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Sample records for growth factor-2 polynucleotides

  1. Fibroblast Growth Factor-2 Alters the Nature of Extinction

    Science.gov (United States)

    Graham, Bronwyn M.; Richardson, Rick

    2011-01-01

    These experiments examined the effects of the NMDA-receptor (NMDAr) antagonist MK801 on reacquisition and re-extinction of a conditioned fear that had been previously extinguished before injection of fibroblast growth factor-2 (FGF2) or vehicle. Recent findings have shown that relearning and re-extinction, unlike initial learning and extinction,…

  2. Individual Differences in the Expression of Conditioned Fear Are Associated with Endogenous Fibroblast Growth Factor 2

    Science.gov (United States)

    Graham, Bronwyn M.; Richardson, Rick

    2016-01-01

    These experiments examined the relationship between the neurotrophic factor fibroblast growth factor 2 (FGF2) and individual differences in the expression of conditioned fear. Experiments 1 and 2 demonstrated that rats naturally expressing low levels of contextual or cued fear have higher levels of hippocampal FGF2 relative to rats that express…

  3. Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis

    OpenAIRE

    Bianchessi, Marta; Chen, Yuwen; Durgam, Sushmitha; Pondenis, Holly; Stewart, Matthew

    2015-01-01

    Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP) cells in equine synovial fluid (SF) and to determine the effect of fibroblast growth factor 2 (FGF-2) on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU) assa...

  4. Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components

    Czech Academy of Sciences Publication Activity Database

    Steringer, J. P.; Lange, S.; Čujová, Sabína; Šachl, Radek; Poojari, C.; Lolicato, F.; Beutel, O.; Müller, H.-M.; Unger, S.; Coskun, U.; Honigmann, A.; Vattulainen, I.; Hof, Martin; Freund, Ch.; Nickel, W.

    2017-01-01

    Roč. 6, č. 2017 (2017), č. článku e28985. ISSN 2050-084X R&D Projects: GA ČR(CZ) GC14-03141J Institutional support: RVO:61388955 Keywords : Unconventional protein secretion * Fibroblast Growth Factor 2 * Protein translocation across membranes Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 7.725, year: 2016

  5. Fibroblast growth factor-2 stimulates adipogenic differentiation of human adipose-derived stem cells

    International Nuclear Information System (INIS)

    Kakudo, Natsuko; Shimotsuma, Ayuko; Kusumoto, Kenji

    2007-01-01

    Adipose-derived stem cells (ASCs) have demonstrated a capacity for differentiating into a variety of lineages, including bone, cartilage, or fat, depending on the inducing stimuli and specific growth and factors. It is acknowledged that fibroblast growth factor-2 (FGF-2) promotes chondrogenic and inhibits osteogenic differentiation of ASCs, but thorough investigations of its effects on adipogenic differentiation are lacking. In this study, we demonstrate at the cellular and molecular levels the effect of FGF-2 on adipogenic differentiation of ASCs, as induced by an adipogenic hormonal cocktail consisting of 3-isobutyl-1-methylxanthine (IBMX), dexamethasone, insulin, and indomethacin. FGF-2 significantly enhances the adipogenic differentiation of human ASCs. Furthermore, in cultures receiving FGF-2 before adipogenic induction, mRNA expression of peroxisome proliferator-activated receptor γ2 (PPARγ2), a key transcription factor in adipogenesis, was upregulated. The results of FGF-2 supplementation suggest the potential applications of FGF-2 and ASCs in adipose tissue regeneration

  6. Selection and characterization of a human neutralizing antibody to human fibroblast growth factor-2

    International Nuclear Information System (INIS)

    Tao, Jun; Xiang, Jun-Jian; Li, Dan; Deng, Ning; Wang, Hong; Gong, Yi-Ping

    2010-01-01

    Compelling evidences suggest that fibroblast growth factor-2 (FGF-2) plays important roles in tumor growth, angiogenesis and metastasis. Molecules blocking the FGF-2 signaling have been proposed as anticancer agents. Through screening of a human scFv phage display library, we have isolated several human single-chain Fv fragments (scFvs) that bind to human FGF-2. After expression and purification in bacteria, one scFv, named 1A2, binds to FGF-2 with a high affinity and specificity, and completes with FGF-2 binding to its receptor. This 1A2 scFv was then cloned into the pIgG1 vector and expressed in 293T cells. The purified hIgG1-1A2 antibody showed a high binding affinity of 8 x 10 -9 M to rhFGF-2. In a set of vitro assays, it inhibited various biological activities of FGF-2 such as the proliferation, migration and tube formation of human umbilical vein endothelial cells. More importantly, hIgG1-1A2 antibody also efficiently blocked the growth while inducing apoptosis of glioma cells. For the first time, we generated a human anti-FGF-2 antibody with proven in vitro anti-tumor activity. It may therefore present a new therapeutic candidate for the treatment of cancers that are dependent on FGF-2 signaling for growth and survival.

  7. Use of fibroblast growth factor 2 for expansion of chondrocytes and tissue engineering

    Science.gov (United States)

    Vunjak-Novakovic, Gordana (Inventor); Martin, Ivan (Inventor); Freed, Lisa E. (Inventor); Langer, Robert (Inventor)

    2003-01-01

    The present invention provides an improved method for expanding cells for use in tissue engineering. In particular the method provides specific biochemical factors to supplement cell culture medium during the expansion process in order to reproduce events occurring during embryonic development with the goal of regenerating tissue equivalents that resemble natural tissues both structurally and functionally. These specific biochemical factors improve proliferation of the cells and are capable of de-differentiation mature cells isolated from tissue so that the differentiation potential of the cells is preserved. The bioactive molecules also maintain the responsiveness of the cells to other bioactive molecules. Specifically, the invention provides methods for expanding chondrocytes in the presence of fibroblast growth factor 2 for use in regeneration of cartilage tissue.

  8. Expression of insulin-like growth factor-2 receptors on EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Farmer, John T; Weigent, Douglas A

    2007-01-01

    In the present study, we report the upregulation of functional IGF-2Rs in cells overexpressing growth hormone (GH). EL4 lymphoma cells stably transfected with an rGH cDNA overexpression vector (GHo) exhibited an increase in the binding of (125)I-IGF-2 with no change in the binding affinity compared to vector alone controls. An increase in the expression of the insulin-like growth factor-2 receptor (IGF-2R) in cells overexpressing GH was confirmed by Western blot analysis and IGF-2R promoter luciferase assays. EL4 cells produce insulin-like growth factor-2 (IGF-2) as detected by the reverse transcription-polymerase chain reaction (RT-PCR); however, no IGF-2 protein was detected by Western analysis. The increase in the expression of the IGF-2R resulted in greater levels of IGF-2 uptake in GHo cells compared to vector alone controls. The data suggest that one of the consequences of the overexpression of GH is an increase in the expression of the IGF-2R.

  9. Paternal Insulin-like Growth Factor 2 (Igf2) Regulates Stem Cell Activity During Adulthood.

    Science.gov (United States)

    Barroca, Vilma; Lewandowski, Daniel; Jaracz-Ros, Agnieszka; Hardouin, Sylvie-Nathalie

    2017-02-01

    Insulin-like Growth Factor 2 (IGF2) belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC) successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood. We show that Igf2 is specifically expressed in adult HSC and we analyze HSC from adult mice deficient in Igf2 transcripts. We demonstrate that Igf2 deficiency avoids the age-related attrition of the HSC pool and that Igf2 is necessary for tissue homeostasis and regeneration. Our study reveals that the expression level of Igf2 is critical to maintain the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSC and their niche. Our data have major clinical interest for transplantation: understanding the changes in adult stem cells and their environments will improve the efficacy of regenerative medicine and impact health- and life-span. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Paternal Insulin-like Growth Factor 2 (Igf2 Regulates Stem Cell Activity During Adulthood

    Directory of Open Access Journals (Sweden)

    Vilma Barroca

    2017-02-01

    Full Text Available Insulin-like Growth Factor 2 (IGF2 belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood. We show that Igf2 is specifically expressed in adult HSC and we analyze HSC from adult mice deficient in Igf2 transcripts. We demonstrate that Igf2 deficiency avoids the age-related attrition of the HSC pool and that Igf2 is necessary for tissue homeostasis and regeneration. Our study reveals that the expression level of Igf2 is critical to maintain the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSC and their niche. Our data have major clinical interest for transplantation: understanding the changes in adult stem cells and their environments will improve the efficacy of regenerative medicine and impact health- and life-span.

  11. Celecoxib suppresses fibroblast growth factor-2 expression in pancreatic ductal adenocarcinoma PANC-1 cells.

    Science.gov (United States)

    Li, Jing; Luo, Miaosha; Wang, Yan; Shang, Boxin; Dong, Lei

    2016-09-01

    The inhibition of cyclooxygenase (COX)-2 has been reported to suppress growth and induce apoptosis in human pancreatic cancer cells. Nevertheless, the precise biological mechanism of how celecoxib, a selective COX-2 inhibitor, regulates the growth and invasion of pancreatic tumors is not completely understood. It has been shown that fibroblast growth factor-2 (FGF-2) and its receptor levels correlate with the inhibition of cancer cell proliferation, migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Therefore, the aim of the present study was to examine the hypothesis that the antitumor activity of celecoxib in PDAC may be exerted through modulation of FGF-2 function. In the present study, we evaluated the effects of celecoxib on the proliferation, migration, invasion and apoptosis of the PANC-1 cell line. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of FGF-2, FGFR-2, ERK1/2 and MMPs. In the present study, FGF-2 and FGFR-2 were expressed in PANC-1 cells and FGF-2 exerted a stimulatory effect on phosphorylated extracellular signal regulated kinase (p-ERK) expression. Celecoxib treatment suppressed FGF-2 and FGFR-2 expression and decreased MMP-2, MMP-9 and p-ERK expression in the PANC-1 cells. Furthermore, celecoxib treatment caused the resistance of PANC-1 cells to FGF-2 induced proliferation, migration and invasion ability, as well as the increase in their apoptotic rate. Our data provide evidence that targeting FGF-2 with celecoxib may be used as an effective treatment in PDAC.

  12. Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis

    Directory of Open Access Journals (Sweden)

    Marta Bianchessi

    2016-01-01

    Full Text Available Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP cells in equine synovial fluid (SF and to determine the effect of fibroblast growth factor 2 (FGF-2 on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU assays were performed during primary cultures. At first passage, SF-cells were seeded at low density, with or without FGF-2. Following monolayer expansion and serial immunophenotyping, cells were transferred to chondrogenic pellet cultures. Pellets were analyzed for chondrogenic mRNA expression and cartilage matrix secretion. There was a mean of 59.2 CFU/mL of SF. FGF-2 increased the number of population doublings during two monolayer passages and halved the population doubling times. FGF-2 did not alter the immunophenotype of SF-CPs during monolayer expansion, nor did FGF-2 compromise chondrogenesis. Hypertrophic phenotypic markers were not expressed in control or FGF-2 groups. FGF-2 did prevent the development of a “fibroblastic” cell layer around pellet periphery. FGF-2 significantly accelerates in vitro SF-CP expansion, the major hurdle to clinical application of this cell population, without detrimentally affecting subsequent chondrogenic capacity.

  13. Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation.

    LENUS (Irish Health Repository)

    Walsh, Marie-Therese

    2011-11-01

    Eosinophils exert many of their inflammatory effects in allergic disorders through the degranulation and release of intracellular mediators, including a set of cationic granule proteins that include eosinophil peroxidase. Studies suggest that eosinophils are involved in remodeling. In previous studies, we showed that eosinophil granule proteins activate mitogen-activated protein kinase signaling. In this study, we investigated the receptor mediating eosinophil peroxidase-induced signaling and downstream effects. Human cholinergic neuroblastoma IMR32 and murine melanoma B16.F10 cultures, real-time polymerase chain reaction, immunoprecipitations, and Western blotting were used in the study. We showed that eosinophil peroxidase caused a sustained increase in both the expression of epidermal growth factor-2 (HER2) and its phosphorylation at tyrosine 1248, with the consequent activation of extracellular-regulated kinase 1\\/2. This, in turn, promoted a focal adhesion kinase-dependent egress of the cyclin-dependent kinase inhibitor p27(kip) from the nucleus to the cytoplasm. Eosinophil peroxidase induced a HER2-dependent up-regulation of cell proliferation, indicated by an up-regulation of the nuclear proliferation marker Ki67. This study identifies HER2 as a novel mediator of eosinophil peroxidase signaling. The results show that eosinophil peroxidase, at noncytotoxic levels, can drive cell-cycle progression and proliferation, and contribute to tissue remodeling and cell turnover in airway disease. Because eosinophils are a feature of many cancers, these findings also suggest a role for eosinophils in tumorigenesis.

  14. TRX is up-regulated by fibroblast growth factor-2 in lung carcinoma.

    Science.gov (United States)

    Deng, Zheng-Hao; Cao, Hui-Qiu; Hu, Yong-Bin; Wen, Ji-Fang; Zhou, Jian-Hua

    2011-01-01

    We have previously shown that exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis of the small-cell lung cancer (SCLC) cell line NCI-H446, but the underlying mechanism remains unknown. In this study, the protein profiles of FGF-2-treated and untreated NCI-H446 cells were determined by 2-D gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics. Differential expression analysis of the protein profiles after FGF-2 treatment identified a total of 24 protein spots, of which nine were up-regulated and 15 were down-regulated. Four proteins were identified by MALDI-TOF-MS: thioredoxin (TRX), visfatin, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) and Cu/Zn superoxide dismutase (CuZn-SOD). Western blotting revealed that TRX was up-regulated in NCI-H446 and A549 cells treated with FGF-2. Furthermore, immunohistochemical staining confirmed that both FGF-2 and TRX were overexpressed in lung cancer tissues and could be correlated with both lymph node metastasis and clinical stage. These data indicate that TRX may be involved in the FGF-2 signaling pathway. © 2010 The Authors. APMIS © 2010 APMIS.

  15. Preparation and biological evaluation of a fibroblast growth factor-2-apatite composite layer on polymeric material

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Kenkichi; Kamitakahara, Masanobu; Ioku, Koji [Graduate School of Environmental Studies, Tohoku University, Aoba 6-6-20, Aramaki, Aoba-ku, Sendai 980-8579 (Japan); Oyane, Ayako [Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562 (Japan); Hyodo, Koji [Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-2-1 Namiki, Tsukuba, Ibaraki 305-8564 (Japan); Ito, Atsuo; Sogo, Yu, E-mail: a-oyane@aist.go.j [Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566 (Japan)

    2010-12-15

    A polymeric percutaneous device with good biocompatibility and resistance to bacterial infection is required clinically. In this study, a fibroblast growth factor-2 (FGF-2)-hydroxyapatite (HAp) composite layer (FHAp layer) was formed on the surfaces of ethylene-vinyl alcohol copolymer (EVOH) specimens using a coating process in a supersaturated calcium phosphate solution supplemented with FGF-2. FGF-2 in the FHAp layer retained its biological activity to promote proliferation of fibroblasts. The EVOH specimens coated with HAp and FHAp layers were percutaneously implanted in the scalp of rats. Not only the HAp layer but also the FHAp layer showed good biocompatibility, and FGF-2 showed no harmful effects on the skin tissue responses to the implanted specimen as long as 14 d. No significantly higher infection resistance was verified for the FHAp layer over the HAp layer, although an FHAp layer coated on a metallic percutaneous device for bone fixation demonstrated higher resistance to bacterial infection over an HAp layer in the previous study. The efficacy of FHAp layers coated on percutaneous implants in resistance to bacterial infection depends on physical factors including fixation condition, stiffness and movement of implants.

  16. Decreased levels of serum fibroblast growth factor-2 in children with autism spectrum disorder.

    Science.gov (United States)

    Esnafoglu, Erman; Ayyıldız, Sema Nur

    2017-11-01

    The neurodevelopment and functioning of the central nervous system, and especially the cerebral cortex, have basic importance to understand neuropsychiatric disorders like autism. Fibroblast growth factor-2 (FGF-2) plays a very important role in the development and functioning of the cortex. FGF-2 is related to developmental processes in the central nervous system such as neurogenesis, migration, differentiation and survival. This study researched the serum FGF-2 levels in children with autism spectrum disorder (ASD). With this aim, 60 ASD children and 40 healthy controls were compared. We applied a sociodemographic form and the Childhood Autism Rating Scale (CARS) to each subject with their family to assess the severity of autism. Additionally, all subjects had routine laboratory tests performed. Serum samples were studied with ELISA. The results found that serum FGF-2 levels were statistically significantly low in the patient group compared to the healthy control group (p value 0.003). Additionally there was a statistically significant negative correlation identified between serum FGF-2 levels and CARS score for all subjects (r = -0.300; p = 0.02). In conclusion, FGF-2 may contribute to the etiopathogenesis of ASD. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Polypeptides having catalase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ye; Duan, Junxin; Zhang, Yu; Tang, Lan

    2017-05-02

    Provided are isolated polypeptides having catalase activity and polynucleotides encoding the polypeptides. Also provided are nucleic acid constructs, vectors and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  18. Polypeptides having xylanase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Spodsberg, Nikolaj

    2018-02-06

    The present invention relates to isolated polypeptides having xylanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  19. Application of chitosan scaffolds on vascular endothelial growth factor and fibroblast growth factor 2 expressions in tissue engineering principles

    Directory of Open Access Journals (Sweden)

    Ariyati Retno Pratiwi

    2015-12-01

    Full Text Available Background: Tissue engineering has given satisfactory results as biological tissue substitutes to restore, replace, or regenerate tissues that have a defect. Chitosan is an organic biomaterial often used in the biomedical field. Chitosan has biocompatible, antifungal, and antibacterial properties. Chitosan is osteoconductive, suitable for bone regeneration applications. Bone defect healing begins with inflammatory phase as a response to the presence of vascular injury, so new vascularization is required. Vascular endothelial growth factor (VEGF and basic fibroblast growth factor-2 (FGF2 are indicators of the beginning of bone regeneration process, playing an important role in angiogenesis. Purpose: This research was aimed to determine the effects of chitosan scaffold application on the expressions of VEGF and FGF2 in tissue engineering principles. Method: Chitosan was dissolved in CH3COOH and NaOH to form a gel. Chitosan gel was then printed in mould to freeze dry for 24 hours. Those rats with defected bones were divided into two groups. Group 1 was the control group which defected bones were not administrated with chitosan scaffolds. Group 2 was the treatment group which defected bones were administrated with chitosan scaffolds. Those rats were sacrificed on day 14. Tissue preparations were made, and then immunohistochemical staining was conducted. Finally, a statistical analysis was conducted using Kruskal Wallis test. Result: There was no significant difference in the expressions of VEGF and FGF2 between the control group and the treatment group (p>0.05. Conclusion: Chitosan scaffolds do not affect the expressions of VEGF and FGF2 during bone regeneration process on day 14 in tissue engineering principles

  20. Enhancement of insulin-like growth factor 2 receptors in glioblastoma

    International Nuclear Information System (INIS)

    Sara, V.; Prisell, Per; Sjoegren, Barbro; Enberg, Goesta

    1986-01-01

    The somatomedins (IGF-1/IGF-2) are a family of growth-promoting hormones which have been identified in the human central nervous system where their specific receptors are distributed. The present study identified somatomedin receptors in glioblastoma and compared them with those found in normal brain. A significant enhancement in the binding of 125 1-IGF-2 but not 125 1-IGF-1 to glioblastoma membranes was found. A fourfold increase in IGF-2 receptor concentration was observed. These findings indicate enhanced expression of the IGF-2 receptor in glioblastoma. (author)

  1. Enhancement of insulin-like growth factor 2 receptors in glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Sara, V; Prisell, P; Sjoegren, B; Persson, L; Boethius, J; Enberg, G

    1986-09-01

    The somatomedins (IGF-1/IGF-2) are a family of growth-promoting hormones which have been identified in the human central nervous system where their specific receptors are distributed. The present study identified somatomedin receptors in glioblastoma and compared them with those found in normal brain. A significant enhancement in the binding of /sup 125/1-IGF-2 but not /sup 125/1-IGF-1 to glioblastoma membranes was found. A fourfold increase in IGF-2 receptor concentration was observed. These findings indicate enhanced expression of the IGF-2 receptor in glioblastoma. 14 refs.

  2. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Tomblin, Justin K.; Salisbury, Travis B.

    2014-01-01

    Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR

  3. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tomblin, Justin K.; Salisbury, Travis B., E-mail: salisburyt@marshall.edu

    2014-01-17

    Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR.

  4. RANTES and fibroblast growth factor 2 in jawbone cavitations: triggers for systemic disease?

    Directory of Open Access Journals (Sweden)

    Lechner J

    2013-04-01

    Full Text Available Johann Lechner,1 Volker von Baehr2 1Clinic for Integrative Dentistry, Munich, Germany; 2Compartment of Immunology and Allergology on Institute for Medical Diagnostics in MVZ GbR, Berlin, Germany Background: Jawbone cavitations (JC are hollow dead spaces in jawbones with dying or dead bone marrow. These areas are defined as fatty degenerative osteonecrosis of the jawbone or neuralgia-inducing cavitational osteonecrosis and may produce facial pain. These afflictions have been linked to the immune system and chronic illnesses. Surgical debridement of JC is reported to lead to an improvement in immunological complaints, such as rheumatic, allergic, and other inflammatory diseases (ID. Little is known about the underlying cause/effect relationship. Objectives: JC bone samples were analyzed to assess the expression and quantification of immune modulators that can play a role in the pathogenesis of IDs. The study supports a potential mechanism where JC is a mediating link in IDs. Materials and methods: Samples of fatty softened bone taken from JCs were extracted from 31 patients. The specimens were analyzed by bead-based multiplex technology and tested for seven immune messengers. Results: Regulated upon activation, normal T-cell expressed, and secreted (RANTES and fibroblast growth factor (FGF-2 were found at high levels in the JCs tested. Other cytokines could not be detected at excessive levels. Discussion: The study confirms that JC is able to produce inflammatory messengers, primarily RANTES, and, secondarily, FGF-2. Both are implicated in many serious illnesses. The excessive levels of RANTES/FGF-2 in JC patients with amyotrophic lateral sclerosis, multiple sclerosis, rheumatoid arthritis, and breast cancer are compared to levels published in medical journals. Levels detected in JCs are higher than in the serum and cerebrospinal fluid of amyotrophic lateral sclerosis and multiple sclerosis patients and four-fold higher than in breast cancer

  5. Paracrine Pathways in Uterine Leiomyoma Stem Cells Involve Insulinlike Growth Factor 2 and Insulin Receptor A.

    Science.gov (United States)

    Moravek, Molly B; Yin, Ping; Coon, John S; Ono, Masanori; Druschitz, Stacy A; Malpani, Saurabh S; Dyson, Matthew T; Rademaker, Alfred W; Robins, Jared C; Wei, Jian-Jun; Kim, J Julie; Bulun, Serdar E

    2017-05-01

    Uterine leiomyomas (fibroids) are the most common benign tumors in women. Recently, three populations of leiomyoma cells were discovered on the basis of CD34 and CD49b expression, but molecular differences between these populations remain unknown. To define differential gene expression and signaling pathways in leiomyoma cell populations. Cells from human leiomyoma tissue were sorted by flow cytometry into three populations: CD34+/CD49b+, CD34+/CD49b-, and CD34-/CD49b-. Microarray gene expression profiling and pathway analysis were performed. To investigate the insulinlike growth factor (IGF) pathway, real-time quantitative polymerase chain reaction, immunoblotting, and 5-ethynyl-2'-deoxyuridine incorporation studies were performed in cells isolated from fresh leiomyoma. Research laboratory. Eight African American women. None. Gene expression patterns, cell proliferation, and differentiation. A total of 1164 genes were differentially expressed in the three leiomyoma cell populations, suggesting a hierarchical differentiation order whereby CD34+/CD49b+ stem cells differentiate to CD34+/CD49b- intermediary cells, which then terminally differentiate to CD34-/CD49b- cells. Pathway analysis revealed differential expression of several IGF signaling pathway genes. IGF2 was overexpressed in CD34+/CD49b- vs CD34-/CD49b- cells (83-fold; P leiomyoma stem cell proliferation and may represent paracrine signaling between leiomyoma cell types. Therapies targeting the IGF pathway should be investigated for both treatment and prevention of leiomyomas. Copyright © 2017 by the Endocrine Society

  6. Brittlestars contain highly sulfated chondroitin sulfates/dermatan sulfates that promote fibroblast growth factor 2-induced cell signaling.

    Science.gov (United States)

    Ramachandra, Rashmi; Namburi, Ramesh B; Ortega-Martinez, Olga; Shi, Xiaofeng; Zaia, Joseph; Dupont, Sam T; Thorndyke, Michael C; Lindahl, Ulf; Spillmann, Dorothe

    2014-02-01

    Glycosaminoglycans (GAGs) isolated from brittlestars, Echinodermata class Ophiuroidea, were characterized, as part of attempts to understand the evolutionary development of these polysaccharides. A population of chondroitin sulfate/dermatan sulfate (CS/DS) chains with a high overall degree of sulfation and hexuronate epimerization was the major GAG found, whereas heparan sulfate (HS) was below detection level. Enzymatic digestion with different chondroitin lyases revealed exceptionally high proportions of di- and trisulfated CS/DS disaccharides. The latter unit appears much more abundant in one of four individual species of brittlestars, Amphiura filiformis, than reported earlier in other marine invertebrates. The brittlestar CS/DS was further shown to bind to growth factors such as fibroblast growth factor 2 and to promote FGF-stimulated cell signaling in GAG-deficient cell lines in a manner similar to that of heparin. These findings point to a potential biological role for the highly sulfated invertebrate GAGs, similar to those ascribed to HS in vertebrates.

  7. Chimeric polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Science.gov (United States)

    Wogulis, Mark; Sweeney, Matthew; Heu, Tia

    2017-06-14

    The present invention relates to chimeric GH61 polypeptides having cellulolytic enhancing activity. The present invention also relates to polynucleotides encoding the chimeric GH61 polypeptides; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the chimeric GH61 polypeptides.

  8. Polypeptides having xylanase activity and polynucleotides encoding same

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    Spodsberg, Nikolaj; Shaghasi, Tarana

    2017-06-20

    The present invention relates to polypeptides having xylanase activity, catalytic domains, and carbohydrate binding domains, and polynucleotides encoding the polypeptides, catalytic domains, and carbohydrate binding domains. The present invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains, and carbohydrate binding domains.

  9. Beta-glucosidase variants and polynucleotides encoding same

    Science.gov (United States)

    Wogulis, Mark; Harris, Paul; Osborn, David

    2017-06-27

    The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

  10. Polypeptides having beta-glucosidase activity and polynucleotides encoding same

    Science.gov (United States)

    Harris, Paul; Golightly, Elizabeth

    2012-11-27

    The present invention relates to isolated polypeptides having beta-glucosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  11. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Science.gov (United States)

    Morant, Marc D.; Harris, Paul

    2015-10-13

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  12. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Science.gov (United States)

    Maiyuran, Suchindra; Kramer, Randall; Harris, Paul

    2013-10-29

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  13. Polynucleotides encoding polypeptides having beta-glucosidase activity

    Science.gov (United States)

    Harris, Paul; Golightly, Elizabeth

    2010-03-02

    The present invention relates to isolated polypeptides having beta-glucosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  14. Biologic Roles of Estrogen Receptor-β and Insulin-Like Growth Factor-2 in Triple-Negative Breast Cancer

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    Nalo Hamilton

    2015-01-01

    Full Text Available Triple-negative breast cancer (TNBC occurs in 10–15% of patients yet accounts for almost half of all breast cancer deaths. TNBCs lack expression of estrogen and progesterone receptors and HER-2 overexpression and cannot be treated with current targeted therapies. TNBCs often occur in African American and younger women. Although initially responsive to some chemotherapies, TNBCs tend to relapse and metastasize. Thus, it is critical to find new therapeutic targets. A second ER gene product, termed ERβ, in the absence of ERα may be such a target. Using human TNBC specimens with known clinical outcomes to assess ERβ expression, we find that ERβ1 associates with significantly worse 5-year overall survival. Further, a panel of TNBC cell lines exhibit significant levels of ERβ protein. To assess ERβ effects on proliferation, ERβ expression in TNBC cells was silenced using shRNA, resulting in a significant reduction in TNBC proliferation. ERβ-specific antagonists similarly suppressed TNBC growth. Growth-stimulating effects of ERβ may be due in part to downstream actions that promote VEGF, amphiregulin, and Wnt-10b secretion, other factors associated with tumor promotion. In vivo, insulin-like growth factor-2 (IGF-2, along with ERβ1, is significantly expressed in TNBC and stimulates high ERβ mRNA in TNBC cells. This work may help elucidate the interplay of metabolic and growth factors in TNBC.

  15. Fibroblast growth factor 2 and DNA repair involvement in the keratinocyte stem cells response to ionizing radiation

    International Nuclear Information System (INIS)

    Harfouche, L'Emira Ghida

    2010-02-01

    Keratinocyte stem cells (KSCs) from the human inter follicular epidermis are regarded as the major target to radiation during radiotherapy. We found herein that KSCs are more resistant to ionizing radiation than their direct progeny, and presented more rapid DNA damage repair kinetics than the progenitors. Furthermore, we provided evidence describing the effect of fibroblast growth factor 2 (FGF2) signaling on the ability of KSCs and progenitors to repair damaged DNA. Despite our knowledge of the fact, that FGF is an anti-apoptotic factor in multiple cell types, the direct link between DNA repair and FGF2 signaling has rarely been shown. Existence of such link is an important issue with implications not only to stem cell field but also to cancer therapy. (author)

  16. Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2

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    Jung-Seok Lee

    2018-04-01

    Full Text Available This study aimed to determine the cellular characteristics and behaviors of human bone marrow stromal cells (hBMSCs expanded in media in a hypoxic or normoxic condition and with or without fibroblast growth factor-2 (FGF-2 treatment. hBMSCs isolated from the vertebral body and expanded in these four groups were evaluated for cellular proliferation/migration, colony-forming units, cell-surface characterization, in vitro differentiation, in vivo transplantation, and gene expression. Culturing hBMSCs using a particular environmental factor (hypoxia and with the addition of FGF-2 increased the cellular proliferation rate while enhancing the regenerative potential, modulated the multipotency-related processes (enhanced chondrogenesis-related processes/osteogenesis, but reduced adipogenesis, and increased cellular migration and collagen formation. The gene expression levels in the experimental samples showed activation of the hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with this not being affected by the addition of FGF-2. The concurrent application of hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be used in clinical applications associated with bone tissue engineering, due to the enhancement of cellular proliferation and regenerative potential. Keywords: Bone marrow stromal cells, Hypoxia, Fibroblast growth factor, Tissue regeneration, Microenvironment interactions

  17. Concentration- and time-dependent response of human gingival fibroblasts to fibroblast growth factor 2 immobilized on titanium dental implants

    Directory of Open Access Journals (Sweden)

    Ma Q

    2012-04-01

    Full Text Available Qianli Ma1*, Wei Wang1*, Paul K Chu2, Shenglin Mei1,2, Kun Ji3, Lei Jin4, Yumei Zhang11Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China; 2Department of Physics and Materials Science, City University of Hong Kong, Kowloon, Hong Kong, People's Republic of China; 3Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China; 4Stomatology Department, Jinling Hospital, School of Medicine, Southern Medical University, Nanjing, People's Republic of China*These authors contributed equally to this workBackground: Titanium (Ti implants are widely used clinically, but peri-implantitis remains one of the most common and serious complications. Healthy integration between gingival tissue and the implant surface is critical to long-term success in dental implant therapy. The objective of this study was to investigate how different concentrations of immobilized fibroblast growth factor 2 (FGF2 on the titania nanotubular surface influence the response of human gingival fibroblasts (HGFs.Methods: Pure Ti metal was anodized at 20 V to form a vertically organized titanium dioxide nanotube array on which three concentrations of FGF2 (250 ng/mL, 500 ng/mL, or 1000 ng/mL were immobilized by repeated lyophilization. Surface topography was observed and FGF2 elution was detected using enzyme-linked immunosorbent assay. The bioactivity changes of dissolvable immobilized FGF2 were measured by methyl-thiazolyl-tetrazolium assay. Behavior of HGFs was evaluated using adhesion and methyl-thiazolyl-tetrazolium bromide assays.Results: The FGF2 remained for several days on the modified surface on which HGFs were cultured. Over 90% of the dissolvable immobilized FGF2 had been eluted by Day 9, whereas the FGF2 activity was found to diminish gradually from Day 1 to Day 9. The titania nanotubular surface with an optimal preparing

  18. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

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    Ribeiro-Resende Victor

    2012-07-01

    Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

  19. Osteoconductivity and Biodegradability of Collagen Scaffold Coated with Nano-β-TCP and Fibroblast Growth Factor 2

    Directory of Open Access Journals (Sweden)

    Asako Ibara

    2013-01-01

    Full Text Available Nanoparticle bioceramics have become anticipated for biomedical applications. Highly bioactive and biodegradable scaffolds would be developed using nanoparticles of β-tricalcium phosphate (β-TCP. We prepared collagen scaffolds coated by nano-β-TCP and fibroblast growth factor 2 (FGF2 and evaluated the effects on new bone augmentation and biodegradation. The collagen sponge was coated with the nano-TCP dispersion and freeze-dried. Scaffold was characterized by SEM, TEM, XRD, compressive testing and cell seeding. Subsequently, the nano-β-TCP/collagen scaffold, collagen sponge, and each material loaded with FGF2 were implanted on rat cranial bone. As a control, no implantation was performed. Nano-TCP particles were found to be attached to the fibers of the collagen sponge by SEM and TEM observations. Scaffold coated with nano-TCP showed higher compressive strength and cytocompatibility. In histological evaluations at 10 days, inflammatory cells were rarely seen around the residual scaffold, suggesting that the nano-TCP material possesses good tissue compatibility. At 35 days, bone augmentation and scaffold degradation in histological samples receiving nano-β-TCP scaffold were significantly greater than those in the control. By loading of FGF2, advanced bone formation is facilitated, indicating that a combination with FGF2 would be effective for bone tissue engineering.

  20. Early-life exposure to fibroblast growth factor-2 facilitates context-dependent long-term memory in developing rats.

    Science.gov (United States)

    Graham, Bronwyn M; Richardson, Rick

    2010-06-01

    Fibroblast growth factor-2 (FGF2) is a potent neurotrophic factor that is involved in brain development and the formation of long-term memory. It has recently been shown that acute FGF2, administered at the time of learning, enhances long-term memory for contextual fear conditioning as well as extinction of conditioned fear in developing rats. As other research has shown that administering FGF2 on the first day of life leads to long-term morphological changes in the hippocampus, in the present study we investigated whether early life exposure to FGF2 affects contextual fear conditioning, and renewal following extinction, later in life. Experiment 1 demonstrated that a single injection of FGF2 on Postnatal Day (PND) 1 did not lead to any detectable changes in contextual fear conditioning in PND 16 or PND 23 rats. Experiments 2 and 3 demonstrated that 5 days of injections of FGF2 (from PND 1-5) facilitated contextual fear conditioning in PND 16 and PND 23 rats. Experiment 4 demonstrated that the observed facilitation of memory was not due to FGF2 increasing rats' sensitivity to foot shock. Experiment 5 showed that early life exposure to FGF2 did not affect learning about a discrete conditioned stimulus, but did allow PND 16 rats to use contextual information in more complex ways, leading to context-dependent extinction of conditioned fear. These results further implicate FGF2 as a critical signal involved in the development of learning and memory.

  1. Fibroblast growth factor-2 induces osteogenic differentiation through a Runx2 activation in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Nakahara, Takehiro; Sato, Hiroko; Shimizu, Takehisa; Tanaka, Toru; Matsui, Hiroki; Kawai-Kowase, Keiko; Sato, Mahito; Iso, Tatsuya; Arai, Masashi [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Kurabayashi, Masahiko, E-mail: mkuraba@med.gunma-u.ac.jp [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511 (Japan)

    2010-04-02

    Expression of bone-associated proteins and osteoblastic transcription factor Runx2 in arterial cells has been implicated in the development of vascular calcification. However, the signaling upstream of the Runx2-mediated activation of osteoblastic program in vascular smooth muscle cells (VSMC) is poorly understood. We examined the effects of fibroblast growth factor-2 (FGF-2), an important regulator of bone formation, on osteoblastic differentiation of VSMC. Stimulation of cultured rat aortic SMC (RASMC) with FGF-2 induced the expression of the osteoblastic markers osteopontin (OPN) and osteocalcin. Luciferase assays showed that FGF-2 induced osteocyte-specific element (OSE)-dependent transcription. Downregulation of Runx2 by siRNA repressed the basal and FGF-2-stimulated expression of the OPN gene in RASMC. FGF-2 produced hydrogen peroxide in RASMC, as evaluated by fluorescent probe. Induction of OPN expression by FGF-2 was inhibited not only by PD98059 (MEK1 inhibitor) and PP1 (c-Src inhibitor), but also by an antioxidant, N-acetyl cysteine. Nuclear extracts from FGF-2-treated RASMC exhibited increased DNA-binding of Runx2 to its target sequence. Immunohistochemistry of human coronary atherectomy specimens and calcified aortic tissues showed that expression of FGF receptor-1 and Runx2 was colocalized. In conclusion, these results suggest that FGF-2 plays a role in inducing osteoblastic differentiation of VSMC by activating Runx2 through mitogen-activated protein kinase (MAPK)-dependent- and oxidative stress-sensitive-signaling pathways.

  2. Up-regulation of insulin-like growth factor 2 by ketamine requires glycogen synthase kinase-3 inhibition

    Science.gov (United States)

    Grieco, Steven F.; Cheng, Yuyan; Eldar-Finkelman, Hagit; Jope, Richard S.; Beurel, Eléonore

    2016-01-01

    An antidepressant dose of the rapidly-acting ketamine inhibits glycogen synthase kinase-3 (GSK3) in mouse hippocampus, and this inhibition is required for the antidepressant effect of ketamine in learned helplessness depression-like behavior. Here we report that treatment with an antidepressant dose of ketamine (10 mg/kg) increased expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect that required ketamine-induced inhibition of GSK3. Ketamine also inhibited hippocampal GSK3 and increased expression of hippocampal IGF2 in mice when administered after the induction of learned helplessness. Treatment with the specific GSK3 inhibitor L803-mts was sufficient to up-regulate hippocampal IGF2 expression. Administration of IGF2 siRNA reduced ketamine's antidepressant effect in the learned helplessness paradigm. Mice subjected to the learned helplessness paradigm were separated into two groups, those that were resilient (non-depressed) and those that were susceptible (depressed). Non-depressed resilient mice displayed higher expression of IGF2 than susceptible mice. These results indicate that IGF2 contributes to ketamine's antidepressant effect and that IGF2 may confer resilience to depression-like behavior. PMID:27542584

  3. Insulin-like growth factor 2 (IGF2) modulates murine hematopoietic stem cell maintenance through upregulation of p57

    Science.gov (United States)

    Thomas, Dolly D.; Sommer, Andreia Gianotti; Balazs, Alejandro B.; Beerman, Isabel; Murphy, George J.; Rossi, Derrick; Mostoslavsky, Gustavo

    2017-01-01

    Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found Insulin-like growth factor 2 (IGF2) to be predominantly expressed within long-term HSC. This study examines IGF2 expression patterns and the effects of the gene in HSC. Through the overexpression and knockdown of IGF2 within purified HSC, we demonstrate that IGF2 expression increases HSC-derived multilineage colonies in vitro and enhances hematopoietic contribution in vivo upon competitive bone marrow transplantation. The effects of IGF2 are mediated by direct upregulation of the CDKi p57, exclusively within long-term HSC, via activation of the PI3K-Akt pathway. Increased expression of p57 resulted in a concomitant increase of HSC in the G0/G1 stage of the cell cycle. Analysis of genomic DNA methylation revealed that HSC exhibited a hypomethylated state within the promoter region of the CDKN1C (p57) gene, providing a potential mechanism for the exclusive effects of IGF2 within HSC. Our studies demonstrate a novel role for IGF2 in regulating HSC cell cycle and illustrate potential novel therapeutic targets for hematological diseases. PMID:26872540

  4. Effects of fibroblast growth factor-2 on the expression and regulation of chemokines in human dental pulp cells.

    Science.gov (United States)

    Kim, Young-Suk; Min, Kyung-San; Jeong, Dong-Ho; Jang, Jun-Hyeog; Kim, Hae-Won; Kim, Eun-Cheol

    2010-11-01

    Fibroblast growth factor-2 (FGF-2) participates in both hematopoiesis and osteogenesis; however, the effects of FGF-2 on chemokines during odontoblastic differentiation have not been reported. This study investigated whether human dental pulp cells (HDPCs) treated with FGF-2 could express chemokines during differentiation into odontoblastic cells and sought to identify its underlying mechanism of action. To analyze differentiation, we measured alkaline phosphatase (ALP) activity, calcified nodule formation by alizarin red staining, and marker RNA (mRNA) expression by reverse-transcriptase polymerase chain reaction (RT-PCR). Expression of chemokines, such as interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and MIP-3α, were evaluated by RT-PCR. ALP activity, the mineralization, and mRNA expression for odontoblastic markers were enhanced by FGF-2 in HDPCs. FGF-2 also up-regulated the expression of IL-6, IL-8, MCP-1, MIP-1α, and MIP-3α mRNAs, which were attenuated by inhibitors of p38, ERK1/2 and p38 MAP kinases, protein kinase C, phosphoinositide-3 kinase, and NF-κB. Taken together, these data suggest that FGF-2 plays a role not only as a differentiation inducing factor in the injury repair processes of pulpal tissue but also as a positive regulator of chemokine expression, which may help in tissue engineering and pulp regeneration using HDPCs. However, the fate of odontoblastic or osteoblastic differentiation, effective local delivery for FGF-2, interaction of chemotatic and odontogenic factors, and other limitations will need to be overcome before a major modality for the treatment of pulp disease. Copyright © 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Low Endogenous Fibroblast Growth Factor 2 Levels Are Associated With Heightened Conditioned Fear Expression in Rats and Humans.

    Science.gov (United States)

    Graham, Bronwyn M; Zagic, Dino; Richardson, Rick

    2017-10-15

    Hippocampal concentrations of the neurotrophic factor fibroblast growth factor 2 (FGF2) are negatively associated with the expression of fear following conditioning in rats. Heightened conditioned fear expression may be a prospective risk factor for the development of human anxiety and trauma disorders. However, the relationship between conditioned fear expression and FGF2 is yet to be established in humans. Using a cross-species approach, we first investigated the relationship between serum concentrations of FGF2 and individual differences in conditioned fear expression in rats (n = 19). We then subjected 88 human participants, who were recruited from university and community advertisements, to a differential fear conditioning procedure and assessed the relationship between salivary concentrations of FGF2 and fear expression to a conditioned stimulus (CS) (a stimulus paired with a shock) and a CS that was never paired with shock. Rats with low serum levels of FGF2 exhibited significantly more freezing than rats with high serum levels of FGF2. Similarly, relative to those with high salivary FGF2, human participants with low salivary FGF2 exhibited significantly heightened skin conductance responses to the CS without shock during fear conditioning and to both the CS with shock and CS without shock during fear recall. These studies establish that peripheral markers of FGF2 concentrations are negatively associated with fear expression in both rats and humans. To the extent that conditioned fear expression predicts anxiety and trauma disorder vulnerability, FGF2 may be a clinically useful biomarker in the prediction and eventual prevention of these disorders. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Evidence for fibroblast growth factor-2 as a mediator of amphetamine-enhanced motor improvement following stroke.

    Directory of Open Access Journals (Sweden)

    William A Wolf

    Full Text Available Previously we have shown that addition of amphetamine to physical therapy results in enhanced motor improvement following stroke in rats, which was associated with the formation of new motor pathways from cortical projection neurons of the contralesional cortex. It is unclear what mechanisms are involved, but amphetamine is known to induce the neuronal release of catecholamines as well as upregulate fibroblast growth factor-2 (FGF-2 expression in the brain. Since FGF-2 has been widely documented to stimulate neurite outgrowth, the present studies were undertaken to provide evidence for FGF-2 as a neurobiological mechanism underlying amphetamine-induced neuroplasticity. In the present study rats that received amphetamine plus physical therapy following permanent middle cerebral artery occlusion exhibited significantly greater motor improvement over animals receiving physical therapy alone. Amphetamine plus physical therapy also significantly increased the number of FGF-2 expressing pyramidal neurons of the contralesional cortex at 2 weeks post-stroke and resulted in significant axonal outgrowth from these neurons at 8 weeks post-stroke. Since amphetamine is a known releaser of norepinephrine, in vitro analyses focused on whether noradrenergic stimulation could lead to neurite outgrowth in a manner requiring FGF-2 activity. Primary cortical neurons did not respond to direct stimulation by norepinephrine or amphetamine with increased neurite outgrowth. However, conditioned media from astrocytes exposed to norepinephrine or isoproterenol (a beta adrenergic agonist significantly increased neurite outgrowth when applied to neuronal cultures. Adrenergic agonists also upregulated FGF-2 expression in astrocytes. Pharmacological analysis indicated that beta receptors and alpha1, but not alpha2, receptors were involved in both effects. Antibody neutralization studies demonstrated that FGF-2 was a critical contributor to neurite outgrowth induced by

  7. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Boér K

    2016-10-01

    Full Text Available Katalin Boér Department of Medical Oncology, Szent Margit Hospital, Budapest, Hungary Abstract: Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6 inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2-ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant

  8. [Liposome-mediated glial growth factor 2 gene therapy in brain injury: an experimental study with rats].

    Science.gov (United States)

    Xue, Ya-jun; Dong, Yan; Han, Xi; Wei, Mei-yang; Ge, Jun-hui; Cai, Ru-jue; Hu, Guo-han; Luo, Chun; Zhu, Cheng; Lu, Yi-cheng

    2006-09-05

    To explore the protective effect of glial growth factor-2 (GGF2) on brain injury. Thirty-four SD rats underwent lateral fluid percussion to establish brain injury models and then were randomly divided into 4 groups: treatment group (n = 10, the plasmid pEGFP-N1-GGF2 mixed with liposome was injected into the brain tissue directly), vector control group (n = 10, the vector pEGFP-N1 mixed with liposome was injected into the brain tissue directly), liposome control group (n = 10, liposome was injected), and sham operation group (n = 4). Three assessment tasks were performed for neurobehavioral evaluation: Clivas Test, Beam Balance Test and Beam Walking Test. 10 days after brain injury, the rats were sacrificed and their brains were embedded in paraffin for HE staining, Nissle staining and immunohistochemical examination of MBP, NSE, and GFAP. The Clivas test score of the treatment group was 66.25 +/- 3.54, significantly higher than those of the vector control group and. liposome control group (58.31 +/- 3.72 and 57.21 +/- 3.93 respectively, both P beam test score of the treatment group was 2.59 +/- 0.21, significantly lower than those the vector control group and liposome control group (3.41 +/- 0.25 and 3.24 +/- 0.22 respectively, both P walking test score of the treatment group was 20.15 +/- 2.59, significantly lower than those of control group and liposome control group (27.00 +/- 3.47 and 27.80 +/- 3.00 respectively, both P beam walking test was the greatest. The neuron number in the external granular layer and external pyramidal layer in cortex of the treatment group was 98 +/- 10, significantly more than those of the vector control group and liposome group (75 +/- 7 and 67 +/- 8, both P < 0.05). The neuron number in the internal pyramidal layer in cortex of the treatment group was 37 +/- 4, significantly more than those of the vector control group and liposome group (19 +/- 3 and 23 +/- 4 respectively, both P < 0.05). The neuron number in the CA1 region in

  9. Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

    Science.gov (United States)

    Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

    2007-04-01

    Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

  10. Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb.

    Science.gov (United States)

    Wang, Kimberley C W; Zhang, Lei; McMillen, I Caroline; Botting, Kimberley J; Duffield, Jaime A; Zhang, Song; Suter, Catherine M; Brooks, Doug A; Morrison, Janna L

    2011-10-01

    Reduced growth in fetal life together with accelerated growth in childhood, results in a ~50% greater risk of coronary heart disease in adult life. It is unclear why changes in patterns of body and heart growth in early life can lead to an increased risk of cardiovascular disease in adulthood. We aimed to investigate the role of the insulin-like growth factors in heart growth in the growth-restricted fetus and lamb. Hearts were collected from control and placentally restricted (PR) fetuses at 137-144 days gestation and from average (ABW) and low (LBW) birth weight lambs at 21 days of age. We quantified cardiac mRNA expression of IGF-1, IGF-2 and their receptors, IGF-1R and IGF-2R, using real-time RT-PCR and protein expression of IGF-1R and IGF-2R using Western blotting. Combined bisulphite restriction analysis was used to assess DNA methylation in the differentially methylated region (DMR) of the IGF-2/H19 locus and of the IGF-2R gene. In PR fetal sheep, IGF-2, IGF-1R and IGF-2R mRNA expression was increased in the heart compared to controls. LBW lambs had a greater left ventricle weight relative to body weight as well as increased IGF-2 and IGF-2R mRNA expression in the heart, when compared to ABW lambs. No changes in the percentage of methylation of the DMRs of IGF-2/H19 or IGF-2R were found between PR and LBW when compared to their respective controls. In conclusion, a programmed increased in cardiac gene expression of IGF-2 and IGF-2R may represent an adaptive response to reduced substrate supply (e.g. glucose and/or oxygen) in order to maintain heart growth and may be the underlying cause for increased ventricular hypertrophy and the associated susceptibility of cardiomyocytes to ischaemic damage later in life.

  11. Interference of tolerance to human gamma globulin by synthetic polynucleotides

    International Nuclear Information System (INIS)

    Rey, O.A.; Azar, M.M.

    1975-01-01

    A complex of polyadenylic-polyuridylic acids effectively inhibits the in vivo production of immunologic tolerance to human gamma globulin in mice. Moreover, this effect can be obtained only when the polynucleotide complex is given within 4 hr after antigen administration. Reconstitution of irradiated mice with combinations of T and B cells originating from tolerant or previously untreated mice demonstrates that poly A:U is responsible for the adjuvant effect observed. Poly A:U exerts its adjuvant effect primarily upon T cells, while B cells remain essentially uninfluenced by the polynucleotides

  12. Paternally expressed, imprinted insulin-like growth factor-2 in chorionic villi correlates significantly with birth weight.

    Directory of Open Access Journals (Sweden)

    Charalambos Demetriou

    Full Text Available Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight.The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight.Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS (n = 260 collected at 11-13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors.Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively. No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3.6 × 10(-7.Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. This research reveals an imprinted, parentally driven rheostat for in utero growth.

  13. Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells

    Czech Academy of Sciences Publication Activity Database

    Dvořák, Petr; Dvořáková, D.; Košková, S.; Vidinská, M.; Najvirtová, M.; Krekáč, D.; Hampl, Aleš

    2005-01-01

    Roč. 23, č. 8 (2005), s. 1200-1211 ISSN 1066-5099 R&D Projects: GA ČR(CZ) GA301/03/1122; GA ČR(CZ) GA305/05/0434; GA MŠk(CZ) LN00A065 Institutional research plan: CEZ:AV0Z50390512 Keywords : growth factor * human embryonic stem cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.094, year: 2005

  14. Peptides derived from specific interaction sites of the fibroblast growth factor 2 - FGF receptor complexes induce receptor activation and signaling

    DEFF Research Database (Denmark)

    Manfè, Valentina; Kochoyan, Artur; Bock, Elisabeth

    2010-01-01

    J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06718.x Abstract Basic fibroblast growth factor (FGF2, bFGF) is the most extensively studied member of the FGF family and is involved in neurogenesis, differentiation, neuroprotection, and synaptic plasticity in the CNS. FGF2 executes its pleiotropic...... biologic actions by binding, dimerizing, and activating FGF receptors (FGFRs). The present study reports the physiologic impact of various FGF2-FGFR1 contact sites employing three different synthetic peptides, termed canofins, designed based on structural analysis of the interactions between FGF2 and FGFR1...

  15. Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Doherty, Jennifer A; Van Den Berg, David J

    2011-01-01

    The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial...... disease, whereas five tSNPs in IGF2 were associated with risk of invasive epithelial ovarian cancer at Pcases and 5382 additional controls and were able to independently replicate our initial...... findings. In the combined set of studies, rs4320932 was associated with a 13% decreased risk of ovarian cancer per copy of the minor allele carried (95% confidence interval 0.81–0.93, P-trend=7.4 × 10-5). No heterogeneity of effect across study centers was observed (phet=0.25). IGF2 is emerging...

  16. A role for Insulin-like growth factor 2 in specification of the fast skeletal muscle fibre

    Directory of Open Access Journals (Sweden)

    Ting Tao

    2007-06-01

    Full Text Available Abstract Background Fibre type specification is a poorly understood process beginning in embryogenesis in which skeletal muscle myotubes switch myosin-type to establish fast, slow and mixed fibre muscle groups with distinct function. Growth factors are required to establish slow fibres; it is unknown how fast twitch fibres are specified. Igf-2 is an embryonically expressed growth factor with established in vitro roles in skeletal muscle. Its localisation and role in embryonic muscle differentiation had not been established. Results Between E11.5 and E15.5 fast Myosin (FMyHC localises to secondary myotubes evenly distributed throughout the embryonic musculature and gradually increasing in number so that by E15.5 around half contain FMyHC. The Igf-2 pattern closely correlates with FMyHC from E13.5 and peaks at E15.5 when over 90% of FMyHC+ myotubes also contain Igf-2. Igf-2 lags FMyHC and it is absent from muscle myotubes until E13.5. Igf-2 strongly down-regulates by E17.5. A striking feature of the FMyHC pattern is its increased heterogeneity and attenuation in many fibres from E15.5 to day one after birth (P1. Transgenic mice (MIG which express Igf-2 in all of their myotubes, have increased FMyHC staining, a higher proportion of FMyHC+ myotubes and loose their FMyHC staining heterogeneity. In Igf-2 deficient mice (MatDi FMyHC+ myotubes are reduced to 60% of WT by E15.5. In vitro, MIG induces a 50% excess of FMyHC+ and a 30% reduction of SMHyC+ myotubes in C2 cells which can be reversed by Igf-2-targeted ShRNA resulting in 50% reduction of FMyHC. Total number of myotubes was not affected. Conclusion In WT embryos the appearance of Igf-2 in embryonic myotubes lags FMyHC, but by E15.5 around 45% of secondary myotubes contain both proteins. Forced expression of Igf-2 into all myotubes causes an excess, and absence of Igf-2 suppresses, the FMyHC+ myotube component in both embryonic muscle and differentiated myoblasts. Igf-2 is thus required, not for

  17. Insulin Like Growth Factor 2 Expression in the Rat Brain Both in Basal Condition and following Learning Predominantly Derives from the Maternal Allele.

    Directory of Open Access Journals (Sweden)

    Xiaojing Ye

    Full Text Available Insulin like growth factor 2 (Igf2 is known as a maternally imprinted gene involved in growth and development. Recently, Igf2 was found to also be regulated and required in the adult rat hippocampus for long-term memory formation, raising the question of its allelic regulation in adult brain regions following experience and in cognitive processes. We show that, in adult rats, Igf2 is abundantly expressed in brain regions involved in cognitive functions, like hippocampus and prefrontal cortex, compared to the peripheral tissues. In contrast to its maternal imprinting in peripheral tissues, Igf2 is mainly expressed from the maternal allele in these brain regions. The training-dependent increase in Igf2 expression derives proportionally from both parental alleles, and, hence, is mostly maternal. Thus, Igf2 parental expression in the adult rat brain does not follow the imprinting rules found in peripheral tissues, suggesting differential expression regulation and functions of imprinted genes in the brain.

  18. Polypeptides having beta-glucosidase activity and polynucleotides encoding the same

    Science.gov (United States)

    Brown, Kimberly; Harris, Paul

    2013-12-17

    The present invention relates to isolated polypeptides having beta-glucosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  19. Vasohibin 2 promotes human luminal breast cancer angiogenesis in a non-paracrine manner via transcriptional activation of fibroblast growth factor 2.

    Science.gov (United States)

    Tu, Min; Lu, Cheng; Lv, Nan; Wei, Jishu; Lu, Zipeng; Xi, Chunhua; Chen, Jianmin; Guo, Feng; Jiang, Kuirong; Li, Qiang; Wu, Junli; Song, Guoxin; Wang, Shui; Gao, Wentao; Miao, Yi

    2016-12-28

    Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts via paracrine mechanisms. Here, we investigated the angiogenic function and mechanism of action of VASH2 in 200 human breast cancer tissues by performing immunohistochemical staining, western blot, indirect sandwich enzyme-linked immunosorbent assay (ELISA), and a semi-quantitative sandwich-based antibody array. Breast cancer cells stably overexpressing VASH2 or with knocked-down VASH2 were established and used for in vivo and in vitro models. In human luminal tissue, but not in HER2-positive or basal-like breast cancer tissues, VASH2 was positively correlated with CD31-positive microvascular density, induced angiogenesis in xenograft tumors, and promoted human umbilical vein endothelial cell tube formation in vitro. VASH2 expression was absent in the concentrated conditioned medium collected from knocked-down VASH2 and VASH2-overexpressing luminal breast cancer cells. Further, VASH2 regulated the expression of fibroblast growth factor 2 (FGF2) in human luminal breast cancer cells, and the pro-angiogenic effect induced by VASH2 overexpression was blocked by FGF2 neutralization in vitro. Additionally, dual luciferase reporter assay and Chromatin immunoprecipitation analysis results showed that FGF2 promoter was transcriptionally activated by VASH2 via histone modifications. In conclusion, VASH2 expression is positively correlated with FGF2 expression and promotes angiogenesis in human luminal breast cancer by transcriptional activation of fibroblast growth factor 2 through non-paracrine mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Knockdown of NF-E2-related factor 2 inhibits the proliferation and growth of U251MG human glioma cells in a mouse xenograft model.

    Science.gov (United States)

    Ji, Xiang-Jun; Chen, Sui-Hua; Zhu, Lin; Pan, Hao; Zhou, Yuan; Li, Wei; You, Wan-Chun; Gao, Chao-Chao; Zhu, Jian-Hong; Jiang, Kuan; Wang, Han-Dong

    2013-07-01

    NF-E2-related factor 2 (Nrf2) is a pivotal transcription factor of cellular responses to oxidative stress and recent evidence suggests that Nrf2 plays an important role in cancer pathobiology. However, the underlying mechanism has yet to be elucidated, particularly in glioma. In the present study, we investigated the role of Nrf2 in the clinical prognosis, cell proliferation and tumor growth of human glioblastoma multiforme (GBM). We detected overexpression of Nrf2 protein levels in GBM compared to normal brain tissues. Notably, higher protein levels of Nrf2 were significantly associated with poorer overall survival and 1-year survival for GBM patients. Furthermore, we constructed the plasmid Si-Nrf2 and transduced it into U251MG cells to downregulate the expression of Nrf2 and established stable Nrf2 knockdown cells. The downregulation of Nrf2 suppressed cell proliferation in vitro and tumor growth in mouse xenograft models. We performed immunohistochemistry staining to detect the protein levels of Nrf2, Ki-67, caspase-3 and CD31 in the xenograft tumors and found that the expression levels of Nrf2 and Ki-67 were much lower in the Si-Nrf2 group compared to the Si-control group. In addition, the number of caspase-3-positive cells was significantly increased in the Si-Nrf2 group. By analysis of microvessel density (MVD) assessed by CD31, the MVD value in the Si-Nrf2 group decreased significantly compared to the Si-control group. These findings indicate that the knockdown of Nrf2 may suppress tumor growth by inhibiting cell proliferation, increasing cell apoptosis and inhibiting angiogenesis. These results highlight the potential of Nrf2 as a candidate molecular target to control GBM cell proliferation and tumor growth.

  1. Immobilization of bioactive fibroblast growth factor-2 into cubic proteinous microcrystals (Bombyx mori cypovirus polyhedra) that are insoluble in a physiological cellular environment.

    Science.gov (United States)

    Mori, Hajime; Shukunami, Chisa; Furuyama, Akiko; Notsu, Hiroyuki; Nishizaki, Yuriko; Hiraki, Yuji

    2007-06-08

    The supramolecular architecture of the extracellular matrix and the disposition of its specific accessory molecules give rise to variable heterotopic signaling cues for single cells. Here we have described the successful occlusion of human fibroblast growth factor-2 (FGF-2) into the cubic inclusion bodies (FGF-2 polyhedra) of the Bombyx mori cytoplasmic polyhedrosis virus (BmCPV). The polyhedra are proteinous cubic crystals of several microns in size that are insoluble in the extracellular milieu. Purified FGF-2 polyhedra were found to stimulate proliferation and phosphorylation of p44/p42 mitogen-activated protein kinase in cultured fibroblasts. Moreover, cellular responses were blocked by a synthetic inhibitor of the FGF signaling pathway, SU5402, suggesting that FGF-2 polyhedra indeed act through FGF receptors. Furthermore, FGF-2 polyhedra retained potent growth stimulatory properties even after desiccation. We have demonstrated that BmCPV polyhedra microcrystals that occlude extracellular signaling proteins are a novel and versatile tool that can be employed to analyze cellular behavior at the single cell level.

  2. A benzoxazine derivative induces vascular endothelial cell apoptosis in the presence of fibroblast growth factor-2 by elevating NADPH oxidase activity and reactive oxygen species levels.

    Science.gov (United States)

    Zhao, Jing; He, Qiuxia; Cheng, Yizhe; Zhao, Baoxiang; Zhang, Yun; Zhang, Shangli; Miao, Junying

    2009-09-01

    Previously, we found that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (DBO) promoted apoptosis of human umbilical vascular endothelial cells (HUVECs) deprived of growth factors. In this study, we aimed to investigate the effect of DBO and its mechanism of action on angiogenesis and apoptosis of HUVECs in the presence of fibroblast growth factor-2 (FGF-2), which promotes angiogenesis and inhibits apoptosis in vivo and in vitro. DBO significantly inhibited capillary-like tube formation by promoting apoptosis of HUVECs in the presence of FGF-2 in vitro. Furthermore, DBO elevated the levels of reactive oxygen species (ROS) and nitric oxide (NO) and increased the activity of NADPH oxidase and inducible nitric oxide synthase (iNOS) in promoting apoptosis under this condition. Moreover, when NADPH oxidase was inhibited by its specific inhibitor, dibenziodolium chloride (DPI), DBO could not elevate ROS and NO levels in HUVECs. The data suggest that DBO is a new modulator of apoptosis in vitro, and it might function by increasing the activity of NADPH oxidase and iNOS, subsequently elevating the levels of ROS and NO in HUVECs. The findings of this study provide a new small molecule for investigating the FGF-2/NADPH oxidase/iNOS signaling pathway in apoptosis.

  3. Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Doaa Aboalola

    2017-01-01

    Full Text Available Insulin-like growth factors (IGFs are critical components of the stem cell niche, as they regulate proliferation and differentiation of stem cells into different lineages, including skeletal muscle. We have previously reported that insulin-like growth factor binding protein-6 (IGFBP-6, which has high affinity for IGF-2, alters the differentiation process of placental mesenchymal stem cells (PMSCs into skeletal muscle. In this study, we determined the roles of IGF-1 and IGF-2 and their interactions with IGFBP-6. We showed that IGF-1 increased IGFBP-6 levels within 24 hours but decreased after 3 days, while IGF-2 maintained higher levels of IGFBP-6 throughout myogenesis. IGF-1 increased IGFBP-6 in the early phase as a requirement for muscle commitment. In contrast, IGF-2 enhanced muscle differentiation as shown by the expression of muscle differentiation markers MyoD, MyoG, and MHC. IGF-1 and IGF-2 had different effects on muscle differentiation with IGF-1 promoting early commitment to muscle and IGF-2 promoting complete muscle differentiation. We also showed that PMSCs acquired increasing capacity to synthesize IGF-2 during muscle differentiation, and the capacity increased as the differentiation progressed suggesting an autocrine and/or paracrine effect. Additionally, we demonstrated that IGFBP-6 could enhance the muscle differentiation process in the absence of IGF-2.

  4. Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Biver, Emmanuel, E-mail: ebiver@yahoo.fr [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Soubrier, Anne-Sophie [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Thouverey, Cyril [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Cortet, Bernard [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Broux, Odile [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Caverzasio, Joseph [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Hardouin, Pierre [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.

  5. Gastric cancer: the role of insulin-like growth factor 2 (IGF 2) and its receptors (IGF 1R and M6-P/IGF 2R).

    Science.gov (United States)

    Pavelić, Kresimir; Kolak, Toni; Kapitanović, Sanja; Radosević, Senka; Spaventi, Sime; Kruslin, Bozo; Pavelić, Jasminka

    2003-11-01

    Insulin-like growth factor 2 (IGF 2) appears to be involved in the progression of many tumours. It binds to at least two different types of receptor: IGF type 1 (IGF 1R) and mannose 6-phosphate/IGF type 2 (M6-P/IGF 2R). Ligand binding to IGF 1R provokes mitogenic and anti-apoptotic effects. M6-P/IGF 2R has a tumour suppressor function--it mediates IGF 2 degradation. Mutation of M6-P/IGF 2R causes both diminished growth suppression and augmented growth stimulation. The aim of this study was to investigate the role of IGF 2 and its receptors (IGF 1R and IGF 2R) in human gastric cancer. The expression of IGF 2 and its receptors was measured in order to analyse the possible correlation between the activity of these genes and cell proliferation in two different gastric tumour types: diffuse and intestinal. The effect of IGF 1 receptor blockage on cell proliferation and anchorage-independent cell growth was also examined. Increased expression of IGF 2 and IGF 1R genes (at the mRNA and protein level) was found in gastric cancer when compared with non-tumour tissue. Furthermore, there was a significant difference between IGF 2 expression in the more aggressive diffuse type and that in the intestinal type of gastric cancer. Moreover, the IGF 2 peptide level in the culture media obtained from the diffuse type of cancer cells was significantly higher when compared with the intestinal type. The level of IGF 2 peptide in the conditioned media strongly correlated with [3H]thymidine incorporation and cell proliferation. On the contrary, IGF 2R mRNA expression was much higher in the intestinal type of cancer than in the diffuse type. In addition, IGF 2R protein expression was substantially lower with progression of the diffuse cancer type to a higher stage. The alphaIR3 monoclonal antibody strongly inhibited [3H]thymidine incorporation and decreased the number of colonies in soft agar of cells overexpressing IGF 2. These findings suggest that members of the IGF family are involved

  6. Targeted silencing of elongation factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer.

    Directory of Open Access Journals (Sweden)

    Ibrahim Tekedereli

    Full Text Available Eukaryotic elongation factor 2 kinase (eEF-2K, through its phosphorylation of elongation factor 2 (eEF2, provides a mechanism by which cells can control the rate of the elongation phase of protein synthesis. The activity of eEF-2K is increased in rapidly proliferating malignant cells, is inhibited during mitosis, and may contribute to the promotion of autophagy in response to anti-cancer therapies. The purpose of this study was to examine the therapeutic potential of targeting eEF-2K in breast cancer tumors. Through the systemic administration of liposomal eEF-2K siRNA (twice a week, i.v. 150 µg/kg, the expression of eEF-2K was down-regulated in vivo in an orthotopic xenograft mouse model of a highly aggressive triple negative MDA-MB-231 tumor. This targeting resulted in a substantial decrease in eEF2 phosphorylation in the tumors, and led to the inhibition of tumor growth, the induction of apoptosis and the sensitization of tumors to the chemotherapy agent doxorubicin. eEF-2K down-modulation in vitro resulted in a decrease in the expression of c-Myc and cyclin D1 with a concomitant increase in the expression of p27(Kip1. A decrease in the basal activity of c-Src (phospho-Tyr-416, focal adhesion kinase (phospho-Tyr-397, and Akt (phospho-Ser-473 was also detected following eEF-2K down-regulation in MDA-MB-231 cells, as determined by Western blotting. Where tested, similar results were seen in ER-positive MCF-7 cells. These effects were also accompanied by a decrease in the observed invasive phenotype of the MDA-MB-231 cells. These data support the notion that the disruption of eEF-2K expression in breast cancer cells results in the down-regulation of signaling pathways affecting growth, survival and resistance and has potential as a therapeutic approach for the treatment of breast cancer.

  7. Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes.

    Science.gov (United States)

    Strunz, Célia Maria Cássaro; Roggerio, Alessandra; Cruz, Paula Lázara; Pacanaro, Ana Paula; Salemi, Vera Maria Cury; Benvenuti, Luiz Alberto; Mansur, Antonio de Pádua; Irigoyen, Maria Cláudia

    2017-02-01

    Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Enhancement of rotator cuff tendon-bone healing with fibroblast growth factor 2 impregnated in gelatin hydrogel sheets in a rabbit model.

    Science.gov (United States)

    Tokunaga, Takuya; Karasugi, Tatsuki; Arimura, Hitoshi; Yonemitsu, Ryuji; Sakamoto, Hidetoshi; Ide, Junji; Mizuta, Hiroshi

    2017-10-01

    Application of fibroblast growth factor 2 (FGF-2) may improve the healing response after rotator cuff (RC) surgical repair. This study aimed to determine whether FGF-2-impregnated gelatin hydrogel sheet (GHS) incorporation into the bony trough on the greater tuberosity facilitates healing after RC surgical repair in rabbits. We assigned 120 adult male Japanese white rabbits treated with unilateral surgery for supraspinatus tendon repair into the following groups: suture-only group (suture); suture and GHS with phosphate-buffered saline (carrier); suture and GHS with 3 µg of FGF-2 (F3); and suture and GHS with 30 µg of FGF-2 (F30). The effect of FGF-2 was assessed using histologic, biomechanical, and microcomputed tomography evaluations at 2, 6, and 12 weeks. At 12 weeks, loose fibrovascular tissues emerged at the repair site in the suture and carrier groups and dense tendon-like tissues in the F3 and F30 groups, which demonstrated significantly higher ultimate load-to-failure and stress-to-failure at 12 weeks than that in the suture and carrier groups. Microcomputed tomography imaging showed ectopic calcification formation in some specimens from each group. Appearances or frequencies were similar among groups. The histologic and biomechanical effects of FGF-2 on RC healing were obvious at ≥6 weeks postoperatively. FGF-2-impregnated GHS incorporation into the bony trough on the greater tuberosity before RC surgical repair is feasible and results in histologic and biomechanical improvements during RC healing in rabbits. No detrimental effect on ectopic calcification was observed. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  9. Fibroblast growth factor-2 up-regulates the expression of nestin through the Ras–Raf–ERK–Sp1 signaling axis in C6 glioma cells

    International Nuclear Information System (INIS)

    Chang, Kai-Wei; Huang, Yuan-Li; Wong, Zong-Ruei; Su, Peng-Han; Huang, Bu-Miin; Ju, Tsai-Kai; Yang, Hsi-Yuan

    2013-01-01

    Highlights: •Nestin expression in C6 glioma cells is induced by FGF-2. •Nestin expression is induced by FGF-2 via de novo RNA and protein synthesis. •The FGFR inhibitor SU5402 blocks the FGF-2-induced nestin expression. •The mRNA of FGFR1 and 3 are detected in C6 glioma cells. •Ras–Raf–ERK–Sp1 signaling pathway is responsibe for FGF-2-induced nestin expression. -- Abstract: Nestin is a 240-kDa intermediate filament protein expressed mainly in neural and myogenic stem cells. Although a substantial number of studies have focused on the expression of nestin during development of the central nervous system, little is known about the factors that induce and regulate its expression. Fibroblast growth factor-2 (FGF-2) is an effective mitogen and stimulates the proliferation and differentiation of a subset of nestin-expressing cells, including neural progenitor cells, glial precursor cells, and smooth muscle cells. To assess whether FGF-2 is a potent factor that induces the expression of nestin, C6 glioma cells were used. The results showed that nestin expression was up-regulated by FGF-2 via de novo RNA and protein synthesis. Our RT-PCR results showed that C6 glioma cells express FGFR1/3, and FGFRs is required for FGF-2-induced nestin expression. Further signaling analysis also revealed that FGF-2-induced nestin expression is mediated through FGFR–MAPK–ERK signaling axis and the transcriptional factor Sp1. These findings provide new insight into the regulation of nestin in glial system and enable the further studies on the function of nestin in glial cells

  10. Fibroblast growth factor-2 up-regulates the expression of nestin through the Ras–Raf–ERK–Sp1 signaling axis in C6 glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kai-Wei [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China); Huang, Yuan-Li [Department of Biotechnology, College of Health Science, Asia University, Taichung 413, Taiwan (China); Wong, Zong-Ruei; Su, Peng-Han [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China); Huang, Bu-Miin [Department of Cell Biology and Anatomy, National Cheng-Kung University, Tainan 701, Taiwan (China); Ju, Tsai-Kai [Instrumentation Center, National Taiwan University, Taipei 106, Taiwan (China); Technology Commons, College of Life Science, National Taiwan University, Taipei 106, Taiwan (China); Yang, Hsi-Yuan, E-mail: hyhy@ntu.edu.tw [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China)

    2013-05-17

    Highlights: •Nestin expression in C6 glioma cells is induced by FGF-2. •Nestin expression is induced by FGF-2 via de novo RNA and protein synthesis. •The FGFR inhibitor SU5402 blocks the FGF-2-induced nestin expression. •The mRNA of FGFR1 and 3 are detected in C6 glioma cells. •Ras–Raf–ERK–Sp1 signaling pathway is responsibe for FGF-2-induced nestin expression. -- Abstract: Nestin is a 240-kDa intermediate filament protein expressed mainly in neural and myogenic stem cells. Although a substantial number of studies have focused on the expression of nestin during development of the central nervous system, little is known about the factors that induce and regulate its expression. Fibroblast growth factor-2 (FGF-2) is an effective mitogen and stimulates the proliferation and differentiation of a subset of nestin-expressing cells, including neural progenitor cells, glial precursor cells, and smooth muscle cells. To assess whether FGF-2 is a potent factor that induces the expression of nestin, C6 glioma cells were used. The results showed that nestin expression was up-regulated by FGF-2 via de novo RNA and protein synthesis. Our RT-PCR results showed that C6 glioma cells express FGFR1/3, and FGFRs is required for FGF-2-induced nestin expression. Further signaling analysis also revealed that FGF-2-induced nestin expression is mediated through FGFR–MAPK–ERK signaling axis and the transcriptional factor Sp1. These findings provide new insight into the regulation of nestin in glial system and enable the further studies on the function of nestin in glial cells.

  11. Dynamics of polynucleotide transport through nanometre-scale pores

    CERN Document Server

    Meller, A

    2003-01-01

    The transport of biopolymers through large membrane channels is a ubiquitous process in biology. It is central to processes such as gene transfer by transduction and RNA transport through nuclear pore complexes. The transport of polymers through nanoscopic channels is also of interest to physicists and chemists studying the effects of steric, hydrodynamic, and electrostatic interactions between polymers and confining walls. Single-channel ion current measurements have been recently used to study the transport of biopolymers, and in particular single-stranded DNA and RNA molecules, through nanometre-size channels. Under the influence of an electric field, the negatively charged polynucleotides can be captured and drawn through the channel in a process termed 'translocation'. During translocation, the ion current flowing through the channel is mostly blocked, indicating the presence of the polymer inside the channel. The current blockades were found to be sensitive to the properties of the biopolymers such as t...

  12. Ridge augmentation using recombinant human fibroblast growth factor-2 with biodegradable gelatin sponges incorporating β-tricalcium phosphate: a preclinical study in dogs.

    Science.gov (United States)

    Hoshi, S; Akizuki, T; Matsuura, T; Ikawa, T; Kinoshita, A; Oda, S; Tabata, Y; Matsui, M; Izumi, Y

    2016-02-01

    Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of osteogenic cells, resulting in the promotion of bone formation. Biodegradable gelatin sponges incorporating β-tricalcium phosphate (β-TCP) have been reported as a scaffold, which has the ability to control growth factor release, offering sufficient mechanical strength and efficient migration of mesenchymal cells. In this study, we evaluated the effects of the combined use of recombinant human FGF-2 (rhFGF-2) and gelatin/β-TCP sponge on ridge augmentation in dogs. Six male beagle dogs were used in this study. Twelve wk after tooth extraction, bilateral 10 × 5 mm (width × depth) saddle-type defects were created 3 mm apart from the mesial side of the maxillary canine. At the experimental sites, the defects were filled with gelatin/β-TCP sponge infiltrated with 0.3% rhFGF-2, whereas gelatin/β-TCP sponge infiltrated with saline was applied to the control sites. Eight wk after surgery, qualitative and quantitative analyses were performed. There were no signs of clinical inflammation at 8 wk after surgery. Histometric measurements revealed that new bone height at the experimental sites (2.98 ± 0.65 mm) was significantly greater than that at the control sites (1.56 ± 0.66 mm; p = 0.004). The total tissue height was greater at the experimental sites (6.62 ± 0.66 mm) than that at the control sites (5.95 ± 0.74 mm), although there was no statistical significant difference (p = 0.051). Cast model measurements revealed that the residual defect height at the experimental sites (2.31 ± 0.50 mm) was significantly smaller than that at the control sites (3.51 ± 0.78 mm; p = 0.012). The combined use of rhFGF-2 and gelatin/β-TCP sponge promotes ridge augmentation in canine saddle-type bone defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Effect of Fibroblast Growth Factor 2 (FGF2 and Insulin Transferrin Selenium (ITS on In Vitro Maturation, Fertilization and Embryo Development in Sheep

    Directory of Open Access Journals (Sweden)

    Sukanta Mondal

    2015-08-01

    Full Text Available The present study evaluated the effect of fibroblast growth factor 2 (FGF2 and insulin-transferrin-selenium (ITS to the in vitro maturation and embryo culture media on ovine oocyte maturation, cleavage and embryo development. Oocytes having more than five layers of unexpanded cumulus cells and granular homogenous ooplasm were cultured into 50 μL droplets of eight different culture systems: (i TCM-199 (Tissue Culture Medium-199; (ii TCM-199+10 ng/mL FGF2; (iii TCM-199+20 ng/mL FGF2; (iv TCM-199+30 ng/mL FGF2; (v TCM-199+10 ng/mL ITS; (vi TCM-199+20 ng/mL ITS; (vii TCM-199+30 ng/mL ITS and (viii TCM-199+20 ng/mL ITS+20 ng/mL FGF2 in a CO2 incubator at 38.50C for 24 h. All the oocyte culture media were supplemented with 10% FBS, FSH (10 μg/mL and gentamicin (50 µg/mL. The maturation rate was assessed based on the degree of expansion of cumulus cells and identifying first polar body extrusion into perivitelline space. The matured oocytes were inseminated with 1 to 2 million spermatozoa/mL in Brackett and Oliphant medium and the cleavage rate was checked after 42-48 h post insemination and further cultured for 6-7 days. Maturation and cleavage rates were significantly higher (P<0.05 in the oocytes cultured in TCM-199 +10% FBS+FSH (10 μg/mL supplemented with both 20 ng/mL ITS and 20 ng/mL FGF2 as compared to the control. It was concluded that the supplementation of ITS and FGF2 in maturation medium was beneficial for improving maturation and cleavage rates of sheep oocytes. The addition of ITS and FGF2 in embryo culture medium did not improve the development of sheep embryos.

  14. Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Rades, D.; Seibold, N.D.; Gebhard, M.P.; Noack, F.; Schild, S.E.

    2014-01-01

    Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95 %-confidence interval (CI): 2.88-19.05; p < 0.001], lower T-category (RR: 2.42; 95 %-CI: 1.47-4.33; p < 0.001), lower N-category (RR: 12.36; 95 %-CI: 3.48-78.91; p < 0.001), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 4.18; 95 %-CI: 1.73-10.53; p = 0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95 %-CI: 0.97-2.82; p = 0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p < 0.001), lower T-category (RR: 2.17; 95 %-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95 %-CI: 1.60-10.85; p = 0.002), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 3.20; 95 %-CI: 1.46-7.30; p = 0.004). HPV-positivity showed a trend (RR: 2.36; 95 %-CI: n.a.; p = 0.054). Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials. (orig.)

  15. Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D.; Seibold, N.D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Gebhard, M.P.; Noack, F. [University of Luebeck, Institute of Pathology, Luebeck (Germany); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale (United States)

    2014-01-15

    Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95 %-confidence interval (CI): 2.88-19.05; p < 0.001], lower T-category (RR: 2.42; 95 %-CI: 1.47-4.33; p < 0.001), lower N-category (RR: 12.36; 95 %-CI: 3.48-78.91; p < 0.001), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 4.18; 95 %-CI: 1.73-10.53; p = 0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95 %-CI: 0.97-2.82; p = 0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p < 0.001), lower T-category (RR: 2.17; 95 %-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95 %-CI: 1.60-10.85; p = 0.002), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 3.20; 95 %-CI: 1.46-7.30; p = 0.004). HPV-positivity showed a trend (RR: 2.36; 95 %-CI: n.a.; p = 0.054). Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials. (orig.)

  16. Regulation of physicochemical properties, osteogenesis activity, and fibroblast growth factor-2 release ability of β-tricalcium phosphate for bone cement by calcium silicate

    International Nuclear Information System (INIS)

    Su, Ching-Chuan; Kao, Chia-Tze; Hung, Chi-Jr; Chen, Yi-Jyun; Huang, Tsui-Hsien; Shie, Ming-You

    2014-01-01

    β-Tricalcium phosphate (β-TCP) is an osteoconductive material. For this research we have combined it with a low degradation calcium silicate (CS) to enhance its bioactive and osteostimulative properties. To check its effectiveness, a series of β-TCP/CS composites with different ratios were prepared to make new bioactive and biodegradable biocomposites for bone repair. Formation of bone-like apatite, the diametral tensile strength, and weight loss of composites were considered before and after immersion in simulated body fluid (SBF). In addition, we also examined the effects of fibroblast growth factor-2 (FGF-2) released from β-TCP/CS composites and in vitro human dental pulp cell (hDPC) and studied its behavior. The results showed that the apatite deposition ability of the β-TCP/CS composites was enhanced as the CS content was increased. For composites with more than 50% CS contents, the samples were completely covered by a dense bone-like apatite layer. At the end of the immersion point, weight losses of 19%, 24%, 33%, 42%, and 51% were observed for the composites containing 0%, 30%, 50%, 70% and 100% β-TCP cements, respectively. In vitro cell experiments show that the CS-rich composites promote human dental pulp cell (hDPC) proliferation and differentiation. However, when the CS quantity in the composite is less than 70%, the amount of cells and osteogenesis protein of hDPCs was stimulated by FGF-2 released from β-TCP/CS composites. The combination of FGF-2 in degradation of β-TCP and osteogenesis of CS gives a strong reason to believe that these calcium-based composite cements may prove to be promising bone repair materials. - Highlights: • CS improved physicochemical properties and osteogenic activity of β-TCP. • The higher the CS in the cement, the shorter the setting time and the higher the DTS. • The cell behavior was stimulated by FGF-2 released from composite containing 50% CS. • β-TCP/CS composite with FGF-2 has optimal properties for

  17. Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-β/activin/nodal signalling inhibition.

    Science.gov (United States)

    Koel, Mariann; Võsa, Urmo; Krjutškov, Kaarel; Einarsdottir, Elisabet; Kere, Juha; Tapanainen, Juha; Katayama, Shintaro; Ingerpuu, Sulev; Jaks, Viljar; Stenman, Ulf-Hakan; Lundin, Karolina; Tuuri, Timo; Salumets, Andres

    2017-09-01

    Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days. Genes differentially expressed compared with untreated cells were identified at seven time points. Additionally, expression of total human chorionic gonadotrophin (HCG) and its hyperglycosylated form (HCG-H) were determined by immunoassay from cell culture media. We showed that FGF2 inhibition with BMP4 activation up-regulates syncytiotrophoblast-specific genes (CGA, CGB and LGALS16), induces several molecular pathways involved in embryo implantation and triggers HCG-H production. In contrast, inhibition of the TGF-β/activin/nodal pathway decreases the ability of hESC to form trophoblast-like cells. Information about the conditions needed for hESC differentiation toward trophoblast-like cells helps us to find an optimal model for studying the early development of human trophoblasts in normal and in complicated pregnancy. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. The exoribonuclease Polynucleotide Phosphorylase influences the virulence and stress responses of yersiniae and many other pathogens

    Directory of Open Access Journals (Sweden)

    Jason A. Rosenzweig

    2013-11-01

    Full Text Available Microbes are incessantly challenged by both biotic and abiotic stressors threatening their existence. Therefore, bacterial pathogens must possess mechanisms to successfully subvert host immune defenses as well as overcome the stress associated with host-cell encounters. To achieve this, bacterial pathogens typically experience a genetic re-programming whereby anti-host/stress factors become expressed and eventually translated into effector proteins. In that vein, the bacterial host-cell induced stress-response is similar to any other abiotic stress to which bacteria respond by up-regulating specific stress-responsive genes. Following the stress encounter, bacteria must degrade unnecessary stress responsive transcripts through RNA decay mechanisms. The 3 pathogenic yersiniae (Yersinia pestis, Y. pseudo-tuberculosis, and Y. enterocolitica are all psychrotropic bacteria capable of growth at 4˚C; however, cold growth is dependent on the presence of an exoribonuclease, polynucleotide phosphorylase (PNPase. PNPase has also been implicated as a virulence factor in several notable pathogens including the salmonellae, Helicobacter pylori, and the yersiniae (where it typically influences the type three secretion system. Further, PNPase has been shown to associate with ribonuclease E (endoribonuclease, RhlB (RNA helicase, and enolase (glycolytic enzyme in several Gram-negative bacteria forming a large, multi-protein complex known as the RNA degradosome. This review will highlight studies demonstrating the influence of PNPase on the virulence potentials and stress responses of various bacterial pathogens as well as focusing on the degradosome- dependent and -independent roles played by PNPase in yersiniae stress responses.

  19. Using long ssDNA polynucleotides to amplify STRs loci in degraded DNA samples

    Science.gov (United States)

    Pérez Santángelo, Agustín; Corti Bielsa, Rodrigo M.; Sala, Andrea; Ginart, Santiago; Corach, Daniel

    2017-01-01

    Obtaining informative short tandem repeat (STR) profiles from degraded DNA samples is a challenging task usually undermined by locus or allele dropouts and peak-high imbalances observed in capillary electrophoresis (CE) electropherograms, especially for those markers with large amplicon sizes. We hereby show that the current STR assays may be greatly improved for the detection of genetic markers in degraded DNA samples by using long single stranded DNA polynucleotides (ssDNA polynucleotides) as surrogates for PCR primers. These long primers allow a closer annealing to the repeat sequences, thereby reducing the length of the template required for the amplification in fragmented DNA samples, while at the same time rendering amplicons of larger sizes suitable for multiplex assays. We also demonstrate that the annealing of long ssDNA polynucleotides does not need to be fully complementary in the 5’ region of the primers, thus allowing for the design of practically any long primer sequence for developing new multiplex assays. Furthermore, genotyping of intact DNA samples could also benefit from utilizing long primers since their close annealing to the target STR sequences may overcome wrong profiling generated by insertions/deletions present between the STR region and the annealing site of the primers. Additionally, long ssDNA polynucleotides might be utilized in multiplex PCR assays for other types of degraded or fragmented DNA, e.g. circulating, cell-free DNA (ccfDNA). PMID:29099837

  20. The increasing of fibroblast growth factor 2, osteocalcin, and osteoblast due to the induction of the combination of Aloe vera and 2% xenograft concelous bovine

    Directory of Open Access Journals (Sweden)

    Utari Kresnoadi

    2012-12-01

    Full Text Available Background: To make a successfull denture prominent ridge is needed, preservation on tooth extraction socket is needed in order to prevent alveol bone resorption caused by revocation trauma. An innovative modification of the material empirically suspected to be able reduce inflammation caused by the revocation trauma is a combination of Aloe vera and xenograft concelous bovine (XCB and Aloe vera is a biogenic stimulator and accelerating the growth of alveolar ridge bone after tooth extraction. Purpose: The research was aimed to determine of the increasing alveol bone formation by inducing the combination of Aloe vera and 2% xenograft concelous bovine. Methods: To address the problems, the combination of Aloe vera and xenograft concelous bovine was induced into the tooth extraction sockets of Cavia cabayas which devided on 8 groups. Groups control, filled with XCB, Aloe vera and Aloe vera and XCB combination, at 7 days and 30 days after extraction. Afterwards, immunohistochemical examination was conducted to examine the expressions of FGF-2 and osteocalcin, as the product of the growth of osteoblasts. Results: There were significantly increases expression of FGF-2 and osteocalcyn on group which filled with XCB, Aloe vera and combined Aloe vera and XCB. Conclusion: It may be concluded that the induction of the combination of Aloe vera and xenograft concelous bovine into the tooth sockets can enhance the growth expressions of FGF-2 and osteocalcin as the product of osteoblasts, thus, the growth of alveolar bone was increased.Latar belakang: Untuk keberhasilan pembuatan gigitiruan diperlukan ridge yang prominent, maka diperlukan suatu preservasi soket pencabutan gigi untuk mencegah terjadinya resopsi tulang alveolar akibat trauma pencabutan. Suatu inovasi modifikasi bahan yang diduga secara empiris dapat mengurangi keradangan karena trauma pencabutan adalah berupa kombinasi Aloe vera dan xenograft concelous bovine (XCB. Aloe vera yang merupakan

  1. Elemental Diet Accelerates the Recovery From Oral Mucositis and Dermatitis Induced by 5-Fluorouracil Through the Induction of Fibroblast Growth Factor 2.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Kobayashi, Hiroaki; Ueyama, Yoshiya

    2018-06-01

    Mucositis and dermatitis induced by anticancer agents are common complications of anticancer therapies. In this study, we evaluated the efficacy of Elental (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis and dermatitis was induced through a combination of 5-FU treatment and mild abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice respectively. These animals received saline, dextrin or Elental suspension (18 kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral mucositis and dermatitis more effectively than dextrin in the animal model. Moreover, growth facilitating effects of Elental on HaCaT cells were examined in vitro. MTT assay, wound healing assay, and migration assay revealed that Elental could enhance the growth, invasion, and migration ability of HaCaT. ELISA and Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings suggest that Elental is effective for the treatment of mucositis and dermatitis, and may accelerate mucosal and skin recovery through FGF2 induction and reepithelization.

  2. Insulin-like growth factor 2

    DEFF Research Database (Denmark)

    Valleh, Mehdi Vafaye; Hyttel, Poul; Rasmussen, Mikkel Aabech

    2014-01-01

    Intrinsic defects within the embryos, reflected by elevated cell death and low proliferative ability, are considered the most critical factors associated with bovine infertility. The identification of embryonic factors, which are responsible for successful embryo development, is thus critical...

  3. Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2)-dependent Oligomerization of Fibroblast Growth Factor 2 (FGF2) Triggers the Formation of a Lipidic Membrane Pore Implicated in Unconventional Secretion*

    Science.gov (United States)

    Steringer, Julia P.; Bleicken, Stephanie; Andreas, Helena; Zacherl, Sonja; Laussmann, Mareike; Temmerman, Koen; Contreras, F. Xabier; Bharat, Tanmay A. M.; Lechner, Johannes; Müller, Hans-Michael; Briggs, John A. G.; García-Sáez, Ana J.; Nickel, Walter

    2012-01-01

    Fibroblast growth factor 2 (FGF2) is a critical mitogen with a central role in specific steps of tumor-induced angiogenesis. It is known to be secreted by unconventional means bypassing the endoplasmic reticulum/Golgi-dependent secretory pathway. However, the mechanism of FGF2 membrane translocation into the extracellular space has remained elusive. Here, we show that phosphatidylinositol 4,5-bisphosphate-dependent membrane recruitment causes FGF2 to oligomerize, which in turn triggers the formation of a lipidic membrane pore with a putative toroidal structure. This process is strongly up-regulated by tyrosine phosphorylation of FGF2. Our findings explain key requirements of FGF2 secretion from living cells and suggest a novel self-sustained mechanism of protein translocation across membranes with a lipidic membrane pore being a transient translocation intermediate. PMID:22730382

  4. Cloned polynucleotide and synthetic oligonucleotide probes used in colony hybridization are equally efficient in the identification of enterotoxigenic Escherichia coli

    International Nuclear Information System (INIS)

    Sommerfelt, H.; Kalland, K.H.; Raj, P.; Moseley, S.L.; Bhan, M.K.; Bjorvatn, B.

    1988-01-01

    Restriction endonuclease-generated polynucleotide and synthetically produced oligonucleotide gene probes used in colony hybridization assays proved to be efficient for the detection and differentiation of enterotoxigenic Escherichia coli. To compare their relative efficiencies, these two sets of probes were radiolabeled with 32 P and were applied to 74 strains of E. coli with known enterotoxin profiles and to 156 previously unexamined E. coli isolates. The enterotoxigenic bacteria Vibrio cholerae O1, Vibrio cholerae non-O1 (NAG), Yersinia enterocolitica, and E. coli harboring the plasmid vectors of the polynucleotide gene probes were examined for further evaluation of probe specificity. The two classes of probes showed a perfect concordance in their specific detection and differentiation of enterotoxigenic E. coli. In the analysis of six strains, the signal strength on autoradiography after hybridization with oligonucleotides was weaker than that obtained after hybridization with polynucleotide probes. The probes did not hybridize with DNA from V. cholerae O1, V. cholerae non-O1 (NAG), or Y. enterocolitica. The strains of E. coli harboring the plasmid vectors of the polynucleotide gene probes were, likewise, negative in the hybridization assays

  5. Cloned polynucleotide and synthetic oligonucleotide probes used in colony hybridization are equally efficient in the identification of enterotoxigenic Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Sommerfelt, H.; Kalland, K.H.; Raj, P.; Moseley, S.L.; Bhan, M.K.; Bjorvatn, B.

    1988-11-01

    Restriction endonuclease-generated polynucleotide and synthetically produced oligonucleotide gene probes used in colony hybridization assays proved to be efficient for the detection and differentiation of enterotoxigenic Escherichia coli. To compare their relative efficiencies, these two sets of probes were radiolabeled with /sup 32/P and were applied to 74 strains of E. coli with known enterotoxin profiles and to 156 previously unexamined E. coli isolates. The enterotoxigenic bacteria Vibrio cholerae O1, Vibrio cholerae non-O1 (NAG), Yersinia enterocolitica, and E. coli harboring the plasmid vectors of the polynucleotide gene probes were examined for further evaluation of probe specificity. The two classes of probes showed a perfect concordance in their specific detection and differentiation of enterotoxigenic E. coli. In the analysis of six strains, the signal strength on autoradiography after hybridization with oligonucleotides was weaker than that obtained after hybridization with polynucleotide probes. The probes did not hybridize with DNA from V. cholerae O1, V. cholerae non-O1 (NAG), or Y. enterocolitica. The strains of E. coli harboring the plasmid vectors of the polynucleotide gene probes were, likewise, negative in the hybridization assays.

  6. Long-chain polynucleotide filler for skin rejuvenation: efficacy and complications in five patients.

    Science.gov (United States)

    Park, Kui Young; Seok, Joon; Rho, Nark Kyoung; Kim, Beom Joon; Kim, Myeung Nam

    2016-01-01

    Aging well has become the new target of preventative medicine, and aesthetic dermatology can contribute to this request. The polynucleotide (PN) containing products not only fill the space, but improve tissue regeneration, resulting in more natural tissue regeneration. Five Korean women received four times injections of long-chain PN filler in two-week intervals for skin rejuvenation. About 0.05 mL of material was injected in 40 points of one-side cheek. The pore and skin thickness were markedly improved in the patients in their 30s, whereas skin tone, melanin, wrinkles, and sagging were noticeably improved for patients in their 40s. There are no serious side effects. In conclusion, intradermal long-chain PN filler injection seems to be an effective and safe treatment for skin rejuvenation. © 2015 Wiley Periodicals, Inc.

  7. Detection of single-copy functional genes in prokaryotic cells by two-pass TSA-FISH with polynucleotide probes.

    Science.gov (United States)

    Kawakami, Shuji; Hasegawa, Takuya; Imachi, Hiroyuki; Yamaguchi, Takashi; Harada, Hideki; Ohashi, Akiyoshi; Kubota, Kengo

    2012-02-01

    In situ detection of functional genes with single-cell resolution is currently of interest to microbiologists. Here, we developed a two-pass tyramide signal amplification (TSA)-fluorescence in situ hybridization (FISH) protocol with PCR-derived polynucleotide probes for the detection of single-copy genes in prokaryotic cells. The mcrA gene and the apsA gene in methanogens and sulfate-reducing bacteria, respectively, were targeted. The protocol showed bright fluorescence with a good signal-to-noise ratio and achieved a high efficiency of detection (>98%). The discrimination threshold was approximately 82-89% sequence identity. Microorganisms possessing the mcrA or apsA gene in anaerobic sludge samples were successfully detected by two-pass TSA-FISH with polynucleotide probes. The developed protocol is useful for identifying single microbial cells based on functional gene sequences. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Biomimetic nanoparticles with polynucleotide and PEG mixed-monolayers enhance calcium phosphate mineralization

    Energy Technology Data Exchange (ETDEWEB)

    Vasconcellos, Kayla B.; McHugh, Sean M.; Dapsis, Katherine J.; Petty, Alexander R.; Gerdon, Aren E., E-mail: gerdoar@emmanuel.edu [Emmanuel College (United States)

    2013-09-15

    Biomineralization of hydroxyapatite (Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2}) is of significant importance in biomedical applications such as bone and dental repair, and biomimetic control of mineral formation may lead to more effective restorative procedures. Gold nanoparticles are functional scaffolds on which to assemble multi-component monolayers capable of mimicking protein activity in the templated synthesis of calcium phosphate. The goal of this research was to explore nanoparticle templates with mixed-monolayers of uncharged polar polyethylene glycol (PEG) molecules and highly charged polynucleotide and amino acid molecules in their ability to influence mineralization rates and mineral particle size and morphology. This research demonstrates through time-resolved optical density and dynamic light scattering measurements that the combination of tiopronin, PEG, and DNA presented on a nanoparticle surface decreases nanoparticle aggregation from 59 to 21 nm solvated radius, increases mineralization kinetics from 1.5 Multiplication-Sign 10{sup -3} to 3.1 Multiplication-Sign 10{sup -3} OD/min, and decreases mineral particle size from 685 to 442 nm average radius. FT-IR and TEM data demonstrate that mineralized material, while initially amorphous, transforms to a semi-crystalline material when guided by template interactions. This demonstrates that surface-tailored monolayer protected cluster scaffolds are successful and controllable mineralization templates with further potential for biomedical applications involving calcium phosphate and other biomaterials.

  9. Gold nanoparticles for the bare-eye based and spectrophotometric detection of proteins, polynucleotides and DNA

    International Nuclear Information System (INIS)

    Lepoitevin, Mathilde; Lemouel, Marie; Bechelany, Mikhael; Janot, Jean-Marc; Balme, Sebastien

    2015-01-01

    We have explored the potential of using gold nanoparticles (Au-NPs) in optical and bare-eye discrimination of (a) proteins (such as bovine serum albumin and lysozyme), (b) homo-polynucleotides (such as poly-adenylic acid, poly-cytidylic acid, poly-uridylic acid and poly-inosinic acid), and (c) long chain DNA (from salmon, herring and thym). Such biomacromolecules can be detected and discriminated due to their ability to prevent the formation of blue aggregates from red (non-aggregated) citrate capped Au-NPs on addition of NaCl. The effect of these biomacromolecules on the aggregation was investigated by colorimetry and UV–vis spectrometry. The results show that the two proteins can be differentiated by colorimetry, and also salmon ssDNA and dsDNA. The Au-NPs can also discriminate the dsDNAs of salmon and herring. We conclude that the use of Au-NPs represent a viable candidate to future methods of DNA analysis on the basis of visual testing, particularly in the area of food analysis. (author)

  10. Biomimetic nanoparticles with polynucleotide and PEG mixed-monolayers enhance calcium phosphate mineralization

    Science.gov (United States)

    Vasconcellos, Kayla B.; McHugh, Sean M.; Dapsis, Katherine J.; Petty, Alexander R.; Gerdon, Aren E.

    2013-09-01

    Biomineralization of hydroxyapatite (Ca10(PO4)6(OH)2) is of significant importance in biomedical applications such as bone and dental repair, and biomimetic control of mineral formation may lead to more effective restorative procedures. Gold nanoparticles are functional scaffolds on which to assemble multi-component monolayers capable of mimicking protein activity in the templated synthesis of calcium phosphate. The goal of this research was to explore nanoparticle templates with mixed-monolayers of uncharged polar polyethylene glycol (PEG) molecules and highly charged polynucleotide and amino acid molecules in their ability to influence mineralization rates and mineral particle size and morphology. This research demonstrates through time-resolved optical density and dynamic light scattering measurements that the combination of tiopronin, PEG, and DNA presented on a nanoparticle surface decreases nanoparticle aggregation from 59 to 21 nm solvated radius, increases mineralization kinetics from 1.5 × 10-3 to 3.1 × 10-3 OD/min, and decreases mineral particle size from 685 to 442 nm average radius. FT-IR and TEM data demonstrate that mineralized material, while initially amorphous, transforms to a semi-crystalline material when guided by template interactions. This demonstrates that surface-tailored monolayer protected cluster scaffolds are successful and controllable mineralization templates with further potential for biomedical applications involving calcium phosphate and other biomaterials.

  11. Use of alternative alkali chlorides in RT and PCR of polynucleotides containing G quadruplex structures.

    Science.gov (United States)

    Ramos-Alemán, Fabiola; González-Jasso, Eva; Pless, Reynaldo C

    2018-02-15

    Several alkali chlorides were compared for their use in reverse transcription (RT) and PCR of different types of nucleic acid templates. On a test region of biological DNA incapable of forming G quadruplex (G4) structures, Taq DNA polymerase showed similar PCR performance with 50 mM KCl, CsCl, LiCl, and NaCl. In contrast, on a synthetic model polydeoxyribonucleotide prone to G4 formation, good PCR amplification was obtained with 50 mM CsCl, but little or none with LiCl or KCl. Similarly, in RT of a G4-prone model polyribonucleotide, MMLV reverse transcriptase produced a good yield with 50 mM CsCl, mediocre yields with LiCl or without added alkali chloride, and a poor yield with 50 mM KCl. The full RT-PCR assay starting from the G4-prone polyribonucleotide, showed good results with CsCl in both stages, poor results with LiCl, and no product formation with KCl. The model polynucleotides showed fast G quadruplex formation under PCR or RT conditions with 50 mM KCl, but not with CsCl or LiCl. The results argue for the use of CsCl instead of KCl for RT and PCR of G4-prone sequences. No advantage was observed when using the 7-deaza type nucleotide analog c 7 dGTP in PCR amplification of the G4-prone polydeoxyribonucleotide. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Hepatitis C virus NS3 protein polynucleotide-stimulated nucleoside triphosphatase and comparison with the related pestivirus and flavivirus enzymes.

    Science.gov (United States)

    Suzich, J A; Tamura, J K; Palmer-Hill, F; Warrener, P; Grakoui, A; Rice, C M; Feinstone, S M; Collett, M S

    1993-01-01

    Sequence motifs within the nonstructural protein NS3 of members of the Flaviviridae family suggest that this protein possesses nucleoside triphosphatase (NTPase) and RNA helicase activity. The RNA-stimulated NTPase activity of this protein from prototypic members of the Pestivirus and Flavivirus genera has recently been established and enzymologically characterized. Here, we experimentally demonstrate that the NS3 protein from a member of the third genus of Flaviviridae, human hepatitis C virus (HCV), also possesses a polynucleotide-stimulated NTPase activity. Characterization of the purified HCV NTPase activity showed that it exhibited reaction condition optima with respect to pH, MgCl2, and salt identical to those of the representative pestivirus and flavivirus enzymes. However, each NTPase also possessed several unique properties when compared with one another. Notably, the profile of polynucleotide stimulation of the NTPase activity was distinct for the three enzymes. The HCV NTPase was the only one whose activity was significantly enhanced by a deoxyribopolynucleotide. Additional distinguishing features among the three enzymes relating to the kinetic properties of their NTPase activities are discussed. These studies provide a foundation for investigation of the putative RNA helicase activity of these proteins and for further study of the role of the NS3 proteins of members of the Flaviviridae in the replication cycle of these viruses. Images PMID:8396675

  13. Hematopoietic stem cell cytokines and fibroblast growth factor-2 stimulate human endothelial cell-pericyte tube co-assembly in 3D fibrin matrices under serum-free defined conditions.

    Directory of Open Access Journals (Sweden)

    Annie O Smith

    Full Text Available We describe a novel 3D fibrin matrix model using recombinant hematopoietic stem cell cytokines under serum-free defined conditions which promotes the assembly of human endothelial cell (EC tubes with co-associated pericytes. Individual ECs and pericytes are randomly mixed together and EC tubes form that is accompanied by pericyte recruitment to the EC tube abluminal surface over a 3-5 day period. These morphogenic processes are stimulated by a combination of the hematopoietic stem cell cytokines, stem cell factor, interleukin-3, stromal derived factor-1α, and Flt-3 ligand which are added in conjunction with fibroblast growth factor (FGF-2 into the fibrin matrix. In contrast, this tube morphogenic response does not occur under serum-free defined conditions when VEGF and FGF-2 are added together in the fibrin matrices. We recently demonstrated that VEGF and FGF-2 are able to prime EC tube morphogenic responses (i.e. added overnight prior to the morphogenic assay to hematopoietic stem cell cytokines in collagen matrices and, interestingly, they also prime EC tube morphogenesis in 3D fibrin matrices. EC-pericyte interactions in 3D fibrin matrices leads to marked vascular basement membrane assembly as demonstrated using immunofluorescence and transmission electron microscopy. Furthermore, we show that hematopoietic stem cell cytokines and pericytes stimulate EC sprouting in fibrin matrices in a manner dependent on the α5β1 integrin. This novel co-culture system, under serum-free defined conditions, allows for a molecular analysis of EC tube assembly, pericyte recruitment and maturation events in a critical ECM environment (i.e. fibrin matrices that regulates angiogenic events in postnatal life.

  14. Silencing of reversion-inducing cysteine-rich protein with Kazal motifs stimulates hyperplastic phenotypes through activation of epidermal growth factor receptor and hypoxia-inducible factor-2α.

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    You Mie Lee

    Full Text Available Reversion-inducing cysteine-rich protein with Kazal motifs (RECK, a tumor suppressor is down-regulated by the oncogenic signals and hypoxia, but the biological function of RECK in early tumorigenic hyperplastic phenotypes is largely unknown. Knockdown of RECK by small interfering RNA (siRECK or hypoxia significantly promoted cell proliferation in various normal epithelial cells. Hypoxia as well as knockdown of RECK by siRNA increased the cell cycle progression, the levels of cyclin D1 and c-Myc, and the phosphorylation of Rb protein (p-pRb, but decreased the expression of p21(cip1, p27(kip1, and p16(ink4A. HIF-2α was upregulated by knockdown of RECK, indicating HIF-2α is a downstream target of RECK. As knockdown of RECK induced the activation of epidermal growth factor receptor (EGFR and treatment of an EGFR kinase inhibitor, gefitinib, suppressed HIF-2α expression induced by the silencing of RECK, we can suggest that the RECK silenicng-EGFR-HIF-2α axis might be a key molecular mechanism to induce hyperplastic phenotype of epithelial cells. It was also found that shRNA of RECK induced larger and more numerous colonies than control cells in an anchorage-independent colony formation assay. Using a xenograft assay, epithelial cells with stably transfected with shRNA of RECK formed a solid mass earlier and larger than those with control cells in nude mice. In conclusion, the suppression of RECK may promote the development of early tumorigenic hyperplastic characteristics in hypoxic stress.

  15. Polymorphisms and haplotypes in the bovine neuropeptide Y, growth hormone receptor, ghrelin, insulin-like growth factor 2, and uncoupling proteins 2 and 3 genes and their associations with measures of growth, performance, feed efficiency, and carcass merit in beef cattle.

    Science.gov (United States)

    Sherman, E L; Nkrumah, J D; Murdoch, B M; Li, C; Wang, Z; Fu, A; Moore, S S

    2008-01-01

    Genes that regulate metabolism and energy partitioning have the potential to influence economically important traits in farm animals, as do polymorphisms within these genes. In the current study, SNP in the bovine neuropeptide Y (NPY), growth hormone receptor (GHR), ghrelin (GHRL), uncoupling proteins 2 and 3 (UCP2 and UCP3), IGF2, corticotrophin-releasing hormone (CRH), cocaine and amphetamine regulated transcript (CART), melanocortin-4 receptor (MC4R), proopiomelanocortin (POMC), and GH genes were evaluated for associations with growth, feed efficiency, and carcass merit in beef steers. In total, 24 SNP were evaluated for associations with these traits and haplotypes were constructed within each gene when 2 or more SNP showed significant associations. An A/G SNP located in intron 4 of the GHR gene had the largest effects on BW of the animals (dominance effect P GHRL gene tended to show effects on residual feed intake, FCR, and partial efficiency of growth (P < 0.10). The IGF2 SNP most strongly affected LM area (P < 0.01), back fat, ADG, and FCR (P < 0.05). The SNP in the CART, MC4R, POMC, GH, and CRH genes did not show associations at P < 0.05 with any of the traits. Although most of the SNP that showed associations do not cause amino acid changes, these SNP could be linked to other yet to be detected causative mutations or nearby QTL. It will be very important to verify these results in other cattle populations.

  16. Growth

    Science.gov (United States)

    John R. Jones; George A. Schier

    1985-01-01

    This chapter considers aspen growth as a process, and discusses some characteristics of the growth and development of trees and stands. For the most part, factors affecting growth are discussed elsewhere, particularly in the GENETICS AND VARIATION chapter and in chapters in PART 11. ECOLOGY. Aspen growth as it relates to wood production is examined in the WOOD RESOURCE...

  17. The anti-oxidative transcription factor Nuclear factor E2 related factor-2 (Nrf2) counteracts TGF-β1 mediated growth inhibition of pancreatic ductal epithelial cells -Nrf2 as determinant of pro-tumorigenic functions of TGF-β1

    International Nuclear Information System (INIS)

    Genrich, Geeske; Kruppa, Marcus; Lenk, Lennart; Helm, Ole; Broich, Anna; Freitag-Wolf, Sandra; Röcken, Christoph; Sipos, Bence; Schäfer, Heiner; Sebens, Susanne

    2016-01-01

    Nuclear factor E2 related factor-2 (Nrf2) is an oxidative stress inducible transcription factor being essential in regulating cell homeostasis. Thus, acute induction of Nrf2 in epithelial cells exposed to inflammation confers protection from oxidative cell damage and mutagenesis supporting an anti-tumorigenic role for Nrf2. However, pancreatic ductal adenocarcinoma (PDAC) is characterized by persistent Nrf2 activity conferring therapy resistance which points to a pro-tumorigenic role of Nrf2. A similar dichotomous role in tumorigenesis is described for the Transforming Growth Factor-beta 1 (TGF-β1). The present study therefore aimed at elucidating whether the switch of Nrf2 function towards a tumor promoting one relates to the modulation of TGF-β1 induced cell responses and whether this might occur early in PDAC development. In situ analysis comprised immunohistochemical stainings of activated (phosphorylated) Nrf2 and Ki67 in pancreatic tissues containing normal ducts and pancreatic intraepithelial neoplasia (PanINs). In vitro, Nrf2 levels in benign (H6c7-pBp), premalignant (H6c7-kras) and malignant (Colo357) pancreatic ductal epithelial cells were modulated by Nrf2 specific siRNA or Nrf2 overexpression. Then, the effect of Nrf2 alone and in combination with TGF-β1 on cell growth and survival was investigated by cell counting, Ki67 staining and apoptosis assays. The underlying cell signaling was investigated by western blotting. Statistical analysis was performed by Shapiro-Wilk test for normal distribution. Parametric data were analyzed by one-way ANOVA, while non-parametric data were analyzed by Kruskal-Wallis one-way ANOVA on ranks. Significantly elevated expression of activated Nrf2 and Ki67 could be detected in PanINs but not in normal pancreatic ductal epithelium. While the effect of Nrf2 on basal cell growth of H6c7-pBp, H6c7-kras and Colo357 cells was minor, it clearly attenuated the growth inhibiting effects of TGF-β1 in all cell lines. This enhanced

  18. Surface-enhanced Raman Scattering Study of the Binding Modes of a Dibenzotetraaza[14]annulene Derivative with DNA/RNA Polynucleotides

    OpenAIRE

    Miljanić, Snežana; Dijanošić, Adriana; Kalac, Matea; Radić Stojković, Marijana; Piantanida, Ivo; Pawlica, Dariusz; Eilmes, Julita

    2012-01-01

    Binding modes of a dibenzotetraaza14annulene (DBTAA) derivative with synthetic nucleic acids were studied using surface-enhanced Raman spectroscopy (SERS). Changes in SERS intensity and appearance of new bands in spectra were attributed to different complexes formed between the DBTAA molecules and DNA/RNA polynucleotides. A decrease in intensity pointed to intercalation as the dominant binding mode of the annulene derivative with poly dGdC-poly dGdC and poly rA-poly rU, whereas new bands in...

  19. Identification of genes potentially regulated by human polynucleotide phosphorylase (hPNPase old-35 using melanoma as a model.

    Directory of Open Access Journals (Sweden)

    Upneet K Sokhi

    Full Text Available Human Polynucleotide Phosphorylase (hPNPase(old-35 or PNPT1 is an evolutionarily conserved 3'→ 5' exoribonuclease implicated in the regulation of numerous physiological processes including maintenance of mitochondrial homeostasis, mtRNA import and aging-associated inflammation. From an RNase perspective, little is known about the RNA or miRNA species it targets for degradation or whose expression it regulates; except for c-myc and miR-221. To further elucidate the functional implications of hPNPase(old-35 in cellular physiology, we knocked-down and overexpressed hPNPase(old-35 in human melanoma cells and performed gene expression analyses to identify differentially expressed transcripts. Ingenuity Pathway Analysis indicated that knockdown of hPNPase(old-35 resulted in significant gene expression changes associated with mitochondrial dysfunction and cholesterol biosynthesis; whereas overexpression of hPNPase(old-35 caused global changes in cell-cycle related functions. Additionally, comparative gene expression analyses between our hPNPase(old-35 knockdown and overexpression datasets allowed us to identify 77 potential "direct" and 61 potential "indirect" targets of hPNPase(old-35 which formed correlated networks enriched for cell-cycle and wound healing functional association, respectively. These results provide a comprehensive database of genes responsive to hPNPase(old-35 expression levels; along with the identification new potential candidate genes offering fresh insight into cellular pathways regulated by PNPT1 and which may be used in the future for possible therapeutic intervention in mitochondrial- or inflammation-associated disease phenotypes.

  20. HPLC analysis of 4',5'-monoadduct formation in calf thymus DNA and synthetic polynucleotides treated with UVA and 8-methoxypsoralen

    International Nuclear Information System (INIS)

    Gasparro, F.P.; Bagel, J.; Edelson, R.L.

    1985-01-01

    8-methoxypsoralen monoadduct formation in calf thymus DNA irradiated with subbands of ultraviolet A light has been quantitated by HPLC analysis of the enzymatic hydrolysates of the DNA. Normalization of the yield of monoadducts for the variation in source output and the absorptivity of 8-MOP at each of the irradiating wavelengths showed that the 4',5'-furan monoadduct was the principal photoproduct and the efficiency of its formation was independent of irradiating wavelength. Synthetic polynucleotides irradiated with ultraviolet A light demonstrated a base composition and sequence dependence for 8-MOP photoreactivity: (poly(dAdT.dAdT)>poly(dA.dT)>poly(dGdC.dGdC) in both the B and Z forms>poly(dT). (author)

  1. Characterization of Runella slithyformis HD-Pnk, a bifunctional DNA/RNA end-healing enzyme composed of an N-terminal 2',3' -phosphoesterase HD domain and a C-terminal 5' -OH polynucleotide kinase domain.

    Science.gov (United States)

    Munir, Annum; Shuman, Stewart

    2016-11-28

    5' and 3' end healing are key steps in nucleic acid break repair in which 5' -OH ends are phosphorylated by a polynucleotide kinase and 3' -PO 4 or 2',3' -cyclic-PO 4 ends are hydrolyzed by a phosphoesterase to generate the 5' -PO 4 and 3' -OH termini required for sealing by classic polynucleotide ligases. End healing and sealing enzymes are present in diverse bacterial taxa, often organized as modular units within a single multifunctional polypeptide or as subunits of a repair complex. Here we identify and characterize Runella slithyformis HD-Pnk as a novel bifunctional end-healing enzyme composed of an N-terminal 2',3' -phosphoesterase HD domain and a C-terminal 5' -OH polynucleotide kinase P-loop domain. HD-Pnk phosphorylates 5' -OH polynucleotides (9-mers or longer) in the presence of magnesium and any NTP donor. HD-Pnk dephosphorylates RNA 2',3' -cyclic phosphate, RNA 3' -phosphate, RNA 2' -phosphate, and DNA 3' -phosphate ends in the presence of a transition metal cofactor, which can be nickel, copper or cobalt. HD-Pnkp homologs are present in genera from eleven bacterial phyla and are often encoded in an operon with a putative ATP-dependent polynucleotide ligase. The present study provides insights to the diversity of nucleic acid repair strategies via the characterization of Runella slithyformis HD-Pnkp as the exemplar of a novel clade of dual 5' and 3' end-healing enzymes that phosphorylate 5' -OH termini and dephosphorylate 2',3' -cyclic-PO 4 , 3' -PO 4 , and 2' -PO 4 ends. The distinctive feature of HD-Pnk is its domain composition: a fusion of an N-terminal HD phosphohydrolase module to a C-terminal P-loop polynucleotide kinase module. Homologs of Runella HD-Pnk with the same domain composition, domain order, and similar polypeptide size are distributed widely among genera from eleven bacterial phyla. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. S100ß and fibroblast growth factor-2 are present in cultured Schwann cells and may exert paracrine actions on the peripheral nerve injury S100ß e fator de crescimento de fibroblasto-2 estão presentes nas células de Schwann cultivadas e exercem ações parácrinas na lesão do nervo

    Directory of Open Access Journals (Sweden)

    Tatiana Duobles

    2008-12-01

    Full Text Available PURPOSE: The neurotrophic factor fibroblast growth factor-2 (FGF-2, bFGF and Ca++ binding protein S100ß are expressed by the Schwann cells of the peripheral nerves and by the satellite cells of the dorsal root ganglia (DRG. Recent studies have pointed out the importance of the molecules in the paracrine mechanisms related to neuronal maintenance and plasticity of lesioned motor and sensory peripheral neurons. Moreover, cultured Schwann cells have been employed experimentally in the treatment of central nervous system lesions, in special the spinal cord injury, a procedure that triggers an enhanced sensorymotor function. Those cells have been proposed to repair long gap nerve injury. METHODS: Here we used double labeling immunohistochemistry and Western blot to better characterize in vitro and in vivo the presence of the proteins in the Schwann cells and in the satellite cells of the DRG as well as their regulation in those cells after a crush of the rat sciatic nerve. RESULTS: FGF-2 and S100ß are present in the Schwann cells of the sciatic nerve and in the satellite cells of the DRG. S100ß positive satellite cells showed increased size of the axotomized DRG and possessed elevated amount of FGF-2 immunoreactivity. Reactive satellite cells with increased FGF-2 labeling formed a ring-like structure surrounding DRG neuronal cell bodies.Reactive S100ß positive Schwann cells of proximal stump of axotomized sciatic nerve also expressed higher amounts of FGF-2. CONCLUSION: Reactive peripheral glial cells synthesizing FGF-2 and S100ß may be important in wound repair and restorative events in the lesioned peripheral nerves.OBJETIVO: O fator neurotrófico fator de crescimento de fibroblastos-2 (FGF-2, bFGF e a proteína ligante de Ca++ S100ß são expressos pelas células de Schwann dos nervos e por células satélites do gânglio da raiz dorsal (GRD. Estudos recentes indicam a importância das moléculas nos mecanismos parácrinos relacionados

  3. Damage to uracil- and adenine-containing bases, nucleosides, nucleotides and polynucleotides: quantum yields on irradiation at 193 and 254 nm

    International Nuclear Information System (INIS)

    Gurzadyan, G.G.; Goerner, H.

    1994-01-01

    Photoreactions, such as base release and decomposition of the base moeity, induced by either 20 ns laser pulses at 193 nm or continuous 254 nm irradiation, were studied for a series of uracil and adenine derivatives in neutral aqueous solution. The quantum yield of chromophore loss (Φ cl ) depends significantly on the nature of the nucleic acid constituent and the saturating gas (Ar, N 2 O or O 2 ). In the case of polynucleotides the destruction of nucleotides was measured by high-performance liquid chromatography after hydrolysis; the quantum yields (Φ dn ) are comparable to those of chromophore loss or larger. The Φ cl and Φ dn of 0.04-0.1 for poly(U) and poly(dU), obtained for both wavelengths of irradiation, are due to processes originating from the lowest excited singlet state, i.e. formation of photohydrates and photodimers, and a second part from photoionization using λ irr = 193 nm. Irradiation at 193 nm effectively splits pyrimidine dimers and thus reverts them into monomers. (author)

  4. Lingering single-strand breaks trigger Rad51-independent homology-directed repair of collapsed replication forks in the polynucleotide kinase/phosphatase mutant of fission yeast.

    Directory of Open Access Journals (Sweden)

    Arancha Sanchez

    2017-09-01

    Full Text Available The DNA repair enzyme polynucleotide kinase/phosphatase (PNKP protects genome integrity by restoring ligatable 5'-phosphate and 3'-hydroxyl termini at single-strand breaks (SSBs. In humans, PNKP mutations underlie the neurological disease known as MCSZ, but these individuals are not predisposed for cancer, implying effective alternative repair pathways in dividing cells. Homology-directed repair (HDR of collapsed replication forks was proposed to repair SSBs in PNKP-deficient cells, but the critical HDR protein Rad51 is not required in PNKP-null (pnk1Δ cells of Schizosaccharomyces pombe. Here, we report that pnk1Δ cells have enhanced requirements for Rad3 (ATR/Mec1 and Chk1 checkpoint kinases, and the multi-BRCT domain protein Brc1 that binds phospho-histone H2A (γH2A at damaged replication forks. The viability of pnk1Δ cells depends on Mre11 and Ctp1 (CtIP/Sae2 double-strand break (DSB resection proteins, Rad52 DNA strand annealing protein, Mus81-Eme1 Holliday junction resolvase, and Rqh1 (BLM/WRN/Sgs1 DNA helicase. Coupled with increased sister chromatid recombination and Rad52 repair foci in pnk1Δ cells, these findings indicate that lingering SSBs in pnk1Δ cells trigger Rad51-independent homology-directed repair of collapsed replication forks. From these data, we propose models for HDR-mediated tolerance of persistent SSBs with 3' phosphate in pnk1Δ cells.

  5. DNA synthesis and degradation in UV-irradiated toluene treated cells of E. coli K12: the role of polynucleotide ligase

    International Nuclear Information System (INIS)

    Strike, P.

    1977-01-01

    Toluene treated cells have been used to study the processes of DNA synthesis and DNA degradation in ultra-violet irradiated Escherichia coli K12. Synthesis and degradation are both shown to occur extensively if polynucleotide ligase is inhibited, and to occur to a much lesser extent if ligase activity is optimal. Extensive UV-induced DNA synthesis in toluene-treated cells requires ATP for the initial incision step, and DNA polymerase I. Extensive degradation also depends on the early ATP-dependent incision step, and the subsequent degradation shows a partial requirement for ATP. Curtailment of degradation by ligase requires DNA polymerase activity, but is not dependent upon DNA polymerase I. Apparently this process can be carried out with equal facility by either DNA polymerase II or polymerase III. These observations suggest that extensive DNA polymerase I-dependent repair synthesis and extensive DNA degradation are facets of two divergent pathways of excision repair, both of which depend upon the early uvrABC determined ATP-dependent incision step. (orig.) [de

  6. Polynucleotide probes that target a hypervariable region of 16S rRNA genes to identify bacterial isolates corresponding to bands of community fingerprints.

    Science.gov (United States)

    Heuer, H; Hartung, K; Wieland, G; Kramer, I; Smalla, K

    1999-03-01

    Temperature gradient gel electrophoresis (TGGE) is well suited for fingerprinting bacterial communities by separating PCR-amplified fragments of 16S rRNA genes (16S ribosomal DNA [rDNA]). A strategy was developed and was generally applicable for linking 16S rDNA from community fingerprints to pure culture isolates from the same habitat. For this, digoxigenin-labeled polynucleotide probes were generated by PCR, using bands excised from TGGE community fingerprints as a template, and applied in hybridizations with dot blotted 16S rDNA amplified from bacterial isolates. Within 16S rDNA, the hypervariable V6 region, corresponding to positions 984 to 1047 (Escherichia coli 16S rDNA sequence), which is a subset of the region used for TGGE (positions 968 to 1401), best met the criteria of high phylogenetic variability, required for sufficient probe specificity, and closely flanking conserved priming sites for amplification. Removal of flanking conserved bases was necessary to enable the differentiation of closely related species. This was achieved by 5' exonuclease digestion, terminated by phosphorothioate bonds which were synthesized into the primers. The remaining complementary strand was removed by single-strand-specific digestion. Standard hybridization with truncated probes allowed differentiation of bacteria which differed by only two bases within the probe target site and 1.2% within the complete 16S rDNA. However, a truncated probe, derived from an excised TGGE band of a rhizosphere community, hybridized with three phylogenetically related isolates with identical V6 sequences. Only one of the isolates comigrated with the excised band in TGGE, which was shown to be due to identical sequences, demonstrating the utility of a combined TGGE and V6 probe approach.

  7. Label-free and sensitive detection of T4 polynucleotide kinase activity via coupling DNA strand displacement reaction with enzymatic-aided amplification.

    Science.gov (United States)

    Cheng, Rui; Tao, Mangjuan; Shi, Zhilu; Zhang, Xiafei; Jin, Yan; Li, Baoxin

    2015-11-15

    Several fluorescence signal amplification strategies have been developed for sensitive detection of T4 polynucleotide kinase (T4 PNK) activity, but they need fluorescence dye labeled DNA probe. We have addressed the limitation and report here a label-free strategy for sensitive detection of PNK activity by coupling DNA strand displacement reaction with enzymatic-aided amplification. A hairpin oligonucleotide (hpDNA) with blunt ends was used as the substrate for T4 PNK phosphorylation. In the presence of T4 PNK, the stem of hpDNA was phosphorylated and further degraded by lambda exonuclease (λ exo) from 5' to 3' direction to release a single-stranded DNA as a trigger of DNA strand displacement reaction (SDR). The trigger DNA can continuously displace DNA P2 from P1/P2 hybrid with the help of specific cleavage of nicking endonuclease (Nt.BbvCI). Then, DNA P2 can form G-quadruplex in the presence of potassium ions and quadruplex-selective fluorphore, N-methyl mesoporphyrin IX (NMM), resulting in a significant increase in fluorescence intensity of NMM. Thus, the accumulative release of DNA P2 led to fluorescence signal amplification for determining T4 PNK activity with a detection limit of 6.6×10(-4) U/mL, which is superior or comparative with established approaches. By ingeniously utilizing T4 PNK-triggered DNA SDR, T4 PNK activity can be specifically and facilely studied in homogeneous solution containing complex matrix without any external fluorescence labeling. Moreover, the influence of different inhibitors on the T4 PNK activity revealed that it also can be explored to screen T4 PNK inhibitors. Therefore, this label-free amplification strategy presents a facile and cost-effective approach for nucleic acid phosphorylation related research. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. New ribosome-inactivating proteins with polynucleotide:adenosine glycosidase and antiviral activities from Basella rubra L. and bougainvillea spectabilis Willd.

    Science.gov (United States)

    Bolognesi, A; Polito, L; Olivieri, F; Valbonesi, P; Barbieri, L; Battelli, M G; Carusi, M V; Benvenuto, E; Del Vecchio Blanco, F; Di Maro, A; Parente, A; Di Loreto, M; Stirpe, F

    1997-12-01

    New single-chain (type 1) ribosome-inactivating proteins (RIPs) were isolated from the seeds of Basella rubra L. (two proteins) and from the leaves of Bougainvillea spectabilis Willd. (one protein). These RIPs inhibit protein synthesis both in a cell-free system, with an IC50 (concentration causing 50% inhibition) in the 10(-10) M range, and by various cell lines, with IC50S in the 10(-8)-10(-6) M range. All three RIPs released adenine not only from rat liver ribosomes but also from Escherichia coli rRNA, polyadenylic acid, herring sperm DNA, and artichoke mottled crinkle virus (AMCV) genomic RNA, thus being polynucleotide:adenosine glycosidases. The proteins from Basella rubra had toxicity to mice similar to that of most type 1 RIPs (Barbieri et al., 1993, Biochim Biophys Acta 1154: 237-282) with an LD50 (concentration that is 50% lethal) Bougainvillea spectabilis had an LD50 > 32 mg.kg-1. The N-terminal sequence of the two RIPs from Basella rubra had 80-93% identity, whereas it differed from the sequence of the RIP from Bougainvillea spectabilis. When tested with antibodies against various RIPs, the RIPs from Basella gave some cross-reactivity with sera against dianthin 32, and weak cross-reactivity with momordin I and momorcochin-S, whilst the RIP from Bougainvillea did not cross-react with any antiserum tested. An RIP from Basella rubra and one from Bougainvillea spectabilis were tested for antiviral activity, and both inhibited infection of Nicotiana benthamiana by AMCV.

  9. The life and death of translation elongation factor 2

    DEFF Research Database (Denmark)

    Jørgensen, Rene; Merrill, A.R.; Andersen, Gregers Rom

    2006-01-01

    The eukaryotic elongation factor 2 (eEF2) occupies an essential role in protein synthesis where it catalyses the translocation of the two tRNAs and the mRNA after peptidyl transfer on the 80S ribosome. Recent crystal structures of eEF2 and the cryo-EM reconstruction of its 80S complex now provide...... diphthamide residue, which is ADP-ribosylated by diphtheria toxin from Corynebacterium diphtheriae and exotoxin A from Pseudomonas aeruginosa....

  10. Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

    Science.gov (United States)

    Qin, Jun; He, Yue; Duan, Ming; Luo, Meng

    2017-05-01

    We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Polynucleotide Phosphorylase, RNase E/G, and YbeY Are Involved in the Maturation of 4.5S RNA in Corynebacterium glutamicum.

    Science.gov (United States)

    Maeda, Tomoya; Tanaka, Yuya; Wachi, Masaaki; Inui, Masayuki

    2017-03-01

    Corynebacterium glutamicum has been applied for the industrial production of various metabolites, such as amino acids. To understand the biosynthesis of the membrane protein in this bacterium, we investigated the process of signal recognition particle (SRP) assembly. SRP is found in all three domains of life and plays an important role in the membrane insertion of proteins. SRP RNA is initially transcribed as precursor molecules; however, relatively little is known about its maturation. In C. glutamicum , SRP consists of the Ffh protein and 4.5S RNA lacking an Alu domain. In this study, we found that 3'-to-5' exoribonuclease, polynucleotide phosphorylase (PNPase), and two endo-type RNases, RNase E/G and YbeY, are involved in the 3' maturation of 4.5S RNA in C. glutamicum The mature form of 4.5S RNA was inefficiently formed in Δ rneG Δ pnp mutant cells, suggesting the existence of an alternative pathway for the 3' maturation of 4.5S RNA. Primer extension analysis also revealed that the 5' mature end of 4.5S RNA corresponds to that of the transcriptional start site. Immunoprecipitated Ffh protein contained immature 4.5S RNA in Δ pnp , Δ rneG , and Δ ybeY mutants, suggesting that 4.5S RNA precursors can interact with Ffh. These results imply that the maturation of 4.5S RNA can be performed in the 4.5S RNA-Ffh complex. IMPORTANCE Overproduction of a membrane protein, such as a transporter, is useful for engineering of strains of Corynebacterium glutamicum , which is a workhorse of amino acid production. To understand membrane protein biogenesis in this bacterium, we investigated the process of signal recognition particle (SRP) assembly. SRP contains the Ffh protein and SRP RNA and plays an important role in the membrane insertion of proteins. Although SRP RNA is highly conserved among the three domains of life, relatively little is known about its maturation. We show that PNPase, RNase E/G, and YbeY are involved in the 3' maturation of the SRP RNA (4.5S RNA) in

  12. Expression pattern of vascular endothelial growth factor 2 during sea urchin development.

    Science.gov (United States)

    Kipryushina, Yulia O; Yakovlev, Konstantin V; Kulakova, Milana A; Odintsova, Nelly A

    2013-12-01

    The VEGF family in the sea urchin is comprised of three members designated Vegf1 through Vegf3. In this study, we found a high level of similarity between the PDGF/VEGF domain of the predicted gene Sp-Vegf2 in the sea urchin Strongylocentrotus purpuratus and the same domain of a gene that we found in a closely related sea urchin, Strongylocentrotus intermedius. The sequence of the Si-Vegf2 cDNA was determined, and the expression of the Si-Vegf2 mRNA throughout early sea urchin development was studied by RT-PCR and in situ hybridization. Also we analyzed phylogenetic relationships of Si-Vegf2 and other members of the PDGF and VEGF families. We have found that the Si-Vegf2 present during the time span from the egg to the 4-arm pluteus stage. This mRNA is uniformly distributed in eggs, cleaving embryos and early blastulae. At the gastrula stage, the Si-Vegf2 transcripts are localized in the ventrolateral clusters of primary mesenchyme cells, and later, at the prism stage, they are detected in the forming apex. At the early pluteus stage, Si-Vegf2 mRNAs are found in two groups of mesenchyme cells in the scheitel region on the apical pole. We have determined that Si-Vegf2 is a mesenchyme-expressed factor but its developmental function is unknown. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Characterization of Runella slithyformis HD-Pnk, a Bifunctional DNA/RNA End-Healing Enzyme Composed of an N-Terminal 2′,3′-Phosphoesterase HD Domain and a C-Terminal 5′-OH Polynucleotide Kinase Domain

    Science.gov (United States)

    Munir, Annum

    2016-01-01

    ABSTRACT 5′- and 3′-end-healing reactions are key steps in nucleic acid break repair in which 5′-OH ends are phosphorylated by a polynucleotide kinase (Pnk) and 3′-PO4 or 2′,3′-cyclic-PO4 ends are hydrolyzed by a phosphoesterase to generate the 5′-PO4 and 3′-OH termini required for sealing by classic polynucleotide ligases. End-healing and sealing enzymes are present in diverse bacterial taxa, often organized as modular units within a single multifunctional polypeptide or as subunits of a repair complex. Here we identify and characterize Runella slithyformis HD-Pnk as a novel bifunctional end-healing enzyme composed of an N-terminal 2′,3′-phosphoesterase HD domain and a C-terminal 5′-OH polynucleotide kinase P-loop domain. HD-Pnk phosphorylates 5′-OH polynucleotides (9-mers or longer) in the presence of magnesium and any nucleoside triphosphate donor. HD-Pnk dephosphorylates RNA 2′,3′-cyclic phosphate, RNA 3′-phosphate, RNA 2′-phosphate, and DNA 3′-phosphate ends in the presence of a transition metal cofactor, which can be nickel, copper, or cobalt. HD-Pnk homologs are present in genera from 11 bacterial phyla and are often encoded in an operon with a putative ATP-dependent polynucleotide ligase. IMPORTANCE The present study provides insights regarding the diversity of nucleic acid repair strategies via the characterization of Runella slithyformis HD-Pnk as the exemplar of a novel clade of dual 5′- and 3′-end-healing enzymes that phosphorylate 5′-OH termini and dephosphorylate 2′,3′-cyclic-PO4, 3′-PO4, and 2′-PO4 ends. The distinctive feature of HD-Pnk is its domain composition, i.e., a fusion of an N-terminal HD phosphohydrolase module and a C-terminal P-loop polynucleotide kinase module. Homologs of Runella HD-Pnk with the same domain composition, same domain order, and similar polypeptide sizes are distributed widely among genera from 11 bacterial phyla. PMID:27895092

  14. Phosphorylation of protein synthesis initiation factor 2 (elF-2) in the yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Romero, D.P.

    1986-01-01

    Initiation Factor 2 (elF-2) in the yeast Saccharomyces cerevisiae is comprised of 3 subunits. The control of protein synthesis in mammalian cells have been shown to involve the phosphorylation of the small (alpha) subunit by a specific protein kinase. Phosphorylation results in an inhibition of protein synthesis. In order to determine whether or not an analogous system is operative in yeast, the phosphorylation state of the alpha subunit of elF-2 in Saccharomyces was determined during various growth and nongrowth conditions. Cells were radiolabelled with 32 P and 35 S, and the whole cell lysates were analyzed by two dimensional gel electrophoresis. These experiments revealed that the smallest subunit (alpha, M/sub r/ = 31,000) is a phosphoprotein in vivo under a variety of growth and nongrowth conditions. This is in direct contrast to the pattern exhibited in mammalian cells. The fact that the small subunit of elF-2 in yeast is phosphorylated under a variety of physiological conditions indicates that such a covalent modification is important for some aspects of elF-2 function. In order to investigate this problem further, a protein kinase that specifically labels the alpha subunit of elF-2 in vitro was isolated. The kinase is not autophosphorylating, utilizes ATP as a phosphate donor, phosphorylates an exogenous protein, casein, modifies serine residues in elF-2, is cyclic nucleotide-independent, and is strongly inhibited by heparin

  15. Expression of paired-like homeodomain transcription factor 2c (PITX2c) in epidermal keratinocytes

    International Nuclear Information System (INIS)

    Shi, Ge; Sohn, Kyung-Cheol; Choi, Tae-Young; Choi, Dae-Kyoung; Lee, Sang-Sin; Ou, Bai-sheng; Kim, Sooil; Lee, Young Ho; Yoon, Tae-Jin; Kim, Seong-Jin; Lee, Young; Seo, Young-Joon; Lee, Jeung-Hoon; Kim, Chang Deok

    2010-01-01

    Paired-like homeodomain transcription factor 2 (PITX2) has been implicated as one of the genes responsible for Rieger syndrome. It has been also shown to play a central role during development. In this study, we investigated the functional role of PITX2 in keratinocyte differentiation. RT-PCR analysis showed that PITX2c isoform was predominantly expressed in a differentiation-dependent manner. Consistent with, immunohistochemical staining showed that PITX2 expression was increased in the upper layer of epidermis. When PITX2c was overexpressed in cultured keratinocytes by a recombinant adenovirus, the differentiation markers such as involucrin and loricrin were significantly increased at both mRNA and protein levels. In addition, PITX2c overexpression led to the decrease of cell growth, concomitantly with the upregulation of cell cycle-related genes p21. To investigate the effect of PITX2c in vivo, we microinjected PITX2c expression vector into zebrafish embryo. Interestingly, overexpression of PITX2c in zebrafish embryo led to the formation of horn-like structure and thickening of epidermis, together with the increase of keratin 8 (K8) expression. These results suggest that PITX2c has a role in proliferation and differentiation of epidermal keratinocytes.

  16. Expression of paired-like homeodomain transcription factor 2c (PITX2c) in epidermal keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Ge [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Department of Dermatology, The First Affiliated Hospital, Guangxi Traditional Chinese Medical University, Guangxi, Nanning, 530023 (China); Sohn, Kyung-Cheol; Choi, Tae-Young; Choi, Dae-Kyoung; Lee, Sang-Sin [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Ou, Bai-sheng [Department of Dermatology, The First Affiliated Hospital, Guangxi Traditional Chinese Medical University, Guangxi, Nanning, 530023 (China); Kim, Sooil; Lee, Young Ho [Department of Anatomy, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Yoon, Tae-Jin [Department of Dermatology, School of Medicine, Gyeongsang National University, Jinju, 660-702 (Korea, Republic of); Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 660-702 (Korea, Republic of); Kim, Seong-Jin [Department of Dermatology, Chonnam National University Medical School, Gwangju, 501-757 (Korea, Republic of); Lee, Young; Seo, Young-Joon; Lee, Jeung-Hoon [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Kim, Chang Deok, E-mail: cdkimd@cnu.ac.kr [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of)

    2010-11-15

    Paired-like homeodomain transcription factor 2 (PITX2) has been implicated as one of the genes responsible for Rieger syndrome. It has been also shown to play a central role during development. In this study, we investigated the functional role of PITX2 in keratinocyte differentiation. RT-PCR analysis showed that PITX2c isoform was predominantly expressed in a differentiation-dependent manner. Consistent with, immunohistochemical staining showed that PITX2 expression was increased in the upper layer of epidermis. When PITX2c was overexpressed in cultured keratinocytes by a recombinant adenovirus, the differentiation markers such as involucrin and loricrin were significantly increased at both mRNA and protein levels. In addition, PITX2c overexpression led to the decrease of cell growth, concomitantly with the upregulation of cell cycle-related genes p21. To investigate the effect of PITX2c in vivo, we microinjected PITX2c expression vector into zebrafish embryo. Interestingly, overexpression of PITX2c in zebrafish embryo led to the formation of horn-like structure and thickening of epidermis, together with the increase of keratin 8 (K8) expression. These results suggest that PITX2c has a role in proliferation and differentiation of epidermal keratinocytes.

  17. The Rev1 interacting region (RIR) motif in the scaffold protein XRCC1 mediates a low-affinity interaction with polynucleotide kinase/phosphatase (PNKP) during DNA single-strand break repair.

    Science.gov (United States)

    Breslin, Claire; Mani, Rajam S; Fanta, Mesfin; Hoch, Nicolas; Weinfeld, Michael; Caldecott, Keith W

    2017-09-29

    The scaffold protein X-ray repair cross-complementing 1 (XRCC1) interacts with multiple enzymes involved in DNA base excision repair and single-strand break repair (SSBR) and is important for genetic integrity and normal neurological function. One of the most important interactions of XRCC1 is that with polynucleotide kinase/phosphatase (PNKP), a dual-function DNA kinase/phosphatase that processes damaged DNA termini and that, if mutated, results in ataxia with oculomotor apraxia 4 (AOA4) and microcephaly with early-onset seizures and developmental delay (MCSZ). XRCC1 and PNKP interact via a high-affinity phosphorylation-dependent interaction site in XRCC1 and a forkhead-associated domain in PNKP. Here, we identified using biochemical and biophysical approaches a second PNKP interaction site in XRCC1 that binds PNKP with lower affinity and independently of XRCC1 phosphorylation. However, this interaction nevertheless stimulated PNKP activity and promoted SSBR and cell survival. The low-affinity interaction site required the highly conserved Rev1-interacting region (RIR) motif in XRCC1 and included three critical and evolutionarily invariant phenylalanine residues. We propose a bipartite interaction model in which the previously identified high-affinity interaction acts as a molecular tether, holding XRCC1 and PNKP together and thereby promoting the low-affinity interaction identified here, which then stimulates PNKP directly. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Novel characteristics of the biological properties of the yeast Saccharomyces cerevisiae eukaryotic initiation factor 2A.

    Science.gov (United States)

    Komar, Anton A; Gross, Stephane R; Barth-Baus, Diane; Strachan, Ryan; Hensold, Jack O; Goss Kinzy, Terri; Merrick, William C

    2005-04-22

    Eukaryotic initiation factor 2A (eIF2A) has been shown to direct binding of the initiator methionyl-tRNA (Met-tRNA(i)) to 40 S ribosomal subunits in a codon-dependent manner, in contrast to eIF2, which requires GTP but not the AUG codon to bind initiator tRNA to 40 S subunits. We show here that yeast eIF2A genetically interacts with initiation factor eIF4E, suggesting that both proteins function in the same pathway. The double eIF2A/eIF4E-ts mutant strain displays a severe slow growth phenotype, which correlated with the accumulation of 85% of the double mutant cells arrested at the G(2)/M border. These cells also exhibited a disorganized actin cytoskeleton and elevated actin levels, suggesting that eIF2A might be involved in controlling the expression of genes involved in morphogenic processes. Further insights into eIF2A function were gained from the studies of eIF2A distribution in ribosomal fractions obtained from either an eIF5BDelta (fun12Delta) strain or a eIF3b-ts (prt1-1) strain. It was found that the binding of eIF2A to 40 and 80 S ribosomes was not impaired in either strain. We also found that eIF2A functions as a suppressor of Ure2p internal ribosome entry site-mediated translation in yeast cells. The regulation of expression from the URE2 internal ribosome entry site appears to be through the levels of eIF2A protein, which has been found to be inherently unstable with a half-life of approximately 17 min. It was hypothesized that this instability allows for translational control through the level of eIF2A protein in yeast cells.

  19. Fibroblast Growth Factor-2 regulates proliferation of cardiac myocytes in normal and hypoplastic left ventricles in the developing chick

    Czech Academy of Sciences Publication Activity Database

    Dealmeida, A.; Sedmera, David

    2009-01-01

    Roč. 19, č. 2 (2009), s. 159-169 ISSN 1047-9511 R&D Projects: GA ČR GA304/08/0615 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50110509 Keywords : Chick embryo * Hypoplastic left heart syndrome * Adenovirus Subject RIV: EA - Cell Biology Impact factor: 1.183, year: 2009

  20. Drosophila imaginal disc growth factor 2 is a trophic factor involved in energy balance, detoxification, and innate immunity

    Czech Academy of Sciences Publication Activity Database

    Brož, Václav; Kučerová, Lucie; Rouhová, L.; Fleischmannová, Jana; Strnad, Hynek; Bryant, P. J.; Žurovec, Michal

    2017-01-01

    Roč. 7, FEB 23 (2017), č. článku 43273. ISSN 2045-2322 R&D Projects: GA ČR GA14-27816S; GA ČR GA14-07172S Institutional support: RVO:60077344 ; RVO:68378050 Keywords : Drosophila * innate immunity * IDGF2 Subject RIV: CE - Biochemistry; CE - Biochemistry (UMG-J) OBOR OECD: Biochemistry and molecular biology; Biochemistry and molecular biology (UMG-J) Impact factor: 4.259, year: 2016 http://www.nature.com/articles/srep43273

  1. Fibroblast Growth Factor-2 Enhances Expansion of Human Bone Marrow-Derived Mesenchymal Stromal Cells without Diminishing Their Immunosuppressive Potential

    OpenAIRE

    Auletta, Jeffery J.; Zale, Elizabeth A.; Welter, Jean F.; Solchaga, Luis A.

    2011-01-01

    Allogeneic hematopoietic stem cell transplantation is the main curative therapy for many hematologic malignancies. Its potential relies on graft-versus-tumor effects which associate with graft-versus-host disease. Mesenchymal stromal cells (MSCs) possess immunomodulatory properties that make them attractive therapeutic alternatives. We evaluated the in vitro immunosuppressive activity of medium conditioned by human MSCs from 5 donors expanded 13 passages with or without FGF-2. FGF-2 supplemen...

  2. Nonnegative Matrix Factor 2-D Deconvolution for Blind Single Channel Source Separation

    DEFF Research Database (Denmark)

    Schmidt, Mikkel N.; Mørup, Morten

    2006-01-01

    We present a novel method for blind separation of instruments in polyphonic music based on a non-negative matrix factor 2-D deconvolution algorithm. Using a model which is convolutive in both time and frequency we factorize a spectrogram representation of music into components corresponding...

  3. Sparse Non-negative Matrix Factor 2-D Deconvolution for Automatic Transcription of Polyphonic Music

    DEFF Research Database (Denmark)

    Schmidt, Mikkel N.; Mørup, Morten

    2006-01-01

    We present a novel method for automatic transcription of polyphonic music based on a recently published algorithm for non-negative matrix factor 2-D deconvolution. The method works by simultaneously estimating a time-frequency model for an instrument and a pattern corresponding to the notes which...... are played based on a log-frequency spectrogram of the music....

  4. Delayed growth

    Science.gov (United States)

    ... Slow rate of growth; Retarded growth and development; Growth delay Images Toddler development References Cooke DW, Divall SA, Radovick S. Normal and aberrant growth in children. In: Melmed S, Polonsky KS, Larsen PR, ...

  5. A New Hypoxia Inducible Factor-2 Inhibitory Pyrrolinone Alkaloid from Roots and Stems of Piper sarmentosum

    OpenAIRE

    BOKESCH, Heidi Rose; GARDELLA, Roberta Scott; RABE, Daniel Christopher; BOTTARO, Donald Paul; LINEHAN, William Marston; MCMAHON, James Brislin; MCKEE, Tawnya Carlene

    2011-01-01

    A new trimethoxycinnamoyl-2-pyrrolinone alkaloid, langkamide (1), along with the known compounds piplartine (2) and 3,4,5-trimethoxycinnamic acid (3) were isolated from the roots and stems of the shrub Piper sarmentosum Roxb. The structures were established by spectroscopic analyses and comparison of their spectral data with values reported in the literature. The compounds were tested for their ability to modulate hypoxia inducible factor-2 (HIF-2) transcription activity and all three showed ...

  6. Decoding the biosynthesis and function of diphthamide, an enigmatic modification of translation elongation factor 2 (EF2

    Directory of Open Access Journals (Sweden)

    Raffael Schaffrath

    2014-05-01

    Full Text Available Diphthamide is a highly conserved modification of archaeal and eukaryal translation elongation factor 2 (EF2 and yet why cells need EF2 to contain diphthamide is unclear. In yeast, the first steps of diphthamide synthesis and the genes (DPH1-DPH5 required to form the intermediate diphthine are well-documented. However, the last step, amidadation of diphthine to diphthamide, had largely been ill-defined. Remarkably, through mining genome-wide synthetic gene array (SGA and chemical genomics databases, recent studies by Uthman et al. [PLoS Genetics (2013 9, e1003334] and Su et al. [Proc. Natl. Acad. Sci. USA (2012 109, 19983-19987] have identified two more diphthamide players, DPH6 and DPH7. Consistent with roles in the amidation step, dph6 and dph7 deletion strains fail to complete diphthamide synthesis and accumulate diphthine-modified EF2. In contrast to Dph6, the catalytically relevant amidase, Dph7 appears to be regulatory. As shown by Uthman et al., it promotes dissociation of diphthine synthase (Dph5 from EF2, allowing diphthine amidation by Dph6 to occur and thereby coupling diphthine synthesis to the terminal step in the pathway. Remarkably, the study by Uthman et al. suggests that Dph5 has a novel role as an EF2 inhibitor that affects cell growth when diphthamide synthesis is blocked or incomplete and, importantly, shows that diphthamide promotes the accuracy of EF2 performance during translation.

  7. Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells.

    Science.gov (United States)

    Pettazzoni, Piergiorgio; Ciamporcero, Eric; Medana, Claudio; Pizzimenti, Stefania; Dal Bello, Federica; Minero, Valerio Giacomo; Toaldo, Cristina; Minelli, Rosalba; Uchida, Koji; Dianzani, Mario Umberto; Pili, Roberto; Barrera, Giuseppina

    2011-10-15

    4-Hydroxynonenal (HNE) is an end product of lipoperoxidation with antiproliferative and proapoptotic properties in various tumors. Here we report a greater sensitivity to HNE in PC3 and LNCaP cells compared to DU145 cells. In contrast to PC3 and LNCaP cells, HNE-treated DU145 cells showed a smaller reduction in growth and did not undergo apoptosis. In DU145 cells, HNE did not induce ROS production and DNA damage and generated a lower amount of HNE-protein adducts. DU145 cells had a greater GSH and GST A4 content and GSH/GST-mediated HNE detoxification. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a regulator of the antioxidant response. Nrf2 protein content and nuclear accumulation were higher in DU145 cells compared to PC3 and LNCaP cells, whereas the expression of KEAP1, the main negative regulator of Nrf2 activity, was lower. Inhibition of Nrf2 expression with specific siRNA resulted in a reduction in GST A4 expression and GS-HNE formation, indicating that Nrf2 controls HNE metabolism. In addition, Nrf2 knockdown sensitized DU145 cells to HNE-mediated antiproliferative and proapoptotic activity. In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. The human polynucleotide kinase/phosphatase (hPNKP) inhibitor A12B4C3 radiosensitizes human myeloid leukemia cells to Auger electron-emitting anti-CD123 111In-NLS-7G3 radioimmunoconjugates

    International Nuclear Information System (INIS)

    Zereshkian, Arman; Leyton, Jeffrey V.; Cai, Zhongli; Bergstrom, Dane; Weinfeld, Michael; Reilly, Raymond M.

    2014-01-01

    Introduction: Leukemia stem cells (LSCs) are believed to be responsible for initiating and propagating acute myeloid leukemia (AML) and for causing relapse after treatment. Radioimmunotherapy (RIT) targeting these cells may improve the treatment of AML, but is limited by the low density of target epitopes. Our objective was to study a human polynucleotide kinase/phosphatase (hPNKP) inhibitor that interferes with DNA repair as a radiosensitizer for the Auger electron RIT agent, 111 In-NLS-7G3, which recognizes the CD123 + /CD131 - phenotype uniquely displayed by LSCs. Methods: The surviving fraction (SF) of CD123 + /CD131 - AML-5 cells exposed to 111 In-NLS-7G3 (33–266 nmols/L; 0.74 MBq/μg) or to γ-radiation (0.25-5 Gy) was determined by clonogenic assays. The effect of A12B4C3 (25 μmols/L) combined with 111 In-NLS-7G3 (16–66 nmols/L) or with γ-radiation (0.25–2 Gy) on the SF of AML-5 cells was assessed. The density of DNA double-strand breaks (DSBs) in the nucleus was measured using the γ-H2AX assay. Cellular dosimetry was estimated based on the subcellular distribution of 111 In-NLS-7G3 measured by cell fractionation. Results: Binding of 111 In-NLS-7G3 to AML-5 cells was reduced by 2.2-fold in the presence of an excess (1 μM) of unlabeled NLS-7G3, demonstrating specific binding to the CD123 + /CD131 - epitope. 111 In-NLS-7G3 reduced the SF of AML-5 cells from 86.1 ± 11.0% at 33 nmols/L to 10.5 ± 3.6% at 266 nmols/L. Unlabeled NLS-7G3 had no significant effect on the SF. Treatment of AML-5 cells with γ-radiation reduced the SF from 98.9 ± 14.9% at 0.25 Gy to 0.03 ± 0.1% at 5 Gy. A12B4C3 combined with 111 In-NLS-7G3 (16–66 nmols/L) enhanced the cytotoxicity up to 1.7-fold compared to treatment with radioimmunoconjugates alone and was associated with a 1.6-fold increase in DNA DSBs in the nucleus. A12B4C3 enhanced the cytotoxicity of γ-radiation (0.25–0.5 Gy) on AML-5 cells by up to 1.5-fold, and DNA DSBs were increased by 1.7-fold. Exposure to

  9. Electrochemical impedance spectroscopy of polynucleotide adsorption

    Czech Academy of Sciences Publication Activity Database

    Strašák, Luděk; Dvořák, Jakub; Hasoň, Stanislav; Vetterl, Vladimír

    2002-01-01

    Roč. 56, 1/2 (2002), s. 37-41 ISSN 1567-5394 R&D Projects: GA AV ČR IAA4004002; GA AV ČR IBS5004107; GA ČR GV204/97/K084 Grant - others:GA FRVŠ(XC) G40583; GA FRVŠ(XC) F40564 Institutional research plan: CEZ:AV0Z5004920 Keywords : electrochemical impedance spectroscopy * DNA adsorption * poly A adsorption Subject RIV: BO - Biophysics Impact factor: 1.463, year: 2002

  10. A high-throughput screening assay for eukaryotic elongation factor 2 kinase inhibitors

    Directory of Open Access Journals (Sweden)

    Ting Xiao

    2016-10-01

    Full Text Available Eukaryotic elongation factor 2 kinase (eEF2K inhibitors may aid in the development of new therapeutic agents to combat cancer. Purified human eEF2K was obtained from an Escherichia coli expression system and a luminescence-based high-throughput screening (HTS assay was developed using MH-1 peptide as the substrate. The luminescent readouts correlated with the amount of adenosine triphosphate remaining in the kinase reaction. This method was applied to a large-scale screening campaign against a diverse compound library and subsequent confirmation studies. Nine initial hits showing inhibitory activities on eEF2K were identified from 56,000 synthetic compounds during the HTS campaign, of which, five were chosen to test their effects in cancer cell lines.

  11. Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes

    Science.gov (United States)

    Das, Hiranmoy; Kumar, Ajay; Lin, Zhiyong; Patino, Willmar D.; Hwang, Paul M.; Feinberg, Mark W.; Majumder, Pradip K.; Jain, Mukesh K.

    2006-01-01

    The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, KLF2 inhibits the transcriptional activity of both NF-κB and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation. PMID:16617118

  12. Growth Disorders

    Science.gov (United States)

    ... too little of it may be very short. Treatment with growth hormone can stimulate growth. People can also have too much growth hormone. Usually the cause is a pituitary gland tumor, which is not cancer. Too much growth hormone can cause gigantism in children, where their bones and their body ...

  13. Immune Reactions Against Elongation Factor 2 Kinase: Specific Pathogenesis of Gastric Ulcer from Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Kiyoshi Ayada

    2009-01-01

    Full Text Available Helicobacter pylori (H. pylori infection is a definite causative factor for gastric ulcers (GUs. In the present study we detected a specific antigen of gastric epithelial cells (HGC-27 using cell ELISA, which was recognized by the sera of GU patients (n=20 but not in patients with chronic gastritis (CG; n=20 or in healthy volunteers (HC; n=10. This antigen was over-expressed by a stressful (heat-stressed environment, and was identified as elongation factor 2 kinase (EF-2K by western blotting. The GU patients' lymphocytes stimulated by H. pylori specifically disrupted heat-stressed HGC-27 cells in a cytotoxic assay. In flow cytometry, the effector cells (lymphocytes from GU patients were significantly differentiated to T helper type 1 lymphocyte (Th1 and cytotoxic T lymphocyte (CTL as opposed to those from CG patients. The target cells (HGC-27 expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of GU.

  14. Eukaryotic elongation factor 2 controls TNF-α translation in LPS-induced hepatitis

    Science.gov (United States)

    González-Terán, Bárbara; Cortés, José R.; Manieri, Elisa; Matesanz, Nuria; Verdugo, ρngeles; Rodríguez, María E.; González-Rodríguez, ρgueda; Valverde, ρngela; Martín, Pilar; Davis, Roger J.; Sabio, Guadalupe

    2012-01-01

    Bacterial LPS (endotoxin) has been implicated in the pathogenesis of acute liver disease through its induction of the proinflammatory cytokine TNF-α. TNF-α is a key determinant of the outcome in a well-established mouse model of acute liver failure during septic shock. One possible mechanism for regulating TNF-α expression is through the control of protein elongation during translation, which would allow rapid cell adaptation to physiological changes. However, the regulation of translational elongation is poorly understood. We found that expression of p38γ/δ MAPK proteins is required for the elongation of nascent TNF-α protein in macrophages. The MKK3/6-p38γ/δ pathway mediated an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) kinase, which in turn promoted eEF2 activation (dephosphorylation) and subsequent TNF-α elongation. These results identify a new signaling pathway that regulates TNF-α production in LPS-induced liver damage and suggest potential cell-specific therapeutic targets for liver diseases in which TNF-α production is involved. PMID:23202732

  15. growth stimulant

    African Journals Online (AJOL)

    Effects of timing and duration of supplementation of LIVFIT VET ® (growth stimulant) as substitute for fish meal on the growth performance, haematology and clinical enzymes concentration of growing pigs.

  16. Distribution of clonal growth forms in wetlands

    Czech Academy of Sciences Publication Activity Database

    Sosnová, Monika; van Diggelen, R.; Klimešová, Jitka

    2010-01-01

    Roč. 92, č. 1 (2010), s. 33-39 ISSN 0304-3770 R&D Projects: GA ČR GD206/08/H044 Institutional research plan: CEZ:AV0Z60050516 Keywords : clonal growth organ * the Netherlands * wetland plant community Subject RIV: EF - Botanics Impact factor: 2.087, year: 2010

  17. Trefoil factor-2 reverses airway remodeling changes in allergic airways disease.

    Science.gov (United States)

    Royce, Simon G; Lim, Clarice; Muljadi, Ruth C; Samuel, Chrishan S; Ververis, Katherine; Karagiannis, Tom C; Giraud, Andrew S; Tang, Mimi L K

    2013-01-01

    Trefoil factor 2 (TFF2) is a small peptide with an important role in mucosal repair. TFF2 is up-regulated in asthma, suggesting a role in asthma pathogenesis. Given its known biological role in promoting epithelial repair, TFF2 might be expected to exert a protective function in limiting the progression of airway remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was investigated by examining the expression of TFF2 in the airway and lung, and evaluating the effects of recombinant TFF2 treatment on established airway remodeling in a murine model of chronic allergic airways disease (AAD). BALB/c mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks, whereas mice with established OVA-induced AAD were treated with TFF2 or vehicle control (intranasally for 14 d). Effects on airway remodeling, airway inflammation, and airway hyperresponsiveness were then assessed, whereas TFF2 expression was determined by immunohistochemistry. TFF2 expression was significantly increased in the airways of mice with AAD, compared with expression levels in control mice. TFF2 treatment resulted in reduced epithelial thickening, subepithelial collagen deposition, goblet-cell metaplasia, bronchial epithelium apoptosis, and airway hyperresponsiveness (all P < 0.05, versus vehicle control), but TFF2 treatment did not influence airway inflammation. The increased expression of endogenous TFF2 in response to chronic allergic inflammation is insufficient to prevent the progression of airway inflammation and remodeling in a murine model of chronic AAD. However, exogenous TFF2 treatment is effective in reversing aspects of established airway remodeling. TFF2 has potential as a novel treatment for airway remodeling in asthma.

  18. Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway.

    Science.gov (United States)

    Ha, Ae Wha; Kim, Woo Kyoung

    2017-06-01

    Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly ( P concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly ( P antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

  19. Identification of a phosphorylation-dependent nuclear localization motif in interferon regulatory factor 2 binding protein 2.

    Directory of Open Access Journals (Sweden)

    Allen C T Teng

    Full Text Available Interferon regulatory factor 2 binding protein 2 (IRF2BP2 is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known.Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS to an evolutionarily conserved sequence (354ARKRKPSP(361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360. Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C(2C(12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C(2C(12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2.Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status

  20. Human SUV3 helicase regulates growth rate of the HeLa cells and can localize in the nucleoli.

    Science.gov (United States)

    Szewczyk, Maciej; Fedoryszak-Kuśka, Natalia; Tkaczuk, Katarzyna; Dobrucki, Jurek; Waligórska, Agnieszka; Stępień, Piotr P

    2017-01-01

    The human SUV3 helicase (SUV3, hSUV3, SUPV3L1) is a DNA/RNA unwinding enzyme belonging to the class of DexH-box helicases. It localizes predominantly in the mitochondria, where it forms an RNA-degrading complex called mitochondrial degradosome with exonuclease PNP (polynucleotide phosphorylase). Association of this complex with the polyA polymerase can modulate mitochondrial polyA tails. Silencing of the SUV3 gene was shown to inhibit the cell cycle and to induce apoptosis in human cell lines. However, since small amounts of the SUV3 helicase were found in the cell nuclei, it was not clear whether the observed phenotypes of SUV3 depletion were of mitochondrial or nuclear origin. In order to answer this question we have designed gene constructs able to inhibit the SUV3 activity exclusively in the cell nuclei. The results indicate that the observed growth rate impairment upon SUV3 depletion is due to its nuclear function(s). Unexpectedly, overexpression of the nuclear-targeted wild-type copies of the SUV3 gene resulted in a higher growth rate. In addition, we demonstrate that the SUV3 helicase can be found in the HeLa cell nucleoli, but it is not detectable in the DNA-repair foci. Our results indicate that the nucleolar-associated human SUV3 protein is an important factor in regulation of the cell cycle.

  1. Krüppel-like factor 2 is required for normal mouse cardiac development.

    Directory of Open Access Journals (Sweden)

    Aditi R Chiplunkar

    Full Text Available Krüppel-like factor 2 (KLF2 is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5 in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By E10.5, traditional and endothelial-specific FVB/N KLF2-/- AV cushions are hypocellular, suggesting that the cells accumulating at the AV canal have a defect in endothelial to mesenchymal transformation (EMT. E10.5 FVB/N KLF2-/- hearts have reduced glycosaminoglycans in the cardiac jelly, correlating with the reduced EMT. However, the number of mesenchymal cells migrating from FVB/N KLF2-/- AV explants into a collagen matrix is reduced considerably compared to wild-type, suggesting that the EMT defect is not due solely to abnormal cardiac jelly. Echocardiography of E10.5 FVB/N KLF2-/- embryos indicates that they have abnormal heart function compared to wild-type. E10.5 C57BL/6 KLF2-/- hearts have largely normal AV cushions. However, E10.5 FVB/N and C57BL/6 KLF2-/- embryos have a delay in the formation of the atrial septum that is not observed in a defined mixed background. KLF2 ablation results in reduced Sox9, UDP-glucose dehydrogenase (Ugdh, Gata4 and Tbx5 mRNA in FVB/N AV canals. KLF2 binds to the Gata4, Tbx5 and Ugdh promoters in chromatin immunoprecipitation assays, indicating that KLF2 could directly regulate these genes. In conclusion, KLF2-/- heart phenotypes are genetic background-dependent. KLF2 plays a role in EMT through its regulation of important cardiovascular genes.

  2. Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Guoyu Yu

    Full Text Available Protease-activated receptor 4 (PAR4, a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2, a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38, western blotting (n=38 and tissue microarrays (n = 66. The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the

  3. Heat shock factor 2 levels are associated with the severity of ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Jiarong Miao

    Full Text Available BACKGROUND AND AIMS: The morbidity of ulcerative colitis (UC is increasing in China every year. In addition, there is a lack of accurate diagnostic indices with which to evaluate the activity of the disease. The aim of this study was to identify UC-associated proteins as biomarkers for the diagnosis, and objective assessment of disease activity. METHODS: Differential expression of serum proteins from UC patients compared to normal controls was analyzed by two-dimensional electrophoresis (2-DE and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS. The expression of heat shock factor 2(HSF2in colonic mucosa in Crohn's disease, Behcet's disease, ulcerative colitis, intestinal tuberculosis, infective enteritis, intestinal lymphoma, and normal controls was investigated by immunohistochemistry (IHC. The expression of the HSF2 in colonic mucosa of UC subjects with varying severity of disease was measured by real time-PCR and Western Blots. The expression of HSF2 was inhibited by HSF2 small interfering RNA (siRNA transfection in Caco-2 cells. The concentrations of HSF2, IL-1β, and TNF-α in serum and IL-1β, and TNF-α in the supernatants of transfected Caco-2 cells were determined by ELISA. RESULTS: HSF2 was differentially expressed in UC patients compared to normal controls. HSF2 expression was significantly higher in the intestinal mucosa of UC patients compared to other six groups. The results of immunohistochemistry, real time-PCR, Western Blots, and ELISA showed that the expression of HSF2 increased in parallel with the severity of UC. The serum concentration of HSF2 also positively correlated with levels of IL-1β and TNF-α. After down-regulation expression of HSF2 in Caco-2 cells by RNA interference, the productions of IL-1β and TNF-α stimulated by lipopolysaccharide (LPS increased dramatically. CONCLUSIONS: HSF2 appears to be a potential novel molecular marker for UC activity, and may provide a basis

  4. Growth references

    NARCIS (Netherlands)

    Buuren, S. van

    2007-01-01

    A growth reference describes the variation of an anthropometric measurement within a group of individuals. A reference is a tool for grouping and analyzing data and provides a common basis for comparing populations.1 A well known type of reference is the age-conditional growth diagram. The

  5. Growth Problems

    Science.gov (United States)

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... hypothyroidism is feeling tired or sluggish. A blood test measuring thyroid ... not affect intelligence or brain function. The cause of growth hormone ...

  6. Growth Disorders

    Science.gov (United States)

    ... the changes your body goes through during puberty. Puberty is the stage of your life when sexual development happens, like breast development and menstrual periods in girls and growth of the penis and testicles in boys. One of the body ...

  7. Abnormal grain growth: a non-equilibrium thermodynamic model for multi-grain binary systems

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Jiří; Fischer, F. D.

    2014-01-01

    Roč. 22, č. 1 (2014), Art . No. 015013 ISSN 0965-0393 Institutional support: RVO:68081723 Keywords : grain boundary segregation * abnormal grain growth * theory * modelling * solute drag Subject RIV: BJ - Thermodynamics Impact factor: 2.167, year: 2014

  8. Population growth and economic growth.

    Science.gov (United States)

    Narayana, D L

    1984-01-01

    This discussion of the issues relating to the problem posed by population explosion in the developing countries and economic growth in the contemporary world covers the following: predictions of economic and social trends; the Malthusian theory of population; the classical or stationary theory of population; the medical triage model; ecological disaster; the Global 2000 study; the limits to growth; critiques of the Limits to Growth model; nonrenewable resources; food and agriculture; population explosion and stabilization; space and ocean colonization; and the limits perspective. The Limits to Growth model, a general equilibrium anti-growth model, is the gloomiest economic model ever constructed. None of the doomsday models, the Malthusian theory, the classical stationary state, the neo-Malthusian medical triage model, the Global 2000 study, are so far reaching in their consequences. The course of events that followed the publication of the "Limits to Growth" in 1972 in the form of 2 oil shocks, food shock, pollution shock, and price shock seemed to bear out formally the gloomy predictions of the thesis with a remarkable speed. The 12 years of economic experience and the knowledge of resource trends postulate that even if the economic pressures visualized by the model are at work they are neither far reaching nor so drastic. Appropriate action can solve them. There are several limitations to the Limits to Growth model. The central theme of the model, which is overshoot and collapse, is unlikely to be the course of events. The model is too aggregative to be realistic. It exaggerates the ecological disaster arising out of the exponential growth of population and industry. The gross underestimation of renewable resources is a basic flaw of the model. The most critical weakness of the model is its gross underestimation of the historical trend of technological progress and the technological possiblities within industry and agriculture. The model does correctly emphasize

  9. Preclinical pharmacokinetics, interspecies scaling, and pharmacokinetics of a Phase I clinical trial of TTAC-0001, a fully human monoclonal antibody against vascular endothelial growth factor 2

    Directory of Open Access Journals (Sweden)

    Lee WS

    2018-03-01

    Full Text Available Weon Sup Lee,1 Sang Ryeol Shim,1 Seon Young Lee,1 Jin San Yoo,1 Sung Kweon Cho2 1PharmAbcine, Inc., Daejeon, Republic of Korea; 2Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea Background: VEGF is a highly selective mitogen that serves as the central regulator of tumor angiogenesis by mediating endothelial proliferation, permeability, and survival. Tanibirumab (TTAC-0001 is a fully human IgG1 monoclonal antibody derived from a fully human naïve single-chain variable fragment (ScFv phage library that was developed to inhibit the effects of VEGF in the treatment of solid tumors, especially those of the brain. Methods: In the present study, we conducted intravenous pharmacokinetic studies of TTAC-0001 in mice, rats, and cynomolgus monkeys. At the doses studied (3 mg/kg, 10 mg/kg, 30 mg/kg, TTAC-0001 exhibited dose proportionality in mice and monkeys. At a dose of ~10 mg/kg, the clearance of TTAC-0001 from serum was 0.017 mL/h in mice, 0.35 mL/h in rats, and 2.19 mL/h in cynomolgus monkeys, and the terminal half-life ranged from 20–30 h among the three species. Pharmacokinetic data in mice, rats, and cynomolgus monkeys were used to predict the pharmacokinetics of TTAC-0001 in humans using allometric scaling. The predicted serum clearance of TTAC-0001 in humans was 102.45 mL/h and the terminal half-life was 27.52 h. Results: The maximum life span-corrected clearance value was 72.92 mL/h. The observed clearance in humans was more similar to the predicted scaled clearance. Conclusion: We investigated the pharmacokinetics of TTAC-0001 in mice, rats, and cynomolgus monkeys after intravenous administration. At the doses studied, TTAC-0001 exhibited dose proportionality in mice and monkeys. The scaled pharmacokinetics of TTAC-0001 reported here was useful for designing first-in-human studies. Allometric scaling in the therapeutic antibody is feasible. Keywords: VEGF2, tanibirumab, pharmacokinetics, allometry, clearance, biodistribution

  10. Risk factors for breast cancer and expression of insulin-like growth factor-2 (IGF-2 in women with breast cancer in Wuhan City, China.

    Directory of Open Access Journals (Sweden)

    Jun Qiu

    Full Text Available PURPOSE: The purpose of this study was to explore the risk factors for breast cancer and establish the expression rate of IGF-2 in female patients. METHODS: A case control study with 500 people in case group and 500 people in control group. A self-administered questionnaire was used to investigate risk factors for breast cancer. All cases were interviewed during a household survey. Immune-histochemical method was used to inspect the expression of IGF-2 in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue. RESULTS: Multivariate adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. High body mass index (OR = 1.012,95%CI = 1.008-1.016, working attributes (OR = 1.004, 95%CI = 1.002 = 1.006, long menstrual period (OR = 1.007, 95%CI = 1.005-1.009, high parity OR = 1.003, 95%CI = 1.001-1.005 , frequent artificial abortion (OR = 1.004, 95%CI = 1.001-1.005, family history of cancer (OR = 1.003, 95%CI = 1.000-1.005, period of night shift (OR = 1.003, 95%CI = 1.001-1.006, live in high risk environment (OR = 1.005, 95%CI = 1.002-1.008, and family problems (OR = 1.010, 95%CI = 1.005-1.014 were associated with increased risk for breast cancer. In this study, good sleeping status, positive coping strategies, subjective support, and utility degree of social support were associated with reduced risk for breast cancer (OR = 0.998, 0.997, 0.985, 0.998 respectively; 95%CI = 0.996-1.000, 0.994-1.000, 0.980-0.989, 0.996-1.000, respectively. In benign breast lesions, breast cancer and tumor-adjacent tissue, IGF-2 was mainly expressed in the cytoplasm, but its expression rate was different (p<0.05. CONCLUSIONS: The incidence of breast cancer is a common result of multiple factors. IGF-2 is involved in the development of breast cancer, and its expression varies in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue.

  11. Translational Pharmacologic Efficacy Studies of Glial Growth Factor 2 (GGF2) in Spinal Cord Injury Models and in the Veterinary Clinical Setting

    Science.gov (United States)

    2015-07-01

    Center at Georgetown University. The MR imager used is a 7.0 Tesla horizontal Bruker magnet with a 20 cm bore equipped with 100 gauss/cm microimaging...gradients and run by Paravision 5.0 software. The samples were imaged in a 40 mm transmit-receive volume RF coil . To acquire anatomical images, a two...for MRI imaging at the PIRL. The MR imager used is a 7.0 Tesla horizontal Bruker magnet with a 20 cm bore equipped with 100 gauss/cm microimaging

  12. Excessive growth.

    Science.gov (United States)

    Narayanaswamy, Vasudha; Rettig, Kenneth R; Bhowmick, Samar K

    2008-09-01

    Tall stature and excessive growth syndrome are a relatively rare concern in pediatric practice. Nevertheless, it is important to identify abnormal accelerated growth patterns in children, which may be the clue in the diagnosis of an underlying disorder. We present a case of pituitary gigantism in a 2 1/2-year-old child and discuss the signs, symptoms, laboratory findings, and the treatment. Brief discussions on the differential diagnosis of excessive growth/tall stature have been outlined. Pituitary gigantism is very rare in the pediatrics age group; however, it is extremely rare in a child that is less than 3 years of age. The nature of pituitary adenoma and treatment options in children with this condition have also been discussed.

  13. Synthesis of interleukin 6 (interferon-β2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

    International Nuclear Information System (INIS)

    Zhange, Y.; Lin, J.X.; Vilcek, J.

    1988-01-01

    Interleukin 6 (IL-6; also referred to as interferon-β 2 , 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1

  14. Development of a cell-based reporter assay for screening of inhibitors of hypoxia-inducible factor 2-induced gene expression.

    Science.gov (United States)

    Woldemichael, Girma M; Vasselli, James R; Gardella, Roberta S; McKee, Tawnya C; Linehan, W Marston; McMahon, James B

    2006-09-01

    Reporter cell lines have been developed for the identification of inhibitors of gene expression enhanced by hypoxia-inducible factor 2, which has been implicated as a transcription factor involved in the tumorigenesis of clear cell renal carcinoma. Stably transformed reporter clones of the human renal clear cell carcinoma cell line 786-O were generated by transfection or retroviral infection. Luciferase reporter expression in the vectors used was driven by either the natural human vascular endothelial growth factor (VEGF) promoter-enhancer or by the VEGF and the human endothelial nitric oxide synthase enhancers modulating minimal human cytomegalovirus promoter. Utility of the generated reporter cell lines was validated by introducing the von Hippel-Lindau protein complex and testing for reporter inducibility by hypoxia. The dynamic range in reporter activity under hypoxic stress was found to be at least 30- to 40-fold, with a signal-to-noise ratio of 60:1. Properties of the cell lines such as tolerance to up to 3% DMSO, signal stability with multiple in vitro passages, and utility in both 96- and 384-well plate formats indicated their suitability for use in a high-throughput screen. In addition, the potential use of these reporter lines in the evaluation of high-throughput screening hits in vivo in various mice models has been demonstrated.

  15. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    International Nuclear Information System (INIS)

    Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio; Hazemann, Isabelle; Jenner, Lasse; Urzhumtsev, Alexandre; Gualerzi, Claudio O.; Klaholz, Bruno P.

    2013-01-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue

  16. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    Energy Technology Data Exchange (ETDEWEB)

    Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

    2013-06-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

  17. Universal growth modes of high-elevation conifers

    Czech Academy of Sciences Publication Activity Database

    Datsenko, N. M.; Sonechkin, D. M.; Büntgen, Ulf; Yang, B.

    2016-01-01

    Roč. 38, JUN (2016), s. 38-50 ISSN 1125-7865 Institutional support: RVO:67179843 Keywords : tree-ring chronologies * summer temperature-variations * northeastern tibetan plateau * climate signal * fennoscandian summers * annual precipitation * density * variability * qinghai * Growth modes * Ring width and maximum latewood density * Eigenvector analysis Subject RIV: EF - Botanics Impact factor: 2.259, year: 2016

  18. How wind affects growth in treeline Picea abies

    Czech Academy of Sciences Publication Activity Database

    Kašpar, J.; Hošek, Jiří; Treml, V.

    2017-01-01

    Roč. 127, č. 2 (2017), s. 1-12 ISSN 1664-2201 Institutional support: RVO:68378289 Keywords : height increment * picea abies * radial growth * thigmomorphogenesis * tree rings Subject RIV: GK - Forestry OBOR OECD: Forestry Impact factor: 2.281, year: 2016 https://link.springer.com/content/pdf/10.1007%2Fs00035-017-0186-x.pdf

  19. Androgen signaling promotes translation of TMEFF2 in prostate cancer cells via phosphorylation of the α subunit of the translation initiation factor 2.

    Directory of Open Access Journals (Sweden)

    Ryan F Overcash

    Full Text Available The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2, is expressed mainly in brain and prostate. Expression of TMEFF2 is deregulated in prostate cancer, suggesting a role in this disease, but the molecular mechanism(s involved in this effect are not clear. Although androgens promote tmeff2 transcription, androgen delivery to castrated animals carrying CWR22 xenografts increases TMEFF2 protein levels in the absence of mRNA changes, suggesting that TMEFF2 may also be post-transcriptionally regulated. Here we show that translation of TMEFF2 is regulated by androgens. Addition of physiological concentrations of dihydrotestosterone (DHT to prostate cancer cell lines increases translation of endogenous TMEFF2 or transfected TMEFF2-Luciferase fusions, and this effect requires the presence of upstream open reading frames (uORFs in the 5'-untranslated region (5'-UTR of TMEFF2. Using chemical and siRNA inhibition of the androgen receptor (AR, we show that the androgen effect on TMEFF2 translation is mediated by the AR. Importantly, DHT also promotes phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α in an AR-dependent manner, paralleling the effect on TMEFF2 translation. Moreover, endoplasmic reticulum (ER stress conditions, which promote eIF2α phosphorylation, also stimulate TMEFF2 translation. These results indicate that androgen signaling promotes eIF2α phosphorylation and subsequent translation of TMEFF2 via a mechanism that requires uORFs in the 5'-UTR of TMEFF2.

  20. Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2α Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model

    Directory of Open Access Journals (Sweden)

    Weifeng Lu

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P<0.05. rMSCHIF-2α transplantation also markedly increased the expression of proangiogenic factors VEGF, bFGF, and SDF1 and Notch signaling proteins including DII4, NICD, Hey1, and Hes1, whereas it reduced the expression of proapoptotic factor Bax in the muscle of the ischemic hindlimb. Overexpression of HIF-2α did not affect rMSC stemness and proliferation under normoxia but significantly increased rMSC migration and tube formation in matrigel under hypoxia (all P<0.05. RMSCsHIF-2α stimulated endothelial cell invasion under hypoxia significantly (P<0.05. Genetic modification of rMSCs via overexpression of HIF-2α improves posttransplantation outcomes in a rat hindlimb ischemia model possibly by stimulating proangiogenic growth factors and cytokines.

  1. Regulation of oxidative enzyme activity and eukaryotic elongation factor 2 in human skeletal muscle: influence of gender and exercise

    DEFF Research Database (Denmark)

    Roepstorff, Carsten; Schjerling, P.; Vistisen, Bodil

    2005-01-01

    AIM: To investigate gender-related differences in the responses of oxidative enzymes and eukaryotic elongation factor-2 (eEF2) to exercise. METHODS: The influence of exercise (90 min, 60%VO(2peak)) on citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (HAD) activity and mRNA content...... expression and phosphorylation were unaffected by training status (NS). CONCLUSION: Basal transcriptional, translational, and/or post-translational control of CS and HAD seems to be gender-dependent. Also, gender differences in translation and/or post-translational protein modification of CS occur during...... not differ between females and males (NS). In females only, CS activity was enhanced (P differ between UT and ET but, nevertheless, CS activity was 56% higher in ET than in UT volunteers (P

  2. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

    International Nuclear Information System (INIS)

    Kim, Jiyoung; Cha, Young-Nam; Surh, Young-Joon

    2010-01-01

    Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

  3. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jiyoung [National Research Laboratory, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Cha, Young-Nam [Inha University College of Medicine, Incheon 382-751 (Korea, Republic of); Surh, Young-Joon, E-mail: surh@plaza.snu.ac.kr [National Research Laboratory, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul 110-799 (Korea, Republic of)

    2010-08-07

    Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

  4. Endogenous ADP-ribosylation of elongation factor 2 in polyoma virus-transformed baby hamster kidney cells

    Energy Technology Data Exchange (ETDEWEB)

    Fendrick, J.L.; Iglewski, W.J. (Univ. of Rochester, NY (USA))

    1989-01-01

    Polyoma virus-transformed baby hamster kidney (pyBHK) cells were cultured in medium containing ({sup 32}P)orthophosphate and 105 (vol/vol) fetal bovine serum. A {sup 32}P-labeled protein with an apparent molecular mass of 97 kDa was immunoprecipitated from cell lysates with antiserum to ADP-ribosylated elongation factor 2 (EF-2). The {sup 32}P labeling of the protein was enhanced by culturing cells in medium containing 2% serum instead of 10% serum. The {sup 32}P label was completely removed from the protein by treatment with snake venom phosphodiesterase and the digestion product was identified as ({sup 32}P)AMP, indicating the protein was mono-ADP-ribosylated. HPLC analysis of tryptic peptides of the {sup 32}P-labeled 97-kDa protein and purified EF-2, which was ADP-ribosylated in vitro with diphtheria toxin fragment A and ({sup 32}P)NAD, demonstrated an identical labeled peptide in the two proteins. The data strongly suggest that EF-2 was endogenously ADP-ribosylated in pyBHK cells. Maximum incorporation of radioactivity in EF-2 occurred by 12 hr and remained constant over the subsequent 12 hr. It was estimated that 30-35% of the EF-2 was ADP-ribosylated in cells cultured in medium containing 2% serum. When {sup 32}P-labeled cultures were incubated in medium containing unlabeled phosphate, the {sup 32}P label was lost from the EF-2 within 30 min.

  5. Activated Integrin-Linked Kinase Negatively Regulates Muscle Cell Enhancement Factor 2C in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Zhenguo Dong

    2015-01-01

    Full Text Available Our previous study reported that muscle cell enhancement factor 2C (MEF2C was fully activated after inhibition of the phosphorylation activity of integrin-linked kinase (ILK in the skeletal muscle cells of goats. It enhanced the binding of promoter or enhancer of transcription factor related to proliferation of muscle cells and then regulated the expression of these genes. In the present investigation, we explored whether ILK activation depended on PI3K to regulate the phosphorylation and transcriptional activity of MEF2C during C2C12 cell proliferation. We inhibited PI3K activity in C2C12 with LY294002 and then found that ILK phosphorylation levels and MEF2C phosphorylation were decreased and that MCK mRNA expression was suppressed significantly. After inhibiting ILK phosphorylation activity with Cpd22 and ILK-shRNA, we found MEF2C phosphorylation activity and MCK mRNA expression were increased extremely significantly. In the presence of Cpd22, PI3K activity inhibition increased MEF2C phosphorylation and MCK mRNA expression indistinctively. We conclude that ILK negatively and independently of PI3K regulated MEF2C phosphorylation activity and MCK mRNA expression in C2C12 cells. The results provide new ideas for the study of classical signaling pathway of PI3K-ILK-related proteins and transcription factors.

  6. Endogenous ADP-ribosylation of elongation factor 2 in polyoma virus-transformed baby hamster kidney cells

    International Nuclear Information System (INIS)

    Fendrick, J.L.; Iglewski, W.J.

    1989-01-01

    Polyoma virus-transformed baby hamster kidney (pyBHK) cells were cultured in medium containing [ 32 P]orthophosphate and 105 (vol/vol) fetal bovine serum. A 32 P-labeled protein with an apparent molecular mass of 97 kDa was immunoprecipitated from cell lysates with antiserum to ADP-ribosylated elongation factor 2 (EF-2). The 32 P labeling of the protein was enhanced by culturing cells in medium containing 2% serum instead of 10% serum. The 32 P label was completely removed from the protein by treatment with snake venom phosphodiesterase and the digestion product was identified as [ 32 P]AMP, indicating the protein was mono-ADP-ribosylated. HPLC analysis of tryptic peptides of the 32 P-labeled 97-kDa protein and purified EF-2, which was ADP-ribosylated in vitro with diphtheria toxin fragment A and [ 32 P]NAD, demonstrated an identical labeled peptide in the two proteins. The data strongly suggest that EF-2 was endogenously ADP-ribosylated in pyBHK cells. Maximum incorporation of radioactivity in EF-2 occurred by 12 hr and remained constant over the subsequent 12 hr. It was estimated that 30-35% of the EF-2 was ADP-ribosylated in cells cultured in medium containing 2% serum. When 32 P-labeled cultures were incubated in medium containing unlabeled phosphate, the 32 P label was lost from the EF-2 within 30 min

  7. Nuclear factor erythroid 2-related factor 2 deletion impairs glucose tolerance and exacerbates hyperglycemia in type 1 diabetic mice.

    Science.gov (United States)

    Aleksunes, Lauren M; Reisman, Scott A; Yeager, Ronnie L; Goedken, Michael J; Klaassen, Curtis D

    2010-04-01

    The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) induces a battery of cytoprotective genes after oxidative stress. Nrf2 aids in liver regeneration by altering insulin signaling; however, whether Nrf2 participates in hepatic glucose homeostasis is unknown. Compared with wild-type mice, mice lacking Nrf2 (Nrf2-null) have lower basal serum insulin and prolonged hyperglycemia in response to an intraperitoneal glucose challenge. In the present study, blood glucose, serum insulin, urine flow rate, and hepatic expression of glucose-related genes were quantified in male diabetic wild-type and Nrf2-null mice. Type 1 diabetes was induced with a single intraperitoneal dose (200 mg/kg) of streptozotocin (STZ). Histopathology and serum insulin levels confirmed depleted pancreatic beta-cells in STZ-treated mice of both genotypes. Five days after STZ, Nrf2-null mice had higher blood glucose levels than wild-type mice. Nine days after STZ, polyuria occurred in both genotypes with more urine output from Nrf2-null mice (11-fold) than wild-type mice (7-fold). Moreover, STZ-treated Nrf2-null mice had higher levels of serum beta-hydroxybutyrate, triglycerides, and fatty acids 10 days after STZ compared with wild-type mice. STZ reduced hepatic glycogen in both genotypes, with less observed in Nrf2-null mice. Increased urine output and blood glucose in STZ-treated Nrf2-null mice corresponded with enhanced gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase)- and reduced glycolysis (pyruvate kinase)-related mRNA expression in their livers. Furthermore, the Nrf2 activator oltipraz lowered blood glucose in wild-type but not Nrf2-null mice administered STZ. Collectively, these data indicate that the absence of Nrf2 worsens hyperglycemia in type I diabetic mice and Nrf2 may represent a therapeutic target for reducing circulating glucose levels.

  8. Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells

    Directory of Open Access Journals (Sweden)

    Uchida Daisuke

    2009-08-01

    Full Text Available Abstract Background We have demonstrated that the stromal cell-derived factor-1 (SDF-1; CXCL12/CXCR4 system is involved in the establishment of lymph node metastasis in oral squamous cell carcinoma (SCC. Chemotherapy is a powerful tool for the treatment of oral cancer, including oral SCC; however, the effects of chemotherapeutic agents on the expression of CXCR4 are unknown. In this study, we examined the expression of CXCR4 associated with the chemotherapeutic agents in oral cancer cells. Results The expression of CXCR4 was examined using 3 different chemotherapeutic agents; 5-fluorouracil, cisplatin, and vesnarinone (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl-1-piperazinyl]-2-(1H-quinolinone in B88, a line of oral cancer cells that exhibits high levels of CXCR4 and lymph node metastatic potential. Of the 3 chemotherapeutic agents that we examined, only vesnarinone downregulated the expression of CXCR4 at the mRNA as well as the protein level. Vesnarinone significantly inhibited lymph node metastasis in tumor-bearing nude mice. Moreover, vesnarinone markedly inhibited 2.7-kb human CXCR4 promoter activity, and we identified the transcription factor, Krüppel-like factor 2 (KLF2, as a novel vesnarinone-responsive molecule, which was bound to the CXCR4 promoter at positions -300 to -167 relative to the transcription start site. The forced-expression of KLF2 led to the downregulation of CXCR4 mRNA and impaired CXCR4 promoter activity. The use of siRNA against KLF2 led to an upregulation of CXCR4 mRNA. Conclusion These Results indicate that vesnarinone downregulates CXCR4 via the upregulation of KLF2 in oral cancer.

  9. DJ-1 Modulates Nuclear Erythroid 2-Related Factor-2-Mediated Protection in Human Primary Alveolar Type II Cells in Smokers.

    Science.gov (United States)

    Bahmed, Karim; Messier, Elise M; Zhou, Wenbo; Tuder, Rubin M; Freed, Curt R; Chu, Hong Wei; Kelsen, Steven G; Bowler, Russell P; Mason, Robert J; Kosmider, Beata

    2016-09-01

    Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2-related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases.

  10. Characterization of the interaction of yeast enolase with polynucleotides.

    Science.gov (United States)

    al-Giery, A G; Brewer, J M

    1992-09-23

    Yeast enolase is inhibited under certain conditions by DNA. The enzyme binds to single-stranded DNA-cellulose. Inhibition was used for routine characterization of the interaction. The presence of the substrate 2-phospho-D-glycerate reduces inhibition and binding. Both yeast enolase isozymes behave similarly. Impure yeast enolase was purified by adsorption onto a single-stranded DNA-cellulose column followed by elution with substrate. Interaction with RNA, double-stranded DNA, or degraded DNA results in less inhibition, suggesting that yeast enolase preferentially binds single-stranded DNA. However, yeast enolase is not a DNA-unwinding protein. The enzyme is inhibited by the short synthetic oligodeoxynucleotides G6, G8 and G10 but not T8 or T6, suggesting some base specificity in the interaction. The interaction is stronger at more acid pH values, with an apparent pK of 5.6. The interaction is prevented by 0.3 M KCl, suggesting that electrostatic factors are important. Histidine or lysine reverse the inhibition at lower concentrations, while phosphate is still more effective. Binding of single-stranded DNA to enolase reduces the reaction of protein histidyl residues with diethylpyrocarbonate. The inhibition of yeast enolase by single-stranded DNA is not total, and suggests the active site is not directly involved in the interaction. Binding of substrate may induce a conformational change in the enzyme that interferes with DNA binding and vice versa.

  11. The origin of polynucleotide-directed protein synthesis

    Science.gov (United States)

    Orgel, Leslie E.

    1989-01-01

    If protein synthesis evolved in an RNA world it was probably preceded by simpler processes by means of which interaction with amino acids conferred selective advantage on replicating RNA molecules. It is suggested that at first the simple attachment of amino acids to the 2'(3') termini of RNA templates favored initiation of replication at the end of the template rather than at internal positions. The second stage in the evolution of protein synthesis would probably have been the association of pairs of charged RNA adaptors in such a way as to favor noncoded formation of peptides. Only after this process had become efficient could coded synthesis have begun.

  12. Characterization of Proteins, Peptides, and Polynucleotides by Mass Spectrometry

    NARCIS (Netherlands)

    Bischoff, Rainer

    2002-01-01

    Hyphenation of efficient separation methods such as high performance liquid chromatography (HPLC) or capillary electrophoresis (CE) with detection methods that provide structural or functional information is a powerful tool for the analysis of biological macromolecules. In particular,

  13. Hypochlorite-induced damage to DNA, RNA, and polynucleotides

    DEFF Research Database (Denmark)

    Hawkins, Clare Louise; Davies, Michael Jonathan

    2002-01-01

    favored exocyclic amines. EPR experiments have also provided evidence for the rapid addition of pyrimidine-derived nitrogen-centered radicals to other nucleobases to give dimers and the oxidation of DNA by radicals derived from preformed nucleoside chloramines. Direct reaction of HOCl with plasmid DNA...... on the nature of the nucleobase on which they are formed, with chloramines formed from ring heterocyclic amine groups being less stable than those formed on exocyclic amines (RNH2 groups). Evidence is presented for chlorine transfer from the former, kinetically favored, sites to the more thermodynamically...

  14. Solid-phase synthesis of polynucleotides. III. Synthesis of polynucleotides with defined sequences by the block coupling phosphotriester method.

    OpenAIRE

    Miyoshi, K; Huang, T; Itakura, K

    1980-01-01

    Preparation of the three hexadecanucleotides, dGpTpApTpCpApCpGpApGpGpCpCpCpTpT, dCpGpApCpGpApGpCpGpTpGpApCpApCpC and cTpGpCpCpGpGpCpCpApCpGpApTpGpCpG, is described by a rapid and simple solid-phase method on polyacrylamide supports. The synthesis were performed by the extension of the method described in the previous paper using di and trinucleotides of defined sequences as an incoming 3'-phosphodiester unit. Although the coupling yields to form phosphotriester bonds are slightly lower than t...

  15. NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.

    Science.gov (United States)

    Ziros, Panos G; Habeos, Ioannis G; Chartoumpekis, Dionysios V; Ntalampyra, Eleni; Somm, Emmanuel; Renaud, Cédric O; Bongiovanni, Massimo; Trougakos, Ioannis P; Yamamoto, Masayuki; Kensler, Thomas W; Santisteban, Pilar; Carrasco, Nancy; Ris-Stalpers, Carrie; Amendola, Elena; Liao, Xiao-Hui; Rossich, Luciano; Thomasz, Lisa; Juvenal, Guillermo J; Refetoff, Samuel; Sykiotis, Gerasimos P

    2018-06-01

    The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated

  16. Expression and localization of forkhead transcriptional factor 2 (Foxl2 in the gonads of protogynous wrasse, Halichoeres trimaculatus

    Directory of Open Access Journals (Sweden)

    Kobayashi Yasuhisa

    2010-11-01

    Full Text Available Abstract Background Three-spot wrasse, Halichoeres trimaculatus, is a marine protogynous hermaphrodite fish. Individuals mature either as initial phase (IP males or females. Appropriate social cues induce the sex change from IP female to terminal phase (TP male. However, the molecular mechanisms behind such a sex change remain largely unknown. Recently, the forkhead transcription factor 2 (Foxl2 was identified as an essential regulator of vertebrate ovarian development/function/phenotype. Inspired by this information, we characterized the expression patterns of Foxl2 in the protogynous wrasse assuming Foxl2 as the female-specific marker in this species. Methods First, we clonedFoxl2 cDNA from ovary by reverse transcription polymerase chain reaction (RT-PCR followed by rapid amplification of cDNA ends (RACE. Next, we analysed expression pattern of Foxl2 messenger RNA (mRNA and protein in gonads of different sexual phases by real time quantitative PCR assay and flour fluorescence immunohistochemical method, respectively. Additionally, we studied the changes in Foxl2 expression pattern during aromatase inhibitor (AI-induced sex change. Results The amino acid sequence (306 AA of wrasse Foxl2, especially the forkhead domain, shows high identity with that of other reported teleost Foxl2s. Quite unexpectedly, no sexual dimorphism was observable between the testes and ovary in the expression pattern of Foxl2. In female phase fish, signals for Foxl2 protein were detectable in the granulosa cells, but not the theca cells. Transcript levels of Foxl2 in the testes of IP and TP males were identical to that in the ovaries of females and, further, Foxl2 protein was found to be localized in the interstitial cells including tubules and Leydig cells. Treatment with AI induced sex change in male gonads and an up-regulation was seen in the expression of Foxl2 in these gonads. Conclusions Unlike in other vertebrates, including teleosts, Foxl2 may have a different

  17. The interaction between coagulation factor 2 receptor and interleukin 6 haplotypes increases the risk of myocardial infarction in men.

    Directory of Open Access Journals (Sweden)

    Bruna Gigante

    Full Text Available The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R and the interleukin 6 (IL6 haplotypes modulates the risk of myocardial infarction (MI in the Stockholm Heart Epidemiology Program (SHEEP. Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S, indicates the presence of a synergy (S>1 or of an antagonism (S<1. None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI of 1.58 (1.05-2.41 (p = 0.02 in the crude and an OR of 1.72 (1.11-2.67 (p = 0.01 in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI of 2.24 (1.27-3.95 (p = 0.005 and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI of 1.56 (1.02-2.37 (p = 0.03 and S of 1.66 (0.89-31. In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI.

  18. Hypoxia Inducible Factor-2 Alpha and Prolinhydroxylase 2 Polymorphisms in Patients with Acute Respiratory Distress Syndrome (ARDS

    Directory of Open Access Journals (Sweden)

    Annika Dötsch

    2017-06-01

    Full Text Available Hypoxia-inducible-factor-2α (HIF-2α and HIF-2 degrading prolyl-hydroxylases (PHD are key regulators of adaptive hypoxic responses i.e., in acute respiratory distress syndrome (ARDS. Specifically, functionally active genetic variants of HIF-2α (single nucleotide polymorphism (SNP [ch2:46441523(hg18] and PHD2 (C/T; SNP rs516651 and T/C; SNP rs480902 are associated with improved adaptation to hypoxia i.e., in high-altitude residents. However, little is known about these SNPs’ prevalence in Caucasians and impact on ARDS-outcome. Thus, we tested the hypotheses that in Caucasian ARDS patients SNPs in HIF-2α or PHD2 genes are (1 common, and (2 independent risk factors for 30-day mortality. After ethics-committee approval, 272 ARDS patients were prospectively included, genotyped for PHD2 (Taqman SNP Genotyping Assay and HIF-2α-polymorphism (restriction digest + agarose-gel visualization, and genotype dependent 30-day mortality was analyzed using Kaplan-Meier-plots and multivariate Cox-regression analyses. Frequencies were 99.62% for homozygous HIF-2α CC-carriers (CG: 0.38%; GG: 0%, 2.3% for homozygous PHD2 SNP rs516651 TT-carriers (CT: 18.9%; CC: 78.8%, and 3.7% for homozygous PHD2 SNP rs480902 TT-carriers (CT: 43.9%; CC: 52.4%. PHD2 rs516651 TT-genotype in ARDS was independently associated with a 3.34 times greater mortality risk (OR 3.34, CI 1.09–10.22; p = 0.034 within 30-days, whereas the other SNPs had no significant impact (p = ns. The homozygous HIF-2α GG-genotype was not present in our Caucasian ARDS cohort; however PHD2 SNPs exist in Caucasians, and PHD2 rs516651 TT-genotype was associated with an increased 30-day mortality suggesting a relevance for adaptive responses in ARDS.

  19. Simulating Population Growth.

    Science.gov (United States)

    Byington, Scott

    1997-01-01

    Presents a strategy to help students grasp the important implications of population growth. Involves an interactive demonstration that allows students to experience exponential and logistic population growth followed by a discussion of the implications of population-growth principles. (JRH)

  20. AMSAA Reliability Growth Guide

    National Research Council Canada - National Science Library

    Broemm, William

    2000-01-01

    ... has developed reliability growth methodology for all phases of the process, from planning to tracking to projection. The report presents this methodology and associated reliability growth concepts.

  1. Growth/differentiation factor-15: prostate cancer suppressor or promoter?

    Czech Academy of Sciences Publication Activity Database

    Vaňhara, P.; Hampl, A.; Kozubík, Alois; Souček, Karel

    2012-01-01

    Roč. 15, č. 4 (2012), s. 320-328 ISSN 1365-7852 R&D Projects: GA MZd NS9600; GA MZd NS9956 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : MACROPHAGE-INHIBITORY CYTOKINE-1 * GROWTH-DIFFERENTIATION FACTOR-15 * TGF-BETA SUPERFAMILY Subject RIV: BO - Biophysics Impact factor: 2.811, year: 2012

  2. Green growth in fisheries

    DEFF Research Database (Denmark)

    Nielsen, Max; Ravensbeck, Lars; Nielsen, Rasmus

    2014-01-01

    harming the environment. Fishery is an environment-dependent sector and it has been argued that there is no potential for green growth in the sector owing to global overexploitation, leaving no scope for production growth. The purpose of this paper is to explain what green growth is and to develop......Climate change and economic growth have gained a substantial amount of attention over the last decade. Hence, in order to unite the two fields of interest, the concept of green growth has evolved. The concept of green growth focuses on how to achieve growth in environment-dependent sectors, without...... a conceptual framework. Furthermore, the aim is to show that a large green growth potential actually exists in fisheries and to show how this potential can be achieved. The potential green growth appears as value-added instead of production growth. The potential can be achieved by reducing overcapacity...

  3. Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC.

    Science.gov (United States)

    Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

    2017-02-14

    Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy.

  4. Fatigue cracks in Eurofer 97 steel: Part II. Comparison of small and long fatigue crack growth

    Czech Academy of Sciences Publication Activity Database

    Kruml, Tomáš; Hutař, Pavel; Náhlík, Luboš; Seitl, Stanislav; Polák, Jaroslav

    2011-01-01

    Roč. 412, 1 (2011), s. 7-12 ISSN 0022-3115 R&D Projects: GA ČR GA106/09/1954; GA ČR GA101/09/0867 Institutional research plan: CEZ:AV0Z20410507 Keywords : ferritic-martensitic steel * long crack growth * small crack growth * crack closure Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.052, year: 2011

  5. Globalization, Growth and Poverty

    International Development Research Centre (IDRC) Digital Library (Canada)

    One-pagers are a publication of IDRC's “Globalization, Growth and Poverty” Program Initiative, and are based on ... countries, mainly the fast-growing economies of East Asia. ... had no significant overall impact on investment and growth. Other.

  6. Measuring multifactor productivity growth

    Czech Academy of Sciences Publication Activity Database

    Wölfl, A.; Hájková, Dana

    -, 2007/5 (2007), s. 1-45 Institutional research plan: CEZ:AV0Z70850503 Keywords : multifactor productivity growth * GDP growth * measuring Subject RIV: AH - Economics http://www.oecd.org/dataoecd/61/17/39522985.pdf

  7. Growth hormone test

    Science.gov (United States)

    ... is called acromegaly . In children it is called gigantism . Too little growth hormone can cause a slow ... growth due to excess GH during childhood, called gigantism. (A special test is done to confirm this ...

  8. CDC Child Growth Charts

    Data.gov (United States)

    U.S. Department of Health & Human Services — CDC child growth charts consist of a series of percentile curves that illustrate the distribution of selected body measurements in U.S. children. Pediatric growth...

  9. Growth hormone stimulation test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of ...

  10. Normal growth and development

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002456.htm Normal growth and development To use the sharing features on this page, please enable JavaScript. A child's growth and development can be divided into four periods: ...

  11. Spatial heterogeneity of diatom silicification and growth in a eutrophic reservoir

    Czech Academy of Sciences Publication Activity Database

    Znachor, Petr; Visocka, V.; Nedoma, Jiří; Rychtecký, Pavel

    2013-01-01

    Roč. 58, č. 9 (2013), s. 1889-1902 ISSN 0046-5070 R&D Projects: GA ČR(CZ) GAP504/11/2177; GA ČR(CZ) GAP504/11/2182 Institutional support: RVO:60077344 Keywords : phytoplankton * PDMPO * growth rate * silica deposition * fluorescence Subject RIV: DA - Hydrology ; Limnology Impact factor: 2.905, year: 2013

  12. Long fatigue crack growth in Inconel 718 produced by selective laser melting

    Czech Academy of Sciences Publication Activity Database

    Konečná, R.; Kunz, Ludvík; Nicoletto, G.; Bača, A.

    2016-01-01

    Roč. 92, NOV (2016), s. 499-506 ISSN 0142-1123. [CP 2015 - International Conference on Crack Paths /5./. Ferrara, 16.09.2015-18.09.2015] Institutional support: RVO:68081723 Keywords : Inconel 718 * Selective laser melting * Microstructure * Fatigue crack growth * Fractography Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.899, year: 2016

  13. Random nucleation and growth of Pt nanoparticles at the polarized interface between two immiscible electrolyte solutions

    Czech Academy of Sciences Publication Activity Database

    Trojánek, Antonín; Langmaier, Jan; Samec, Zdeněk

    2007-01-01

    Roč. 599, č. 2 (2007), s. 160-166 ISSN 0022-0728 R&D Projects: GA AV ČR IAA4040407 Institutional research plan: CEZ:AV0Z40400503 Keywords : polarized ITIES * deposition * platinum * random nucleation and growth Subject RIV: CG - Electrochemistry Impact factor: 2.580, year: 2007

  14. The Arabidopsis PLAT domain protein1 promotes abiotic stress tolerance and growth in tobacco

    Czech Academy of Sciences Publication Activity Database

    Hyun, T.K.; Albacete, A.; van der Graaff, E.; Eom, S. H.; Großkinsky, D.K.; Böhm, H.; Janschek, U.; Rim, Y.; Ali, W.; Kim, S.Y.; Roitsch, Thomas

    2015-01-01

    Roč. 24, č. 4 (2015), s. 651-663 ISSN 0962-8819 Institutional support: RVO:67179843 Keywords : Abiotic stress * Biotic stress * Plant growth * AtPLAT1 gene * Tobacco Subject RIV: EH - Ecology, Behaviour Impact factor: 2.054, year: 2015

  15. Surface hydrophobicity and roughness influences the morphology and biochemistry of streptomycetes during attached growth and differentiation

    Czech Academy of Sciences Publication Activity Database

    Petráčková, Denisa; Buriánková, Karolína; Tesařová, E.; Bobková, Šárka; Bezoušková, Silvia; Benada, Oldřich; Kofroňová, Olga; Janeček, Jiří; Halada, Petr; Weiser, Jaroslav

    2013-01-01

    Roč. 342, č. 2 (2013), s. 147-156 ISSN 0378-1097 R&D Projects: GA AV ČR IAA500200913 Institutional support: RVO:61388971 Keywords : streptomycetes * attached growth * glass beads Subject RIV: EE - Microbiology, Virology Impact factor: 2.046, year: 2013

  16. Spatiotemporal variability of stone pine (Pinus pinea L.) growth response to climate across the Iberian Peninsula

    Czech Academy of Sciences Publication Activity Database

    Natalini, F.; Alejano, R.; Vazquez-Pique, J.; Pardos, M.; Calama, R.; Büntgen, Ulf

    2016-01-01

    Roč. 40, dec (2016), s. 72-84 ISSN 1125-7865 Institutional support: RVO:67179843 Keywords : tree-rings * genetically depauperate * mediterranean climate * phenotypic plasticity * cambial activity * fagus-sylvatica * spain * drought * widespread * halepensis * Climate change * Dendroecology * Growth plasticity * Mediterranean * Tree rings * Drought Subject RIV: EH - Ecology, Behaviour Impact factor: 2.259, year: 2016

  17. Fishing-induced evolution of growth: concepts, mechanisms and the empirical evidence

    Czech Academy of Sciences Publication Activity Database

    Enberg, K.; Jørgensen, C.; Dunlop, E. S.; Varpe, Ø.; Boukal S., David; Baulier, L.; Eliassen, S.; Heino, M.

    2012-01-01

    Roč. 33, č. 1 (2012), s. 1-25 ISSN 0173-9565 Institutional research plan: CEZ:AV0Z50070508 Keywords : fisheries -induced evolution * fishing-induced evolution * growth Subject RIV: ED - Physiology Impact factor: 2.561, year: 2012 http://onlinelibrary.wiley.com/doi/10.1111/j.1439-0485.2011.00460.x/pdf

  18. Impact of arbuscular mycorrhizal fungi (AMF) on cucumber growth and phosphorus uptake under cold stress

    Czech Academy of Sciences Publication Activity Database

    Ma, J.; Janoušková, Martina; Li, Y.; Yu, X.; Yan, Y.; Zou, Z.; He, C.

    2015-01-01

    Roč. 42, č. 12 (2015), s. 1158-1167 ISSN 1445-4408 R&D Projects: GA MŠk LH12178 Institutional support: RVO:67985939 Keywords : mycorrhizal growth response * phosphate transporter * Rhizophagus irregularis Subject RIV: ED - Physiology Impact factor: 2.491, year: 2015

  19. Highly plastic resource allocation to growth and reproduction in females of an African annual fish

    Czech Academy of Sciences Publication Activity Database

    Vrtílek, Milan; Reichard, Martin

    2015-01-01

    Roč. 24, č. 4 (2015), s. 616-628 ISSN 0906-6691 R&D Projects: GA ČR(CZ) GAP506/11/0112 Keywords : Nothobranchius * compensatory growth * egg size * life history * diet restriction Subject RIV: EG - Zoology Impact factor: 2.052, year: 2015

  20. Effect of adenosine on the growth of human T-lymphocyte leukemia cell line MOLT-4

    Czech Academy of Sciences Publication Activity Database

    Štreitová, Denisa; Weiterová, Lenka; Hofer, Michal; Holá, Jiřina; Horváth, Viktor; Kozubík, Alois; Znojil, V.

    2007-01-01

    Roč. 25, č. 6 (2007), s. 419-426 ISSN 0735-7907 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : MOLT-4 leukemia cell s * cell growth * adenosine Subject RIV: BO - Biophysics Impact factor: 2.106, year: 2007

  1. Growth kinetics of racemic heptahelicene-2-carboxylic acid nanowires on calcite (104)

    Czech Academy of Sciences Publication Activity Database

    Einax, M.; Richter, T.; Nimmrich, M.; Rahe, P.; Stará, Irena G.; Starý, Ivo; Kühnle, A.; Maass, P.

    2016-01-01

    Roč. 145, č. 13 (2016), č. článku 134702. ISSN 0021-9606 Institutional support: RVO:61388963 Keywords : heptahelicene-2-carboxylic acid nanowires * nc-AFM * calcite * growth kinetics Subject RIV: CC - Organic Chemistry Impact factor: 2.965, year: 2016

  2. Synechococcus growth in the ocean may depend on the lysis of heterotrophic bacteria

    Czech Academy of Sciences Publication Activity Database

    Weinbauer, M.G.; Bonilla-Findji, O.; Chan, A.M.; Dolan, J. R.; Short, S.M.; Šimek, Karel; Wilhelm, S. W.; Suttle, C.A.

    2011-01-01

    Roč. 33, č. 10 (2011), s. 1465-1476 ISSN 0142-7873 R&D Projects: GA ČR(CZ) GA206/08/0015 Institutional research plan: CEZ:AV0Z60170517 Keywords : viruses * growth control of cyanobacteria * heterotrophic bacterioplankton Subject RIV: EE - Microbiology, Virology Impact factor: 2.079, year: 2011

  3. Systemic Crises and Growth

    OpenAIRE

    Romain Ranciere; Aaron Tornell; Frank Westermann

    2005-01-01

    In this paper, we document the fact that countries that have experienced occasional financial crises have, on average, grown faster than countries with stable financial conditions. We measure the incidence of crisis with the skewness of credit growth, and find that it has a robust negative effect on GDP growth. This link coexists with the negative link between variance and growth typically found in the literature. To explain the link between crises and growth we present a model where contract...

  4. Urban tree growth modeling

    Science.gov (United States)

    E. Gregory McPherson; Paula J. Peper

    2012-01-01

    This paper describes three long-term tree growth studies conducted to evaluate tree performance because repeated measurements of the same trees produce critical data for growth model calibration and validation. Several empirical and process-based approaches to modeling tree growth are reviewed. Modeling is more advanced in the fields of forestry and...

  5. Unemployment and endogenous growth

    NARCIS (Netherlands)

    van Schaik, A.B.T.M.; de Groot, H.L.F.

    1995-01-01

    In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.

  6. Toddler Growth and Development

    Science.gov (United States)

    ... the AAP Schedule of Well-Child Care Visits . ​​ Toddler Growth & Development Physical Skills Walks alone Pulls toys behind when ... 18 to 23 Month Old Language Delays in Toddlers: Information for Parents ... Physical Appearance and Growth: Your 1 Year Old Physical Appearance and Growth: ...

  7. Growth Charts (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Growth Charts KidsHealth / For Parents / Growth Charts What's in ... Problem? Print en español Tablas de crecimiento About Growth Charts Look at any class picture, and you' ...

  8. Growth hormone, growth factors, and acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Ludecke, D.K.; Tolis, G.T.

    1987-01-01

    This book contains five sections, each consisting of several papers. The section headings are: Biochemistry and Physiology of GH and Growth Factors, Pathology of Acromegaly, Clinical Endocrinology of Acromegaly, Nonsurgical Therapy of Acromegaly, and Surgical Therapy of Acromegaly.

  9. Lung growth and development.

    Science.gov (United States)

    Joshi, Suchita; Kotecha, Sailesh

    2007-12-01

    Human lung growth starts as a primitive lung bud in early embryonic life and undergoes several morphological stages which continue into postnatal life. Each stage of lung growth is a result of complex and tightly regulated events governed by physical, environmental, hormonal and genetic factors. Fetal lung liquid and fetal breathing movements are by far the most important determinants of lung growth. Although timing of the stages of lung growth in animals do not mimic that of human, numerous animal studies, mainly on sheep and rat, have given us a better understanding of the regulators of lung growth. Insight into the genetic basis of lung growth has helped us understand and improve management of complex life threatening congenital abnormalities such as congenital diaphragmatic hernia and pulmonary hypoplasia. Although advances in perinatal medicine have improved survival of preterm infants, premature birth is perhaps still the most important factor for adverse lung growth.

  10. Adult growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

  11. Aid and growth regressions

    DEFF Research Database (Denmark)

    Hansen, Henrik; Tarp, Finn

    2001-01-01

    This paper examines the relationship between foreign aid and growth in real GDP per capita as it emerges from simple augmentations of popular cross country growth specifications. It is shown that aid in all likelihood increases the growth rate, and this result is not conditional on ‘good’ policy....... investment. We conclude by stressing the need for more theoretical work before this kind of cross-country regressions are used for policy purposes.......This paper examines the relationship between foreign aid and growth in real GDP per capita as it emerges from simple augmentations of popular cross country growth specifications. It is shown that aid in all likelihood increases the growth rate, and this result is not conditional on ‘good’ policy...

  12. City Population Growth and Economic Growth

    DEFF Research Database (Denmark)

    Freire-Gibb, L. Carlos

    2008-01-01

    This article looks at the relationship between city population growth (intimately related to population proximity), and economic development. The hypothesis is that wherever dynamic and inclusive networks exist, there are more opportunities for economic development in this place. When these types...... of networks choose a tool (project, policy) to implement in the city, success will be more likely. Furthermore, virtuous circles will arise. The author gives an overview of two historical cases in urban growth, in Europe (1200-1800) and the U.S.A. (1800 to today)....

  13. Earthquakes and economic growth

    OpenAIRE

    Fisker, Peter Simonsen

    2012-01-01

    This study explores the economic consequences of earthquakes. In particular, it is investigated how exposure to earthquakes affects economic growth both across and within countries. The key result of the empirical analysis is that while there are no observable effects at the country level, earthquake exposure significantly decreases 5-year economic growth at the local level. Areas at lower stages of economic development suffer harder in terms of economic growth than richer areas. In addition,...

  14. Luxury-based Growth

    OpenAIRE

    Shiro Kuwahara

    2006-01-01

    Assuming that there exists a preference for luxury goods and a knowledge spillover from luxury goods production to goods production, this paper constructs an endogenous economic growth model. The model predicts two steady states: one is a steady positive growth state with regard to luxury goods production, and the other is a zero growth state in the absence of luxury goods production. Thus, this study examines the polarization of economies based on luxury goods consumption

  15. Robust Growth Determinants

    OpenAIRE

    Doppelhofer, Gernot; Weeks, Melvyn

    2011-01-01

    This paper investigates the robustness of determinants of economic growth in the presence of model uncertainty, parameter heterogeneity and outliers. The robust model averaging approach introduced in the paper uses a flexible and parsi- monious mixture modeling that allows for fat-tailed errors compared to the normal benchmark case. Applying robust model averaging to growth determinants, the paper finds that eight out of eighteen variables found to be significantly related to economic growth ...

  16. Thailand's growth rebalancing

    OpenAIRE

    Jitsuchon, Somchai; Sussangkarn, Chalongphob

    2009-01-01

    This paper reviews Thailand's structural changes, the 1997 crisis experience, and recovery and lessons from the crisis. The paper then discusses the impacts of the subprime crisis on the Thai economy and the policy responses to date. The paper ends by discussing strategies to rebalance growth by reducing the dependence on exports as the main growth engine. The recovery from the 1997 crisis left Thailand more dependent than ever on exports as the main engine of growth, with the ratio of export...

  17. Smart Growth and Transportation

    Science.gov (United States)

    Describes the relationship between smart growth and transportation, focusing smart and sustainable street design, transit-oriented development, parking management, sustainable transportation planning, and related resources.

  18. FDI- Economic Growth Nexus

    DEFF Research Database (Denmark)

    Bujac, Andreea Ioana; Corado Cretu, Emanuel

    2017-01-01

    Conducting a systematic literature review on the topic of FDI and Economic Growth and investigating this relationship, along with the determinants of an economy that attract FDI and the externalities resulting from Foreign activities, it is found that FDI does have a positive effect on a host...... country’s economic growth but only with the preexistence of certain determinants which facilitate the absorption capacity of the host country on reaping the spillover effects (externalities) of FDI. Lastly, a framework was built to illustrate the interaction between FDI, Determinants and condition...... of the host economy, barriers to growth, economic growth and externalities....

  19. Aid, growth, and development

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    2010-01-01

    The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro- and meso-levels, recent literature doubts the ability of foreign aid to foster economic growth and development. This paper assesses the aid-growth literature and, taking inspiration from the program...... evaluation literature, we re-examine key hypotheses. In our findings, aid has a positive and statistically significant causal effect on growth over the long run, with confidence intervals conforming to levels suggested by growth theory. Aid remains a key tool for enhancing the development prospects of poor...

  20. Optimising growth in phenylketonuria

    DEFF Research Database (Denmark)

    Dokoupil, Katharina; Gokmen-Ozel, Hulya; Lammardo, Anna Maria

    2012-01-01

    populations. We reviewed the literature searching for evidence regarding PKU and growth as well as possible links between dietary management of PKU and growth. The search retrieved only limited evidence on the effect of PKU and its dietary management on growth. Physical development in PKU remains an under....... Protein requirements in dietary management of PKU are met mostly from Phe-free protein substitutes with the intake of natural protein restricted to patient tolerance. Several reports have suggested that growth in early childhood in PKU is sub-optimal, relative to non-PKU control groups or reference...

  1. Triplet ultrasound growth parameters.

    Science.gov (United States)

    Vora, Neeta L; Ruthazer, Robin; House, Michael; Chelmow, David

    2006-03-01

    To create ultrasound growth curves for normal growth of fetal triplets using statistical methodology that properly accounts for similarities of growth of fetuses within a mother as well as repeated measurements over time for each fetus. In this longitudinal study, all triplet pregnancies managed at a single tertiary center from 1992-2004 were reviewed. Fetuses with major anomalies, prior selective reduction, or fetal demise were excluded. Data from early and late gestation in which there were fewer than 30 fetal measurements available for analysis were excluded. We used multilevel models to account for variation in growth within a single fetus over time, variations in growth between multiple fetuses within a single mother, and variations in fetal growth between mothers. Medians (50th), 10th, and 90th percentiles were estimated by the creation of multiple quadratic growth models from bootstrap samples adapting a previously published method to compute prediction intervals. Estimated fetal weight was derived from Hadlock's formula. One hundred fifty triplet pregnancies were identified. Twenty-seven pregnancies were excluded for the following reasons: missing records (23), fetal demise (3), and fetal anomaly (1). The study group consisted of 123 pregnancies. The gestational age range was restricted to 14-34 weeks. Figures and tables were developed showing medians, 10th and 90th percentiles for estimated fetal weight, femur length, biparietal diameter, abdominal circumference, and head circumference. Growth curves for triplet pregnancies were derived. These may be useful for identification of abnormal growth in triplet fetuses. III.

  2. Incentives and Earnings Growth

    DEFF Research Database (Denmark)

    Frederiksen, Anders

    2013-01-01

    The career prospects of newly recruited employees differ substantially within an organization. The stars experience considerable growth in earnings; others can hardly maintain their entry salaries. This article sheds light on the mechanisms generating the observed heterogeneity in earnings growth...... by investigating the effects that explicit short-run incentives and implicit incentives have on earnings growth. The model’s predictions are tested using personnel records from a large bank and are found to be consistent with the observed earnings growth during the first half of the employees’ careers....

  3. Sustainable growth in Europe

    International Nuclear Information System (INIS)

    Andreini, P.

    1993-01-01

    The measures till now adopted did not stop environmental deterioration in Europe and the growth of economic activities in the future will make the situation more and more heavy. The European Communities (EEC) Cabinet launched a long term program for a sustainable growth in Europe, which could conciliate economic needs with environmental protection. This paper presents the first part of the program

  4. Nutrition and growth

    Energy Technology Data Exchange (ETDEWEB)

    Forbes, G.B.

    1977-07-01

    Longitudinal growth data on children who developed obesity during childhood reveal a distinct tendency for height gain to accelerate coincident with or after the onset of excessive weight gain. The magnitude of the relative height increment is related to the degree of overweight. Overnutrition accelerates growth, just as undernutrition retards it.

  5. Growth Modulation in Achondroplasia.

    Science.gov (United States)

    McClure, Philip K; Kilinc, Eray; Birch, John G

    2017-09-01

    Achondroplasia is the most common skeletal dysplasia with a rate of nearly 1/10,000. The development of lower extremity deformity is well documented, and various modes of correction have been reported. There are no reports on the use of growth modulation to correct angular deformity in achondroplasia. Medical Records from 1985 to 2015 were reviewed for the diagnosis of achondroplasia and growth modulation procedures. Patients who had been treated for angular deformity of the legs by growth modulation were identified. A detailed analysis of their medical record and preoperative and final lower extremity radiographs was completed. Four patients underwent growth modulation procedures, all to correct existing varus deformity of the legs. Three of the 4 patients underwent bilateral distal femoral and proximal tibial growth modulation. The remaining patient underwent tibial correction only. Two of the 4 patients had a combined proximal fibular epiphysiodesis. All limbs had some improvement of alignment; however, 1 patient went on to bilateral osteotomies. Only 1 limb corrected to a neutral axis with growth modulation alone at last follow-up, initial implantation was done before 5 years of age. Growth modulation is an effective means for deformity correction in the setting of achondroplasia. However implantation may need to be done earlier than would be typical for patients without achondroplasia. Osteotomy may still be required after growth modulation for incomplete correction.

  6. Empowering growth in Pakistan?

    NARCIS (Netherlands)

    K.A. Siegmann (Karin Astrid); H. Majid (Hadia)

    2014-01-01

    textabstractPakistan's Vision 2025 connects a policy commitment to greater gender equality with inclusive growth. It prioritises a "good quality of life and high living standard for all citizens across regions, gender" and to "achieve an annual average growth rate of 7 to 8 per cent that is

  7. Strategic growth options

    NARCIS (Netherlands)

    Kulatilaka, N.; Perotti, E.C.

    1998-01-01

    We provide a strategic rationale for growth options under uncertainty and imperfect corn-petition. In a market with strategic competition, investment confers a greater capability to take advantage of future growth opportunities. This strategic advantage leads to the capture of a greater share of the

  8. Modeling Exponential Population Growth

    Science.gov (United States)

    McCormick, Bonnie

    2009-01-01

    The concept of population growth patterns is a key component of understanding evolution by natural selection and population dynamics in ecosystems. The National Science Education Standards (NSES) include standards related to population growth in sections on biological evolution, interdependence of organisms, and science in personal and social…

  9. Cluster growth kinetics

    International Nuclear Information System (INIS)

    Dubovik, V.M.; Gal'perin, A.G.; Rikhvitskij, V.S.; Lushnikov, A.A.

    2000-01-01

    Processes of some traffic blocking coming into existence are considered as probabilistic ones. We study analytic solutions for models for the dynamics of both cluster growth and cluster growth with fragmentation in the systems of finite number of objects. Assuming rates constancy of both coalescence and fragmentation, the models under consideration are linear on the probability functions

  10. SLOWER BUT HEALTHIER GROWTH

    Institute of Scientific and Technical Information of China (English)

    LAN XINZHEN

    2010-01-01

    @@ China's economic growth has slowed,economic statistics released on July 15 show,confirming market expectations.But officials said the country's economy is still on track. The recovery has gained traction in China,which registered a double-digit growth of 11.1 percent in the first half of this year.

  11. Trade, Growth, and Poverty

    OpenAIRE

    Dollar, David; Kraay, Aart

    2001-01-01

    The evidence from individual cases and from cross-country analysis supports the view that globalization leads to faster growth and poverty reduction in poor countries. To determine the effect of globalization on growth, poverty, and inequality, the authors first identify a group of developing countries that are participating more in globalization. China, India, and several other large coun...

  12. Measures of Student Growth

    Science.gov (United States)

    Texas Education Agency, 2016

    2016-01-01

    Beginning in the 2017-2018 school year, appraisal systems in Texas, whether the state-recommended system or a locally developed system, will need to include a measure of student growth at the individual teacher level. Student growth measures how much a student progresses academically during his or her time with a particular teacher. It takes into…

  13. Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats.

    Science.gov (United States)

    Troib, Ariel; Guterman, Mayan; Rabkin, Ralph; Landau, Daniel; Segev, Yael

    2016-08-01

    Childhood chronic kidney disease (CKD) is associated with both short stature and abnormal bone mineralization. Normal longitudinal growth depends on proper maturation of epiphyseal growth plate (EGP) chondrocytes, leading to the formation of trabecular bone in the primary ossification centre. We have recently shown that linear growth impairment in CKD is associated with impaired EGP growth hormone (GH) receptor signalling and that exercise improved insulin-like growth factor I (IGF-I) signalling in CKD-related muscle atrophy. In this study, 20-day-old rats underwent 5/6 nephrectomy (CKD) or sham surgery (C) and were exercised with treadmill, with or without GH supplementation. CKD-related growth retardation was associated with a widened EGP hypertrophic zone. This was not fully corrected by exercise (except for tibial length). Exercise in CKD improved the expression of EGP key factors of endochondral ossification such as IGF-I, vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteocalcin. Combining GH treatment with treadmill exercise for 2 weeks improved the decreased trabecular bone volume in CKD, as well as the expression of growth plate runt-related transcription factor 2, RANKL, metalloproteinase 13 and VEGF, while GH treatment alone could not do that. Treadmill exercise improves tibial bone linear growth, as well as growth plate local IGF-I. When combined with GH treatment, running exercise shows beneficial effects on trabecular bone formation, suggesting the potential benefit of this combination for CKD-related short stature and bone disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  14. Aid and Growth

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    , are being drawn on the basis of fragile evidence. This paper first assesses the aid-growth literature with a focus on recent contributions. The aid-growth literature is then framed, for the first time, in terms of the Rubin Causal Model, applied at the macroeconomic level. Our results show that aid has......The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro and meso-levels, recent literature has turned decidedly pessimistic with respect to the ability of foreign aid to foster economic growth. Policy implications, such as the complete cessation of aid to Africa...... a positive and statistically significant causal effect on growth over the long run with point estimates at levels suggested by growth theory. We conclude that aid remains an important tool for enhancing the development prospects of poor nations....

  15. Rejuveniles and Growth

    DEFF Research Database (Denmark)

    Barnett, Richard C.; Bhattacharya, Joydeep

    Rejuveniles are "people who cultivate tastes and mind-sets tradi- tionally associated with those younger than themselves." (Noxon, 2006) In this paper, we study a standard AK growth model of overlapping generations populated by rejuve- niles. For our purposes, rejuveniles are old agents who derive...... utility from "keeping up" their consumption with that of the current young. We find that such cross-generational keeping up is capable of generating interesting equilibrium growth dynamics, including growth cycles. No such growth dynamics is possible either in the baseline model, one where...... no such generational consumption externality exists, or for almost any other form of keeping up. Steady-state growth in a world with rejuveniles may be higher than that obtained in the baseline model....

  16. Aid Effectiveness on Growth

    DEFF Research Database (Denmark)

    Doucouliagos, Hristos; Paldam, Martin

    The AEL (aid effectiveness literature) is econo¬metric studies of the macroeconomic effects of development aid. It contains about 100 papers of which 68 are reduced form estimates of theeffect of aid on growth in the recipient country. The raw data show that growth is unconnected to aid......, but the AEL has put so much structure on the data that all results possible have emerged. The present meta study considers both the best-set of the 68 papers and the all-set of 543 regressions published. Both sets have a positive average aid-growth elasticity, but it is small and insignificant: The AEL has...... betweenstudies is real. In particular, the aid-growth association is stronger for Asian countries, and the aid-growth association is shown to have been weaker in the 1970s....

  17. Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

    Science.gov (United States)

    Kulkarni, Supriya R.; Donepudi, Ajay C.; Xu, Jialin; Wei, Wei; Cheng, Qiuqiong C.; Driscoll, Maureen V.; Johnson, Delinda A.; Johnson, Jeffrey A.; Li, Xiaoling

    2014-01-01

    Abstract Aims: The purpose of this study was to determine whether 3′-5′-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2–4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2- and SIRT1–dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20, 15–30. PMID:23725046

  18. Aid and Growth

    DEFF Research Database (Denmark)

    Tarp, Finn; Mekasha, Tseday Jemaneh

    2013-01-01

    Recent litterature in the meta-analysis category where results from a range of studies are brought together throws doubt on the ability of foreign aid to foster economic growth and development. This article assesses what meta-analysis has to contribute to the litterature on the effectiveness...... of foreign aid in terms of growth impact. We re-examine key hypotheses, and find that the effect of aid on growth is positive and statistically significant. This significant effect is genuine, and not an artefact of publication selection. We also show why our results differ from those published elsewhere....

  19. Aid and Growth

    DEFF Research Database (Denmark)

    Mekasha, Tseday Jemaneh; Tarp, Finn

    Some recent literature in the meta-analysis category where results from a range of studies are brought together throws doubt on the ability of foreign aid to foster economic growth and development. This paper assesses what meta-analysis has to say about the effectiveness of foreign aid in terms...... of the growth impact. We re-examine key hypotheses, and find that the effect of aid on growth is positive and statistically significant. This significant effect is genuine, and not an artefact of publication selection. We also show why our results differ from those published elsewhere....

  20. Environment and Growth

    DEFF Research Database (Denmark)

    Horii, Ryo; Ikefuji, Masako

    . In a less developed country, this link, which we call “limits to growth,” emerges as the “poverty-environment trap,” which explains the persistent international inequality both in terms of income and environment. This link also threatens the sustainability of the world’s economic growth, particularly when...... the emission of greenhouse gases raises the risk of natural disasters. Stronger environmental policies are required to overcome this link. While there is a trade-off between the environment and growth in the short run, we show that an appropriate policy can improve both in the long run....

  1. Survival analysis according to the receiver tumoral expression profile of the epidermal growth factor - 2 (HER2), the estrogen receptor (ER) and progesterone receptor (RP) in Uruguayan patients with breast cancer

    International Nuclear Information System (INIS)

    Camejo, N.; Gonzalez, V.; Ferrero, L.; Castillo, C.; Delgado, L.; Fresco, R.; Santander, G.; Aguiar, S.; Heinzen, S.; Martinez, A.; Maurizt, S.; Meyer, C.; Sena, G.; Spera, G.; Ubillos, L.; Xavier, F.; Deneo, H.; Aghazarian, M.; Rodriguez, R.; Sabini, G.

    2010-01-01

    Breast cancer (CM), the leading cause of death from cancer in Uruguayan women, is a heterogeneous disease. The study of the expression level of tumor hormone receptor (H R) and Her-2 neu can recognize subtypes with different characteristics. We have previously reported the relationship of these with the clinico pathological features. To analyze the PFS (SVLP) as the biological subtype (patients HR + / HER2 - triple negative (TN) and HER2 +) in Uruguayan patients with breast cancer EI-IIII Methodology: A retrospective study where SVLP 169 cancer patients carrying analyzed breast E I-III, diagnosed between March 2006 and March 2008 from the Clinical Hospital, Military Hospital, INCA and CASMU. SVLP analysis was performed according to different biological subtypes using the Kaplan method Meier and statistical significance of differences was assessed by the log-rank test. Results: The median follow-up was 43 months. At the time of analysis 160 patients (94.7%) are alive and 141 (83.4%) are relapse-free. One hundred twenty-three patients were HR + / HER2 - (72.7%), 32 patients were TN (18.9%) and 14 were HER2 + patients (8.2%). The SVLP to two years for the total of patients was 92.3%, 94% for HR + / HER2 - 91% for TN and 71.4% for HER2 +. Comparing the curves for different subtypes SVLP showed lower for SVLP He r2 + patients compared to patients HR + / HER2 - (p = 0.03) and TN (p 0.11). The median survival was not reached globally or in the subgroup analysis. Conclusions: He r2 + patients have a shorter time to relapse which coincides as reported in the literature. SVLP similar to 2 years and overlapping of curves SVLP Patients HR + / HER2 - and TN not be explained by differences in characteristics clinico pathological

  2. Knock-in of Enhanced Green Fluorescent Protein or/and Human Fibroblast Growth Factor 2 Gene into β-Casein Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein.

    Science.gov (United States)

    Lee, Sang Mi; Kim, Ji Woo; Jeong, Young-Hee; Kim, Se Eun; Kim, Yeong Ji; Moon, Seung Ju; Lee, Ji-Hye; Kim, Keun-Jung; Kim, Min-Kyu; Kang, Man-Jong

    2014-11-01

    Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo) as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5' arm and 3' arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP) was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands.

  3. Diabetic macular oedema treated with intravitreal anti-vascular endothelial growth factor - 2-4 years follow-up of visual acuity and retinal thickness in 566 patients following Danish national guidelines

    DEFF Research Database (Denmark)

    Hodzic-Hadzibegovic, Delila; Sander, Birgit Agnes; Monberg, Tine Juul

    2017-01-01

    : Retrospective cohort study of 566 eyes in 566 patients with centre-involved DME who started intravitreal treatment with ranibizumab between January 2011 and December 2013 in the Greater Copenhagen region. Data were retrieved from a database and patient records between January 2011 and March 2016 and analysed...... using mixed-model statistics. Results: At the conclusion of follow-up, 24.6% were in active ranibizumab follow-up, 25.4% had switched to other intravitreal pharmacotherapy, 31.6% had been discontinued because of disease stability, 13.8% had been lost to follow-up, 1.4% had been discontinued because...... of low visual acuity (VA), and 3.2% had died. At baseline, mean best-corrected visual acuity (BCVA) and mean central subfield thickness (CST) were 64.9 (±15.0) letters and 400.2 (±120.3) μm. Mean change in BCVA and mean change in CST from baseline to 3, 12, 24, 36 and 48 months of follow-up were +3.9, +3...

  4. Normal and abnormal growth plate

    International Nuclear Information System (INIS)

    Kumar, R.; Madewell, J.E.; Swischuk, L.E.

    1987-01-01

    Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities

  5. Growth assessment in diagnosis of Fetal Growth Restriction. Review.

    Science.gov (United States)

    Albu, A R; Horhoianu, I A; Dumitrascu, M C; Horhoianu, V

    2014-06-15

    The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the truly growth restricted fetus who is predisposed to perinatal complications, even if its parameters are above the cut-off limits established. In this article, we present the clinical tools of fetal growth assessment: Symphyseal-Fundal Height (SFH) measurement, the fetal ultrasound parameters widely taken into consideration when discussing fetal growth: Abdominal Circumference (AC) and Estimated Fetal Weight (EFW); several types of growth charts and their characteristics: populational growth charts, standard growth charts, individualized growth charts, customized growth charts and growth trajectories.

  6. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    IAS Admin

    known to improve plant growth in many ways when compared to ... roles in agricultural productivity. ... Sustainable agriculture: Sustainable agriculture involves the successful management of agricultural re- ... For the first time Kloepper et al.

  7. Planar elliptic growth

    Energy Technology Data Exchange (ETDEWEB)

    Mineev, Mark [Los Alamos National Laboratory

    2008-01-01

    The planar elliptic extension of the Laplacian growth is, after a proper parametrization, given in a form of a solution to the equation for areapreserving diffeomorphisms. The infinite set of conservation laws associated with such elliptic growth is interpreted in terms of potential theory, and the relations between two major forms of the elliptic growth are analyzed. The constants of integration for closed form solutions are identified as the singularities of the Schwarz function, which are located both inside and outside the moving contour. Well-posedness of the recovery of the elliptic operator governing the process from the continuum of interfaces parametrized by time is addressed and two examples of exact solutions of elliptic growth are presented.

  8. Floods and Mold Growth

    Science.gov (United States)

    Mold growth may be a problem after flooding. Excess moisture in the home is cause for concern about indoor air quality primarily because it provides breeding conditions for pests, molds and other microorganisms.

  9. Environmentally Sustainable Economic Growth

    Directory of Open Access Journals (Sweden)

    Stelian Brad

    2016-05-01

    Full Text Available Economic growth and sustainable development are important issues for social prosperity. Sustainable development strives for moderate and responsible use within the economic activity of the limited resources of our planet, whereas economic growth does not limit the resource exploitation and energy, being mainly focused on productivity increase. From this perspective, both conceptual and operational contradictions occur between the two pillars of prosperity. This paper looks to these contradictions and proposes some streams of intervention such as economic growth and environmental sustainability to operate in harmony. A structured framework for innovative problem solving is considered in this respect. Results of this research show that it is possible to induce smart measures in the economic system for directing businesses towards new paradigms where economic growth is possible without negative effects on environmental sustainability.

  10. Growth and Your Newborn

    Science.gov (United States)

    ... drink alcohol, or use illegal drugs during pregnancy. Nutrition during pregnancy . Good nutrition is essential for a baby's growth in the uterus and beyond. A poor diet during pregnancy can affect how much a newborn weighs and ...

  11. Globalization, Growth and Poverty

    International Development Research Centre (IDRC) Digital Library (Canada)

    One-pagers are a publication of IDRC's “Globalization, Growth and Poverty” Program Initiative, and are based on findings from the ... Does exporting matter for the poor in South Africa? ... strategies to promote employment and higher wages in.

  12. Globalization, Growth and Poverty

    International Development Research Centre (IDRC) Digital Library (Canada)

    One-pagers are a publication of IDRC's “Globalization, Growth and Poverty” Program Initiative, and are ... great disparities, with earnings among urban workers with higher education being four or five times larger than those of illiterate rural.

  13. Growth of dopamine crystals

    Energy Technology Data Exchange (ETDEWEB)

    Patil, Vidya, E-mail: vidya.patil@ruparel.edu; Patki, Mugdha, E-mail: mugdha.patki@ruparel.edu [D. G. Ruparel College, Senapati Bapat Marg, Mahim, Mumbai – 400 016 (India)

    2016-05-06

    Many nonlinear optical (NLO) crystals have been identified as potential candidates in optical and electro-optical devices. Use of NLO organic crystals is expected in photonic applications. Hence organic nonlinear optical materials have been intensely investigated due to their potentially high nonlinearities, and rapid response in electro-optic effect compared to inorganic NLO materials. There are many methods to grow organic crystals such as vapor growth method, melt growth method and solution growth method. Out of these methods, solution growth method is useful in providing constraint free crystal. Single crystals of Dopamine have been grown by evaporating the solvents from aqueous solution. Crystals obtained were of the size of orders of mm. The crystal structure of dopamine was determined using XRD technique. Images of crystals were obtained using FEG SEM Quanta Series under high vacuum and low KV.

  14. Intrauterine Growth Restriction

    Science.gov (United States)

    ... org editorial staff Categories: Family Health, Infants and Toddlers, Pregnancy and Childbirth, WomenTags: Amniocentesis, Delivery - Cesarean, female, Growth and Development, Obstetrical, Obstetrical ultrasound, Pregnant Women, prenatal care September ...

  15. Growth in liquid media.

    Science.gov (United States)

    Elbing, Karen; Brent, Roger

    2002-08-01

    The procedure for inoculating overnight (starter) cultures of E. coli from a single colony is described along with considerations for growing larger cultures. Also included are two methods for monitoring cell growth using a spectrophotometer or a hemacytometer.

  16. Armenia's Economic Growth Sustainability

    OpenAIRE

    Hayakawa, Tatsuji

    2015-01-01

    Armenia enjoyed 15 years of uninterrupted high economic growth prior to the global financial crisis in 2009. Investment, particularly in the mining and metallurgy sectors, played a key role as a driver of economic growth. Remittances,mostly from Russia, had an effect in sustaining consumption and boosting construction. Armenia has shown some weaknesses in the external sector, due to demands for natural gas, mineral products, machinery, and equipment. Armenia's exports and FDI suffer from the ...

  17. Macroeconomics and Growth Policies

    OpenAIRE

    Jayati Ghosh

    2007-01-01

    This United Nations Background Note on Macroeconomics and Growth provides practical guidance on how to operationalize alternative equitable and employment-generating macroeconomic and growth policies in National Development Strategies. This Policy Note has been developed in cooperation with UN agencies, and has been officially reviewed by distinguished academics/ development specialists such as Jose Antonio Ocampo, Jomo K.S. and Nobel Laureate Joseph Stiglitz.

  18. SMEs, Growth, and Poverty

    OpenAIRE

    Beck, Thorsten; Demirgüç-Kunt, Asli

    2004-01-01

    This Note explores the relationship between the size of the small and medium-size enterprise (SME) sector and economic growth and poverty reduction. A new study finds no support for the widely held belief that SMEs promote higher growth and lower pover ty. But it does provide some support for the view that the quality of the business environment facing all firms, large and small, influen...

  19. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  20. Entrepreneurship, Information, and Growth

    Science.gov (United States)

    Bunten, Devin; Weiler, Stephan; Weiler, Stephan; Zahran, Sammy

    2016-01-01

    We examine the contribution to economic growth of entrepreneurial “marketplace information” within a regional endogenous growth framework. Entrepreneurs are posited to provide an input to economic growth through the information revealed by their successes and failures. We empirically identify this information source with the regional variation in establishment births and deaths, which create geographic information asymmetries that influence subsequent entrepreneurial activity and economic growth. We find that local establishment birth and death rates are significantly and positively correlated with subsequent entrepreneurship for US counties. To account for the potential endogeneity caused by forward-looking entrepreneurs, we utilize instruments based on historic mining activity. We find that the information spillover component of local establishment birth and death rates have significant positive effects on subsequent entrepreneurship and employment growth for US counties and metropolitan areas. With the help of these intruments, we show that establishment births have a positive and significant effect on future employment growth within all counties, and that in line with the information hypothesis, local establishment death rates have a similar positive effect within metropolitan counties. PMID:27516625

  1. Bacterial growth kinetics

    International Nuclear Information System (INIS)

    Boonkitticharoen, V.; Ehrhardt, J.C.; Kirchner, P.T.

    1989-01-01

    Quantitative measurement of bacterial growth may be made using a radioassay technique. This method measures, by scintillation counting, the 14 CO 2 derived from the bacterial metabolism of a 14 C-labeled substrate. Mathematical growth models may serve as reliable tools for estimation of the generation rate constant (or slope of the growth curve) and provide a basis for evaluating assay performance. Two models, i.e., exponential and logistic, are proposed. Both models yielded an accurate fit to the data from radioactive measurement of bacterial growth. The exponential model yielded high precision values of the generation rate constant, with an average relative standard deviation of 1.2%. Under most conditions the assay demonstrated no changes in the slopes of growth curves when the number of bacteria per inoculation was changed. However, the radiometric assay by scintillation method had a growth-inhibiting effect on a few strains of bacteria. The source of this problem was thought to be hypersensitivity to trace amounts of toluene remaining on the detector

  2. Endogenous growth and the environment

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  3. Endogenous growth and environmental policy

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  4. Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Alma Y. Galvez-Contreras

    2017-07-01

    Full Text Available Growth factors (GFs are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD and autism spectrum disorders (ASD. In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF, glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD. We also highlight the potential use of these GFs as clinical markers for diagnosis and prognosis of these neurodevelopmental disorders.

  5. Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Galvez-Contreras, Alma Y.; Campos-Ordonez, Tania; Gonzalez-Castaneda, Rocio E.; Gonzalez-Perez, Oscar

    2017-01-01

    Growth factors (GFs) are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF), glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD. We also highlight the potential use of these GFs as clinical markers for diagnosis and prognosis of these neurodevelopmental disorders. PMID:28751869

  6. Rapid population growth.

    Science.gov (United States)

    1972-01-01

    At the current rate of population growth, world population by 2000 is expected to reach 7 billion or more, with developing countries accounting for some 5.4 billion, and economically advanced nations accounting for 1.6 billion. 'Population explosion' is the result of falling mortality rates and continuing high birth rates. Many European countries, and Japan, have already completed what is termed as demographic transition, that is, birth rates have fallen to below 20 births per 1000 population, death rates to 10/1000 population, and annual growth rates are 1% or less; annual growth rates for less developed countries ranged from 2 to 3.5%. Less developed countries can be divided into 3 groups: 1) countries with both high birth and death rates; 2) countries with high birth rates and low death rates; and 3) countries with intermediate and declining birth rates and low death rates. Rapid population growth has serious economic consequences. It encourages inequities in income distribution; it limits rate of growth of gross national product by holding down level of savings and capital investments; it exerts pressure on agricultural production and land; and it creates unemployment problems. In addition, the quality of education for increasing number of chidren is adversely affected, as high proportions of children reduce the amount that can be spent for the education of each child out of the educational budget; the cost and adequacy of health and welfare services are affected in a similar way. Other serious consequences of rapid population growth are maternal death and illness, and physical and mental retardation of children of very poor families. It is very urgent that over a billion births be prevented in the next 30 years to reduce annual population growth rate from the current 2% to 1% per year.

  7. Population growth and consumption.

    Science.gov (United States)

    Chalkley, K

    1997-04-01

    The relationship between population growth, resource consumption, and environmental degradation is complex. The rise in "greenhouse gases" that will cause climatic change is clearly due to human activity, and pollutants are often concentrated in densely populated areas. However, even an area with a negative population growth, such as Russia, can experience severe environmental degradation due to poor management. Consumption patterns have the most effect on ozone depletion, while population growth threatens biodiversity of and within species through the destruction of ecosystems. Migration joins population growth and social factors, such as land inequality, as major causes of deforestation, and global demand for water is expected to increase faster than the rate of population growth. Coastal development and over-fishing threaten to deplete the oceans, while soil quality is threatened by inappropriate land use. Estimates of the earth's carrying capacity range from less than 3 billion to more than 44 billion people, indicating how difficult it is to assess this figure. Development efforts throughout the world may lead to human gains that will ultimately be negated by environmental losses. These factors have led to growing support for environmentally sustainable development.

  8. The Growth Delusion

    Directory of Open Access Journals (Sweden)

    Bob Lloyd

    2009-08-01

    Full Text Available Concern for the environment and a move towards “sustainable development” has assisted progress in a wide range of renewable energy technologies in recent years. The science suggests that a transition from fossil fuels to sustainable sources of energy in a time frame commensurate with the demise of the fossil fuels and prevention of runaway climate change is needed. However, while the movement towards sustainable energy technologies is underway, the World does not want to give up the idea of continuing economic growth. In recent times the financial collapse of October 2008 has given rise to yet another set of pleas from corporations and politicians alike to restart the growth machine. The transition to renewable energy technologies will be difficult to achieve as nowhere within existing economic and political frameworks are the limits to when growth will be curtailed being set. It is possible that the irrational insistence on endless growth as a non negotiable axiom, by a large proportion of the world’s population, may in fact be akin to the similarly irrational belief, by a similarly large proportion of the world’s population, that a supernatural being controls our existence and destiny. The irrationality of religion has recently been examined by Richard Dawkins in “The God Delusion”. Dawkins’ book is used as a starting point to investigate similarities between a belief in God and a belief in continuous growth.

  9. Genetic and environmental overlap between borderline personality disorder traits and psychopathy: evidence for promotive effects of factor 2 and protective effects of factor 1.

    Science.gov (United States)

    Hunt, E; Bornovalova, M A; Patrick, C J

    2015-05-01

    Previous studies have reported strong genetic and environmental overlap between antisocial-externalizing (factor 2; F2) features of psychopathy and borderline personality disorder (BPD) tendencies. However, this line of research has yet to examine etiological associations of affective-interpersonal (factor 1, F1) features of psychopathy with BPD tendencies. The current study investigated differential phenotypic and genetic overlap of psychopathy factors 1 and 2 with BPD tendencies in a sample of over 250 male and female community-recruited adult twin pairs. Consistent with previous research, biometric analyses revealed strong genetic and non-shared environmental correlations of F2 with BPD tendencies, suggesting that common genetic and non-shared environmental factors contribute to both phenotypes. In contrast, negative genetic and non-shared environmental correlations were observed between F1 and BPD tendencies, indicating that the genetic factors underlying F1 serve as protective factors against BPD. No gender differences emerged in the analyses. These findings provide further insight into associations of psychopathic features - F1 as well as F2 - and BPD tendencies. Implications for treatment and intervention are discussed, along with how psychopathic traits may differentially influence the manifestation of BPD tendencies.

  10. Kruppel-like factor 2 inhibit the angiogenesis of cultured human liver sinusoidal endothelial cells through the ERK1/2 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Xiao-Qing, E-mail: zeng.xiaoqing@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Li, Na, E-mail: Linala.2009@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Pan, Du-Yi, E-mail: lasikesmi@hotmail.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Miao, Qing, E-mail: sadsadvenus@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Gui-Fen, E-mail: ma.guifen@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Liu, Yi-Mei, E-mail: liuyimei1988@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Tseng, Yu-Jen, E-mail: dianatseng14@gmail.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Li, Feng, E-mail: li.feng2@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Xu, Li-Li, E-mail: xu.lili3@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: chen.shiyao@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Institute of Endoscopic Research of Zhongshan Hospital, Fudan University, Shanghai (China)

    2015-09-04

    Kruppel-like factor 2 (KLF2) is a crucial anti-angiogenic factor. However, its precise role in hepatic angiogenesis induced by liver sinusoidal endothelial cells (LSECs) remain unclear. This study was aimed to evaluate the effect of KLF2 on angiogenesis of LSECs and to explore the corresponding mechanism. Cultured human LSECs were infected with different lentiviruses to overexpress or suppress KLF2 expression. The CCK-8 assay, transwell migration assay and tube formation test, were used to investigate the roles of KLF2 in the proliferation, migration and vessel tube formation of LSECs, respectively. The expression and phosphorylation of ERK1/2 were detected by western blot. We discovered that the up-regulation of KLF2 expression dramatically inhibited proliferation, migration and tube formation in treated LSECs. Correspondingly, down-regulation of KLF2 expression significantly promoted proliferation, migration and tube formation in treated LSECs. Additionally, KLF2 inhibited the phosphorylation of ERK1/2 pathway, followed by the function of KLF2 in the angiogenesis of LSECs disrupted. In conclusion, KLF2 suppressed the angiogenesis of LSECs through inhibition of cell proliferation, migration, and vessel tube formation. These functions of KLF2 may be mediated through the ERK1/2 signaling pathway. - Highlights: • Overexpression of KLF2 inhibits the proliferation and migration of LSECs. • Overexpression of KLF2 inhibits the angiogenesis of LSECs. • ERK1/2 signaling pathway involved in the anti-angiogenic process of KLF2 on LSECs.

  11. The role of nuclear factor E2-Related factor 2 and uncoupling protein 2 in glutathione metabolism: Evidence from an in vivo gene knockout study

    International Nuclear Information System (INIS)

    Chen, Yanyan; Xu, Yuanyuan; Zheng, Hongzhi; Fu, Jingqi; Hou, Yongyong; Wang, Huihui; Zhang, Qiang; Yamamoto, Masayuki; Pi, Jingbo

    2016-01-01

    Nuclear factor E2-related factor 2 (NRF2) and uncoupling protein 2 (UCP2) are indicated to protect from oxidative stress. They also play roles in the homeostasis of glutathione. However, the detailed mechanisms are not well understood. In the present study, we found Nrf2-knockout (Nrf2-KO) mice exhibited altered glutathione homeostasis and reduced expression of various genes involved in GSH biosynthesis, regeneration, utilization and transport in the liver. Ucp2-knockout (Ucp2-KO) mice exhibited altered glutathione homeostasis in the liver, spleen and blood, as well as increased transcript of cystic fibrosis transmembrane conductance regulator in the liver, a protein capable of mediating glutathione efflux. Nrf2-Ucp2-double knockout (DKO) mice showed characteristics of both Nrf2-KO and Ucp2-KO mice. But no significant difference was observed in DKO mice when compared with Nrf2-KO or Ucp2-KO mice, except in blood glutathione levels. These data suggest that ablation of Nrf2 and Ucp2 leads to disrupted GSH balance, which could result from altered expression of genes involved in GSH metabolism. DKO may not evoke more severe oxidative stress than the single gene knockout. - Highlights: • Nrf2/Ucp2 deficiency leads to alteration of glutathione homeostasis. • Nrf2 regulates expression of genes in glutathione generation and utilization. • Ucp2 affects glutathione metabolism by regulating hepatic efflux of glutathione. • Nrf2 deficiency may not aggravate oxidative stress in Ucp2-deficient mice.

  12. The C-terminal helix of ribosomal P stalk recognizes a hydrophobic groove of elongation factor 2 in a novel fashion.

    Science.gov (United States)

    Tanzawa, Takehito; Kato, Koji; Girodat, Dylan; Ose, Toyoyuki; Kumakura, Yuki; Wieden, Hans-Joachim; Uchiumi, Toshio; Tanaka, Isao; Yao, Min

    2018-04-06

    Archaea and eukaryotes have ribosomal P stalks composed of anchor protein P0 and aP1 homodimers (archaea) or P1•P2 heterodimers (eukaryotes). These P stalks recruit translational GTPases to the GTPase-associated center in ribosomes to provide energy during translation. The C-terminus of the P stalk is known to selectively recognize GTPases. Here we investigated the interaction between the P stalk and elongation factor 2 by determining the structures of Pyrococcus horikoshii EF-2 (PhoEF-2) in the Apo-form, GDP-form, GMPPCP-form (GTP-form), and GMPPCP-form bound with 11 C-terminal residues of P1 (P1C11). Helical structured P1C11 binds to a hydrophobic groove between domain G and subdomain G' of PhoEF-2, where is completely different from that of aEF-1α in terms of both position and sequence, implying that such interaction characteristic may be requested by how GTPases perform their functions on the ribosome. Combining PhoEF-2 P1-binding assays with a structural comparison of current PhoEF-2 structures and molecular dynamics model of a P1C11-bound GDP form, the conformational changes of the P1C11-binding groove in each form suggest that in response to the translation process, the groove has three states: closed, open, and release for recruiting and releasing GTPases.

  13. The role of nuclear factor E2-Related factor 2 and uncoupling protein 2 in glutathione metabolism: Evidence from an in vivo gene knockout study

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yanyan [The First Affiliated Hospital, China Medical University, Shenyang, Liaoning (China); The Hamner Institutes for Health Sciences, Research Triangle Park, NC (United States); Xu, Yuanyuan, E-mail: yyxu@cmu.edu.cn [School of Public Health, China Medical University, Shenyang, Liaoning (China); Zheng, Hongzhi [The First Affiliated Hospital, China Medical University, Shenyang, Liaoning (China); The Hamner Institutes for Health Sciences, Research Triangle Park, NC (United States); Fu, Jingqi; Hou, Yongyong; Wang, Huihui [School of Public Health, China Medical University, Shenyang, Liaoning (China); Zhang, Qiang [Rollins School of Public Health, Emory University, Atlanta, GA (United States); Yamamoto, Masayuki [Graduate School of Medicine, Tohoku University, Sendai (Japan); Pi, Jingbo, E-mail: jbpi@cmu.edu.cn [School of Public Health, China Medical University, Shenyang, Liaoning (China); The Hamner Institutes for Health Sciences, Research Triangle Park, NC (United States)

    2016-09-09

    Nuclear factor E2-related factor 2 (NRF2) and uncoupling protein 2 (UCP2) are indicated to protect from oxidative stress. They also play roles in the homeostasis of glutathione. However, the detailed mechanisms are not well understood. In the present study, we found Nrf2-knockout (Nrf2-KO) mice exhibited altered glutathione homeostasis and reduced expression of various genes involved in GSH biosynthesis, regeneration, utilization and transport in the liver. Ucp2-knockout (Ucp2-KO) mice exhibited altered glutathione homeostasis in the liver, spleen and blood, as well as increased transcript of cystic fibrosis transmembrane conductance regulator in the liver, a protein capable of mediating glutathione efflux. Nrf2-Ucp2-double knockout (DKO) mice showed characteristics of both Nrf2-KO and Ucp2-KO mice. But no significant difference was observed in DKO mice when compared with Nrf2-KO or Ucp2-KO mice, except in blood glutathione levels. These data suggest that ablation of Nrf2 and Ucp2 leads to disrupted GSH balance, which could result from altered expression of genes involved in GSH metabolism. DKO may not evoke more severe oxidative stress than the single gene knockout. - Highlights: • Nrf2/Ucp2 deficiency leads to alteration of glutathione homeostasis. • Nrf2 regulates expression of genes in glutathione generation and utilization. • Ucp2 affects glutathione metabolism by regulating hepatic efflux of glutathione. • Nrf2 deficiency may not aggravate oxidative stress in Ucp2-deficient mice.

  14. From Limits to Growth to Limitless Growth

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2012-04-01

    Full Text Available The publication of the Club of Rome’s landmark report ‘The Limits to Growth’ in 1972 shook the intellectual foundations of social theory and challenged the very premises on which modern economy and prosperity are based. Once set in motion, it led to a revolutionary re-evaluation of human aspirations and economic activities. Among its many consequences, it has stimulated creative minds to look freshly at the underlying processes governing the wealth and welfare of nations. The article then traces their creative impact on the mind of one of the most original economic theorists of our age – Orio Giarini.[*] As ‘The Limits to Growth’ alarmed the world by the unsustainability and dire consequences of unbridled economic growth, Giarini offers a correspondingly affirmative vision of economics with unlimited potential for wealth and welfare.

  15. Experimental intrauterine growth retardation.

    Science.gov (United States)

    van Marthens, E; Harel, S; Zamenshof, S

    1975-01-01

    The effects of experimental intrauterine growth retardation on subsequent fetal development, especially with respect to brain development, were studied in a new animal model. The rabbit was chosen since it has a perinatal pattern of brain development similar to that of the human. Experimental ischemia was induced during the last trimester by ligation of spiral arterioles and the differential effects on fetal development at term (30th gestational day) are reported. Specific brain regions were examined for wet weight, total cell number (DNA) and total protein content. Highly significant decreases in all these parameters were found in both the cortex and cerebellum following experimental intrauterine growth retardation; these two organs were differentially affected. The prospects and advantages of using this animal model for the study of the postnatal "catch-up growth" are discussed.

  16. Urban growth management

    DEFF Research Database (Denmark)

    Jørgensen, Gertrud; Alexander Sick Nielsen, Thomas; Grünfelder, Julien

    2011-01-01

    , and finally urban attractivity policies. Effective regional bodies are needed to deal with urban expansion and peri-urbanisation at a relevant scale; European rural and agricultural policies makes up the main ‘policy complex’ targeting the non-urban area including its land uses; while lastly leverage of urban...... urban growth and curb urban sprawl in a wider sense. Methodology The main methodology of the paper is a desk-research based review of policy options supplemented with field study and interviews in selected cased study regions. This paper consists of two parts. The first part is based on literature...... there are contradictions in the evidence presented in the literature, we believe that it may be safely said that urban growth management policies have an influence on urban growth under certain preconditions including: sufficient time for implementation and continuity of efforts; choice of appropriate policy measures...

  17. New microbial growth factor

    Science.gov (United States)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  18. Moral Personality Growth

    Directory of Open Access Journals (Sweden)

    Jana Kalin

    1998-12-01

    Full Text Available Learning in terms of personality growth is a life-long process, just as personality growth itself is a life-long process. Kalin presents a number of psychological theories and their impact on moral development - which is an integral part of personality growth. The paper further treats the formation and changing of beliefs, and the role of education in the two processes. Great emphasis is put on cognitive theories; Kalin explains those formulated by L. Kohlberg and J. Rest. In discussing the process of shaping and changing one's views, special emphasis is put on the environment, or rather the social group an individual belongs to, and on the influence of personality traits and experience. The paper juxtaposes the influence - strengths and weaknesses - of the psychology of persuasion and education on forming and changing one's views, taken into consideration that views consist of cognitive, emotive and conative dimensions.

  19. The double Laplacian growth

    International Nuclear Information System (INIS)

    Loutsenko, I.; Yermolayeva, O.

    2008-06-01

    The dynamics of the idealized Laplacian growth (or the Hele-Shaw problem) can be approximated by the Poiselle flow which in appropriate units takes the form of the Darcy law. In this paper we account for the liquid inertia in the Hele-Shaw problem at zero surface tension limit. The Laplace dynamics for the pressure is extended here with one more for the velocity potential for which we call this growth process the Double Laplacian. The application of the conformal mappings technique leads to doubled dynamics for both the conformal map and the complex potential, which is presented in the paper for the radial and the planar growth. We apply the stability analysis and discuss the integrability for the stated problem. (author)

  20. Stochastic ontogenetic growth model

    Science.gov (United States)

    West, B. J.; West, D.

    2012-02-01

    An ontogenetic growth model (OGM) for a thermodynamically closed system is generalized to satisfy both the first and second law of thermodynamics. The hypothesized stochastic ontogenetic growth model (SOGM) is shown to entail the interspecies allometry relation by explicitly averaging the basal metabolic rate and the total body mass over the steady-state probability density for the total body mass (TBM). This is the first derivation of the interspecies metabolic allometric relation from a dynamical model and the asymptotic steady-state distribution of the TBM is fit to data and shown to be inverse power law.

  1. Time for Growth

    DEFF Research Database (Denmark)

    Boerner, Lars; Severgnini, Battista

    This paper studies the impact of the early adoption of one of the most important high-technology machines in history, the public mechanical clock, on long-run growth in Europe. We avoid endogeneity by considering the relationship between the adoption of clocks with two sets of instruments: distance...... from the first adopters and the appearance of repeated solar eclipses. The latter instrument is motivated by the predecessor technologies of mechanical clocks, astronomic instruments that measured the course of heavenly bodies. We find significant growth rates between 1500 and 1700 in the range of 30...

  2. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  3. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  4. Gaussian radial growth

    DEFF Research Database (Denmark)

    Jónsdóttir, Kristjana Ýr; Jensen, Eva B. Vedel

    The growth of planar and spatial objects is often modelled using one-dimensional size parameters, e.g. volume, area or average radius. We take a more detailed approach and model how the boundary of a growing object expands in time. We mainly consider star-shaped planar objects. The model can...... be regarded as a dynamic deformable template model. The limiting shape of the object may be circular but this is only one possibility among a range of limiting shapes. An application to tumour growth is presented. Two extensions of the model, involving time series and Lévy bases, respectively, are briefly...

  5. Round-shape gold nanoparticles: effect of particle size and concentration on Arabidopsis thaliana root growth

    Czech Academy of Sciences Publication Activity Database

    Siegel, J.; Záruba, K.; Švorčík, V.; Kroumanová, Kristýna; Burketová, Lenka; Martinec, Jan

    2018-01-01

    Roč. 13, APR 10 (2018), č. článku 95. ISSN 1556-276X R&D Projects: GA ČR GA17-10907S; GA ČR(CZ) GBP108/12/G108 Institutional support: RVO:61389030 Keywords : Arabidopsis thaliana * Concentration * Gold nanoparticles * Root growth * Size Subject RIV: JJ - Other Materials OBOR OECD: Plant sciences, botany Impact factor: 2.833, year: 2016

  6. Evaluating the robustness of three ring-width measurement methods for growth release reconstruction

    Czech Academy of Sciences Publication Activity Database

    Maes, S. L.; Vannoppen, A.; Altman, Jan; Van den Bulcke, J.; Decocq, G.; De Mil, T.; Depauw, L.; Landuyt, D.; Perring, M. P.; Van Acker, J.; Vanhellemont, M.; Verheyen, K.

    2017-01-01

    Roč. 46, DEC 2017 (2017), s. 67-76 ISSN 1125-7865 R&D Projects: GA ČR(CZ) GA17-07378S; GA ČR(CZ) GA14-12262S Institutional support: RVO:67985939 Keywords : Dendrochronology * Growth release * Ring-width measurement Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 2.259, year: 2016

  7. Fatigue cracks in Eurofer 97 steel: Part I. Nucleation and small crack growth kinetics

    Czech Academy of Sciences Publication Activity Database

    Kruml, Tomáš; Polák, Jaroslav

    2011-01-01

    Roč. 412, 1 (2011), s. 2-6 ISSN 0022-3115 R&D Projects: GA ČR GA106/09/1954; GA ČR GA101/09/0867 Institutional research plan: CEZ:AV0Z20410507 Keywords : ferritic-martensitic steel * low cycle fatigue * small crack growth * fatigue life prediction Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.052, year: 2011

  8. Intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Bernardita Donoso Bernales

    2012-07-01

    Full Text Available It is estimated that the true prevalence of intrauterine growth restriction is 3-10% of all pregnancies, making this fetal condition one of the most frequent obstetric problems, together with premature labor and premature rupture of membranes. The article stresses the importance of early diagnosis because of the associated risks.

  9. Crystal growth and doping

    International Nuclear Information System (INIS)

    Paorici, C.

    1980-01-01

    Section 1 contains a self-consistent review of the basic growth features. After a short introduction concerning the driving force acting in a crystallization process, three main topics are broadly discussed: (i) interface kinetics; (ii) transport kinetics, and (iii) growth stability conditions. On point (i), after definition of the nature of interface, using Temkin's model, the growth mechanisms predicted by Burton, Cabrera and Frank (BCF) and bidimensional nucleation theories are fully developed. On points (ii) and (iii), the differential equations of the constitutional (concentration) and thermal fields are presented and discussed in terms of relevant approximations, suitable boundary conditions and limit values expected in order to have growth stability. Section 2 reports various experimental procedures for growing bulk crystals from the melt, from solutions and from the vapour phase. The basic concepts of Section 1 are amply employed for a critical discussion of possibilities, advantages and drawbacks of the methods described. Along the same lines, in Section 3 the principal epitaxial deposition procedures are highlighted. Section 4 contains a brief account of doping and of stoichiometry-defect control procedures. There is a long, carefully chosen list of bibliographical references. (author)

  10. [Growth of the neurocranium].

    Science.gov (United States)

    Hodacová, Z; Skalská, H

    1998-01-01

    The present study demonstrates the results of evaluation of growth changes of the neurocranium in a set of 98 human skulls of immature individuals aged 6-18/20/ years from the XIII.-XVIII. century. Craniometric values were matched with the corresponding values measured on the skulls of the same age groups from the IX. century and IX.-XII. centuries.

  11. Carboxydotrophic growth of

    NARCIS (Netherlands)

    Geelhoed, J.; Henstra, A.M.; Stams, A.J.M.

    2016-01-01

    This study shows that Geobacter sulfurreducensgrows on carbon monoxide (CO) as electron donor with fumarateas electron acceptor. Geobacter sulfurreducens wastolerant to high CO levels, with up to 150 kPa in the headspacetested. During growth, hydrogen was detected in very slightamounts (~5 Pa). In

  12. Economic Growth Models Transition

    Directory of Open Access Journals (Sweden)

    Coralia Angelescu

    2006-03-01

    Full Text Available The transitional recession in countries of Eastern Europe has been much longer than expected. The legacy and recent policy mistakes have both contributed to the slow progress. As structural reforms and gradual institution building have taken hold, the post-socialist economics have started to recover, with some leading countries building momentum toward faster growth. There is a possibility that in wider context of globalization several of these emerging market economies will be able to catch up with the more advanced industrial economies in a matter of one or two generations. Over the past few years, most candidate countries have made progress in the transition to a competitive market economy, macroeconomic stabilization and structural reform. However their income levels have remained far below those in the Member States. Measured by per capita income in purchasing power standards, there has been a very limited amount of catching up over the past fourteen years. Prior, the distinctions between Solow-Swan model and endogenous growth model. The interdependence between transition and integration are stated in this study. Finally, some measures of macroeconomic policy for sustainable growth are proposed in correlation with real macroeconomic situation of the Romanian economy. Our study would be considered the real convergence for the Romanian economy and the recommendations for the adequate policies to achieve a fast real convergence and sustainable growth.

  13. Economic Growth Models Transition

    Directory of Open Access Journals (Sweden)

    Coralia Angelescu

    2006-01-01

    Full Text Available The transitional recession in countries of Eastern Europe has been much longer than expected. The legacy and recent policy mistakes have both contributed to the slow progress. As structural reforms and gradual institution building have taken hold, the post-socialist economics have started to recover, with some leading countries building momentum toward faster growth. There is a possibility that in wider context of globalization several of these emerging market economies will be able to catch up with the more advanced industrial economies in a matter of one or two generations. Over the past few years, most candidate countries have made progress in the transition to a competitive market economy, macroeconomic stabilization and structural reform. However their income levels have remained far below those in the Member States. Measured by per capita income in purchasing power standards, there has been a very limited amount of catching up over the past fourteen years. Prior, the distinctions between Solow-Swan model and endogenous growth model. The interdependence between transition and integration are stated in this study. Finally, some measures of macroeconomic policy for sustainable growth are proposed in correlation with real macroeconomic situation of the Romanian economy. Our study would be considered the real convergence for the Romanian economy and the recommendations for the adequate policies to achieve a fast real convergence and sustainable growth.

  14. Aid, Growth, and Development

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    ) ability to pay, and (iv) level of interaction with public officials. Moreover, when informal firms become formal the probability of paying bribes increases. Becoming formal is also associated with a revenue growth premium that is not driven by self-selection of well-performing firms. On average...

  15. Fibroblast growth factor 23

    African Journals Online (AJOL)

    Dr Olaleye

    Systemic phosphate homeostasis is maintained through several hormonal mechanisms which involve fibroblast growth factor 23 (FGF-23), α-klotho, vitamin D and parathyroid hormone. FGF-23 is known to be the major regulator of phosphate balance (Mirams et al., 2004). FGF-23 is a phosphaturic hormone, which is.

  16. Perspectives on population growth.

    Science.gov (United States)

    1996-09-01

    Assume that everyone has the same information on population growth. There are many different opinions on what that information means and what should be done about it. Some people worry about current rates of growth, especially in the context of growing per capita consumption, and believe that all reasonable steps should be taken to reduce rates and stabilize population size. Others believe that growing populations can be accommodated by reducing consumption in rich countries, that technological progress will supply the new resources needed, that the development needed to support a larger population can be sustained, that large population size fosters prosperity, or that birth rates are falling and current growth is just temporary. These are all valid positions worthy of at least debate. Interest groups commonly acknowledgement population growth as a significant issue, but offer no response to it. Sometimes the issue goes unrecognized because it conflicts with a more highly valued personal agenda item. Finally, some responses come from confusion and anger rather than reasoning or self-interest. The proponents of these latter arguments bring nothing constructive to the debate.

  17. Consumption growth accounting

    NARCIS (Netherlands)

    Dietzenbacher, Erik; de Groot, Olaf J.; Los, Bart

    The methodology in this paper combines an input-output structural decomposition approach with the supply-side perspective of mainstream growth accounting. In explaining the intertemporal change in consumption per worker, three sets of effects are distinguished. First, contributions due to several

  18. Global Green Growth Institute

    DEFF Research Database (Denmark)

    Müller, Anders Riel

    2017-01-01

    Har man fulgt historien om Venstres gruppeformand Lars Løkkes rejser på 1. klasse i forbindelse med formandsposten for Global Green Growth Institute (GGGI) er der sikkert nogle der undrer sig over, hvad GGGI er for en størrelse. Medierne præsenterer GGGI som en international klimaorganisation, der...

  19. Geometrical approach to tumor growth

    OpenAIRE

    Escudero, Carlos

    2006-01-01

    Tumor growth has a number of features in common with a physical process known as molecular beam epitaxy. Both growth processes are characterized by the constraint of growth development to the body border, and surface diffusion of cells/particles at the growing edge. However, tumor growth implies an approximate spherical symmetry that makes necessary a geometrical treatment of the growth equations. The basic model was introduced in a former article [C. Escudero, Phys. Rev. E 73, 020902(R) (200...

  20. Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling.

    Science.gov (United States)

    Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G; Bezprozvanny, Ilya; Huber, Kimberly M; Wu, Jiang I

    2016-01-01

    Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Serine/arginine rich splicing factor 2 expression and clinic pathological features indicating a prognostic factor in human hepatocellular carcinoma patients.

    Science.gov (United States)

    Wang, Pingan; Guo, Lingyu; Li, Kaipeng; Ning, Shanglei; Shi, Weichen; Liu, Zhaochen; Chen, Yuxin

    2018-02-14

    This research was aimed to study the expression of Serine/arginine rich splicing factor 2 (SRSF2) in tissues of hepatocellular carcinoma, and explore the relationship between the expression and the clinic pathological and prognosis of human hepatocellular carcinoma (HCC). One hundred and fifty-three pairs HCC tissues and adjacent normal tissue were collected from January 2010 to March 2013. The expression of SRSF2 gene was detected by immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction (PCR), and the relationship between the expression and the clinic pathological and prognosis of HCC being analyzed. In 153 cases of hepatocellular carcinoma, SRSF2 was highly expressed in 93 cases, low expression of 60 cases, immunohistochemistry score (6.50 ± 2.82), which was significantly higher than that in adjacent normal tissues (2.94 ± 1.23) (Phepatocellular carcinoma was positively correlated (r = 0.704, Phepatocellular carcinoma were 74.19%, 44.09%, 26.88%, 24.73% and 21.51% at 1 year, 2 years, 3 years, 4 years and 5 years respectively, which were lower than those of SRSF2 low expression group (93.33%, 71.67%, 56.67%, 51.67% and 50.00%). SRSF2 is highly expressed in hepatocellular carcinoma and its expression increases with the degree of tumor differentiation and TNM staging. It is related to lymph node metastasis and metastasis of tumor cells, and is positively related to serum alpha fetoprotein content, and affects the postoperative survival time of HCC patients.

  2. Transcriptional activation of LON Gene by a new form of mitochondrial stress: A role for the nuclear respiratory factor 2 in StAR overload response (SOR).

    Science.gov (United States)

    Bahat, Assaf; Perlberg, Shira; Melamed-Book, Naomi; Isaac, Sara; Eden, Amir; Lauria, Ines; Langer, Thomas; Orly, Joseph

    2015-06-15

    High output of steroid hormone synthesis in steroidogenic cells of the adrenal cortex and the gonads requires the expression of the steroidogenic acute regulatory protein (StAR) that facilitates cholesterol mobilization to the mitochondrial inner membrane where the CYP11A1/P450scc enzyme complex converts the sterol to the first steroid. Earlier studies have shown that StAR is active while pausing on the cytosolic face of the outer mitochondrial membrane while subsequent import of the protein into the matrix terminates the cholesterol mobilization activity. Consequently, during repeated activity cycles, high level of post-active StAR accumulates in the mitochondrial matrix. To prevent functional damage due to such protein overload effect, StAR is degraded by a sequence of three to four ATP-dependent proteases of the mitochondria protein quality control system, including LON and the m-AAA membranous proteases AFG3L2 and SPG7/paraplegin. Furthermore, StAR expression in both peri-ovulatory ovarian cells, or under ectopic expression in cell line models, results in up to 3-fold enrichment of the mitochondrial proteases and their transcripts. We named this novel form of mitochondrial stress as StAR overload response (SOR). To better understand the SOR mechanism at the transcriptional level we analyzed first the unexplored properties of the proximal promoter of the LON gene. Our findings suggest that the human nuclear respiratory factor 2 (NRF-2), also known as GA binding protein (GABP), is responsible for 88% of the proximal promoter activity, including the observed increase of transcription in the presence of StAR. Further studies are expected to reveal if common transcriptional determinants coordinate the SOR induced transcription of all the genes encoding the SOR proteases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β-Cell Damage

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    Jingqi Fu

    2015-01-01

    Full Text Available Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2 is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD and islets isolated from Nrf2-knockout mice expressed substantially reduced levels of antioxidant enzymes in response to a variety of stressors. In scramble MIN6 cells or wild-type islets, acute exposure to oxidative stressors, including hydrogen peroxide (H2O2 and S-nitroso-N-acetylpenicillamine, resulted in cell damage as determined by decrease in cell viability, reduced ATP content, morphology changes of islets, and/or alterations of apoptotic biomarkers in a concentration- and/or time-dependent manner. In contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In addition, pretreatment of MIN6 β-cells with NRF2 activators, including CDDO-Im, dimethyl fumarate (DMF, and tert-butylhydroquinone (tBHQ, protected the cells from high levels of H2O2-induced cell damage. Given that reactive oxygen species (ROS are involved in regulating glucose-stimulated insulin secretion (GSIS and persistent activation of NRF2 blunts glucose-triggered ROS signaling and GSIS, the present study highlights the distinct roles that NRF2 may play in pancreatic β-cell dysfunction that occurs in different stages of diabetes.

  4. A network of hydrophobic residues impeding helix alphaC rotation maintains latency of kinase Gcn2, which phosphorylates the alpha subunit of translation initiation factor 2.

    Science.gov (United States)

    Gárriz, Andrés; Qiu, Hongfang; Dey, Madhusudan; Seo, Eun-Joo; Dever, Thomas E; Hinnebusch, Alan G

    2009-03-01

    Kinase Gcn2 is activated by amino acid starvation and downregulates translation initiation by phosphorylating the alpha subunit of translation initiation factor 2 (eIF2alpha). The Gcn2 kinase domain (KD) is inert and must be activated by tRNA binding to the adjacent regulatory domain. Previous work indicated that Saccharomyces cerevisiae Gcn2 latency results from inflexibility of the hinge connecting the N and C lobes and a partially obstructed ATP-binding site in the KD. Here, we provide strong evidence that a network of hydrophobic interactions centered on Leu-856 also promotes latency by constraining helix alphaC rotation in the KD in a manner relieved during amino acid starvation by tRNA binding and autophosphorylation of Thr-882 in the activation loop. Thus, we show that mutationally disrupting the hydrophobic network in various ways constitutively activates eIF2alpha phosphorylation in vivo and bypasses the requirement for a key tRNA binding motif (m2) and Thr-882 in Gcn2. In particular, replacing Leu-856 with any nonhydrophobic residue activates Gcn2, while substitutions with various hydrophobic residues maintain kinase latency. We further provide strong evidence that parallel, back-to-back dimerization of the KD is a step on the Gcn2 activation pathway promoted by tRNA binding and autophosphorylation. Remarkably, mutations that disrupt the L856 hydrophobic network or enhance hinge flexibility eliminate the need for the conserved salt bridge at the parallel dimer interface, implying that KD dimerization facilitates the reorientation of alphaC and remodeling of the active site for enhanced ATP binding and catalysis. We propose that hinge remodeling, parallel dimerization, and reorientation of alphaC are mutually reinforcing conformational transitions stimulated by tRNA binding and secured by the ensuing autophosphorylation of T882 for stable kinase activation.

  5. Eukaryotic translation initiation factor 2B-beta (eIF2Bβ), a new class of plant virus resistance gene.

    Science.gov (United States)

    Shopan, Jannat; Mou, Haipeng; Zhang, Lili; Zhang, Changtong; Ma, Weiwei; Walsh, John A; Hu, Zhongyuan; Yang, Jinghua; Zhang, Mingfang

    2017-06-01

    Recessive resistances to plant viruses in the Potyvirus genus have been found to be based on mutations in the plant eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms. Here we report that natural, monogenic recessive resistance to the Potyvirus Turnip mosaic virus (TuMV) has been found in a number of mustard (Brassica juncea) accessions. Bulked segregant analysis and sequencing of resistant and susceptible plant lines indicated the resistance is controlled by a single recessive gene, recessive TuMV resistance 03 (retr03), an allele of the eukaryotic translation initiation factor 2B-beta (eIF2Bβ). Silencing of eIF2Bβ in a TuMV-susceptible mustard plant line and expression of eIF2Bβ from a TuMV-susceptible line in a TuMV-resistant mustard plant line confirmed the new resistance mechanism. A functional copy of a specific allele of eIF2Bβ is required for efficient TuMV infection. eIF2Bβ represents a new class of virus resistance gene conferring resistance to any pathogen. eIF2B acts as a guanine nucleotide exchange factor (GEF) for its GTP-binding protein partner eIF2 via interaction with eIF2·GTP at an early step in translation initiation. Further genotyping indicated that a single non-synonymous substitution (A120G) in the N-terminal region of eIF2Bβ was responsible for the TuMV resistance. A reproducible marker has been developed, facilitating marker-assisted selection for TuMV resistance in B. juncea. Our findings provide a new target for seeking natural resistance to potyviruses and new opportunities for the control of potyviruses using genome editing techniques targeted on eIF2Bβ. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  6. Dual Role for Hsc70 in the Biogenesis and Regulation of the Heme-Regulated Kinase of the α Subunit of Eukaryotic Translation Initiation Factor 2

    Science.gov (United States)

    Uma, Sheri; Thulasiraman, Vanitha; Matts, Robert L.

    1999-01-01

    The heme-regulated kinase of the α subunit of eukaryotic initiation factor 2 (HRI) is activated in rabbit reticulocyte lysate (RRL) in response to a number of environmental conditions, including heme deficiency, heat shock, and oxidative stress. Activation of HRI causes an arrest of initiation of protein synthesis. Recently, we have demonstrated that the heat shock cognate protein Hsc70 negatively modulates the activation of HRI in RRL in response to these environmental conditions. Hsc70 is also known to be a critical component of the Hsp90 chaperone machinery in RRL, which plays an obligatory role for HRI to acquire and maintain a conformation that is competent to activate. Using de novo-synthesized HRI in synchronized pulse-chase translations, we have examined the role of Hsc70 in the regulation of HRI biogenesis and activation. Like Hsp90, Hsc70 interacted with nascent HRI and HRI that was matured to a state which was competent to undergo stimulus-induced activation (mature-competent HRI). Interaction of HRI with Hsc70 was required for the transformation of HRI, as the Hsc70 antagonist clofibric acid inhibited the folding of HRI into a mature-competent conformation. Unlike Hsp90, Hsc70 also interacted with transformed HRI. Clofibric acid disrupted the interaction of Hsc70 with transformed HRI that had been matured and transformed in the absence of the drug. Disruption of Hsc70 interaction with transformed HRI in heme-deficient RRL resulted in its hyperactivation. Furthermore, activation of HRI in response to heat shock or denatured proteins also resulted in a similar blockage of Hsc70 interaction with transformed HRI. These results indicate that Hsc70 is required for the folding and transformation of HRI into an active kinase but is subsequently required to negatively attenuate the activation of transformed HRI. PMID:10454533

  7. Expression of angiopoietin-1 in hypoxic pericytes: Regulation by hypoxia-inducible factor-2α and participation in endothelial cell migration and tube formation.

    Science.gov (United States)

    Park, Yoon Shin; Kim, Gyungah; Jin, Yoon Mi; Lee, Jee Young; Shin, Jong Wook; Jo, Inho

    2016-01-08

    We previously reported that hypoxia increases angiopoietin-1 (Ang1), but not Ang2, mRNA expression in bovine retinal pericytes (BRP). However, the mechanism underlying Ang1 expression is unknown. Here, we report that Ang1 protein expression increased in hypoxic BRP in a dose- and time-dependent manner. This increase was accompanied by an increase in hypoxia-inducible factor-2α (HIF2α) expression. Transfection with an antisense oligonucleotide for HIF2α partially inhibited the hypoxia-induced increase in Ang1 expression. HIF2α overexpression further potentiated hypoxia-stimulated Ang1 expression, suggesting that HIF2α plays an important role in Ang1 regulation in BRP. When fused the Ang1 promoter (-3040 to +199) with the luciferase reporter gene, we found that hypoxia significantly increased promoter activity by 4.02 ± 1.68 fold. However, progressive 5'-deletions from -3040 to -1799, which deleted two putative hypoxia response elements (HRE), abolished the hypoxia-induced increase in promoter activity. An electrophoretic mobility shift assay revealed that HIF2α was predominantly bound to a HRE site, located specifically at nucleotides -2715 to -2712. Finally, treatment with conditioned medium obtained from hypoxic pericytes stimulated endothelial cell migration and tube formation, which was completely blocked by co-treatment with anti-Ang1 antibody. This study is the first to demonstrate that hypoxia upregulates Ang1 expression via HIF2α-mediated transcriptional activation in pericytes, which plays a key role in angiogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Reciprocal regulation by hypoxia-inducible factor-2α and the NAMPT-NAD(+)-SIRT axis in articular chondrocytes is involved in osteoarthritis.

    Science.gov (United States)

    Oh, H; Kwak, J-S; Yang, S; Gong, M-K; Kim, J-H; Rhee, J; Kim, S K; Kim, H-E; Ryu, J-H; Chun, J-S

    2015-12-01

    Hypoxia-inducible factor-2α (HIF-2α) transcriptionally upregulates Nampt in articular chondrocytes. NAMPT, which exhibits nicotinamide phosphoribosyltransferase activity, in turn causes osteoarthritis (OA) in mice by stimulating the expression of matrix-degrading enzymes. Here, we sought to elucidate whether HIF-2α activates the NAMPT-NAD(+)-SIRT axis in chondrocytes and thereby contributes to the pathogenesis of OA. Assays of NAD levels, SIRT activity, reporter gene activity, mRNA, and protein levels were conducted in primary cultured mouse articular chondrocytes. Experimental OA in mice was induced by intra-articular (IA) injection of adenovirus expressing HIF-2α (Ad-Epas1) or NAMPT (Ad-Nampt). The functions of SIRT in OA were examined by IA co-injection of SIRT inhibitors or adenovirus expressing individual SIRT isoforms or shRNA targeting specific SIRT isoforms. HIF-2α activated the NAMPT-NAD(+)-SIRT axis in chondrocytes by upregulating NAMPT, which stimulated NAD(+) synthesis and thereby activated SIRT family members. The activated NAMPT-SIRT pathway, in turn, promoted HIF-2α protein stability by negatively regulating its hydroxylation and 26S proteasome-mediated degradation, resulting in increased HIF-2α transcriptional activity. Among SIRT family members (SIRT1-7), SIRT2 and SIRT4 were positively associated with HIF-2α stability and transcriptional activity in chondrocytes. This reciprocal regulation was required for the expression of catabolic matrix metalloproteinases (MMP3, MMP12, and MMP13) and OA cartilage destruction caused by IA injection of Ad-Epas1 Ad-Nampt. The reciprocal regulation of HIF-2α and the NAMPT-NAD(+)-SIRT axis in articular chondrocytes is involved in OA cartilage destruction caused by HIF-2α or NAMPT. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. PfeIK1, a eukaryotic initiation factor 2α kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation

    Directory of Open Access Journals (Sweden)

    Ranford-Cartwright Lisa

    2009-05-01

    Full Text Available Abstract Background Post-transcriptional control of gene expression is suspected to play an important role in malaria parasites. In yeast and metazoans, part of the stress response is mediated through phosphorylation of eukaryotic translation initiation factor 2α (eIF2α, which results in the selective translation of mRNAs encoding stress-response proteins. Methods The impact of starvation on the phosphorylation state of PfeIF2α was examined. Bioinformatic methods were used to identify plasmodial eIF2α kinases. The activity of one of these, PfeIK1, was investigated using recombinant protein with non-physiological substrates and recombinant PfeIF2α. Reverse genetic techniques were used to disrupt the pfeik1 gene. Results The data demonstrate that the Plasmodium falciparum eIF2α orthologue is phosphorylated in response to starvation, and provide bioinformatic evidence for the presence of three eIF2α kinases in P. falciparum, only one of which (PfPK4 had been described previously. Evidence is provided that one of the novel eIF2α kinases, PfeIK1, is able to phosphorylate the P. falciparum eIF2α orthologue in vitro. PfeIK1 is not required for asexual or sexual development of the parasite, as shown by the ability of pfeik1- parasites to develop into sporozoites. However, eIF2α phosphorylation in response to starvation is abolished in pfeik1- asexual parasites Conclusion This study strongly suggests that a mechanism for versatile regulation of translation by several kinases with a similar catalytic domain but distinct regulatory domains, is conserved in P. falciparum.

  10. Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice.

    Science.gov (United States)

    Abdo, Shaaban; Shi, Yixuan; Otoukesh, Abouzar; Ghosh, Anindya; Lo, Chao-Sheng; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao Ling; Chan, John S D

    2014-10-01

    This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2-related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. DJ-1 Modulates Nuclear Erythroid 2–Related Factor-2–Mediated Protection in Human Primary Alveolar Type II Cells in Smokers

    Science.gov (United States)

    Bahmed, Karim; Messier, Elise M.; Zhou, Wenbo; Tuder, Rubin M.; Freed, Curt R.; Chu, Hong Wei; Kelsen, Steven G.; Bowler, Russell P.; Mason, Robert J.

    2016-01-01

    Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2–related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases. PMID:27093578

  12. Reciprocal Regulation of Hypoxia-Inducible Factor 2α and GLI1 Expression Associated With the Radioresistance of Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jiancheng [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wu, Kaijie [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Gao, Dexuan [Department of Urology, Shandong Provincial Hospital affiliated with Shandong University, Ji' nan (China); Zhu, Guodong; Wu, Dapeng; Wang, Xinyang; Chen, Yule; Du, Yuefeng; Song, Wenbin; Ma, Zhenkun [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Authement, Craig; Saha, Debabrata [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong, E-mail: jt.hsieh@utsouthwestern.edu [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); He, Dalin, E-mail: dalinhe@yahoo.com [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China)

    2014-11-15

    Purpose: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. Methods and Materials: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. Results: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. Conclusions: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment.

  13. Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-κB and activation of nuclear factor erythroid 2-related factor 2.

    Science.gov (United States)

    Kim, Jae Kwang; Lee, Ji Eun; Jung, Eun Hye; Jung, Ji Yun; Jung, Dae Hwa; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan

    2018-01-01

    Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H 2 O 2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Anti-oxidative stress regulator NF-E2-related factor 2 mediates the adaptive induction of antioxidant and detoxifying enzymes by lipid peroxidation metabolite 4-hydroxynonenal

    Directory of Open Access Journals (Sweden)

    Huang Ying

    2012-11-01

    Full Text Available Abstract Background NF-E2-related factor 2 (NRF2 regulates a battery of antioxidative and phase II drug metabolizing/detoxifying genes through binding to the antioxidant response elements (ARE. NRF2-ARE signaling plays a central role in protecting cells from a wide spectrum of reactive toxic species including reactive oxygen/nitrogen species (RONS. 4-hydroxylnonenal (4-HNE is a major end product from lipid peroxidation of omega-6 polyunsaturated fatty acids (PUFA induced by oxidative stress, and it is highly reactive to nucleophilic sites in DNA and proteins, causing cytotoxicity and genotoxicity. In this study, we examined the role of NRF2 in regulating the 4-HNE induced gene expression of antioxidant and detoxifying enzymes. Results When HeLa cells were treated with 4-HNE, NRF2 rapidly transloated into the nucleus, as determined by the distribution of NRF2 tagged with the enhanced green fluorescent protein (EGFP and increased NRF2 protein in the nuclear fraction. Transcriptional activity of ARE-luciferase was significantly induced by 0.01-10 μM of 4-HNE in a dose-dependent manner, and the induction could be blocked by pretreatment with glutathione (GSH. 4-HNE induced transcriptional expression of glutathione S-transferase (GST A4, aldoketone reductase (AKR 1C1 and heme oxygenase-1 (HO-1, and the induction was attenuated by knocking down NRF2 using small interfering RNA. Conclusions NRF2 is critical in mediating 4-HNE induced expression of antioxidant and detoxifying genes. This may account for one of the major cellular defense mechanisms against reactive metabolites of lipids peroxidation induced by oxidative stress and protect cells from cytotoxicity.

  15. Hydrogen sulfide upregulated mRNA expressions of sodium bicarbonate cotransporter1, trefoil factor1 and trefoil factor2 in gastric mucosa in rats.

    Science.gov (United States)

    Cheraghi, Parisa; Mard, Seyyed Ali; Nagi, Tahereh

    2016-01-01

    Hydrogen sulfide (H 2 S) has been shown to protect the gastric mucosa through several protective mechanisms but till now its effect on mRNA expression of sodium bicarbonate cotransporter 1 (NBC1), trefoil factor1 (TFF1) and trefoil factor2 (TFF2) was not investigated. This study was aimed to evaluate the effect of H 2 S on mRNA expression of NBC1, TFF1 and TFF2 in rat gastric mucosa in response to gastric distention. Thirty two rats were randomly assigned into four equal groups. They were control (C), distention (D), propargylglycine (PAG)-, and NaHS-treated groups. To evaluate the effect of exogenous and endogenous H 2 S on gene expression of NBC1, TFF1 and TFF2, two groups of rats were received H 2 S donor, intra-peritoneal NaHS (80 µg Kg -1 ), and PAG (50 mg kg -1 ), accompanied to stimulate the gastric acid secretion, respectively. Under general anesthesia and laparotomy, a catheter was inserted into the stomach through duodenum for instillation of isotonic saline for gastric distention. Ninety min after beginning the experiment, animals were sacrificed and the gastric mucosa was collected to determine total acid content of gastric effluents and to quantify the mRNA expression of studied genes by quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that A) gastric distention increased the level of mRNA expressions of NBC1, TFF1 and TFF2; B) these levels in NaHS-treated rats were significantly higher than those in Distention group; and C) PAG decreased the expression levels of NBC1 and TFF1. The Findings showed H 2 S upregulated gene expression of NBC1, TFF1 and TFF2 in gastric mucosa.

  16. Epidermal growth factor and growth in vivo

    International Nuclear Information System (INIS)

    Rhodes, J.A.

    1986-01-01

    Epidermal growth factor (EGF) causes a dose-dependent thickening of the epidermis in suckling mice. The cellular mechanisms underlying this thickening were analyzed by measuring the effect of EGF on the cell-cycle. Neonatal mice were given daily injections of either 2ug EGF/g body weight/day or an equivalent volume of saline, and on the seventh day received a single injection of 3 H-thymidine. At various times the mice were perfused with fixative; 1um sections of skin were stained with a modification of Harris' hematoxylin and were autoradiographed. The sections were analyzed using three methods based on the dependence on time after injection of 3 H-thymidine of: frequency of labelled mitoses, labelling index, and reciprocal grains/nucleus. It was found that EGF caused a two-fold increase in the cell production rate. The effect of exogenous EGF on the morphology of gastric mucosa and incisors of suckling mice was also studied. The gastric mucosa appeared thicker in EGF-treated animals, but the effect was not statistically significant. In contrast to its effect on epidermis and gastric mucosa, EGF caused a significant, dose-dependent decrease in the size of the incisors. Because the mouse submandibular salivary gland is the major source of EGF the effect of sialoadenectomy on female reproductive functions was examined. Ablation of the submandibular gland had no effect on: length of estrus cycle, ability of the female to produce litters, length of the gestation period, litter size, and weight of the litter at birth. There was also no effect on survival of the offspring or on age at which the eyelids separated

  17. Unsustainable growth, unsustainable capitalism

    DEFF Research Database (Denmark)

    Næss, Petter

    2006-01-01

    problems, but serve to further highlight the difficulties of changing capitalism towards sustainability. In a profit-oriented economy, capital accumulation is a prime driving force, and non-growth for the economy at large tends to result in serious economic and social crises. On the other hand, a de...... according to which the powers and mechanisms of the natural world are considered totally controllable by humans as if they were mere epiphenomena of the human world. On the other hand, the assumptions of certain ecological economists about the possibility of steady-state capitalism disregard the relation...... between capital and surplus value, which constitutes a strong mechanism driving the capitalist economy toward limitless growth....

  18. Growth and Poverty

    DEFF Research Database (Denmark)

    Arndt, Channing; Leyaro, Vincent; Mahrt, Kristi

    2017-01-01

    This chapter considers the evolution of welfare of the Tanzanian population using a multi-dimensional approach. It also employs a detailed economy-wide model of the Tanzanian economy to explore growth and monetary poverty reduction scenarios from 2007 to 2015. This approach permits assessment...... of the coherence of observed trends in macroeconomic variables and projects consumption poverty outcomes to 2015. In the multi-dimensional approach, we find that real gains have been achieved. On monetary poverty, our model broadly reproduces key macroeconomic features of the past eight years. We find...... that published consumption poverty reductions for 2007 to 2011/12 from the most recent assessment fall within a reasonable to optimistic range. And, the simulations generate broader based growth across the income distribution compared with the recent assessment. Looking forward, the simulations from 2012 to 2105...

  19. Old-growth Policy

    Directory of Open Access Journals (Sweden)

    Diane Vosick

    2007-12-01

    Full Text Available Most federal legislation and policies (e.g., the Wilderness Act, Endangered Species Act, National Forest Management Act fail to speak directly to the need for old-growth protection, recruitment, and restoration on federal lands. Various policy and attitudinal barriers must be changed to move beyond the current situation. For example, in order to achieve the goal of healthy old growth in frequent-fire forests, the public must be educated regarding the evolutionary nature of these ecosystems and persuaded that collaborative action rather than preservation and litigation is the best course for the future of these forests. Land managers and policy makers must be encouraged to look beyond the single-species management paradigm toward managing natural processes, such as fire, so that ecosystems fall within the natural range of variability. They must also see that, given their recent evidence of catastrophic fires, management must take place outside the wildland-urban interface in order to protect old-growth forest attributes and human infrastructure. This means that, in some wilderness areas, management may be required. Land managers, researchers, and policy makers will also have to agree on a definition of old growth in frequent-fire landscapes; simply adopting a definition from the mesic Pacific Northwest will not work. Moreover, the culture within the federal agencies needs revamping to allow for more innovation, especially in terms of tree thinning and wildland fire use. Funding for comprehensive restoration treatments needs to be increased, and monitoring of the Healthy Forest Initiative and Healthy Forest Restoration Act must be undertaken.

  20. Analyzing growth trajectories

    Czech Academy of Sciences Publication Activity Database

    McKeague, I. W.; López-Pintado, S.; Hallin, M.; Šiman, Miroslav

    2011-01-01

    Roč. 2, č. 6 (2011), s. 322-329 ISSN 2040-1744 R&D Projects: GA MŠk(CZ) 1M06047 Institutional research plan: CEZ:AV0Z10750506 Keywords : data depth contours * growth curves * nonparametric Bayes Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.556, year: 2011 http://library.utia.cas.cz/separaty/2011/SI/siman-0376411.pdf

  1. Globalization, Growth and Poverty

    International Development Research Centre (IDRC) Digital Library (Canada)

    One-pagers are a publication of IDRC's “Globalization, Growth and Poverty” Program Initiative, ... was among the largest in the world, at 90 percent of the entire value of ... the workforce—including young adults, women, and the elderly who are ... UN ECLAC, 2010. 0. 1. 2. 3. 4. 5. 0. 10. 20. 30. 40. 50. 60. 70. 80. 90+. C o n.

  2. Valuation relationships under growth

    OpenAIRE

    Benavides Franco, Julián

    2003-01-01

    One of the most important topics on valuation is the appropriate relationships between cash flows and rate of returns. I review those relationships under the premise, by Myers (1974), of the cost of debt as the right discount for the tax shield. Different hypotheses have been advanced for the tax shield risk, each one producing different valuation results, especially when growth is present. The consequences of some common mistakes on valuation are explored. One difference between the results ...

  3. DETERMINANTS OF ECONOMIC GROWTH

    OpenAIRE

    Bartosz Totleben

    2013-01-01

    The article is examines the impact of macroeconomic indicators, in particular: human capital, government spending, innovation, political and social stability, on economic growth. In total 12 different indicators describing the economical, political and social conditions are taken into account. The study considers 102 countries between years 1960 and 2012 and two methods of estimation are performed: generalized method of moments (GMM) and fixed effects (FE). The results show the positive impac...

  4. Geography, Depreciation, and Growth

    OpenAIRE

    Solomon M. Hsiang; Amir S. Jina

    2015-01-01

    It has been proposed that geography influences economic growth for many reasons. Previous analyses of comparative development seem to have sidestepped the question of location-dependent depreciation. However the construction of new measures of tropical cyclone exposure enables us to consider the potential impact of this single source of capital depreciation. Using an estimate of asset destruction due to tropical cyclones, we identify the "sandcastle depreciation" rate, and find support for lo...

  5. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    International Nuclear Information System (INIS)

    Xu, Ling; Hausmann, Martin; Dietmaier, Wolfgang; Kellermeier, Silvia; Pesch, Theresa; Stieber-Gunckel, Manuela; Lippert, Elisabeth; Klebl, Frank; Rogler, Gerhard

    2010-01-01

    Cholangiocarcinoma (CC) is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Expression of EGFR (epithelial growth factor receptor), HGFR (hepatocyte growth factor receptor) IGF1R (insulin-like growth factor 1 receptor), IGF2R (insulin-like growth factor 2 receptor) and VEGFR1-3 (vascular endothelial growth factor receptor 1-3) were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1). The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml), with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D). HuH28, OZ and TFK-1 lacked KRAS mutation. CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab

  6. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Kellermeier Silvia

    2010-06-01

    Full Text Available Abstract Background Cholangiocarcinoma (CC is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Methods Expression of EGFR (epithelial growth factor receptor, HGFR (hepatocyte growth factor receptor IGF1R (insulin-like growth factor 1 receptor, IGF2R (insulin-like growth factor 2 receptor and VEGFR1-3 (vascular endothelial growth factor receptor 1-3 were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1. The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. Results EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml, with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D. HuH28, OZ and TFK-1 lacked KRAS mutation. Conclusion CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab.

  7. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Raymond; Matthews, Jason, E-mail: jason.matthews@utoronto.ca

    2013-07-15

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  8. Nuclear factor E2-related factor 2’s activation in transgenic mice fed with dosage of saturated or unsaturated fatty acids using in vivo bioluminescent imaging

    Directory of Open Access Journals (Sweden)

    Elena Mariani

    2017-05-01

    Full Text Available To counteract oxidative stress cells developed several mechanisms, including the transcription factor Nuclear Factor E2-related factor 2 (Nrf2. The aim of the study was to evaluate the activation of Nrf2 in transgenic mice fed saturated or polyunsaturated fatty acids and the anti-inflammatory effect of estrogens on organism. Forty-eight ARE CRE OMO reporter mice were divided into 3 groups, consisting of 16 animals, based on presence/absence of estrogens (ovariectomized or sham female, OVX - SH; male, MA. Each group was further split in 4 subgroups of 4 animals each and fed different diets (7.5% lard, 7.5% tuna oil, 20.0 % lard and 20.0% tuna oil. Two times a week animals were anaesthetized and injected i.p. with 100µL luciferin 15 min before the imaging session. Using the Living Image Software, photon emission was mapped for selected body areas. On day 70, animals were sacrificed after a challenge with Sodium Arsenite. Specific organs were dissected and immediately subjected to ex vivo imaging session. MIXED and GLM procedures of SAS software were used for statistical analysis. Dietary treatments did not affect body weight and feed intake as well as Nrf2 expression in both pre- and post-challenge phases, with the exception of the abdominal region (P=0.031 pre-challenge; in this area, during the pre-challenge phase, OVX showed lower Nrf2 activation (P<0.001. Ex vivo results outlined a significant effect of the challenge on all the considered organs (P<0.001, while OVX subjects had higher Nrf2 expression on urinary bladder and kidney (P<0.05 and high fat diet increased Nrf2 in urinary bladder (P<0.05. The present trial shows how saturated or polyunsaturated fatty acids supplementation in the diet do not exert significant effects on oxidative stress in mice, but confirms the protective role of estrogens under physiological condition.

  9. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Lo, Raymond; Matthews, Jason

    2013-01-01

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  10. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage

    International Nuclear Information System (INIS)

    Yang, Bei; Fu, Jingqi; Zheng, Hongzhi; Xue, Peng; Yarborough, Kathy; Woods, Courtney G.; Hou, Yongyong; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2012-01-01

    Chronic human exposure to inorganic arsenic (iAs), a potent environmental oxidative stressor, is associated with increased prevalence of type 2 diabetes, where impairment of pancreatic β-cell function is a key pathogenic factor. Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress. However, persistent activation of Nrf2 in response to chronic oxidative stress, including inorganic arsenite (iAs 3+ ) exposure, blunts glucose-triggered reactive oxygen species (ROS) signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current study, we found that MIN6 pancreatic β-cells with stable knockdown of Nrf2 (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout (Nrf2−/−) mice exhibited reduced expression of several antioxidant and detoxification enzymes in response to acute iAs 3+ exposure. As a result, Nrf2-KD MIN6 cells and Nrf2−/− islets were more susceptible to iAs 3+ and monomethylarsonous acid (MMA 3+ )-induced cell damage, as measured by decreased cell viability, augmented apoptosis and morphological change. Pretreatment of MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from iAs 3+ -induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant N‐acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of iAs 3+ . The present study demonstrates that Nrf2-mediated antioxidant response is critical in the pancreatic β-cell defense mechanism against acute cytotoxicity by arsenic. The findings here, combined with our previous results on the inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2 plays paradoxical roles in pancreatic β-cell dysfunction induced by environmental arsenic exposure. -- Highlights: ► Lack of Nrf2 reduced expression of antioxidant genes induced by iAs 3+ in β-cells. ► Deficiency of Nrf2 in β-cells sensitized to iAs 3+ and MMA 3

  11. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bei [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Department of Histology and Embryology, College of Basic Medical Sciences, China Medical University, Shenyang 110001 (China); Fu, Jingqi; Zheng, Hongzhi; Xue, Peng; Yarborough, Kathy; Woods, Courtney G.; Hou, Yongyong; Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2012-11-01

    Chronic human exposure to inorganic arsenic (iAs), a potent environmental oxidative stressor, is associated with increased prevalence of type 2 diabetes, where impairment of pancreatic β-cell function is a key pathogenic factor. Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress. However, persistent activation of Nrf2 in response to chronic oxidative stress, including inorganic arsenite (iAs{sup 3+}) exposure, blunts glucose-triggered reactive oxygen species (ROS) signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current study, we found that MIN6 pancreatic β-cells with stable knockdown of Nrf2 (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout (Nrf2−/−) mice exhibited reduced expression of several antioxidant and detoxification enzymes in response to acute iAs{sup 3+} exposure. As a result, Nrf2-KD MIN6 cells and Nrf2−/− islets were more susceptible to iAs{sup 3+} and monomethylarsonous acid (MMA{sup 3+})-induced cell damage, as measured by decreased cell viability, augmented apoptosis and morphological change. Pretreatment of MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from iAs{sup 3+}-induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant N‐acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of iAs{sup 3+}. The present study demonstrates that Nrf2-mediated antioxidant response is critical in the pancreatic β-cell defense mechanism against acute cytotoxicity by arsenic. The findings here, combined with our previous results on the inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2 plays paradoxical roles in pancreatic β-cell dysfunction induced by environmental arsenic exposure. -- Highlights: ► Lack of Nrf2 reduced expression of antioxidant genes induced by iAs{sup 3+} in β-cells. ► Deficiency of Nrf2 in

  12. Can Growth Be Green?

    Science.gov (United States)

    Gough, Ian

    2015-01-01

    This short article, based on a presentation at the London School of Economics, criticizes the common opinion that "green growth" offers a relatively painless - some even say pain-free - transition path for capitalist economies. After a brief summary of the daunting arithmetic entailed in combining fast decarbonization with continuing growth, the article advances 3 propositions. First, market-based carbon mitigation programs, such as carbon trading, cannot be sufficient and must be coupled with other policy pillars that foster transformative investment and widespread regulation. Second, a political economy of climate policy needs to draw on the lessons of comparative social policy research, which emphasizes the role of international pressures, interests, institutions, and ideas. Taking these into account gives a more realistic perspective on climate policy making in today's neoliberal world. Third, more radical policies on both consumption and production are called for, to ensure that carbon mitigation is not pursued at the expense of equity and social welfare. These include policies to restrain high-carbon luxury consumption and a transition toward shorter paid working time. The conclusion is that a realistic program of green growth will be immensely difficult and entail radical political change. © SAGE Publications 2015.

  13. Facilitating post traumatic growth

    Directory of Open Access Journals (Sweden)

    Cox Helen

    2004-07-01

    Full Text Available Abstract Background Whilst negative responses to traumatic injury have been well documented in the literature, there is a small but growing body of work that identifies posttraumatic growth as a salient feature of this experience. We contribute to this discourse by reporting on the experiences of 13 individuals who were traumatically injured, had undergone extensive rehabilitation and were discharged from formal care. All participants were injured through involvement in a motor vehicle accident, with the exception of one, who was injured through falling off the roof of a house. Methods In this qualitative study, we used an audio-taped in-depth interview with each participant as the means of data collection. Interviews were transcribed verbatim and analysed thematically to determine the participants' unique perspectives on the experience of recovery from traumatic injury. In reporting the findings, all participants' were given a pseudonym to assure their anonymity. Results Most participants indicated that their involvement in a traumatic occurrence was a springboard for growth that enabled them to develop new perspectives on life and living. Conclusion There are a number of contributions that health providers may make to the recovery of individuals who have been traumatically injured to assist them to develop new views of vulnerability and strength, make changes in relationships, and facilitate philosophical, physical and spiritual growth.

  14. Crystal Growth Technology

    Science.gov (United States)

    Scheel, Hans J.; Fukuda, Tsuguo

    2004-06-01

    This volume deals with the technologies of crystal fabrication, of crystal machining, and of epilayer production and is the first book on industrial and scientific aspects of crystal and layer production. The major industrial crystals are treated: Si, GaAs, GaP, InP, CdTe, sapphire, oxide and halide scintillator crystals, crystals for optical, piezoelectric and microwave applications and more. Contains 29 contributions from leading crystal technologists covering the following topics: General aspects of crystal growth technology Silicon Compound semiconductors Oxides and halides Crystal machining Epitaxy and layer deposition Scientific and technological problems of production and machining of industrial crystals are discussed by top experts, most of them from the major growth industries and crystal growth centers. In addition, it will be useful for the users of crystals, for teachers and graduate students in materials sciences, in electronic and other functional materials, chemical and metallurgical engineering, micro-and optoelectronics including nanotechnology, mechanical engineering and precision-machining, microtechnology, and in solid-state sciences.

  15. [Hormones and hair growth].

    Science.gov (United States)

    Trüeb, R M

    2010-06-01

    With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

  16. Multiple growth regimes: Insights from unified growth theory

    OpenAIRE

    Galor, Oded

    2007-01-01

    Unified Growth Theory uncovers the forces that contributed to the existence of multiple growth regimes and the emergence of convergence clubs. It suggests that differential timing of take-offs from stagnation to growth segmented economies into three fundamental regimes: slow growing economies in a Malthusian regime, fast growing countries in a sustained growth regime, and economies in the transition between these regimes. In contrast to existing research that links regime switching thresholds...

  17. Gambling on growth.

    Science.gov (United States)

    Feeney, A

    1990-01-01

    When the assumption is made that economic growth must be increased by 10% to accommodate population increases and to reduce poverty, the question is raised as to whether or not sustainable development is possible. The human population increased 3 times since 1900, and global economic activity has increased 7 times faster than population. Use of fossil fuels has increased by 30 times, and industrial production has increased by 50 times. The by-products of population growth and economic activity are loss of tropical rainforests; species extinction; desertification in Africa, India, and the US; toxic and radioactive pollution; and greenhouse warming and ozone depletion. The atmosphere's stability and human habitation is threatened. Sustainable development, as defined by the World Commission on Environment and Development (WCED) in "Our Common Future," is meeting present needs but not at the expense of future needs. Economic growth must proceed at different rates in different countries to close the gap between the rich and poor. Economic expansion has been criticized by the president of Negative Population Growth and the Environmental Defense Fund's coordinator of reform for the World Bank's environmental policies and Third World countries. US government response during the Reagan administration has been indifference, while support has come from the World Resources Institute, the Worldwatch Institute, the US National Wildlife Federation, and the Population Reference Bureau. Recent support has come from signers of the "G-7 Summit" and from IBM and the Dow Chemical Company. A few shared tenets are 1) that economic development is not sustainable, 2) environmental reforms are necessary to make development sustainable, 3) a trade-off is needed to increase Third World energy use, and 4) population must be stabilized. Many proposals have been offered including reducing population to 2 billion, or 40% of the current level. Reducing poverty globally is an environmentally sound

  18. Growth arrest despite growth hormone replacement, post-craniopharyngioma surgery.

    Science.gov (United States)

    DeVile, C J; Hayward, R D; Neville, B G; Grant, D B; Stanhope, R

    1995-01-01

    Children with growth failure, whether secondary to an endocrinopathy such as growth hormone deficiency or secondary to neurological handicap with poor nutrient intake, grow at a subnormal rate but it is most unusual for a child to have complete growth arrest. PMID:7745571

  19. Growth throughout childhood of children born growth restricted

    NARCIS (Netherlands)

    Beukers, Fenny; Rotteveel, Joost; van Weissenbruch, Mirjam M.; Ganzevoort, Wessel; van Goudoever, Johannes B.; van Wassenaer-Leemhuis, Aleid G.

    2017-01-01

    Many studies that examine growth in growth-restricted children at birth do not discriminate between fetal growth restriction (FGR) and small for gestational age (SGA). These terms however are not synonymous. In SGA, stunting and increased weight gain have been reported. We do not know if this holds

  20. Entrepreneurial Diversity and Economic Growth

    NARCIS (Netherlands)

    I. Verheul (Ingrid); A.J. van Stel (André)

    2007-01-01

    textabstractMost studies investigating the relationship between entrepreneurship and economic growth treat entrepreneurs as a homogeneous group. This study investigates the impact of entrepreneurial diversity on national economic growth. Using data for 36 countries participating in the Global

  1. Market Acceptance of Smart Growth

    Science.gov (United States)

    This report finds that smart growth developments enjoy market acceptance because of stability in prices over time. Housing resales in smart growth developments often have greater appreciation than their conventional suburban counterparts.

  2. Your Baby's Growth: 12 Months

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Your Baby's Growth: 12 Months KidsHealth / For Parents / Your Baby's ... doubled his or her birth weight. Is My Baby Growing Normally? Babies' growth begins to slow as ...

  3. Development of real-time reverse transcription polymerase chain reaction assays to quantify insulin-like growth factor receptor and insulin receptor expression in equine tissue

    Directory of Open Access Journals (Sweden)

    Stephen B. Hughes

    2013-08-01

    Full Text Available The insulin-like growth factor system (insulin-like growth factor 1, insulin-like growth factor 2, insulin-like growth factor 1 receptor, insulin-like growth factor 2 receptor and six insulin-like growth factor-binding proteins and insulin are essential to muscle metabolism and most aspects of male and female reproduction. Insulin-like growth factor and insulin play important roles in the regulation of cell growth, differentiation and the maintenance of cell differentiation in mammals. In order to better understand the local factors that regulate equine physiology, such as muscle metabolism and reproduction (e.g., germ cell development and fertilisation, real-time reverse transcription polymerase chain reaction assays for quantification of equine insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were developed. The assays were sensitive: 192 copies/µLand 891 copies/µL for insulin-like growth factor 1 receptor, messenger ribonucleic acid and insulin receptor respectively (95%limit of detection, and efficient: 1.01 for the insulin-like growth factor 1 receptor assay and 0.95 for the insulin receptor assay. The assays had a broad linear range of detection (seven logs for insulin-like growth factor 1 receptor and six logs for insulin receptor. This allowed for analysis of very small amounts of messenger ribonucleic acid. Low concentrations of both insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were detected in endometrium, lung and spleen samples, whilst high concentrations were detected in heart, muscle and kidney samples, this was most likely due to the high level of glucose metabolism and glucose utilisation by these tissues. The assays developed for insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid expression have been shown to work on equine tissue and will contribute to the understanding of insulin and insulin-like growth factor 1

  4. Factors affecting growth and viability of natural diatom populations in the meso-eutrophic Římov Reservoir (Czech Republic)

    Czech Academy of Sciences Publication Activity Database

    Znachor, Petr; Rychtecký, Pavel; Nedoma, Jiří; Visocká, Veronika

    2015-01-01

    Roč. 762, č. 1 (2015), s. 253-265 ISSN 0018-8158 R&D Projects: GA ČR(CZ) GAP504/11/2177; GA ČR(CZ) GAP504/11/2182 Institutional support: RVO:60077344 Keywords : diatom * growth rate * viability * PDMPO * SYTOX green * reservoir Subject RIV: DA - Hydrology ; Limnology Impact factor: 2.051, year: 2015

  5. Gene expression analysis of pig cumulus-oocyte complexes stimulated in vitro with follicle stimulating hormone or epidermal growth factor-like peptides

    Czech Academy of Sciences Publication Activity Database

    Blaha, Milan; Němcová, Lucie; Vodičková Kepková, Kateřina; Vodička, P.; Procházka, Radek

    2015-01-01

    Roč. 13, č. 113 (2015) ISSN 1477-7827 R&D Projects: GA ČR GAP502/11/0593; GA MZe(CZ) QJ1510138 Institutional support: RVO:67985904 Keywords : FSH * growth factors * cumulus cell Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.147, year: 2015

  6. Tax Havens, Growth, and Welfare

    OpenAIRE

    Chu, Hsun; Lai, Ching-Chong; Cheng, Chu-Chuan

    2013-01-01

    This paper develops an endogenous growth model featuring tax havens, and uses it to examine how the existence of tax havens affects the economic growth rate and social welfare in high-tax countries. We show that the presence of tax havens generates two conflicting channels in determining the growth effect. First, the public investment effect states that tax havens may erode tax revenues and in turn decrease the government’s infrastructure expenditure, thereby reducing growth. Second, the t...

  7. Corporate Stability and Economic Growth

    OpenAIRE

    He, Kathy S.; Morck, Randall; Yeung, Bernard

    2003-01-01

    Greater instability in a country's list of top corporations is associated with faster economic growth. This faster growth is primarily due to faster growth in total factor productivity in industrialized countries, and faster capital accumulation in developing countries. These findings are consistent with the view that economic growth is more closely tied to the rise of new large firms than to the prosperity of established large firms. Although a stable list of leading corporations is highly c...

  8. The poverty elasticity of growth

    OpenAIRE

    Heltberg, Rasmus

    2002-01-01

    How much does economic growth contribute to poverty reduction? I discuss analytical and empirical approches to assess the poverty elasticity of growth, and emphasize that the relationship between growth and poverty change is non-constant. For a given poverty measure, it depends on initial inequality and on the location of the poverty line relative to mean income. In most cases, growth is more important for poverty reduction than changes in inequality, but this does not tender inequality unimp...

  9. Economic growth and business cycles

    NARCIS (Netherlands)

    Canton, E.J.F.

    1997-01-01

    This thesis contains five essays on economic growth and business cycles. The main focus is on the interaction between economic growth and the cycle: is cyclical variability good or bad for the long-run rate of economic growth? The introduction aims to provide some empirical evidence for an

  10. PUBLIC GOODS, CORRUPTION AND GROWTH???

    OpenAIRE

    Ratbek Dzhumashev

    2006-01-01

    In this paper, we analyse implications of corruption on growth. We extend existing growth models by incorporating ubiquitous corruption as a by-product of the public sector. Corruption affects both taxation and public good provision, and therefore causes income redistribution and inefficiencies in the public sector. These effects of corruption lead to lower growth through distortions of investment incentives and resources allocation.

  11. Advanced dendritic web growth development

    Science.gov (United States)

    Hopkins, R. H.

    1985-01-01

    A program to develop the technology of the silicon dendritic web ribbon growth process is examined. The effort is being concentrated on the area rate and quality requirements necessary to meet the JPL/DOE goals for terrestrial PV applications. Closed loop web growth system development and stress reduction for high area rate growth is considered.

  12. Regulators of growth plate maturation

    NARCIS (Netherlands)

    Emons, Joyce Adriana Mathilde

    2010-01-01

    Estrogen is known to play an important role in longitudinal bone growth and growth plate maturation, but the mechanism by which estrogens exert their effect is not fully understood. In this thesis this role is further explored. Chapter 1 contains a general introduction to longitudinal bone growth

  13. Nuclear factor erythroid 2-related factor 2 antioxidant response element pathways protect bovine mammary epithelial cells against H2O2-induced oxidative damage in vitro.

    Science.gov (United States)

    Ma, Y F; Wu, Z H; Gao, M; Loor, J J

    2018-03-21

    The experiment was conducted to determine the role of nuclear factor (erythroid-derived 2)-like factor 2 (NFE2L2, formerly Nrf2) antioxidant response element (ARE) pathway in protecting bovine mammary epithelial cells (BMEC) against H 2 O 2 -induced oxidative stress injury. An NFE2L2 small interfering RNA (siRNA) interference or a pCMV6-XL5-NFE2L2 plasmid fragment was transfected to independently downregulate or upregulate expression of NFE2L2. Isolated BMEC in triplicate were exposed to H 2 O 2 (600 μM) for 6 h to induce oxidative stress before transient transfection with scrambled siRNA, NFE2L2-siRNA, pCMV6-XL5, and pCMV6-XL5-NFE2L2. Cell proliferation, apoptosis and necrosis rates, antioxidant enzyme activities, reactive oxygen species (ROS) and malondialdehyde (MDA) production, protein and mRNA expression of NFE2L2 and downstream target genes, and fluorescence activity of ARE were measured. The results revealed that compared with the control, BMEC transfected with NFE2L2-siRNA3 had proliferation rates that were 9 or 65% lower without or with H 2 O 2 , respectively. These cells also had apoptosis and necrosis rates that were 27 and 3.5 times greater with H 2 O 2 compared with the control group, respectively. In contrast, transfected pCMV6-XL5-NFE2L2 had proliferation rates that were 64.3% greater or 17% lower without or with H 2 O 2 compared with the control group, respectively. Apoptosis rates were 1.8 times lower with H 2 O 2 compared with the control. In addition, compared with the control, production of ROS and MDA and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione-S-transferase (GST) increased markedly in cells transfected with pCMV6-XL5-NFE2L2 and without H 2 O 2 . However, compared with the control, production of ROS and MDA and activity of CAT and GSH-Px increased markedly, whereas activities of SOD and GST decreased in cells transfected with pCMV6-XL5-NFE2L2 and incubated with H 2 O 2

  14. Great growth debate: an argument for rational growth policies

    Energy Technology Data Exchange (ETDEWEB)

    Bond, E; Koven, A

    1978-05-01

    The argument for rational growth policies in Canada advocates an expanding economy as the only one able to compensate both winners and losers. A constant growth rate--whether it is positive, negative, or zero--cannot work. A desirable growth rate must be flexible in the long term, which means that policies for zero growth must select only parts of the economy. On one hand, the creation of aritifical needs by advertising, urban expansion, and demographic growth in over-populated countries should be halted. On the other hand, we must expand necessary human welfare services. Zero growth does not mean that we must go back to poverty, asceticism, and constraint. An optimum growth policy will aim for moderation in all things. (Abstract, edited)

  15. Growth hormone in intra-uterine growth retarded newborns.

    Science.gov (United States)

    Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Latha

    2007-11-01

    To study growth hormone levels in IUGR and healthy controls and its association with birth weight and ponderal index. We studied 50 Intra uterine growth retarded (IUGR) and 50 healthy newborns born at term by vaginal delivery in JIPMER, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of growth hormone. When compared with healthy newborns, IUGR newborns had higher growth hormone levels (mean +/- SD, 23.5 +/- 15.6 vs 16.2 +/- 7.61 ngm/ml, P = 0.019). A negative correlation was identified between growth hormone levels and birth weight (r2 = - 0.22, P = 0.03) and ponderal index (r2 = - 0.36, P = 0.008). Correlation of growth hormone levels was much more confident with ponderal index than with birth weight. At birth IUGR infants display increased growth hormone levels which correlate with ponderal index much more confidently than with birth weight.

  16. Biofuels, poverty, and growth

    DEFF Research Database (Denmark)

    Arndt, Channing; Benfica, Rui; Tarp, Finn

    2010-01-01

    and accrual of land rents to smallholders, compared with the more capital-intensive plantation approach. Moreover, the benefits of outgrower schemes are enhanced if they result in technology spillovers to other crops. These results should not be taken as a green light for unrestrained biofuels development...... Mozambique's annual economic growth by 0.6 percentage points and reduces the incidence of poverty by about 6 percentage points over a 12-year phase-in period. Benefits depend on production technology. An outgrower approach to producing biofuels is more pro-poor, due to the greater use of unskilled labor...

  17. Aid and sectoral growth

    DEFF Research Database (Denmark)

    Selaya, Pablo; Thiele, Rainer

    2010-01-01

    This article examines empirically the proposition that aid to poor countries is detrimental for external competitiveness, giving rise to Dutch disease type effects. At the aggregate level, aid is found to have a positive effect on growth. A sectoral decomposition shows that the effect is (i......) significant and positive in the tradable and the nontradable sectors, and (ii) equally strong in both sectors. The article thus provides no empirical support for the hypothesis that aid reduces external competitiveness in developing countries. A possible reason for this finding is the existence of large idle...

  18. Modeling urban fire growth

    International Nuclear Information System (INIS)

    Waterman, T.E.; Takata, A.N.

    1983-01-01

    The IITRI Urban Fire Spread Model as well as others of similar vintage were constrained by computer size and running costs such that many approximations/generalizations were introduced to reduce program complexity and data storage requirements. Simplifications were introduced both in input data and in fire growth and spread calculations. Modern computational capabilities offer the means to introduce greater detail and to examine its practical significance on urban fire predictions. Selected portions of the model are described as presently configured, and potential modifications are discussed. A single tract model is hypothesized which permits the importance of various model details to be assessed, and, other model applications are identified

  19. Growth, Development and Sustainability

    Directory of Open Access Journals (Sweden)

    Irina-Virginia Dragulanescu

    2013-11-01

    Full Text Available Describing the relationship of interdependence through the materials balance, will be argued how the economy is a subset of the environment and the environment the natural limit to any economic initiative, or the limits imposed by the laws of thermodynamics. The theoretical debate moves, then, from the concept of growth to that of development, understood this in its three dimensions: economic, social, environmental. Bring the different environmental positions in four versions of sustainability, with the gained awareness that it’s “a spectrum of overlapping sustainability positions from very weak to very strong”.

  20. Urban Growth and Transportation

    OpenAIRE

    Gilles Duranton; Matthew A. Turner

    2012-01-01

    We estimate the effects of major roads and public transit on the growth of major cities in the US between 1980 and 2000. We find that a 10% increase in a city’s stock of roads causes about a 2% increase in its population and employment and a small decrease in its share of poor households over this 20 year period. We also find that a 10% increase in a city’s stock of large buses causes about a 0.8% population increase and a small increase in the share of poor households over this period. To es...

  1. Developing principles of growth

    DEFF Research Database (Denmark)

    Neergaard, Helle; Fleck, Emma

    of the principles of growth among women-owned firms. Using an in-depth case study methodology, data was collected from women-owned firms in Denmark and Ireland, as these countries are similar in contextual terms, e.g. population and business composition, dominated by micro, small and medium-sized enterprises....... Extending on principles put forward in effectuation theory, we propose that women grow their firms according to five principles which enable women’s enterprises to survive in the face of crises such as the current financial world crisis....

  2. Ion beam assisted film growth

    CERN Document Server

    Itoh, T

    2012-01-01

    This volume provides up to date information on the experimental, theoretical and technological aspects of film growth assisted by ion beams.Ion beam assisted film growth is one of the most effective techniques in aiding the growth of high-quality thin solid films in a controlled way. Moreover, ion beams play a dominant role in the reduction of the growth temperature of thin films of high melting point materials. In this way, ion beams make a considerable and complex contribution to film growth. The volume will be essential reading for scientists, engineers and students working in thi

  3. Leverage, Investment, and Firm Growth

    OpenAIRE

    Larry Lang; Eli Ofek; Rene M. Stulz

    1995-01-01

    We show that there is a negative relation between leverage and future growth at the firm level and, for diversified firms, at the segment level. Further, this negative relation between leverage and growth holds for firms with low Tobin's q, but not for high-q firms or firms in high-q industries. Therefore, leverage does not reduce growth for firms known to have good investment opportunities, but is negatively related to growth for firms whose growth opportunities are either not recognized by ...

  4. Probabilistic Mass Growth Uncertainties

    Science.gov (United States)

    Plumer, Eric; Elliott, Darren

    2013-01-01

    Mass has been widely used as a variable input parameter for Cost Estimating Relationships (CER) for space systems. As these space systems progress from early concept studies and drawing boards to the launch pad, their masses tend to grow substantially, hence adversely affecting a primary input to most modeling CERs. Modeling and predicting mass uncertainty, based on historical and analogous data, is therefore critical and is an integral part of modeling cost risk. This paper presents the results of a NASA on-going effort to publish mass growth datasheet for adjusting single-point Technical Baseline Estimates (TBE) of masses of space instruments as well as spacecraft, for both earth orbiting and deep space missions at various stages of a project's lifecycle. This paper will also discusses the long term strategy of NASA Headquarters in publishing similar results, using a variety of cost driving metrics, on an annual basis. This paper provides quantitative results that show decreasing mass growth uncertainties as mass estimate maturity increases. This paper's analysis is based on historical data obtained from the NASA Cost Analysis Data Requirements (CADRe) database.

  5. FACET Emittance Growth

    Energy Technology Data Exchange (ETDEWEB)

    Frederico, J; Hogan, M.J.; Nosochkov, Y.; Litos, M.D.; Raubenheimer, T.; /SLAC

    2011-04-05

    FACET, the Facility for Advanced Accelerator and Experimental Tests, is a new facility being constructed in sector 20 of the SLAC linac primarily to study beam driven plasma wakefield acceleration. The FACET beamline consists of a chicane and final focus system to compress the 23 GeV, 3.2 nC electron bunches to {approx}20 {micro}m long and {approx}10 {micro}m wide. Simulations of the FACET beamline indicate the short-duration and large, 1.5% rms energy spread beams may suffer a factor of four emittance growth from a combination of chromaticity, incoherent synchrotron radiation (ISR), and coherent synchrotron radiation (CSR). Emittance growth is directly correlated to head erosion in plasma wakefield acceleration and is a limiting factor in single stage performance. Studies of the geometric, CSR, and ISR components are presented. Numerical calculation of the rms emittance can be overwhelmed by long tails in the simulated phase space distributions; more useful definitions of emittance are given. A complete simulation of the beamline is presented as well, which agrees with design specifications.

  6. China urges rapid growth

    International Nuclear Information System (INIS)

    Hendry, S.

    1993-01-01

    This time last year China's paramount leader, Deng Xiaoping, launched the country on another bout of fast-paced economic growth and restructuring. After three years of riding out political and economic clampdown, foreign chemical companies were jerked awake by major changes in China's chemical industry. As the state becomes less involved with managing the economy, unleashing 12% gross national product growth, closer involvement with domestic factories has become attractive and essential. MCI officials say government funds will now be channeled toward clearing energy and transport bottlenecks, and chemical enterprises will be given more chance to turn a profit. They will be allowed to issue shares, seek foreign investment partners themselves, and bypass trading companies like China National Import-Export Corp. (Sinochem), the former state monopoly. Foreign analysts question whether China's finances and oil resources can support expansion. Even if they can, Cai estimates that ethylene imports will remain around the present level of 1 million tons. To further guarantee chemical supplies, China has invested in urea and polypropylene plants in the US and polystyrene plant in Hong Kong

  7. FACET Emittance Growth

    International Nuclear Information System (INIS)

    Frederico, Joel

    2011-01-01

    FACET, the Facility for Advanced Accelerator and Experimental Tests, is a new facility being constructed in sector 20 of the SLAC linac primarily to study beam driven plasma wakefield acceleration. The FACET beamline consists of a chicane and final focus system to compress the 23 GeV, 3.2 nC electron bunches to ∼20 (micro)m long and ∼10 (micro)m wide. Simulations of the FACET beamline indicate the short-duration and large, 1.5% rms energy spread beams may suffer a factor of four emittance growth from a combination of chromaticity, incoherent synchrotron radiation (ISR), and coherent synchrotron radiation (CSR). Emittance growth is directly correlated to head erosion in plasma wakefield acceleration and is a limiting factor in single stage performance. Studies of the geometric, CSR, and ISR components are presented. Numerical calculation of the rms emittance can be overwhelmed by long tails in the simulated phase space distributions; more useful definitions of emittance are given. A complete simulation of the beamline is presented as well, which agrees with design specifications.

  8. Molecular mechanisms of crystal growth

    International Nuclear Information System (INIS)

    Pina, C. M.

    2000-01-01

    In this paper I present an example of the research that the Mineral Surface Group of the Munster University is conducting in the field of Crystal Growth. Atomic Force Microscopy (Am) in situ observations of different barite (BaSO4) faces growing from aqueous solutions, in combination with computer simulations of the surface attachment of growth units allows us to test crystal growth models. Our results demonstrate the strong structural control that a crystal can exert on its own growth, revealing also the limitation of the classical crystal growth theories (two dimensional nucleation and spiral growth models) in providing a complete explanation for the growth behaviour at a molecular scale. (Author) 6 refs

  9. Springer Handbook of Crystal Growth

    CERN Document Server

    Dhanaraj, Govindhan; Prasad, Vishwanath; Dudley, Michael

    2010-01-01

    Over the years, many successful attempts have been made to describe the art and science of crystal growth. Most modern advances in semiconductor and optical devices would not have been possible without the development of many elemental, binary, ternary, and other compound crystals of varying properties and large sizes. The objective of the Springer Handbook of Crystal Growth is to present state-of-the-art knowledge of both bulk and thin-film crystal growth. The goal is to make readers understand the basics of the commonly employed growth processes, materials produced, and defects generated. Almost 100 leading scientists, researchers, and engineers from 22 different countries from academia and industry have been selected to write chapters on the topics of their expertise. They have written 52 chapters on the fundamentals of bulk crystal growth from the melt, solution, and vapor, epitaxial growth, modeling of growth processes and defects, techniques of defect characterization as well as some contemporary specia...

  10. Geometrical approach to tumor growth.

    Science.gov (United States)

    Escudero, Carlos

    2006-08-01

    Tumor growth has a number of features in common with a physical process known as molecular beam epitaxy. Both growth processes are characterized by the constraint of growth development to the body border, and surface diffusion of cells and particles at the growing edge. However, tumor growth implies an approximate spherical symmetry that makes necessary a geometrical treatment of the growth equations. The basic model was introduced in a former paper [C. Escudero, Phys. Rev. E 73, 020902(R) (2006)], and in the present work we extend our analysis and try to shed light on the possible geometrical principles that drive tumor growth. We present two-dimensional models that reproduce the experimental observations, and analyze the unexplored three-dimensional case, for which interesting conclusions on tumor growth are derived.

  11. Transforming growth factor-beta, but not ciliary neurotrophic factor, inhibits DNA synthesis of adrenal medullary cells in vitro

    DEFF Research Database (Denmark)

    Wolf, N; Krohn, K; Bieger, S

    1999-01-01

    by the neuroendocrine chromaffin cells, which also express the transforming growth factor-beta receptor type II. In contrast to the developmentally related sympathetic neurons, chromaffin cells continue to proliferate throughout postnatal life. Using 5-bromo-2'-deoxyuridine pulse labeling and tyrosine hydroxylase...... immunocytochemistry as a marker for young postnatal rat chromaffin cells, we show that treatment with fibroblast growth factor-2 (1 nM) and insulin-like growth factor-II (10 nM) increased the fraction of 5-bromo-2'-deoxyuridine-labeled nuclei from 1% to about 40% of the cells in the absence of serum. In the presence...... of fibroblast growth factor-2 and insulin-like growth factor-II, transforming growth factor-beta1 (0.08 nM) reduced 5-bromo-2'-deoxyuridine labeling by about 50%, without interfering with chromaffin cell survival or death. Doses lower and higher than 0.08 nM were less effective. Similar effects were seen...

  12. Succinate dehydrogenase assembly factor 2 is needed for assembly and activity of mitochondrial complex II and for normal root elongation in Arabidopsis.

    Science.gov (United States)

    Huang, Shaobai; Taylor, Nicolas L; Ströher, Elke; Fenske, Ricarda; Millar, A Harvey

    2013-02-01

    Mitochondria complex II (succinate dehydrogenase, SDH) plays a central role in respiratory metabolism as a component of both the electron transport chain and the tricarboxylic acid cycle. We report the identification of an SDH assembly factor by analysis of T-DNA insertions in At5g51040, a protein with unknown function that was identified by mass spectrometry analysis as a low abundance mitochondrial protein. This gene is co-expressed with a number of genes encoding mitochondrial proteins, including SDH1-1, and has low partial sequence similarity to human SDHAF2, a protein required for flavin-adenine dinucleotide (FAD) insertion into SDH. In contrast to observations of other SDH deficient lines in Arabidopsis, the sdhaf2 line did not affect photosynthetic rate or stomatal conductance, but instead showed inhibition of primary root elongation with early lateral root emergence, presumably due to the low SDH activity caused by the reduced abundance of SDHAF2. Both roots and leaves showed succinate accumulation but different responses in the abundance of other organic acids and amino acids assayed. Isolated mitochondria showed lowered SDH1 protein abundance, lowered maximal SDH activity and less protein-bound flavin-adenine dinucleotide (FAD) at the molecular mass of SDH1 in the gel separation. The short root phenotype and SDH function of sdhaf2 was fully complemented by transformation with SDHAF2. Application of the SDH inhibitor, malonate, phenocopied the sdhaf2 root architecture in WT. Whole root respiratory assays showed no difference between WT and sdhaf2, but micro-respirometry of the tips of roots clearly showed low oxygen consumption in sdhaf2 which could explain a metabolic deficit responsible for root tip growth. © 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.

  13. Rapid growth within India

    International Nuclear Information System (INIS)

    Hayes, D.

    2000-01-01

    The Indian government has published (in Hydrocarbon Vision 2025) its ideas for a long term strategy for its oil industry which is currently growing at an unprecedented rate. Increasing domestic production and investment in oil exploration and production overseas figure strongly in the plan. At present, India has a refining surplus but with an annual growth of 8-10%, this will disappear in the next 2-3 years. The report recommends that India should maintain 90% self-sufficiency in refining. The report sees development of the domestic oil industry as globally competitive and helping safeguard India's assets. The capability of India's refineries, current upgrading, the newer refineries and plans for new projects are all mentioned

  14. 2010 responsible growth report

    International Nuclear Information System (INIS)

    2010-01-01

    The report addresses several development and growth perspectives for AREVA: its integrated business model, the synergy and complementarities between nuclear and renewable energies, the sustainable development dimension of its industrial development, its sales revenue result, the reduction of its environmental footprint, its development on all continents, its balanced governance, the simplification of its capital structure, and the actions performed by its Foundation. Then, it discusses ten challenges for the company: ensuring safety and performance throughout the reactor life cycle, making the EPR reactor a standard of safety, maintaining relations based on trust with our stake holders, staying in the lead, accelerating the development of renewable energies, being a trusted partner to growing economies, being a model in mine management, promoting sustainable, effective and safe recycling of used fuel, improving performance continuously, offering development prospects to all employees. It briefly presents ten successes achieved in 2010 and indicates ten sustainable development commitments. Document in French and in English

  15. Employment without Growth

    DEFF Research Database (Denmark)

    Nørgaard, Jørgen

    work over more income and consumption. Lower work input to production can take many differnet forms, such as job sharing, lowering production efficiency, reduction in labor force, etc. In this light it seems ridiculous to argue for certain economic development course on the ground that it will create...... more work. There are no indication that growth at Western economies increases satisfaction or happiness. A new look at the full economy divides it into professional economy and amateur economy, and it is suggested that a reversal of the trend hitherto to draw still more of the whole economy...... into the professional sphere, GDP, could contribute at the same time to a better satisfaction and a more sustainable development....

  16. Growth outside the core.

    Science.gov (United States)

    Zook, Chris; Allen, James

    2003-12-01

    Growth in an adjacent market is tougher than it looks; three-quarters of the time, the effort fails. But companies can change those odds dramatically. Results from a five-year study of corporate growth conducted by Bain & Company reveal that adjacency expansion succeeds only when built around strong core businesses that have the potential to become market leaders. And the best place to look for adjacency opportunities is inside a company's strongest customers. The study also found that the most successful companies were able to consistently, profitably outgrow their rivals by developing a formula for pushing out the boundaries of their core businesses in predictable, repeatable ways. Companies use their repeatability formulas to expand into any number of adjacencies. Some companies make repeated geographic moves, as Vodafone has done in expanding from one geographic market to another over the past 13 years, building revenues from $1 billion in 1990 to $48 billion in 2003. Others apply a superior business model to new segments. Dell, for example, has repeatedly adapted its direct-to-customer model to new customer segments and new product categories. In other cases, companies develop hybrid approaches. Nike executed a series of different types of adjacency moves: it expanded into adjacent customer segments, introduced new products, developed new distribution channels, and then moved into adjacent geographic markets. The successful repeaters in the study had two common characteristics. First, they were extraordinarily disciplined, applying rigorous screens before they made an adjacency move. This discipline paid off in the form of learning curve benefits, increased speed, and lower complexity. And second, in almost all cases, they developed their repeatable formulas by studying their customers and their customers' economics very, very carefully.

  17. International growth of neuropsychology.

    Science.gov (United States)

    Ponsford, Jennie

    2017-11-01

    Twenty-five years ago, the field of neuropsychology was well established in North America, Europe, and Australia, with less presence elsewhere. This article discusses the development of neuropsychology over the last 25 years in other regions. The growth of neuropsychology in Asia, Africa, the Middle East, Central and South America, and New Zealand is reviewed. Sources drawn on include a 2016 edition of The Clinical Neuropsychologist describing the practice of neuropsychology in 18 countries; papers on the profession of neuropsychology in Latin America (Arango-Lasprilla, Stevens, Paredes, Ardila, & Rivera, 2016), the history of neuropsychology in Asia (Lee, Wang, & Collinson, 2016), and neuropsychology in Central America (Judd, 2017); INSNET; and personal communications. There has been tremendous variability in the development of neuropsychology across these regions over the last 25 years. Obstacles to the growth of neuropsychology have included economic constraints on health care provision, limited availability of appropriate assessment and treatment methods, linguistic diversity and illiteracy, stigma toward and/or lack of awareness of neuropsychological disorders, lack of graduate training and clinical supervision, absence of accreditation of neuropsychologists as a clinical profession, poor pay, and diminished visibility of the field within the regional culture. Despite these obstacles, neuropsychological research and practice is establishing itself in these regions and has grown significantly over the last quarter century. Major challenges remain in establishing awareness of the significance of and developing culturally appropriate methods of assessing and rehabilitating cognitive aspects of brain disorders, training programs, recognition as a profession, and dedicated funding for neuropsychology positions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  18. Thermodynamics of firms' growth

    Science.gov (United States)

    Zambrano, Eduardo; Hernando, Alberto; Hernando, Ricardo; Plastino, Angelo

    2015-01-01

    The distribution of firms' growth and firms' sizes is a topic under intense scrutiny. In this paper, we show that a thermodynamic model based on the maximum entropy principle, with dynamical prior information, can be constructed that adequately describes the dynamics and distribution of firms' growth. Our theoretical framework is tested against a comprehensive database of Spanish firms, which covers, to a very large extent, Spain's economic activity, with a total of 1 155 142 firms evolving along a full decade. We show that the empirical exponent of Pareto's law, a rule often observed in the rank distribution of large-size firms, is explained by the capacity of economic system for creating/destroying firms, and that can be used to measure the health of a capitalist-based economy. Indeed, our model predicts that when the exponent is larger than 1, creation of firms is favoured; when it is smaller than 1, destruction of firms is favoured instead; and when it equals 1 (matching Zipf's law), the system is in a full macroeconomic equilibrium, entailing ‘free’ creation and/or destruction of firms. For medium and smaller firm sizes, the dynamical regime changes, the whole distribution can no longer be fitted to a single simple analytical form and numerical prediction is required. Our model constitutes the basis for a full predictive framework regarding the economic evolution of an ensemble of firms. Such a structure can be potentially used to develop simulations and test hypothetical scenarios, such as economic crisis or the response to specific policy measures. PMID:26510828

  19. [Economic growth with zero population growth and with declining population].

    Science.gov (United States)

    Kurz, R

    1982-05-01

    The effects of both zero population growth and a declining population on economic growth are considered. Although the neoclassical theory of economic growth leads to optimistic results in such cases, the author suggests that this theory cannot be used as a basis for political action. The need for further research into the economic effects of a stationary or declining population is stressed. (summary in ENG)

  20. Growth assessment in diagnosis of Fetal Growth Restriction. Review

    OpenAIRE

    Albu, AR; Horhoianu, IA; Dumitrascu, MC; Horhoianu, V

    2014-01-01

    Abstract The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the t...

  1. SNP and haplotype analysis reveal IGF2 variants associated with growth traits in Chinese Qinchuan cattle.

    Science.gov (United States)

    Huang, Yong-Zhen; Zhan, Zhao-Yang; Li, Xin-Yi; Wu, Sheng-Ru; Sun, Yu-Jia; Xue, Jing; Lan, Xian-Yong; Lei, Chu-Zhao; Zhang, Chun-Lei; Jia, Yu-Tang; Chen, Hong

    2014-02-01

    Insulin-like growth factor 2 (IGF2) is a potent cell growth and differentiation factor and is implicated in mammals' growth and development. The objective of this study was to evaluate the effects of the mutations in the bovine IGF2 with growth traits in Chinese Qinchuan cattle. Four single nucleotide polymorphisms (SNPs) were detected of the bovine IGF2 by DNA pool sequencing and forced polymerase chain reaction-restriction fragment length polymorphism (forced PCR-RFLP) methods. We also investigated haplotype structure and linkage disequilibrium (LD) coefficients for four SNPs in 817 individuals representing two main cattle breeds from China. The result of haplotype analysis showed eight different haplotypes and 27 combined genotypes within the study population. The statistical analyses indicated that the four SNPs, combined genotypes and haplotypes are associated with the withers height, body length, chest breadth, chest depth and body weight in Qinchuan cattle population (P growth traits; the heterozygote diplotype was associated with higher growth traits compared to wild-type homozygote. Our results provide evidence that polymorphisms in the IGF2 gene are associated with growth traits, and may be used for marker-assisted selection in beef cattle breeding program.

  2. Growth of LiF/LiBaF.sub.3./sub. eutectic scintillator crystals and their optical properties

    Czech Academy of Sciences Publication Activity Database

    Kurosawa, S.; Yamaji, A.; Pejchal, Jan; Yokota, Y.; Ohashi, Y.; Kamada, K.; Yoshikawa, A.

    2017-01-01

    Roč. 52, č. 10 (2017), s. 5531-5536 ISSN 0022-2461 Grant - others:AV ČR(CZ) JSPS-17-18 Program:Bilaterální spolupráce Institutional support: RVO:68378271 Keywords : scintillators * eutectics * crystal growth Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 2.599, year: 2016

  3. Resistance of direct metal laser sintered Ti6Al4V alloy against growth of fatigue cracks

    Czech Academy of Sciences Publication Activity Database

    Konečná, R.; Kunz, Ludvík; Bača, A.; Nicoletto, G.

    2017-01-01

    Roč. 185, NOV (2017), s. 82-91 ISSN 0013-7944 Institutional support: RVO:68081723 Keywords : Titanium alloys * Ti6Al4V * Fatigue crack growth * Threshold value of stress intensity factor * Direct metal laser sintering Subject RIV: JL - Materials Fatigue, Friction Mechanics OBOR OECD: Audio engineering, reliability analysis Impact factor: 2.151, year: 2016 http://www.sciencedirect.com/science/article/pii/S0013794417300292

  4. Characterization of a model cyanobacterium Synechocystis sp. PCC 6803 autotrophic growth in a flat-panel photobioreactor

    Czech Academy of Sciences Publication Activity Database

    Zavřel, T.; Sinětova, M. A.; Búzová, Diana; Literáková, Petra; Červený, Jan

    2015-01-01

    Roč. 15, č. 1 (2015), s. 122-132 ISSN 1618-0240 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073; GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : Carbon dioxide * Exponential phase * Growth optimization * Light * Temperature Subject RIV: EH - Ecology, Behaviour Impact factor: 2.168, year: 2015

  5. Growth Mechanism of Microbial Colonies

    Science.gov (United States)

    Zhu, Minhui; Martini, K. Michael; Kim, Neil H.; Sherer, Nicholas; Lee, Jia Gloria; Kuhlman, Thomas; Goldenfeld, Nigel

    Experiments on nutrient-limited E. coli colonies, growing on agar gel from single cells reveal a power-law distribution of sizes, both during the growth process and in the final stage when growth has ceased. We developed a Python simulation to study the growth mechanism of the bacterial population and thus understand the broad details of the experimental findings. The simulation takes into account nutrient uptake, metabolic function, growth and cell division. Bacteria are modeled in two dimensions as hard circle-capped cylinders with steric interactions and elastic stress dependent growth characteristics. Nutrient is able to diffuse within and between the colonies. The mechanism of microbial colony growth involves reproduction of cells within the colonies and the merging of different colonies. We report results on the dynamic scaling laws and final state size distribution, that capture in semi-quantitative detail the trends observed in experiment. Supported by NSF Grant 0822613.

  6. SECTORAL SHARES AND ECONOMIC GROWTH

    DEFF Research Database (Denmark)

    Ahmad, Nisar; Naveed, Amjad; Naz, Amber

    2013-01-01

    believe that structural change is an unimportant side effect of the economic development. On the contrary, economists associated with the World Bank and some others posit that growth is brought about by the changes in sectoral composition. The objective of this study is to empirically test...... the relationship between sectoral shares and economic growth by using the panel data for 20 developed countries. The results of the granger causality suggest that both services and agriculture sectors do granger cause economic growth, whereas industrial sector does not granger cause growth. Reverse causality does...... not hold for any of the three sectors. The results of Barro and Non-Barro regressions along with the set of control variables have suggested that services sector is negatively affecting growth, whereas both industrial and agriculture shares are positively affect economic growth....

  7. Hopper Growth of Salt Crystals.

    Science.gov (United States)

    Desarnaud, Julie; Derluyn, Hannelore; Carmeliet, Jan; Bonn, Daniel; Shahidzadeh, Noushine

    2018-06-07

    The growth of hopper crystals is observed for many substances, but the mechanism of their formation remains ill understood. Here we investigate their growth by performing evaporation experiments on small volumes of salt solutions. We show that sodium chloride crystals that grow very fast from a highly supersaturated solution form a peculiar form of hopper crystal consisting of a series of connected miniature versions of the original cubic crystal. The transition between cubic and such hopper growth happens at a well-defined supersaturation where the growth rate of the cubic crystal reaches a maximum (∼6.5 ± 1.8 μm/s). Above this threshold, the growth rate varies as the third power of supersaturation, showing that a new mechanism, controlled by the maximum speed of surface integration of new molecules, induces the hopper growth of cubic crystals in cascade.

  8. Growth patterns and annual growth cycle of Acacia karroo Hayne in ...

    African Journals Online (AJOL)

    ... karroo; alice; botany; compensatory growth; condition; development; eastern cape; emergence; environmental conditions; field study; growth cycle; growth initiation; growth patterns; growth strategy; leaf growth; plant growth; savanna; shoot growth; soil depth; soil moisture; south africa; university of fort hare; water stress ...

  9. Growth factor involvement in tension-induced skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  10. Population growth and infant mortality

    OpenAIRE

    Fabella, Christina

    2008-01-01

    The relationship between population growth and economic outcomes is an issue of great policy significance. In the era of the Millennium Development Goals, poverty and its correlates have become the compelling issues. Economic growth may not automatically translate into reductions in poverty and its correlates (may not trickle down) if income distribution is at the same time worsening. We therefore investigate the direct effect of population growth on infant mortality for various income catego...

  11. Financing Asia’s Growth

    OpenAIRE

    Estrada, Gemma; Noland, Marcus; Park, Donghyun; Ramayandi, Arief

    2015-01-01

    Recent key challenges highlight the need to revisit Asia's financial development. These include the region's growth slowdown since the global crisis, compounded by a less benign external environment; internal structural challenges, such as population aging; and the maturing of much of the region into middle-income status. The evolving shift in the region's growth paradigm from one based primarily on investment to one based on both investment and productivity growth also underscores the urgenc...

  12. Linking Ethics and Economic Growth

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul

    2012-01-01

    Hunt (2012) builds on his work concerning ethics and resource-advantage theory to link personal ethical standards, societal norms, and economic growth but offers few details concerning the precise mechanisms that link ethics and growth. This comment suggests a number of such mechanisms – for exam...... – for example, the influence of prevailing ethical norms on the aggregate elasticity of substitution and, therefore, total factor productivity and growth....

  13. Stochastic models for tumoral growth

    OpenAIRE

    Escudero, Carlos

    2006-01-01

    Strong experimental evidence has indicated that tumor growth belongs to the molecular beam epitaxy universality class. This type of growth is characterized by the constraint of cell proliferation to the tumor border, and surface diffusion of cells at the growing edge. Tumor growth is thus conceived as a competition for space between the tumor and the host, and cell diffusion at the tumor border is an optimal strategy adopted for minimizing the pressure and helping tumor development. Two stoch...

  14. Growth curves for Laron syndrome.

    OpenAIRE

    Laron, Z; Lilos, P; Klinger, B

    1993-01-01

    Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14 girls) of the 41 patients with this syndrome investigated in our clinic. Growth retardation was already noted at birth, the birth length ranging from 42 to 46 cm in the 12/20 available measurements. The postnatal growth curves deviated sharply from the normal from infancy on. Both sexes showed no clear pubertal spurt. Girls co...

  15. Electricity regulation and economic growth

    OpenAIRE

    Costa, M. Teresa (Maria Teresa), 1951-; Garcia-Quevedo, Jose; Trujillo-Baute, Elisa

    2018-01-01

    The main objective of this paper is to analyse the effect of electricity regulation on economic growth. Although the relationship between electricity consumption and economic growth has been extensively analysed in the empirical literature, this framework has not been used to estimate the effect of electricity regulation on economic growth. Understanding this effect is essential for the assessment of regulatory policy. Specifically, we assess the effects of two major areas of regulation, rene...

  16. Political Instability and Economic Growth

    OpenAIRE

    Alberto Alesina; Sule Ozler; Nouriel Roubini; Phillip Swagel

    1992-01-01

    This paper investigates the relationship between political instability and per capita GDP growth in a sample of 113 countries for the period 1950-1982. We define ?political instability? as the propensity of a government collapse, and we estimate a model in which political instability and economic growth are jointly determined. The main result of this paper is that in countries and time periods with a high propensity of government collapse, growth is significantly lower than otherwise. This ef...

  17. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth.

    Science.gov (United States)

    Wu, Shufang; Yang, Wei; De Luca, Francesco

    2015-07-01

    GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

  18. Gene regulation by growth factors

    International Nuclear Information System (INIS)

    Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

    1988-01-01

    To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

  19. Growth, Employment and Structural Change

    DEFF Research Database (Denmark)

    Aggarwal, Aradhna

    2016-01-01

    This paper studies the decomposition of GSDP growth per capita in Punjab via-a-vis 15 other states in India during 1993–94 and 2011–12 in terms of employment and productivity growth. Specifically, it focuses on the role of employment growth and structural change in employment on economic growth...... but structural shifts have paid off well in terms of diversification of the economy and their contribution to labour productivity especially for manufacturing. Overall employment effect had been negative but this was essentially due to contraction in the labour force; the employment rate effect turned out...

  20. Quality, Export and Economic Growth

    DEFF Research Database (Denmark)

    Madsen, Erik Strøjer; Pedersen, Kurt

    1998-01-01

    in an international context. The paper, therefore, addresses the complicated interactions between economic growth, export performance and quality. The contribution of the paper, compared to other growth accounting research, is the inclusion of quality data, quality being a significant mirror of technological...... development. The countries covered by the research represent a wide variation in terms of economic development, from poor LDC's to the most developed industrial nations. The empirical results reveal a probable strong relationship between quality/price and export growth as well as economic growth. This new...

  1. Variations in growth pattern and predictablity of liveweight growth of ...

    African Journals Online (AJOL)

    The prediction equations results for rate of liveweight growth showed that of the four models used, the quadratic function was the best predictor of liveweight growth, as indicated by the highest and significant R2 value of 90.7 %. This was closely followed by the linear function which had a significant R2 value of 88.1 %.

  2. Can extrauterine growth approximate intrauterine growth? Should it?

    NARCIS (Netherlands)

    Sauer, Pieter J. J.

    Most studies evaluating the growth of preterm infants use the so-called intrauterine growth curve and reference fetus as standards. These curves might not be the optimal standards, however, for several reasons. The curves were constructed from small numbers of infants with uncertainty about

  3. Growth of the Pamir

    Science.gov (United States)

    Gloaguen, R.; Ratschbacher, L.

    2009-04-01

    We aim to establish the Late Cenozoic deformation field of the Pamir by localizing and characterizing active and neotectonic deformation structures, and setting up the drainage-basin, river-capture, river- reversal, and regional erosion history. The project thus aims to record the short-term, upper crustal response to active intra-continental subduction, orocline formation, and erosion. Our hypothesis is that the neotectonics is governed by subduction beneath the frontal part of the orocline, E-W extension in the intra-plateau Karakul-lake rift, and transtension (east) and transpression (west) along the lateral margins of the orocline, a result of oroclinal formation, rotation of the Indian indenter, and focused precipitation caused by the Westerlies. The model for the evolution of the drainage system involves: growth of the Pamir by N-ward propagating deformation, establishing E-trending belts of shortening and rivers/drainages; diversion and blocking of these rivers by the development of the lateral boundaries of the orocline that resulted in river capture and reversal. Even the present-day Panj (Amu Darya) is affected by ongoing uplift: tilted river terraces, wind gaps, and abnormal intersection of streams of different order indicate that large parts of the river have changed flow direction. The determination of a number of geomorphic indices with remote sensing techniques help us to identify areas experiencing tectonic deformation.

  4. Posttraumatic growth in psychosis

    Directory of Open Access Journals (Sweden)

    Yael Mazor

    2016-12-01

    Full Text Available Objective: Recent research has shown high rates of exposure to trauma among people with serious mental illness (SMI. In addition studies suggest that psychosis and mental illness-related experiences can be extremely traumatic. While some individuals develop full blown PTSD related to these experiences, it has been noted that some may also experience posttraumatic growth (PTG. However, few studies have examined PTG as a possible outcome in people who have experienced psychosis. Method: To further understand the relationships between psychosis and PTG, 121 participants were recruited from community mental health rehabilitation centers and administered trauma and psychiatric questionnaires. Results: High levels of traumatic exposure were found in the sample. Regarding our main focus of study we observed that people who endured psychosis can experience PTG, and that PTG is mediated by meaning making and coping self-efficacy appraisal. Psychotic symptoms were found to be a major obstacle to meaning making, coping self-efficacy, and PTG, whereas negative symptoms were found to be significantly related to PTG when mediated by meaning making and coping self-efficacy. Conclusion: The current research provides preliminary evidence for potential role of meaning making and coping self-efficacy as mediators of PTG in the clinical, highly traumatized population of people with SMI who have experienced psychosis. This may have both research as well as clinical practice relevance for the field of psychiatric rehabilitation.

  5. ECOLOGICAL GROWTH BOUNDARIES

    Directory of Open Access Journals (Sweden)

    Anna BLUSZCZ

    2017-01-01

    Full Text Available The trends of the society for the continuous growth, combined with the demographic changes, today have led to the important ecological problems on a global scale, which include, among others: the increased use of non-renewable natu-ral resources, an increase of the greenhouse gas emissions, contamination of soil, water, air and the progressive degra-dation of ecosystems. In the face of such serious threats the global initiatives of all countries are important to limit the results of the excessive consumption. The aim of the article is to present the methods of measurement of the consump-tion level of natural resources by the societies and the examination of relationships between the level of development of the societies and the use of resources. The popular measure – the ecological footprint – was used as a measurement method for the consumption of the today’s generations in relation to the regenerative possibilities of the natural envi-ronment. On the other hand, as the assessment method for the level of development of societies – the Human Develop-ment Index (HDI, including three basic areas: the life expectancy, GDP level per capita and education was used. The results of the research indicate that the current trend of the unlimited consumption of the highly developed countries takes place at the expense of the future generations.

  6. The initial growth stage in PVT growth of aluminum nitride

    Energy Technology Data Exchange (ETDEWEB)

    Heimann, P.; Epelbaum, B.M.; Bickermann, M.; Winnacker, A. [Department of Materials Science 6, University of Erlangen-Nuernberg, Martensstr. 7, 91058 Erlangen (Germany); Nagata, S. [Functional Materials Development Center, Research Laboratories, JFE Mineral Company, Ltd., 1, Niihama-cho, Chuou-ku, Chiba-shi, Chiba 260-0826 (Japan)

    2006-06-15

    The main issue in homoepitaxial growth of aluminum nitride (AlN) on native seed substrates is the formation of an aluminum oxynitride (AlON) layer at temperatures between 1850-1950 C leading to polycrystalline growth. On the contrary, heteroepitaxial growth of AlN on silicon carbide (SiC) is relatively easy to achieve due to natural formation of a thin molten layer of (Al{sub 2}OC{sub x}) on the seed surface and consequent growth of AlN via the molten buffer layer. Optimization of the seeding process can be achieved by use of ultra-pure starting material. Another critical issue of AlN growth on SiC is cracking of the grown layer upon cooling as a result of different thermal expansion coefficients. (copyright 2006 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  7. Corruption and economic growth with non constant labor force growth

    Science.gov (United States)

    Brianzoni, Serena; Campisi, Giovanni; Russo, Alberto

    2018-05-01

    Based on Brianzoni et al. [1] in the present work we propose an economic model regarding the relationship between corruption in public procurement and economic growth. We extend the benchmark model by introducing endogenous labor force growth, described by the logistic equation. The results of previous studies, as Del Monte and Papagni [2] and Mauro [3], show that countries are stuck in one of the two equilibria (high corruption and low economic growth or low corruption and high economic growth). Brianzoni et al. [1] prove the existence of a further steady state characterized by intermediate levels of capital per capita and corruption. Our aim is to investigate the effects of the endogenous growth around such equilibrium. Moreover, due to the high number of parameters of the model, specific attention is given to the numerical simulations which highlight new policy measures that can be adopted by the government to fight corruption.

  8. Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness.

    Science.gov (United States)

    Nakagawa, S; Pawelek, P; Grinnell, F

    1989-06-01

    To learn more about the relationship between extracellular matrix organization, cell shape, and cell growth control, we studied DNA synthesis by fibroblasts in collagen gels that were either attached to culture dishes or floating in culture medium during gel contraction. After 4 days of contraction, the collagen density (initially 1.5 mg/ml) reached 22 mg/ml in attached gels and 55 mg/ml in floating gels. After contraction, attached collagen gels were well organized; collagen fibrils were aligned in the plane of cell spreading; and fibroblasts had an elongated, bipolar morphology. Floating collagen gels, however, were unorganized; collagen fibrils were arranged randomly; and fibroblasts had a stellate morphology. DNA synthesis by fibroblasts in contracted collagen gels was suppressed if the gels were floating in medium but not if the gels were attached, and inhibition was independent of the extent of gel contraction. Therefore, growth of fibroblasts in contracted collagen gels could be regulated by differences in extracellular matrix organization and cell shape independently of extracellular matrix density. We also compared the responses of fibroblasts in contracted collagen gels and monolayer culture to peptide growth factors including fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, and interleukin 1. Cells in floating collagen gels were generally unresponsive to any of the growth factors. Cells in attached collagen gels and monolayer culture were affected similarly by fibroblast growth factor but not by the others. Our results indicate that extracellular matrix organization influenced not only cell growth, but also fibroblast responsiveness to peptide growth factors.

  9. Growth at adolescence. Clinical correlates.

    Science.gov (United States)

    Daniel, W A

    1985-03-01

    Several highly significant changes occur within a relatively short period of time during adolescence. Great alteration in physique, developmental progress in thinking, and psychologic gains toward attaining ego identity take place but not always synchronously. Attention is paid to physical changes because they are visible and are of intense concern to adolescents, but physicians and other professionals should remember cognitive and psychosocial growth are affected by physical growth, and vice versa. Often there is a temporary disequilibrium in the relationship of these three areas of growth, and this can affect one or another part of the developmental pattern. It is therefore necessary to remind ourselves of the diversity of adolescent growth, and of adolescents, when caring for a young patient and be cognizant of growth in areas other than physical. More and more children with congenital or acquired handicaps are living to become adolescents and perhaps adults. Handicaps can be limited to one of the three major areas of growth or involve them all in varying degrees. For example, sickle cell disease, Crohn's disease, or ulcerative colitis may postpone physical growth for a significant period; this lack of pubertal change can affect psychosocial development but usually does not impair cognitive growth. Mental retardation may have no apparent effect on physical growth but can handicap the adolescent's psychosocial development. Growth still occurs in a sequential pattern but often it seems that handicapped youngsters reach a developmental milestone by a series of "detours." Physicians must recognize these lags or differences and try to facilitate progress, promote self-esteem, and provide understanding. Much can be done with anticipatory guidance. Adolescence often provides the opportunity to overcome past damage or, in some instances, to start anew on a more optimal program for physical and psychosocial growth. Young adolescent boys and girls usually look to the

  10. Nutritional catch-up growth.

    Science.gov (United States)

    Gat-Yablonski, Galia; Pando, Rakefet; Phillip, Moshe

    2013-01-01

    Malnutrition, marked by variant nutrient deficiencies, is considered a leading cause of stunted growth worldwide. In developing countries, malnutrition is caused mainly by food shortage and infectious diseases. Malnutrition may also be found in the developed world, where it is due mostly to prematurity, chronic diseases, and anorexia nervosa. In most cases, when food consumption is corrected, spontaneous catch-up (CU) growth occurs. However, CU growth is not always complete, leading to growth deficits. Therefore, it is important to understand the mechanisms that govern this process. Using a rat model of food restriction followed by refeeding, we established a nutrition-induced CU growth model. Levels of leptin and insulin-like growth factor-1 were found to significantly decrease when food was restricted and to increase already 1 day after refeeding. Gene expression analysis of the growth plate revealed that food restriction specifically affects transcription factors such as the hypoxia inducible factor-1 and its downstream targets on the one hand, and global gene expression, indicating epigenetic regulation, on the other. Food restriction also reduced the level of several microRNAs, including the chondrocyte-specific miR-140, which led to an increase in its target, SIRT1, a class III histone deacetylase. These findings may explain the global changes in gene expression observed under nutritional manipulation. We suggest that multiple levels of regulation, including transcription factors, epigenetic mechanisms, and microRNAs respond to nutritional cues and offer a possible explanation for some of the effects of food restriction on epiphyseal growth plate growth. The means whereby these components sense changes in nutritional status are still unknown. Deciphering the role of epigenetic regulation in growth may pave the way for the development of new treatments for children with growth disorders. Copyright © 2013 S. Karger AG, Basel.

  11. Helicobacter pylori VacA enhances prostaglandin E2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells

    DEFF Research Database (Denmark)

    Hisatsune, Junzo; Yamasaki, Eiki; Nakayama, Masaaki

    2007-01-01

    of a COX-2 promoter reporter gene and activated a COX-2 promoter containing mutated NF-kappaB or NF-interleukin-6 sites but not a mutated cis-acting replication element (CRE) site, suggesting direct involvement of the activating transcription factor 2 (ATF-2)/CREB-binding region in VacA-induced COX-2...... to activation of the CRE site in the COX-2 promoter....

  12. Entrepreneurship Education and Economic Growth

    DEFF Research Database (Denmark)

    Pedersen, Jonna; Lindquist, Carl Rickard

    . This paper addresses the presumptions behind the project. The presumptions in relation to entrepreneurship demonstrate that the effort should target both growth entrepreneurs and SMEs in a wide sense; there is a need for growth entrepreneurs with ambitions to generate breakthrough innovation as well...

  13. Ecological economics and economic growth.

    Science.gov (United States)

    Victor, Peter A

    2010-01-01

    Boulding's 1966 paper on the economics of spaceship Earth established the framework for ecological economics and an understanding of economic growth. In ecological economics, economies are conceptualized as open subsystems of the closed biosphere and are subject to biophysical laws and constraints. Economic growth measured as an increase in real gross domestic product (GDP) has generally been associated with increases in the use of energy and materials and the generation of wastes. Scale, composition, and technology are the proximate determinants of environmental impacts. They are often reduced to two: scale (GDP) and intensity (impact per unit GDP). New work described in this paper defines "green" growth as intensity that declines faster than scale increases. Similarly, "brown" growth occurs when intensity declines more slowly than increases in scale, and "black" growth happens when both scale and intensity increase. These concepts are then related to the environmental Kuznets curve, which can be understood as a transition from brown to green growth. Ecological economics provides a macroperspective on economic growth. It offers broad policy principles, and it challenges the primacy of economic growth as a policy objective, but many important questions remain.

  14. Technical Education and Economic Growth

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Technical Education and Economic Growth. Technical Education and Economic Growth. Review of the Present Status. Expanding no.s and impairment of quality; Faculty shortage; Grim situation at Masters and PhD levels; Regional imbalance; Absence of International flavour ...

  15. Chemical Control of Plant Growth.

    Science.gov (United States)

    Agricultural Research Center (USDA), Beltsville, MD.

    Seven experiments are presented in this Science Study Aid to help students investigate the control of plant growth with chemicals. Plant growth regulators, weed control, and chemical pruning are the topics studied in the experiments which are based on investigations that have been and are being conducted at the U. S. Agricultural Research Center,…

  16. Growth curves for Laron syndrome.

    Science.gov (United States)

    Laron, Z; Lilos, P; Klinger, B

    1993-01-01

    Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14 girls) of the 41 patients with this syndrome investigated in our clinic. Growth retardation was already noted at birth, the birth length ranging from 42 to 46 cm in the 12/20 available measurements. The postnatal growth curves deviated sharply from the normal from infancy on. Both sexes showed no clear pubertal spurt. Girls completed their growth between the age of 16-19 years to a final mean (SD) height of 119 (8.5) cm whereas the boys continued growing beyond the age of 20 years, achieving a final height of 124 (8.5) cm. At all ages the upper to lower body segment ratio was more than 2 SD above the normal mean. These growth curves constitute a model not only for primary, hereditary insulin-like growth factor-I (IGF-I) deficiency (Laron syndrome) but also for untreated secondary IGF-I deficiencies such as growth hormone gene deletion and idiopathic congenital isolated growth hormone deficiency. They should also be useful in the follow up of children with Laron syndrome treated with biosynthetic recombinant IGF-I. PMID:8333769

  17. ICT, Innovation and Productivity Growth

    DEFF Research Database (Denmark)

    Fosse, Henrik; Jacobsen, Joannes; Sørensen, Anders

    This CEBR report presents new evidence which suggests that investments in Information and Communication Technology (ICT) further productivity growth in Danish firms by stimulating innovation activities.......This CEBR report presents new evidence which suggests that investments in Information and Communication Technology (ICT) further productivity growth in Danish firms by stimulating innovation activities....

  18. The Growth-Inequality Association:

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2008-01-01

    This note suggests that the association between income inequality and economic growth rates might arguably depend on the political ideology of incumbent governments. Estimates indicate that under leftwing governments, inequality is negatively associated with growth while the association is positive...... under rightwing governments. This may provide a qualification to recent studies of inequality....

  19. Forces Influencing Rural Community Growth.

    Science.gov (United States)

    Rainey, Kenneth D.

    The paper briefly focuses on two questions: Can the recent growth trend be expected to continue into the future? and What does this imply as far as public policy and programs are concerned? Statistics on growth in the seventies suggest three possibilities: a change in the functions of metropolitan and nonmetropolitan areas; the decline of the city…

  20. Mould growth on building materials

    DEFF Research Database (Denmark)

    Fog Nielsen, K.

    Mould growth in buildings is associated with adverse health effects among the occupants of the building. However actual growth only occurs in damp and water-damaged materials, and is an increasing problem in Denmark, due to less robust constructions, inadequate maintenance, and too little...

  1. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K W; Choe, K O; Park, C Y; Lee, H; Son, H Y; Huh, K B; Ryu, K J [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  2. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  3. Growth Hormone and Endocrinopathies

    International Nuclear Information System (INIS)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J.

    1979-01-01

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  4. Stochastic models for tumoral growth

    Science.gov (United States)

    Escudero, Carlos

    2006-02-01

    Strong experimental evidence has indicated that tumor growth belongs to the molecular beam epitaxy universality class. This type of growth is characterized by the constraint of cell proliferation to the tumor border and the surface diffusion of cells at the growing edge. Tumor growth is thus conceived as a competition for space between the tumor and the host, and cell diffusion at the tumor border is an optimal strategy adopted for minimizing the pressure and helping tumor development. Two stochastic partial differential equations are reported in this paper in order to correctly model the physical properties of tumoral growth in (1+1) and (2+1) dimensions. The advantage of these models is that they reproduce the correct geometry of the tumor and are defined in terms of polar variables. An analysis of these models allows us to quantitatively estimate the response of the tumor to an unfavorable perturbation during growth.

  5. Dietary arginine and linear growth

    DEFF Research Database (Denmark)

    van Vught, Anneke J A H; Dagnelie, Pieter C; Arts, Ilja C W

    2013-01-01

    Child Intervention Study during 2001-2 (baseline), and at 3-year and 7-year follow-up, were used. Arginine intake was estimated via a 7 d precoded food diary at baseline and 3-year follow-up. Data were analysed in a multilevel structure in which children were embedded within schools. Random intercept......The amino acid arginine is a well-known growth hormone (GH) stimulator and GH is an important modulator of linear growth. The aim of the present study was to investigate the effect of dietary arginine on growth velocity in children between 7 and 13 years of age. Data from the Copenhagen School...... and slopes were defined to estimate the association between arginine intake and growth velocity, including the following covariates: sex; age; baseline height; energy intake; puberty stage at 7-year follow-up and intervention/control group. The association between arginine intake and growth velocity...

  6. A nonpeptidyl growth hormone secretagogue.

    Science.gov (United States)

    Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

    1993-06-11

    A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

  7. Population growth, poverty and health.

    Science.gov (United States)

    Kibirige, J S

    1997-07-01

    One of the most popular explanations for the many problems that face Africa is population growth. Africa's population has doubled since 1960. Africa has the highest fertility rate in the world and the rate of population growth is higher than in any other region. At the same time, Africa faces a social and economic situation that is viewed by many as alarming. Among the problems that devastate Africa is that of persistent poor health. Africa has lower life expectancy, higher mortality rates and is affected by more disease and illness conditions than any other region. Focusing on sub-Saharan Africa, this paper examines the relationship between population growth, poverty and poor health. While most analyses have focused on population growth as an original cause of poverty and underdevelopment, this paper argues that while both population growth and poor health play a significant role in exacerbating the problem of poverty, they are themselves primary consequences of poverty rather than its cause.

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

    Directory of Open Access Journals (Sweden)

    Anirene G T Pereira

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

  9. Growth morphologies of crystal surfaces

    Science.gov (United States)

    Xiao, Rong-Fu; Alexander, J. Iwan D.; Rosenberger, Franz

    1991-03-01

    We have expanded our earlier Monte Carlo model [Phys. Rev. A 38, 2447 (1988); J. Crystal Growth 100, 313 (1990)] to three dimensions and included reevaporation after accommodation and growth on dislocation-induced steps. We found again that, for a given set of growth parameters, the critical size, beyond which a crystal cannot retain its macroscopically faceted shape, scales linearly with the mean free path in the vapor. However, the three-dimensional (3D) the systems show increased shape stability compared to corresponding 2D cases. Extrapolation of the model results to mean-free-path conditions used in morphological stability experiments leads to order-of-magnitude agreement of the predicted critical size with experimental findings. The stability region for macroscopically smooth (faceted) surfaces in the parameter space of temperature and supersaturation depends on both the surface and bulk diffusion. While surface diffusion is seen to smooth the growth morphology on the scale of the surface diffusion length, bulk diffusion is always destabilizing. The atomic surface roughness increases with increase in growth temperature and supersaturation. That is, the tendency of surface kinetics anisotropies to stabilize the growth shape is reduced through thermal and kinetic roughening. It is also found that the solid-on-solid assumption, which can be advantageously used at low temperatures and supersaturations, is insufficient to describe the growth dynamics of atomically rough interfaces where bulk diffusion governs the process. For surfaces with an emerging screw dislocation, we find that the spiral growth mechanism dominates at low temperatures and supersaturations. The polygonization of a growth spiral decreases with increasing temperature or supersaturation. When the mean free path in the nutrient is comparable to the lattice constant, the combined effect of bulk and surface diffusion reduces the terrace width of a growth spiral in its center region. At elevated

  10. Growth of maize coleoptiles in the presence of natural and synthetic growth regulators. Growth correlations

    Directory of Open Access Journals (Sweden)

    Ewa Raczek

    2014-01-01

    Full Text Available The effect of natural (IAA, FC, ABA and synthetic (2,4-D growth substances on the increase of the fresh weight of maize coleoptile segments and change of the pH of the incubation medium, accepted here as criteria of maize coleoptile growth, was studied. The growth of maize coleoptiles depended on the concentration of the growth substances, as well as, on the composition of the incubation medium. The highest stimulation of coleoptile growth was seen with FC at a concentration of 10-4M, whereas ABA at 10-3 M gave the highest inhibition of maize coleoptile fresh weight increase and caused alkalization of the medium. The presence of K+ ions in the incubation medium enhanced the stimulatory effect of IAA and FC on the increase of the coleoptile fresh weight, whereas the presence of these ions and phosphate buffer abolished the growth-promoting effect of IAA and FC. The best correlation of the "fresh weight" and "pH" effects was found in the case of the growth of maize coleoptiles in the presence of FC (rxy = 0.67. The inhibition of maize coleoptile growth in the presence of high concentrations of IAA can be explained by the destructive effect of natural auxin at these concentrations on the integrity of mitochondrial membranes, and therefore on the normal functioning of mitochondria.

  11. l-2-Oxothiazolidine-4-Carboxylic Acid or α-Lipoic Acid Attenuates Airway Remodeling: Involvement of Nuclear Factor-κB (NF-κB, Nuclear Factor Erythroid 2p45-Related Factor-2 (Nrf2, and Hypoxia-Inducible Factor (HIF

    Directory of Open Access Journals (Sweden)

    Heung Bum Lee

    2012-06-01

    Full Text Available Reactive oxygen species (ROS play a crucial role in the pathogenesis of acute and chronic respiratory diseases. Antioxidants have been found to ameliorate airway inflammation and hyperresponsiveness in animal models employing short-term exposure to allergen. However, little data are available on the effect of antioxidants on airway remodeling and signaling pathways in chronic asthma. In the present study, we used a long-term exposure murine model of allergic airway disease to evaluate the effects of an antioxidant, l-2-oxothiazolidine-4-carboxylic acid (OTC or α-lipoic acid (LA on airway remodeling, focusing on the ROS-related hypoxia-inducible signaling. Long-term challenge of ovalbumin (OVA increased ROS production, airway inflammation, and airway hyperresponsiveness, and developed features of airway remodeling such as excessive mucus secretion, subepithelial fibrosis, and thickening of the peribronchial smooth muscle layer. Administration of OTC or LA reduced these features of asthma, including airway remodeling, which was accompanied by suppression of transforming growth factor-β1, vascular endothelial growth factor, and T-helper 2 cytokines. In addition, OVA-induced activation of nuclear factor-κB (NF-κB, nuclear factor erythroid 2p45-related factor-2 (Nrf2, hypoxia-inducible factor (HIF-1α, and HIF-2α was reduced by OTC or LA. Our results also showed that OTC or LA down-regulated phosphoinositide 3-kinase activity and decreased phosphorylation of p38 mitogen-activated protein kinase but not extracellular signal-regulated kinase 1/2 or c-Jun N-terminal kinase. These findings demonstrate that OTC and LA can inhibit activation of NF-κB, Nrf2, and HIF, leading to attenuate allergen-induced airway remodeling.

  12. The relative value of growth.

    Science.gov (United States)

    Mass, Nathaniel J

    2005-04-01

    Most executives would say that adding a point of growth and gaining a point of operating-profit margin contribute about equally to shareholder value. Margin improvements hit the bottom line immediately, while growth compounds value over time. But the reality is that the two are rarely equivalent. Growth often is far more valuable than managers think. For some companies, convincing the market that they can grow by just one additional percentage point can be worth six, seven, or even ten points of margin improvement. This article presents a new strategic metric, called the relative value of growth (RVG), which gives managers a clear picture of how growth projects and margin improvement initiatives affect shareholder value. Using basic balance sheet and income sheet data, managers can determine their companies' RVGs, as well as those of their competitors. Calculating RVGs gives managers insights into which corporate strategies are working to deliver value and whether their companies are pulling the most powerful value-creation levers. The author examines a number of well-known companies and explains what their RVG numbers say about their strategies. He reviews the unspoken assumption that growth and profits are incompatible over the long term and shows that a fair number of companies are effective at delivering both. Finally, he explains how managers can use the RVG framework to help them define strategies that balance growth and profitability at both the corporate and business unit levels.

  13. Sociological explanations of economic growth.

    Science.gov (United States)

    Marsh, R M

    1988-01-01

    Even if questions of how resources are distributed within and between societies are the main concern, it is necessary to continue to grapple with the issue of the causes of economic growth since economic growth and level of development continue to be among the most important causes of inequality, poverty, unemployment, and the quality of life. This paper's dependent variable is the economic growth rate of 55 less developed countries (LDCs) over 2 time periods. 1970-78 and 1965-84. The causal model consists of control variables--level of development and domestic investment in 1965--and a variety of independent variables drawn from major sociological theories of economic growth published during the last 3 decades. Multiple regression analysis shows that, net of the effects of the 2 control variables, the variables which have the strongest effect on economic growth are: 1) direct foreign investment, which has a negative effect, 2) the proportion of the population in military service, and 3) the primary school enrollment ratio, both of which have positive effects on economic growth. On the other hand, variables drawn from some theories receive no empirical support. The mass media of communications, ethnolinguistic heterogeneity, democracy and human rights, income inequality, and state-centric theory's key variable, state strength, all fail to show any significant impact on economic growth rates when the control variables and the significant independent variables are held constant. The theoretical implications of these findings are discussed.

  14. Growth factors and new periodontology

    Directory of Open Access Journals (Sweden)

    Paknejad M

    1999-06-01

    Full Text Available Growth factors are biological mediators that have a key roll in proliferation, chemotaxy and"ndifferentiation by acting on specific receptors on the surface of cells and regulating events in wound"nhealing.They can be considered hormones that are not released in to the blood stream but have one a"nlocal action. Some of these factors can regulate premature change in GO to Gl phase in cell devesion"ncycle and even may stimulate synthesis of DNA in suitable cells, Growth substances, primarily secreted"nby fibroblasts, endothelia! cells, macrophages and platelet, include platelet derived growth factor"n(PDGF, insulin like growth factor (IGF transforming growth factor (TGFa and (3 and bone"nmorphogenetic proteins BMPs that approximately are the most important of them. (BMPs could be"nused to control events during periodontal, craniofacial and implant wound healing through favoring bone"nformation"nAccording toLynch, combination of PGDF and IGF1 would be effective in promoting growth of all the"ncomponents of the periodontium."nThe aim of this study was to characterize growth factor and review the literature to determine the"nmechanism of their function, classification and application in implant and periodontal treatment.

  15. Pro Poor Growth in Cameroon

    Directory of Open Access Journals (Sweden)

    Samuel Fambon

    2017-06-01

    Full Text Available The purpose of this paper is to analyze the relationship between economic growth, poverty and income distribution in Cameroon, using both the data derived from three Cameroonian household surveys and the Poverty Equivalent Growth Rate (PEGR methodology developed by Kakwani et al. (2004, The study found that economic growth in Cameroon was pro poor over the period 1996–2007, which suggests that instead of increasing the economic growth rate alone, the poverty equivalent growth rate should also be maximized to achieve the poverty reduction objective, meaning that on the one hand, the growth rate should be boosted, and on the other, the distribution of income should also be concurrently improved. A decomposition of changes in poverty using the Kakwani (1997 approach reveal that the growth component dominates the redistribution component in the reduction of poverty. This suggests that the fall in absolute poverty over the survey period may be attributed to an increase in average household income, and not to the redistributive policies of the government.

  16. Towards Sustainable Growth Business Models

    Energy Technology Data Exchange (ETDEWEB)

    Kamp-Roelands, N.; Balkenende, J.P.; Van Ommen, P.

    2012-03-15

    The Dutch Sustainable Growth Coalition (DSGC) has the following objectives: The DSGC aims to pro-actively drive sustainable growth business models along three lines: (1) Shape. DSGC member companies aim to connect economic profitability with environmental and social progress on the basis of integrated sustainable growth business models; (2) Share. DSGC member companies aim for joint advocacy of sustainable growth business models both internationally and nationally; and (3) Stimulate. DSGC member companies aim to stimulate and influence the policy debate on enabling sustainable growth - with a view to finding solutions to the environmental and social challenges we are facing. This is their first report. The vision, actions and mission of DSGC are documented in the Manifesto in Chapter 2 of this publication. Chapter 3 contains an overview of key features of an integrated sustainable growth business model and the roadmap towards such a model. In Chapter 4, project examples of DSGC members are presented, providing insight into the hands-on reality of implementing the good practices. Chapter 5 offers an overview of how the Netherlands provides an enabling environment for sustainable growth business models. Chapter 6 offers the key conclusions.

  17. Growth Data - Characterization of Sexual Growth Dimorphism in Sablefish

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Sexual growth dimorphism (SGD) is a common phenomenon in nature. Numerous marine fishes exhibit SGD, with females often growing faster and attaining larger sizes...

  18. Methods for transforming and expression screening of filamentous fungal cells with a DNA library

    Science.gov (United States)

    Teter, Sarah; Lamsa, Michael; Cherry, Joel; Ward, Connie

    2015-06-02

    The present invention relates to methods for expression screening of filamentous fungal transformants, comprising: (a) isolating single colony transformants of a DNA library introduced into E. coli; (b) preparing DNA from each of the single colony E. coli transformants; (c) introducing a sample of each of the DNA preparations of step (b) into separate suspensions of protoplasts of a filamentous fungus to obtain transformants thereof, wherein each transformant contains one or more copies of an individual polynucleotide from the DNA library; (d) growing the individual filamentous fungal transformants of step (c) on selective growth medium, thereby permitting growth of the filamentous fungal transformants, while suppressing growth of untransformed filamentous fungi; and (e) measuring activity or a property of each polypeptide encoded by the individual polynucleotides. The present invention also relates to isolated polynucleotides encoding polypeptides of interest obtained by such methods, to nucleic acid constructs, expression vectors, and recombinant host cells comprising the isolated polynucleotides, and to methods of producing the polypeptides encoded by the isolated polynucleotides.

  19. Mathematical analysis of a model for the growth of the bovine corpus luteum

    KAUST Repository

    Prokopiou, Sotiris A.

    2013-12-13

    The corpus luteum (CL) is an ovarian tissue that grows in the wound space created by follicular rupture. It produces the progesterone needed in the uterus to maintain pregnancy. Rapid growth of the CL and progesterone transport to the uterus require angiogenesis, the creation of new blood vessels from pre-existing ones, a process which is regulated by proteins that include fibroblast growth factor 2 (FGF2). In this paper we develop a system of time-dependent ordinary differential equations to model CL growth. The dependent variables represent FGF2, endothelial cells (ECs), luteal cells, and stromal cells (like pericytes), by assuming that the CL volume is a continuum of the three cell types. We assume that if the CL volume exceeds that of the ovulated follicle, then growth is inhibited. This threshold volume partitions the system dynamics into two regimes, so that the model may be classified as a Filippov (piecewise smooth) system. We show that normal CL growth requires an appropriate balance between the growth rates of luteal and stromal cells. We investigate how angiogenesis influences CL growth by considering how the system dynamics depend on the dimensionless EC proliferation rate, {Mathematical expression}. We find that weak (low {Mathematical expression}) or strong (high {Mathematical expression}) angiogenesis leads to \\'pathological\\' CL growth, since the loss of CL constituents compromises progesterone production or delivery. However, for intermediate values of {Mathematical expression}, normal CL growth is predicted. The implications of these results for cow fertility are also discussed. For example, inadequate angiogenesis has been linked to infertility in dairy cows. © 2013 Springer-Verlag Berlin Heidelberg.

  20. Juvenile eye growth, when completed?

    DEFF Research Database (Denmark)

    Fledelius, Hans C; Christensen, Anders S; Fledelius, Christian

    2014-01-01

    PURPOSE: To test Sorsby's classical statement of axial eye growth as completed at the age of 13 years, with a view also to differentiating between basic eye growth and juvenile elongation associated with eventual refractive change towards myopia. METHODS: (i) A total of 160 healthy eyes close...... about age 13 as general limit found support from the cross-sectional data, which suggested stable emmetropic eye size from about 11-12 years, with an average apparently outgrown male emmetropic value of 23.5 mm versus females' 22.9 mm. The longitudinal data, however, showed emmetropic growth also beyond...

  1. The biophysics of neuronal growth

    International Nuclear Information System (INIS)

    Franze, Kristian; Guck, Jochen

    2010-01-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  2. A Model of Controlled Growth

    Science.gov (United States)

    Bressan, Alberto; Lewicka, Marta

    2018-03-01

    We consider a free boundary problem for a system of PDEs, modeling the growth of a biological tissue. A morphogen, controlling volume growth, is produced by specific cells and then diffused and absorbed throughout the domain. The geometric shape of the growing tissue is determined by the instantaneous minimization of an elastic deformation energy, subject to a constraint on the volumetric growth. For an initial domain with C}^{2,α boundary, our main result establishes the local existence and uniqueness of a classical solution, up to a rigid motion.

  3. Imitation of radiation-induced damages to DNA with a radionuclide incorporated into polynucleotides

    International Nuclear Information System (INIS)

    Korolev, V.G.

    1984-01-01

    Because of a great variety and different reparability of radiation-induced DNA lesions it is difficult to evaluate the radiobiologacal significance of certain individual alterations. It is suggested that the radionuclides incorporated anto DNA can be used to imitate different types of radiation damages to DNA. Both qualitative and quantitative aspects of the problem are discussed

  4. Triple helical polynucleotidic structures: an FTIR study of the C+ .G. Ctriplet.

    Science.gov (United States)

    Akhebat, A; Dagneaux, C; Liquier, J; Taillandier, E

    1992-12-01

    Triple helixes containing one homopurine poly dG or poly rG strand and two homopyrimidine poly dC or poly rC strands have been prepared and studied by FTIR spectroscopy in H2O and D2O solutions. The spectra are discussed by comparison with those of the corresponding third strands (auto associated or not) and of double stranded poly dG.poly dC and poly rG.poly rC in the same concentration range and salt conditions. The triplex formation is characterized by the study of the base-base interactions reflected by changes in the spectral domain involving the in-plane double bond vibrations of the bases. Modifications of the initial duplex conformation (A family form for poly rG.poly rC, B family form for poly dG.poly dC) when the triplex is formed have been investigated. Two spectral domains (950-800 and 1450-1350 cm-1) containing absorption bands markers of the N and S type sugar geometries have been extensively studied. The spectra of the triplexes prepared starting with a double helix containing only riboses (poly rC+.poly rG.poly rC and poly dC+.poly rG.poly rC) as well as that of poly rC+.poly dG.poly dC present exclusively markers of the North type geometry of the sugars. On the contrary in the case of the poly dC+.poly dG.poly dC triplex both N and S type sugars are shown to coexist. The FTIR spectra allow us to propose that in this case the sugars of the purine (poly dG) strand adopt the S type geometry.

  5. [Reconstruction of long polynucleotide sequences from fragments using the Iskra-226 personal computer

    Science.gov (United States)

    Kostetskiĭ, P V; Dobrova, I E

    1988-04-01

    An algorithm for reconstructing long DNA sequences, i.e. arranging all overlapping gel readings in the contigs, and the corresponding BASIC programme for personal computer "Iskra-226" (USSR) are described. The contig construction begins with the search for all fragments overlapping the basic (longest) one follower by determination of coordinates of 5' ends of the overlapping fragments. Then the gel reading with minimal 5' end coordinate and the gel reading with maximal 3' end coordinate are selected and used as basic ones at the next assembly steps. The procedure is finished when no gel reading overlapping the basic one can be found. All gel readings entered the contig are ignored at the next steps of the assembly. Finally, one or several contigs consisted of DNA fragments are obtained. Effectiveness of the algorithm was tested on a model based on the multiple assembly of the nucleotide sequence, encoding the Na, K-ATPase alpha-subunit of pig kidney. The programme does not call for user's participation and can comprise contigs up to 10,000 nucleotides long.

  6. Polynucleotides. XXXII. Further studies on the synthesis of oligonucleotides containing 8,2'-S-cycloadenosine.

    Science.gov (United States)

    Ikehara, M; Tezuka, T

    1975-01-01

    A dinucleoside monophosphate, 8,2'-anhydro-8-mercapto-9-beta-D-arabinofuranosyladenine phosphoryl-(3'-5')-inosine (AspI) was synthesized by the condensation of protected 8-mercapto-adenosine 2',3'-cyclic phosphate and 2',3'-isopropylideneinosine with diphenylphosphorochloridate. 8-Mercaptoadenosine 2',3'-cyclic phosphate was polymerized by using tetraphenyl pyrophosphate as the condensing reagent. As oligonucleotides, thus obtained, contained some uncyclized 8-mercaptoadenosine residues and were cleaved at these sites with 0.3N KOH. As 5'-phosphate was synthesized and polymerized with DCC to give oligonucleotides with chain lengths 2 to 9. PMID:170595

  7. Epitaxial growth of hybrid nanostructures

    Science.gov (United States)

    Tan, Chaoliang; Chen, Junze; Wu, Xue-Jun; Zhang, Hua

    2018-02-01

    Hybrid nanostructures are a class of materials that are typically composed of two or more different components, in which each component has at least one dimension on the nanoscale. The rational design and controlled synthesis of hybrid nanostructures are of great importance in enabling the fine tuning of their properties and functions. Epitaxial growth is a promising approach to the controlled synthesis of hybrid nanostructures with desired structures, crystal phases, exposed facets and/or interfaces. This Review provides a critical summary of the state of the art in the field of epitaxial growth of hybrid nanostructures. We discuss the historical development, architectures and compositions, epitaxy methods, characterization techniques and advantages of epitaxial hybrid nanostructures. Finally, we provide insight into future research directions in this area, which include the epitaxial growth of hybrid nanostructures from a wider range of materials, the study of the underlying mechanism and determining the role of epitaxial growth in influencing the properties and application performance of hybrid nanostructures.

  8. VT Designated Growth Center Boundary

    Data.gov (United States)

    Vermont Center for Geographic Information — Growth centers aim to align public infrastructure and private building investments with a local framework of policies and regulations to ensure that 20 years of...

  9. Corruption, Growth, and Public Finances

    OpenAIRE

    Vito Tanzi; Hamid R Davoodi

    2000-01-01

    The paper discusses some channels through which corruption affects growth such as the impact of corruption on enterprises, on the allocation of talent, and on investment. It also discusses the impact of corruption on some aspects of public finance.

  10. The Market for Smart Growth

    Science.gov (United States)

    Based on several studies of market demand, the authors determined that consumer demand for smart growth would translate into more than 600,000 houses out of the approximately 2 million new housing units built in 2007.

  11. Your Baby's Growth: 5 Months

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Your Baby's Growth: 5 Months KidsHealth / For Parents / Your Baby's ... a cause for concern. How Much Will My Baby Grow? By 5 months, your baby's birth weight ...

  12. Investor Protections and Economic Growth

    OpenAIRE

    Haidar, Jamal Ibrahim

    2009-01-01

    Using objective measures of investor protections in 170 countries, I establish that the level of investor protection matters for cross-country differences in GDP growth: countries with stronger protections tend to grow faster than those with poor investor protections.

  13. Traffic fatalities and economic growth

    Science.gov (United States)

    2003-04-01

    As countries develop death rates usually fall, especially for diseases that affect the young and result in substantial life-years lost. Deaths due to traffic accidents are a notable exception: the growth in motor vehicles that accompanies economic gr...

  14. National Survey of Family Growth

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Survey of Family Growth (NSFG) gathers information on family life, marriage and divorce, pregnancy, infertility, use of contraception, and men's and...

  15. Limits to the growth debate

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, L.

    The first two major studies sponsored by the club of Rome were the report of the Meadows team at MIT, The Limits to Growth, published in 1972, and the Mesarovic and Pestel report, Mankind at the Turning Point, published in 1974. When the Club of Rome met in Philadelphia in April of 1976, its pronouncements reflected a frame of mind quite different from that of 1972. Recently, Herman Kahn and his colleagues at the Hudson Institute have published The Next 200 Years, a book evidently inspired as much by antagonism to the limits-to-growth school of thought as by affirmative faith in its own vision of technological optimism. The author discusses the content of the studies and summarizes his own position in four areas. (1) While no trend of growth of anything can continue indefinitely in the real world, there are not global physical limits to economic growth within a time frame susceptible to plausible foresight or relevant to policy making. (2) In some world regions, notably South Asia and tropical Africa, population growth rates do indeed threaten to create a kind of Malthusian trap, and the rapid reduction of fertility is critically important to their development prospects and urgent in time. (3) For other parts of the world, both rates and directions of growth will be more influenced by changes in preferences for consumption and in attitudes toward production than by physical constraints, although higher energy costs and environmental pressures will also be important influences in generating such changes in growth patterns. (4) Probable changes in directions of growth will generate new and important issues in international economic and political relations, with both dangers and opportunities for the evolving world order. (MCW)

  16. Military Expenditure, Threats, and Growth

    OpenAIRE

    Aizenman, Joshua; Glick, Reuven

    2003-01-01

    This paper clarifies one of the puzzling results of the economic growth literature: the impact of military expenditure is frequently found to be non-significant or negative, yet most countries spend a large fraction of their GDP on defense and the military. We start by empirical evaluation of the non- linear interactions between military expenditure, external threats, corruption, and other relevant controls. While growth falls with higher levels of military spending, given the values of the o...

  17. Retail payments and economic growth

    OpenAIRE

    Hasan, Iftekhar; De Renzis, Tania; Schmiedel , Heiko

    2012-01-01

    This paper examines the fundamental relationship between retail payments and overall economic growth. Using data from across 27 European markets over the period 1995–2009, the results confirm that migration to efficient electronic retail payments stimulates overall economic growth, consumption and trade. Among different payment instruments, this relationship is strongest for card payments, followed by credit transfers and direct debits. Cheque payments are found to have a relatively low macro...

  18. Growth, unemployment and wage inertia

    OpenAIRE

    Raurich, Xavier; Sorolla, Valeri

    2014-01-01

    We introduce wage setting via efficiency wages in the neoclassical one-sector growth model to study the growth effects of wage inertia. We compare the dynamic equilibrium of an economy with wage inertia with the equilibrium of an economy without wage inertia. We show that wage inertia affects the long run employment rate and that the transitional dynamics of the main economic variables will be different because wages are a state variable when wage inertia is introduced. In particular, we show...

  19. International Outsourcing and Productivity Growth

    OpenAIRE

    Martin Falk; Yvonne Wolfmayr

    2008-01-01

    This study investigates the impact of international outsourcing to low? and high income countries on total factor productivity growth based on manufacturing industry data for 14 OECD countries from 1995 ? 2000. We find that the broad measure of international outsourcing of material inputs to low income countries is significantly negatively related to productivity growth. Furthermore, while the narrow measure of international outsourcing of materials is not significant, purchased services from...

  20. Human Development and Economic Growth

    OpenAIRE

    Ranis, Gustav

    2004-01-01

    Recent literature has contrasted Human Development, described as the ultimate goal of the development process, with economic growth, described as an imperfect proxy for more general welfare, or as a means toward enhanced human development. This debate has broadened the definitions and goals of development but still needs to define the important interrelations between human development (HD) and economic growth (EG). To the extent that greater freedom and capabilities improve economic performan...

  1. [Saarland Growth Study: sampling design].

    Science.gov (United States)

    Danker-Hopfe, H; Zabransky, S

    2000-01-01

    The use of reference data to evaluate the physical development of children and adolescents is part of the daily routine in the paediatric ambulance. The construction of such reference data is based on the collection of extensive reference data. There are different kinds of reference data: cross sectional references, which are based on data collected from a big representative cross-sectional sample of the population, longitudinal references, which are based on follow-up surveys of usually smaller samples of individuals from birth to maturity, and mixed longitudinal references, which are a combination of longitudinal and cross-sectional reference data. The advantages and disadvantages of the different methods of data collection and the resulting reference data are discussed. The Saarland Growth Study was conducted for several reasons: growth processes are subject to secular changes, there are no specific reference data for children and adolescents from this part of the country and the growth charts in use in the paediatric praxis are possibly not appropriate any more. Therefore, the Saarland Growth Study served two purposes a) to create actual regional reference data and b) to create a database for future studies on secular trends in growth processes of children and adolescents from Saarland. The present contribution focusses on general remarks on the sampling design of (cross-sectional) growth surveys and its inferences for the design of the present study.

  2. Phenomenology of stochastic exponential growth

    Science.gov (United States)

    Pirjol, Dan; Jafarpour, Farshid; Iyer-Biswas, Srividya

    2017-06-01

    Stochastic exponential growth is observed in a variety of contexts, including molecular autocatalysis, nuclear fission, population growth, inflation of the universe, viral social media posts, and financial markets. Yet literature on modeling the phenomenology of these stochastic dynamics has predominantly focused on one model, geometric Brownian motion (GBM), which can be described as the solution of a Langevin equation with linear drift and linear multiplicative noise. Using recent experimental results on stochastic exponential growth of individual bacterial cell sizes, we motivate the need for a more general class of phenomenological models of stochastic exponential growth, which are consistent with the observation that the mean-rescaled distributions are approximately stationary at long times. We show that this behavior is not consistent with GBM, instead it is consistent with power-law multiplicative noise with positive fractional powers. Therefore, we consider this general class of phenomenological models for stochastic exponential growth, provide analytical solutions, and identify the important dimensionless combination of model parameters, which determines the shape of the mean-rescaled distribution. We also provide a prescription for robustly inferring model parameters from experimentally observed stochastic growth trajectories.

  3. Placental Adaptations in Growth Restriction

    Science.gov (United States)

    Zhang, Song; Regnault, Timothy R.H.; Barker, Paige L.; Botting, Kimberley J.; McMillen, Isabella C.; McMillan, Christine M.; Roberts, Claire T.; Morrison, Janna L.

    2015-01-01

    The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions. PMID:25580812

  4. Anticavitation and Differential Growth in Elastic Shells

    KAUST Repository

    Moulton, Derek E.; Goriely, Alain

    2010-01-01

    infinite growth or resorption is imposed at the inner surface of the shell. However, void collapse can occur in a limiting sense when radial and circumferential growth are properly balanced. Growth functions which diverge or vanish at a point arise

  5. Economic growth and gender equality | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    And conversely, does gender equality impact economic growth? ... change and growth in the economy on women's employment opportunities and the type ... sectors and their overall effect on development outcomes, such as economic growth ...

  6. Student Augmentation for Crystal Growth Research

    National Research Council Canada - National Science Library

    Prasad, V

    1999-01-01

    ... intelligent modeling, design and control of crystal growth processes. One doctoral student worked on integrating the radiation heat transfer model into MASTRAPP, the crystal growth model developed by the Consortium for Crystal Growth Research...

  7. Best practices for rural smart growth.

    Science.gov (United States)

    2010-07-01

    Smart growth is a development strategy that encompasses economic, environmental and social objectives to manage : the growth of a community. The basic principles of smart growth are to: : Mix land uses. : Take advantage of compact building de...

  8. Growth and Economic Opportunities for Women: Strengthening ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Asian outlook: New growth dependent on new productivity. There is no doubt that Canada is tying its future growth prospects to Asia. View moreAsian outlook: New growth dependent on new productivity ...

  9. Understanding "Inclusive Growth": Advancing the global agenda ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2013-03-27

    Mar 27, 2013 ... Increasingly, the concept of "inclusive growth," where the benefits of economic growth are ... Growth is less likely to be sustainable with high and/or growing inequalities, and ... A global vision for small business in Egypt.

  10. Nutritionally-Induced Catch-Up Growth

    Directory of Open Access Journals (Sweden)

    Galia Gat-Yablonski

    2015-01-01

    Full Text Available Malnutrition is considered a leading cause of growth attenuation in children. When food is replenished, spontaneous catch-up (CU growth usually occurs, bringing the child back to its original growth trajectory. However, in some cases, the CU growth is not complete, leading to a permanent growth deficit. This review summarizes our current knowledge regarding the mechanism regulating nutrition and growth, including systemic factors, such as insulin, growth hormone, insulin- like growth factor-1, vitamin D, fibroblast growth factor-21, etc., and local mechanisms, including autophagy, as well as regulators of transcription, protein synthesis, miRNAs and epigenetics. Studying the molecular mechanisms regulating CU growth may lead to the establishment of better nutritional and therapeutic regimens for more effective CU growth in children with malnutrition and growth abnormalities. It will be fascinating to follow this research in the coming years and to translate the knowledge gained to clinical benefit.

  11. Determinants of economic growth in BRIC countries

    OpenAIRE

    Rajjev K. Goel

    2011-01-01

    We study economic growth in four emerging economies - Brazil, Russia, India, and China (BRIC). Questions addressed are: (a) How do medium term growth determinants differ from short term determinants? (b) What are differences between growth effects of aggregate versus disaggregated exports? And (c) Does lower institutional quality hinder growth? Results show that while BRIC nations have higher growth, there are significant within-group differences. China and Russia mostly showed higher growth,...

  12. Stem secondary growth of tundra shrubs

    DEFF Research Database (Denmark)

    Campioli, Matteo; Leblans, Niki; Michelsen, Anders

    2012-01-01

    Our knowledge of stem secondary growth of arctic shrubs (a key component of tundra net primary production, NPP) is very limited. Here, we investigated the impact of the physical elements of the environment on shrub secondary growth by comparing annual growth rates of model species from similar...... growth (stem apical growth, stem length, and apical growth of stem plus leaves), in some cases even with opposite responses. Thus caution should be taken when estimating the impact of the environment on shrub growth from apical growth only. Integration of our data set with the (very limited) previously...

  13. Growth and Predictors of Growth Restraint in Moderately Preterm Children Aged 0 to 4 Years

    NARCIS (Netherlands)

    Bocca-Tjeertes, I.F.; Kerstjens, J.M.; Reijneveld, S.A.; de Winter, A.F.; Bos, A.F.

    2011-01-01

    OBJECTIVE: To describe growth in moderately preterm-born children, determine the prevalence of growth restraint at the age of 4, and identify predictors of growth restraint. We hypothesized that growth in moderately preterm-born children differs from growth in term-born children and that growth

  14. Green growth in the Netherlands

    International Nuclear Information System (INIS)

    Balde, K.; Boelens, A.; Brinksma, E.; Edens, B.; Hiethaar, S.; Klein, P.; Schenau, S.

    2011-04-01

    In 2009 the Ministerial Council Meeting of the Organisation for Economic Co-operation and Development (OECD) committed itself to a green growth strategy. Such a strategy fosters economic growth and development while ensuring that natural resources can continue to provide the ecosystem services on which our well-being relies. It also endorses investment, competition and innovation which will underpin sustained growth and give rise to new economic opportunities. Green growth provides both a policy strategy for implementing this economic transformation and a monitoring framework with a proposed set of indicators. This report presents an overview of the state of green growth in the Netherlands. It should be regarded as a benchmark for a more thorough and comprehensive assessment of green growth in the future. It is based on the set of indicators proposed by the OECD in their intermediate report of February 2011. Data relevant to the Dutch situation are presented for twenty of these indicators, illustrating the observed trends. The indicators are grouped in four themes. For the first theme, environmental efficiency of production, on the whole the indicators show increased efficiency. However, indicators such as greenhouse gas intensity, energy efficiency and material intensity show only relative decoupling, which on its own is not enough to ensure green growth. In addition, the increase in environmental efficiency is partly explained by substitution of imports for domestic production, which is not conducive to green growth on a global scale: the efficiency gains in domestic production, for example, are offset by increases in foreign greenhouse gas emissions. Water use and agricultural nutrient surpluses are the only indicators where absolute decoupling has occurred. The second theme contains indicators regarding the natural assets base. This group of indicators provides a mixed picture. Natural gas reserves are decreasing and the overall level of threat to animal

  15. Phytochrome, plant growth and flowering

    Science.gov (United States)

    King, R. W.; Bagnall, D. J.

    1994-01-01

    Attempts to use artificially lit cabinets to grow plants identical to those growing in sunlight have provided compelling evidence of the importance of light quality for plant growth. Changing the balance of red (R) to far-red (FR) radiation, but with a fixed photosynthetic input can shift the phytochrome photoequilibrium in a plant and generate large differences in plant growth. With FR enrichment the plants elongate, and may produce more leaf area and dry matter. Similar morphogenic responses are also obtained when light quality is altered only briefly (15-30 min) at the end-of-the-day. Conversely, for plants grown in natural conditions the response of plant form to selective spectral filtering has again shown that red and far-red wavebands are important as found by Kasperbauer and coworkers. Also, where photosynthetic photon flux densities (PPFD) of sunlight have been held constant, the removal of far-red alone alters plant growth. With FR depletion plants grown in sunlight are small, more branched and darker green. Here we examine the implications for plant growth and flowering when the far-red composition of incident radiation in plant growth chambers is manipulated.

  16. Universality in stochastic exponential growth.

    Science.gov (United States)

    Iyer-Biswas, Srividya; Crooks, Gavin E; Scherer, Norbert F; Dinner, Aaron R

    2014-07-11

    Recent imaging data for single bacterial cells reveal that their mean sizes grow exponentially in time and that their size distributions collapse to a single curve when rescaled by their means. An analogous result holds for the division-time distributions. A model is needed to delineate the minimal requirements for these scaling behaviors. We formulate a microscopic theory of stochastic exponential growth as a Master Equation that accounts for these observations, in contrast to existing quantitative models of stochastic exponential growth (e.g., the Black-Scholes equation or geometric Brownian motion). Our model, the stochastic Hinshelwood cycle (SHC), is an autocatalytic reaction cycle in which each molecular species catalyzes the production of the next. By finding exact analytical solutions to the SHC and the corresponding first passage time problem, we uncover universal signatures of fluctuations in exponential growth and division. The model makes minimal assumptions, and we describe how more complex reaction networks can reduce to such a cycle. We thus expect similar scalings to be discovered in stochastic processes resulting in exponential growth that appear in diverse contexts such as cosmology, finance, technology, and population growth.

  17. Phytochrome, plant growth and flowering

    Energy Technology Data Exchange (ETDEWEB)

    King, R.W.; Bagnall, D.J. [CSIRO, Canberra (Australia)

    1994-12-31

    Attempts to use artificially lit cabinets to grow plants identical to those growing in sunlight have provided compelling evidence of the importance of light quality for plant growth. Changing the balance of red (R) to far-red (FR) radiation, but with a fixed photosynthetic input can shift the phytochrome photoequilibrium in a plant and generate large differences in plant growth. With FR enrichment the plants elongate, and may produce more leaf area and dry matter. Similar morphogenic responses are also obtained when light quality is altered only briefly (15-30 min) at the end-of-the-day. Conversely, for plants grown in natural conditions the response of plant form to selective spectral filtering has again shown that red and far-red wavebands are important as found by Kasperbauer and coworkers. Also, where photosynthetic photon flux densities (PPFD) of sunlight have been held constant, the removal of far-red alone alters plant growth. As shown for chrysanthemum, with FR depletion plants grown in sunlight are small, more branched and darker green. We examine the implications for plant growth and flowering when the far-red composition of incident radiation in plant growth chambers is manipulated.

  18. American growth and Napoleonic Wars

    Directory of Open Access Journals (Sweden)

    Vergil Hasan

    2013-01-01

    Full Text Available Four years after the French Revolution, in 1793 a series of wars among France and other major powers of Europe began and they lasted until 1815. There is disagreement among economic historians about the effects of these wars on the trend of US economic growth. This paper aims to answer the following question. Did America as a neutral nation take advantage of economic possibilities caused by Europe at war through trade? To put it differently, this paper questions whether there was an export-led growth due to the war. To answer this question, we re-examined the export-led growth hypothesis for the period 1790-1860 using the ARDL methodology. Based on this methodology, a cointegrated relationship is found among the variables of real GDP, labor, exports and exchange rates. The results suggest that the economic growth of the US was not export-driven. In addition, parallel to the results of unit root tests with structural breaks, the coefficient of the dummy variable was statistically significant in the long run, implying that the war did have a significant effect on the economic growth trend of the US.

  19. SME Cooperation on Innovation & Growth

    DEFF Research Database (Denmark)

    Brink, Tove; Neville, Mette

    2016-01-01

    The research in this paper reveals how cooperation of SMEs can enable innovation and growth. The research is conducted in a four-year period with 24 SMEs participating from different industry branches. The research is now in the late part of the 3rd. year starting in 2013 and finished January 2017....... Preliminary findings are revealed here and discussed with the SMEs. Shorter-term cooperation and especially longer-term collaboration is important for SMEs to enable innovation and growth. The content of collaboration is based on the cross-disciplinary trinity of organisational- and managerial development......, business model development and financial development. The trinity requires time to get the specific insight on application for each SME. An enhanced contribution is made to the field of SMEs, to academia and to public bodies to understand the needed initiatives to support SMEs for innovation and growth...

  20. Filamentous Growth in Eremothecium Fungi

    DEFF Research Database (Denmark)

    Oskarsson, Therese

    , this thesis deals with some of the aspects of hyphal growth, which is an important virulence factor for pathogenic fungi infecting both humans and plants. Hyphal establishment through continuous polar growth is a complex process, requiring the careful coordination of a large subset of proteins involved......-regulatory activity of AgGts1, the protein could have additional actin organizing properties. In the second and third part, this thesis addresses the use of A. gossypii and its relative E. cymbalariae as model organisms for filamentous growth. A series of assays analyzed the capability of Eremothecium genus fungi...... of molecular tools for E. cymbalariae to enable a faster and more efficient approach for genetic comparisons between Eremothecium genus fungi....

  1. Energy consumption and economic growth

    Energy Technology Data Exchange (ETDEWEB)

    Brookes, L G

    1972-10-01

    A mathematical model relating Gross National Product (GNP) per capita to useful energy consumed per capita is demonstrated to predict the shift in this relationship actually experienced in the U.K. and the U.S. over a period of years. World GNP growths in the recent past are used to forecast GNP growth to the year 2030 and also (via the model) the necessary fuel consumption for such growth; likewise, potential production of fossil fuels (exclusive of tar sands and oil shale) is shown to 2030, based on two different assumptions about total world reserves. Fossil fuel ceases to meet world requirements for energy at some time between 1985 and 1995. The most likely candidate for filling the gap is nuclear power.

  2. Employment growth and regional development

    DEFF Research Database (Denmark)

    Eriksson, Rikard; Hansen, Høgni Kalsø; Winther, Lars

    2017-01-01

    This paper explores the potential drivers behind uneven regional development in the context of employment growth in Denmark and Sweden. In particular, we are interested in the roles of urbanization, industrial change and the rise of the new economy as manifested in the growth of the two economies...... in 2002–2007. The aim of this paper is, therefore, to analyse the impact of a number of key industrial sectors on regional employment growth in the two countries. The empirical analysis is based on longitudinal matched employer–employee data retrieved from official registers in each economy from 2002...... economies, we find that, although in general these economies react relatively similarly to changes, embarking on a narrower analysis of the individual sectors reveals marked national differences. This indicates that context matters in the analysis of regional economic dynamics in terms of structure, system...

  3. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Simian, M.; Harail, Y.; Navre, M.; Werb, Z.; Lochter, A.; Bissell, M.J.

    2002-03-06

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

  4. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    International Nuclear Information System (INIS)

    Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

    2002-01-01

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland

  5. Nerve growth factor promotes human hemopoietic colony growth and differentiation

    International Nuclear Information System (INIS)

    Matsuda, H.; Coughlin, M.D.; Bienenstock, J.; Denburg, J.A.

    1988-01-01

    Nerve growth factor (NGF) is a neurotropic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons. Much is now known of the structural and functional characteristics of NGF, whose gene has recently been clones. Since it is synthesized in largest amounts by the male mouse submandibular gland, its role exclusively in nerve growth is questionable. These experiments indicate that NGF causes a significant stimulation of granulocyte colonies grown from human peripheral blood in standard hemopoietic methylcellulose assays. Further, NGF appears to act in a relatively selective fashion to induce the differentiation of eosinophils and basophils/mast cells. Depletion experiments show that the NGF effect may be T-cell dependent and that NGF augments the colony-stimulating effect of supernatants from the leukemic T-cell (Mo) line. The hemopoietic activity of NGF is blocked by 125 I-polyclonal and monoclonal antibodies to NGF. The authors conclude that NGF may indirectly act as a local growth factor in tissues other than those of the nervous system by causing T cells to synthesize or secrete molecules with colony-stimulating activity. In view of the synthesis of NGF in tissue injury, the involvement of basophils/mast cells and eosinophils in allergic and other inflammatory processes, and the association of mast cells with fibrosis and tissue repair, they postulate that NGF plays an important biological role in a variety of repair processes

  6. Surfactant-Mediated Growth Revisited

    International Nuclear Information System (INIS)

    Meyerheim, H. L.; Sander, D.; Popescu, R.; Pan, W.; Kirschner, J.; Popa, I.

    2007-01-01

    The x-ray structure analysis of the oxygen-surfactant-mediated growth of Ni on Cu(001) identifies up to 0.15 monolayers of oxygen in subsurface octahedral sites. This questions the validity of the general view that surfactant oxygen floats on top of the growing Ni film. Rather, the surfactant action is ascribed to an oxygen-enriched zone extending over the two topmost layers. Surface stress measurements support this finding. Our results have important implications for the microscopic understanding of surfactant-mediated growth and the change of the magnetic anisotropy of the Ni films

  7. Monitoring crack growth using thermography

    International Nuclear Information System (INIS)

    Djedjiga, Ait Aouita; Abdeldjalil, Ouahabi

    2008-01-01

    The purpose of this work is to present a novel strategy for real-time monitoring crack growth of materials. The process is based on the use of thermal data extracted along the horizontal axis of symmetry of single edge notch tension (SENT) specimens, during fatigue tests. These data are exploited using an implemented program to detect in situ the growth of fatigue crack, with the critical size and propagation speed of the crack. This technique has the advantage to be applicable to a wide range of materials regardless of their electrical conductivity and their surface texture. (authors)

  8. Innovation, resources and economic growth

    International Nuclear Information System (INIS)

    Curzio, A.Q.; Fortis, M.; Zoboli, R.

    1994-01-01

    The book is concerned with the following items: 1. Technological Creativity and Institutions, 2. Innovation at Work in an Historical-Economic Perspective: Energy and Industrial Materials, 3. Scientific Revolutions and Strategies of Economic Supremacy: Advanced Materials and Biotechnologies, 4. Economic Growth and Agro-Food Policies in Key Problem Regions: Former USSR and LDCs, 5. Economic Growth and Natural Resources at Risk: Climate Change, Forests and Water and in Conclusion: Innovation and Resources in a Global Policy Perspective. Only one chapter have regard to energy problems: Energie efficient technologies: past and future perspectives. (UA)

  9. The gendered politics of growth

    DEFF Research Database (Denmark)

    Neergaard, Helle; Bøllingtoft, Anne

    Based on a review of existing research on growth and gender, this paper challenges the traditional financial and economic assumptions about new venture growth. It proposes that there are numerous ways in which a new venture may 'grow' other than growing the business organically and that women...... simply choose other strategic avenues for growing their business that do not produce performance data measurable in traditional ways. Nevertheless, they contribute considerably to turning the wheels of the economy, wherefore it is necessary to produce an understanding of their choices which goes beyond...

  10. The Simplest Unified Growth Theory

    DEFF Research Database (Denmark)

    Strulik, Holger; Weisdorf, Jacob Louis

    This paper provides a unified growth theory, i.e. a model that explains the very long-run economic and demographic development path of industrialized economies, stretching from the pre-industrial era to present-day and beyond. Making strict use of Malthus' (1798) so-called preventive check...... hypothesis - that fertility rates vary inversely with the price of food - the current study offers a new and straightforward explanation for the demographic transition and the break with the Malthusian era. The current framework lends support to existing unified growth theories and is well in tune...

  11. Converting Insulin-like Growth Factors 1 and 2 into High-Affinity Ligands for Insulin Receptor Isoform A by the Introduction of an Evolutionarily Divergent Mutation

    Czech Academy of Sciences Publication Activity Database

    Macháčková, Kateřina; Chrudinová, Martina; Radosavljević, Jelena; Potalitsyn, Pavlo; Křížková, Květoslava; Fábry, Milan; Selicharová, Irena; Collinsová, Michaela; Brzozowski, A. M.; Žáková, Lenka; Jiráček, Jiří

    2018-01-01

    Roč. 57, č. 16 (2018), s. 2373-2382 ISSN 0006-2960 R&D Projects: GA ČR GA15-19018S Institutional support: RVO:61388963 ; RVO:68378050 Keywords : insulin-like growth factor * insulin * receptor * analog Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 2.938, year: 2016 https://pubs.acs.org/doi/10.1021/acs.biochem.7b01260

  12. Growth and scintillation properties of praseodymium doped (Lu,Gd).sub.3./sub.(Ga,Al).sub.5./sub.O.sub.12./sub. single crystals

    Czech Academy of Sciences Publication Activity Database

    Kamada, K.; Nikl, Martin; Kurosawa, S.; Shoji, Y.; Pejchal, Jan; Ohashi, Y.; Yokota, Y.; Yoshikawa, A.

    2016-01-01

    Roč. 169, Jan (2016), s. 811-815 ISSN 0022-2313. [International Conference on Luminescence and Optical Spectroscopy of Condensed Matter /17./. Wroclaw, 13.07.2014-18.07.2014] R&D Projects: GA MŠk(CZ) LH14266 EU Projects: European Commission(XE) 316906 - LUMINET Institutional support: RVO:68378271 Keywords : single crystal growth * oxides * scintillators * praseodymium * garnet Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.686, year: 2016

  13. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1994-01-01

    The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

  14. When economic growth is less than exponential

    DEFF Research Database (Denmark)

    Groth, Christian; Koch, Karl-Josef; Steger, Thomas

    2010-01-01

    This paper argues that growth theory needs a more general notion of "regularity" than that of exponential growth. We suggest that paths along which the rate of decline of the growth rate is proportional to the growth rate itself deserve attention. This opens up for considering a richer set...

  15. When Economic Growth is Less than Exponential

    DEFF Research Database (Denmark)

    Groth, Christian; Koch, Karl-Josef; Steger, Thomas M.

    This paper argues that growth theory needs a more general notion of "regularity" than that of exponential growth. We suggest that paths along which the rate of decline of the growth rate is proportional to the growth rate itself deserve attention. This opens up for considering a richer set...

  16. The Growth Opportunity Channel of Debt Structure

    NARCIS (Netherlands)

    Giambona, E.; Golec, J.

    2013-01-01

    This paper studies the importance of growth opportunities for debt structure decisions. High growth firms use more unsecured debt to preserve financial flexibility (in the form of untapped secured debt capacity) in connection with future growth opportunities: the growth opportunity channel of debt

  17. Nonlinear Growth Curves in Developmental Research

    Science.gov (United States)

    Grimm, Kevin J.; Ram, Nilam; Hamagami, Fumiaki

    2011-01-01

    Developmentalists are often interested in understanding change processes, and growth models are the most common analytic tool for examining such processes. Nonlinear growth curves are especially valuable to developmentalists because the defining characteristics of the growth process such as initial levels, rates of change during growth spurts, and…

  18. The relative volume growth of minimal submanifolds

    DEFF Research Database (Denmark)

    Markvorsen, Steen; Palmer, V.

    2002-01-01

    The volume growth of certain well-defined subsets of minimal submanifolds in riemannian spaces are compared with the volume growth of balls and spheres ill space forms of constant curvature.......The volume growth of certain well-defined subsets of minimal submanifolds in riemannian spaces are compared with the volume growth of balls and spheres ill space forms of constant curvature....

  19. Energy, economic growth, and human welfare

    International Nuclear Information System (INIS)

    Schurr, S.H.

    1984-01-01

    The subject is covered in sections, entitled: economic growth and human welfare; world-wide economic growth; economic growth and energy consumption; assessing the future; caution advised; energy supply and economic growth; supply as constraint; sound policies needed. (U.K.)

  20. Obesity, growth hormone and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael Højby

    2009-01-01

    Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk...