink4a. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of LSGs.p16ink4a immunoreactivity was observed in LSG ductal, myoepithelial, and stromal cells, but not in acinar cells. The mean relative expression of p16ink4a in LSGs was higher in the group of participants with decline in cognitive performance. A logistic regression analysis revealed that the relative p16 expression was predictive of the participant's group assignment. A negative correlation was found between relative p16ink4a expression and the participant's standardized regression residuals from early adulthood to late midlife cognitive performance scores.p16ink4a expression in human LSGs may constitute a potential peripheral correlate of cognitive decline. Human labial

  1. Cooperative Actions of CRP-cAMP and FNR Increase the Fosfomycin Susceptibility of Enterohaemorrhagic Escherichia coli (EHEC) by Elevating the Expression of glpT and uhpT under Anaerobic Conditions.

    Science.gov (United States)

    Kurabayashi, Kumiko; Tanimoto, Koichi; Tomita, Haruyoshi; Hirakawa, Hidetada

    2017-01-01

    Bacterial infections to anaerobic site are often hard to be treated because the activity of most of antimicrobials decreases under anaerobic conditions. However, fosfomycin rather provides a greater activity under anaerobic conditions than aerobic conditions. Previously, we found that expression of glpT and uhpT , fosfomycin symporters in enterohaemorrhagic Escherichia coli (EHEC) was upregulated by FNR, a global regulator during the anaerobiosis of the bacterium, which led to increased uptake and susceptibility to this drug. In this study, we showed that expression of glpT and uhpT is induced by CRP-cAMP, the regulator complex under both aerobic and anaerobic conditions. The activity of CRP-cAMP in EHEC was elevated under anaerobic conditions because levels of both CRP and cAMP were higher in the cells when grown anaerobically than those when grown aerobically. Results of expression study using mutants indicated that CRP-cAMP is indispensable for expression of glpT but not uhpT -whereas that of uhpT requires UhpA that is the response regulator composing of two-component system with the sensor kinase, UhpB. The CRP-cAMP protein bound to a region that overlaps RNA polymerase binding site for glpT and region upstream of UhpA binding site for uhpT . FNR bound to a region further upstream of CRP-cAMP binding site on region upstream of the glpT gene. These combined results suggested that increased antibacterial activity of fosfomycin to EHEC under anaerobic conditions is due to activation of FNR and increment of CRP-cAMP activity. Then, FNR enhances the expression of glpT activated by CRP-cAMP while CRP-cAMP and FNR cooperatively aids the action of UhpA to express uhpT to maximum level.

  2. Deregulated MicroRNA-21 Expression in Monocytes from HIV-Infected Patients Contributes to Elevated IP-10 Secretion in HIV Infection

    Directory of Open Access Journals (Sweden)

    Xian Wu

    2017-09-01

    Full Text Available Persistent activation and inflammation impair immune response and trigger disease progression in HIV infection. Emerging evidence supports the supposition that excessive production of interferon-inducible protein 10 (IP-10, a critical inflammatory cytokine, leads to immune dysfunction and disease progression in HIV infection. In this study, we sought to elucidate the cause of the upregulated production of IP-10 in HIV infection and explore the underlying mechanisms. Bolstering miR-21 levels using mimics resulted in the obvious suppression of lipopolysaccharide (LPS-induced IP-10 in monocyte leukemia cells THP-1 and vice versa. The analysis of the primary monocytes of HIV patients revealed significantly less miR-21 than in healthy controls; this was opposite to the tendency of IP-10 levels in plasma. The secretion of IP-10 due to LPS stimulation was not affected by miR-21 modulation in the differentiated THP-1 macrophages (THP-1-MA. We found a novel switch, IFN-stimulated gene 15 (ISG15, which triggers the expression of IP-10 and is significantly upregulated during the differentiation of THP-1 into THP-1-MA. The inhibition of ISG15 can restore the regulation of IP-10 by miR-21. In summary, IP-10 expression in monocytes is regulated by miR-21, whereas in macrophages, this fine-tuning is attenuated by the enhanced expression of ISG15. This study paves the way to a comprehensive understanding of the molecular regulatory mechanism of IP-10, a key point in immune intervention strategy.

  3. Over-accumulation of nuclear IGF-1 receptor in tumor cells requires elevated expression of the receptor and the SUMO-conjugating enzyme Ubc9

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Hua; Lin, Yingbo; Badin, Margherita; Vasilcanu, Daiana; Stroemberg, Thomas [Department of Oncology and Pathology, The Karolinska Institute, Cancer Center Karolinska, SE-17176 Stockholm (Sweden); Jernberg-Wiklund, Helena [Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala (Sweden); Sehat, Bita [Department of Oncology and Pathology, The Karolinska Institute, Cancer Center Karolinska, SE-17176 Stockholm (Sweden); Larsson, Olle, E-mail: olle.larsson@ki.se [Department of Oncology and Pathology, The Karolinska Institute, Cancer Center Karolinska, SE-17176 Stockholm (Sweden)

    2011-01-14

    Research highlights: {yields} SUMOylation mediates nuclear translocation of IGF-1R which activates transcription. {yields} Here we show that nuclear IGF-1R over-accumulates in tumor cells. {yields} This requires overexpression of the receptor that is a common feature in tumor cells. {yields} An increased expression of the SUMO ligase Ubc9 seems to be an involved mechanism too. -- Abstract: The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in tumor cell growth and is overexpressed in many cancers. IGF-1R's trans-membrane kinase signaling pathways have been well characterized. Very recently, we showed that SUMOylation mediates nuclear translocation of the IGF-1R, and that nuclear IGF-1R (nIGF-1R) binds to enhancer regions and activates transcription. We identified three lysine residues in the {beta}-subunit of the receptor and that mutation of these blocks nuclear translocation and gene activation. Furthermore, accumulation of nIGF-1R was proven strongly dependent on the specific SUMO-conjugating enzyme Ubc9. Here we show that nIGF-1R originates solely from the cell membrane and that phosphorylation of the core tyrosine residues of the receptor kinase is crucial for nuclear accumulation. We also compared the levels of nIGF-1R, measured as nuclear/membrane ratios, in tumor and normal cells. We found that the breast cancer cell line MCF-7 has 13-fold higher amounts of nIGF-1R than breast epithelial cells (IME) which showed only a small amount of nIGF-1R. In comparison, the total expression of IGF-1R was only 3.7- higher in MCF-7. Comparison of several other tumor and normal cell lines showed similar tumor cell over-accumulation of nIGF-1R, exceeding the total receptor expression substantially. Ectopic overexpression (>10-fold) of the receptor increased nIGF-1R in IME cells but not to that high level as in wild type MCF-7. The levels of Ubc9 were higher in all tumor cell lines, compared to the normal cells, and this probably contributes to over

  4. Over-accumulation of nuclear IGF-1 receptor in tumor cells requires elevated expression of the receptor and the SUMO-conjugating enzyme Ubc9

    International Nuclear Information System (INIS)

    Deng, Hua; Lin, Yingbo; Badin, Margherita; Vasilcanu, Daiana; Stroemberg, Thomas; Jernberg-Wiklund, Helena; Sehat, Bita; Larsson, Olle

    2011-01-01

    Research highlights: → SUMOylation mediates nuclear translocation of IGF-1R which activates transcription. → Here we show that nuclear IGF-1R over-accumulates in tumor cells. → This requires overexpression of the receptor that is a common feature in tumor cells. → An increased expression of the SUMO ligase Ubc9 seems to be an involved mechanism too. -- Abstract: The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in tumor cell growth and is overexpressed in many cancers. IGF-1R's trans-membrane kinase signaling pathways have been well characterized. Very recently, we showed that SUMOylation mediates nuclear translocation of the IGF-1R, and that nuclear IGF-1R (nIGF-1R) binds to enhancer regions and activates transcription. We identified three lysine residues in the β-subunit of the receptor and that mutation of these blocks nuclear translocation and gene activation. Furthermore, accumulation of nIGF-1R was proven strongly dependent on the specific SUMO-conjugating enzyme Ubc9. Here we show that nIGF-1R originates solely from the cell membrane and that phosphorylation of the core tyrosine residues of the receptor kinase is crucial for nuclear accumulation. We also compared the levels of nIGF-1R, measured as nuclear/membrane ratios, in tumor and normal cells. We found that the breast cancer cell line MCF-7 has 13-fold higher amounts of nIGF-1R than breast epithelial cells (IME) which showed only a small amount of nIGF-1R. In comparison, the total expression of IGF-1R was only 3.7- higher in MCF-7. Comparison of several other tumor and normal cell lines showed similar tumor cell over-accumulation of nIGF-1R, exceeding the total receptor expression substantially. Ectopic overexpression (>10-fold) of the receptor increased nIGF-1R in IME cells but not to that high level as in wild type MCF-7. The levels of Ubc9 were higher in all tumor cell lines, compared to the normal cells, and this probably contributes to over-accumulation of nIGF-1R

  5. Reduced volume and increased training intensity elevate muscle Na+/K+ pump {alpha}2-subunit expression as well as short- and long-term work capacity in humans

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Gunnarsson, Thomas Petursson; Wendell, Jesper

    2009-01-01

    was unaltered, but the 3-K (3,000 m) time was reduced (Pexpression and performance remained unaltered in CON. The present data suggest that both short- and long-term......% reduction in the amount of training but including speed endurance training consisting of 6-12 30-s sprint runs 3-4 times a week (SET, n=12) or a control group (CON, n=5), which continued the endurance training (about 55 km(.)wk(-1)). For SET the expression of the muscle Na(+)/K(+) pump alpha2-subunit was 68...

  6. Behavioral evaluation of transgenic mice with CNS expression of IFN-α by elevated plus-maze and Porsolt swim test

    OpenAIRE

    Zhang, Hua; Tian, Zhanzhuang; Wang, Jianping

    2010-01-01

    Chronic IFN-α treatment as an antiviral or anti-cancer therapy can lead to severe psychiatric complications, including depression and anxiety in patients. In many animal models of IFN-α-induced behavioral dysfunction, the opposite results have frequently been reported. In an attempt to overcome the limitation of pharmacological studies, IFN-α-transgenic mice with CNS-targeted expression of the IFN-α transgene were used to study depression- and anxiety-like behaviors by Porsolt swim and elevat...

  7. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  8. National Elevation Dataset (NED)

    Data.gov (United States)

    Kansas Data Access and Support Center — The U.S. Geological Survey has developed a National Elevation Database (NED). The NED is a seamless mosaic of best-available elevation data. The 7.5-minute elevation...

  9. Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria

    DEFF Research Database (Denmark)

    Shabani, Estela; Hanisch, Benjamin; Opoka, Robert O.

    2017-01-01

    Background: Expression of group A and the A-like subset of group B Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying...... the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM). The question of whether children with clinical CM but no retinopathy represent...... a completely different disease process or a subgroup within the spectrum of CM remains an important question in malaria. In the current study, we use newly designed primer sets with the best coverage to date in a large cohort of children with SM to determine the role of var genes in malaria disease severity...

  10. Elevated expression of serotonin 5-HT2A receptors in the rat ventral tegmental area enhances vulnerability to the behavioral effects of cocaine

    Directory of Open Access Journals (Sweden)

    David V. Herin

    2013-02-01

    Full Text Available The dopamine mesocorticoaccumbens pathway which originates in the ventral tegmental area (VTA and projects to the nucleus accumbens and prefrontal cortex is a circuit important in mediating the actions of psychostimulants. The function of this circuit is modulated by the actions of serotonin (5-HT at 5-HT2A receptors (5-HT2AR localized to the VTA. In the present study, we tested the hypothesis that virally-mediated overexpression of 5-HT2AR in the VTA would increase cocaine-evoked locomotor activity in the absence of alterations in basal locomotor activity. A plasmid containing the gene for the 5-HT2AR linked to a synthetic marker peptide (Flag was created and the construct was packaged in an adeno-associated virus vector (rAAV-5-HT2AR-Flag. This viral vector (2 µl; 109-10 transducing units/ml was unilaterally infused into the VTA of male rats, while control animals received an intra-VTA infusion of Ringer’s solution. Virus-pretreated rats exhibited normal spontaneous locomotor activity measured in a modified open-field apparatus at 7, 14, and 21 days following infusion. After an injection of cocaine (15 mg/kg, ip, both horizontal hyperactivity and rearing were significantly enhanced in virus-treated rats (p<0.05. Immunohistochemical analysis confirmed expression of Flag and overexpression of the 5-HT2AR protein. These data indicate that the vulnerability of adult male rats to hyperactivity induced by cocaine is enhanced following increased levels of expression of the 5-HT2AR in the VTA and suggest that the 5-HT2AR receptor in the VTA plays a role in regulation of responsiveness to cocaine.

  11. Punica granatum L. Fruit Aqueous Extract Suppresses Reactive Oxygen Species-Mediated p53/p65/miR-145 Expressions followed by Elevated Levels of irs-1 in Alloxan-Diabetic Rats.

    Science.gov (United States)

    Gharib, Ehsan; Montasser Kouhsari, Shideh; Izad, Maryam

    2018-01-01

    Reactive oxygen species (ROS) is an apoptosis inducer in pancreatic β-cells that stimulates p53/p65 mediated microRNA (miR)-145 expression. Punica granatum L. (pomegranate) is an antioxidant fruit that attenuates ROS generation. This study examines the effects of pomegranate fruit aqueous extract (PGE) on the levels of ROS, p53, p65, miR-145, and its target insulin receptor substrate 1 (irs-1) mRNA in Alloxan-diabetic male Wistar rats. In this experimental study, diabetic rats received different doses of PGE. The effects of the PGE polyphenols were examined through a long-term PGE treatment period model, followed by an evaluation of the plasma and tissue contents of free fatty acids (FFAs), triglycerides (TG), and glycogen compared with diabetic controls (DC) and normal controls (NC). We used real-time polymerase chain reaction (PCR) to investigate the modulation of p53, p65, miR-145, and irs-1 expression levels. There was a noticeable reduction in fasting blood glucose (FBG) and ROS generation compared to DC. We observed marked decreases in p53, p65, miR-145 expression levels followed by an elevated level of irs-1, which contributed to improvement in insulin sensitivity. PGE administration downregulated miR-145 levels in Alloxan-diabetic Wistar rats by suppression of ROS-mediated p53 and p65 overexpression. Copyright© by Royan Institute. All rights reserved.

  12. Elevated p16ink4a Expression in Human Labial Salivary Glands as a Potential Correlate of Cognitive Aging in Late Midlife

    DEFF Research Database (Denmark)

    Sørensen, Christiane Elisabeth; Tritsaris, Katerina; Reibel, Jesper

    2016-01-01

    BACKGROUND: The cell-cycle inhibitor and tumor suppressor cyclin dependent kinase inhibitor, p16ink4a, is one of the two gene products of the ink4a/ARF (cdkn2a) locus on chromosome 9q21. Up-regulation of p16ink4a has been linked to cellular senescence, and findings from studies on different...... mammalian tissues suggest that p16ink4a may be a biomarker of organismal versus chronological age. OBJECTIVE: The aim of this study was to examine the immunolocalization pattern of p16ink4a in human labial salivary gland (LSG) tissue, and to analyze whether its expression level in LSGs is a peripheral...... correlate of cognitive decline in late midlife. METHODS: The present study was a part of a study of causes and predictors of cognitive decline in middle-aged men in a Danish birth cohort. It is based on data from 181 male participants from the Danish Metropolit birth cohort, born in 1953, who were examined...

  13. Strontium doping promotes bioactivity of rhBMP-2 upon calcium phosphate cement via elevated recognition and expression of BMPR-IA.

    Science.gov (United States)

    Huang, Baolin; Tian, Yu; Zhang, Wenjing; Ma, Yifan; Yuan, Yuan; Liu, Changsheng

    2017-11-01

    Preserving and improving osteogenic activity of bone morphogenetic protein-2 (BMP-2) upon implants remains one of the key limitations in bone regeneration. With calcium phosphate cement (CPC) as model, we have developed a series of strontium (Sr)-doped CPC (SCPC) to address this issue. The effects of fixed Sr on the bioactivity of recombinant human BMP-2 (rhBMP-2) as well as the underlying mechanism were investigated. The results suggested that the rhBMP-2-induced osteogenic activity was significantly promoted upon SCPCs, especially with a low amount of fixed Sr (SrCO 3 content IA (BMPR-IA) to rhBMP-2 and an increased expression of BMPR-IA in C2C12 model cells. As a result, the activations of BMP-induced signaling pathways were different in C2C12 cells incubated upon CPC/rhBMP-2 and SCPCs/rhBMP-2. These findings explicitly decipher the mechanism of SCPCs promoting osteogenic bioactivity of rhBMP-2 and signify the promising application of the SCPCs/rhBMP-2 matrix in bone regeneration implants. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Tobacco expressing pap1 increases the responses to par and uv-a by enhancing soluble sugars and flavonoids and elevating plant protections

    International Nuclear Information System (INIS)

    Sompornpailin, K.; Kanthang, S.

    2015-01-01

    Five lines of transgenic tobacco over-expressing Production of Anthocyanin Pigment 1 (PAP1) cDNA were analysis of metabolic response against the radiation and their protection of the plant under tissue culture condition. PAP1 transgenic and wild type (WT) plants were treated with the radiations of photosynthetically activate radiation (PAR) or PAR combined with UV-A. All lines of transgenic significantly increased in amounts of p-coumaric acid, naringenin apigenin more than WT under both treatments. Additional UV-A radiating to plant rose up kaempferol content in WT plant (1.5 times) and in PAP1 transgenics (1.8 times). These transgenic plants treated under both conditions had also increased anthocyanin substances (pelargonidin) with significant value after compared to WT. Content of total soluble sugar (TSS) was related to the content of total flavonoids in transgenic. PAR combined with UV-A had a lower induction of the electrolyte leakage percentage and malondialdehyde (MDA) level in the transgenic leaf tissue compared to WT tissue. The metabolic substance levels were considered on its protection of plant cells. In transgenic tissue, the enhancement of apigenin level strongly diminished the increase level of electrolyte leakage while the levels of TSS, p-coumaric acid and naringinin less affected. Moreover, the increase levels of kaempferol and pelargonidin associated with the decrease level of MDA, while the TSS level reversely responded. The PAP1 transgenic increased response of light by adaptation of their metabolites (TSS, p-coumaric acid and flavonoids) consequently enhance parameter indicating protections of the cell. (author)

  15. Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

    Energy Technology Data Exchange (ETDEWEB)

    Kwong, Raymond W.M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Andres, Jose A. [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada); Niyogi, Som, E-mail: som.niyogi@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada)

    2011-03-15

    Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

  16. Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

    International Nuclear Information System (INIS)

    Kwong, Raymond W.M.; Andres, Jose A.; Niyogi, Som

    2011-01-01

    Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

  17. A common signaling pathway is activated in erythroid cells expressing high levels of fetal hemoglobin: a potential role for cAMP-elevating agents in β-globin disorders

    Directory of Open Access Journals (Sweden)

    Ikuta T

    2013-12-01

    Full Text Available Tohru Ikuta,1 Yuichi Kuroyanagi,1 Nadine Odo,1 Siyang Liu21Department of Anesthesiology and Perioperative Medicine, 2Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GA, USABackground: Although erythroid cells prepared from fetal liver, cord blood, or blood from β-thalassemia patients are known to express fetal hemoglobin at high levels, the underlying mechanisms remain elusive. We previously showed that cyclic nucleotides such as cAMP and cGMP induce fetal hemoglobin expression in primary erythroid cells. Here we report that cAMP signaling contributes to high-level fetal hemoglobin expression in erythroid cells prepared from cord blood and β-thalassemia.Methods: The status of the cAMP signaling pathway was investigated using primary erythroid cells prepared from cord blood and the mononuclear cells of patients with β-thalassemia; erythroid cells from adult bone marrow mononuclear cells served as the control.Results: We found that intracellular cAMP levels were higher in erythroid cells from cord blood and β-thalassemia than from adult bone marrow. Protein kinase A activity levels and cAMP-response element binding protein phosphorylation were higher in erythroid cells from cord blood or β-thalassemia than in adult bone marrow progenitors. Mitogen-activated protein kinase pathways, which play a role in fetal hemoglobin expression, were not consistently activated in cord blood or β-thalassemia erythroid cells. When cAMP signaling was activated in adult erythroid cells, fetal hemoglobin was induced at high levels and associated with reduced expression of BCL11A, a silencer of the β-globin gene.Conclusion: These results suggest that activated cAMP signaling may be a common mechanism among erythroid cells with high fetal hemoglobin levels, in part because of downregulation of BCL11A. Activation of the cAMP signaling pathway with cAMP-elevating agents may prove to be an important signaling mechanism to

  18. EFFECTS OF ELEVATED TEMPERATURE ON ELEVATED ...

    African Journals Online (AJOL)

    eobe

    concrete. Data obtained at 7 and 28 days for the effects of temperature with compressive strength are shown in Tables 1 and 2 respectively while the loss of weight as related to elevated temperature and age, are in. Figure 1. The effect of elevated temperature on the compressive strength at 7 days and 28 days for concrete ...

  19. Iowa Bedrock Surface Elevation

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — This Digital Elevation Model (DEM) of the bedrock surface elevation in Iowa was compiled using all available data, principally information from GEOSAM, supplemented...

  20. Expression of the cytochrome P450s, CYP6P3 and CYP6M2 are significantly elevated in multiple pyrethroid resistant populations of Anopheles gambiae s.s. from Southern Benin and Nigeria

    Directory of Open Access Journals (Sweden)

    Ranson Hilary

    2008-11-01

    Full Text Available Abstract Background Insecticide resistance in Anopheles mosquitoes is threatening the success of malaria control programmes. This is particularly true in Benin where pyrethroid resistance has been linked to the failure of insecticide treated bed nets. The role of mutations in the insecticide target sites in conferring resistance has been clearly established. In this study, the contribution of other potential resistance mechanisms was investigated in Anopheles gambiae s.s. from a number of localities in Southern Benin and Nigeria. The mosquitoes were sampled from a variety of breeding sites in a preliminary attempt to investigate the role of contamination of mosquito breeding sites in selecting for resistance in adult mosquitoes. Results All mosquitoes sampled belonged to the M form of An. gambiae s.s. There were high levels of permethrin resistance in an agricultural area (Akron and an urban area (Gbedjromede, low levels of resistance in mosquito samples from an oil contaminated site (Ojoo and complete susceptibility in the rural Orogun location. The target site mutation kdrW was detected at high levels in two of the populations (Akron f = 0.86 and Gbedjromede f = 0.84 but was not detected in Ojoo or Orogun. Microarray analysis using the Anopheles gambiae detox chip identified two P450s, CYP6P3 and CYP6M2 up regulated in all three populations, the former was expressed at particularly high levels in the Akron (12.4-fold and Ojoo (7.4-fold populations compared to the susceptible population. Additional detoxification and redox genes were also over expressed in one or more populations including two cuticular pre-cursor genes which were elevated in two of the three resistant populations. Conclusion Multiple resistance mechanisms incurred in the different breeding sites contribute to resistance to permethrin in Benin. The cytochrome P450 genes, CYP6P3 and CYP6M2 are upregulated in all three resistant populations analysed. Several additional potential

  1. Imidacloprid, a neonicotinoid insecticide, facilitates tyrosine hydroxylase transcription and phenylethanolamine N-methyltransferase mRNA expression to enhance catecholamine synthesis and its nicotine-evoked elevation in PC12D cells.

    Science.gov (United States)

    Kawahata, Ichiro; Yamakuni, Tohru

    2018-02-01

    protein expression, and simultaneous enhancement of nicotine-elevated adrenaline secretion also took place. These findings thus suggest that imidacloprid may facilitate the physiological functions of adrenal glands in mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. De stille elever

    DEFF Research Database (Denmark)

    Winther-Lindqvist, Ditte Alexandra

    2012-01-01

    Det er blevet en afgørende samværskompetence i uddannelsessystemet at stå aktivt frem og deltage verbalt i skoleklassens liv både fagligt og socialt. Men ikke alle elever deltager lige villigt verbalt i plenum. Artiklen handler om de stille elever og konsekvenserne af stillehed i skolen. Det...... foreslås at skolesystemet sanktionerer ældre elever hårdere for stillehed end yngre elever og det forklares med at skolelivet også er en kultivering henimod elevhed som social identitet og denne er der forventning om at eleverne mestrer i udskolingen....

  3. Release of Hormones from Conjugates: Chloroplast Expression of β-Glucosidase Results in Elevated Phytohormone Levels Associated with Significant Increase in Biomass and Protection from Aphids or Whiteflies Conferred by Sucrose Esters1[C][OA

    Science.gov (United States)

    Jin, Shuangxia; Kanagaraj, Anderson; Verma, Dheeraj; Lange, Theo; Daniell, Henry

    2011-01-01

    Transplastomic tobacco (Nicotiana tabacum) plants expressing β-glucosidase (Bgl-1) show modified development. They flower 1 month earlier with an increase in biomass (1.9-fold), height (1.5-fold), and leaf area (1.6-fold) than untransformed plants. Trichome density on the upper and lower leaf surfaces of BGL-1 plants increase by 10- and 7-fold, respectively, harboring 5-fold more glandular trichomes (as determined by rhodamine B staining), suggesting that BGL-1 lines produce more sugar esters than control plants. Gibberellin (GA) levels were investigated because it is a known regulator of flowering time, plant height, and trichome development. Both GA1 and GA4 levels are 2-fold higher in BGL-1 leaves than in untransformed plants but do not increase in other organs. In addition, elevated levels of other plant hormones, including zeatin and indole-3-acetic acid, are observed in BGL-1 lines. Protoplasts from BGL-1 lines divide and form calli without exogenous hormones. Cell division in protoplasts is enhanced 7-fold in the presence of exogenously applied zeatin-O-glucoside conjugate, indicating the release of active hormones from their conjugates. Whitefly (Bemisia tabaci) and aphid (Myzus persicae) populations in control plants are 18 and 15 times higher than in transplastomic lines, respectively. Lethal dose to kill 50% of the test population values of 26.3 and 39.2 μg per whitefly and 23.1 and 35.2 μg per aphid for BGL-1 and untransformed control exudates, respectively, confirm the enhanced toxicity of transplastomic exudates. These data indicate that increase in sugar ester levels in BGL-1 lines might function as an effective biopesticide. This study provides a novel strategy for designing plants for enhanced biomass production and insect control by releasing plant hormones or sugar esters from their conjugates stored within their chloroplasts. PMID:21068365

  4. Release of hormones from conjugates: chloroplast expression of β-glucosidase results in elevated phytohormone levels associated with significant increase in biomass and protection from aphids or whiteflies conferred by sucrose esters.

    Science.gov (United States)

    Jin, Shuangxia; Kanagaraj, Anderson; Verma, Dheeraj; Lange, Theo; Daniell, Henry

    2011-01-01

    Transplastomic tobacco (Nicotiana tabacum) plants expressing β-glucosidase (Bgl-1) show modified development. They flower 1 month earlier with an increase in biomass (1.9-fold), height (1.5-fold), and leaf area (1.6-fold) than untransformed plants. Trichome density on the upper and lower leaf surfaces of BGL-1 plants increase by 10- and 7-fold, respectively, harboring 5-fold more glandular trichomes (as determined by rhodamine B staining), suggesting that BGL-1 lines produce more sugar esters than control plants. Gibberellin (GA) levels were investigated because it is a known regulator of flowering time, plant height, and trichome development. Both GA(1) and GA(4) levels are 2-fold higher in BGL-1 leaves than in untransformed plants but do not increase in other organs. In addition, elevated levels of other plant hormones, including zeatin and indole-3-acetic acid, are observed in BGL-1 lines. Protoplasts from BGL-1 lines divide and form calli without exogenous hormones. Cell division in protoplasts is enhanced 7-fold in the presence of exogenously applied zeatin-O-glucoside conjugate, indicating the release of active hormones from their conjugates. Whitefly (Bemisia tabaci) and aphid (Myzus persicae) populations in control plants are 18 and 15 times higher than in transplastomic lines, respectively. Lethal dose to kill 50% of the test population values of 26.3 and 39.2 μg per whitefly and 23.1 and 35.2 μg per aphid for BGL-1 and untransformed control exudates, respectively, confirm the enhanced toxicity of transplastomic exudates. These data indicate that increase in sugar ester levels in BGL-1 lines might function as an effective biopesticide. This study provides a novel strategy for designing plants for enhanced biomass production and insect control by releasing plant hormones or sugar esters from their conjugates stored within their chloroplasts.

  5. Undervisning af tosprogede elever

    DEFF Research Database (Denmark)

    Horst, Christian

    2003-01-01

    Artiklen fremdrager hovedresultaterne fra Virginia P. Collier's og Wayne P. Thomas's længdeundersøgelser af tosprogede elever i USA, som formentlig er de mest omfattende undersøgelser af undervisningen af tosprogede elever overhovedet. Resultaterne diskuteres i relation til udviklingen af en...

  6. Elevators or stairs?

    Science.gov (United States)

    Shah, Sachin; O’Byrne, Michael; Wilson, Merne; Wilson, Thomas

    2011-01-01

    Background: Staff in hospitals frequently travel between floors and choose between taking the stairs or elevator. We compared the time savings with these two options. Methods: Four people aged 26–67 years completed 14 trips ranging from one to six floors, both ascending and descending. We compared the amount of time per floor travelled by stairs and by two banks of elevators. Participants reported their fatigue levels using a modified Borg scale. We performed two-way analysis of variance to compare the log-transformed data, with participant and time of day as independent variables. Results: The mean time taken to travel between each floor was 13.1 (standard deviation [SD] 1.7) seconds by stairs and 37.5 (SD 19.0) and 35.6 (SD 23.1) seconds by the two elevators (F = 8.61, p elevator equaled about 15 minutes a day. Self-reported fatigue was less than 13 (out of 20) on the Borg scale for all participants, and they all stated that they were able to continue their duties without resting. The extra time associated with elevator use was because of waiting for its arrival. There was a difference in the amount of time taken to travel by elevator depending on the time of day and day of the week. Interpretation: Taking the stairs rather than the elevator saved about 15 minutes each workday. This 3% savings per workday could translate into improved productivity as well as increased fitness. PMID:22159365

  7. Photoreflectance at elevated temperatures

    Science.gov (United States)

    Shen, Hongen

    1990-08-01

    Using the contactiess modulation spectroscopy technique of photoreflectance, the temperature variations of the direct gap E0 of GaAs, InP, GaA1As, InGaAs have been measured at elevated temperatures up to 600°C. The parameters which describe the temperature dependence of the band gap energies have been evaluated. The ability to measure the band gap at elevated temperatures opens up many new possibilities for in-situ monitoring of MBE and MOCVD processes. In this paper, we review some of the recent developments in the use of photoreflectance at elevated temperatures.

  8. Indsatser for tosprogede elever

    DEFF Research Database (Denmark)

    Andersen, Dines; Jakobsen, Vibeke; Jensen, Vibeke Myrup

    Fagligt set klarer tosprogede elever sig dårligere i skolen og det videre uddannelsessystem end ’danske’ elever. Kommuner og folkeskoler har derfor sat en række tiltag i værk, som sigter mod at forbedre de tosprogede elevers skole- og uddannelsessituation. Rapporten kortlægger og analyserer...... af klasseundervisningen. Analysen viser, at de elever, der bliver taget ud af klassen for at få ekstra undervisning i dansk som andetsprog, klarer sig dårligere end elever, der modtager ekstraundervisningen i klassen eller uden for skoletid. Undersøgelsen er baseret på spørgeskemaundersøgelser blandt...... kommunale forvaltningschefer, skoleledere, lærere og forældre til børn i 2. klasse samt lærere til og elever i 9. klasse, SFI’s forløbsundersøgelse af årgang 1995 og registerdata. Undersøgelsen er via Ministeriet for Børn og Undervisning betalt med midler fra satspuljeaftalen 2009 om integration....

  9. Plants with elevated levels of glucan

    Energy Technology Data Exchange (ETDEWEB)

    Pauly, Markus; Kraemer, Florian J.; Hake, Sarah

    2018-03-20

    The present disclosure relates to mutations in licheninase genes encoding polypeptides with decreased licheninase activity, which when expressed in plants results in elevated levels of glucan in the plants. In particular, the disclosure relates to licheninase nucleic acids and polypeptides related to glucan accumulation in plants, plants with reduced expression of a licheninase nucleic acid, and methods related to the generation of plants with increased glucan content in the cell walls of leaf tissue.

  10. Interaktive tavler - interaktive elever

    DEFF Research Database (Denmark)

    Reusch, Charlotte; Otzen, Elsebeth

    Abstract, Poster-præsentation 13.-14. juni 2012, Pilotprojekt: Interaktive tavler ? interaktive elever Lektor, cand. pæd., Elsebeth Otzen og Lektor, cand. mag., Charlotte Reusch, Institut for Skole og Læring, Læreruddannelsen, Professionshøjskolen Metropol, København Hvordan motiverer en interaktiv...... tavle lærere og elever? Hvad sker der mellem elev, stof og lærer, når læreren bliver i stand til at billedliggøre og dynamisere sine oplæg på tavlen? Bliver læreroplæg prioriteret? Bliver eleverne aktive, eller ender den interaktive tavle med blot at understøtte lærerens envejskommunikation til klassen......? Og hvad sker der mellem eleverne? Disse spørgsmål var igangsættende for arbejdet med pilotprojektet Interaktive tavler ? interaktive elever, som blev afviklet i skoleåret 2010-2011. Projektet blev udført af en tværfaglig gruppe, bestående af lektorer i matematik, biologi og dansk i læreruddannelsen...

  11. Udeskole og elevers handlekompetence

    DEFF Research Database (Denmark)

    Breiting, Søren

    2011-01-01

    Elever elsker at komme væk fra undervisningen i skolen. Er det positivt eller negativt? Og hvad har betydning for, at eleverne får mest muligt ud af oplevelserne uden for skolen? Forskellige former for udeskole giver nogle oplagte muligheder, så eleverne udvikler sig som engagerede borgere i et...

  12. Interaktive tavler - interaktive elever

    DEFF Research Database (Denmark)

    Reusch, Charlotte F.; Otzen, Elsebeth

    Abstract, Poster-præsentation 13.-14. juni 2012, Pilotprojekt: Interaktive tavler – interaktive elever Lektor, cand. pæd., Elsebeth Otzen og Lektor, cand. mag., Charlotte Reusch, Institut for Skole og Læring, Læreruddannelsen, Professionshøjskolen Metropol, København Hvordan motiverer en interaktiv...... tavle lærere og elever? Hvad sker der mellem elev, stof og lærer, når læreren bliver i stand til at billedliggøre og dynamisere sine oplæg på tavlen? Bliver læreroplæg prioriteret? Bliver eleverne aktive, eller ender den interaktive tavle med blot at understøtte lærerens envejskommunikation til klassen......? Og hvad sker der mellem eleverne? Disse spørgsmål var igangsættende for arbejdet med pilotprojektet Interaktive tavler – interaktive elever, som blev afviklet i skoleåret 2010-2011. Projektet blev udført af en tværfaglig gruppe, bestående af lektorer i matematik, biologi og dansk i læreruddannelsen...

  13. Influence of elevated CO

    NARCIS (Netherlands)

    Annibale, D' Alessandra; Larsen, Thomas; Sechi, Valentina; Cortet, Jérôme; Strandberg, Beate; Vincze, Éva; Filser, Juliane; Audisio, Paolo Aldo; Krogh, Paul Henning

    2015-01-01

    We hypothesized that the combined effect of rising levels of atmospheric carbon dioxide (CO2) and increasing use of genetically modified (GM) crops in agriculture may affect soil food-webs. So we designed a study for the assessment of the effects of elevated CO2

  14. Skuldertesten "Kombineret Elevation"

    DEFF Research Database (Denmark)

    Clausen, Mikkel Bek; Overkær, Brian

    2010-01-01

    Formål: At udarbejde en testprotokol for testen Kombineret Elevation (KE) og undersøge test-retest variationen ved test af elite svømmere, samt diskutere testens relevans og validitet. Materiale og Metode: 9 elite og 10 sub-elite svømmere, heraf var 11 mænd og 8 kvinder, gennemførte testen KE 2...

  15. Elevation data for floodplain mapping

    National Research Council Canada - National Science Library

    Committee on Floodplain Mapping Technologies; National Research Council; Division on Earth and Life Studies; National Research Council

    2007-01-01

    .... Elevation Data for Floodplain Mapping shows that there is sufficient two-dimensional base map imagery to meet FEMA's flood map modernization goals, but that the three-dimensional base elevation data...

  16. Elevated Dengue Virus Nonstructural Protein 1 Serum Levels and Altered Toll-Like Receptor 4 Expression, Nitric Oxide, and Tumor Necrosis Factor Alpha Production in Dengue Hemorrhagic Fever Patients

    Directory of Open Access Journals (Sweden)

    Denise Maciel Carvalho

    2014-01-01

    Full Text Available Background. During dengue virus (DV infection, monocytes produce tumor necrosis factor alpha (TNF-α and nitric oxide (NO which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1 on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1 serum levels and innate immune response (TLR4 expression and TNF-α/NO production of DV infected patients presenting different clinical outcomes. Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA, TNF-α production by peripheral blood mononuclear cells (PBMCs, and TLR4 expression on CD14+ cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF was detected compared to patients with dengue hemorrhagic fever (DHF. Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-α production when compared to DF patients. Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes.

  17. Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor α (LXRα) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type 1.

    Science.gov (United States)

    Grefhorst, Aldo; Schreurs, Marijke; Oosterveer, Maaike H; Cortés, Victor A; Havinga, Rick; Herling, Andreas W; Reijngoud, Dirk-Jan; Groen, Albert K; Kuipers, Folkert

    2010-12-01

    GSD-1 (glycogen storage disease type 1) is caused by an inherited defect in glucose-6-phosphatase activity, resulting in a massive accumulation of hepatic glycogen content and an induction of de novo lipogenesis. The chlorogenic acid derivative S4048 is a pharmacological inhibitor of the glucose 6-phosphate transporter, which is part of glucose-6-phosphatase, and allows for mechanistic studies concerning metabolic defects in GSD-1. Treatment of mice with S4048 resulted in an ~60% reduction in blood glucose, increased hepatic glycogen and triacylglycerol (triglyceride) content, and a markedly enhanced hepatic lipogenic gene expression. In mammals, hepatic expression of lipogenic genes is regulated by the co-ordinated action of the transcription factors SREBP (sterol-regulatory-element-binding protein)-1c, LXRα (liver X receptor α) and ChREBP (carbohydrate-response-element-binding protein). Treatment of Lxra-/- mice and Chrebp-/- mice with S4048 demonstrated that ChREBP, but not LXRα, mediates the induction of hepatic lipogenic gene expression in this murine model of GSD-1. Thus ChREBP is an attractive target to alleviate derangements in lipid metabolism observed in patients with GSD-1.

  18. Reduced volume but increased training intensity elevates muscle Na+-K+ pump alpha1-subunit and NHE1 expression as well as short-term work capacity in humans

    DEFF Research Database (Denmark)

    Iaia, F. Marcello; Thomassen, Martin; Kolding, Helle

    2008-01-01

    by 30-s sprint runs three to four times a week, whereas CON continued the endurance training ( approximately 45 km/wk). After the 4-wk sprint period, the expression of the muscle Na(+)-K(+) pump alpha(1)-subunit and Na(+)/H(+)-exchanger isoform 1 was 29 and 30% higher (P ... pulmonary maximum oxygen uptake and 10-k time were unchanged. No changes in CON were observed. The present data suggest a role of the Na(+)-K(+) pump in the control of K(+) homeostasis and in the development of fatigue during repeated high-intensity exercise. Furthermore, performance during intense exercise....... Furthermore, plasma K(+) concentration was reduced (P

  19. Immunosuppression during active tuberculosis is characterized by decreased interferon- gamma production and CD25 expression with elevated forkhead box P3, transforming growth factor- beta , and interleukin-4 mRNA levels.

    Science.gov (United States)

    Roberts, Teri; Beyers, Nulda; Aguirre, Ana; Walzl, Gerhard

    2007-03-15

    The balance between effector and regulatory responses after Mycobacterium tuberculosis infection may dictate outcome and progression to active disease. We investigated effector and regulatory T cell responses in bacille Calmette-Guerin (BCG)-stimulated peripheral blood mononuclear cells and whole blood cultures from persons with active tuberculosis (TB), persons with TB at the end of 6 months of treatment, and healthy control subjects with latent TB infection. All 3 groups displayed BCG-induced increases in effector and regulatory T cell phenotypes as defined by CD4(+)CD25(lo) and CD4(+)CD25(hi) T cells, respectively. In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4(+)CD25(hi), CTLA-4, and interferon- gamma . However, these case patients expressed the highest mRNA levels of forkhead box P3, transforming growth factor (TGF)- beta , and interleukin (IL)-4 and a lower T-bet : GATA-3 ratio. There were no significant differences in IL-4 delta 2, IL-10, or TGF- beta receptor-II mRNA expression between groups. Together, these results suggest that immunosuppression seen after mycobacterial stimulation in case patients with active TB is associated with naturally occurring regulatory T cells.

  20. Tanzania Elevation and Surface Characteristics

    Data.gov (United States)

    US Agency for International Development — The dataset displays Elevation, Slope, Aspect, Topographic Position Index, Terrain Ruggedness, and Roughness based on Shuttle Radar Topography Mission (SRTM) (3...

  1. Lærer-elev-relationer

    DEFF Research Database (Denmark)

    Laursen, Per Fibæk; Nielsen, Anne Maj

    2015-01-01

    I kapitlet belyser vi relationskompetence i forholdet mellem lærer og elever og hvordan læreren kan arbejde med forhold til elever og med sin opmærksomhed på relationsarbejdet. Afslutningsvis ser vi på hvordan lærere fortsat kan udvikle deres relationskompetence.......I kapitlet belyser vi relationskompetence i forholdet mellem lærer og elever og hvordan læreren kan arbejde med forhold til elever og med sin opmærksomhed på relationsarbejdet. Afslutningsvis ser vi på hvordan lærere fortsat kan udvikle deres relationskompetence....

  2. Elevation of the diaphragmatic cupola

    International Nuclear Information System (INIS)

    Semenov, V.M.; Talesnik, M.R.

    1988-01-01

    Altogether 45 patients with elevation of the diaphragmatic cupola were examined. A high frequency of erroneous initial interpretation of examination results was noted in inflammatory and tumorous lesions and congenital conditions. Routine and contrast methods (pneumoperitoneum, bronchography, pleurography and fistulography) were used. Disease-related methods of X-ray investigation were proposed. A variety of causes of diaphragm elevation was indicated

  3. Space Station tethered elevator system

    Science.gov (United States)

    Haddock, Michael H.; Anderson, Loren A.; Hosterman, K.; Decresie, E.; Miranda, P.; Hamilton, R.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The tethered elevator is an unmanned, mobile structure which operates on a ten-kilometer tether spanning the distance between Space Station Freedom and a platform. Its capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The report discusses the potential uses, parameters, and evolution of the spacecraft design. Emphasis is placed on the elevator's structural configuration and three major subsystem designs. First, the design of elevator robotics used to aid in elevator operations and tethered experimentation is presented. Second, the design of drive mechanisms used to propel the vehicle is discussed. Third, the design of an onboard self-sufficient power generation and transmission system is addressed.

  4. Maternal exposure of rats to nicotine via infusion during gestation produces neurobehavioral deficits and elevated expression of glial fibrillary acidic protein in the cerebellum and CA1 subfield in the offspring at puberty

    International Nuclear Information System (INIS)

    Abdel-Rahman, Ali; Dechkovskaia, Anjelika M.; Sutton, Jazmine M.; Chen, Wei-Chung; Guan, Xiangrong; Khan, Wasiuddin A.; Abou-Donia, Mohamed B.

    2005-01-01

    increased expression of GFAP in cerebellum and CA1 subfield of hippocampus of the offspring on PND 30 and 60. The results show that although 60-day-old male and female rat offspring of mothers exposed to nicotine during gestation did not differ from control in body weight gain or nicotinic acetylcholine receptors ligand binding, they exhibited significant sensorimotor deficits that were consistent with the neuropathological alterations seen in the brain. These neurobehavioral and pathological deficits indicate that maternal nicotine exposure may produce long-term adverse health effects in the offspring

  5. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R

    2013-01-01

    showed over expression to be confined to primarily the cortex, hippocampus, cerebellum, and only in neurons. The level and expression pattern of endogenous Neuroglobin was unaffected by insertion of the over expressing Ngb transgene. Neuroglobin over expression resulted in a significant reduction...... previous reports, Neuroglobin over expression is not global but confined to a few well-defined brain regions, and only in neurons. This study confirms previous reports showing a correlation between reduced infarct volume and elevated Neuroglobin levels, but underlines the need to study the likely...

  6. Differential Gene Expression in Brassica rapa Roots After Reorientation and Clinorotation.

    Science.gov (United States)

    Edge, Andrea; Hasenstein, Karl H.

    Seedlings align their growth axes parallel to the gravity vector. Any growth adjustment affects genes. We examined these changes in Brassica rapa roots that were reoriented and clinorotated. Gene expression levels related to the actin cytoskeleton (ACT7 and ADK1) and auxin transport (IAA5, PIN1, PIN3, AGR1, ARG1) were assessed in roots grown for 42 hours and then either reoriented to 90° for 15 min, 1, 2 and 3 hours or clinorotated vertically or horizontally for 42 hrs at 2 rpm. After these treatments, roots from 20 seedlings were divided into three sections, the root tip, elongation zone, and maturation zone. The samples from corresponding treatments were combined for RNA extraction, reverse transcription and analysis by quantitative PCR. The results show that gene expression changes in response to duration of reorientation and orientation during clinorotation. All genes, except PIN1 and AGR1 were upregulated in the tip after 2 hours of reorientation. Expression of genes also varied between the root sections except for PIN1, which was uniformly expressed. ADK1 was the only gene that showed consistent down-regulation in all three root regions in vertically and horizontally clinorotated roots (ca 30% of controls). In contrast, ADK1 was upregulated (more than 150 fold) in the tip of roots that were reoriented for 2 hours but little upregulation after one hour (less than 2 fold compared to controls). Our results indicate that gene expression during the gravitropic response changes over time with the tip region being the most dynamic tissue in the root. The large upregulation of ADK1 at 2 h after reorientation may be related to the persistence of the gravitropic response. Because of the variability of the expression profiles, analyses that are based on the entire root miss tissue specific changes in gene expression. Differences in gene expression after vertical and horizontal clinorotation indicates that the graviresponse system is sensitive not just to the magnitude

  7. Base Flood Elevation (BFE) Lines

    Data.gov (United States)

    Department of Homeland Security — The Base Flood Elevation (BFE) table is required for any digital data where BFE lines will be shown on the corresponding Flood Insurance Rate Map (FIRM). Normally if...

  8. Elevated Fixed Platform Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Elevated Fixed Platform (EFP) is a helicopter recovery test facility located at Lakehurst, NJ. It consists of a 60 by 85 foot steel and concrete deck built atop...

  9. FEMA DFIRM Base Flood Elevations

    Data.gov (United States)

    Minnesota Department of Natural Resources — The Base Flood Elevation (BFE) table is required for any digital data where BFE lines will be shown on the corresponding Flood Insurance Rate Map (FIRM). Normally,...

  10. Coastal Digital Elevation Models (DEMs)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Digital elevation models (DEMs) of U.S. and other coasts that typically integrate ocean bathymetry and land topography. The DEMs support NOAA's mission to understand...

  11. Troponin elevation in subarachnoid hemorrhage

    OpenAIRE

    Ioannis N. Mavridis; Maria Meliou; Efstratios-Stylianos Pyrgelis

    2015-01-01

    Troponin (tr) elevation in aneurysmal subarachnoid hemorrhage (SAH) patients is often difficult to be appropriately assessed by clinicians, causing even disagreements regarding its management between neurosurgeons and cardiologists. The purpose of this article was to review the literature regarding the clinical interpretation of tr elevation in SAH. We searched for articles in PubMed using the key words: “troponin elevation” and “subarachnoid hemorrhage”. All of them, as well as relative neur...

  12. Troponin elevation in subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    Ioannis N. Mavridis

    2015-03-01

    Full Text Available Troponin (tr elevation in aneurysmal subarachnoid hemorrhage (SAH patients is often difficult to be appropriately assessed by clinicians, causing even disagreements regarding its management between neurosurgeons and cardiologists. The purpose of this article was to review the literature regarding the clinical interpretation of tr elevation in SAH. We searched for articles in PubMed using the key words: “troponin elevation” and “subarachnoid hemorrhage”. All of them, as well as relative neurosurgical books, were used for this review. Some type of cardiovascular abnormality develops in most SAH patients. Neurogenic stunned myocardium is a frequent SAH complication, due to catecholamine surge which induces cardiac injury, as evidenced by increased serum tr levels, electrocardiographic (ECG changes and cardiac wall motion abnormalities. Tr elevation, usually modest, is an early and specific marker for cardiac involvement after SAH and its levels peak about two days after SAH. Cardiac tr elevation predictors include poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, female sex, large body surface area, lower systolic blood pressure, higher heart rate and prolonged Q-Tc interval. Elevated tr levels are associated with disability and death (especially tr >1 μg/L, worse neurological grade, systolic and diastolic cardiac dysfunction, pulmonary congestion, longer intensive care unit stay and incidence of vasospasm. Tr elevation is a common finding in SAH patients and constitutes a rightful cause of worry about the patients' cardiac function and prognosis. It should be therefore early detected, carefully monitored and appropriately managed by clinicians.

  13. Historie i spillefilm - for elever

    DEFF Research Database (Denmark)

    Tønnesen, Lone Guldbrandt

    2016-01-01

    MOOC om historiebrug i spillefilm, hvor elever kan lære om, hvordan spillefilm bruger fortiden, og om hvordan vores opfattelse af historien både sætter sig spor i filmene og bliver påvirket af dem.......MOOC om historiebrug i spillefilm, hvor elever kan lære om, hvordan spillefilm bruger fortiden, og om hvordan vores opfattelse af historien både sætter sig spor i filmene og bliver påvirket af dem....

  14. Tether Elevator Crawler Systems (TECS)

    Science.gov (United States)

    Swenson, Frank R.

    1987-01-01

    One of the needs of the experimenters on the space station is access to steady and controlled-variation microgravity environments. A method of providing these environments is to place the experiment on a tether attached to the space station. This provides a high degree of isolation from structural oscillations and vibrations. Crawlers can move these experiments along the tethers to preferred locations, much like an elevator. This report describes the motion control laws developed for these crawlers and the testing of laboratory models of these tether elevator crawlers.

  15. Methylphenidatinduceret ST-elevations-myokardieinfarkt

    DEFF Research Database (Denmark)

    Ruwald, Martin Huth; Ruwald, Anne-Christine Huth; Tønder, Niels

    2012-01-01

    Adult attention deficit and hyperkinetic disorder (ADHD) is increasingly diagnosed and treated with methylphenidate. We present the case of an 20 year-old man, who was diagnosed with ADHD and suffered a ST elevation acute myocardial infarction due to coronary vasospasm related to an overdose...

  16. Dannelsen af den ansvarlige elev

    DEFF Research Database (Denmark)

    Larsen, Jesper

    2010-01-01

    Denne artikel handler om den del af lærergerningen, der har at gøre med udarbejdelse af elevplaner. Der tages udgangspunkt i en foucaultsk forståelse, hvor beskrivelsen af den enkelte elev udtrykker et særligt normativt ideal om, hvilke former for elevhed der er de ønskværdige i den danske...

  17. 46 CFR 120.540 - Elevators.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Elevators. 120.540 Section 120.540 Shipping COAST GUARD... Requirements § 120.540 Elevators. Each elevator on a vessel must meet the requirements of American National Standards Institute (ANSI) A17.1. “Safety Code for Elevators, and Escalators,” or other standard specified...

  18. Elevator deflections on the icing process

    Science.gov (United States)

    Britton, Randall K.

    1990-01-01

    The effect of elevator deflection of the horizontal stabilizer for certain icing parameters is investigated. Elevator deflection can severely change the lower and upper leading-edge impingement limits, and ice can accrete on the elevator itself. Also, elevator deflection had practically no effect on the maximum local collection efficiency. It is shown that for severe icing conditions (large water droplets), elevator deflections that increase the projected height of the airfoil can significantly increase the total collection efficiency of the airfoil.

  19. Når elever producerer

    DEFF Research Database (Denmark)

    Bremholm, Jesper; Hansen, Rune; Slot, Marie Falkesgaard

    2017-01-01

    Dette kapitel præsenterer centrale resultater fra studiet Elevopgaver og elevproduktion i det 21. århundrede der blandt andet rummer den første større kvantitative undersøgelse af opgavedidaktik og elevers produktive arbejde i den danske grundskole. Studiet omfatter også en kvalitativ del, og i...... undersøgelsen præsenteres og diskuteres gennem en række konkrete eksempler fra de berørte fag. I forhold til elevers produktive arbejde peger undersøgelsens resultater både på potentialer og særlige barrierer i forbindelse med at udvikle en kompetenceorienteret undervisning. I kapitlet argumenteres desuden...

  20. Læring mellem elever

    DEFF Research Database (Denmark)

    Georgsen, Marianne; Davidsen, Jacob

    2010-01-01

    I denne rapport præsenteres resultater fra følgeforskningen til projektet Læring gennem Bevægelse, som er gennemført på Søndervangskolen i Hammel i perioden august 2009 - maj 2010. Projektet er gennemført i samspil mellem lærere, it-vejleder, elever og skolens ledelse. Projektets overordnede formål...

  1. Systemic elevation of PTEN induces a tumor-suppressive metabolic state

    NARCIS (Netherlands)

    Garcia-Cao, Isabel; Song, Min Sup; Hobbs, Robin M.; Laurent, Gaelle; Giorgi, Carlotta; de Boer, Vincent C. J.; Anastasiou, Dimitrios; Ito, Keisuke; Sasaki, Atsuo T.; Rameh, Lucia; Carracedo, Arkaitz; Vander Heiden, Matthew G.; Cantley, Lewis C.; Pinton, Paolo; Haigis, Marcia C.; Pandolfi, Pier Paolo

    2012-01-01

    Decremental loss of PTEN results in cancer susceptibility and tumor progression. PTEN elevation might therefore be an attractive option for cancer prevention and therapy. We have generated several transgenic mouse lines with PTEN expression elevated to varying levels by taking advantage of bacterial

  2. Operation experience with elevated ammonia

    International Nuclear Information System (INIS)

    Vankova, Katerina; Kysela, Jan; Malac, Miroslav; Petrecky, Igor; Svarc, Vladimir

    2011-01-01

    The 10 VVER units in the Czech and Slovak Republics are all in very good water chemistry and radiation condition, yet questions have arisen regarding the optimization of cycle chemistry and improved operation in these units. To address these issues, a comprehensive experimental program for different water chemistries of the primary circuit was carried out at the Rez Nuclear Research Institute, Czech Republic, with the goal of judging the influence of various water chemistries on radiation build-up. Four types of water chemistries were compared: standard VVER water chemistry (in common use), direct hydrogen dosing without ammonia, standard VVER water chemistry with elevated ammonia levels, and zinc dosing to standard VVER water chemistry. The test results showed that the types of water chemistry other than the common one have benefits for the operation of the nuclear power plant (NPP) primary circuit. Operation experience with elevated ammonia at NPP Dukovany Units 3 and 4 is presented which validates the experimental results, demonstrating improved corrosion product volume activity. (orig.)

  3. Myofibroblast Numbers are Elevated in Human Elbow Capsules After Trauma

    OpenAIRE

    Hildebrand, Kevin A.; Zhang, Mei; van Snellenberg, Wistara; King, Graham J. W.; Hart, David A.

    2004-01-01

    Elbow contractures, a frequent problem after injury, can be treated by excision of the joint capsule. However, the underlying changes in the joint capsule are poorly understood. Based on skin healing work, we examined the hypotheses that myofibroblast numbers and expression of a myofibroblast marker α-smooth muscle actin, are elevated in patients with posttraumatic joint contractures. Anterior capsules were obtained from six patients who had operative release of posttraumatic contractures gre...

  4. Global variation in elevational diversity patterns.

    Science.gov (United States)

    Guo, Qinfeng; Kelt, Douglas A; Sun, Zhongyu; Liu, Hongxiao; Hu, Liangjun; Ren, Hai; Wen, Jun

    2013-10-25

    While horizontal gradients of biodiversity have been examined extensively in the past, vertical diversity gradients (elevation, water depth) are attracting increasing attention. We compiled data from 443 elevational gradients involving diverse organisms worldwide to investigate how elevational diversity patterns may vary between the Northern and Southern hemispheres and across latitudes. Our results show that most elevational diversity curves are positively skewed (maximum diversity below the middle of the gradient) and the elevation of the peak in diversity increases with the elevation of lower sampling limits and to a lesser extent with upper limit. Mountains with greater elevational extents, and taxonomic groups that are more inclusive, show proportionally more unimodal patterns whereas other ranges and taxa show highly variable gradients. The two hemispheres share some interesting similarities but also remarkable differences, likely reflecting differences in landmass and mountain configurations. Different taxonomic groups exhibit diversity peaks at different elevations, probably reflecting both physical and physiological constraints.

  5. Digtial Elevation Model (DEM) 250K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USGS to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  6. Digitial Elevation Model (DEM) 100K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USG to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  7. Digital Elevation Model (DEM) 24K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USGS to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  8. Seasonal elevational movements of Eastern Olive Sunbird ...

    African Journals Online (AJOL)

    Little is known about the seasonal elevational movements for most tropical avifauna species. Seasonal elevational movements of the Eastern Olive Sunbird Cyanomitra olivacea were studied along an elevational gradient from 600 to 1 500 m above sea level in the Uluguru Mountains, Tanzania, between May 2005 and ...

  9. Elevated Tank Due to Earthquake Even

    Directory of Open Access Journals (Sweden)

    Kotrasová Kamila

    2017-12-01

    Full Text Available Elevated reservoirs are mainly used for storing of variety water. During earthquake activity the fluid exerts impulsive and convective (sloshing effects on the walls and bottom of tank. This paper provides theoretical background for analytical calculating of elevated water tank due to earthquake even and deals with simplified seismic design procedures for elevated tanks.

  10. Global variation in elevational diversity patterns

    Science.gov (United States)

    Qinfeng Guo; Douglas A. Kelt; Zhongyu Sun; Hongxiao Liu; Liangjun Hu; Hai Ren; Jun We

    2013-01-01

    While horizontal gradients of biodiversity have been examined extensively in the past, vertical diversity gradients (elevation, water depth) are attracting increasing attention. We compiled data from 443 elevational gradients involving diverse organisms worldwide to investigate how elevational diversity patterns may vary between the Northern and Southern hemispheres...

  11. 21 CFR 890.3930 - Wheelchair elevator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Wheelchair elevator. 890.3930 Section 890.3930 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... elevator. (a) Identification. A wheelchair elevator is a motorized lift device intended for medical...

  12. 46 CFR 183.540 - Elevators.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Elevators. 183.540 Section 183.540 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) ELECTRICAL INSTALLATION Miscellaneous Systems and Requirements § 183.540 Elevators. Each elevator on a vessel must meet...

  13. Community and ecosystem responses to elevational gradients

    DEFF Research Database (Denmark)

    Sundqvist, Maja K.; Sanders, Nate; Wardle, David A.

    2013-01-01

    elevational gradients for understanding community and ecosystem responses to global climate change at much larger spatial and temporal scales than is possible through conventional ecological experiments. However, future studies that integrate elevational gradient approaches with experimental manipulations...... will provide powerful information that can improve predictions of climate change impacts within and across ecosystems.......Community structure and ecosystem processes often vary along elevational gradients. Their responses to elevation are commonly driven by changes in temperature, and many community- and ecosystem-level variables therefore frequently respond similarly to elevation across contrasting gradients...

  14. Plasma proteome profiling of atherosclerotic disease manifestations reveals elevated levels of the cytoskeletal protein vinculin

    DEFF Research Database (Denmark)

    Kristensen, Lars P; Larsen, Martin Røssel; Mickley, Hans

    2014-01-01

    an increased expression profile from group 1 to 4. The top-most elevated protein, vinculin (Vcl) displayed a similar profile. Immunoassays confirmed the expression profile of apo(a) and CRP. A 5-plex SRM-MS assay for Vcl, SAA, CRP, apo(a) and thrombospondin-4 (TSP-4) was developed for multiplex verification...

  15. The space station tethered elevator system

    Science.gov (United States)

    Anderson, Loren A.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The elevator is an unmanned mobile structure which operates on a ten kilometer tether spanning the distance between the Space Station and a tethered platform. Elevator capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The potential uses, parameters, and evolution of the spacecraft design are discussed. Engineering development of the tethered elevator is the result of work conducted in the following areas: structural configurations; robotics, drive mechanisms; and power generation and transmission systems. The structural configuration of the elevator is presented. The structure supports, houses, and protects all systems on board the elevator. The implementation of robotics on board the elevator is discussed. Elevator robotics allow for the deployment, retrieval, and manipulation of tethered objects. Robotic manipulators also aid in hooking the elevator on a tether. Critical to the operation of the tethered elevator is the design of its drive mechanisms, which are discussed. Two drivers, located internal to the elevator, propel the vehicle along a tether. These modular components consist of endless toothed belts, shunt-wound motors, regenerative power braking, and computer controlled linear actuators. The designs of self-sufficient power generation and transmission systems are reviewed. Thorough research indicates all components of the elevator will operate under power provided by fuel cells. The fuel cell systems will power the vehicle at seven kilowatts continuously and twelve kilowatts maximally. A set of secondary fuel cells provides redundancy in the unlikely event of a primary system failure. Power storage exists in the form of Nickel-Hydrogen batteries capable of powering the elevator under maximum loads.

  16. Prostaglandin F2alpha elevates blood pressure and promotes atherosclerosis

    DEFF Research Database (Denmark)

    Yu, Ying; Lucitt, Margaret B; Stubbe, Jane

    2009-01-01

    Little is known about prostaglandin F(2alpha) in cardiovascular homeostasis. Prostaglandin F(2alpha) dose-dependently elevates blood pressure in WT mice via activation of the F prostanoid (FP) receptor. The FP is expressed in preglomerular arterioles, renal collecting ducts, and the hypothalamus...... that exhibit mild polyuria and polydipsia. Atherogenesis is retarded by deletion of the FP, despite the absence of detectable receptor expression in aorta or in atherosclerotic lesions in Ldlr KOs. Although vascular TNF(alpha), inducible nitric oxide enzyme and TGF(beta) are reduced and lesional macrophages...... are depleted in the FP/Ldlr double KOs, this result reflects the reduction in lesion burden, as the FP is not expressed on macrophages and its deletion does not alter macrophage cytokine generation. Blockade of the FP offers an approach to the treatment of hypertension and its attendant systemic vascular...

  17. Elevated body mass index and fatty liver

    Directory of Open Access Journals (Sweden)

    Marović Dragana

    2008-01-01

    Full Text Available Introduction Obesity and overweight, expressed by elevated Body Mass Index (BMI, result from excessive consumption of fatty food and carbohydrates above the body needs. The fat from the blood, through free fatty acids, is taken directly into the liver. Objective The aim of this study was to examine correlation among the accepted ultrasonography findings of the fatty liver and the normal ultrasonography findings and the elevated average level of BMI and those with normal BMI in examinees in one investigation. All was done aimed at proving that the BMI is one of the direct factors of the increased occurence of fatty liver. METHOD The method of the investigation consisted of anthropometric measuring of height and weight on the basis of which there were established BMI values. Consequently, the examinees were divided in two groups: one with normal BMI (under 24.9 kg/m2 and the other with increased BMI (over 25 kg/m2. Fatty liver was diagnosed when the liver of the examinees was observed by ultrasonography. Thus there were given subgroups of the examinees, one with the findings of fatty liver and the second with a normal finding, without changes. After that, the obtained results were statistically analysed. Results It was found that the average level of BMI in the examinees was by two units higher in the subgroup with ultrasonography findings of fatty liver than the average value of BMI in the subgroup with the normal ultrasonography findings of the liver. The difference was tested by the Student's t-test and a significant difference was found. The difference in frequencies of the appearance of the finding of fatty liver in the subgroups was tested by χ2-test. A statistically significant difference was found in frequencies of the appearance of fatty liver in the subgroup with the increased value of BMI. Conclusion The increased BMI, which is represented by overweight and obesity, is one of the direct risk factors which cause fatty liver, checked by

  18. Scientific Return of a Lunar Elevator

    OpenAIRE

    Eubanks, T. M.; Radley, C. F.

    2016-01-01

    The concept of a space elevator dates back to Tsilokovsky, but they are not commonly considered in near-term plans for space exploration, perhaps because a terrestrial elevator would not be possible without considerable improvements in tether material. A Lunar Space Elevator (LSE), however, can be built with current technology using commercially available tether polymers. This paper considers missions leading to infrastructure capable of shortening the time, lowering the cost and enhancing th...

  19. Cholecystokinin elevates mouse plasma lipids.

    Directory of Open Access Journals (Sweden)

    Lichun Zhou

    Full Text Available Cholecystokinin (CCK is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR(-/- mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR(-/- mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine.

  20. Soil nematodes show a mid-elevation diversity maximum and elevational zonation on Mt. Norikura, Japan.

    Science.gov (United States)

    Dong, Ke; Moroenyane, Itumeleng; Tripathi, Binu; Kerfahi, Dorsaf; Takahashi, Koichi; Yamamoto, Naomichi; An, Choa; Cho, Hyunjun; Adams, Jonathan

    2017-06-08

    Little is known about how nematode ecology differs across elevational gradients. We investigated the soil nematode community along a ~2,200 m elevational range on Mt. Norikura, Japan, by sequencing the 18S rRNA gene. As with many other groups of organisms, nematode diversity showed a high correlation with elevation, and a maximum in mid-elevations. While elevation itself, in the context of the mid domain effect, could predict the observed unimodal pattern of soil nematode communities along the elevational gradient, mean annual temperature and soil total nitrogen concentration were the best predictors of diversity. We also found nematode community composition showed strong elevational zonation, indicating that a high degree of ecological specialization that may exist in nematodes in relation to elevation-related environmental gradients and certain nematode OTUs had ranges extending across all elevations, and these generalized OTUs made up a greater proportion of the community at high elevations - such that high elevation nematode OTUs had broader elevational ranges on average, providing an example consistent to Rapoport's elevational hypothesis. This study reveals the potential for using sequencing methods to investigate elevational gradients of small soil organisms, providing a method for rapid investigation of patterns without specialized knowledge in taxonomic identification.

  1. An Automatic System for Elevator Monitoring

    OpenAIRE

    Md. Haidar Sharif; Ibrahim Furkan Ince

    2015-01-01

    An elevator is a conveyor device or transport equipment that moves people or goods between floors or levels or decks of a building, vessel, or other structures. It has become a part and parcel of modern life in developed countries. The number of floors in high buildings, skyscrapers, and towers generate the usage of elevators. If it is simply assumed that each floor has at least two elevators in a thirty-floor building, people call the elevators in each floor even they are already occupied in...

  2. National requirements for improved elevation data

    Science.gov (United States)

    Snyder, Gregory I.; Sugarbaker, Larry J.; Jason, Allyson L.; Maune, David F.

    2014-01-01

    This report presents the results of surveys, structured interviews, and workshops conducted to identify key national requirements for improved elevation data for the United States and its territories, including coastlines. Organizations also identified and reported the expected economic benefits that would be realized if their requirements for improved elevation were met (appendixes 1–3). This report describes the data collection methodology and summarizes the findings. Participating organizations included 34 Federal agencies, 50 States and two territories, and a sampling of local governments, tribes, and nongovernmental orgnizations. The nongovernmental organizations included The Nature Conservancy and a sampling of private sector businesses. These data were collected in 2010-2011 as part of the National Enhanced Elevation Assessment (NEEA), a study to identify program alternatives for better meeting the Nation’s elevation data needs. NEEA tasks included the collection of national elevation requirements; analysis of the benefits and costs of meeting these requirements; assessment of emerging elevation technologies, lifecycle data management needs, and costs for managing and distributing a national-scale dataset and derived products; and candidate national elevation program alternatives that balance costs and benefits in meeting the Nation’s elevation requirements. The NEEA was sponsored by the National Digital Elevation Program (NDEP), a government coordination body with the U.S. Geological Survey (USGS) as managing partner that includes the National Geospatial-Intelligence Agency (NGA), the Federal Emergency Management Agency (FEMA), the Natural Resources Conservation Service (NRCS), the U.S. Army Corps of Engineers (USACE), and the National Oceanic and Atmospheric Administration (NOAA), among the more than a dozen agencies and organizations. The term enhanced elevation data as used in this report refers broadly to three-dimensional measurements of land or

  3. 28 CFR 36.404 - Alterations: Elevator exemption.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Elevator exemption. 36.404... Alterations: Elevator exemption. (a) This section does not require the installation of an elevator in an... facility has an elevator. ...

  4. Genomics and relative expression analysis identifies key genes associated with high female to male flower ratio in Jatropha curcas L.

    Science.gov (United States)

    Gangwar, Manali; Sood, Hemant; Chauhan, Rajinder Singh

    2016-04-01

    Jatropha curcas, has been projected as a major source of biodiesel due to high seed oil content (42 %). A major roadblock for commercialization of Jatropha-based biodiesel is low seed yield per inflorescence, which is affected by low female to male flower ratio (1:25-30). Molecular dissection of female flower development by analyzing genes involved in phase transitions and floral organ development is, therefore, crucial for increasing seed yield. Expression analysis of 42 genes implicated in floral organ development and sex determination was done at six floral developmental stages of a J. curcas genotype (IC561235) with inherently higher female to male flower ratio (1:8-10). Relative expression analysis of these genes was done on low ratio genotype. Genes TFL1, SUP, AP1, CRY2, CUC2, CKX1, TAA1 and PIN1 were associated with reproductive phase transition. Further, genes CUC2, TAA1, CKX1 and PIN1 were associated with female flowering while SUP and CRY2 in female flower transition. Relative expression of these genes with respect to low female flower ratio genotype showed up to ~7 folds increase in transcript abundance of SUP, TAA1, CRY2 and CKX1 genes in intermediate buds but not a significant increase (~1.25 folds) in female flowers, thereby suggesting that these genes possibly play a significant role in increased transition towards female flowering by promoting abortion of male flower primordia. The outcome of study has implications in feedstock improvement of J. curcas through functional validation and eventual utilization of key genes associated with female flowering.

  5. Preventing hairline elevation in endoscopic browlifts.

    Science.gov (United States)

    Hamas, R S; Rohrich, R J

    1997-04-01

    An endoscopic-assisted method of brow elevation using galea aponeurosis plication with direct suture fixation is presented. This technique does not elevate the hairline, nor is any skin or scalp resected. Dissection is easy because it is limited to the subgaleal plane of the forehead.

  6. 78 FR 22221 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2013-04-15

    ... referenced ground [caret] Communities affected elevation ** Elevation in meters (MSL) Effective Modified Pitt... feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. \\**\\ BFEs to be changed... inspection at the Department of Public Works, 1500 Beatty Street, Greenville, NC 27834. Unincorporated Areas...

  7. 75 FR 77762 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-12-14

    ... Flooding source(s) elevation in feet above Communities affected ground [caret] Elevation in meters (MSL..., rounded to the nearest 0.1 meter. ADDRESSES City of Aurora Maps are available for inspection at 15151 East... Arapahoe County Department of Public Works and Development, 10730 West Briarwood Avenue, Centennial, CO...

  8. 75 FR 69892 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-11-16

    ...: * Elevation in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth... county +899 City of Norwich, Town boundary. of Greene, Town of North Norwich, Town of Oxford, Town of...). Susquehanna River At the downstream county +965 Town of Afton, Town of boundary. Bainbridge, Village of Afton...

  9. 77 FR 6980 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-02-10

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in feet above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Nowata County... Bayou An area bounded by the +100 Town of Mayersville, county boundary to the Unincorporated Areas of...

  10. 76 FR 1535 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-01-11

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in feet above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Poinsett County... with the St. Francis River...... +212 Areas of Poinsett County. Approximately 0.45 mile downstream of...

  11. 77 FR 66737 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-11-07

    ... follows: * Elevation in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding... +43 Town of Kingstree, Unincorporated Areas of Williamsburg County. Approximately 0.3 mile +48... Town of Hemingway, confluence. Unincorporated Areas of Williamsburg County. Approximately 0.3 mile +50...

  12. 75 FR 29253 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2010-05-25

    ...: * Elevation in feet (NGVD) + Elevation in feet (NAVD) Depth in feet above State City/town/county Source of... +21 Town of Ebro, upstream of the Unincorporated Areas confluence with the of Washington County. East... County, Colorado, and Incorporated Areas Willow Creek At the confluence with None +8,154 Unincorporated...

  13. 75 FR 68710 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-11-09

    ...: * Elevation in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth... County, California Docket Nos.: FEMA-B-7762, FEMA-B-7795, and FEMA-B-1053 California Unincorporated Oregon Slough..... City of Montague +2503 Areas of Siskiyou and County. Unincorporated Siskiyou County...

  14. 77 FR 45262 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-07-31

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of Location Depth in feet flooding above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Solano County... Areas of Solano upstream of the County. McCune Creek confluence. Approximately 930 feet +149 upstream of...

  15. 76 FR 50918 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-08-17

    ... in feet (NGVD) + Elevation in feet (NAVD) Depth in feet State City/town/county Source of flooding... affected [caret] Elevation in meters (MSL) Modified Jones County, Texas, and Incorporated Areas Docket No.: FEMA-B-1122 Lake Fort Phantom Hill Just downstream of County +1642 City of Abilene, Highway 1082...

  16. 78 FR 10066 - Final Flood Elevation Determinations

    Science.gov (United States)

    2013-02-13

    ... follows: * Elevation in feet (NGVD) + Elevation in feet (NAVD) Depth in feet State City/town/county Source...). Scriba Creek Approximately 0.90 mile +546 Town of Amboy. upstream of County Route 23 (Potter Road.... Town of Palermo Maps are available for inspection at the Palermo Town Municipal Offices, 53 County...

  17. 77 FR 49367 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-08-16

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in feet above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Chickasaw County... Chickasaw County. (backwater effects feet upstream of from Cedar River). the Cedar River confluence...

  18. 77 FR 49379 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-08-16

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in feet above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Washington County... of the +35 Areas of railroad. Washington County. Approximately 2.1 miles upstream of the railroad...

  19. 75 FR 43418 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-07-26

    ... follows: * Elevation in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding... +869 Town of Peoria, upstream of Main Street. Unincorporated Areas of Ottawa County. Approximately 1.... Town of Peoria Maps are available for inspection at the Ottawa County Courthouse, 102 East Central...

  20. Insect Population Dynamics in Commercial Grain Elevators

    Science.gov (United States)

    Data were collected in 1998-2002 from wheat stored in commercial grain elevators in south-central Kansas. Storage bins at these elevators had concrete walls and were typically 6-9 m in diameter and 30-35 m tall. A vacuum-probe sampler was used to collect ten 3-kg grain samples in the top 12 m of the...

  1. High elevation white pines educational website

    Science.gov (United States)

    Anna W. Schoettle; Michele Laskowski

    2011-01-01

    The high elevation five-needle white pines are facing numerous challenges ranging from climate change to invasion by a non-native pathogen to escalation of pest outbreaks. This website (http://www.fs.fed.us/rm/highelevationwhitepines/) serves as a primer for managers and the public on the high elevation North American five-needle pines. It presents information on each...

  2. The benefits of improved national elevation data

    Science.gov (United States)

    Snyder, Gregory I.

    2013-01-01

    This article describes how the National Enhanced Elevation Assessment (NEEA) has identified substantial benefits that could come about if improved elevation data were publicly available for current and emerging applications and business uses such as renewable energy, precision agriculture, and intelligent vehicle navigation and safety. In order to support these diverse needs, new national elevation data with higher resolution and accuracy are needed. The 3D Elevation Program (3DEP) initiative was developed to meet the majority of these needs and it is expected that 3DEP will result in new, unimagined information services that would result in job growth and the transformation of the geospatial community. Private-sector data collection companies are continuously evolving sensors and positioning technologies that are needed to collect improved elevation data. An initiative of this scope might also provide an opportunity for companies to improve their capabilities and produce even higher data quality and consistency at a pace that might not have otherwise occurred.

  3. Elevers refleksjoner over naturvitenskapens egenart

    Directory of Open Access Journals (Sweden)

    Anne Bergliot Øyehaug

    2014-05-01

    Full Text Available This paper reports from a study where a teacher and researchers collaborated on designing science teaching promoting scientific inquiry for a group of students (age 11 – 13. Guided by the Norwegian science curriculum, students were during a two year intervention period regularly engaged in inquiry-based science learning. The students formed and tested hypotheses, were to various degrees engaged in developing research design and took extensively part in evaluation of evidence. In connection with each inquiry task, students were encouraged to express their ideas about professional or formal science emphasized in the Norwegian science curriculum (Why do scientists form and test hypothesis? What characterize scientific inquiry? Why do scientists compare results?. Data (video recordings of classroom instructions and interviews in addition to written tests from four students were collected during a two year period. Results indicate that the students’ epistemological beliefs remained fairly naïve through the intervention period, in spite of intensive participation in inquiry learning. The students’ lack of epistemological development may be understood in terms of the instructional emphasis on formal epistemology, in favor of practical epistemology.

  4. Elevated tumour marker: an indication for imaging?

    LENUS (Irish Health Repository)

    McMahon, Colm J

    2012-02-01

    INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and\\/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of \\'elevated tumour marker\\' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: \\'elevated tumour marker\\'. They underwent 29 imaging studies (mean [+\\/-standard deviation (SD)] per patient = 1.2 [+\\/-0.4]), and had 42 elevated tumour marker serology tests (mean [+\\/-SD] per patient = 1.7 [+\\/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of \\'elevated tumour marker\\'. \\'Elevated tumour marker\\

  5. King Cove, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  6. Midway Atoll Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  7. Arecibo, Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  8. Keauhou, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  9. Craig, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  10. Shemya, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  11. Daytona Beach, Florida Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  12. Kawaihae, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  13. Cordova, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  14. Arena Cove, California Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  15. Sand Point, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  16. Montauk, New York Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  17. Atka, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  18. Monterey, California Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  19. Garibaldi, Oregon Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  20. Increasing heel skin perfusion by elevation.

    Science.gov (United States)

    Huber, Jacqueline; Reddy, Raj; Pitham, Tom; Huber, David

    2008-01-01

    To determine the efficacy of elevation in the primary prevention and treatment of pressure ulcers by studying the blood flow in tissue at risk of ulceration. A prospective study was used to compare different preventative devices with an elevating prosthesis. : Wollongong Hospital Wollongong, New South Wales, Australia. Normal subjects and subjects with vasculopathy were tested with their heel resting on a hospital bed, medical-grade lamb's wool, or a viscoelastic gel overlay, with or without the test prosthesis. Skin perfusion was measured throughout using a laser Doppler monitor. A device designed to elevate the heel off the bed and distribute the weight of the leg and foot on the calf. Heel capillary blood perfusion. Perfusion in the heel was significantly greater when elevated than when using the other devices tested. The differences in mean red blood cell flux were significant, with P pressure ulcer prevention and treatment and should be incorporated into health care practice.

  1. Juneau, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  2. Chenega, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  3. Mariana Trench Bathymetric Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) created a bathymetric digital elevation model (DEM) for the Mariana Trench and adjacent seafloor in the Western...

  4. Shaded Relief of Minnesota Elevation - Black & White

    Data.gov (United States)

    Minnesota Department of Natural Resources — This file is a product of a shaded relief process on the 30 meter resolution Digital Elevation Model data (dem30im3). This image was created using a custom AML...

  5. Nikolski, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  6. ASTER Global Digital Elevation Model V002

    Data.gov (United States)

    National Aeronautics and Space Administration — The Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global Digital Elevation Model (GDEM) was developed jointly by the U.S. National...

  7. La Push, Washington Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  8. Nantucket, Massachusetts Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  9. Ocean City, Maryland Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  10. Hilo, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  11. Portland, Maine Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  12. Hanalei, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  13. Chignik, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  14. Adak, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  15. Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  16. Kachemak Bay, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  17. Lahaina, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  18. Oahu, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  19. Santa Barbara, California Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  20. Central Oregon Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  1. Virginia Beach, Virginia Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  2. Galveston, Texas Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  3. Biloxi, Mississippi Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  4. Ponce, Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  5. Corpus Christi, Texas Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  6. ASTER Digital Elevation Model V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The ASTER Digital Elevation Model (DEM) product is generated using bands 3N (nadir-viewing) and 3B (backward-viewing) of an ASTER Level-1A image acquired by the...

  7. Savannah, Georgia Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  8. Moral elevation reduces prejudice against gay men.

    Science.gov (United States)

    Lai, Calvin K; Haidt, Jonathan; Nosek, Brian A

    2014-01-01

    Disgust is linked to social evaluation. People with higher disgust sensitivity exhibit more sexual prejudice, and inducing disgust increases sexual prejudice. We tested whether inducing moral elevation, the theoretical opposite of disgust, would reduce sexual prejudice. In four studies (N = 3622), we induced elevation with inspiring videos and then measured sexual prejudice with implicit and explicit measures. Compared to control videos that elicited no particular affective state, we found that elevation reduced implicit and explicit sexual prejudice, albeit very slightly. No effect was observed when the target of social evaluation was changed to race (Black-White). Inducing amusement, another positive emotion, did not significantly affect sexual prejudice. We conclude that elevation weakly but reliably reduces prejudice towards gay men.

  9. Grain Elevators: New Source Performance Standards (NSPS)

    Science.gov (United States)

    The New Source Performance Standards (NSPS) for Grain Elevators aims to reduce particulate matter pollution. The new amendments seek to clarify definitions, and requirements, as well as propose new regulations on particulate matter emissions

  10. Elevator mechanism and method for scintillation detectors

    International Nuclear Information System (INIS)

    Frank, E.

    1975-01-01

    An elevator mechanism and method for raising and lowering radioactive samples through a shielded vertical counting chamber in a benchtop scintillation detector is described. The elevator mechanism adds little or nothing to the height of the detector by using an elongated flexible member such as a metal tape secured to the bottom of the elevator platform and extending downwardly through the counting chamber and its bottom shielding, where the tape is bent laterally for connection to a drive means. In the particular embodiment illustrated, the tape is bent laterally below the bottom shielding for the counting chamber, and then upwardly along or through one side of the shielding to a reel at the top of the shielding. The tape is wound onto the reel, and the reel is driven by a reversible motor which winds and unwinds the tape on the reel to raise and lower the elevator platform

  11. Southeast Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  12. Taholah, Washington Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  13. Whittier, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  14. Gustavus, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  15. Fajardo, Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  16. Port Alexander Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  17. Dutch Harbor, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  18. Port Orford, Oregon Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  19. Panama City, Florida Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  20. Guayama, Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  1. Shaded Relief of Minnesota Elevation - Color

    Data.gov (United States)

    Minnesota Department of Natural Resources — This file is a product of a shaded relief process on the 30 meter resolution Digital Elevation Model data (dem30im3). This image was created using a custom AML...

  2. New Orleans, Louisiana Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions in the Gulf of Mexico....

  3. Elevated temperature erosive wear of metallic materials

    International Nuclear Information System (INIS)

    Roy, Manish

    2006-01-01

    Solid particle erosion of metals and alloys at elevated temperature is governed by the nature of the interaction between erosion and oxidation, which, in turn, is determined by the thickness, pliability, morphology, adhesion characteristics and toughness of the oxide scale. The main objective of this paper is to critically review the present state of understanding of the elevated temperature erosion behaviour of metals and alloys. First of all, the erosion testing at elevated temperature is reviewed. This is followed by discussion of the essential features of elevated temperature erosion with special emphasis on microscopic observation, giving details of the erosion-oxidation (E-O) interaction mechanisms. The E-O interaction has been elaborated in the subsequent section. The E-O interaction includes E-O maps, analysis of transition criteria from one erosion mechanism to another mechanism and quantification of enhanced oxidation kinetics during erosion. Finally, the relevant areas for future studies are indicated. (topical review)

  4. Identification and expression analysis of the IPT and CKX gene families during axillary bud outgrowth in apple (Malus domestica Borkh.).

    Science.gov (United States)

    Tan, Ming; Li, Guofang; Qi, Siyan; Liu, Xiaojie; Chen, Xilong; Ma, Juanjuan; Zhang, Dong; Han, Mingyu

    2018-04-20

    Cytokinins (CKs) play a crucial role in promoting axillary bud outgrowth and targeting the control of CK metabolism can be used to enhance branching in plants. CK levels are maintained mainly by CK biosynthesis (isopentenyl transferase, IPT) and degradation (dehydrogenase, CKX) genes in plants. A systematic study of the IPT and CKX gene families in apple, however, has not been conducted. In the present study, 12 MdIPTs and 12 MdCKXs were identified in the apple genome. Systematic phylogenetic, structural, and synteny analyses were performed. Expression analysis of these genes in different tissues was also assessed. MdIPT and MdCKX genes exhibit distinct expression patterns in different tissues. The response of MdIPT, MdCKX, and MdPIN1 genes to various treatments (6-BA, decapitation and Lovastatin, an inhibitor of CKs synthesis) that impact branching were also investigated. Results indicated that most of the MdIPT and MdCKX, and MdPIN1 genes were upregulated by 6-BA and decapitation treatment, but inhibited by Lovastatin, a compound that effectively suppresses axillary bud outgrowth induced by decapitation. These findings suggest that cytokinin biosynthesis is required for the activation of bud break and the export of auxin from buds in apple tree with intact primary shoot apex or decapitated apple tree. MdCKX8 and MdCKX10, however, exhibited little response to decapitation, but were significantly up-regulated by 6-BA and Lovastatin, a finding that warrants further investigation in order to understand their function in bud-outgrowth. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Electrostatic Climber for Space Elevator and Launcher

    OpenAIRE

    Bolonkin, A.

    2007-01-01

    Author details research on the new, very prospective, electrostatic Space Elevator climber based on a new electrostatic linear engine previously offered at the 42nd Joint Propulsion Conference (AIAA-2006-5229) and published in AEAT, Vol.78, No.6, 2006, pp. 502-508. The electrostatic climber discussed can have any speed (and braking), the energy for climber movement is delivered by a lightweight high-voltage line into a Space Elevator-holding cable from Earth electric generator. This electric ...

  6. Elevator Illusion and Gaze Direction in Hypergravity

    Science.gov (United States)

    Cohen, Malcolm M.; Hargens, Alan (Technical Monitor)

    1995-01-01

    A luminous visual target in a dark hypergravity (Gz greater than 1) environment appears to be elevated above its true physical position. This "elevator illusion" has been attributed to changes in oculomotor control caused by increased stimulation of the otolith organs. Data relating the magnitude of the illusion to the magnitude of the changes in oculomotor control have been lacking. The present study provides such data.

  7. Global elevational diversity and diversification of birds.

    Science.gov (United States)

    Quintero, Ignacio; Jetz, Walter

    2018-03-08

    Mountain ranges harbour exceptionally high biodiversity, which is now under threat from rapid environmental change. However, despite decades of effort, the limited availability of data and analytical tools has prevented a robust and truly global characterization of elevational biodiversity gradients and their evolutionary origins. This has hampered a general understanding of the processes involved in the assembly and maintenance of montane communities. Here we show that a worldwide mid-elevation peak in bird richness is driven by wide-ranging species and disappears when we use a subsampling procedure that ensures even species representation in space and facilitates evolutionary interpretation. Instead, richness corrected for range size declines linearly with increasing elevation. We find that the more depauperate assemblages at higher elevations are characterized by higher rates of diversification across all mountain regions, rejecting the idea that lower recent diversification rates are the general cause of less diverse biota. Across all elevations, assemblages on mountains with high rates of past temperature change exhibit more rapid diversification, highlighting the importance of climatic fluctuations in driving the evolutionary dynamics of mountain biodiversity. While different geomorphological and climatic attributes of mountain regions have been pivotal in determining the remarkable richness gradients observed today, our results underscore the role of ongoing and often very recent diversification processes in maintaining the unique and highly adapted biodiversity of higher elevations.

  8. Energy considerations in the partial space elevator

    Science.gov (United States)

    Woo, Pamela; Misra, Arun K.

    2014-06-01

    The space elevator has been proposed as an alternate method for space transportation. A partial elevator is composed of a tether of several hundreds of kilometres, held vertically in tension between two end masses, with its centre of orbit placed at the geosynchronous orbit. A spacecraft can dock at the lower end, and then use the climber on the elevator to ascend to higher altitudes. In this paper, energy calculations are performed, to determine whether a partial elevator can provide sufficient savings in operational costs, compared to the traditional rocket-powered launch. The energy required to launch a spacecraft from a Low Earth Orbit (LEO) to the geostationary orbit (GEO) is calculated for two trajectories. In the first trajectory, the spacecraft travels from LEO to GEO via a Hohmann transfer. In the second trajectory, the spacecraft travels from LEO to the lower end of the partial space elevator with a Hohmann transfer, and then uses the elevator to climb to GEO. The total energy required is compared between the two trajectories. The effects of tether length, spacecraft-to-climber mass ratio, altitude of LEO, and tether material are investigated.

  9. P Elevator: An Innovatively Designed Elevator for Extraction of Third Molars.

    Science.gov (United States)

    Singh, Pradeep; Xiao, Shui Sheng; Ajmera, Deepal Haresh

    2015-01-01

    To modify the conventional straight elevator with a unique and innovative design in respect to approach and accessibility during extraction for patients with abrasions around corners of the mouth and with thick buccal mucosa, without causing overstretching of angles of the mouth. The shank of the straight elevator in the shape of a 'U' was modified, giving it a shape similar to 'P' in the English alphabet hence it is named the P Elevator. The P elevator utilises a 'U' shaped bend in the shank of the conventional straight elevator making space for the buccal soft tissues and the angle of the mouth, to accommodate properly in the 'U' shank. The application of this elevator in the successful removal of third molars is described. Two hundred patients underwent extraction of third molars with the P elevator including 166 patients with disimpaction of all third molars, 23 patients with abrasion around the angle of the mouth, and 11 patients with thick buccal mucosa. Satisfactory results were obtained in all the cases with no postoperative complications. The P elevator permits prudent, meticulous, innovative and proficient extraction of third molars in patients with thick buccal mucosa and abrasions around the angle of the mouth, without overstretching the corners of the mouth. We introduce novel applications of the P elevator in third molar extraction that provide substantial advantages over a conventional straight elevator.

  10. Lunar transportation scenarios utilising the Space Elevator

    Science.gov (United States)

    Engel, Kilian A.

    2005-07-01

    The Space Elevator (SE) concept has begun to receive an increasing amount of attention within the space community over the past couple of years and is no longer widely dismissed as pure science fiction. In light of the renewed interest in a, possibly sustained, human presence on the Moon and the fact that transportation and logistics form the bottleneck of many conceivable lunar missions, it is interesting to investigate what role the SE could eventually play in implementing an efficient Earth to Moon transportation system. The elevator allows vehicles to ascend from Earth and be injected into a trans-lunar trajectory without the use of chemical thrusters, thus eliminating gravity loss, aerodynamic loss and the need of high thrust multistage launch systems. Such a system therefore promises substantial savings of propellant and structural mass and could greatly increase the efficiency of Earth to Moon transportation. This paper analyzes different elevator-based trans-lunar transportation scenarios and characterizes them in terms of a number of benchmark figures. The transportation scenarios include direct elevator-launched trans-lunar trajectories, elevator-launched trajectories via L1 and L2, as well as launch from an Earth-based elevator and subsequent rendezvous with lunar elevators placed either on the near or on the far side of the Moon. The benchmark figures by which the different transfer options are characterized and evaluated include release radius (RR), required Δv, transfer times as well as other factors such as accessibility of different lunar latitudes, frequency of launch opportunities and mission complexity. The performances of the different lunar transfer options are compared with each other as well as with the performance of conventional mission concepts, represented by Apollo.

  11. Epithelial integrity in palatal shelf elevation

    Directory of Open Access Journals (Sweden)

    Shigeru Okuhara

    2012-02-01

    Full Text Available The palate is the ceiling of the oral cavity that separates the nasal and oral cavities in mammals. Anterior two-thirds of the palate that has the bone and the rugae on the oral surface is the hard palate, and the posterior one-third of the palate lacks bone and is referred to as the soft palate. Palate development involves a sequential process of outgrowth, elevation, and fusion of palatal shelves. When these steps are interrupted or compromised, cleft palate, one of the most frequent human congenital anomalies, develops. In particular, during the elevation process, sufficient proliferation of palatal mesenchymal cells and concomitant synthesis of extracellular matrix (ECM are required, and these are referred to as intrinsic factors. One of major extrinsic factors for this process is the functional maturation of masticatory muscles that are responsible for movement of the mandible and lingual muscles, such that the tongue can descend and sufficient space for shelf elevation is provided. In addition to these factors, recent findings have suggested that a third factor, epithelial integrity, may be an essential component for successful shelf elevation. For example, disruption of epithelial integrity can result in ectopic epithelial fusion between the palate and the mandible, or tongue, which anchors the palatal shelf to inhibit its elevation. Although most histological and molecular aspects of palatal elevation have been well reviewed, those of epithelial integrity have not been thoroughly elucidated. Therefore, in this review, features of epithelial integrity, and its contributing molecules, are described in relation to palatal shelf elevation in mice.

  12. Lunar transportation scenarios utilising the Space Elevator.

    Science.gov (United States)

    Engel, Kilian A

    2005-01-01

    The Space Elevator (SE) concept has begun to receive an increasing amount of attention within the space community over the past couple of years and is no longer widely dismissed as pure science fiction. In light of the renewed interest in a, possibly sustained, human presence on the Moon and the fact that transportation and logistics form the bottleneck of many conceivable lunar missions, it is interesting to investigate what role the SE could eventually play in implementing an efficient Earth to Moon transportation system. The elevator allows vehicles to ascend from Earth and be injected into a trans-lunar trajectory without the use of chemical thrusters, thus eliminating gravity loss, aerodynamic loss and the need of high thrust multistage launch systems. Such a system therefore promises substantial savings of propellant and structural mass and could greatly increase the efficiency of Earth to Moon transportation. This paper analyzes different elevator-based trans-lunar transportation scenarios and characterizes them in terms of a number of benchmark figures. The transportation scenarios include direct elevator-launched trans-lunar trajectories, elevator launched trajectories via L1 and L2, as well as launch from an Earth-based elevator and subsequent rendezvous with lunar elevators placed either on the near or on the far side of the Moon. The benchmark figures by which the different transfer options are characterized and evaluated include release radius (RR), required delta v, transfer times as well as other factors such as accessibility of different lunar latitudes, frequency of launch opportunities and mission complexity. The performances of the different lunar transfer options are compared with each other as well as with the performance of conventional mission concepts, represented by Apollo. c2005 Elsevier Ltd. All rights reserved.

  13. Space Elevator Concept Considered a Reality

    Science.gov (United States)

    2000-01-01

    The `once upon a time' science fiction concept of a space elevator has been envisioned and studied as a real mass transportation system in the latter part of the 21st century. David Smitherman of NASA's Marshall Space Flight Center's Advanced Projects Office has compiled plans for such an elevator. The space elevator concept is a structure extending from the surface of the Earth to geostationary Earth orbit (GEO) at 35,786 km in altitude. The tower would be approximately 50 km tall with a cable tethered to the top. Its center mass would be at GEO such that the entire structure orbits the Earth in sync with the Earth's rotation maintaining a stationary position over its base attachment at the equator. Electromagnetic vehicles traveling along the cable could serve as a mass transportation system for transporting people, payloads, and power between space and Earth. This illustration by artist Pat Rawling shows the concept of a space elevator as viewed from the geostationary transfer station looking down the length of the elevator towards the Earth.

  14. Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

    DEFF Research Database (Denmark)

    Hassan-Zahraee, M; Tran, E H; Bourbonnière, L

    2000-01-01

    into transgenic mice which express elevated levels of IFNgamma in the CNS was unsuccessful. By contrast, there was 100% survival of even fully allogeneic, T-depleted transplants to transgenics that over express TNFalpha in the CNS, using the same MBP promoter. IFNgamma was detectable in spleen of irradiated mice...

  15. Scientific return of a lunar elevator

    Science.gov (United States)

    Eubanks, T. M.; Radley, C. F.

    2016-11-01

    The concept of a space elevator dates back to Tsilokovsky, but they are not commonly considered in near-term plans for space exploration, perhaps because a terrestrial elevator would not be possible without considerable improvements in tether material. A Lunar Space Elevator (LSE), however, can be built with current technology using commercially available tether polymers. This paper considers missions leading to infrastructure capable of shortening the time, lowering the cost and enhancing the capabilities of robotic and human explorers. These missions use planetary scale tethers, strings many thousands of kilometers long stabilized either by rotation or by gravitational gradients. These systems promise major reduction in transport costs versus chemical rockets, in a rapid timeframe, for a modest investment. Science will thus benefit as well as commercial activities.

  16. Advanced composite elevator for Boeing 727 aircraft

    Science.gov (United States)

    1979-01-01

    Detail design activities are reported for a program to develop an advanced composites elevator for the Boeing 727 commercial transport. Design activities include discussion of the full scale ground test and flight test activities, the ancillary test programs, sustaining efforts, weight status, and the production status. Prior to flight testing of the advanced composites elevator, ground, flight flutter, and stability and control test plans were reviewed and approved by the FAA. Both the ground test and the flight test were conducted according to the approved plan, and were witnessed by the FAA. Three and one half shipsets have now been fabricated without any significant difficulty being encountered. Two elevator system shipsets were weighed, and results validated the 26% predicted weight reduction. The program is on schedule.

  17. Vertical vibration analysis for elevator compensating sheave

    International Nuclear Information System (INIS)

    Watanabe, Seiji; Nakazawa, Daisuke; Fukui, Daiki; Okawa, Takeya

    2013-01-01

    Most elevators applied to tall buildings include compensating ropes to satisfy the balanced rope tension between the car and the counter weight. The compensating ropes receive tension by the compensating sheave, which is installed at the bottom space of the elevator shaft. The compensating sheave is only suspended by the compensating ropes, therefore, the sheave can move vertically while the car is traveling. This paper shows the elevator dynamic model to evaluate the vertical motion of the compensating sheave. Especially, behavior in emergency cases, such as brake activation and buffer strike, was investigated to evaluate the maximum upward motion of the sheave. The simulation results were validated by experiments and the most influenced factor for the sheave vertical motion was clarified

  18. Vertical vibration analysis for elevator compensating sheave

    Science.gov (United States)

    Watanabe, Seiji; Okawa, Takeya; Nakazawa, Daisuke; Fukui, Daiki

    2013-07-01

    Most elevators applied to tall buildings include compensating ropes to satisfy the balanced rope tension between the car and the counter weight. The compensating ropes receive tension by the compensating sheave, which is installed at the bottom space of the elevator shaft. The compensating sheave is only suspended by the compensating ropes, therefore, the sheave can move vertically while the car is traveling. This paper shows the elevator dynamic model to evaluate the vertical motion of the compensating sheave. Especially, behavior in emergency cases, such as brake activation and buffer strike, was investigated to evaluate the maximum upward motion of the sheave. The simulation results were validated by experiments and the most influenced factor for the sheave vertical motion was clarified.

  19. A new bed elevation dataset for Greenland

    Directory of Open Access Journals (Sweden)

    J. L. Bamber

    2013-03-01

    Full Text Available We present a new bed elevation dataset for Greenland derived from a combination of multiple airborne ice thickness surveys undertaken between the 1970s and 2012. Around 420 000 line kilometres of airborne data were used, with roughly 70% of this having been collected since the year 2000, when the last comprehensive compilation was undertaken. The airborne data were combined with satellite-derived elevations for non-glaciated terrain to produce a consistent bed digital elevation model (DEM over the entire island including across the glaciated–ice free boundary. The DEM was extended to the continental margin with the aid of bathymetric data, primarily from a compilation for the Arctic. Ice thickness was determined where an ice shelf exists from a combination of surface elevation and radar soundings. The across-track spacing between flight lines warranted interpolation at 1 km postings for significant sectors of the ice sheet. Grids of ice surface elevation, error estimates for the DEM, ice thickness and data sampling density were also produced alongside a mask of land/ocean/grounded ice/floating ice. Errors in bed elevation range from a minimum of ±10 m to about ±300 m, as a function of distance from an observation and local topographic variability. A comparison with the compilation published in 2001 highlights the improvement in resolution afforded by the new datasets, particularly along the ice sheet margin, where ice velocity is highest and changes in ice dynamics most marked. We estimate that the volume of ice included in our land-ice mask would raise mean sea level by 7.36 m, excluding any solid earth effects that would take place during ice sheet decay.

  20. Strength properties of concrete at elevated temperatures

    International Nuclear Information System (INIS)

    Freskakis, G.N.; Burrow, R.C.; Debbas, E.B.

    1979-01-01

    A study is presented concerning the compressive strength, modulus of elasticity, and stress-strain relationships of concrete at elevated temperatures. A review of published results provides information for the development of upper and lower bound relationships for compressive strength and the modulus of elasticity and establishes exposure conditions for a lower bound thermal response. The relationships developed from the literature review are confirmed by the results of a verification test program. The strength and elasticity relationships provide a basis for the development of design stress-strain curves for concrete exposed to elevated temperatures

  1. Forest succession at elevated CO2

    Energy Technology Data Exchange (ETDEWEB)

    Clark, James S.; Schlesinger, William H.

    2002-02-01

    We tested hypotheses concerning the response of forest succession to elevated CO2 in the FACTS-1 site at the Duke Forest. We quantified growth and survival of naturally recruited seedlings, tree saplings, vines, and shrubs under ambient and elevated CO2. We planted seeds and seedlings to augment sample sites. We augmented CO2 treatments with estimates of shade tolerance and nutrient limitation while controlling for soil and light effects to place CO2 treatments within the context of natural variability at the site. Results are now being analyzed and used to parameterize forest models of CO2 response.

  2. Nurses' accuracy in estimating backrest elevation

    African Journals Online (AJOL)

    2007-02-08

    Feb 8, 2007 ... associated pneumonia (VAP).1 Backrest elevation is defined as the angle of the backrest ... Aspiration of gastric contents is thought to be a major mechanism in the ... associated pneumonia (VAP) Compliance with this recommendation may be affected by nurses' knowledge of the recommendation and their ...

  3. Complement elevation in spinal cord injury.

    Science.gov (United States)

    Rebhun, J; Botvin, J

    1980-05-01

    Laboratory studies revealed an elevated complement in 66% of patients with spinal cord injury. It is postulated that the activated complement may be a component of self-feeding immunological mechanism responsible for the failure of regeneration of a mature mammalian spinal cord. There was no evidence that such an injury had any effect on pre-existing atopy.

  4. Elevated transferrin saturation and risk of diabetes

    DEFF Research Database (Denmark)

    Ellervik, Christina; Mandrup-Poulsen, Thomas; Andersen, Henrik Ullits

    2011-01-01

    OBJECTIVE We tested the hypothesis that elevated transferrin saturation is associated with an increased risk of any form of diabetes, as well as type 1 or type 2 diabetes separately. RESEARCH DESIGN AND METHODS We used two general population studies, The Copenhagen City Heart Study (CCHS, N = 9...

  5. Elevated fetal steroidogenic activity in autism

    Science.gov (United States)

    Baron-Cohen, S; Auyeung, B; Nørgaard-Pedersen, B; Hougaard, D M; Abdallah, M W; Melgaard, L; Cohen, A S; Chakrabarti, B; Ruta, L; Lombardo, M V

    2015-01-01

    Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism. PMID:24888361

  6. Elevated extracellular potassium ion concentrations suppress ...

    African Journals Online (AJOL)

    To address this question, we examined how elevations of [K+]o affect hippocampal oscillations in Scn1a mutant mouse, a mouse model of Dravet syndrome, a devastating genetic-epilepsy associated with gliosis, a major cause of dysregulated K+ homeostasis in epileptic brain. Methods: To this end, performing local field ...

  7. 75 FR 59181 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2010-09-27

    ...) Depth in feet above State City/town/county Source of flooding Location ** ground [caret] Elevation in... of Southeast. the Town of Southeast. Muscoot River At the county boundary. +512 +509 Town of Carmel.... At the county boundary. +391 +393 Stephens Brook Approximately 250 feet +432 +433 Town of Patterson...

  8. 78 FR 5738 - Final Flood Elevation Determinations

    Science.gov (United States)

    2013-01-28

    ... in feet (NGVD) + Elevation in feet (NAVD) Depth in feet State City/town/county Source of flooding... of Winooski River. Barre, City of Montpelier, Town of Berlin. At county boundary +740 (approximately.... Approximately 60 feet +728 upstream of Water Street. Winooski River At Chittenden County +342 Town of Middlesex...

  9. 76 FR 72661 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2011-11-25

    ...) Depth in feet above State City/town/county Source of flooding Location ** ground [caret] Elevation in meters (MSL) Existing Modified Town of Richland, New York New York Town of Richland........ Lake Ontario Entire shoreline within Selkirk Shores State Park boundary None +249 New York Town of Richland...

  10. 75 FR 62751 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2010-10-13

    .../town/county Source of flooding Location ** ground [caret] Elevation in meters (MSL) Existing Modified Unincorporated Areas of Claiborne County, Tennessee Tennessee Unincorporated Areas of Clinch River Approximately 2.3 miles downstream of Big Barren Creek.... +1055 +1032 Claiborne County. [[Page 62752...

  11. 76 FR 40670 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2011-07-11

    ...) Depth in feet above State City/town/county Source of flooding Location ** ground [caret] Elevation in... Contentnea Creek +76 +77 Town of Black Creek, confluence. Unincorporated Areas of Wilson County... +63 Town of Stantonsburg, confluence. Unincorporated Areas of Wilson County. Approximately 0.8 mile...

  12. 75 FR 3171 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-01-20

    ... City/town/county Source of flooding Location Depth in feet above ground [caret]Elevation in meters (MSL... Approximately 990 feet +388 Unincorporated Areas of upstream of the Lauderdale County, Town confluence of... Unincorporated Areas of Lee County, Town of Shannon. Approximately 6,220 feet +252 upstream of State Highway 145...

  13. 76 FR 50960 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2011-08-17

    ...) Depth in feet above State City/town/county Source of flooding Location ** ground [caret] Elevation in..., Town downstream of the of Snow Hill, Wheat Swamp confluence. Unincorporated Areas of Greene County... Contentnea Creek +47 +41 Town of Snow Hill, confluence. Unincorporated Areas of Greene County. [[Page 50964...

  14. 76 FR 66887 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2011-10-28

    ...) Depth in feet above State City/town/county Source of flooding Location** ground [caret] Elevation in meters (MSL) Existing Modified Town of Richmond, Vermont Vermont Town of Richmond........ Winooski River... Incorporated Areas Little Thompson River At the downstream side None +4935 Town of Berthoud, of Weld County...

  15. 75 FR 67317 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2010-11-02

    ... above State City/town/county Source of flooding Location ** ground [caret] Elevation in meters (MSL) Existing Modified Unincorporated Areas of Butte-Silver Bow County, Montana Montana Unincorporated Areas of Basin Creek Approximately 1,000 feet upstream of I-90 +5468 +5469 Butte-Silver Bow County. Approximately...

  16. 76 FR 69665 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-11-09

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in...) Modified Summit County, Colorado, and Incorporated Areas Docket No.: FEMA-B-1049 Willow Creek At the confluence with + 8682 Town of Silverthorne, the Blue River. Unincorporated Areas of Summit County...

  17. 76 FR 68107 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-11-03

    ... in feet (NGVD) + Elevation in feet (NAVD) Depth in feet State City/town/county Source of flooding... Lee County. Approximately 796 feet +601 upstream of Thach Avenue. Town Creek Tributary 1 At the confluence with +460 City of Auburn, Town Creek. Unincorporated Areas of Lee County. Approximately 602 feet...

  18. 76 FR 59361 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2011-09-26

    ...) Depth in feet above State City/town/county Source of flooding Location ** ground [caret] Elevation in... County. At the Wash 10 East None +1455 divergence. Wash 11 East Approximately 600 feet None +1348 Town of... Town of Surprise, confluence. Unincorporated Areas of Maricopa County. At the Wash 12 East None +1514...

  19. 76 FR 8978 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2011-02-16

    .../town/county Source of flooding Location ** ground [caret] Elevation in meters (MSL) Existing Modified Unincorporated Areas of Yolo County, California California Unincorporated Areas of Cache Creek Settling Basin At........ Entire None +901 Town of shoreline Wolcottvill e, Unincorpora ted Areas of LaGrange County. * National...

  20. 76 FR 36482 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2011-06-22

    .../town/county Source of flooding Location ** ground [caret] Elevation in meters (MSL) Existing Modified City of Colonial Heights, Virginia Virginia City of Colonial Heights Old Town Creek Approximately 0.63... for inspection at 202 James Avenue, Colonial Heights, VA 23834. Unincorporated Areas of Halifax County...

  1. 76 FR 35119 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-06-16

    ... in feet (NGVD) + Elevation in feet (NAVD) Depth in feet State City/town/county Source of flooding... Town of Marana, the vicinity of Central Unincorporated Areas Arizona Project Canal of Pima County.... Messalonskee Stream At the County Road Bridge.... +105 Town of Oakland. At the City of Waterville/ +105...

  2. 77 FR 3625 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-01-25

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in... Sierra County, California, and Incorporated Areas Docket No.: FEMA-B-1128 Downie River Approximately 0.76 mile +2897 Unincorporated Areas of downstream of Jersey Sierra County. Flat Bridge. Approximately 167...

  3. 76 FR 3524 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-01-20

    ... effects from Kentucky River). the Kentucky River to Garrard County. approximately 932 feet upstream of Old..., City of The Colony, Town of Hebron, Unincorporated Areas of Denton County. Approximately 2,940 feet... Communities affected [caret] Elevation in meters (MSL) Modified Ashley County, Arkansas, and Incorporated...

  4. 77 FR 66788 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2012-11-07

    ... Town of Clarkstown. Old Mill Road. Approximately 600 feet +150 +151 downstream of Rockland Lake. Golf..., Orangetown/Town of Town of Orangetown. Clarkstown corporate limit. At the downstream side +67 +66 of Old Mill... and modified elevations, and communities affected for Rockland County, New York (All Jurisdictions...

  5. 76 FR 35111 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-06-16

    .... Conway County. Approximately 2.0 miles +301 upstream of Old Cherokee Road. * National Geodetic Vertical... inspection at the Town Hall, 34 West Main Street, Westborough, MA 01581. Marshall County, Mississippi, and... Communities affected [caret] Elevation in meters (MSL) Modified Conway County, Arkansas, and Incorporated...

  6. Kas Euroopale oma "Elevant"? / Tiina Lokk

    Index Scriptorium Estoniae

    Lokk, Tiina, 1955-

    2007-01-01

    Ilmar Raagi mängufilm "Klass" võitis 42. Karlovy Vary rahvusvahelise filmifestivalil kaks auhinda - ametliku kõrvalvõistlusprogrammi "East of the West" eripreemia "Special mention" ja Euroopa väärtfilmikinode keti Europa Cinemas preemia. Ka teistest võistlusprogrammi filmidest ja "Klassi" võrdlus Gus Van Santi filmiga "Elevant"

  7. Der er nye elever i klassen

    DEFF Research Database (Denmark)

    Weirsøe, Mathilde

    2010-01-01

    Etniske minoritetsbørn bliver udsat for 'naturlig' forskelsbehandling i de danske skoler, hvor der stadig undervises, som om alle elever hedder Jensen og Petersen. Det er på tide, at pædagogikken anerkender den etniske kompleksitet i vores samfund og indretter undervisningen derefter....

  8. Measuring elevated intracranial pressure through noninvasive methods

    DEFF Research Database (Denmark)

    Kristiansson, Helena; Nissborg, Emelie; Bartek, Jiri

    2013-01-01

    Elevated intracranial pressure (ICP) is an important cause of secondary brain injury, and a measurement of ICP is often of crucial value in neurosurgical and neurological patients. The gold standard for ICP monitoring is through an intraventricular catheter, but this invasive technique...

  9. ELEVATED TEMPERATURE EFFECTS ON THE ELECTRICAL ...

    African Journals Online (AJOL)

    The effects of elevated temperatures on the electrical properties of Bi metal probe to Si thin films had been investigated for electric field values 10-100V/m. Measurements of current (I) – voltage (V) characteristics were obtained at temperatures 300,320,340,360,380 and 400K respectively. The results indicated linear I–V ...

  10. Elevated Bladder Cancer Risk in New England

    Science.gov (United States)

    A new study has found that drinking water from private wells, particularly dug wells established during the first half of the 20th century, may have contributed to the elevated risk of bladder cancer that has been observed in Maine, New Hampshire, and Vermont for over 50 years.

  11. Troponin elevation after black widow spider envenomation.

    Science.gov (United States)

    Bush, Sean P; Davy, J Veeran

    2015-09-01

    Black widow spider envenomation generally results in self-limiting pain that can be treated in the emergency department (ED) with analgesics and benzodiazepines, usually with no further intervention. Occasionally, a patient has to be admitted or treated with antivenom for refractory pain or a venom-induced complication. We present the case of an 84-year-old man who presented to our ED with chest pain and dyspnea after being bitten on the foot by a western black widow spider (Lactrodectus hesperus). His initial cardiac troponin I (cTnI) was elevated at 0.07 ng/ml and continued to rise to a peak of 0.17 ng/ml. He also had rhabdomyolysis, another uncommon complication of black widow envenomation. An elevated cTnI generally signifies myocardial injury and is rarely seen after black widow envenomation. We discuss the possible etiologies for an elevated cardiac biomarker, in this context, and review potentially serious complications of widow spider envenomation presenting with chest symptoms and an elevated cardiac biomarker.

  12. Estimating Coastal Digital Elevation Model (DEM) Uncertainty

    Science.gov (United States)

    Amante, C.; Mesick, S.

    2017-12-01

    Integrated bathymetric-topographic digital elevation models (DEMs) are representations of the Earth's solid surface and are fundamental to the modeling of coastal processes, including tsunami, storm surge, and sea-level rise inundation. Deviations in elevation values from the actual seabed or land surface constitute errors in DEMs, which originate from numerous sources, including: (i) the source elevation measurements (e.g., multibeam sonar, lidar), (ii) the interpolative gridding technique (e.g., spline, kriging) used to estimate elevations in areas unconstrained by source measurements, and (iii) the datum transformation used to convert bathymetric and topographic data to common vertical reference systems. The magnitude and spatial distribution of the errors from these sources are typically unknown, and the lack of knowledge regarding these errors represents the vertical uncertainty in the DEM. The National Oceanic and Atmospheric Administration (NOAA) National Centers for Environmental Information (NCEI) has developed DEMs for more than 200 coastal communities. This study presents a methodology developed at NOAA NCEI to derive accompanying uncertainty surfaces that estimate DEM errors at the individual cell-level. The development of high-resolution (1/9th arc-second), integrated bathymetric-topographic DEMs along the southwest coast of Florida serves as the case study for deriving uncertainty surfaces. The estimated uncertainty can then be propagated into the modeling of coastal processes that utilize DEMs. Incorporating the uncertainty produces more reliable modeling results, and in turn, better-informed coastal management decisions.

  13. 76 FR 72627 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-11-25

    ... Areas Docket Nos.: FEMA-B-1022 and FEMA-B-1117 Agua Fria Canyon Approximately 340 feet +3384... Unincorporated Areas of Doyle Drive. Iberia Parish. At the intersection with +16 Adrian Street. Gulf of Mexico... AE zones have been made. Gulf of Mexico Base Flood Elevation +9-15 Unincorporated Areas of changes...

  14. 75 FR 31342 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2010-06-03

    ... flood insurance premium rates for new buildings and the contents in those buildings. DATES: Comments are... these elevations are made final, and for the contents in those buildings. Comments on any aspect of the..., Augusta, ME 04330. Perry County, Missouri, and Incorporated Areas Apple Creek At a dam/unnamed road +400...

  15. Asymptomatic proteinuria and elevated blood pressure among ...

    African Journals Online (AJOL)

    Background: Hypertension and proteinuria are known risk factors for cardiovascular disease and renal impairment. Early detection and treatment will reduce morbidity and mortality associated with them. Objective: To determine the prevalence of asymptomatic proteinuria with or without elevated blood pressure among ...

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

    Science.gov (United States)

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

    2017-07-17

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

  17. Outcomes Following Traumatic Grain Elevator Injuries.

    Science.gov (United States)

    Tolefree, Sydnei; Truong, Anthony; Ward, Jeanette; Dong, Fanglong; Ablah, Elizabeth; Haan, James

    2017-01-01

    The absence of a comprehensive database of grain elevator-associated injuries hinders accurate evaluation of injury prevalence and may lead to discordant information about injury frequencies. The main purpose of this study was to identify the most common mechanisms of injury related to grain elevator events. Comparisons of hospital outcomes between patients who sustained traumatic injuries associated with grain elevators at Occupational Safety and Health Administration (OSHA)-regulated industrial sites versus those on OSHA-exempt farming operations were also made. A retrospective review was conducted of all patients' presenting with grain elevator-related injuries at a level-1 trauma center between January 1, 2003, and December 31, 2013. Data collected included demographics, mechanism of injury, injury severity, hospitalization details, and discharge disposition. Data were summarized, and comparisons were made between the groups. All patients (N = 18) in the study were male, with a mean age of 37 years. Falls and being caught in equipment each accounted for 27.8% of injuries. Among the 18 patients, there were a total of 37 injuries. The majority of injuries were either lower extremity (29.7%) or chest injuries (21.6%). The average hospital length of stay was 4 ± 4.5 days, and one patient required mechanical ventilation. There were no reported deaths. The literature reports entrapments as the leading cause of grain elevator-related injuries; however, this study found that falls and being caught in equipment were the most common mechanisms of injury. This suggests that a greater emphasis should be placed on fall prevention and equipment safety.

  18. Targeted inhibition of metastatic melanoma through interference with Pin1-FOXM1 signaling

    NARCIS (Netherlands)

    Kruiswijk, F; Hasenfuss, S. C.; Sivapatham, R.; Baar, Marjolein P.; Putavet, D.; Naipal, K. A T; van den Broek, N.J.F.; Kruit, W.; Spek, P.J.; Gent, D.C.; Brenkman, A B; Campisi, J.; Burgering, B M T; Hoeijmakers, Jan H. J.; de Keizer, P L J

    2016-01-01

    Melanoma is the most lethal form of skin cancer and successful treatment of metastatic melanoma remains challenging. BRAF/MEK inhibitors only show a temporary benefit due to rapid occurrence of resistance, whereas immunotherapy is mainly effective in selected subsets of patients. Thus, there is a

  19. Targeted inhibition of metastatic melanoma through interference with Pin1-FOXM1 signaling

    NARCIS (Netherlands)

    F. Kruiswijk; S.C. Hasenfuss; R. Sivapatham; M.P. Baar (Marjolein); D. Putavet; K.A.T. Naipal (Kishan A.T.); N.J.F. van den Broek (Niels); W.H.J. Kruit (Wim); P.J. Van Der Spek; D.C. van Gent (Dik); A.B. Brenkman (Arjan); J. Campisi; B.M. Burgering (Boudewijn); J.H.J. Hoeijmakers; P.L.J. de Keizer (Peter)

    2016-01-01

    textabstractMelanoma is the most lethal form of skin cancer and successful treatment of metastatic melanoma remains challenging. BRAF/MEK inhibitors only show a temporary benefit due to rapid occurrence of resistance, whereas immunotherapy is mainly effective in selected subsets of patients. Thus,

  20. Cytokinin Modulates Endocytic Trafficking of PIN1 Auxin Efflux Carrier to Control Plant Organogenesis

    Czech Academy of Sciences Publication Activity Database

    Marhavý, P.; Bielach, A.; Abas, L.; Abuzeineh, A.; Duclercq, J.; Tanaka, H.; Pařezová, Markéta; Petrášek, Jan; Friml, J.; Kleine-Vehn, J.; Benková, E.

    2011-01-01

    Roč. 21, č. 4 (2011), s. 796-804 ISSN 1534-5807 R&D Projects: GA AV ČR(CZ) IAA601630703; GA MŠk(CZ) LC06034 Institutional research plan: CEZ:AV0Z50380511 Keywords : auxin efflux * cytokinin * vacuoles * membrane trafficking Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 14.030, year: 2011

  1. Cerebral Pulsatility Index Is Elevated in Patients with Elevated Right Atrial Pressure.

    Science.gov (United States)

    Lahiri, Shouri; Schlick, Konrad H; Padrick, Matthew M; Rinsky, Brenda; Gonzalez, Nestor; Jones, Heather; Mayer, Stephan A; Lyden, Patrick D

    2018-01-01

    Extracerebral venous congestion can precipitate intracranial hypertension due to obstruction of cerebral blood outflow. Conditions that increase right atrial pressure, such as hypervolemia, are thought to increase resistance to jugular venous outflow and contribute to cerebro-venous congestion. Cerebral pulsatility index (CPI) is considered a surrogate marker of distal cerebrovascular resistance and is elevated with intracranial hypertension. Thus, we sought to test the hypothesis that elevated right atrial pressure is associated with increased CPI compared to normal right atrial pressure. We retrospectively reviewed 61 consecutive patients with subarachnoid hemorrhage. We calculated CPI from transcranial Doppler studies and correlated these with echocardiographic measures of right atrial pressure. CPIs were compared from patients with elevated and normal right atrial pressure. There was a significant difference between CPI obtained from all patients with elevated right atrial pressure compared to those with normal right atrial pressure (P right and left hemispheric CPI from patients with both elevated and normal right atrial pressure. Patients with elevated right atrial pressure had significantly higher CPI compared to patients with normal right atrial pressure. These findings suggest that cerebro-venous congestion due to impaired jugular venous outflow may increase distal cerebrovascular resistance as measured by CPI. Since elevated CPI is associated with poor outcome in numerous neurological conditions, future studies are needed to elucidate the significance of these results in other populations. Copyright © 2017 by the American Society of Neuroimaging.

  2. Reducing elevator energy use: A comparison of posted feedback and reduced elevator convenience

    Science.gov (United States)

    Houten, Ron Van; Nau, Paul A.; Merrigan, Michael

    1981-01-01

    The effects of two different procedures for reducing elevator energy use were assessed using a multiple-baseline design. In the first procedure, feedback about the amount of energy consumed by the elevators each week was posted on each elevator door. Later, signs advocating the use of stairs to save energy and improve health were posted next to the feedback signs. In the second procedure, the time required to travel between floors was increased by adding a delay to the elevator door closing mechanisms. Results indicated that neither feedback alone nor feedback plus educational signs reduced the amount of energy consumed by the elevators. However, use of the door delay reduced consumption by one-third in all elevators. A second experiment replicated the effect of the door delay on energy consumption and, in addition, demonstrated that the door delay also produced a reduction in the number of persons using the elevator. The second experiment also showed that, following an initial period during which a full delay was in effect, a gradual reduction of the delay interval resulted in continued energy conservation. Reduced convenience as a general strategy for energy conservation is discussed. PMID:16795648

  3. Elevated carbon dioxide reduces emission of herbivore-induced volatiles in Zea mays.

    Science.gov (United States)

    Block, Anna; Vaughan, Martha M; Christensen, Shawn A; Alborn, Hans T; Tumlinson, James H

    2017-09-01

    Terpene volatiles produced by sweet corn (Zea mays) upon infestation with pests such as beet armyworm (Spodoptera exigua) function as part of an indirect defence mechanism by attracting parasitoid wasps; yet little is known about the impact of climate change on this form of plant defence. To investigate how a central component of climate change affects indirect defence, we measured herbivore-induced volatile emissions in plants grown under elevated carbon dioxide (CO 2 ). We found that S. exigua infested or elicitor-treated Z. mays grown at elevated CO 2 had decreased emission of its major sesquiterpene, (E)-β-caryophyllene and two homoterpenes, (3E)-4,8-dimethyl-1,3,7-nonatriene and (3E,7E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene. In contrast, inside the leaves, elicitor-induced (E)-β-caryophyllene hyper-accumulated at elevated CO 2 , while levels of homoterpenes were unaffected. Furthermore, gene expression analysis revealed that the induction of terpene synthase genes following treatment was lower in plants grown at elevated CO 2 . Our data indicate that elevated CO 2 leads both to a repression of volatile synthesis at the transcriptional level and to limitation of volatile release through effects of CO 2 on stomatal conductance. These findings suggest that elevated CO 2 may alter the ability of Z. mays to utilize volatile terpenes to mediate indirect defenses. © 2017 John Wiley & Sons Ltd.

  4. Behavioral consequences of predator stress in the rat elevated T-maze.

    Science.gov (United States)

    Bulos, Erika Mondin; Pobbe, Roger Luis Henschel; Zangrossi, Helio

    2015-07-01

    Analyses of the behavioral reactions of rodents to predators have greatly contributed to the understanding of defense-related human psychopathologies such as anxiety and panic.We here investigated the behavioral consequences of exposing male Wistar rats to a live cat using the elevated T-maze test of anxiety. This test allows the measurement of two defensive responses: inhibitory avoidance and escape, which in terms of pathology have been associated with generalized anxiety and panic disorders, respectively. For comparative reasons, the effects of exposure to the cat were also assessed in the elevated plus-maze. The results showed that a 5-min exposure to the cat selectively facilitated inhibitory avoidance acquisition, an anxiogenic effect, without affecting escape expression in the elevated T-maze. This was seen immediately but not 30 min after contact with the predator. This short-lived anxiogenic effect was also detected in the elevated plus-maze. Previous administration of the benzodiazepine anxiolytic diazepam (2 mg/kg) decreased the immediate avoidance response to the predator and the neophobic reaction to a dummy cat used as a control stimulus. The drug also impaired inhibitory avoidance acquisition in the elevated T-maze, indicating an anxiolytic effect, without affecting escape performance. The results indicate that the state of anxiety evoked during contact with the predator generalizes to both elevated plus- and T-mazes, impacting on defensive responses associated with generalized anxiety disorder.

  5. 30 CFR 75.1403-4 - Criteria-Automatic elevators.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Criteria-Automatic elevators. 75.1403-4 Section... Criteria—Automatic elevators. (a) The doors of automatic elevators should be equipped with interlocking switches so arranged that the elevator car will be immovable while any door is opened or unlocked, and...

  6. 29 CFR 1917.116 - Elevators and escalators.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Elevators and escalators. 1917.116 Section 1917.116 Labor... (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.116 Elevators and escalators. (a) “Elevator” means a...) No elevator or escalator with a defect which affects safety shall be used. (d) Elevator safety...

  7. Relationship among expression of basic-fibroblast growth factor ...

    African Journals Online (AJOL)

    Relationship among expression of basic-fibroblast growth factor, MTDH/Astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9,and COX-2 markers with prognostic factors in prostate carcinomas.

  8. Elevated temperature alters carbon cycling in a model microbial community

    Science.gov (United States)

    Mosier, A.; Li, Z.; Thomas, B. C.; Hettich, R. L.; Pan, C.; Banfield, J. F.

    2013-12-01

    Earth's climate is regulated by biogeochemical carbon exchanges between the land, oceans and atmosphere that are chiefly driven by microorganisms. Microbial communities are therefore indispensible to the study of carbon cycling and its impacts on the global climate system. In spite of the critical role of microbial communities in carbon cycling processes, microbial activity is currently minimally represented or altogether absent from most Earth System Models. Method development and hypothesis-driven experimentation on tractable model ecosystems of reduced complexity, as presented here, are essential for building molecularly resolved, benchmarked carbon-climate models. Here, we use chemoautotropic acid mine drainage biofilms as a model community to determine how elevated temperature, a key parameter of global climate change, regulates the flow of carbon through microbial-based ecosystems. This study represents the first community proteomics analysis using tandem mass tags (TMT), which enable accurate, precise, and reproducible quantification of proteins. We compare protein expression levels of biofilms growing over a narrow temperature range expected to occur with predicted climate changes. We show that elevated temperature leads to up-regulation of proteins involved in amino acid metabolism and protein modification, and down-regulation of proteins involved in growth and reproduction. Closely related bacterial genotypes differ in their response to temperature: Elevated temperature represses carbon fixation by two Leptospirillum genotypes, whereas carbon fixation is significantly up-regulated at higher temperature by a third closely related genotypic group. Leptospirillum group III bacteria are more susceptible to viral stress at elevated temperature, which may lead to greater carbon turnover in the microbial food web through the release of viral lysate. Overall, this proteogenomics approach revealed the effects of climate change on carbon cycling pathways and other

  9. Rotating Space Elevators: Classical and Statistical Mechanics

    Science.gov (United States)

    Knudsen, Steven

    We investigate a novel and unique dynamical system, the Rotating Space Elevator (RSE). The RSE is a multiply rotating system of strings reaching beyond the Earth geo-synchronous satellite orbit. Objects sliding along the RSE string ("climbers") do not require internal engines or propulsion to be transported far away from the Earth's surface. The RSE thus solves a major problem in the space elevator technology which is how to supply the energy to the climbers moving along the string. The RSE is a double rotating floppy string. The RSE can be made in various shapes that are stabilized by an approximate equilibrium between the gravitational and inertial forces acting in the double rotating frame. The RSE exhibits a variety of interesting dynamical phenomena studied in this thesis.

  10. Regional elevator survey : grain transportation & industry trends for Great Plains elevators

    Science.gov (United States)

    2001-08-01

    One potential means for gaining insight into the current state of the elevator industry, : and into expectations for future trends, is through a survey. The objective of this study is to profile the transportation and industry characteristics of the ...

  11. Prevalence of elevated serum creatinine among treated ...

    African Journals Online (AJOL)

    A cut off mark of 1.5mg/dl was used to evaluate elevated serum creatinine levels. Results: There were 826patients with a male/female ratio of 1:1.32. Males were 356 (43.1%) and females 470 (56.9%). Among these patients, 118 (14.3%) had a serum creatinine value of over 1.5mg/dl, signifying renal disease. Conclusion: A ...

  12. Experimental prototype of an electric elevator

    Science.gov (United States)

    Gaiceanu, M.; Epure, S.; Ciuta, S.

    2016-08-01

    The main objective is to achieve an elevator prototype powered by a three-phase voltage system via a bidirectional static power converter ac-ac with regenerating capability. In order to diminish the power size of the electric motor up to 1/3 of rated power, the elevator contains two carriages of the same weight, one serving as the payload, and the other as counterweight. Before proper operation of the static power converter, the capacitor must be charged at rated voltage via a precharge circuit. At the moment of stabilizing the DC voltage at nominal value, the AC-AC power converter can operates in the proper limits. The functions of the control structure are: the load control task, speed and torque controls. System includes transducers for current measuring, voltage sensors and encoder. As reserve power sources the hybrid battery-photovoltaic panels are used. The control voltage is modulated by implementing four types of pulse width modulations: sinusoidal, with reduced commutation, third order harmonic insertion, and the space vector modulation. Therefore, the prototype could operates with an increased efficiency, in spite of the existing ones. The experimental results confirm the well design of the chosen solution. The control solution assures bidirectional power flow control, precharge control, and load control and it is implemented on a digital signal processor. The elevator capacity is between 300-450 kg, and it is driven by using a 1.5 kW three-phase asynchronous machine.

  13. Endoscopic laryngeal web formation for pitch elevation.

    Science.gov (United States)

    Anderson, Jennifer

    2007-02-01

    Endoscopic laryngeal web formation has been used to elevate the speaking voice, primarily in male to female transsexuals as part of gender reassignment intervention. The goal of this article is to review the literature regarding surgical treatment for pitch elevation and to describe a novel method of laryngeal web formation. The results of this technique are also reported in a series of six patients. All patients were assessed and treated at the St. Michael's Hospital Voice Disorders Clinic, a tertiary referral centre for voice disorders. Pre- and postoperative voice recordings, acoustic analysis, and videostroboscopic examinations were performed in this series. The acoustic data collected included isolated vowel samples, a reading task, and a modified voice range profile. The patients all underwent successful endoscopic web formation with a Gelfoam augmentation technique. The voice results collected at least 6 months after vocal fold web formation demonstrate a dramatic increase in the habitual speaking fundamental frequency. This new modification for endoscopic web formation has been shown to be a successful procedure for permanent elevation of pitch with little or no morbidity.

  14. Rangeland -- plant response to elevated CO2

    International Nuclear Information System (INIS)

    Owensby, C.E.; Coyne, P.I.; Ham, J.M.; Parton, W.; Rice, C.; Auen, L.M.; Adam, N.

    1993-01-01

    Plots of a tallgrass prairie ecosystem were exposed to ambient and twice-ambient CO 2 concentrations in open-top chambers and compared to unchambered ambient CO 2 plots during the entire growing season from 1989 through 1992. Relative root production among treatments was estimated using root ingrowth bags which remained in place throughout the growing season. Latent heat flux was simulated with and without water stress. Botanical composition was estimated annuallyin all treatments. Open-top chambers appeared to reduce latent heat flux and increase water use efficiency similar to elevated CO 2 when water stress was not severe, but under severe water stress, chamber effect on water use efficiency was limited. In natural ecosystems with periodic moisture stress, increased water use efficiency under elevated CO 2 apparently would have a greater impact on productivity than photosynthetic pathway. Root ingrowth biomass was greater in 1990 and 1991 on elevated CO 2 plots compared to ambient or chambered-ambient plots. In 1992, there was no difference in root ingrowth biomass among treatments

  15. Elevers læring og progression

    DEFF Research Database (Denmark)

    praksisbaserede anbefalinger til, hvordan data om elevernes progression kan indsamles, sammenstilles, vises og understøtte elevernes udvikling, så alle elever bliver så dygtige, som de kan. Rapporten består af et resumé af en forskningskortlægning af danske og internationale studier af, hvordan man måler læring...... og progression, og hvordan fagprofessionelle kan arbejde med elevdata for at understøtte elevers læring og progression. Derefter følger opsamling på en spørgeskemaundersøgelse blandt private leverandører af digitale læremidler til folkeskolen og resultaterne af en erfaringsopsamling blandt lærere......, elever og forældre. Endelig præsenteres erfaringerne med et konkret udviklingsarbejde på en række områder, hvor elevdata spiller en væsentlig rolle samt fagdidaktiske overvejelser om fagprofessionelles brug af elevdata. På baggrund af undersøgelsen præsenteres anbefalinger til overordnede systembehov...

  16. Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

    Science.gov (United States)

    Langley, J.A.; McKee, K.L.; Cahoon, D.R.; Cherry, J.A.; Megonigala, J.P.

    2009-01-01

    Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas.

  17. Elevated O3 and TYLCV Infection Reduce the Suitability of Tomato as a Host for the Whitefly Bemisia tabaci

    Science.gov (United States)

    Cui, Hongying; Sun, Yucheng; Chen, Fajun; Zhang, Youjun; Ge, Feng

    2016-01-01

    The effects of elevated atmospheric ozone (O3) levels on herbivorous insects have been well studied, but little is known about the combined effects of elevated O3 and virus infection on herbivorous insect performance. Using open-top chambers in the field, we determined the effects of elevated O3 and Tomato yellow leaf curl virus (TYLCV) infection on wild-type (Wt) tomato and 35S tomato (jasmonic acid (JA) defense-enhanced genotype) in association with whitefly, Bemisia tabaci Gennadius biotype B. Elevated O3 and TYLCV infection, alone and in combination, significantly reduced the contents of soluble sugars and free amino acids, increased the contents of total phenolics and condensed tannins, and increased salicylic acid (SA) content and the expression of SA-related genes in leaves. The JA signaling pathway was upregulated by elevated O3, but downregulated by TYLCV infection and O3 + TYLCV infection. Regardless of plant genotype, elevated O3, TYLCV infection, or O3 + TYLCV infection significantly decreased B. tabaci fecundity and abundance. These results suggest that elevated O3 and TYLCV infection, alone and in combination, reduce the nutrients available for B. tabaci, increase SA content and SA-related gene expression, and increase secondary metabolites, resulting in decreases in fecundity and abundance of B. tabaci in both tomato genotypes. PMID:27916792

  18. Elevated O3 and TYLCV Infection Reduce the Suitability of Tomato as a Host for the Whitefly Bemisia tabaci

    Directory of Open Access Journals (Sweden)

    Hongying Cui

    2016-11-01

    Full Text Available The effects of elevated atmospheric ozone (O3 levels on herbivorous insects have been well studied, but little is known about the combined effects of elevated O3 and virus infection on herbivorous insect performance. Using open-top chambers in the field, we determined the effects of elevated O3 and Tomato yellow leaf curl virus (TYLCV infection on wild-type (Wt tomato and 35S tomato (jasmonic acid (JA defense-enhanced genotype in association with whitefly, Bemisia tabaci Gennadius biotype B. Elevated O3 and TYLCV infection, alone and in combination, significantly reduced the contents of soluble sugars and free amino acids, increased the contents of total phenolics and condensed tannins, and increased salicylic acid (SA content and the expression of SA-related genes in leaves. The JA signaling pathway was upregulated by elevated O3, but downregulated by TYLCV infection and O3 + TYLCV infection. Regardless of plant genotype, elevated O3, TYLCV infection, or O3 + TYLCV infection significantly decreased B. tabaci fecundity and abundance. These results suggest that elevated O3 and TYLCV infection, alone and in combination, reduce the nutrients available for B. tabaci, increase SA content and SA-related gene expression, and increase secondary metabolites, resulting in decreases in fecundity and abundance of B. tabaci in both tomato genotypes.

  19. Elevational gradient in clutch size of Red-faced Warblers

    Science.gov (United States)

    Dillon, Kristen G.; Conway, Courtney J.

    2015-01-01

    Our understanding of life history evolution has benefited from debates regarding the underlying causes, and geographic ubiquity, of spatial patterns in avian clutch sizes. Past studies have revealed that birds lay smaller clutch sizes at higher elevation. However, in most previous studies, investigators have failed to adequately control for elevational differences in breeding phenology. To better understand the elevational gradient in avian clutch size, we need to know how clutch size changes across the entire elevational breeding range of a species (i.e., the shape of the relationship between elevation and clutch size), and whether the elevational gradient in clutch size is merely an artifact of elevational gradients in breeding phenology or breeding season length. We examined the relationship between breeding elevation and clutch size of Red-faced Warblers (Cardellina rubrifrons) along a 1000-m elevational gradient in Arizona. Our objectives were to determine how clutch size changed with elevation, and if the relationship between clutch size and elevation merely reflected elevational changes in breeding season length or phenology. The proportion of 5-egg clutches decreased and the proportion of 3- and 4-egg clutches increased non-linearly with increasing elevation, even after controlling for the elevational gradient in nest initiation date. Thus, average clutch size declined across the elevational breeding range of Red-faced Warblers, but this decline was not due to elevational variation in breeding phenology. Timing of breeding changed, but the duration of the breeding season did not change appreciably across the elevational gradient. Hence, elevational differences in breeding season length or breeding phenology cannot explain why Red-faced Warblers (and perhaps other birds) breeding at higher elevations have smaller clutches.

  20. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1.

    Science.gov (United States)

    Kang, Dong-Chul; Su, Zao-Zhong; Sarkar, Devanand; Emdad, Luni; Volsky, David J; Fisher, Paul B

    2005-06-20

    We presently describe the full-length cloning and functional characterization of an HIV-1-inducible gene, astrocyte elevated gene (AEG)-1. Additionally, a novel method is outlined for producing tag-free recombinant protein in a baculovirus system and its use in producing AEG-1 protein. AEG-1 mRNA is expressed ubiquitously with higher expression in tissues containing muscular actin and its expression is increased in astrocytes infected with HIV-1 or treated with gp120 or tumor necrosis factor (TNF)-alpha. The mRNA encodes a single pass transmembrane protein of predicted molecular mass of 64-kDa and pI 9.3 that predominantly localizes in the endoplasmic reticulum and perinuclear region. Ectopic expression of AEG-1 inhibits excitatory amino acid transporter 2 (EAAT2) promoter activity with the potential to promote glutamate excitotoxicity and consequently HIV-1-associated dementia (HAD). AEG-1 expression is elevated in subsets of breast carcinomas, malignant gliomas and melanomas and it synergizes with oncogenic Ha-ras to enhance soft agar colony forming ability of non-tumorigenic immortalized melanocytes, documenting its tumor promoting activity. AEG-1 may affect tumor progression in multiple cell lineages by augmenting expression of the transformed phenotype and/or by inducing glutamate excitotoxicity in malignant glioma. In these contexts, an HIV-1-inducible gene, AEG-1, may contribute to multiple brain abnormalities, including HAD and tumor formation, by both common and distinct mechanisms.

  1. Belowground heathland responses after 2 years of combined warming, elevated CO2 and summer drought

    DEFF Research Database (Denmark)

    Andresen, Louise C.; Michelsen, Anders; Ambus, Per

    2010-01-01

    scale experiment on temperate heathland, manipulation of precipitation and temperature was performed with retractable curtains, and atmospheric CO2 concentration was increased by FACE. The combination of elevated CO2 and warming was expected to affect belowground processes additively, through increased...... (1 year after 13C215N-glycine was injected into the soil) increased in warmed plots and in elevated CO2 plots, but not when these treatments were combined. Furthermore, drought led to an increase in Calluna biomass and total plant nitrogen pool. The full combination of warming, elevated CO2...... and periodic drought did not unambiguously express the ecosystem responses of single factors additively, which complicates predictions of ecosystem responses to multifactor climate change....

  2. Mice with chronically elevated dopamine exhibit enhanced motivation, but not learning, for a food reward.

    Science.gov (United States)

    Cagniard, Barbara; Balsam, Peter D; Brunner, Daniela; Zhuang, Xiaoxi

    2006-07-01

    Dopamine has been critically implicated in learning and motivation, although its precise role remains to be determined. In order to investigate the involvement of dopamine in learning and motivation for a food reward, we used dopamine transporter knockdown mice (DAT KD) that have chronically elevated levels of extracellular dopamine. The present study demonstrates that chronically elevated dopamine enhances tendency to work for a food reward without apparent effects on Pavlovian and operant learning for this reward. The increase in dopamine is associated with elevated levels of dynorphin and Fos B expression in the dorsal caudate-putamen and the core but not the shell subregion of the nucleus accumbens. These data suggest that motivation to work, but not learning, for a food reward appears to be under the critical influence of tonic dopaminergic activity in discrete brain areas relevant for a reward-directed behavior.

  3. Towards neuroimmunotherapy for cancer: the neurotransmitters glutamate, dopamine and GnRH-II augment substantially the ability of T cells of few head and neck cancer patients to perform spontaneous migration, chemotactic migration and migration towards the autologous tumor, and also elevate markedly the expression of CD3zeta and CD3epsilon TCR-associated chains.

    Science.gov (United States)

    Saussez, Sven; Laumbacher, Barbara; Chantrain, Gilbert; Rodriguez, Alexandra; Gu, Songhai; Wank, Rudolf; Levite, Mia

    2014-08-01

    In previous studies we found that several Neurotransmitters and Neuropeptides among them: Glutamate, Dopamine, Gonadotropin-releasing-hormone (GnRH) I and II, Somatostatin, CGRP and Neuropeptide Y, can each by itself, at low physiological concentration (~10 nM) bind its receptors in human T cells and trigger several key T cell functions. These findings showed that the nervous system, via Neurotransmitters and Neuropeptides, can 'talk' directly to the immune system, and stimulate what we coined 'Nerve-Driven Immunity': immune responses dictated by the nervous system. In various human cancers, the immune system of the patients, and their T cells in particular, are not functioning well enough against the cancer due to several reasons, among them the suppressive effects on the immune system induced by: (1) the cancer itself, (2) the chemotherapy and radiotherapy, (3) the ongoing/chronic stress, anxiety, depression and pain felt by the cancer patients. In Head and Neck Cancer (HNC), 5-year survival rate remains below 50%, primarily because of local recurrences or second primary tumors. Two-thirds of HNC patients are diagnosed at advanced clinical stage and have significantly poorer prognosis. Most HNC patients have multiple severe immunological defects especially in their T cells. A major defect in T cells of patients with HNC or other types of cancer is low CD3zeta expression that correlates with poor prognosis, decreased proliferation, apoptotic profile, abnormal cytokine secretion and poor abilities of destructing cancer cells. T cells of cancer patients are often also unable to migrate properly towards the tumor. In this study we asked if Glutamate, Dopamine or GnRH-II can augment the spontaneous migration, chemotactic migration and towards autologous HNC migration, and also increase CD3zeta and CD3epsilon expression, of peripheral T cells purified from the blood of five HNC patients. These HNC patients had either primary tumor or recurrence, and have been already

  4. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  5. Genes responsive to elevated CO2 concentrations in triploid white poplar and integrated gene network analysis.

    Directory of Open Access Journals (Sweden)

    Juanjuan Liu

    Full Text Available BACKGROUND: The atmospheric CO2 concentration increases every year. While the effects of elevated CO2 on plant growth, physiology and metabolism have been studied, there is now a pressing need to understand the molecular mechanisms of how plants will respond to future increases in CO2 concentration using genomic techniques. PRINCIPAL FINDINGS: Gene expression in triploid white poplar ((Populus tomentosa ×P. bolleana ×P. tomentosa leaves was investigated using the Affymetrix poplar genome gene chip, after three months of growth in controlled environment chambers under three CO2 concentrations. Our physiological findings showed the growth, assessed as stem diameter, was significantly increased, and the net photosynthetic rate was decreased in elevated CO2 concentrations. The concentrations of four major endogenous hormones appeared to actively promote plant development. Leaf tissues under elevated CO2 concentrations had 5,127 genes with different expression patterns in comparison to leaves under the ambient CO2 concentration. Among these, 8 genes were finally selected for further investigation by using randomized variance model corrective ANOVA analysis, dynamic gene expression profiling, gene network construction, and quantitative real-time PCR validation. Among the 8 genes in the network, aldehyde dehydrogenase and pyruvate kinase were situated in the core and had interconnections with other genes. CONCLUSIONS: Under elevated CO2 concentrations, 8 significantly changed key genes involved in metabolism and responding to stimulus of external environment were identified. These genes play crucial roles in the signal transduction network and show strong correlations with elevated CO2 exposure. This study provides several target genes, further investigation of which could provide an initial step for better understanding the molecular mechanisms of plant acclimation and evolution in future rising CO2 concentrations.

  6. [Diagnostic capability of carcinoembryonic antigen elevation].

    Science.gov (United States)

    Cerezo Ruiz, Antonio; Rosa Jiménez, Francisco; Lobón Hernández, José Antonio; Gómez Jiménez, Francisco Javier

    2014-12-01

    There is little information on the oncologic diagnostic accuracy of carcinoembryonic antigen (CEA) levels more than 3-fold above normal. To determine the prevalence of underlying cancer in patients with mild CEA elevation and the mean cost per patient of CEA determination. A retrospective study was carried out in all patients with CEA elevation (3-10 ng/ml) and suspicion of cancer referred to the gastroenterology or internal medicine outpatient units from 2001 to 2007. We studied 100 patients (60 men and 40 women), with a mean age of 67.4 ± 14.2 years and baseline CEA of 5.8 ± 1.7 ng/ml. The most important symptoms and signs were laboratory abnormalities (19 patients [19%]). Cancer was diagnosed in 4 patients (one gastric, 2 lung and one colon). Among patients without malignancies, 49 patients (49%) had no related processes, and 47 (47%) had benign diseases. During follow-up, one laryngeal cancer, one acute myeloid leukemia, and one colon cancer were detected (54.3 ± 24.6 months). We found no differences between baseline CEA levels in patients with and without cancer (6.6 ± 2.4 vs. 5.8 ± 1.7 ng/ml, p = 0.2). The mean cost per patient was 503.6 ± 257.6 €. Cancer was detected in a small proportion (7%) of patients with mild CEA elevation. The study of these patients is directly and indirectly associated with a not inconsiderable cost. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  7. Cardiac Troponin I elevation after epileptic seizure

    Directory of Open Access Journals (Sweden)

    Sieweke Nicole

    2012-07-01

    Full Text Available Abstract Background Cardiac troponin-I (cTNI is highly specific biomarker to prove myocardial damage, e.g. in acute coronary syndrome (ACS. However, it occurs in other conditions as well. We therefore analysed cTNI increase in patients after generalized convulsive seizure. Methods Consecutive patients admitted with acute generalized convulsive seizure were included in case of cTNI measurement on admission. Among 898 selected cases, 53 patients were referred secondary to our department; in 845 cases cTNI measurements on admission were available. In case of multiple admissions (81 cases, only the first admission entered our analysis. In 17 patients elevated cTNI was determined due to ACS; in one patient a myocarditis was found. 5 patients suffered of relevant renal insufficiency. Finally 741 patients were included in the analysis. A cTNI cut-off level of ≥ 0.1 ng/ml was considered. Factors associated with a cTNI increase were analysed subsequently. Results The mean age of the study population (n = 741 was 47.8 years (SD ± 18.6, 40.9% were female. In 50 patients (6.7% a cTNI elevation of unknown origin was found; no obvious cardiac involvement could be detected in these patients who all remained asymptomatic. A vascular risk profile (including at least hypertension, hypercholesterolemia or diabetes (OR = 3.62; CI: 1.59 to 8.21; p = 0.001 and elevated creatine kinase on admission (OR = 2.36; CI: 1.26 to 4.39; p = 0.002 were independent factors associated with cTNI release. Conclusion cTNI release occurs in patients with generalized convulsive seizure with predominance in patients with vascular risk profile.

  8. ST-elevations-myokardieinfarkt efter terapeutisk adrenalininjektion

    DEFF Research Database (Denmark)

    Rømhild Davidsen, Jesper; Lambrechtsen, Jess; Egstrup, Kenneth

    2006-01-01

    A case of acute myocardial infarction (AMI) following accidental iatrogenic overdose by adrenaline injection is described in a male aged 55 years. This patient was given 1 mg of adrenaline due to anaphylactic symptoms. Afterwards he presented with angina pectoris, dyspnoea and ST-segment elevation...... in the ECG. Plasma TnT and CK-MB were raised. A coronary angiography revealed a 66% stenosis of RCA. This patient had an asymptomatic RCA stenosis that probably became symptomatic due to coronary artery spasm related to adrenaline injection and thereby presented symptoms and signs of AMI....

  9. Pendulum motions of extended lunar space elevator

    Science.gov (United States)

    Burov, A. A.; Kosenko, I. I.

    2014-09-01

    In the usual everyday life, it is well known that the inverted pendulum is unstable and is ready to fall to "all four sides," to the left and to the right, forward and backward. The theoretical studies and the lunar experience of moon robots and astronauts also confirms this property. The question arises: Is this property preserved if the pendulum is "very, very long"? It turns out that the answer is negative; namely, if the pendulum length significantly exceeds the Moon radius, then the radial equilibria at which the pendulum is located along the straight line connecting the Earth and Moon centers are Lyapunov stable and the pendulum does not fall in any direction at all. Moreover, if the pendulum goes beyond the collinear libration points, then it can be extended and manufactured from cables. This property was noted by F. A. Tsander and underlies the so-called lunar space elevator (e.g., see [1]). In the plane of the Earth and Moon orbits, there are some other equilibria which turn out to be unstable. The question is, Are there equilibria at which the pendulum is located outside the orbital plane? In this paper, we show that the answer is positive, but such equilibria are unstable in the secular sense. We also study necessary conditions for the stability of lunar pendulum oscillations in the plane of the lunar orbit. It was numerically discovered that stable and unstable equilibria alternate depending on the oscillation amplitude and the angular velocity of rotation. The study of the lunar elevator dynamics originates in [2]. The concept of lunar elevator was developed in detail in [3, 4]. Several classes of equilibria with the finiteness of the Moon size taken into account were studied in [5]. The possibility of location of an orbital station fixed to the Moon surface by a pair of tethers was investigated in [6]. The problem of orientation of the terminal station of the lunar space elevator was studied in [7]. The influence of the tether length variations on the

  10. Elevation Derivatives for Mojave Desert Tortoise Habitat

    Science.gov (United States)

    Wallace, Cynthia S.A.; Gass, Leila

    2008-01-01

    This report describes the methods used to derive various elevation-derivative grids that were inputted to the Mojave Desert Tortoise Habitat model (L. Gass and others, unpub. data). These grids, which capture information on surface roughness and topographic characteristics, are a subset of the environmental datasets evaluated for the tortoise habitat model. This habitat model is of major importance to the U.S. Fish and Wildlife Service, which is charged with management of this threatened population, including relocating displaced tortoises to areas identified as suitable habitat.

  11. [Functional and mechanical anatomy of arm elevation].

    Science.gov (United States)

    Gagey, O; Bonfait, H; Gillot, C; Mazas, F

    1988-01-01

    Experimental work on the functional anatomy of the shoulder has involved a study of the conditions involved in elevation of the arm. Movements of the upper limb are organised round a very special alignment of the scapulo-humeral joint whose geometric features and exact position have been determined. The ligaments of the joint play a major role in the controlling the attainment of this alignment. The value of this alignment in the physiology of the shoulder is demonstrated. A new terminology of shoulder movement is suggested.

  12. Elevated environmental temperature and methamphetamine neurotoxicity

    International Nuclear Information System (INIS)

    Miller, Diane B.; O'Callaghan, James P.

    2003-01-01

    Amphetamines have been of considerable research interest for the last several decades. More recent work has renewed interest in the role of ambient temperature in both the toxicity and neurotoxicity of these drugs. We have determined that the striatal dopaminergic neurotoxicity observed in the mouse is linked in some fashion to both body and environmental temperature. Most studies of d-methamphetamine (d-METH) neurotoxicity are conducted at standard laboratory ambient temperatures (e.g., ∼21-22 deg. C) and utilizing a repeated dosage regimen (e.g., three to four injections spaced 2 h apart). A lowering of the ambient temperature provides neuro protection, while an elevation increases neurotoxicity. d-METH causes long-term depletions of triatal dopamine (DA) that are accompanied by other changes that are indicative of nerve terminal degeneration. These include argyrophilia, as detected by silver degeneration stains, and an elevation in glial fibrillary acidic protein (GFAP), a marker of reactive gliosis in response to injury, as well as a long-term decrease in tyrosine hydroxylase (TH) protein levels. here we show that increasing the ambient temperature during and for some time following dosing increases the neurotoxicity of d-METH. Mice (female 57BL6/J) given a single dosage of d-METH (20 mg/kg s.c.) and maintained at the usual laboratory ambient temperature show minimal striatal damage (an ∼15% depletion of DA and an ∼ 86% increase in GFAP). substantial striatal damage (e.g., an ∼70% depletion of DA and an ∼200% elevation in GFAP) was induced by this regimen if mice were maintained at 27 deg. C for 24 or 72 h following dosing. An increase in neurotoxicity was also apparent in mice kept at an elevated temperature for only 5 or 9 h, but keeping animals at 27 deg. C for 24 or 72 h was the most effective in increasing the neurotoxicity of d-METH. Our data show how a relatively minor change in ambient temperature can have a major impact on the degree of

  13. Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks

    Directory of Open Access Journals (Sweden)

    James N. Warnock

    2011-01-01

    Full Text Available The study aimed to identify mechanosensitive pathways and gene networks that are stimulated by elevated cyclic pressure in aortic valve interstitial cells (VICs and lead to detrimental tissue remodeling and/or pathogenesis. Porcine aortic valve leaflets were exposed to cyclic pressures of 80 or 120 mmHg, corresponding to diastolic transvalvular pressure in normal and hypertensive conditions, respectively. Linear, two-cycle amplification of total RNA, followed by microarray was performed for transcriptome analysis (with qRT-PCR validation. A combination of systems biology modeling and pathway analysis identified novel genes and molecular mechanisms underlying the biological response of VICs to elevated pressure. 56 gene transcripts related to inflammatory response mechanisms were differentially expressed. TNF-α, IL-1α, and IL-1β were key cytokines identified from the gene network model. Also of interest was the discovery that pentraxin 3 (PTX3 was significantly upregulated under elevated pressure conditions (41-fold change. In conclusion, a gene network model showing differentially expressed inflammatory genes and their interactions in VICs exposed to elevated pressure has been developed. This system overview has detected key molecules that could be targeted for pharmacotherapy of aortic stenosis in hypertensive patients.

  14. The photosynthesis - leaf nitrogen relationship at ambient and elevated atmospheric carbon dioxide: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Andrew G. Peterson; J. Timothy Ball; Yiqi Luo; Christopher B. Field; Peter B. Reich; Peter S. Curtis; Kevin L. Griffin; Carla S Gunderson; Richard J. Norby; David T. Tissue; Manfred Forstreuter; Ana Rey; Christoph S. Vogel; CMEAL collaboration

    1998-09-25

    Estimation of leaf photosynthetic rate (A) from leaf nitrogen content (N) is both conceptually and numerically important in models of plant, ecosystem and biosphere responses to global change. The relationship between A and N has been studied extensively at ambient CO{sub 2} but much less at elevated CO{sub 2}. This study was designed to (1) assess whether the A-N relationship was more similar for species within than between community and vegetation types, and (2) examine how growth at elevated CO{sub 2} affects the A-N relationship. Data were obtained for 39 C{sub 3} species grown at ambient CO{sub 2} and 10 C{sub 3} species grown at ambient and elevated CO{sub 2}. A regression model was applied to each species as well as to species pooled within different community and vegetation types. Cluster analysis of the regression coefficients indicated that species measured at ambient CO{sub 2} did not separate into distinct groups matching community or vegetation type. Instead, most community and vegetation types shared the same general parameter space for regression coefficients. Growth at elevated CO{sub 2} increased photosynthetic nitrogen use efficiency for pines and deciduous trees. When species were pooled by vegetation type, the A-N relationship for deciduous trees expressed on a leaf-mass bask was not altered by elevated CO{sub 2}, while the intercept increased for pines. When regression coefficients were averaged to give mean responses for different vegetation types, elevated CO{sub 2} increased the intercept and the slope for deciduous trees but increased only the intercept for pines. There were no statistical differences between the pines and deciduous trees for the effect of CO{sub 2}. Generalizations about the effect of elevated CO{sub 2} on the A-N relationship, and differences between pines and deciduous trees will be enhanced as more data become available.

  15. A global digital elevation model - GTOP030

    Science.gov (United States)

    1999-01-01

    GTOP030, the U.S. Geological Survey's (USGS) digital elevation model (DEM) of the Earth, provides the flrst global coverage of moderate resolution elevation data.  The original GTOP30 data set, which was developed over a 3-year period through a collaborative effort led by the USGS, was completed in 1996 at the USGS EROS Data Center in Sioux Falls, South Dakota.  The collaboration involved contributions of staffing, funding, or source data from cooperators including the National Aeronautics and Space Administration (NASA), the United Nations Environment Programme Global Resource Information Database (UNEP/GRID), the U.S. Agency for International Development (USAID), the Instituto Nacional de Estadistica Geografia e Informatica (INEGI) of Mexico, the Geographical Survey Institute (GSI) of Japan, Manaaki Whenua Landcare Research of New Zealand, and the Scientific Committee on Antarctic Research (SCAR). In 1999, work was begun on an update to the GTOP030 data set. Additional data sources are being incorporated into GTOP030 with an enhanced and improved data set planned for release in 2000.

  16. CANDU fuel compression tests at elevated temperatures

    International Nuclear Information System (INIS)

    Koehn, E.; Chan, J.K.; Langman, V.J.; Hadaller, G.I.; Fortman, R.A.

    1995-01-01

    An inlet header large break loss of coolant accident (LOCA) in CANDU reactors with fuelling against flow can cause the fuel to shift in the channels with a consequent reactivity insertion. This results in an increased fuel power transient, and a potential increase in the mialyzed consequences for such events. As the reactor's age and the channel axial gaps increase, the magnitude of the predicted power u-dmient increases. A design solution to reduce the power transient is to limit the amount of fuel movement by reducing the channel axial gap. This solution was implemented into Ontario Hydro's Bruce B and Darlington reactors. A consequence of a reduced channel axial gap is the potential for the fuel column axial expansion to become constrained by the channel end components in large break LOCAs. This experimental program investigated the effects of pellet cracking and elevated sheath temperatures on the ability of the fuel elements, of the 37-element bundle design, to sustain axial loads. The unirradiated fuel elements tested were either in the as-received condition or with the U0 2 fuel pellets cracked in a mechanical process to simulate the effect of inufflation. The load deformation characteristics demonstrated that, for a given amount of axial compression. the loads sustainable by the elements at elevated sheath temperatures were low. As a result. excess axial expansion would be easily accommodated without further challenge to pressure tube integrity. (author)

  17. Elevation uncertainty in coastal inundation hazard assessments

    Science.gov (United States)

    Gesch, Dean B.; Cheval, Sorin

    2012-01-01

    Coastal inundation has been identified as an important natural hazard that affects densely populated and built-up areas (Subcommittee on Disaster Reduction, 2008). Inundation, or coastal flooding, can result from various physical processes, including storm surges, tsunamis, intense precipitation events, and extreme high tides. Such events cause quickly rising water levels. When rapidly rising water levels overwhelm flood defenses, especially in heavily populated areas, the potential of the hazard is realized and a natural disaster results. Two noteworthy recent examples of such natural disasters resulting from coastal inundation are the Hurricane Katrina storm surge in 2005 along the Gulf of Mexico coast in the United States, and the tsunami in northern Japan in 2011. Longer term, slowly varying processes such as land subsidence (Committee on Floodplain Mapping Technologies, 2007) and sea-level rise also can result in coastal inundation, although such conditions do not have the rapid water level rise associated with other flooding events. Geospatial data are a critical resource for conducting assessments of the potential impacts of coastal inundation, and geospatial representations of the topography in the form of elevation measurements are a primary source of information for identifying the natural and human components of the landscape that are at risk. Recently, the quantity and quality of elevation data available for the coastal zone have increased markedly, and this availability facilitates more detailed and comprehensive hazard impact assessments.

  18. Engineering Clostridia Neurotoxins with elevated catalytic activity.

    Science.gov (United States)

    Guo, Jiubiao; Pan, Xuehua; Zhao, Yanxiang; Chen, Sheng

    2013-11-01

    BoNT/B and TeNT cleave substrate VAMP2 at the same scissile bond, yet these two toxins showed different efficiency on substrate hydrolysis and had different requirements for the recognition of P2' site of VAMP2, E(78). These differences may be due to their different composition of their substrate recognition pockets in the active site. Swapping of LC/T S1' pocket residue, L(230), with the corresponding isoleucine in LC/B increased LC/T activity by ∼25 fold, while swapping of LC/B S1' pocket residue, S(201), with the corresponding proline in LC/T increased LC/B activity by ∼10 fold. Optimization of both S1 and S1' pocket residues of LC/T, LC/T (K(168)E, L(230)I) elevated LC/T activity by more than 100-fold. The highly active LC/T derivative engineered in this study has the potential to be used as a more effective tool to study mechanisms of exocytosis in central neuron. The LC/B derivative with elevated activity has the potential to be developed into novel therapy to minimize the impact of immunoresistance during BoNT/B therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Elevated carboxyhemoglobin: sources of carbon monoxide exposure.

    Science.gov (United States)

    Buchelli Ramirez, Herminia; Fernández Alvarez, Ramón; Rubinos Cuadrado, Gemma; Martinez Gonzalez, Cristina; Rodriguez Jerez, Francisco; Casan Clara, Pere

    2014-11-01

    Inhalation of carbon monoxide (CO) can result in poisoning, with symptoms ranging from mild and nonspecific to severe, or even death. CO poisoning is often underdiagnosed because exposure to low concentrations goes unnoticed, and threshold values for normal carboxyhemoglobin vary according to different authors. The aim of our study was to analyze carboxyhemoglobin (COHb) levels in an unselected population and detect sources of CO exposure In a cross-sectional descriptive study, we analyzed consecutive arterial blood gas levels processed in our laboratory. We selected those with COHb≥2.5% in nonsmokers and ≥5% in smokers. In these cases a structured telephone interview was conducted. Elevated levels of COHb were found in 64 (20%) of 306 initial determinations. Of these, data from 51 subjects aged 65±12 years, 31 (60%) of which were men, were obtained. Mean COHb was 4.0%. Forty patients (78%) were non-smokers with mean COHb of 3.2%, and 11 were smokers with COHb of 6.7%. In 45 patients (88.2%) we detected exposure to at least one source of ambient CO other than cigarette smoke. A significant proportion of individuals from an unselected sample had elevated levels of COHb. The main sources of CO exposure were probably the home, so this possibility should be explored. The population should be warned about the risks and encouraged to take preventive measures. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  20. Topobathymetric elevation model development using a new methodology: Coastal National Elevation Database

    Science.gov (United States)

    Danielson, Jeffrey J.; Poppenga, Sandra K.; Brock, John C.; Evans, Gayla A.; Tyler, Dean; Gesch, Dean B.; Thatcher, Cindy A.; Barras, John

    2016-01-01

    During the coming decades, coastlines will respond to widely predicted sea-level rise, storm surge, and coastalinundation flooding from disastrous events. Because physical processes in coastal environments are controlled by the geomorphology of over-the-land topography and underwater bathymetry, many applications of geospatial data in coastal environments require detailed knowledge of the near-shore topography and bathymetry. In this paper, an updated methodology used by the U.S. Geological Survey Coastal National Elevation Database (CoNED) Applications Project is presented for developing coastal topobathymetric elevation models (TBDEMs) from multiple topographic data sources with adjacent intertidal topobathymetric and offshore bathymetric sources to generate seamlessly integrated TBDEMs. This repeatable, updatable, and logically consistent methodology assimilates topographic data (land elevation) and bathymetry (water depth) into a seamless coastal elevation model. Within the overarching framework, vertical datum transformations are standardized in a workflow that interweaves spatially consistent interpolation (gridding) techniques with a land/water boundary mask delineation approach. Output gridded raster TBDEMs are stacked into a file storage system of mosaic datasets within an Esri ArcGIS geodatabase for efficient updating while maintaining current and updated spatially referenced metadata. Topobathymetric data provide a required seamless elevation product for several science application studies, such as shoreline delineation, coastal inundation mapping, sediment-transport, sea-level rise, storm surge models, and tsunami impact assessment. These detailed coastal elevation data are critical to depict regions prone to climate change impacts and are essential to planners and managers responsible for mitigating the associated risks and costs to both human communities and ecosystems. The CoNED methodology approach has been used to construct integrated TBDEM models

  1. Severe bleeding after sinus floor elevation using the transcrestal technique

    DEFF Research Database (Denmark)

    Jensen, Simon Storgard; Eriksen, Jacob; Schiodt, Morten

    2012-01-01

    To present a rare but clinically significant complication to sinus floor elevation (SFE) using the transcrestal technique.......To present a rare but clinically significant complication to sinus floor elevation (SFE) using the transcrestal technique....

  2. Elevated carbon dioxide: impacts on soil and plant water relations

    National Research Council Canada - National Science Library

    Kirkham, M. B

    2011-01-01

    .... Focusing on this critical issue, Elevated Carbon Dioxide: Impacts on Soil and Plant Water Relations presents research conducted on field-grown sorghum, winter wheat, and rangeland plants under elevated CO2...

  3. Digital Elevation Models (DEMs) for the main 8 Hawaiian Islands

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Digital elevation model (DEM) data are arrays of regularly spaced elevation values referenced horizontally either to a Universal Transverse Mercator (UTM) projection...

  4. Elevated rheumatoid factor and long term risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Schnohr, Peter

    2012-01-01

    To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.......To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis....

  5. Greenland 5 km DEM, Ice Thickness, and Bedrock Elevation Grids

    Data.gov (United States)

    National Aeronautics and Space Administration — A Digital Elevation Model (DEM), ice thickness grid, and bedrock elevation grid of Greenland acquired as part of the PARCA program are available in ASCII text format...

  6. Diazepam treatment blocks the elevation of hippocampal activity and the accelerated proliferation of hippocampal neural stem cells after focal cerebral ischemia in mice.

    Science.gov (United States)

    Nochi, Rokuya; Kaneko, Jun; Okada, Natsumi; Terazono, Yasushi; Matani, Ayumu; Hisatsune, Tatsuhiro

    2013-11-01

    Hippocampal neurogenesis is accelerated during the elevation of hippocampal neural activities under both physiological and pathophysiological conditions. One of these conditions, middle cerebral artery occlusion (MCAO), induces both the hyperactivities of hippocampal network and the elevation of neural stem cell (NSC) proliferation. However, the causal relationship between the elevated activity and the elevation of NSC proliferation is still unclear. In this study, to block the elevation of hippocampal activity after MCAO in mice, we utilized a typical γ-aminobutyric acid type A (GABAA ) receptor active modulator, diazepam. With MCAO mice treated with diazepam, we observed complete disappearance of the elevation of hippocampal activity. Additionally, the diazepam treatment blocked the elevation of NSC proliferation after MCAO. From this result, it is speculated that the increased NSC proliferation is blocked by the suppression of elevated neural activity. However, diazepam might have effects other than the suppression of hippocampal activity, so we performed additional experiment and found that diazepam did not affect the number of bromodeoxyuridine-positive cells under the normal condition, whereas the GABA agonist pentobarbital stimulated NSC/neural progenitor cell proliferation and differentiation. Next, we evaluated the expression of the diazepam-binding inhibitor (DBI) protein and found that the cells expressed DBI in soma and on the surface of cell membrane. From these observations, we can propose that diazepam blocks the elevation of hippocampal activity and also NSC proliferation after MCAO. Copyright © 2013 Wiley Periodicals, Inc.

  7. 46 CFR 116.438 - Stairtowers, stairways, ladders, and elevators.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Stairtowers, stairways, ladders, and elevators. 116.438... AND ARRANGEMENT Fire Protection § 116.438 Stairtowers, stairways, ladders, and elevators. (a) A vessel... the requirements for stairways, ladders, and elevators in § 72.05-20 of this chapter. (b) Materials...

  8. 7 CFR 800.25 - Required elevator and merchandising records.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Required elevator and merchandising records. 800.25... REGULATIONS Recordkeeping and Access to Facilities § 800.25 Required elevator and merchandising records. (a) Elevator and merchandiser recordkeeping. Every person and every State or political subdivision of a State...

  9. 30 CFR 77.1400 - Personnel hoists and elevators.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Personnel hoists and elevators. 77.1400 Section... MINES Personnel Hoisting § 77.1400 Personnel hoists and elevators. Except as provided in § 77.1430, the sections in this Subpart O apply only to hoists and elevators, together with their appurtenances, that are...

  10. 29 CFR 1918.87 - Ship's cargo elevators.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Ship's cargo elevators. 1918.87 Section 1918.87 Labor... (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.87 Ship's cargo elevators. (a) Safe working load. The safe working loads of ship's cargo elevators shall be determined and followed...

  11. 46 CFR 72.05-20 - Stairways, ladders, and elevators.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Stairways, ladders, and elevators. 72.05-20 Section 72... CONSTRUCTION AND ARRANGEMENT Structural Fire Protection § 72.05-20 Stairways, ladders, and elevators. (a)(1..., ladders, and elevators within main machinery spaces or cargo holds are not covered by the general...

  12. 14 CFR 23.155 - Elevator control force in maneuvers.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Elevator control force in maneuvers. 23.155 Section 23.155 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Controllability and Maneuverability § 23.155 Elevator control force in maneuvers. (a) The elevator control force...

  13. Elevated temperature forming method and preheater apparatus

    Science.gov (United States)

    Krajewski, Paul E; Hammar, Richard Harry; Singh, Jugraj; Cedar, Dennis; Friedman, Peter A; Luo, Yingbing

    2013-06-11

    An elevated temperature forming system in which a sheet metal workpiece is provided in a first stage position of a multi-stage pre-heater, is heated to a first stage temperature lower than a desired pre-heat temperature, is moved to a final stage position where it is heated to a desired final stage temperature, is transferred to a forming press, and is formed by the forming press. The preheater includes upper and lower platens that transfer heat into workpieces disposed between the platens. A shim spaces the upper platen from the lower platen by a distance greater than a thickness of the workpieces to be heated by the platens and less than a distance at which the upper platen would require an undesirably high input of energy to effectively heat the workpiece without being pressed into contact with the workpiece.

  14. Elevated temperature fatigue testing of metals

    Science.gov (United States)

    Hirschberg, M. H.

    1981-01-01

    The major technology areas needed to perform a life prediction of an aircraft turbine engine hot section component are discussed and the steps required for life prediction are outlined. These include the determination of the operating environment, the calculation of the thermal and mechanical loading of the component, the cyclic stress-strain and creep behavior of the material required for structural analysis, and the structural analysis to determine the local stress-strain-temperature-time response of the material at the critical location in the components. From a knowledge of the fatigue, creep, and failure resistance of the material, a prediction of the life of the component is made. Material characterization and evaluation conducted for the purpose of calculating fatigue crack initiation lives of components operating at elevated temperatures are emphasized.

  15. Effects of lixisenatide on elevated liver transaminases

    DEFF Research Database (Denmark)

    Gluud, Lise L; Knop, Filip K; Vilsbøll, Tina

    2014-01-01

    identified on AST, alkaline phosphatase or bilirubin. No evidence of bias was identified. Mixed effect multilevel meta-regression analyses suggest that the benefit of lixisenatide on ALT was limited to patients who were overweight or obese. CONCLUSIONS: This review suggests that lixisenatide increases......) on lixisenatide versus placebo or active comparators for type 2 diabetes were included. PARTICIPANTS: Individual patient data were retrieved to calculate outcomes for patients with elevated liver blood tests. MAIN OUTCOME MEASURES: Normalisation of alanine aminotransferase (ALT) and aspartate aminotransferase...... (AST). DATA SYNTHESIS: The results of included trials were combined in meta-analyses. Sequential, subgroup and regression analyses were performed to evaluate heterogeneity and bias. RESULTS: We included 12 RCTs on lixisenatide versus placebo and 3 RCTs with the active comparators liraglutide, exenatide...

  16. ICESat: Ice, Cloud and Land Elevation Satellite

    Science.gov (United States)

    Zwally, Jay; Shuman, Christopher

    2002-01-01

    Ice exists in the natural environment in many forms. The Earth dynamic ice features shows that at high elevations and/or high latitudes,snow that falls to the ground can gradually build up tu form thick consolidated ice masses called glaciers. Glaciers flow downhill under the force of gravity and can extend into areas that are too warm to support year-round snow cover. The snow line, called the equilibrium line on a glacier or ice sheet, separates the ice areas that melt on the surface and become show free in summer (net ablation zone) from the ice area that remain snow covered during the entire year (net accumulation zone). Snow near the surface of a glacier that is gradually being compressed into solid ice is called firm.

  17. Magnesium sacrificial anode behavior at elevated temperature

    International Nuclear Information System (INIS)

    Othman, Mohsen Othman

    2006-01-01

    Magnesium sacrificial anode coupled to mild steel was tasted in sodium chloride and tap water environments at elevated temperatures. The anode failed to protect the mild steel specimens in tap water environment at all temperatures specified. This was partly due to low conductivity of this medium. The temperature factor did not help to activate the anode in this medium. In sodium chloride environment the anode demonstrated good protection for steel cathodes. The weight loss was high for magnesium in sodium chloride environment particularly beyond 60 degree centigrade. In tap water environment the weight loss was negligible for the anode. It also suffered localized shallow pitting corrosion. Magnesium anode cannot be utilized where high temperature is involved particularly in high conductivity mediums. Protection of structures containing high resistivity waters is not feasible using sacrificial anode system. (author)

  18. Dynamic expression pattern of kinesin accessory protein in Drosophila

    Indian Academy of Sciences (India)

    Unknown

    in figure 4A) and in follicle cells (arrowhead, figure. 4A) has persisted through out development. However, the level of expression in nurse cells is elevated from stage 10b (figure 4C, a single nurse cell is marked by dotted lines). This is likely to contribute to the maternal component to oocyte. DmKAP gene expression is also.

  19. Unusual head and neck injury in elevator: autopsy study.

    Science.gov (United States)

    Eren, B; Türkmen, N; Dokgöz, H

    2012-10-01

    Industrial injuries related to auto-load-carrying vehicles were not frequently reported in the literature. Presented case was, 31-year-old male furniture worker. Deceased was found in awkward position in furniture workshop. Victim was observed on his knees in front of the elevator, head and neck lodged within openings of the elevator, and head and neck structures compressed-guillotined by the lower platform of the elevator were detected. We presented rare case of head and neck compression by elevator. Key words: head - neck - accidents - elevator - autopsy.

  20. HDAC inhibition induces increased choline uptake and elevated phosphocholine levels in MCF7 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Christopher S Ward

    Full Text Available Histone deacetylase (HDAC inhibitors have emerged as effective antineoplastic agents in the clinic. Studies from our lab and others have reported that magnetic resonance spectroscopy (MRS-detectable phosphocholine (PC is elevated following SAHA treatment, providing a potential noninvasive biomarker of response. Typically, elevated PC is associated with cancer while a decrease in PC accompanies response to antineoplastic treatment. The goal of this study was therefore to elucidate the underlying biochemical mechanism by which HDAC inhibition leads to elevated PC. We investigated the effect of SAHA on MCF-7 breast cancer cells using (13C MRS to monitor [1,2-(13C] choline uptake and phosphorylation to PC. We found that PC synthesis was significantly higher in treated cells, representing 154±19% of control. This was within standard deviation of the increase in total PC levels detected by (31P MRS (129±7% of control. Furthermore, cellular choline kinase activity was elevated (177±31%, while cytidylyltransferase activity was unchanged. Expression of the intermediate-affinity choline transporter SLC44A1 and choline kinase α increased (144% and 161%, respectively relative to control, as determined by mRNA microarray analysis with protein-level confirmation by Western blotting. Taken together, our findings indicate that the increase in PC levels following SAHA treatment results from its elevated synthesis. Additionally, the concentration of glycerophosphocholine (GPC increased significantly with treatment to 210±45%. This is likely due to the upregulated expression of several phospholipase A2 (PLA2 isoforms, resulting in increased PLA2 activity (162±18% in SAHA-treated cells. Importantly, the levels of total choline (tCho-containing metabolites, comprised of choline, PC and GPC, are readily detectable clinically using (1H MRS. Our findings thus provide an important step in validating clinically translatable non-invasive imaging methods for follow

  1. Cokriging model for estimation of water table elevation

    International Nuclear Information System (INIS)

    Hoeksema, R.J.; Clapp, R.B.; Thomas, A.L.; Hunley, A.E.; Farrow, N.D.; Dearstone, K.C.

    1989-01-01

    In geological settings where the water table is a subdued replica of the ground surface, cokriging can be used to estimate the water table elevation at unsampled locations on the basis of values of water table elevation and ground surface elevation measured at wells and at points along flowing streams. The ground surface elevation at the estimation point must also be determined. In the proposed method, separate models are generated for the spatial variability of the water table and ground surface elevation and for the dependence between these variables. After the models have been validated, cokriging or minimum variance unbiased estimation is used to obtain the estimated water table elevations and their estimation variances. For the Pits and Trenches area (formerly a liquid radioactive waste disposal facility) near Oak Ridge National Laboratory, water table estimation along a linear section, both with and without the inclusion of ground surface elevation as a statistical predictor, illustrate the advantages of the cokriging model

  2. Traction sheave elevator, hoisting unit and machine space

    Science.gov (United States)

    Hakala, Harri; Mustalahti, Jorma; Aulanko, Esko

    2000-01-01

    Traction sheave elevator consisting of an elevator car moving along elevator guide rails, a counterweight moving along counterweight guide rails, a set of hoisting ropes (3) on which the elevator car and counterweight are suspended, and a drive machine unit (6) driving a traction sheave (7) acting on the hoisting ropes (3) and placed in the elevator shaft. The drive machine unit (6) is of a flat construction. A wall of the elevator shaft is provided with a machine space with its open side facing towards the shaft, the essential parts of the drive machine unit (6) being placed in the space. The hoisting unit (9) of the traction sheave elevator consists of a substantially discoidal drive machine unit (6) and an instrument panel (8) mounted on the frame (20) of the hoisting unit.

  3. Geared-elevator flutter study. [transonic flutter characteristics of empennage

    Science.gov (United States)

    Ruhlin, C. L.; Doggett, R. V., Jr.; Gregory, R. A.

    1976-01-01

    The paper describes an experimental and analytical study of the transonic flutter characteristics of an empennage flutter model having an all-movable horizontal tail with a geared elevator. Two configurations were flutter tested: one with a geared elevator and one with a locked elevator with the model cantilever-mounted on a sting in the wind tunnel. The geared-elevator configuration fluttered experimentally at about 20% higher dynamic pressures than the locked-elevator configuration. The experimental flutter boundary was nearly flat at transonic speeds for both configurations. It was found that an analysis which treated the elevator as a discrete surface predicted flutter dynamic pressure levels better than analyses which treated the stabilizer and elevator as a warped surface. Warped-surface methods, however, predicted more closely the experimental flutter frequencies and Mach number trends.

  4. Purwarupa Sistem Kontrol Elevator Berbasis Programable Logic Control

    Directory of Open Access Journals (Sweden)

    Fathahillah Fathahillah

    2017-12-01

    Full Text Available Various methods / types of controls developed in accordance with industry needs one of them in the field of building automation system. One of the controls in the field of building automation system is the elevator control system (elevator. Early elevator control systems that transport humans or goods as vertical transportation vehicles are still conventional using human power, then evolved using steam engines, until now the elevators use AC motors equipped with control systems. The purpose of this research is to design the prototype of elevator control system using programmable logic control (PLC. The type of PLC controller used in the study using Omron PLC. The results show the design of prototype of elevator control system using PLC successfully and can control eleveator in accordance with its function, besides its programming form can be more simple.

  5. Design of a powered elevator control system. [powered elevator system for modified C-8A aircraft for STOL operation

    Science.gov (United States)

    Glende, W. L. B.

    1974-01-01

    The design, fabrication and flight testing of a powered elevator system for the Augmentor Wing Jet STOL Research Aircraft (AWJSRA or Mod C-8A) are discussed. The system replaces a manual spring tab elevator control system that was unsatisfactory in the STOL flight regime. Pitch control in the AWJSRA is by means of a single elevator control surface. The elevator is used for both maneuver and trim control as the stabilizer is fixed. A fully powered, irreversible flight control system powered by dual hydraulic sources was designed. The existing control columns and single mechanical cable system of the AWJSRA have been retained as has been the basic elevator surface, except that the elevator spring tab is modified into a geared balance tab. The control surface is directly actuated by a dual tandem moving body actuator. Control signals are transmitted from the elevator aft quadrant to the actuator by a linkage system that includes a limited authority series servo actuator.

  6. The surface elevation table: marker horizon method for measuring wetland accretion and elevation dynamics

    Science.gov (United States)

    Callaway, John C.; Cahoon, Donald R.; Lynch, James C.

    2014-01-01

    Tidal wetlands are highly sensitive to processes that affect their elevation relative to sea level. The surface elevation table–marker horizon (SET–MH) method has been used to successfully measure these processes, including sediment accretion, changes in relative elevation, and shallow soil processes (subsidence and expansion due to root production). The SET–MH method is capable of measuring changes at very high resolution (±millimeters) and has been used worldwide both in natural wetlands and under experimental conditions. Marker horizons are typically deployed using feldspar over 50- by 50-cm plots, with replicate plots at each sampling location. Plots are sampled using a liquid N2 cryocorer that freezes a small sample, allowing the handling and measurement of soft and easily compressed soils with minimal compaction. The SET instrument is a portable device that is attached to a permanent benchmark to make high-precision measurements of wetland surface elevation. The SET instrument has evolved substantially in recent decades, and the current rod SET (RSET) is widely used. For the RSET, a 15-mm-diameter stainless steel rod is pounded into the ground until substantial resistance is achieved to establish a benchmark. The SET instrument is attached to the benchmark and leveled such that it reoccupies the same reference plane in space, and pins lowered from the instrument repeatedly measure the same point on the soil surface. Changes in the height of the lowered pins reflect changes in the soil surface. Permanent or temporary platforms provide access to SET and MH locations without disturbing the wetland surface.

  7. Association Between Geographic Elevation, Bone Status, and Exercise Habits: The Shimane CoHRE Study

    Directory of Open Access Journals (Sweden)

    Miwako Takeda

    2015-06-01

    Full Text Available In recent years, there has been growing interest in the association between the residential environment and health. The association between residential environment (i.e., geographic elevation and bone status is unknown. Furthermore, these associations could differ by exercise habits due to the chronically greater daily activity caused by steep slopes in mountainous areas. The aim of this study was to test whether the association between bone status of elderly people measured using quantitative ultrasound (QUS and elevation varied according to the exercise habits in a mountainous area population. Data were collected from a cross-sectional study conducted during 2012–2013. QUS value was expressed as a proportion of the young adult mean (%YAM, with higher scores donating better bone status. After excluding subjects with missing data, we analyzed the data for 321 men and 500 women. Our results indicate that %YAM was not associated with elevation among men, or among women with exercise habits. However, elevation was associated with %YAM among women without exercise habits. Our results highlight the importance of considering residential environment and exercise habits when establishing promotion strategies to maintain bone status of the elderly people who live in rural mountainous areas.

  8. Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

    Science.gov (United States)

    Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

    2017-07-01

    Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

  9. Elevated expression levels of lysyl oxidases protect against aortic aneurysm progression in Marfan syndrome

    NARCIS (Netherlands)

    Busnadiego, O.; Gorbenko del Blanco, D.; González-Santamaría, J.; Habashi, J.P.; Calderon, J.F.; Sandoval, P.; Bedja, D.; Guinea-Viniegra, J.; Lopez-Cabrera, M.; Rosell-Garcia, T.; Snabel, J.M.; Hanemaaijer, R.; Forteza, A.; Dietz, H.C.; Egea, G.; Rodriguez-Pascual, F.

    2015-01-01

    Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic dissections. The condition is caused by mutations in the gene encoding fibrillin-1, an essential component in the formation of elastic fibers. While experimental findings in animal models of the disease have shown the

  10. Expression of the gene for large subunit of m-calpain is elevated in ...

    Indian Academy of Sciences (India)

    To test whether the reported increase in calpain activity in DMD results from de novo synthesis of the protease, we have assessed the quantitative changes in mRNA ... Institute of Genetics, Begumpet, Hyderabad 500 016, India; Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500 076, India; Nizam's ...

  11. Elevated Immune Gene Expression Is Associated with Poor Reproductive Success of Urban Blue Tits

    NARCIS (Netherlands)

    Capilla-Lasheras, Pablo; Dominoni, D.M.; Babayan, Simon; O'Shaughnessy, Peter; Mladenova, Magdalena; Woodford, Luke; Pollock, Christopher J.; Barr, Tom; Baldini, Francesco; Helm, Barbara

    2017-01-01

    Urban and forest habitats differ in many aspects that can lead to modifications of the immune system of wild animals. Altered parasite communities, pollution, and artificial light at night in cities have been associated with exacerbated inflammatory responses, with possibly negative fitness

  12. Expression of the gene for large subunit of m-calpain is elevated in ...

    Indian Academy of Sciences (India)

    (EMG), muscle histology and estimation of serum creatine kinase. Histological details of muscle tissue from studied individuals are presented in table 1. Collection of clinical materials: Part (about 500 mg) of the muscle tissue (vastus lateralis or gastrocnemius muscle) biopsied from DMD patients who were referred for.

  13. Elevated expression of metal transporter genes in three accessions of the metal hyperaccumulator Thlaspi caerulescens

    NARCIS (Netherlands)

    Gonçalves Leite de Assunção, A.; Costa Martins, Da P.; Folter, de S.; Vooijs, R.; Aarts, M.G.M.

    2001-01-01

    Heavy metal hyperaccumulation in plants is an intriguing and poorly understood phenomenon. Transmembrane metal transporters are assumed to play a key role in this process. We describe the cloning and isolation of three zinc transporter cDNAs from the Zn hyperaccumulator Thlaspi caerulescens. The

  14. Elevated expression of metal transporter genes in three accessions of the metal hyperaccumulator Thlaspi caerulescens.

    NARCIS (Netherlands)

    Assunção, A.G.L.; Da Costa Martins, P.; de Folter, S.; Schat, H.; Vooijs, H.; Aarts, M.G.M.

    2001-01-01

    Heavy metal hyperaccumulation in plants is an intriguing and poorly understood phenomenon. Transmembrane metal transporters are assumed to play a key role in this process. We describe the cloning and isolation of three zinc transporter cDNAs from the Zn hyperaccumulator Thlaspi caerulescens. The

  15. Elevated Enterotoxin A Expression and Formation in Staphylococcus aureus and Its Association with Prophage Induction

    OpenAIRE

    Cao, Rong; Zeaki, Nikoleta; Wallin-Carlquist, Nina; Skandamis, Panagiotis N.; Schelin, Jenny; Rådström, Peter

    2012-01-01

    Staphylococcus aureus strains producing the bacteriophage-encoded staphylococcal enterotoxin A (SEA) were divided into two groups, high- and low-SEA-producing strains, based on the amount of SEA produced. After growth under favorable conditions in batch cultures, 10 of the 21 strains tested produced more than 1,000 ng/ml SEA, and 9 strains produced less than 10 ng/ml SEA; two enterotoxigenic strains, MRSA252 and Newman, produced intermediate levels of SEA (around 450 ng/ml). The differences i...

  16. Clutch size declines with elevation in tropical birds

    Science.gov (United States)

    Boyce, A.J.; Freeman, Benjamin G.; Mitchell, Adam E.; Martin, Thomas E.

    2015-01-01

    Clutch size commonly decreases with increasing elevation among temperate-zone and subtropical songbird species. Tropical songbirds typically lay small clutches, thus the ability to evolve even smaller clutch sizes at higher elevations is unclear and untested. We conducted a comparative phylogenetic analysis using data gathered from the literature to test whether clutch size varied with elevation among forest passerines from three tropical biogeographic regions—the Venezuelan Andes and adjacent lowlands, Malaysian Borneo, and New Guinea. We found a significant negative effect of elevation on variation in clutch size among species. We found the same pattern using field data sampled across elevational gradients in Venezuela and Malaysian Borneo. Field data were not available for New Guinea. Both sets of results demonstrate that tropical montane species across disparate biogeographic realms lay smaller clutches than closely related low-elevation species. The environmental sources of selection underlying this pattern remain uncertain and merit further investigation.

  17. Patterns of care and persistence after incident elevated blood pressure.

    Science.gov (United States)

    Daley, Matthew F; Sinaiko, Alan R; Reifler, Liza M; Tavel, Heather M; Glanz, Jason M; Margolis, Karen L; Parker, Emily; Trower, Nicole K; Chandra, Malini; Sherwood, Nancy E; Adams, Kenneth; Kharbanda, Elyse O; Greenspan, Louise C; Lo, Joan C; O'Connor, Patrick J; Magid, David J

    2013-08-01

    Screening for hypertension in children occurs during routine care. When blood pressure (BP) is elevated in the hypertensive range, a repeat measurement within 1 to 2 weeks is recommended. The objective was to assess patterns of care after an incident elevated BP, including timing of repeat BP measurement and likelihood of persistently elevated BP. This retrospective study was conducted in 3 health care organizations. All children aged 3 through 17 years with an incident elevated BP at an outpatient visit during 2007 through 2010 were identified. Within this group, we assessed the proportion who had a repeat BP measured within 1 month of their incident elevated BP and the proportion who subsequently met the definition of hypertension. Multivariate analyses were used to identify factors associated with follow-up BP within 1 month of initial elevated BP. Among 72,625 children and adolescents in the population, 6108 (8.4%) had an incident elevated BP during the study period. Among 6108 with an incident elevated BP, 20.9% had a repeat BP measured within 1 month. In multivariate analyses, having a follow-up BP within 1 month was not significantly more likely among individuals with obesity or stage 2 systolic elevation. Among 6108 individuals with an incident elevated BP, 84 (1.4%) had a second and third consecutive elevated BP within 12 months. Whereas >8% of children and adolescents had an incident elevated BP, the great majority of BPs were not repeated within 1 month. However, relatively few individuals subsequently met the definition of hypertension.

  18. Investigation on cause of the elevator turbine wear

    Science.gov (United States)

    Zhang, J.; Ouyang, W. P.; Xue, J. A.

    2018-03-01

    Elevator traction turbine is often worn for various reasons, causing serious safety hazard. It is explained the main causes of traction wheel wear in detail in combination with a large number of engineering experience. The effect of turbine wear on the actual operation of the elevator is verified by contrast experiment, which is helpful to identify risks early. It is put forward on some reasonable suggestions for elevator inspection, maintenance and management.

  19. Increased parathyroid expression of klotho in uremic rats

    DEFF Research Database (Denmark)

    Hofman-Bang, J.; Martuseviciene, G.; Santini, M.A.

    2010-01-01

    /6 nephrectomy rat model of secondary hyperparathyroidism. Parathyroid klotho gene expression and protein were significantly increased in severely uremic hyperphosphatemic rats, but not affected by moderate uremia and normal serum phosphorus. Calcitriol suppressed klotho gene and protein expression in severe...... secondary hyperparathyroidism, despite a further increase in plasma phosphate. Both FGFR1 IIIC and Na+/K+-ATPase gene expression were significantly elevated in severe secondary hyperparathyroidism. Parathyroid gland klotho expression and the plasma calcium ion concentration were inversely correlated. Thus......, our study suggests that klotho may act as a positive regulator of PTH expression and secretion in secondary hyperparathyroidism....

  20. Unexpected Elevated Free Thyroid Hormones in Pregnancy.

    Science.gov (United States)

    Teti, Claudia; Nazzari, Elena; Galletti, Marina Raffaella; Mandolfino, Mattia Grazia; Pupo, Francesca; Pesce, Giampaola; Lillo, Flavia; Bagnasco, Marcello; Benvenga, Salvatore

    2016-11-01

    The use of thyrotropin and free thyroid hormone assays to evaluate thyroid function is widespread, but in some situations the results are inconsistent with the patient's thyroid status. A 35-year-old woman with a known diagnosis of chronic autoimmune thyroiditis was referred to the authors' clinic at week 26 of her second pregnancy. The patient was clinically euthyroid. Consistent with this, her serum thyrotropin (TSH) was normal (0.79 mIU/L), but she had elevated free thyroid hormones-free triiodothyronine (fT3) and free thyroxine (fT4)-as determined by a one-step chemiluminescent assay. The patient was taking levothyroxine replacement therapy (125 μg/day), and the dose was confirmed. Previous blood tests showed concordance between TSH and free thyroid hormone values. The patient was followed up throughout gestation and at 12 months postpartum. During gestation, her free thyroid hormones remained high using one-step methods, while the total thyroid hormone concentration values were within the reference range, in agreement with the TSH values. Postpartum fT4 and fT3 values returned progressively to normality, in agreement with the TSH values. The presence of circulating thyroid hormone autoantibodies (THAb) was hypothesized, which are known to interfere, although to a variable extent, with thyroid hormone one-step assays. Using stored frozen sera, this hypothesis was confirmed indirectly by measuring normal levels of fT3 and fT4 with a two-step method, and directly by demonstrating THAb against the two hormones. Despite their relative rarity, circulating THAb may be suspected when laboratory data are not consistent and contrast with the clinical picture. To the authors' knowledge, no previous case of transient appearance of THAb in pregnancy has been described.