WorldWideScience

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. Prebiotic polynucleotides and polypeptides

    Science.gov (United States)

    Orgel, L. E.

    1975-01-01

    Work on the nonenzymatic replication of polynucleotides is discussed emphasizing sequence dependence and showing that alternating polynucleotides should replicate more easily than any others. Experimental work is described showing that polypeptides in which hydrophobic and hydrophilic residues alternate, adopt a beta structure in aqueous solution. The possible relevance of these observations for the evolution of the genetic code is given.

  3. Fuzzy polynucleotide spaces and metrics.

    Science.gov (United States)

    Nieto, Juan J; Torres, A; Georgiou, D N; Karakasidis, T E

    2006-04-01

    The study of genetic sequences is of great importance in biology and medicine. Mathematics is playing an important role in the study of genetic sequences and, generally, in bioinformatics. In this paper, we extend the work concerning the Fuzzy Polynucleotide Space (FPS) introduced in Torres, A., Nieto, J.J., 2003. The fuzzy polynucleotide Space: Basic properties. Bioinformatics 19(5); 587-592 and Nieto, J.J., Torres, A., Vazquez-Trasande, M.M. 2003. A metric space to study differences between polynucleotides. Appl. Math. Lett. 27:1289-1294: by studying distances between nucleotides and some complete genomes using several metrics. We also present new results concerning the notions of similarity, difference and equality between polynucleotides. The results are encouraging since they demonstrate how the notions of distance and similarity between polynucleotides in the FPS can be employed in the analysis of genetic material.

  4. 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…

  5. 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...

  6. 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

  7. 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

  8. Fibroblast growth factor-2 promotes keratan sulfate proteoglycan expression by keratocytes in vitro

    Science.gov (United States)

    Long, C. J.; Roth, M. R.; Tasheva, E. S.; Funderburgh, M.; Smit, R.; Conrad, G. W.; Funderburgh, J. L.

    2000-01-01

    Keratocytes of the corneal stroma produce a specialized extracellular matrix responsible for corneal transparency. Corneal keratan sulfate proteoglycans (KSPG) are unique products of keratocytes that are down-regulated in corneal wounds and in vitro. This study used cultures of primary bovine keratocytes to define factors affecting KSPG expression in vitro. KSPG metabolically labeled with [(35)S]sulfate decreased during the initial 2-4 days of culture in quiescent cultures with low serum concentrations (0.1%). Addition of fetal bovine serum, fibroblast growth factor-2 (FGF-2), transforming growth factor beta, or platelet derived growth factor all stimulated cell division, but only FGF-2 stimulated KSPG secretion. Combined with serum, FGF-2 also prevented serum-induced KSPG down-regulation. KSPG secretion was lost during serial subculture with or without FGF-2. Expression of KSPG core proteins (lumican, mimecan, and keratocan) was stimulated by FGF-2, and steady state mRNA pools for these proteins, particularly keratocan, were significantly increased by FGF-2 treatment. KSPG expression therefore is supported by exogenous FGF-2 and eliminated by subculture of the cells in presence of serum. FGF-2 stimulates KSPG core protein expression primarily through an increase in mRNA pools.

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

    Science.gov (United States)

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

  10. Chicken stem cell factor enhances primordial germ cell proliferation cooperatively with fibroblast growth factor 2.

    Science.gov (United States)

    Miyahara, Daichi; Oishi, Isao; Makino, Ryuichi; Kurumisawa, Nozomi; Nakaya, Ryuma; Ono, Tamao; Kagami, Hiroshi; Tagami, Takahiro

    2016-04-22

    An in vitro culture system of chicken primordial germ cells (PGCs) has been recently developed, but the growth factor involved in the proliferation of PGCs is largely unknown. In the present study, we investigated the growth effects of chicken stem cell factor (chSCF) on the in vitro proliferation of chicken PGCs. We established two feeder cell lines (buffalo rat liver cells; BRL cells) that stably express the putative secreted form of chSCF (chSCF1-BRL) and membrane bound form of chSCF (chSCF2-BRL). Cultured PGC lines were incubated on chSCF1 or chSCF2-BRL feeder cells with fibroblast growth factor 2 (FGF2), and growth effects of each chSCF isoform were investigated. The in vitro proliferation rate of the PGCs cultured on chSCF2-BRL at 20 days of culture was more than threefold higher than those cultured on chSCF1-BRL cells and more than fivefold higher than those cultured on normal BRL cells. Thus, use of chSCF2-BRL feeder layer was effective for in vitro proliferation of chicken PGCs. However, the acceleration of PGC proliferation on chSCF2-BRL was not observed without FGF2, suggesting that chSCF2 would act as a proliferation co-factor of FGF2. We transferred the PGCs cultured on chSCF2-BRL cells to recipient embryos, generated germline chimeric chickens and assessed the germline competency of cultured PGCs by progeny test. Donor-derived progenies were obtained, and the frequency of germline transmission was 3.39%. The results of this study demonstrate that chSCF2 induces hyperproliferation of chicken PGCs retaining germline competency in vitro in cooperation with FGF2.

  11. Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2*

    Science.gov (United States)

    La Venuta, Giuseppe; Wegehingel, Sabine; Sehr, Peter; Müller, Hans-Michael; Dimou, Eleni; Steringer, Julia P.; Grotwinkel, Mareike; Hentze, Nikolai; Mayer, Matthias P.; Will, David W.; Uhrig, Ulrike; Lewis, Joe D.; Nickel, Walter

    2016-01-01

    Fibroblast growth factor 2 (FGF2) is a potent mitogen promoting both tumor cell survival and tumor-induced angiogenesis. It is secreted by an unconventional secretory mechanism that is based upon direct translocation across the plasma membrane. Key steps of this process are (i) phosphoinositide-dependent membrane recruitment, (ii) FGF2 oligomerization and membrane pore formation, and (iii) extracellular trapping mediated by membrane-proximal heparan sulfate proteoglycans. Efficient secretion of FGF2 is supported by Tec kinase that stimulates membrane pore formation based upon tyrosine phosphorylation of FGF2. Here, we report the biochemical characterization of the direct interaction between FGF2 and Tec kinase as well as the identification of small molecules that inhibit (i) the interaction of FGF2 with Tec, (ii) tyrosine phosphorylation of FGF2 mediated by Tec in vitro and in a cellular context, and (iii) unconventional secretion of FGF2 from cells. We further demonstrate the specificity of these inhibitors for FGF2 because tyrosine phosphorylation of a different substrate of Tec is unaffected in their presence. Building on previous evidence using RNA interference, the identified compounds corroborate the role of Tec kinase in unconventional secretion of FGF2. In addition, they are valuable lead compounds with great potential for drug development aiming at the inhibition of FGF2-dependent tumor growth and metastasis. PMID:27382052

  12. 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.

  13. 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.

  14. Impact of fibroblast growth factor-2 on tumor microvascular architecture. A tridimensional morphometric study.

    Science.gov (United States)

    Konerding, M. A.; Fait, E.; Dimitropoulou, C.; Malkusch, W.; Ferri, C.; Giavazzi, R.; Coltrini, D.; Presta, M.

    1998-01-01

    Three cell clones originated by transfection of human endometrial adenocarcinoma HEC-1-B cells with fibroblast growth factor-2 (FGF-2) cDNA and characterized by a different capacity to produce and secrete the growth factor were transplanted subcutaneously in nude mice. Corrosion casting of the tumor microvasculature of xenografts produced by injection of 2 x 10(6) or 10 x 10(6) FGF-2-B9 cells (which produce and secrete significant amounts of FGF-2), 10 x 10(6) FGF-2-A8 cells (which produce comparable amounts of FGF-2 but do not secrete it), or 10 x 10(6) control FGF-2-B8 cells (which produce only trace amounts of FGF-2) was performed after 14 days of growth. Interbranching distances, intervascular distances, branching angles, and vessel diameters were then determined using tridimensional stereo pairs of the casted tumor vascularity. When transplanted at the same concentration, FGF-2-B9 cells grew faster in nude mice compared with FGF-2-A8 and FGF-2-B8 clones. The total amount of new vessel formation was far higher in FGF-2-B9 tumors than in FGF-2-B8 or FGF-2-A8 tumors. Also, vessel courses were more irregular and blind-ending vessels and evasates were more frequent in FGF-2-B9 tumors. Moreover, FGF-2-B9 tumor microvasculature was characterized by a wider average vascular diameter and by an extreme variability of the diameter of each individual vessel along its course between two ramifications. No statistical differences were observed when the distribution curves of the values of intervascular distances, interbranching distances, and branching angles of the microvessel network were compared among the different experimental groups. The distinctive features of the microvasculature of FGF-2-B9 tumors were retained, at least in part, in the smaller lesions produced by injection of a limited number of cells. The data indicate that FGF-2 production and release confer to FGF-2-B9 cells the ability to stimulate the formation of new blood vessels with distinctive

  15. Long days enhance recognition memory and increase insulin-like growth factor 2 in the hippocampus.

    Science.gov (United States)

    Dellapolla, Adriano; Kloehn, Ian; Pancholi, Harshida; Callif, Ben; Wertz, David; Rohr, Kayla E; Hurley, Matthew M; Baker, Kimberly M; Hattar, Samer; Gilmartin, Marieke R; Evans, Jennifer A

    2017-06-20

    Light improves cognitive function in humans; however, the neurobiological mechanisms underlying positive effects of light remain unclear. One obstacle is that most rodent models have employed lighting conditions that cause cognitive deficits rather than improvements. Here we have developed a mouse model where light improves cognitive function, which provides insight into mechanisms underlying positive effects of light. To increase light exposure without eliminating daily rhythms, we exposed mice to either a standard photoperiod or a long day photoperiod. Long days enhanced long-term recognition memory, and this effect was abolished by loss of the photopigment melanopsin. Further, long days markedly altered hippocampal clock function and elevated transcription of Insulin-like Growth Factor2 (Igf2). Up-regulation of Igf2 occurred in tandem with suppression of its transcriptional repressor Wilm's tumor1. Consistent with molecular de-repression of Igf2, IGF2 expression was increased in the hippocampus before and after memory training. Lastly, long days occluded IGF2-induced improvements in recognition memory. Collectively, these results suggest that light changes hippocampal clock function to alter memory, highlighting novel mechanisms that may contribute to the positive effects of light. Furthermore, this study provides insight into how the circadian clock can regulate hippocampus-dependent learning by controlling molecular processes required for memory consolidation.

  16. 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.

  17. 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.

  18. Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion.

    Science.gov (United States)

    Ebert, Antje D; Laussmann, Mareike; Wegehingel, Sabine; Kaderali, Lars; Erfle, Holger; Reichert, Jürgen; Lechner, Johannes; Beer, Hans-Dietmar; Pepperkok, Rainer; Nickel, Walter

    2010-06-01

    Fibroblast growth factor 2 (FGF2) is a potent mitogen that is exported from cells by an endoplasmic reticulum (ER)/Golgi-independent mechanism. Unconventional secretion of FGF2 occurs by direct translocation across plasma membranes, a process that depends on the phosphoinositide phosphatidylinositol 4,5-biphosphate (PI(4,5)P(2)) at the inner leaflet as well as heparan sulfate proteoglycans at the outer leaflet of plasma membranes; however, additional core and regulatory components of the FGF2 export machinery have remained elusive. Here, using a highly effective RNAi screening approach, we discovered Tec kinase as a novel factor involved in unconventional secretion of FGF2. Tec kinase does not affect FGF2 secretion by an indirect mechanism, but rather forms a heterodimeric complex with FGF2 resulting in phosphorylation of FGF2 at tyrosine 82, a post-translational modification shown to be essential for FGF2 membrane translocation to cell surfaces. Our findings suggest a crucial role for Tec kinase in regulating FGF2 secretion under various physiological conditions and, therefore, provide a new perspective for the development of a novel class of antiangiogenic drugs targeting the formation of the FGF2/Tec complex.

  19. Chronically increased ciliary neurotrophic factor and fibroblast growth factor-2 expression after spinal contusion in rats.

    Science.gov (United States)

    Tripathi, Richa B; McTigue, Dana M

    2008-09-10

    Demyelination and oligodendrocyte loss following spinal cord injury (SCI) are well documented. Recently, we showed oligodendrocyte progenitor cell (OPC) accumulation and robust oligodendrocyte genesis occurring along SCI lesion borders. We have since begun investigating potential mechanisms for this endogenous repair response. Here, we examined ciliary neurotrophic factor (CNTF) and fibroblast growth factor-2 (FGF-2) expression, because both factors alter progenitor proliferation and differentiation and are increased in several CNS disorders. We hypothesized that CNTF and FGF-2 would increase after SCI, especially in regions of enhanced oligogenesis. First, CNTF protein was quantified using Western blots, which revealed that CNTF protein continually rose through 28 days post injury (dpi). Next, by using immunohistochemistry, we examined the spatiotemporal expression of CNTF in cross-sections spanning the injury site. CNTF immunoreactivity was observed on astrocytes and oligodendrocytes in naïve and contused spinal cords. Significantly increased CNTF was detected in spared white and gray matter between 5 and 28 dpi compared with uninjured controls. By 28 dpi, CNTF expression was significantly higher along lesion borders compared with outlying spared tissue; a similar distribution of phosphorylated STAT3, a transcription factor up-regulated by CNTF and to a lesser extent FGF-2, was also detected. Because CNTF can potentiate FGF-2 expression, we examined the distribution of FGF-2+ cells. Significantly more FGF-2+ cells were noted along lesion borders at 7 and 28 dpi. Thus, both CNTF and FGF-2 are present in regions of elevated OPC proliferation and oligodendrocyte generation after SCI and therefore may play a role in injury-induced gliogenesis. (c) 2008 Wiley-Liss, Inc.

  20. Bone augmentation using a highly porous PLGA/β-TCP scaffold containing fibroblast growth factor-2.

    Science.gov (United States)

    Yoshida, T; Miyaji, H; Otani, K; Inoue, K; Nakane, K; Nishimura, H; Ibara, A; Shimada, A; Ogawa, K; Nishida, E; Sugaya, T; Sun, L; Fugetsu, B; Kawanami, M

    2015-04-01

    Beta-tricalcium phosphate (β-TCP), a bio-absorbable ceramic, facilitates bone conductivity. We constructed a highly porous three-dimensional scaffold, using β-TCP, for bone tissue engineering and coated it with co-poly lactic acid/glycolic acid (PLGA) to improve the mechanical strength and biological performance. The aim of this study was to examine the effect of implantation of the PLGA/β-TCP scaffold loaded with fibroblast growth factor-2 (FGF-2) on bone augmentation. The β-TCP scaffold was fabricated by the replica method using polyurethane foam, then coated with PLGA. The PLGA/β-TCP scaffold was characterized by scanning electron miscroscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction, compressive testing, cell culture and a subcutaneous implant test. Subsequently, a bone-forming test was performed using 52 rats. The β-TCP scaffold, PLGA-coated scaffold, and β-TCP and PLGA-coated scaffolds loaded with FGF-2, were implanted into rat cranial bone. Histological observations were made at 10 and 35 d postsurgery. SEM and TEM observations showed a thin PLGA layer on the β-TCP particles after coating. High porosity (> 90%) of the scaffold was exhibited after PLGA coating, and the compressive strength of the PLGA/β-TCP scaffold was six-fold greater than that of the noncoated scaffold. Good biocompatibility of the PLGA/β-TCP scaffold was found in the culture and implant tests. Histological samples obtained following implantation of PLGA/β-TCP scaffold loaded with FGF-2 showed significant bone augmentation. The PLGA coating improved the mechanical strength of β-TCP scaffolds while maintaining high porosity and tissue compatibility. PLGA/β-TCP scaffolds, in combination with FGF-2, are bioeffective for bone augmentation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. miR-203 facilitates tumor growth and metastasis by targeting fibroblast growth factor 2 in breast cancer

    Directory of Open Access Journals (Sweden)

    He S

    2016-10-01

    Full Text Available Shuqian He, Guihui Zhang, He Dong, Maoqiang Ma, Qing Sun Department of Pathology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Abstract: Breast cancer is the second leading cause of cancer mortality in women worldwide. Molecular therapy is needed to improve the outcome in patients with breast cancer. miR-203 participates in cancer cell proliferation, transformation, and apoptosis. This study showed that miR-203 was upregulated in breast cancer tissues and the MCF-7 cell line. miR-203 knockdown suppressed colony formation and transformation and also limited migration in MCF-7 cells. Fibroblast growth factor 2 (FGF2 was confirmed as a novel target of miR-203, as miR-203 knockdown induced an enhanced expression of FGF2 in MCF-7 cells. Moreover, FGF2 can reverse transforming growth factor-β signal pathway to suppress breast cancer. These findings provide new insights with potential therapeutic applications for the treatment of breast cancer. Keywords: breast cancer, miR-203, FGF2

  2. Polynucleotide phosphorylase and the T3SS.

    Science.gov (United States)

    Rosenzweig, Jason A; Schesser, Kurt

    2007-01-01

    Low temperatures as well as encounters with host phagocytes are two stresses that have been relatively well studied in many species of bacteria. The exoribonuclease polynucleotide phosphorylase (PNPase) has previously been shown to be required by several species of bacteria, including Yersinia, for low-temperature growth. We have shown that PNPase also enhances the ability of Yersinia to withstand the killing activities of murine macrophages. We have gone on to show that PNPase is required for the optimal functioning of Yersinia's type three secretion system (T3SS), an organelle that injects effector proteins directly into host cells. Surprisingly, the PNPase-mediated effect on T3SS activity is independent of PNPase's ribonuclease activity and instead requires only its S1 RNA-binding domain. In stark contrast, the catalytic activity of PNPase is strictly required for enhanced growth at low temperature. Preliminary experiments suggest that the RNA-binding interface of the S1 domain is critical for its T3SS-enhancing activity. Our findings indicate that PNPase plays versatile roles in promoting Yersinia's survival in response to stressful conditions.

  3. 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.

  4. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Science.gov (United States)

    Spodsberg, Nikolaj

    2015-07-14

    The present invention relates to isolated polypeptides having cellobiohydrolase 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.

  5. Hybrid polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ye; Shaghasi, Tarana

    2016-11-01

    The present invention provides hybrid polypeptides having cellobiohydrolase activity. The present invention also provides polynucleotides encoding the hybrid polypeptides; nucleic acid constructs, vectors and host cells comprising the polynucleotides; and processes of using the hybrid polypeptides.

  6. Polypeptides having beta-xylosidase activity and polynucleotides encoding same

    Science.gov (United States)

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

    2017-04-18

    Provided are isolated polypeptides having beta-xylosidase 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-09-26

    Provided are isolated polypeptides having beta-glucosidase 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.

  8. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Spodsberg, Nikolaj

    2016-06-28

    The present invention relates to isolated polypeptides having cellobiohydrolase 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.

  9. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Spodsberg, Nikolaj

    2016-12-13

    The present invention relates to isolated polypeptides having cellobiohydrolase 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.

  10. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Spodsberg, Nikolaj

    2017-11-21

    The present invention relates to isolated polypeptides having cellobiohydrolase 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.

  11. Polypeptides having endoglucanase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-07-18

    Provided are isolated polypeptides having endoglucanase activity and isolated 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.

  12. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Science.gov (United States)

    Spodsberg, Nikolaj

    2015-11-17

    The present invention relates to isolated polypeptides having cellobiohydrolase 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.

  13. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu; Tang, Lan; Henriksen, Svend Hostgaard Bang

    2016-05-17

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

  14. Polypeptides having xylanase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Spodsberg, Nikolaj

    2017-05-02

    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.

  15. Polypeptides having cellobiohydrolase activitiy and polynucleotides encoding same

    Science.gov (United States)

    Liu, Ye; Tang, Lan; Duan, Junxin

    2015-12-15

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

  16. 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.

  17. Polypeptides having laccase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-08-22

    The present invention relates to isolated polypeptides having laccase activity and polynucleotides encoding the polypeptides 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.

  18. Insulin-like growth factor-2 regulates early neural and cardiovascular system development in zebrafish embryos.

    Science.gov (United States)

    Hartnett, Lori; Glynn, Catherine; Nolan, Catherine M; Grealy, Maura; Byrnes, Lucy

    2010-01-01

    The insulin-like growth factor (IGF) family is essential for normal embryonic growth and development and it is highly conserved through vertebrate evolution. However, the roles that the individual members of the IGF family play in embryonic development have not been fully elucidated. This study focuses on the role of IGF-2 in zebrafish embryonic development. Two igf-2 genes, igf-2a and igf-2b, are present in the zebrafish genome. Antisense morpholinos were designed to knock down both igf-2 genes. The neural and cardiovascular defects in IGF-2 morphant embryos were then examined further using wholemount in situ hybridisation, TUNEL analysis and O-dianisidine staining. Knockdown of igf-2a or igf-2b resulted in ventralised embryos with reduced growth, reduced eyes, disrupted brain structures and a disrupted cardiovascular system, with igf-2b playing a more significant role in development. During gastrulation, igf-2a and igf-2b are required for development of anterior neural structures and for regulation of genes critical to dorsal-ventral patterning. As development proceeds, igf-2a and igf-2b play anti-apoptotic roles. Gene expression analysis demonstrates that igf-2a and igf-2b play overlapping roles in angiogenesis and cardiac outflow tract development. Igf-2b is specifically required for cardiac valve development and cardiac looping. Injection of a dominant negative IGF-1 receptor led to similar defects in angiogenesis and cardiac valve development, indicating IGF-2 signals through this receptor to regulate cardiovascular development. This is the first study describing two functional igf-2 genes in zebrafish. This work demonstrates that igf-2a and igf-2b are critical to neural and cardiovascular development in zebrafish embryos. The finding that igf-2a and igf-2b do not act exclusively in a redundant manner may explain why both genes have been stably maintained in the genome.

  19. 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)

  20. 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.

  1. The effects of calcium silicate cement/fibroblast growth factor-2 composite on osteogenesis accelerator in human dental pulp cells

    OpenAIRE

    Wu, Buor-Chang; Youn, Su-Chung; Kao, Chia-Tze; Huang, Shu-Ching; Hung, Chi-Jr; Chou, Ming-Yung; Huang, Tsui-Hsien; Shie, Ming-You

    2015-01-01

    Background/purpose: To examine the effects of fibroblast growth factor-2 (FGF-2)/calcium silicate (CS) cement on material characters and in vitro primary human dental pulp cell (hDPC) behavior. Materials and methods: Setting time and diametral tensile strength (DTS) of CS and CS/FGF-2 composite were measured. PrestoBlue assay was used for evaluating primary hDPC proliferation. Alkaline phosphatase and osteocalcin expression in HDPCs cultured on the specimens were determined by enzyme-linke...

  2. 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

  3. Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

    Science.gov (United States)

    Rhoads, D. N.; Eskin, S. G.; McIntire, L. V.

    2000-01-01

    This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (PFlow cytometry detected a 50% increase in mean fluorescence of cells exposed to 25 dyne/cm(2) versus control cells. This indicates that the observed FGF-2 release from human aortic smooth muscle cells is likely due to transient membrane disruption on initiation of flow.

  4. Influence of polymerization properties of 4-META/MMA-based resin on the activity of fibroblast growth factor-2.

    Science.gov (United States)

    Kitagawa, Haruaki; Takeda, Kahoru; Tsuboi, Ririko; Hayashi, Mikako; Sasaki, Jun-Ichi; Imazato, Satoshi

    2017-11-29

    Dental adhesive resins based on 4-methacryloxyethyl trimellitate anhydride (4-META)/methyl methacrylate (MMA) have been utilized for root-end filling and the bonding of fractured roots. To increase the success rate of these treatments, it would be beneficial to promote the healing of surrounding tissue by applying growth factors. In this study, the influences of the polymerization properties of 4-META/MMA-based resins on the activity of fibroblast growth factor-2 (FGF-2) were evaluated in vitro. The temperature increase caused by the heat generation during polymerization of the 4-META/MMA-based resin was insufficient to change the structure and function of FGF-2. Unpolymerized monomers released from the cured 4-META/MMA-based resin had no negative influences on the ability of FGF-2 to promote the proliferation of osteoblast-like cells. These findings suggest that it is possible to use FGF-2 in combination with 4-META/MMA-based resins.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2.

    Science.gov (United States)

    Zhang, Huanji; Wang, Tong; Zhang, Kun; Liu, Yu; Huang, Feifei; Zhu, Xinhong; Liu, Yang; Wang, Mong-Heng; Tang, Wanchun; Wang, Jingfeng; Huang, Hui

    2014-05-01

    Inhibition of soluble epoxide hydrolase (Ephx2) has been shown to play a protective role in cardiac hypertrophy, but the mechanism is not fully understood. We tested the hypothesis that deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2. Prospective, controlled, and randomized animal study. University laboratory. Male wild-type C57BL/6 mice and Ephx2 (-/-) mice. Male wild-type or Ephx2 (-/-) mice were subjected to transverse aorta constriction surgery. Four weeks after transverse aorta constriction, Ephx2 (-/-) mice did not develop significant cardiac hypertrophy as that of wild-type mice, indicated by no changes in the ratio of heart weight/body weight and ventricular wall thickness after transverse aorta constriction. Cardiac fibroblast growth factor-2 increased in wild-type-transverse aorta constriction group but this did not change in Ephx2 (-/-)-transverse aorta constriction group, and the serum level of fibroblast growth factor-2 did not change in both groups. In vitro, cardiac fibroblasts were stimulated by angiotensin II to analyze the expression of fibroblast growth factor-2. The effect of increased fibroblast growth factor-2 from cardiac fibroblasts induced by angiotensin II was attenuated by soluble epoxide hydrolase deletion. ERK1/2, p38, and AKT kinase were involved in fibroblast growth factor-2 expression regulated by angiotensin II, and soluble epoxide hydrolase deletion lowered the phosphorylation of ERK1/2 not p38 or AKT to mediate fibroblast growth factor-2 expression. In addition, soluble epoxide hydrolase deletion did not attenuate cardiomyocytes hypertrophy induced by exogenous fibroblast growth factor-2. Our present data demonstrated that deletion of soluble epoxide hydrolase prevented cardiac hypertrophy not only directly to cardiomyocytes but also to cardiac fibroblasts by reducing expression of fibroblast growth factor-2.

  7. 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)

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

    Directory of Open Access Journals (Sweden)

    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

  9. Fibroblast growth factor-2 counteracts the effect of ciliary neurotrophic factor on spontaneous differentiation in adult hippocampal progenitor cells.

    Science.gov (United States)

    He, Zhili; Ding, Jun; Zhang, Jianfang; Liu, Ying; Gong, Chengxin; Sun, Shenggang; Chen, Honghui

    2012-12-01

    Neural stem/progenitor cells (NSCs) can spontaneously differentiate into neurons and glial cells in the absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF) in medium and the spontaneous differentiation of NSCs is mediated partially by endogenous ciliary neurotrophic factor (CNTF). This study examined the relationship of FGF-2 and CNTF in the spontaneous differentiation of adult hippocampal progenitor cells (AHPs). AHPs were cultured in the medium containing different concentration of FGF-2 (1-100 ng/mL). Western blotting and immunofluorescence staining were applied to detect the expression of the astrocytic marker GFAP, the neuronal marker Tuj1, the oligodendrocytic marker CNPase and, Nestin, the marker of AHPs. The expression of endogenous CNTF in AHPs at early (passage 4) and late stage (passage 22) was also measured by Western blotting. The results showed that FGF-2 increased the expression of Nestin, dramatically inhibited the expression of GFAP and Tuj1 and slightly suppressed the expression of CNPase. FGF-2 down-regulated the expression of endogenous CNTF in AHPs at both early (passage 4) and late stage (passage 22). These results suggested that FGF-2 could inhibit the spontaneous differentiation of cultured AHPs by negatively regulating the expression of endogenous CNTF in AHPs.

  10. The characterization of protein release from sericin film in the presence of an enzyme: towards fibroblast growth factor-2 delivery.

    Science.gov (United States)

    Nishida, Ayumu; Naganuma, Tsuyoshi; Kanazawa, Takanori; Takashima, Yuuki; Yamada, Masaki; Okada, Hiroaki

    2011-07-29

    Aqueous preparations of silk protein (sericin) films were prepared to evaluate their biodegradation properties. In the absence of trypsin, sericin film swelled rapidly, kept its shape, and remained unaltered for 28 days or longer due to form β-sheet structures. In the presence of trypsin, sericin film gradually degraded; since the rate depended on the concentration of trypsin, the films likely underwent enzymatic hydrolysis. Sericin film incorporating the model protein drug fluorescein isothiocyanate-albumin (FA) also gradually degraded in the presence of trypsin and resulted in the sustained release of FA for 2 weeks or longer; in contrast, FA release was quite slow in the absence of trypsin. It is expected that sericin film has potential as a biodegradable and drug-releasing carrier. To evaluate the practical applicability of sericin film for the repair of defective tissues, fibroblast growth factor-2 (FGF-2) was incorporated into sericin films and the films were implanted on skull defects in rats. Whereas FGF-2 release was suppressed in the absence of trypsin in vitro, it appears that FGF-2, immobilized by ionic interactions between sericin and FGF-2, can be sustained-released in vivo from films incorporating 2500 or 250 ng of FGF-2 to support the growth of tissue around wounds. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Maintenance of multipotency in human dermal fibroblasts treated with Xenopus laevis egg extract requires exogenous fibroblast growth factor-2.

    Science.gov (United States)

    Kole, Denis; Ambady, Sakthikumar; Page, Raymond L; Dominko, Tanja

    2014-02-01

    Direct reprogramming of a differentiated somatic cell into a developmentally more plastic cell would offer an alternative to applications in regenerative medicine that currently depend on either embryonic stem cells (ESCs), adult stem cells, or induced pluripotent stem cells (iPSCs). Here we report the potential of select Xenopus laevis egg extract fractions, in combination with exogenous fibroblast growth factor-2 (FGF2), to affect life span, morphology, gene expression, protein translation, and cellular localization of OCT4 and NANOG transcription factors, and the developmental potential of human dermal fibroblasts in vitro. A gradual change in morphology is accompanied by translation of embryonic transcription factors and their nuclear localization and a life span exceeding 60 population doublings. Cells acquire the ability to follow adipogenic, neuronal, and osteogenic differentiation under appropriate induction conditions in vitro. Analysis of active extract fractions reveals that Xenopus egg protein and RNAs as well as exogenously supplemented FGF2 are required and sufficient for induction and maintenance of this phenotypic change. Factors so far identified in the active fractions include FGF2 itself, transforming growth factor-β, maskin, and nucleoplasmin. Identification of critical factors needed for reprogramming may allow for nonviral, chemically defined derivation of human-induced multipotent cells that can be maintained by exogenous FGF2.

  12. Enhanced proliferation and migration of fibroblasts on the surface of fibroblast growth factor-2-loaded fibrin microthreads.

    Science.gov (United States)

    Cornwell, Kevin G; Pins, George D

    2010-12-01

    Fibrin microthreads are discrete biopolymer fibers, 50-100 μm in diameter, produced from the natural extracellular matrix protein of the provisional matrix that promotes tissue regeneration in the in vivo wound healing environment. The goals of this study were to investigate the feasibility of creating fibrin microthreads containing fibroblast growth factor-2 (FGF-2), and to study the potential of a fibrin matrix to bind signaling proteins known to promote wound healing and regulate cell function in localized cellular microenvironments on scaffold surfaces. FGF-2 was loaded into fibrin microthreads in concentrations ranging from 0 to 200 ng/mL, to investigate the effect of the material on fibroblast attachment, proliferation, cellular outgrowth, and alignment. Although FGF-2-loaded microthreads did not affect fibroblast attachment, they significantly increased cellular outgrowth and proliferation relative to unloaded microthreads. The most pronounced effects were observed at day 7 of cell culture. Further, all of the fibrin microthreads promoted the alignment of fibroblasts and their cytoskeletal components along the long axis of threads, independent of the FGF-2 concentration. Ultimately, we anticipate that these fibrin microthreads will be a promising biopolymer material to promote the regeneration of injured tissues because of their mechanical stability and their matrix signaling capabilities, particularly when loaded with matrix-bound growth factors such as FGF-2.

  13. The synergistic effects of fibroblast growth factor-2 and mineral trioxide aggregate on an osteogenic accelerator in vitro.

    Science.gov (United States)

    Liu, C-H; Huang, T-H; Hung, C-J; Lai, W-Y; Kao, C-T; Shie, M-Y

    2014-09-01

    To examine the effects of mineral trioxide aggregate (MTA)/fibroblast growth factor-2 (FGF-2) on material properties and in vitro human dental pulp cell (hDPCs) behaviour. The setting time and diametral tensile strength (DTS) of MTA and MTA/FGF-2 were measured. The structure of specimens before and after soaking in DMEM was examined under a scanning electron microscope. Alamar Blue was used for evaluating hDPCs proliferation. An enzyme-linked immunosorbent assay was employed to determine ALP and osteocalcin (OC) expression in hDPCs cultured on cements. The effect of small interfering RNA (siRNA) transfection targeting fibroblast growth factor receptor (FGFR) was also evaluated. One-way analysis of variance was used to evaluate the significance of the differences between the mean values. Setting time and DTS data were not found to be significant (P > 0.05) between MTA with and without FGF-2. Cell proliferation and differentiation increased significantly (P MTA. After siRNA transfection with FGFR, the proliferation and differentiation behaviour of the hDPCs appreciably decreased when cultured on an MTA/FGF-2 composite. In contrast, no significant amounts (P > 0.05) of ALP and OC were secreted by hDPCs seeded on MTA. Mineral trioxide aggregate with FGF-2 content enhanced the higher expression of hDPCs proliferation and osteogenic differentiation as compared to pure MTA cement. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  14. Insulin-like growth factor 2 enhances regulatory T-cell functions and suppresses food allergy in an experimental model.

    Science.gov (United States)

    Yang, Gui; Geng, Xiao-Rui; Song, Jiang-Ping; Wu, Yingying; Yan, Hao; Zhan, Zhengke; Yang, Litao; He, Weiyi; Liu, Zhi-Qiang; Qiu, Shuqi; Liu, Zhigang; Yang, Ping-Chang

    2014-06-01

    The functions of regulatory T (Treg) cells are important in immunity, and the regulatory mechanisms of Treg cell activities are not fully understood yet. We sought to investigate the role of insulin-like growth factor (IGF) 2 in the upregulation of Treg cell function. The expression of insulin-like growth factor 2 receptor (IGF2R) on T cells was assessed by using flow cytometry. Treg cell functions were evaluated by assessing the suppressor effect on proliferation of other effector T (Teff) cells. The effect of IGF2 on regulating Treg cell functions were evaluated with a cell-culture model and a food allergy mouse model. Expression of IGF2R was observed in more than 90% of murine and human Treg cells but in less than 10% of effector CD4(+) T cells. Activation of IGF2R and T-cell receptor induced marked Treg cell proliferation and release of TGF-β from Treg cells, which enhanced Treg cell immune suppressor effects on other Teff cell activities and allergic inflammation in the intestine. Activation of IGF2R enhances Treg cell functions in suppressing other Teff cell activities and inhibiting allergic inflammation in the intestine. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. Fibroblast growth factor-2 induced by enriched environment enhances angiogenesis and motor function in chronic hypoxic-ischemic brain injury.

    Science.gov (United States)

    Seo, Jung Hwa; Yu, Ji Hea; Suh, Hwal; Kim, Myung-Sun; Cho, Sung-Rae

    2013-01-01

    This study aimed to investigate the effects of enriched environment (EE) on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in seven day-old CD-1® mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC) for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2) was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and α-smooth muscle actin (α-SMA) were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of α-SMA(+) and PECAM-1(+) cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions mediated by

  16. Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2.

    Directory of Open Access Journals (Sweden)

    Say Viengchareun

    2008-02-01

    Full Text Available The lactogenic hormones prolactin (PRL and placental lactogens (PL play central roles in reproduction and mammary development. Their actions are mediated via binding to PRL receptor (PRLR, highly expressed in brown adipose tissue (BAT, yet their impact on adipocyte function and metabolism remains unclear.PRLR knockout (KO newborn mice were phenotypically characterized in terms of thermoregulation and their BAT differentiation assayed for gene expression studies. Derived brown preadipocyte cell lines were established to evaluate the molecular mechanisms involved in PRL signaling on BAT function. Here, we report that newborn mice lacking PRLR have hypotrophic BAT depots that express low levels of adipocyte nuclear receptor PPARgamma2, its coactivator PGC-1alpha, uncoupling protein 1 (UCP1 and the beta3 adrenoceptor, reducing mouse viability during cold challenge. Immortalized PRLR KO preadipocytes fail to undergo differentiation into mature adipocytes, a defect reversed by reintroduction of PRLR. That the effects of the lactogens in BAT are at least partly mediated by Insulin-like Growth Factor-2 (IGF-2 is supported by: i a striking reduction in BAT IGF-2 expression in PRLR KO mice and in PRLR-deficient preadipocytes; ii induction of cellular IGF-2 expression by PRL through JAK2/STAT5 pathway activation; and iii reversal of defective differentiation in PRLR KO cells by exogenous IGF-2.Our findings demonstrate that the lactogens act in concert with IGF-2 to control brown adipocyte differentiation and growth. Given the prominent role of brown adipose tissue during the perinatal period, our results identified prolactin receptor signaling as a major player and a potential therapeutic target in protecting newborn mammals against hypothermia.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

  19. Beta-glucosidase variants and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Polypeptides having xylanase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Polypeptides having endoglucanase activity and polynucleotides encoding same

    Science.gov (United States)

    Spodsberg, Nikolaj

    2016-02-23

    The present invention relates to isolated polypeptides having endoglucanase 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.

  2. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Science.gov (United States)

    Schnorr, Kirk; Kramer, Randall

    2016-04-05

    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.

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

    Science.gov (United States)

    Harris, Paul; Golightly, Elizabeth

    2007-07-17

    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 for producing and using the polypeptides.

  4. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Schnorr, Kirk; Kramer, Randall

    2017-08-08

    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.

  5. Polypeptides having beta-xylosidase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-07-04

    The present invention relates to isolated polypeptides having beta-xylosidase 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.

  6. Polypeptides having xylanase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Lopez de Leon, Alfredo; Rey, Michael

    2017-09-26

    The present invention relates to isolated polypeptides having xylanase 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.

  7. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ye; Tang, Lan; Duan, Junxin

    2017-02-07

    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.

  8. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding the same

    Science.gov (United States)

    Duan, Junxin; Schnorr, Kirk Matthew; Wu, Wenping

    2013-11-19

    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.

  9. 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.

  10. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Stringer, Mary Ann; McBrayer, Brett

    2016-11-29

    The present invention relates to isolated polypeptides having cellobiohydrolase activity, catalytic domains, and cellulose binding domains and polynucleotides encoding the polypeptides, catalytic domains, and cellulose binding domains. 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, catalytic domains, or cellulose binding domains.

  11. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Lan; Liu, Ye; Duan, Junxin; Zhang, Yu; Joergensen, Christian; Kramer, Randall

    2016-11-29

    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.

  12. Polypeptides having xylanase activity and polynucleotides encoding same

    Science.gov (United States)

    Tang, Lan; Liu, Ye; Duan, Junxin; Hanshu, Ding

    2012-10-30

    The present invention relates to isolated polypeptides having xylanase 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. 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.

  15. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu; Duan, Junxin; Tang, Lan; Wu, Wenping

    2016-11-22

    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.

  16. Polypeptides having xylanase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Lopez de Leon, Alfredo; Rey, Michael

    2016-05-31

    The present invention relates to isolated polypeptides having xylanase 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.

  17. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu; Duan, Junxin; Tang, Lan; Wu, Wenping

    2016-06-14

    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.

  18. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Lan; Liu, Ye; Duan, Junxin; Wu, Wenping; Kramer, Randall

    2017-09-19

    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.

  19. Polypeptides having endoglucanase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Spodsberg, Nikolaj; Shagasi, Tarana

    2017-05-30

    The present invention relates to isolated polypeptides having endoglucanase activity, catalytic domains, cellulose binding domains and polynucleotides encoding the polypeptides, catalytic domains or cellulose binding domains. 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, catalytic domains or cellulose binding domains.

  20. Polypeptides having endoglucanase activity and polynucleotides encoding same

    Science.gov (United States)

    Harris, Paul; Lopez de Leon, Alfredo; Rey, Michael; Ding, Hanshu; Vlasenko, Elena

    2010-11-02

    The present invention relates to isolated polypeptides having endoglucanase 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.

  1. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Schnorr, Kirk; Kramer, Randall

    2016-08-09

    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.

  2. Polypeptides having xylanase activity and polynucleotides encoding the same

    Science.gov (United States)

    Spodsberg, Nikolaj [Bagsvaed, DK

    2014-01-07

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

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

    Science.gov (United States)

    Morant, Marc Dominique

    2014-10-14

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase 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.

  4. Polypeptides having endoglucanase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

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

    2018-01-30

    The present invention relates to isolated polypeptides having endoglucanase 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.

  5. Action Mechanism of Fibroblast Growth Factor-2 (FGF-2 in the Promotion of Periodontal Regeneration in Beagle Dogs.

    Directory of Open Access Journals (Sweden)

    Toshie Nagayasu-Tanaka

    Full Text Available Fibroblast growth factor-2 (FGF-2 enhances the formation of new alveolar bone, cementum, and periodontal ligament (PDL in periodontal defect models. However, the mechanism through which FGF-2 acts in periodontal regeneration in vivo has not been fully clarified yet. To reveal the action mechanism, the formation of regenerated tissue and gene expression at the early phase were analyzed in a beagle dog 3-wall periodontal defect model. FGF-2 (0.3% or the vehicle (hydroxypropyl cellulose only were topically applied to the defect in FGF-2 and control groups, respectively. Then, the amount of regenerated tissues and the number of proliferating cells at 3, 7, 14, and 28 days and the number of blood vessels at 7 days were quantitated histologically. Additionally, the expression of osteogenic genes in the regenerated tissue was evaluated by real-time PCR at 7 and 14 days. Compared with the control, cell proliferation around the existing bone and PDL, connective tissue formation on the root surface, and new bone formation in the defect at 7 days were significantly promoted by FGF-2. Additionally, the number of blood vessels at 7 days was increased by FGF-2 treatment. At 28 days, new cementum and PDL were extended by FGF-2. Moreover, FGF-2 increased the expression of bone morphogenetic protein 2 (BMP-2 and osteoblast differentiation markers (osterix, alkaline phosphatase, and osteocalcin in the regenerated tissue. We revealed the facilitatory mechanisms of FGF-2 in periodontal regeneration in vivo. First, the proliferation of fibroblastic cells derived from bone marrow and PDL was accelerated and enhanced by FGF-2. Second, angiogenesis was enhanced by FGF-2 treatment. Finally, osteoblastic differentiation and bone formation, at least in part due to BMP-2 production, were rapidly induced by FGF-2. Therefore, these multifaceted effects of FGF-2 promote new tissue formation at the early regeneration phase, leading to enhanced formation of new bone, cementum

  6. Recombinant human fibroblast growth factor-2 promotes nerve regeneration and functional recovery after mental nerve crush injury.

    Science.gov (United States)

    Lee, Sung Ho; Jin, Wei-Peng; Seo, Na Ri; Pang, Kang-Mi; Kim, Bongju; Kim, Soung-Min; Lee, Jong-Ho

    2017-04-01

    Several studies have shown that fibroblast growth factor-2 (FGF2) can directly affect axon regeneration after peripheral nerve damage. In this study, we performed sensory tests and histological analyses to study the effect of recombinant human FGF-2 (rhFGF2) treatment on damaged mental nerves. The mental nerves of 6-week-old male Sprague-Dawley rats were crush-injured for 1 minute and then treated with 10 or 50 μg/mL rhFGF2 or PBS in crush injury area with a mini Osmotic pump. Sensory test using von Frey filaments at 1 week revealed the presence of sensory degeneration based on decreased gap score and increased difference score. However, at 2 weeks, the gap score and difference score were significantly rebounded in the mental nerve crush group treated with 10 μg/mL rhFGF2. Interestingly, treatment with 10 μg/mL rhFGF had a more obviously positive effect on the gap score than treatment with 50 μg/mL rhFGF2. In addition, retrograde neuronal tracing with Dil revealed a significant increase in nerve regeneration in the trigeminal ganglion at 2 and 4 weeks in the rhFGF2 groups (10 μg/mL and 50 μg/mL) than in the PBS group. The 10 μg/mL rhFGF2 group also showed an obviously robust regeneration in axon density in the mental nerve at 4 weeks. Our results demonstrate that 10 μg/mL rhFGF induces mental nerve regeneration and sensory recovery after mental nerve crush injury.

  7. Membrane-Type 1 Matrix Metalloproteinase Downregulates Fibroblast Growth Factor-2 Binding to the Cell Surface and Intracellular Signaling.

    Science.gov (United States)

    Tassone, Evelyne; Valacca, Cristina; Mignatti, Paolo

    2015-02-01

    Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), a transmembrane proteinase with an extracellular catalytic domain and a short cytoplasmic tail, degrades extracellular matrix components and controls diverse cell functions through proteolytic and non-proteolytic interactions with extracellular, intracellular, and transmembrane proteins. Here we show that in tumor cells MT1-MMP downregulates fibroblast growth factor-2 (FGF-2) signaling by reducing the amount of FGF-2 bound to the cell surface with high and low affinity. FGF-2 induces weaker activation of ERK1/2 MAP kinase in MT1-MMP expressing cells than in cells devoid of MT1-MMP. This effect is abolished in cells that express proteolytically inactive MT1-MMP but persists in cells expressing MT1-MMP mutants devoid of hemopexin-like or cytoplasmic domain, showing that FGF-2 signaling is downregulated by MT1-MMP proteolytic activity. MT1-MMP expression results in downregulation of FGFR-1 and -4, and in decreased amount of cell surface-associated FGF-2. In addition, MT1-MMP strongly reduces the amount of FGF-2 bound to the cell surface with low affinity. Because FGF-2 association with low-affinity binding sites is a prerequisite for binding to its high-affinity receptors, downregulation of low-affinity binding to the cell surface results in decreased FGF-2 signaling. Consistent with this conclusion, FGF-2 induction of tumor cell migration and invasion in vitro is stronger in cells devoid of MT1- MMP than in MT1-MMP expressing cells. Thus, MT1-MMP controls FGF-2 signaling by a proteolytic mechanism that decreases the cell's biological response to FGF-2. © 2014 Wiley Periodicals, Inc.

  8. Fibroblast growth factor-2 is expressed by the bovine uterus and stimulates interferon-tau production in bovine trophectoderm.

    Science.gov (United States)

    Michael, Donna D; Alvarez, Idania M; Ocón, Olga M; Powell, Anne M; Talbot, Neil C; Johnson, Sally E; Ealy, Alan D

    2006-07-01

    Uterine-derived factors are essential for conceptus development and secretion of the maternal recognition-of-pregnancy factor, interferon-tau (IFNT), in ruminant species. The objectives of this study were to determine whether fibroblast growth factor-2 (FGF-2) is expressed in the bovine uterus during early pregnancy in cattle and to determine whether FGF-2 supplementation affects IFNT mRNA and protein abundance in bovine trophectoderm. FGF-2 mRNA was present in endometrium throughout the estrous cycle and was localized to the luminal and glandular endometrial epithelium at d 17-18 after estrus in pregnant and nonpregnant cows. Immunoreactive FGF-2 protein was detected within the endometrium and in the uterine lumen at d 17-18 after estrus, and concentrations did not differ based on pregnancy status. In a bovine trophectoderm cell line, CT-1, supplementation of medium with at least 1 ng/ml FGF-2 increased the incorporation of [(3)H]thymidine into DNA. Similarly, IFNT secretion from CT-1 cells increased after FGF-2 supplementation (1-100 ng/ml) for 72 h. Abundance of IFNT mRNA in CT-1 cells increased after 24 h exposure to 1, 10, or 100 ng/ml FGF-2. In bovine blastocysts, FGF-2 supplementation did not affect cell number after 72 h of culture but did stimulate IFNT protein concentrations in conditioned medium. In summary, FGF-2 is present in the uterine lumen during early pregnancy and increases IFNT mRNA and protein abundance in trophectoderm. The magnitude by which FGF-2 stimulates IFNT expression suggests that this uterine-derived factor plays an active role in regulating the establishment and maintenance of pregnancy in ruminants.

  9. Fibroblast Growth Factor 2 Dimer with Superagonist In Vitro Activity Improves Granulation Tissue Formation During Wound Healing

    Science.gov (United States)

    Decker, Caitlin G.; Wang, Yu; Paluck, Samantha J.; Shen, Lu; Loo, Joseph A.; Levine, Alex J.; Miller, Lloyd S.; Maynard, Heather D.

    2015-01-01

    Site-specific chemical dimerization of fibroblast growth factor 2 (FGF2) with the optimal linker length resulted in a FGF2 homodimer with improved granulation tissue formation and blood vessel formation at exceptionally low concentrations. Homodimers of FGF2 were synthesized through site-specific linkages to both ends of different molecular weight poly(ethylene glycols) (PEGs). The optimal linker length was determined by screening dimer-induced metabolic activity of human dermal fibroblasts and found to be that closest to the inter-cysteine distance, 70 Å, corresponding to 2 kDa PEG. A straightforward analysis of the kinetics of second ligand binding as a function of tether length showed that, as the polymerization index (the number of monomer repeat units in the polymer, N) of the tether decreases, the mean time for second ligand capture decreases as ~N3/2, leading to an enhancement of the number of doubly bound ligands in steady-state for a given (tethered) ligand concentration. FGF2-PEG2k-FGF2 induced greater fibroblast metabolic activity than FGF2 alone, all other dimers, and all monoconjugates, at each concentration tested, with the greatest difference observed at low (0.1 ng/mL) concentration. FGF2-PEG2k-FGF2 further exhibited superior activity compared to FGF2 for both metabolic activity and migration in human umbilical vein endothelial cells, as well as improved angiogenesis in a coculture model in vitro. Efficacy in an in vivo wound healing model was assessed in diabetic mice. FGF2-PEG2k-FGF2 increased granulation tissue and blood vessel density in the wound bed compared to FGF2. The results suggest that this rationally designed construct may be useful for improving the fibroblast matrix formation and angiogenesis in chronic wound healing. PMID:26731578

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

    Science.gov (United States)

    Ma, Qianli; Wang, Wei; Chu, Paul K; Mei, Shenglin; Ji, Kun; Jin, Lei; Zhang, Yumei

    2012-01-01

    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). 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. 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 concentration (500 ng/mL) of FGF2 immobilization exhibited improved HGF functions such as cellular attachment, proliferation, and extracellular matrix-related gene expression. Moreover, significant bidirectional as well as concentration- and time-dependent bioactivity was observed. Synergism of the FGF2-impregnated titanium dioxide nanotubular surface revealed good gingival-implant integration, indicating that these materials might have promising applications in dentistry and other biomedical devices.

  11. Exogenous insulin-like growth factor 2 administration enhances memory consolidation and persistence in a time-dependent manner.

    Science.gov (United States)

    Lee, Younghwan; Lee, Young Woo; Gao, Qingtao; Lee, Younghwa; Lee, Hyung Eun; Ryu, Jong Hoon

    2015-10-05

    Memory consolidation is an important process for the formation of long-term memory. We have previously reported that mature brain-derived neurotrophic factor enhances memory consolidation within 9h after initial learning. Recent studies suggest that insulin-like growth factor 2 (IGF2) significantly enhances memory consolidation and prevents forgetting. Thus, we hypothesized that IGF2 exerts its activity on cognitive performance in a time-dependent manner as observed in our previous study. In the one-trial step-through inhibitory avoidance task, we demonstrate that a bilateral injection of IGF2 into the dorsal hippocampus 6 or 9 h after training significantly enhanced the step-through latencies compared with the vehicle-treated controls in the retention trial, which was conducted 24 h after the acquisition trial. However, 12h post-training, IGF2 injection did not increase the step-through latencies. Intriguingly, in the retention trial at 21 days after the training, hippocampal IGF2 injection 6, 9 or 12 h after the acquisition trial significantly increased the step-through latencies compared with the vehicle-treated controls. IGF2 administration at 9 h and 12 h after the acquisition trial significantly increased discrimination index and exploration time on the novel-located object in the test trial at 24 h and 21 days, respectively, after the acquisition trial in the novel location recognition task. In addition, IGF2-induced an increase in the step-through latencies in the retention trial 24 h or 21 days, respectively, after the initial learning was completely abolished by co-injected anti-IGF2 receptor antibody. These results suggest that IGF2 enhances memory consolidation within 9h after initial learning, and increased IGF2 within the 12 h after the acquisition trial, which represents a delayed consolidation phase, is also critical for memory persistence. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling.

    Science.gov (United States)

    Santiago, Jon-Jon; McNaughton, Leslie J; Koleini, Navid; Ma, Xin; Bestvater, Brian; Nickel, Barbara E; Fandrich, Robert R; Wigle, Jeffrey T; Freed, Darren H; Arora, Rakesh C; Kardami, Elissavet

    2014-01-01

    Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious

  13. Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems

    NARCIS (Netherlands)

    J. Rijlaarsdam (Jolien); C.A.M. Cecil (Charlotte A.M.); E. Walton (Esther); Mesirow, M.S.C. (Maurissa S. C.); C.L. Relton (Caroline); T.R. Gaunt (Tom); W.L. McArdle (Wendy); Barker, E.D. (Edward D.)

    2017-01-01

    textabstractBackground: Conduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to 'unhealthy diet'. Early-life diet also associates with DNA methylation of the insulin-like growth factor 2 gene (IGF2), involved in fetal and neural

  14. 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.

  15. 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.

  16. Variants of polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, Matt; Wogulis, Mark

    2017-11-14

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

  17. 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...

  18. Fibroblast growth factor 2 is required for epithelial recovery, but not for pulmonary fibrosis, in response to bleomycin.

    Science.gov (United States)

    Guzy, Robert D; Stoilov, Ivan; Elton, Timothy J; Mecham, Robert P; Ornitz, David M

    2015-01-01

    The pathogenesis of pulmonary fibrosis involves lung epithelial injury and aberrant proliferation of fibroblasts, and results in progressive pulmonary scarring and declining lung function. In vitro, fibroblast growth factor (FGF) 2 promotes myofibroblast differentiation and proliferation in cooperation with the profibrotic growth factor, transforming growth factor-β1, but the in vivo requirement for FGF2 in the development of pulmonary fibrosis is not known. The bleomycin model of lung injury and pulmonary fibrosis was applied to Fgf2 knockout (Fgf2(-/-)) and littermate control mice. Weight loss, mortality, pulmonary fibrosis, and histology were analyzed after a single intranasal dose of bleomycin. Inflammation was evaluated in bronchoalveolar lavage (BAL) fluid, and epithelial barrier integrity was assessed by measuring BAL protein and Evans Blue dye permeability. Fgf2 is expressed in mouse and human lung epithelial and inflammatory cells, and, in response to bleomycin, Fgf2(-/-) mice have significantly increased mortality and weight loss. Analysis of BAL fluid and histology show that pulmonary fibrosis is unaltered, but Fgf2(-/-) mice fail to efficiently resolve inflammation, have increased BAL cellularity, and, importantly, deficient recovery of epithelial integrity. Fgf2(-/-) mice similarly have deficient recovery of club cell secretory protein(+) bronchial epithelium in response to naphthalene. We conclude that FGF2 is not required for bleomycin-induced pulmonary fibrosis, but rather is essential for epithelial repair and maintaining epithelial integrity after bleomycin-induced lung injury in mice. These data identify that FGF2 acts as a protective growth factor after lung epithelial injury, and call into question the role of FGF2 as a profibrotic growth factor in vivo.

  19. Fibroblast Growth Factor 2 Is Required for Epithelial Recovery, but Not for Pulmonary Fibrosis, in Response to Bleomycin

    Science.gov (United States)

    Guzy, Robert D.; Stoilov, Ivan; Elton, Timothy J.; Mecham, Robert P.

    2015-01-01

    The pathogenesis of pulmonary fibrosis involves lung epithelial injury and aberrant proliferation of fibroblasts, and results in progressive pulmonary scarring and declining lung function. In vitro, fibroblast growth factor (FGF) 2 promotes myofibroblast differentiation and proliferation in cooperation with the profibrotic growth factor, transforming growth factor-β1, but the in vivo requirement for FGF2 in the development of pulmonary fibrosis is not known. The bleomycin model of lung injury and pulmonary fibrosis was applied to Fgf2 knockout (Fgf2−/−) and littermate control mice. Weight loss, mortality, pulmonary fibrosis, and histology were analyzed after a single intranasal dose of bleomycin. Inflammation was evaluated in bronchoalveolar lavage (BAL) fluid, and epithelial barrier integrity was assessed by measuring BAL protein and Evans Blue dye permeability. Fgf2 is expressed in mouse and human lung epithelial and inflammatory cells, and, in response to bleomycin, Fgf2−/− mice have significantly increased mortality and weight loss. Analysis of BAL fluid and histology show that pulmonary fibrosis is unaltered, but Fgf2−/− mice fail to efficiently resolve inflammation, have increased BAL cellularity, and, importantly, deficient recovery of epithelial integrity. Fgf2−/− mice similarly have deficient recovery of club cell secretory protein+ bronchial epithelium in response to naphthalene. We conclude that FGF2 is not required for bleomycin-induced pulmonary fibrosis, but rather is essential for epithelial repair and maintaining epithelial integrity after bleomycin-induced lung injury in mice. These data identify that FGF2 acts as a protective growth factor after lung epithelial injury, and call into question the role of FGF2 as a profibrotic growth factor in vivo. PMID:24988442

  20. 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

  1. Exploiting Surface Plasmon Resonance (SPR Technology for the Identification of Fibroblast Growth Factor-2 (FGF2 Antagonists Endowed with Antiangiogenic Activity

    Directory of Open Access Journals (Sweden)

    Marco Presta

    2009-08-01

    Full Text Available Angiogenesis, the process of new blood vessel formation, is implicated in various physiological/pathological conditions, including embryonic development, inflammation and tumor growth. Fibroblast growth factor-2 (FGF2 is a heparin-binding angiogenic growth factor involved in various physiopathological processes, including tumor neovascularization. Accordingly, FGF2 is considered a target for antiangiogenic therapies. Thus, numerous natural/synthetic compounds have been tested for their capacity to bind and sequester FGF2 in the extracellular environment preventing its interaction with cellular receptors. We have exploited surface plasmon resonance (SPR technique in search for antiangiogenic FGF2 binders/antagonists. In this review we will summarize our experience in SPR-based angiogenesis research, with the aim to validate SPR as a first line screening for the identification of antiangiogenic compounds.

  2. Osteostatin improves the osteogenic activity of fibroblast growth factor-2 immobilized in Si-doped hydroxyapatite in osteoblastic cells.

    Science.gov (United States)

    Lozano, Daniel; Feito, María José; Portal-Núñez, Sergio; Lozano, Rosa María; Matesanz, María Concepción; Serrano, María Concepción; Vallet-Regí, María; Portolés, María Teresa; Esbrit, Pedro

    2012-07-01

    Si-doped hydroxyapatite (Si-HA) is a suitable ceramic for the controlled release of agents to improve bone repair. We recently showed that parathyroid hormone-related protein (PTHrP) (107-111) (osteostatin) has remarkable osteogenic features in various in vitro and in vivo systems. Fibroblast growth factor (FGF)-2 modulates osteoblastic function and induces angiogenesis, and can promote osteoblast adhesion and proliferation after immobilization on Si-HA. In the present study we examined whether osteostatin might improve the biological efficacy of FGF-2-coated Si-HA in osteoblastic MC3T3-E1 cells in vitro. We found that Si-HA/FGF-2 in the presence or absence of osteostatin (100 nM) similarly increased cell growth (by about 50%). However, addition of the latter peptide to Si-HA/FGF-2 significantly enhanced gene expression of Runx2, osteocalcin, vascular endothelial growth factor (VEGF) and the VEGF receptors 1 and 2, without significantly affecting that of FGF receptors in these cells. Moreover, secreted VEGF in the MC3T3-E1 cell conditioned medium, which induced the proliferation of pig endothelial-like cells, was also enhanced by these combined factors. The synergistic action of osteostatin and Si-HA/FGF-2 on the VEGF system was abrogated by a mitogen-activated protein kinase inhibitor (U0126) and by the calcium antagonist verapamil. This action was related to an enhancement of alkaline phosphatase activity and matrix mineralization in MC3T3-E1 cells, and also in primary human osteoblastic cells. These in vitro data show that osteostatin increases the osteogenic efficacy of a Si-HA/FGF-2 biomaterial by a mechanism involving mitogen-activated protein kinases and intracellular Ca(2+). These findings provide an attractive strategy for bone tissue engineering. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

    OpenAIRE

    Pearce, Celeste Leigh; Doherty, Jennifer A.; Van Den Berg, David J.; Moysich, Kirsten; Hsu, Chris; Cushing-Haugen, Kara L.; Conti, David V.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Pharoah, Paul D.P.; Song, Honglin; Kjaer, Susanne K.; Hogdall, Estrid

    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 ovarian cancer and 321 women with borderline epithelial ovarian tumors was carried out to test the association between tag single-nucleotide polymorphisms (tSNPs) (n=58) in this pathway and risk of o...

  4. 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...

  5. Isolated Polynucleotides and Methods of Promoting a Morphology in a Fungus

    Science.gov (United States)

    Lasure, Linda L [Fall City, WA; Dai, Ziyu [Richland, WA

    2008-10-21

    The invention includes isolated polynucleotide molecules that are differentially expressed in a native fungus exhibiting a first morphology relative to the native fungus exhibiting a second morphology. The invention includes a method of enhancing a bioprocess utilizing a fungus. A transformed fungus is produced by transforming a fungus with a recombinant polynucleotide molecule. The recombinant polynucleotide molecule contains an isolated polynucleotide sequence linked operably to a promoter. The polynucleotide sequence is expressed to promote a first morphology. The first morphology of the transformed fungus enhances a bioprocess relative to the bioprocess utilizing a second morphology.

  6. 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

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

    Science.gov (United States)

    Pearce, Celeste Leigh; Doherty, Jennifer A.; Van Den Berg, David J.; Moysich, Kirsten; Hsu, Chris; Cushing-Haugen, Kara L.; Conti, David V.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Pharoah, Paul D.P.; Song, Honglin; Kjaer, Susanne K.; Hogdall, Estrid; Hogdall, Claus; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Gronwald, Jacek; Medrek, Krzysztof; Jakubowska, Anna; Lubinski, Jan; Chenevix-Trench, Georgia; Beesley, Jonathan; Webb, Penelope M.; Berchuck, Andrew; Schildkraut, Joellen M.; Iversen, Edwin S.; Moorman, Patricia G.; Edlund, Christopher K.; Stram, Daniel O.; Pike, Malcolm C.; Ness, Roberta B.; Rossing, Mary Anne; Wu, Anna H.

    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 ovarian cancer and 321 women with borderline epithelial ovarian tumors was carried out to test the association between tag single-nucleotide polymorphisms (tSNPs) (n=58) in this pathway and risk of ovarian cancer. We found no association between variation in IGF1, IGFBP1 or IGFBP3 and risk of invasive disease, whereas five tSNPs in IGF2 were associated with risk of invasive epithelial ovarian cancer at P<0.05 and followed-up one of the associated SNPs. We conducted genotyping in 3216 additional non-Hispanic white cases 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 as an important gene for ovarian cancer; additional genotyping is warranted to further confirm these associations with IGF2 and to narrow down the region harboring the causal SNP. PMID:21422097

  8. 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.

  9. Fibroblast growth factor 2 (FGF2) is present in human spermatozoa and is related with sperm motility. The use of recombinant FGF2 to improve motile sperm recovery.

    Science.gov (United States)

    Garbarino Azúa, D J; Saucedo, L; Giordana, S; Magri, M L; Buffone, M G; Neuspiller, F; Vazquez-Levin, M H; Marín-Briggiler, C I

    2017-09-01

    Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate several functions of somatic cells. In a previous work, we reported FGFR expression in human spermatozoa and their involvement in motility. This study aimed to evaluate the presence and localization of fibroblast growth factor 2 (FGF2) in human spermatozoa, to determine the relationship of FGF2 levels with conventional semen parameters and to assess the effect of recombinant FGF2 (rFGF2) on sperm recovery in a selection procedure. Western immunoblotting analysis using an antibody against FGF2 revealed an 18-kDa band in sperm protein extracts. The protein was immunolocalized in the sperm flagellum and acrosomal region, as well as in all germ cells. Sperm FGF2 levels, assessed by flow cytometry, showed a positive (p recoveries, and increased (p recovery in selection techniques. © 2017 American Society of Andrology and European Academy of Andrology.

  10. Plasticity of mesenchymal stem cells from mouse bone marrow in the presence of conditioned medium of the facial nerve and fibroblast growth factor-2.

    Science.gov (United States)

    Lucena, Eudes Euler de Souza; Guzen, Fausto Pierdoná; Cavalcanti, José Rodolfo Lopes de Paiva; Marinho, Maria Jocileide de Medeiros; Pereira, Wogelsanger Oliveira; Barboza, Carlos Augusto Galvão; Costa, Miriam Stela Mariz de Oliveira; do Nascimento Júnior, Expedito Silva; Cavalcante, Jeferson Sousa

    2014-01-01

    A number of evidences show the influence of the growth of injured nerve fibers in peripheral nervous system as well as potential implant stem cells (SCs). The SCs implementation in the clinical field is promising and the understanding of proliferation and differentiation is essential. This study aimed to evaluate the plasticity of mesenchymal SCs from bone marrow of mice in the presence of culture medium conditioned with facial nerve explants and fibroblast growth factor-2 (FGF-2). The growth and morphology were assessed for over 72 hours. Quantitative phenotypic analysis was taken from the immunocytochemistry for glial fibrillary acidic protein (GFAP), protein OX-42 (OX-42), protein associated with microtubule MAP-2 (MAP-2), protein β-tubulin III (β-tubulin III), neuronal nuclear protein (NeuN), and neurofilament 200 (NF-200). Cells cultured with conditioned medium alone or combined with FGF-2 showed morphological features apparently similar at certain times to neurons and glia and a significant proliferative activity in groups 2 and 4. Cells cultivated only with conditioned medium acquired a glial phenotype. Cells cultured with FGF-2 and conditioned medium expressed GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200. This study improves our understanding of the plasticity of mesenchymal cells and allows the search for better techniques with SCs.

  11. An optimized dosing regimen of cimaglermin (neuregulin 1β3, glial growth factor 2) enhances molecular markers of neuroplasticity and functional recovery after permanent ischemic stroke in rats.

    Science.gov (United States)

    Iaci, Jennifer F; Parry, Tom J; Huang, Zhihong; Pavlopoulos, Elias; Finklestein, Seth P; Ren, Jingmei; Caggiano, Anthony

    2016-03-01

    Cimaglermin (neuregulin 1β3, glial growth factor 2) is a neuregulin growth factor family member in clinical development for chronic heart failure. Previously, in a permanent middle cerebral artery occlusion (pMCAO) rat stroke model, systemic cimaglermin treatment initiated up to 7 days after ischemia onset promoted recovery without reduced lesion volume. Presented here to extend the evidence are two studies that use a rat stroke model to evaluate the effects of cimaglermin dose level and dose frequency initiated 24 hr after pMCAO. Forelimb- and hindlimb-placing scores (proprioceptive behavioral tests), body-swing symmetry, and infarct volume were compared between treatment groups (n = 12/group). Possible mechanisms underlying cimaglermin-mediated neurologic recovery were examined through axonal growth and synapse formation histological markers. Cimaglermin was evaluated over a wider dose range (0.02, 0.1, or 1.0 mg/kg) than doses previously shown to be effective but used the same dosing regimen (2 weeks of daily intravenous administration, then 1 week without treatment). The dose-frequency study used the dose-ranging study's most effective dose (1.0 mg/kg) to compare daily, once per week, and twice per week dosing for 3 weeks (then 1 week without treatment). Dose- and frequency-dependent functional improvements were observed with cimaglermin without reduced lesion volume. Cimaglermin treatment significantly increased growth-associated protein 43 expression in both hemispheres (particularly somatosensory and motor cortices) and also increased synaptophysin expression. These data indicate that cimaglermin enhances recovery after stroke. Immunohistochemical changes were consistent with axonal sprouting and synapse formation but not acute neuroprotection. Cimaglermin represents a potential clinical development candidate for ischemic stroke treatment. © 2015 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

  12. 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.

  13. 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.

  14. Anti‐Remodeling and Anti‐Fibrotic Effects of the Neuregulin‐1β Glial Growth Factor 2 in a Large Animal Model of Heart Failure

    Science.gov (United States)

    Galindo, Cristi L.; Kasasbeh, Ehab; Murphy, Abigail; Ryzhov, Sergey; Lenihan, Sean; Ahmad, Farhaan A.; Williams, Philip; Nunnally, Amy; Adcock, Jamie; Song, Yanna; Harrell, Frank E.; Tran, Truc‐Linh; Parry, Tom J.; Iaci, Jen; Ganguly, Anindita; Feoktistov, Igor; Stephenson, Matthew K.; Caggiano, Anthony O.; Sawyer, Douglas B.; Cleator, John H.

    2014-01-01

    Background Neuregulin‐1β (NRG‐1β) is a growth factor critical for cardiac development and repair with therapeutic potential for heart failure. We previously showed that the glial growth factor 2 (GGF2) isoform of NRG‐1β improves cardiac function in rodents after myocardial infarction (MI), but its efficacy in a large animal model of cardiac injury has not been examined. We therefore sought to examine the effects of GGF2 on ventricular remodeling, cardiac function, and global transcription in post‐MI swine, as well as potential mechanisms for anti‐remodeling effects. Methods and Results MI was induced in anesthetized swine (n=23) by intracoronary balloon occlusion. At 1 week post‐MI, survivors (n=13) received GGF2 treatment (intravenous, biweekly for 4 weeks; n=8) or were untreated (n=5). At 5 weeks post‐MI, fractional shortening was higher (32.8% versus 25.3%, P=0.019), and left ventricular (LV) end‐diastolic dimension lower (4.5 versus 5.3 cm, P=0.003) in GGF2‐treated animals. Treatment altered expression of 528 genes, as measured by microarrays, including collagens, basal lamina components, and matricellular proteins. GGF2‐treated pigs exhibited improvements in LV cardiomyocyte mitochondria and intercalated disk structures and showed less fibrosis, altered matrix structure, and fewer myofibroblasts (myoFbs), based on trichrome staining, electron microscopy, and immunostaining. In vitro experiments with isolated murine and rat cardiac fibroblasts demonstrate that NRG‐1β reduces myoFbs, and suppresses TGFβ‐induced phospho‐SMAD3 as well as αSMA expression. Conclusions These results suggest that GGF2/NRG‐1β prevents adverse remodeling after injury in part via anti‐fibrotic effects in the heart. PMID:25341890

  15. A novel pathway links oxidative stress to loss of insulin growth factor-2 (IGF2 imprinting through NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Bing Yang

    Full Text Available Genomic imprinting is the allele-specific expression of a gene based on parental origin. Loss of imprinting(LOI of Insulin-like Growth Factor 2 (IGF2 during aging is important in tumorigenesis, yet the regulatory mechanisms driving this event are largely unknown. In this study oxidative stress, measured by increased NF-κB activity, induces LOI in both cancerous and noncancerous human prostate cells. Decreased expression of the enhancer-blocking element CCCTC-binding factor(CTCF results in reduced binding of CTCF to the H19-ICR (imprint control region, a major factor in the allelic silencing of IGF2. This ICR then develops increased DNA methylation. Assays identify a recruitment of the canonical pathway proteins NF-κB p65 and p50 to the CTCF promoter associated with the co-repressor HDAC1 explaining gene repression. An IκBα super-repressor blocks oxidative stress-induced activation of NF-κB and IGF2 imprinting is maintained. In vivo experiments using IκBα mutant mice with continuous NF-κB activation demonstrate increased IGF2 LOI further confirming a central role for canonical NF-κB signaling. We conclude CTCF plays a central role in mediating the effects of NF-κB activation that result in altered imprinting both in vitro and in vivo. This novel finding connects inflammation found in aging prostate tissues with the altered epigenetic landscape.

  16. Basic Fibroblast Growth Factor 2 Is a Determinant of CD4 T Cell-Airway Smooth Muscle Cell Communication through Membrane Conduits.

    Science.gov (United States)

    Farahnak, Soroor; McGovern, Toby K; Kim, Rachael; O'Sullivan, Michael; Chen, Brian; Lee, Minhyoung; Yoshie, Haruka; Wang, Anna; Jang, Joyce; Al Heialy, Saba; Lauzon, Anne-Marie; Martin, James G

    2017-11-01

    Activated CD4 T cells connect to airway smooth muscle cells (ASMCs) in vitro via lymphocyte-derived membrane conduits (LMCs) structurally similar to membrane nanotubes with unknown intercellular signals triggering their formation. We examined the structure and function of CD4 T cell-derived LMCs, and we established a role for ASMC-derived basic fibroblast growth factor 2 (FGF2b) and FGF receptor (FGFR)1 in LMC formation. Blocking FGF2b's synthesis and FGFR1 function reduced LMC formation. Mitochondrial flux from ASMCs to T cells was partially FGF2b and FGFR1 dependent. LMC formation by CD4 T cells and mitochondrial transfer from ASMCs was increased in the presence of asthmatic ASMCs that expressed more mRNA for FGF2b compared with normal ASMCs. These observations identify ASMC-derived FGF2b as a factor needed for LMC formation by CD4 T cells, affecting intercellular communication. Copyright © 2017 by The American Association of Immunologists, Inc.

  17. 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.

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

    Science.gov (United States)

    Morant, Marc Dominique

    2014-05-06

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase 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.

  20. Polypeptides having beta-glucosidase activity and beta-xylosidase activity and polynucleotides encoding same

    Science.gov (United States)

    Morant, Marc Dominique

    2014-04-29

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase 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.

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

    Science.gov (United States)

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

    2014-04-01

    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. Copyright © 2014. Published by Elsevier B.V.

  2. Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions.

    Science.gov (United States)

    Fujii, Kimihito; Watanabe, Rie; Ando, Takahito; Kousaka, Junko; Mouri, Yukako; Yoshida, Miwa; Imai, Tsuneo; Nakano, Shogo; Fukutomi, Takashi

    2017-12-01

    In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast

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

    Energy Technology Data Exchange (ETDEWEB)

    Su, Ching-Chuan [Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan (China); Kao, Chia-Tze; Hung, Chi-Jr [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chen, Yi-Jyun [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Dental Department, Taichung Hospital, Ministry of Health and Welfare, Taichung City, Taiwan (China); Huang, Tsui-Hsien, E-mail: thh@csmu.edu.tw [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Shie, Ming-You, E-mail: eviltacasi@gmail.com [Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan (China)

    2014-04-01

    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

  4. 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.)

  5. 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

  6. 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.)

  7. 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.

  8. ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but not by fibroblast growth factor 2: evidence for a distinct fibroblast growth factor receptor response to neural cell adhesion molecule activation

    DEFF Research Database (Denmark)

    Hinsby, Anders M; Lundfald, Line; Ditlevsen, Dorte K

    2004-01-01

    Homophilic binding in trans of the neural cell adhesion molecule (NCAM) mediates adhesion between cells and leads, via activation of intracellular signaling cascades, to neurite outgrowth in primary neurons as well as in the neuronal cell line PC12. NCAM mediates neurite extension in PC12 cells....... Here, we investigated the involvement of adaptor proteins in NCAM and fibroblast growth factor 2 (FGF2)-mediated neurite outgrowth in the PC12-E2 cell line. We found that both FGFR substrate-2 and Grb2 play important roles in NCAM as well as in FGF2-stimulated events. In contrast, the docking protein...... ShcA was pivotal to neurite outgrowth induced by NCAM, but not by FGF2, in PC12 cells. Moreover, in rat cerebellar granule neurons, phosphorylation of ShcA was stimulated by an NCAM mimicking peptide, but not by FGF2. This activation was blocked by inhibitors of both FGFR and Fyn, indicating that NCAM...

  9. Circulating Fibroblast Growth Factor-2, HIV-Tat, and Vascular Endothelial Cell Growth Factor-A in HIV-Infected Children with Renal Disease Activate Rho-A and Src in Cultured Renal Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Jharna R Das

    Full Text Available Renal endothelial cells (REc are the first target of HIV-1 in the kidney. The integrity of REc is maintained at least partially by heparin binding growth factors that bind to heparan sulfate proteoglycans located on their cell surface. However, previous studies showed that the accumulation of two heparin-binding growth factors, Vascular Endothelial Cell Growth Factor-A (VEGF-A and Fibroblast Growth Factor-2 (FGF-2, in combination with the viral protein Tat, can precipitate the progression of HIV-renal diseases. Nonetheless, very little is known about how these factors affect the behavior of REc in HIV+ children. We carried out this study to determine how VEGF-A, FGF-2, and HIV-Tat, modulate the cytoskeletal structure and permeability of cultured REc, identify key signaling pathways involved in this process, and develop a functional REc assay to detect HIV+ children affected by these changes. We found that VEGF-A and FGF-2, acting in synergy with HIV-Tat and heparin, affected the cytoskeletal structure and permeability of REc through changes in Rho-A, Src, and Rac-1 activity. Furthermore, urine samples from HIV+ children with renal diseases, showed high levels of VEGF-A and FGF-2, and induced similar changes in cultured REc and podocytes. These findings suggest that FGF-2, VEGF-A, and HIV-Tat, may affect the glomerular filtration barrier in HIV+ children through the induction of synergistic changes in Rho-A and Src activity. Further studies are needed to define the clinical value of the REc assay described in this study to identify HIV+ children exposed to circulating factors that may induce glomerular injury through similar mechanisms.

  10. 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...

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

    DEFF Research Database (Denmark)

    Hawkins, Clare Louise; Davies, Michael Jonathan

    2002-01-01

    HOCl damage to DNA, RNA, and polynucleotides. Reaction of HOCl with these materials is shown to yield multiple semistable chloramines (RNHCl/RR'NCl), which are the major initial products, and account for 50-95% of the added HOCl. These chloramines decay by thermal and metal-ion catalyzed processes...... 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...... rationalize the preferential formation of chlorinated 2'-deoxycytidine and 2'-deoxyadenosine in DNA and suggest that DNA damage induced by HOCl, and preformed chloramines, occurs at sequence-specific sites....

  12. Gefitinib and Erlotinib Lead to Phosphorylation of Eukaryotic Initiation Factor 2 Alpha Independent of Epidermal Growth Factor Receptor in A549 Cells.

    Science.gov (United States)

    Koyama, Satoshi; Omura, Tomohiro; Yonezawa, Atsushi; Imai, Satoshi; Nakagawa, Shunsaku; Nakagawa, Takayuki; Yano, Ikuko; Matsubara, Kazuo

    2015-01-01

    Gefitinib and erlotinib are anticancer agents, which inhibit epidermal growth factor receptor (EGFR) tyrosine kinase. Interstitial lung disease (ILD) occurs in patients with non-small cell lung cancer receiving EGFR inhibitors. In the present study, we examined whether gefitinib- and erlotinib-induced lung injury related to ILD through endoplasmic reticulum (ER) stress, which is a causative intracellular mechanism in cytotoxicity caused by various chemicals in adenocarcinomic human alveolar basal epithelial cells. These two EGFR inhibitors increased Parkinson juvenile disease protein 2 and C/EBP homologous protein mRNA expressions, and activated the eukaryotic initiation factor (eIF) 2α/activating transcription factor 4 pathway without protein kinase R-like ER kinase activation in A549 cells. Gefitinib and erlotinib caused neither ER stress nor cell death; however, these agents inhibited cell growth via the reduction of cyclin-D1 expression. Tauroursodeoxycholic acid, which is known to suppress eIF2α phosphorylation, cancelled the effects of EGFR inhibitors on cyclin-D1 expression and cell proliferation in a concentration-dependent manner. The results of an EGFR-silencing study using siRNA showed that gefitinib and erlotinib affected eIF2α phosphorylation and cyclin-D1 expression independent of EGFR inhibition. Therefore, the inhibition of cell growth by these EGFR inhibitors might equate to impairment of the alveolar epithelial cell repair system via eIF2α phosphorylation and reduced cyclin-D1 expression.

  13. Targeting myocyte-specific enhancer factor 2D contributes to the suppression of cardiac hypertrophic growth by miR-92b-3p in mice.

    Science.gov (United States)

    Hu, Zhi-Qin; Luo, Jian-Fang; Yu, Xue-Ju; Zhu, Jie-Ning; Huang, Lei; Yang, Jing; Fu, Yong-Heng; Li, Tao; Xue, Yu-Mei; Feng, Ying-Qing; Shan, Zhi-Xin

    2017-11-03

    The role of microRNA-92b-3p (miR-92b-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-92b-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. MiR-92b-3p was markedly decreased in the myocardium of Ang-II-infused mice and of patients with cardiac hypertrophy. However, miR-92b-3p expression was revealed increased in Ang-II-induced neonatal mouse cardiomyocytes. Cardiac hypertrophy was shown attenuated in Ang-II-infused mice received tail vein injection of miR-92b-3p mimic. Moreover, miR-92b-3p inhibited the expression of atrial natriuretic peptide (ANP), skeletal muscle α-actin (ACTA1) and β-myosin heavy chain (MHC) in Ang-II-induced mouse cardiomyocytes in vitro . Myocyte-specific enhancer factor 2D (MEF2D), which was increased in Ang-II-induced mouse hypertrophic myocardium and cardiomyocytes, was identified as a target gene of miR-92b-3p. Functionally, miR-92b-3p mimic, consistent with MEF2D siRNA, inhibited cell size increase and protein expression of ANP, ACTA1 and β-MHC in Ang-II-treated mouse cardiomyocytes. Taken together, we demonstrated that MEF2D is a novel target of miR-92b-3p, and attenuation of miR-92b-3p expression may contribute to the increase of MEF2D in cardiac hypertrophy.

  14. 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

  15. Tyrosine Kinase Expressed in Hepatocellular Carcinoma, TEC, Controls Pluripotency and Early Cell Fate Decisions of Human Pluripotent Stem Cells via Regulation of Fibroblast Growth Factor-2 Secretion.

    Science.gov (United States)

    Vanova, Tereza; Konecna, Zaneta; Zbonakova, Zuzana; La Venuta, Giuseppe; Zoufalova, Karolina; Jelinkova, Sarka; Varecha, Miroslav; Rotrekl, Vladimir; Krejci, Pavel; Nickel, Walter; Dvorak, Petr; Kunova Bosakova, Michaela

    2017-09-01

    Human pluripotent stem cells (hPSC) require signaling provided by fibroblast growth factor (FGF) receptors. This can be initiated by the recombinant FGF2 ligand supplied exogenously, but hPSC further support their niche by secretion of endogenous FGF2. In this study, we describe a role of tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase in this process. We show that TEC-mediated FGF2 secretion is essential for hPSC self-renewal, and its lack mediates specific differentiation. Following both short hairpin RNA- and small interfering RNA-mediated TEC knockdown, hPSC secretes less FGF2. This impairs hPSC proliferation that can be rescued by increasing amounts of recombinant FGF2. TEC downregulation further leads to a lower expression of the pluripotency markers, an improved priming towards neuroectodermal lineage, and a failure to develop cardiac mesoderm. Our data thus demonstrate that TEC is yet another regulator of FGF2-mediated hPSC pluripotency and differentiation. Stem Cells 2017;35:2050-2059. © 2017 AlphaMed Press.

  16. Mutational analysis of polynucleotide phosphorylase from Escherichia coli.

    Science.gov (United States)

    Jarrige, Anne; Bréchemier-Baey, Dominique; Mathy, Nathalie; Duché, Ophélie; Portier, Claude

    2002-08-16

    Polynucleotide phosphorylase (PNPase), a homotrimeric exoribonuclease present in bacteria, is involved in mRNA degradation. In Escherichia coli, expression of this enzyme is autocontrolled at the translational level. We introduced about 30 mutations in the pnp gene by site-directed mutagenesis, most of them in phylogenetically conserved residues, and determined their effects on the three catalytic activities of PNPase, phosphorolysis, polymerisation and phosphate exchange, as well as on the efficiency of translational repression. The data are presented and discussed in the light of the crystallographic structure of PNPase from Streptomyces antibioticus. The results show that both PNPase activity and the presence of the KH and S1 RNA-binding domains are required for autocontrol. Deletions of these RNA-binding domains do not abolish any of the three catalytic activities, indicating that they are contained in a domain independent of the catalytic centre. Moreover, the catalytic centre was located around the tungsten-binding site identified by crystallography. Some mutations affect the three catalytic activities differently, an observation consistent with the presence of different subsites.

  17. 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.

  18. 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...... in designing strategies for infertility intervention. In this experiment, the possible mechanisms involved in both blastomere proliferation and regulation of cell death were studied by analysis of relative expression patterns of IGF-II, BCL2-L1, BAK1, and HSP70 in 3 classes of morphological quality groups (e...

  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. Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Michael N [Benicia, CA; Forte, Trudy M [Berkeley, CA

    2007-05-29

    Functional Apolipoprotein A-I mutant proteins, having one or more cysteine substitutions and polynucleotides encoding same, can be used to modulate paraoxonase's arylesterase activity. These ApoA-I mutant proteins can be used as therapeutic agents to combat cardiovascular disease, atherosclerosis, acute phase response and other inflammatory related diseases. The invention also includes modifications and optimizations of the ApoA-I nucleotide sequence for purposes of increasing protein expression and optimization.

  1. Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same

    Science.gov (United States)

    Oda, Michael N [Benicia, CA; Forte, Trudy M [Berkeley, CA

    2007-05-29

    Functional Apolipoprotein A-I mutant proteins, having one or more cysteine substitutions and polynucleotides encoding same, can be used to modulate paraoxonase's arylesterase activity. These ApoA-I mutant proteins can be used as therapeutic agents to combat cardiovascular disease, atherosclerosis, acute phase response and other inflammatory related diseases. The invention also includes modifications and optimizations of the ApoA-I nucleotide sequence for purposes of increasing protein expression and optimization.

  2. Effect of polynucleotides on the dimerization of glycine. [abiological protein synthesis in primitive earth conditions

    Science.gov (United States)

    Mizutani, H.; Ponnamperuma, C.

    1981-01-01

    Results from experiments to determine the effect of polynucleotides on abiological formation of peptide bonds are reported. The reaction between glycine molecules in an aqueous phase in the presence of a condensing agent was chosen as a model, with polyphosphates being selected as the condensing agent for biologically relevant peptide formation. Four types of polynucleotides were used: polygluanic acid (G), polyuridic acid (U), polyadenylic acid (A), and polycytidylic acid (C); the effects of small anions, acetate, chloride, and phosphate, were also studied. Procedures are given, including concentrations, pH, and incubation time, and the type of amino acid analyzer. The diglycine yields were, in order of most to least: G, C, A, U, and are diagrammed as a function of time; rate of formation followed the same order of magnitude as the final yields. Anion presence displayed no discernible effect. The results are taken to indicate that polynucleotides do have an effect on the formation of peptide bonds, an effect significant in the understanding of chemical evolution.

  3. E.coli polynucleotide phosphorylase expression is autoregulated through an RNase III-dependent mechanism.

    Science.gov (United States)

    Robert-Le Meur, M; Portier, C

    1992-07-01

    It has been previously shown that the pnp messenger RNAs are cleaved by RNase III at the 5' end and that these cleavages induce a rapid decay of these messengers. A translational fusion between pnp and lacZ was introduced into the chromosome of a delta lac strain to study the expression of pnp. In the presence of increased cellular concentrations of polynucleotide phosphorylase, the level of the hybrid beta-galactosidase is repressed, whereas the synthesis rate of the corresponding message is not significantly affected. In the absence of pnp, the level of the hybrid protein increases strongly. Thus, polynucleotide phosphorylase is post-transcriptionally autocontrolled. However, autocontrol is totally abolished in strains where the RNase III site on the pnp message has been deleted or in strains devoid of RNase III. These results suggest that polynucleotide phosphorylase requires RNase III cleavages to autoregulate the translation of its message. Other mutations in the ribosome binding site region support the hypothesis that this 3' to 5' processive enzyme could recognize a specific repressor binding site at the 5' end of pnp mRNA. Implications of these results on the mechanism of regulation and on messenger degradation are discussed.

  4. Initial contact of glioblastoma cells with existing normal brain endothelial cells strengthen the barrier function via fibroblast growth factor 2 secretion: a new in vitro blood-brain barrier model.

    Science.gov (United States)

    Toyoda, Keisuke; Tanaka, Kunihiko; Nakagawa, Shinsuke; Thuy, Dinh Ha Duy; Ujifuku, Kenta; Kamada, Kensaku; Hayashi, Kentaro; Matsuo, Takayuki; Nagata, Izumi; Niwa, Masami

    2013-05-01

    Glioblastoma multiforme (GBM) cells invade along the existing normal capillaries in brain. Normal capillary endothelial cells function as the blood-brain barrier (BBB) that limits permeability of chemicals into the brain. To investigate whether GBM cells modulate the BBB function of normal endothelial cells, we developed a new in vitro BBB model with primary cultures of rat brain endothelial cells (RBECs), pericytes, and astrocytes. Cells were plated on a membrane with 8 μm pores, either as a monolayer or as a BBB model with triple layer culture. The BBB model consisted of RBEC on the luminal side as a bottom, and pericytes and astrocytes on the abluminal side as a top of the chamber. Human GBM cell line, LN-18 cells, or lung cancer cell line, NCI-H1299 cells, placed on either the RBEC monolayer or the BBB model increased the transendothelial electrical resistance (TEER) values against the model, which peaked within 72 h after the tumor cell application. The TEER value gradually returned to baseline with LN-18 cells, whereas the value quickly dropped to the baseline in 24 h with NCI-H1299 cells. NCI-H1299 cells invaded into the RBEC layer through the membrane, but LN-18 cells did not. Fibroblast growth factor 2 (FGF-2) strengthens the endothelial cell BBB function by increased occludin and ZO-1 expression. In our model, LN-18 and NCI-H1299 cells secreted FGF-2, and a neutralization antibody to FGF-2 inhibited LN-18 cells enhanced BBB function. These results suggest that FGF-2 would be a novel therapeutic target for GBM in the perivascular invasive front.

  5. Fibroblast growth factor 2 induces proliferation and distribution of G2 /M phase of bovine endometrial cells involving activation of PI3K/AKT and MAPK cell signaling and prevention of effects of ER stress.

    Science.gov (United States)

    Lim, Whasun; Bae, Hyocheol; Bazer, Fuller W; Song, Gwonhwa

    2018-04-01

    Fibroblast growth factor 2 (FGF2) is abundantly expressed in conceptuses and endometria during pregnancy in diverse animal models including domestic animals. However, its intracellular mechanism of action has not been reported for bovine endometrial cells. Therefore, the aim of this study was to identify functional roles of FGF2 in bovine endometrial (BEND) cell line which has served as a good model system for investigating regulation of signal transduction following treatment with interferon-tau (IFNT) in vitro. Results of present study demonstrated that administration of FGF2 to BEND cells increased their proliferation and regulated the cell cycle through DNA replication by an increase of PCNA and Cyclin D1. FGF2 also increased phosphorylation of AKT, P70S6K, S6, ERK1/2, JNK, and P38 in BEND cells in a dose-dependent manner, and expression of each of those transcription factors was inhibited by their respective pharmacological inhibitor including Wormannin, U0126, and SP600125. In addition, the increase in proliferation of BEND cells and activation of the protein kinases in response to FGF2 was suppressed by BGJ398, a FGFR inhibitor. Furthermore, proliferation of BEND cells was inhibited by tunicamycin, but treatment of BEND cells with FGF2 restored proliferation of BEND cells. Consistent with this result, the stimulated unfolded protein response (UPR) regulatory proteins induced by tunicamycin were down-regulated by FGF2. Results of this study suggest that FGF2 promotes proliferation of BEND cells and likely enhances uterine capacity and maintenance of pregnancy by activating cell signaling via the PI3K and MAPK pathways and by restoring ER stress through the FGFR. © 2017 Wiley Periodicals, Inc.

  6. Polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Morant, Marc

    2017-02-07

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase 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.

  7. 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

  8. 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.

  9. 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.

  10. RNase III-Independent Autogenous Regulation of Escherichia coli Polynucleotide Phosphorylase via Translational Repression.

    Science.gov (United States)

    Carzaniga, Thomas; Dehò, Gianni; Briani, Federica

    2015-06-01

    The complex posttranscriptional regulation mechanism of the Escherichia coli pnp gene, which encodes the phosphorolytic exoribonuclease polynucleotide phosphorylase (PNPase), involves two endoribonucleases, namely, RNase III and RNase E, and PNPase itself, which thus autoregulates its own expression. The models proposed for pnp autoregulation posit that the target of PNPase is a mature pnp mRNA previously processed at its 5' end by RNase III, rather than the primary pnp transcript (RNase III-dependent models), and that PNPase activity eventually leads to pnp mRNA degradation by RNase E. However, some published data suggest that pnp expression may also be regulated through a PNPase-dependent, RNase III-independent mechanism. To address this issue, we constructed isogenic Δpnp rnc(+) and Δpnp Δrnc strains with a chromosomal pnp-lacZ translational fusion and measured β-galactosidase activity in the absence and presence of PNPase expressed by a plasmid. Our results show that PNPase also regulates its own expression via a reversible RNase III-independent pathway acting upstream from the RNase III-dependent branch. This pathway requires the PNPase RNA binding domains KH and S1 but not its phosphorolytic activity. We suggest that the RNase III-independent autoregulation of PNPase occurs at the level of translational repression, possibly by competition for pnp primary transcript between PNPase and the ribosomal protein S1. In Escherichia coli, polynucleotide phosphorylase (PNPase, encoded by pnp) posttranscriptionally regulates its own expression. The two models proposed so far posit a two-step mechanism in which RNase III, by cutting the leader region of the pnp primary transcript, creates the substrate for PNPase regulatory activity, eventually leading to pnp mRNA degradation by RNase E. In this work, we provide evidence supporting an additional pathway for PNPase autogenous regulation in which PNPase acts as a translational repressor independently of RNase III

  11. 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.

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. Linear and circular dichroism characterization of thionine binding mode with DNA polynucleotides

    Science.gov (United States)

    Tuite, Eimer Mary; Nordén, Bengt

    2018-01-01

    The binding mode of thionine (3,7-diamino-5-phenothiazinium) with alternating and non-alternating DNA polynucleotides at low binding ratios was conclusively determined using linear and circular dichroism spectroscopies. The binding to [poly(dG-dC)]2 and poly(dG)·poly(dC) was purely intercalative and was insensitive to ionic strength. Intercalative binding to [poly(dA-dT)]2 is observed at low ionic strength, but a shift of some dye to an non-intercalative mode is observed as the background salt concentration increases. With poly(dA)·poly(dT), intercalative binding is unfavourable, although some dye molecules may intercalate at low ionic strength, and groove binding is strongly promoted with increasing concentration of background salt. However, stacking with bases is observed with single-stranded poly(dA) and with triplex poly(dT)*poly(dA)·poly(dT) which suggests that the unusual structure of poly(dA)·poly(dT) precludes intercalation. Thionine behaves similarly to the related dye methylene blue, and small differences may be attributed either to the ability of thionine to form H-bonds that stabilize intercalation or to its improved stacking interactions in the basepair pocket on steric grounds.

  14. A conserved loop in polynucleotide phosphorylase (PNPase) essential for both RNA and ADP/phosphate binding.

    Science.gov (United States)

    Carzaniga, Thomas; Mazzantini, Elisa; Nardini, Marco; Regonesi, Maria Elena; Greco, Claudio; Briani, Federica; De Gioia, Luca; Dehò, Gianni; Tortora, Paolo

    2014-02-01

    Polynucleotide phosphorylase (PNPase) reversibly catalyzes RNA phosphorolysis and polymerization of nucleoside diphosphates. Its homotrimeric structure forms a central channel where RNA is accommodated. Each protomer core is formed by two paralogous RNase PH domains: PNPase1, whose function is largely unknown, hosts a conserved FFRR loop interacting with RNA, whereas PNPase2 bears the putative catalytic site, ∼20 Å away from the FFRR loop. To date, little is known regarding PNPase catalytic mechanism. We analyzed the kinetic properties of two Escherichia coli PNPase mutants in the FFRR loop (R79A and R80A), which exhibited a dramatic increase in Km for ADP/Pi binding, but not for poly(A), suggesting that the two residues may be essential for binding ADP and Pi. However, both mutants were severely impaired in shifting RNA electrophoretic mobility, implying that the two arginines contribute also to RNA binding. Additional interactions between RNA and other PNPase domains (such as KH and S1) may preserve the enzymatic activity in R79A and R80A mutants. Inspection of enzyme structure showed that PNPase has evolved a long-range acting hydrogen bonding network that connects the FFRR loop with the catalytic site via the F380 residue. This hypothesis was supported by mutation analysis. Phylogenetic analysis of PNPase domains and RNase PH suggests that such network is a unique feature of PNPase1 domain, which coevolved with the paralogous PNPase2 domain. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  15. 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.

  16. 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.

  17. Molecular dynamics and binding selectivity of nucleotides and polynucleotide substrates with EIF2C2/Ago2 PAZ domain.

    Science.gov (United States)

    Kandeel, Mahmoud; Kitade, Yukio

    2018-02-01

    RNA interference (RNAi) constitutes a major target in drug discovery. Recently, we reported that the Argonaute protein 2 (Ago2) PAZ domain selectively binds with all ribonucleotides except adenine and poorly recognizes deoxyribonucleotides. The binding properties of the PAZ domain with polynucleotides and the molecular mechanisms of substrates' selectivity remains unclear. In this study, the binding potencies of polynucleotides and the associated conformational and dynamic changes in PAZ domain are investigated. Coinciding with nucleotides' binding profile with the PAZ domain, polyuridylate (PolyU) and polycytidylate (PolyC) were potent binders. However, K dPolyU and K dPolyC were 15.8 and 9.3μM, respectively. In contrast, polyadenylate (PolyA) binding was not detectable. Molecular dynamics (MD) simulation revealed the highest change in root mean square deviation (RMSD) with ApoPAZ or PAZ domain bound with experimentally approved, low affinity substrates, whereas stronger binding substrates such as UMP or PolyU showed minimal RMSD changes. The loop between α3 and β5 in the β-hairpin subdomain showed the most responsive change in RMSD, being highly movable in the ApoPAZ and PAZ-AMP complex. Favorable substrate recognition was associate with moderate change in secondary structure content. In conclusion, the PAZ domain retains differential substrate selectivity associated with corresponding dynamic and structural changes upon binding. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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

  19. The paired basic amino acid-cleaving enzyme 4 (PACE4) is involved in the maturation of insulin receptor isoform B: an opportunity to reduce the specific insulin receptor-dependent effects of insulin-like growth factor 2 (IGF2).

    Science.gov (United States)

    Kara, Imène; Poggi, Marjorie; Bonardo, Bernadette; Govers, Roland; Landrier, Jean-François; Tian, Sun; Leibiger, Ingo; Day, Robert; Creemers, John W M; Peiretti, Franck

    2015-01-30

    Gaining the full activity of the insulin receptor (IR) requires the proteolytic cleavage of its proform by intra-Golgi furin-like activity. In mammalian cells, IR is expressed as two isoforms (IRB and IRA) that are responsible for insulin action. However, only IRA transmits the growth-promoting and mitogenic effects of insulin-like growth factor 2. Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation. Therefore, in situations of impaired furin activity, the proteolytic maturation of IRB is greater than that of IRA, and accordingly, the amount of phosphorylated IRB is also greater than that of IRA. We highlight the ability of a particular proprotein convertase inhibitor to effectively reduce the maturation of IRA and its associated mitogenic signaling without altering the signals emanating from IRB. In conclusion, the selective PACE4-dependent maturation of IRB occurs when furin activity is reduced; accordingly, the pharmacological inhibition of furin reduces IRA maturation and its mitogenic potential without altering the insulin effects. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Increased expression of Escherichia coli polynucleotide phosphorylase at low temperatures is linked to a decrease in the efficiency of autocontrol.

    Science.gov (United States)

    Mathy, N; Jarrige, A C; Robert-Le Meur, M; Portier, C

    2001-07-01

    Polynucleotide phosphorylase (PNPase) synthesis is translationally autocontrolled via an RNase III-dependent mechanism, which results in a tight correlation between protein level and messenger stability. In cells grown at 18 degrees C, the amount of PNPase is twice that found in cells grown at 30 degrees C. To investigate whether this effect was transcriptional or posttranscriptional, the expression of a set of pnp-lacZ transcriptional and translational fusions was analyzed in cells grown at different temperatures. In the absence of PNPase, there was no increase in pnp-lacZ expression, indicating that the increase in pnp expression occurs at a posttranscriptional level. Other experiments clearly show that increased pnp expression at low temperature is only observed under conditions in which the autocontrol mechanism of PNPase is functional. At low temperature, the destabilizing effect of PNPase on its own mRNA is less efficient, leading to a decrease in repression and an increase in the expression level.

  1. The transcription factor myocyte enhancer factor-2 (MEF2) in cardiac hypertrophy and heart failure

    NARCIS (Netherlands)

    Oort, R.J. van

    2007-01-01

    The heart responds to stress signals by hypertrophic growth, which is the first step towards heart failure (HF). The genetic pattern underlying HF remains largely elusive. Although the transcription factor Myocyte Enhancer Factor-2 (MEF2) is known to be a common endpoint for several hypertrophic

  2. 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...

  3. CvfA Protein and Polynucleotide Phosphorylase Act in an Opposing Manner to Regulate Staphylococcus aureus Virulence*

    Science.gov (United States)

    Numata, Shunsuke; Nagata, Makiko; Mao, Han; Sekimizu, Kazuhisa; Kaito, Chikara

    2014-01-01

    We previously identified CvfA (SA1129) as a Staphylococcus aureus virulence factor using a silkworm infection model. S. aureus cvfA-deleted mutants exhibit decreased expression of the agr locus encoding a positive regulator of hemolysin genes and decreased hemolysin production. CvfA protein hydrolyzes a 2′,3′-cyclic phosphodiester bond at the RNA 3′ terminus, producing RNA with a 3′-phosphate (3′-phosphorylated RNA, RNA with a 3′-phosphate). Here, we report that the cvfA-deleted mutant phenotype (decreased agr expression and hemolysin production) was suppressed by disrupting pnpA-encoding polynucleotide phosphorylase (PNPase) with 3′- to 5′-exonuclease activity. The suppression was blocked by introducing a pnpA-encoding PNPase with exonuclease activity but not by a pnpA-encoding mutant PNPase without exonuclease activity. Therefore, loss of PNPase exonuclease activity suppressed the cvfA-deleted mutant phenotype. Purified PNPase efficiently degraded RNA with 2′,3′-cyclic phosphate at the 3′ terminus (2′,3′-cyclic RNA), but it inefficiently degraded 3′-phosphorylated RNA. These findings indicate that 3′-phosphorylated RNA production from 2′,3′-cyclic RNA by CvfA prevents RNA degradation by PNPase and contributes to the expression of agr and hemolysin genes. We speculate that in the cvfA-deleted mutant, 2′,3′-cyclic RNA is not converted to the 3′-phosphorylated form and is efficiently degraded by PNPase, resulting in the loss of RNA essential for expressing agr and hemolysin genes, whereas in the cvfA/pnpA double-disrupted mutant, 2′,3′-cyclic RNA is not degraded by PNPase, leading to hemolysin production. These findings suggest that CvfA and PNPase competitively regulate RNA degradation essential for S. aureus virulence. PMID:24492613

  4. CvfA protein and polynucleotide phosphorylase act in an opposing manner to regulate Staphylococcus aureus virulence.

    Science.gov (United States)

    Numata, Shunsuke; Nagata, Makiko; Mao, Han; Sekimizu, Kazuhisa; Kaito, Chikara

    2014-03-21

    We previously identified CvfA (SA1129) as a Staphylococcus aureus virulence factor using a silkworm infection model. S. aureus cvfA-deleted mutants exhibit decreased expression of the agr locus encoding a positive regulator of hemolysin genes and decreased hemolysin production. CvfA protein hydrolyzes a 2',3'-cyclic phosphodiester bond at the RNA 3' terminus, producing RNA with a 3'-phosphate (3'-phosphorylated RNA, RNA with a 3'-phosphate). Here, we report that the cvfA-deleted mutant phenotype (decreased agr expression and hemolysin production) was suppressed by disrupting pnpA-encoding polynucleotide phosphorylase (PNPase) with 3'- to 5'-exonuclease activity. The suppression was blocked by introducing a pnpA-encoding PNPase with exonuclease activity but not by a pnpA-encoding mutant PNPase without exonuclease activity. Therefore, loss of PNPase exonuclease activity suppressed the cvfA-deleted mutant phenotype. Purified PNPase efficiently degraded RNA with 2',3'-cyclic phosphate at the 3' terminus (2',3'-cyclic RNA), but it inefficiently degraded 3'-phosphorylated RNA. These findings indicate that 3'-phosphorylated RNA production from 2',3'-cyclic RNA by CvfA prevents RNA degradation by PNPase and contributes to the expression of agr and hemolysin genes. We speculate that in the cvfA-deleted mutant, 2',3'-cyclic RNA is not converted to the 3'-phosphorylated form and is efficiently degraded by PNPase, resulting in the loss of RNA essential for expressing agr and hemolysin genes, whereas in the cvfA/pnpA double-disrupted mutant, 2',3'-cyclic RNA is not degraded by PNPase, leading to hemolysin production. These findings suggest that CvfA and PNPase competitively regulate RNA degradation essential for S. aureus virulence.

  5. 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.

  6. 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)

  7. 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...

  8. Sparse Non-negative Matrix Factor 2-D Deconvolution

    DEFF Research Database (Denmark)

    Mørup, Morten; Schmidt, Mikkel N.

    2006-01-01

    We introduce the non-negative matrix factor 2-D deconvolution (NMF2D) model, which decomposes a matrix into a 2-dimensional convolution of two factor matrices. This model is an extension of the non-negative matrix factor deconvolution (NMFD) recently introduced by Smaragdis (2004). We derive and ...... this form of factorization. The developed algorithms have been used for source separation and music transcription....

  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. 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)

  11. 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

  12. Conformational changes of DNA in the presence of 12-s-12 gemini surfactants (s=2 and 10). Role of the spacer's length in the interaction surfactant-polynucleotide.

    Science.gov (United States)

    García, J P; Marrón, E; Martín, V I; Moyá, M L; Lopez-Cornejo, P

    2014-06-01

    A multifaceted study on the interaction of calf-thymus DNA with two different cationic gemini surfactants alkanediyl-α-ω-bis(dodecyldimethyl-amonium)bromide, 12-s-12,2Br(-) (with s=2, G2, and 10, G10) was carried out. The measurements were done at different molar ratios X=[surfactant]/[DNA]. Results show two different conformational changes in DNA: a first compaction of the polynucleotide corresponding to a partial conformational (not total) change of DNA from an extended coil state to a globular state that happens at the lower molar ratio X. A second change corresponds to a breaking of the partial condensation, that is, the transition from the compacted state to a new more extended conformation (for the higher X values) different to the initial extension. According to circular dichroism spectra and dynamic light scattering measurements, this new state of DNA seems to be similar to a ψ-phase. Measurements confirm that interactions involved in the compaction are different to those previously obtained for the analog surfactant CTAB. X values at which the conformational changes happen depend on the length of the spacer in the surfactant along with the charge of the polar heads. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Steringer, Julia P; Lange, Sascha; Čujová, Sabína

    2017-01-01

    FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membra...

  14. FIBROBLAST GROWTH FACTOR-2 DURING POSTNATAL DEVELOPMENT OF THE TRACHEAL BASEMENT MEMBRANE ZONE. (R827442)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. 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.

  16. Expression and Critical Role of Interleukin Enhancer Binding Factor 2 in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Shaobing Cheng

    2016-08-01

    Full Text Available Interleukin enhancer binding factor 2 (ILF2, a transcription factor, regulates cell growth by inhibiting the stabilization of mRNA. Currently, its role has gained recognition as a factor in the tumorigenic process. However, until now, little has been known about the detailed role ILF2 plays in hepatocellular carcinoma (HCC. In this study, we investigated the expression levels of ILF2 in HCC tissue with Western blot and immunohistochemical assays. To examine the effect of ILF2 on liver cancer cell growth and apoptosis, small interfering RNAs (siRNAs targeting ILF2 were recombined to create lentiviral overexpression vectors. Our results showed higher expression levels of ILF2 mRNA and ILF2 protein in HCC tissue compared with matched peritumoral tissue. Expression of ILF2 may regulate cell growth and apoptosis in liver cancer cells via regulation of B-cell lymphoma 2 (Bcl-2, Bcl-2 related ovarian killer (Bok, Bcl-2-associated X protein (BAX, and cellular inhibitor of apoptosis 1 (cIAP1. Moreover, we inoculated nude mice with liver cancer cells to investigate the effect of ILF2 on tumorigenesis in vivo. As expected, a rapid growth was observed in cancer cells inoculated with a lentiviral vector coding Flag-ILF2 (Lenti-ILF2 compared with the control cells. Hence, these results promote a better understanding of ILF2’s potential role as a therapeutic target in HCC.

  17. Regulation of Myocyte Enhancer Factor-2 Transcription Factors by Neurotoxins

    Science.gov (United States)

    She, Hua; Mao, Zixu

    2011-01-01

    Various isoforms of myocyte enhancer factor-2 (MEF2) constitute a group of nuclear proteins found to play important roles in increasing types of cells. In neurons, MEF2s are required to regulate neuronal development, synaptic plasticity, as well as survival. MEF2s promote the survival of several types of neurons under different conditions. In cellular models, negative regulation of MEF2s by stress and toxic signals contributes to neuronal death. In contrast, enhancing MEF2 activity not only protects cultured primary neurons from death in vitro but also attenuates the loss of dopaminergic neurons in substantia nigra pars compacta in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. In this work, the mechanisms of regulation of MEF2 function by several well-known neurotoxins and their implications in various neurodegenerative diseases are reviewed. PMID:21741404

  18. Plasmonic AuNP/g-C3N4 Nanohybrid-based Photoelectrochemical Sensing Platform for Ultrasensitive Monitoring of Polynucleotide Kinase Activity Accompanying DNAzyme-Catalyzed Precipitation Amplification.

    Science.gov (United States)

    Zhuang, Junyang; Lai, Wenqiang; Xu, Mingdi; Zhou, Qian; Tang, Dianping

    2015-04-22

    A convenient and feasible photoelectrochemical (PEC) sensing platform based on gold nanoparticles-decorated g-C3N4 nanosheets (AuNP/g-C3N4) was designed for highly sensitive monitoring of T4 polynucleotide kinase (PNK) activity, using DNAzyme-mediated catalytic precipitation amplification. To realize our design, the AuNP/g-C3N4 nanohybrid was initially synthesized through in situ reduction of Au(III) on the g-C3N4 nanosheets, which was utilized for the immobilization of hairpin DNA1 (HP1) on the sensing interface. Thereafter, a target-induced isothermal amplification was automatically carried out on hairpin DNA2 (HP2) in the solution phase through PNK-catalyzed 5'-phosphorylation accompanying formation of numerous trigger DNA fragments, which could induce generation of hemin/G-quadruplex-based DNAzyme on hairpin DNA1. Subsequently, the DNAzyme could catalyze the 4-chloro-1-naphthol (4-CN) oxidation to produce an insoluble precipitation on the AuNP/g-C3N4 surface, thereby resulting in the local alternation of the photocurrent. Experimental results revealed that introduction of AuNP on the g-C3N4 could cause a ∼100% increase in the photocurrent because of surface plasmon resonance-enhanced light harvesting and separation of photogenerated e-/h+ pairs. Under the optimal conditions, the percentage of photocurrent decrement (ΔI/I0, relative to background signal) increased with the increasing PNK activity in a dynamic working range from 2 to 100 mU mL(-1) with a low detection limit (LOD) of 1.0 mU mL(-1). The inhibition effect of adenosine diphosphate also received a good performance in PNK inhibitor screening research, thereby providing a useful scheme for practical use in quantitative PNK activity assay for life science and biological research.

  19. Ribonuclease II preserves chloroplast RNA homeostasis by increasing mRNA decay rates, and cooperates with polynucleotide phosphorylase in 3' end maturation.

    Science.gov (United States)

    Germain, Arnaud; Kim, Sang Hu; Gutierrez, Ryan; Stern, David B

    2012-12-01

    Ribonuclease R (RNR1) and polynucleotide phosphorylase (cpPNPase) are the two known 3'→5' exoribonucleases in Arabidopsis chloroplasts, and are involved in several aspects of rRNA and mRNA metabolism. In this work, we show that mutants lacking both RNR1 and cpPNPase exhibit embryo lethality, akin to the non-viability of the analogous double mutant in Escherichia coli. We were successful, however, in combining an rnr1 null mutation with weak pnp mutant alleles, and show that the resulting chlorotic plants display a global reduction in RNA abundance. Such a counterintuitive outcome following the loss of RNA degradation activity suggests a major importance of RNA maturation as a determinant of RNA stability. Detailed analysis of the double mutant demonstrates that the enzymes catalyze a two-step maturation of mRNA 3' ends, with RNR1 polishing 3' termini created by cpPNPase. The bulky quaternary structure of cpPNPase compared with RNR1 could explain this activity split between the two enzymes. In contrast to the double mutants, the rnr1 single mutant overaccumulates most mRNA species when compared with the wild type. The excess mRNAs in rnr1 are often present in non-polysomal fractions, and half-life measurements demonstrate a substantial increase in the stability of most mRNA species tested. Together, our data reveal the cooperative activity of two 3'→5' exoribonucleases in chloroplast mRNA 3' end maturation, and support the hypothesis that RNR1 plays a significant role in the destabilization of mRNAs unprotected by ribosomes. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  20. The Influence of Platelet-Derived Growth Factor and Fibroblast Growth Factor 2 on Oligodendrocyte Development and Remyelination

    National Research Council Canada - National Science Library

    Murtie, Joshua C

    2004-01-01

    ...) characterized by repeated episodes of autoimmune-mediated demyelination. Symptoms of the disease range from loss of vision to paralysis with each episode resulting in a decreased remyelination response...

  1. Structures of bacterial polynucleotide kinase in a michaelis complex with nucleoside triphosphate (NTP)-Mg2+ and 5'-OH RNA and a mixed substrate-product complex with NTP-Mg2+ and a 5'-phosphorylated oligonucleotide.

    Science.gov (United States)

    Das, Ushati; Wang, Li Kai; Smith, Paul; Munir, Annum; Shuman, Stewart

    2014-12-01

    Clostridium thermocellum polynucleotide kinase (CthPnk), the 5'-end-healing module of a bacterial RNA repair system, catalyzes reversible phosphoryl transfer from a nucleoside triphosphate (NTP) donor to a 5'-OH polynucleotide acceptor, either DNA or RNA. Here we report the 1.5-Å crystal structure of CthPnk-D38N in a Michaelis complex with GTP-Mg(2+) and a 5'-OH RNA oligonucleotide. The RNA-binding mode of CthPnk is different from that of the metazoan RNA kinase Clp1. CthPnk makes hydrogen bonds to the ribose 2'-hydroxyls of the 5' terminal nucleoside, via Gln51, and the penultimate nucleoside, via Gln83. The 5'-terminal nucleobase is sandwiched by Gln51 and Val129. Mutating Gln51 or Val129 to alanine reduced kinase specific activity 3-fold. Ser37 and Thr80 donate functionally redundant hydrogen bonds to the terminal phosphodiester; a S37A-T80A double mutation reduced kinase activity 50-fold. Crystallization of catalytically active CthPnk with GTP-Mg(2+) and a 5'-OH DNA yielded a mixed substrate-product complex with GTP-Mg(2+) and 5'-PO4 DNA, wherein the product 5' phosphate group is displaced by the NTP γ phosphate and the local architecture of the acceptor site is perturbed. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. 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.

  3. The Neurospora crassa colonial temperature-sensitive 3 (cot-3) gene encodes protein elongation factor 2.

    Science.gov (United States)

    Propheta, O; Vierula, J; Toporowski, P; Gorovits, R; Yarden, O

    2001-02-01

    At elevated temperatures, the Neurospora crassa mutant colonial, temperature-sensitive 3 (cot-3) forms compact, highly branched colonies. Growth of the cot-3 strain under these conditions also results in the loss of the lower molecular weight (LMW) isoform of the Ser/Thr protein kinase encoded by the unlinked cot-1 gene, whose function is also involved in hyphal elongation. The unique cot-3 gene has been cloned by complementation and shown to encode translation elongation factor 2 (EF-2). As expected for a gene with a general role in protein synthesis, cot-3 mRNA is abundantly expressed throughout all asexual phases of the N. crassa life cycle. The molecular basis of the cot-3 mutation was determined to be an ATT to AAT transversion, which causes an Ile to Asn substitution at residue 278. Treatment with fusidic acid (a specific inhibitor of EF-2) inhibits hyphal elongation and induces hyperbranching in a manner which mimics the cot-3 phenotype, and also leads to a decrease in the abundance of the LMW isoform of COT1. This supports our conclusion that the mutation in cot-3 which results in abnormal hyphal elongation/branching impairs EF-2 function and confirms that the abundance of a LMW isoform of COT1 kinase is dependent on the function of this general translation factor.

  4. Enhancement of +1 frameshift by polyamines during translation of polypeptide release factor 2 in Escherichia coli.

    Science.gov (United States)

    Higashi, Kyohei; Kashiwagi, Keiko; Taniguchi, Shiho; Terui, Yusuke; Yamamoto, Kaneyoshi; Ishihama, Akira; Igarashi, Kazuei

    2006-04-07

    Polypeptide release factor 2 (RF2) in Escherichia coli is known to be synthesized by a +1 frameshift at the 26th UGA codon of RF2 mRNA. Polyamines were found to stimulate the +1 frameshift of RF2 synthesis, an effect that was reduced by excess RF2. Polyamine stimulation of +1 frameshift of RF2 synthesis was observed at the early logarithmic phase, which is the important phase in determination of the overall rate of cell growth. A Shine-Dalgarno-like sequence was necessary for an efficient +1 frameshift of RF2 synthesis, but not for polyamine stimulation. Spectinomycin, tetracycline, streptomycin, and neomycin reduced polyamine stimulation of the +1 frameshift of RF2 synthesis. The results suggest that a structural change of the A site on 30 S ribosomal subunits is important for polyamine stimulation of the +1 frameshift. The level of mRNAs of ribosomal proteins and elongation factors having UAA as termination codon was enhanced by polyamines, and OppA synthesis from OppA mRNA having UAA as termination codon was more enhanced by polyamines than that from OppA mRNA having a UGA termination codon. Furthermore, synthesis of ribosomal protein L20 and elongation factor G from the mRNAs having a UAA termination codon was enhanced by polyamines at the level of translation and transcription. The results suggest that some protein synthesis from mRNAs having a UAA termination codon is enhanced at the level of translation through polyamine stimulation of +1 frameshift of RF2 synthesis. It is concluded that prfB encoding RF2 is a new member of the polyamine modulon.

  5. 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.

  6. Molecular Cloning, Bioinformatics Analysis and Expression of Insulin-Like Growth Factor 2 from Tianzhu White Yak, Bos grunniens

    Directory of Open Access Journals (Sweden)

    Quanwei Zhang

    2014-01-01

    Full Text Available The IGF family is essential for normal embryonic and postnatal development and plays important roles in the immune system, myogenesis, bone metabolism and other physiological functions, which makes the study of its structure and biological characteristics important. Tianzhu white yak (Bos grunniens domesticated under alpine hypoxia environments, is well adapted to survive and grow against severe hypoxia and cold temperatures for extended periods. In this study, a full coding sequence of the IGF2 gene of Tianzhu white yak was amplified by reverse transcription PCR and rapid-amplification of cDNA ends (RACE for the first time. The cDNA sequence revealed an open reading frame of 450 nucleotides, encoding a protein with 179 amino acids. Its expression in different tissues was also studied by Real time PCR. Phylogenetic tree analysis indicated that yak IGF2 was similar to Bos taurus, and 3D structure showed high similarity with the human IGF2. The putative full CDS of yak IGF2 was amplified by PCR in five tissues, and cDNA sequence analysis showed high homology to bovine IGF2. Moreover the super secondary structure prediction showed a similar 3D structure with human IGF2. Its conservation in sequence and structure has facilitated research on IGF2 and its physiological function in yak.

  7. 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 : Chi ck embryo * Hypoplastic left heart syndrome * Adenovirus Subject RIV: EA - Cell Biology Impact factor: 1.183, year: 2009

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

    Directory of Open Access Journals (Sweden)

    Jeffery J. Auletta

    2011-01-01

    Full Text Available 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 supplementation increased expansion 3,500- and 240,000-fold by passages 7 and 13, respectively. There were no differences in immunosuppressive activity between media conditioned by passage-matched cells expanded under different conditions, but media conditioned by FGF-treated MSCs were superior to population doubling-matched controls. The immunosuppressive activity was maintained in three of the preparations but decreased with expansion in two. The proliferation induced by FGF-2 did not result in loss of immunosuppressive activity. However, because the immunosuppressive activity was not consistently preserved, caution must be exercised to ensure that the activity of the cells is sufficient after extensive expansion.

  9. 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

  10. [Effects of Plasmid Fibroblast Growth Factor-2 Magnetic Chitosan Gelatin Microspheres on Proliferation and Differentiation of Mesenchymal Stem Cells].

    Science.gov (United States)

    Ding, Xingpo; Li, Ming; Cao, Yujiang; Yang, Qiong; He, Tongchuan; Luo, Cong; Li, Haibing; Bi, Yang

    2015-10-01

    The purpose of this study is to investigate the effect of superparamagnetic chitosan FGF-2 gelatin microspheres (SPCFGM) on the proliferation and differentiation of mouse mesenchymal stem cells. The superparamagnetic iron oxide chitosan nanoparticles (SPIOCNs) were synthesized by means of chemical co-precipitation, combined with FGF-2. Then The SPCFGM and superparamagnetic chitosan gelatin microspheres (SPCGM) were prepared by means of crosslinking-emulsion. The properties of SPCFGM and SPIONs were measured by laser diffraction particle size analyser and transmisson electron microscopy. The SPCFGM were measured for drug loading capacity, encapsulation efficiency and release pharmaceutical properties in vitro. The C3H10 cells were grouped according to the different ingredients being added to the culture medium: SPCFGM group, SPCGM group and DMEM as control group. Cell apoptosis was analyzed by DAPI staining. The protein expression level of FGF-2 was determined by Western blot. The proliferation activity and cell cycle phase of C3H10 were examined by CCK8 and flow cytometry. The results demonstrated that both of the SPIOCNs and SPCFGM were exhibited structure of spherical crystallization with a diameter of (25 ± 9) nm and (140 ± 12) μm, respectively. There were no apoptosis cells in the three group cells. Both the protein expression level of FGF-2 and cell proliferation activity increased significantly in the SPCFGM group cells (P < 0.05). The SPCFGM is successfully constructed and it can controlled-release FGF-2, remained the biological activity of FGF-2, which can promote proliferation activity of C3H10 cells, and are non-toxic to the cell.

  11. The effects of calcium silicate cement/fibroblast growth factor-2 composite on osteogenesis accelerator in human dental pulp cells

    Directory of Open Access Journals (Sweden)

    Buor-Chang Wu

    2015-06-01

    Conclusion: CS combined with FGF-2 is biocompatible with hDPCs. It not only promotes hDPC proliferation but also helps in differentiating reparative hard tissue. Thus, we suggest that the CS/FGF-2 composite has the potential for hard tissue defect repair.

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

    Science.gov (United States)

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

    2016-09-06

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

  13. 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...

  14. 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 to in...... to individual instruments. Based on this factorization we separate the instruments using spectrogram masking. The proposed algorithm has applications in computational auditory scene analysis, music information retrieval, and automatic music transcription.......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...

  15. Crystal structure of catalytic domain of the initiation factor 2B epsilon subunit

    DEFF Research Database (Denmark)

    Boesen, Thomas; Mohammad, Sarah S.; Pavitt, Graham D.

    , surface exposed acidic patch which might interact with the lysine boxes of eIF2β. Interestingly, Tryptophan 699 was found to be solvent exposed and involved in crystal packing. This residue could possibly be important for the specific interaction with eIF2β. Furthermore, the structure shows the location......CRYSTAL STRUCTURE OF CATALYTIC DOMAIN OF THE INITIATION FACTOR 2B EPSILON SUBUNIT Thomas Boesen1,Sarah S. Mohammad2, Graham Pavitt2, and Gregers R. Andersen1* 1Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Århus C, Denmark 2Department of Biomolecular Sciences......, UMIST, PO Box 88, Manchester, M60 1QD, UK Eukaryotic initiation factor 2B (eIF2B) is the exchange factor of initiation factor 2 (eIF2) and catalyses the reaction where GDP bound to eIF2 is exchanged for GTP, a crucial step in translation. The crystal structure of the C-terminal catalytic domain of the e...

  16. 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.

  17. Eukaryotic elongation factor 2 kinase regulates the cold stress response by slowing translation elongation.

    Science.gov (United States)

    Knight, John R P; Bastide, Amandine; Roobol, Anne; Roobol, Jo; Jackson, Thomas J; Utami, Wahyu; Barrett, David A; Smales, C Mark; Willis, Anne E

    2015-01-15

    Cells respond to external stress conditions by controlling gene expression, a process which occurs rapidly via post-transcriptional regulation at the level of protein synthesis. Global control of translation is mediated by modification of translation factors to allow reprogramming of the translatome and synthesis of specific proteins that are required for stress protection or initiation of apoptosis. In the present study, we have investigated how global protein synthesis rates are regulated upon mild cooling. We demonstrate that although there are changes to the factors that control initiation, including phosphorylation of eukaryotic translation initiation factor 2 (eIF2) on the α-subunit, the reduction in the global translation rate is mediated by regulation of elongation via phosphorylation of eukaryotic elongation factor 2 (eEF2) by its specific kinase, eEF2K (eukaryotic elongation factor 2 kinase). The AMP/ATP ratio increases following cooling, consistent with a reduction in metabolic rates, giving rise to activation of AMPK (5'-AMP-activated protein kinase), which is upstream of eEF2K. However, our data show that the major trigger for activation of eEF2K upon mild cooling is the release of Ca2+ ions from the endoplasmic reticulum (ER) and, importantly, that it is possible to restore protein synthesis rates in cooled cells by inhibition of this pathway at multiple points. As cooling has both therapeutic and industrial applications, our data provide important new insights into how the cellular responses to this stress are regulated, opening up new possibilities to modulate these responses for medical or industrial use at physiological or cooler temperatures.

  18. Nuclear factor E2-related factor 2 knockdown enhances glucose uptake and alters glucose metabolism in AML12 hepatocytes.

    Science.gov (United States)

    Yuan, Xiaoyang; Huang, Huijing; Huang, Yi; Wang, Jinli; Yan, Jinhua; Ding, Ling; Zhang, Cuntai; Zhang, Le

    2017-05-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce the expression of a variety of antioxidant and detoxification genes. Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 ± 11.1% ( P glucose metabolism were then examined in AML12 cells under both high-glucose (33 mmol/L) and low-glucose (4.5 mmol/L) conditions. NK lowered the gene and protein expression of the anti-oxidases heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 and increased p-eukaryotic initiation factor-2α S51 , p-nuclear factor-κB p65 S276 , and its downstream proinflammatory factors, including interleukin-1 beta, tumor necrosis factor-α, matrix metalloproteinase 2, and matrix metalloproteinase 9, at the protein level. NK also altered the protein expression of fibroblast growth factor 21, glucose transporter type 4, insulin-like growth factor 1, forkhead box protein O1, p-AKT S473 , and p-GSK3α/β Y279/Y216 , which are involved in glucose uptake, glycogenesis, and gluconeogenesis in AML12 cells. Our results provide a comprehensive understanding of the central role of Nrf2 in the regulation of glucose metabolism in AML12 hepatocytes, in addition to its classical roles in the regulation of redox signaling, endoplasmic reticulum stress and proinflammatory responses, and support the potential of Nrf2 as a therapeutic target for the prevention and treatment of obesity and other associated metabolic syndromes. Impact statement Increasing evidence supports the complexity of Nrf2 functions beyond the antioxidant and detoxification response. Previous in vivo studies employing either Nrf2-knockout or Nrf2-activated mice have achieved a similar endpoint: protection against an obese and

  19. E74-like factor 2 regulates valosin-containing protein expression

    International Nuclear Information System (INIS)

    Zhang, Binglin; Tomita, Yasuhiko; Qiu, Ying; He, Juxiang; Morii, Eiichi; Noguchi, Shinzaburo; Aozasa, Katsuyuki

    2007-01-01

    Enhanced expression of valosin-containing protein (VCP) correlates with invasion and metastasis of cancers. To clarify the transcription mechanism of VCP, human and mouse genomic sequence was compared, revealing a 260 bp DNA sequence in the 5'-flanking region of VCP gene to be highly conserved between the two, in which binding motif of E74-like factor 2/new Ets-related factor (ELF2/NERF) was identified. Chromatin immunoprecipitation assay showed binding of ELF2/NERF to the 5'-flanking region of VCP gene. Knock-down of ELF2/NERF by siRNA decreased expression level of VCP. Viability of cells under tumor necrosis factor-alpha treatment significantly reduced in ELF2/NERF-knock-down breast cancer cell line. Immunohistochemical analysis on clinical breast cancer specimens showed a correlation of nuclear ELF2/NERF expression with VCP expression and proliferative activity of cells shown by Ki-67 immunohistochemistry. These findings indicate that ELF2/NERF promotes VCP transcription and that ELF2/NERF-VCP pathway might be important for cell survival and proliferation under cytokine stress

  20. 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.

  1. Characterization of the hemin-sensitive eukaryotic initiation factor 2alpha kinase from mouse nonerythroid cells.

    Science.gov (United States)

    Berlanga, J J; Herrero, S; de Haro, C

    1998-11-27

    The heme-regulated eukaryotic initiation factor 2alpha (eIF2alpha) kinase (heme-regulated inhibitor (HRI)) is activated by heme deficiency in reticulocytes and plays an important role in translational control in these cells. Previously, HRI was cloned from rabbit reticulocytes and rat brain, but a heme-regulated eIF2alpha kinase activity has only been purified from erythroid cells. In this study, we report the purification of a heme-sensitive eIF2alpha kinase activity from both mouse liver and NIH 3T3 cell extracts. Furthermore, we have cloned and characterized this mouse liver eIF2alpha kinase (mHRI), which exhibits 83 and 94% identities to rabbit and rat HRIs, respectively. Both the purified enzyme and recombinant mHRI exhibited an autokinase and an eIF2alpha kinase activity, and both activities were inhibited in vitro by hemin. In addition, wild-type mHRI, but not the inactive mHRI-K196R mutant, was autophosphorylated in vivo when it was expressed in 293 cells. Quantitation of mHRI mRNA expression in various mouse tissues by reverse transcription-polymerase chain reaction revealed relatively high levels in liver, kidney, and testis. These results provide strong evidence that mHRI is a ubiquitous eIF2alpha kinase of mammalian cells, suggesting that it could play important roles in the translational regulation of nonerythroid tissues.

  2. Kruppel-Like Factor 2 Regulates Dendritic Cell Activation in Patients with Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Hongcheng Fang

    2013-10-01

    Full Text Available Objective: Dendritic cells (DCs activation is important in atherosclerosis and coronary heart disease, but the mechanisms regulating activation of dendritic cells remain largely unclear. The aim of this study was to evaluate the effect of transcription factor Kruppel-like factor 2 (KLF2 in the proinflammatory activation of DCs in acute coronary syndrome. Methods and Results: In this study, the expression of CD80 and KLF2 was detected in DCs in normal health controls, patients with stable angina (SA, and acute coronary syndrome (ACS. Our study found that compared with normal control and SA, KLF2 expression in DCs is reduced in patients with ACS. Moreover, the surface expression of CD80 was increased in ACS. In vitro experiment, we found that ox-LDL could increase CD80 expression and decrease KLF2 expression. Furthermore, down-regulated KLF2 could in turn increase CD80 expression via NF-κB pathway. Conclusions: These observations identify KLF2 as a novel negative regulator of DC function and it may play an essential role in DC activation in ACS.

  3. The diphthamide modification on elongation factor-2 renders mammalian cells resistant to ricin.

    Science.gov (United States)

    Gupta, Pradeep K; Liu, Shihui; Batavia, Mariska P; Leppla, Stephen H

    2008-08-01

    Diphthamide is a post-translational derivative of histidine in protein synthesis elongation factor-2 (eEF-2) that is present in all eukaryotes with no known normal physiological role. Five proteins Dph1-Dph5 are required for the biosynthesis of diphthamide. Chinese hamster ovary (CHO) cells mutated in the biosynthetic genes lack diphthamide and are resistant to bacterial toxins such as diphtheria toxin. We found that diphthamide-deficient cultured cells were threefold more sensitive than their parental cells towards ricin, a ribosome-inactivating protein (RIP). RIPs bind to ribosomes at the same site as eEF-2 and cleave the large ribosomal RNA, inhibiting translation and causing cell death. We hypothesized that one role of diphthamide may be to protect ribosomes, and therefore all eukaryotic life forms, from RIPs, which are widely distributed in nature. A protective role of diphthamide against ricin was further demonstrated by complementation where dph mutant CHO cells transfected with the corresponding DPH gene acquired increased resistance to ricin in comparison with the control-transfected cells, and resembled the parental CHO cells in their response to the toxin. These data show that the presence of diphthamide in eEF-2 provides protection against ricin and suggest the hypothesis that diphthamide may have evolved to provide protection against RIPs.

  4. Polynucleotides encoding anti-sulfotyrosine antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bertozzi, Carolyn R [Berkeley, CA; Kehoe, John [Saint Davids, PA; Bradbury, Andrew M [Santa Fe, NM

    2011-01-11

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  5. 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

  6. Growth Disorders

    Science.gov (United States)

    ... problem or disease. The pituitary gland makes growth hormone, which stimulates the growth of bone and other tissues. Children who have too little ... gland tumor, which is not cancer. Too much growth hormone can cause gigantism in children, where their bones and their body grow too much. In adults, ...

  7. [Biological characteristics of cleft palate relevant gene thyroid transcription factor-2 transgenic mice].

    Science.gov (United States)

    Huang, Lei; Shi, Bing; Qian, Zheng; Meng, Tian; Wang, Yan

    2014-08-01

    The aim of this study is to establish a transgenic mouse model for cleft palate relevant gene thyroid transcription factor-2 (TTF-2), which can be used to study palatal shelf development when the expression pattern and regular activation of TTF-2 is altered. The C57BL/6J mouse TTF-2 gene was cloned through polymerase chain reaction (PCR) from the mouse genomic DNA. The TTF-2 gene was inserted into the expression vector pBROAD3-mcs to construct the recombinant expression vector pBROAD3-TTF-2. This expression vector was then microinjected into the male pronuclei of the fertilized mouse ovum. Thus, the TTF-2 transgenic mice model was established. The genotype of the transgenic mice was identified by PCR and Southern blot analysis. Immunohistochemistry identified the consistent expression of TTF-2 gene during its palatal shelf development. TTF-2 genes were microinjected into 982 fertilized ova. A total of 580 two-cell-stage embryos cultured and transplanted into the oviducts of 48 pseudopregnant female mice. Overall, 68 embryos were obtained for analysis. The genotype of the mice was determined through PCR and Southern blot analysis using genomic DNA extracted from tail biopsies of the transgenic fetus. A total of 13 TTF-2 transgenic mice were detected. The expression of TTF-2 gene during the palatal shelf development of the transgenic mice was consistently detected by immunohistochemistry. The recombinant expression vector pBROAD3-TTF-2 was integrated into mouse genome through microinjection. The transgenic mouse in the palatal shelf that consistently expressed TTF-2 was successfully established and displayed a cleft palate phenotype.

  8. Innate immune evasion mediated by the Ambystoma tigrinum virus eukaryotic translation initiation factor 2alpha homologue.

    Science.gov (United States)

    Jancovich, James K; Jacobs, Bertram L

    2011-05-01

    Ranaviruses (family Iridoviridae, genus Ranavirus) are large, double-stranded DNA (dsDNA) viruses whose replication is restricted to ectothermic vertebrates. Many highly pathogenic members of the genus Ranavirus encode a homologue of the eukaryotic translation initiation factor 2α (eIF2α). Data in a heterologous vaccinia virus system suggest that the Ambystoma tigrinum virus (ATV) eIF2α homologue (vIF2αH; open reading frame [ORF] 57R) is involved in evading the host innate immune response by degrading the interferon-inducible, dsRNA-activated protein kinase, PKR. To test this hypothesis directly, the ATV vIF2αH gene (ORF 57R) was deleted by homologous recombination, and a selectable marker was inserted in its place. The ATVΔ57R virus has a small plaque phenotype and is 8-fold more sensitive to interferon than wild-type ATV (wtATV). Infection of fish cells with the ATVΔ57R virus leads to eIF2α phosphorylation, in contrast to infection with wtATV, which actively inhibits eIF2α phosphorylation. The inability of ATVΔ57R to prevent phosphorylation of eIF2α correlates with degradation of fish PKZ, an interferon-inducible enzyme that is closely related to mammalian PKR. In addition, salamanders infected with ATVΔ57R displayed an increased time to death compared to that of wtATV-infected salamanders. Therefore, in a biologically relevant system, the ATV vIF2αH gene acts as an innate immune evasion factor, thereby enhancing virus pathogenesis.

  9. 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

  10. 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

  11. 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.

  12. Phosphorylation of Eukaryotic Initiation Factor-2α during Stress and Encystation in Entamoeba Species.

    Science.gov (United States)

    Hendrick, Holland M; Welter, Brenda H; Hapstack, Matthew A; Sykes, Steven E; Sullivan, William J; Temesvari, Lesly A

    2016-12-01

    Entamoeba histolytica is an enteric pathogen responsible for amoebic dysentery and liver abscess. It alternates between the host-restricted trophozoite form and the infective environmentally-stable cyst stage. Throughout its lifecycle E. histolytica experiences stress, in part, from host immune pressure. Conversion to cysts is presumed to be a stress-response. In other systems, stress induces phosphorylation of a serine residue on eukaryotic translation initiation factor-2α (eIF2α). This inhibits eIF2α activity resulting in a general decline in protein synthesis. Genomic data reveal that E. histolytica possesses eIF2α (EheIF2α) with a conserved phosphorylatable serine at position 59 (Ser59). Thus, this pathogen may have the machinery for stress-induced translational control. To test this, we exposed cells to different stress conditions and measured the level of total and phospho-EheIF2α. Long-term serum starvation, long-term heat shock, and oxidative stress induced an increase in the level of phospho-EheIF2α, while short-term serum starvation, short-term heat shock, or glucose deprivation did not. Long-term serum starvation also caused a decrease in polyribosome abundance, which is in accordance with the observation that this condition induces phosphorylation of EheIF2α. We generated transgenic cells that overexpress wildtype EheIF2α, a non-phosphorylatable variant of eIF2α in which Ser59 was mutated to alanine (EheIF2α-S59A), or a phosphomimetic variant of eIF2α in which Ser59 was mutated to aspartic acid (EheIF2α-S59D). Consistent with the known functions of eIF2α, cells expressing wildtype or EheIF2α-S59D exhibited increased or decreased translation, respectively. Surprisingly, cells expressing EheIF2α-S59A also exhibited reduced translation. Cells expressing EheIF2α-S59D were more resistant to long-term serum starvation underscoring the significance of EheIF2α phosphorylation in managing stress. Finally, phospho-eIF2α accumulated during

  13. Crystal structure of the catalytic domain of the initiation factor 2B epsilon subunit from saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Boesen, Thomas; Pavitt, Graham D.; Andersen, Gregers Rom

    residues in the motifs form a surface exposed acidic patch which might interact with the lysine boxes of initiation factor 2 β. Interestingly, tryptophan 699 was found to be solvent exposed and involved in crystal packing. This residue could possibly be important for the specific interaction......Crystal Structure of Catalytic Domain of the Initiation Factor 2B Epsilon Subunit from Saccharomyces cerevisiae by Thomas Boesen1, Graham Pavitt2, and Gregers Rom Andersen1* 1Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Århus C, Denmark 2Department...... of Biomolecular Sciences, UMIST, PO Box 88, Manchester, M60 1QD UK *To whom correspondence should be addressed: grand@imsb.au.dk, Tel: (+45) 8942 5024. Fax: (+45) 8612 3178 Abstract The crystal structure of the C-terminal catalytic domain of the initiation factor 2B epsilon subunit, residues 544-704, from...

  14. Silencing of eIF3e promotes blood perfusion recovery after limb ischemia through stabilization of hypoxia-inducible factor 2α activity.

    Science.gov (United States)

    Hashimoto, Takuya; Chen, Li; Kimura, Hideo; Endler, Alexander; Koyama, Hiroyuki; Miyata, Tetsuro; Shibasaki, Futoshi; Watanabe, Toshiaki

    2016-07-01

    We previously observed that silencing of eukaryotic translation initiation factor 3 subunit e (eIF3e), a hypoxia-independent downregulator of hypoxia-inducible factor 2α (HIF-2α), led to neoangiogenesis by promoting HIF-2α activity under normoxic conditions. In the current study, we investigated whether temporary silencing of eIF3e in muscles affects blood flow recovery in a mouse ischemic limb model. eIF3e silencing was performed using small interfering RNA (siRNA), and changes in gene transcription and protein expression were analyzed in vitro using murine primary skeletal muscle myoblast and human primary skeletal muscle myoblast cell cultures. In unilateral femoral artery ligation experiments, eIF3e siRNA-expressing plasmids were injected into the muscles of BALB/c mice near the ligation sites, and tissue damage and loss of limb function were scored for 28 days while serial measurements of limb perfusions were performed with laser Doppler perfusion imaging. Silencing of eIF3e in murine primary skeletal muscle myoblasts led to stabilization of HIF-2α and upregulation of angiogenic transcripts, including basic fibroblast growth factor and platelet-derived growth factor B (P recovery at days 7, 14, and 21 (P < .05). eIF3e is an angiogenesis suppressor and may be a therapeutic target for promoting angiogenesis after ischemic injuries. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  15. Growth theory and 'green growth'

    NARCIS (Netherlands)

    Smulders, S.; Toman, M.; Withagen, C.A.A.M.

    2014-01-01

    The relatively new and still amorphous concept of 'green growth' can be understood as a call for balancing longer-term investments in sustaining environmental wealth with nearer-term income growth to reduce poverty. We draw on a large body of economic theory available for providing insights on such

  16. 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

  17. Eyelid Growths

    Science.gov (United States)

    ... of the Eyelids and Tears Blepharitis Blepharospasm Canaliculitis Chalazion and Stye (Hordeolum) Dacryocystitis Dacryostenosis Entropion and Ectropion ... mimic other eye disorders (such as blepharitis and chalazion ), so a doctor usually biopsies any growths that ...

  18. 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

  19. Transforming Growth Factor Beta-Induced Factor 2-Linked X (TGIF2LX Regulates Two Morphogenesis Genes, Nir1 and Nir2 in Human Colorectal

    Directory of Open Access Journals (Sweden)

    Gholam Reza Mobini

    2016-05-01

    Full Text Available A member of homeodomain protein namely TGIF2LX has been implicated as a tumor suppressor gene in human malignancy as well as in spermatogenesis. However, to our knowledge, dynamic functional evidence of the TGIF2LX has not yet been provided. The aim of the present study was to investigate the human TGIF2LX target gene(s using a cDNA-AFLP as a differential display method. A pEGFP-TGIF2LX construct containing the wild-type TGIF2LX cDNA was stably transfected into SW48 cells. UV microscopic analysis and Real-time RT-PCR were used to confirm TGIF2LX expression. The mRNA expressions of TGIF2LX in transfected SW48 cells, the cells containing empty vector (pEGFP-N, and untransfected cells were compared. Also, a Real-time PCR technique was applied to validate cDNA-AFLP results. The results revealed a significant down-regulation and up-regulationby TGIF2LX of Nir1 and Nir2 genes, respectively. The genes are engaged in the cell morphogenesis process. Our findings may provide new insight into the complex molecular pathways underlying colorectal cancer development.

  20. The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2

    Directory of Open Access Journals (Sweden)

    Cline Brandon H

    2012-09-01

    Full Text Available Abstract Background A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling. Results Administration of DS (25 mg/kg/day, intraperitoneal in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2. Conclusions Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.

  1. A NciI PCR-RFLP within intron 2 of the porcine insulin-like growth factor 2 (IGF2) gene

    Czech Academy of Sciences Publication Activity Database

    Knoll, Aleš; Putnová, L.; Dvořák, J.; Čepica, Stanislav

    2000-01-01

    Roč. 31, - (2000), s. 140-157 ISSN 0268-9146 R&D Projects: GA ČR GA523/99/P043; GA ČR GA523/99/0842; GA AV ČR KSK2052601 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.863, year: 2000

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

    Science.gov (United States)

    Qiu, Jun; Yang, Rong; Rao, Yanhua; Du, Yukai; Kalembo, Fatch W

    2012-01-01

    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. 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). 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). 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).

  3. 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.

  4. 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

    DTI analysis. Five additional rats were used as uninjured controls and analyzed in parallel to the SCI rats. Rats were anesthetized and...inflammation (mimicking the experimental conditions of Aim 4a and producing some inflammation, as would be encountered with spinal cord injury). The technique ...underwent a standard diagnostic workup including a complete blood cell count (CBC) and serum chemistry panel, radiographs of the spine, followed by

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-05-05

    Interleukin 6 (IL-6; also referred to as interferon-..beta../sub 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.

  6. 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

  7. MicroRNA-17, 20a regulates the proangiogenic function of tumor-associated macrophages via targeting hypoxia-inducible factor 2α.

    Directory of Open Access Journals (Sweden)

    Zhenqun Xu

    Full Text Available Tumor-associated macrophages (TAMs constitute a major component of the leukocyte infiltrate of most solid tumors, and they usually exhibit a proangiogenic phenotype which facilitates tumor growth in most circumstances. However, the precise mechanisms regulating the proangiogenic properties of TAMs remain largely unclear. In the present study, we found that the expression of hypoxia-inducible factor 2α (HIF-2α was significantly up-regulated in macrophages from tumor tissues of several solid tumors. Macrophages exposed to tumor cell line derived-culture supernatants (TSN also expressed high levels of HIF-2α in vitro, without a requirement for hypoxia. We identified miR-17 and miR-20a as the key regulators of HIF-2α expression in TAMs, and autocrine IL-6 played an important role in mediating the expression of miR-17, miR-20a, and thereafter HIF-2α in TAMs. Furthermore, the elevated HIF-2α in TAMs stimulated transcription of a set of proangiogenic genes such as VEGFA and PDGFB, which might in turn contribute to the angiogenic process within tumors. Our data provide evidence in support of the critical role of HIF-2α in the proangiogenic activity of TAMs and also reveal a novel mechanism by which miRNAs regulate TAM functions through modulation of HIF-2α expression under non-hypoxic conditions.

  8. 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.

  9. 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...

  10. 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

  11. 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.

  12. growth conditions

    Directory of Open Access Journals (Sweden)

    Martin Fuchs

    1998-01-01

    Full Text Available We consider the obstacle problem {minimize????????I(u=?OG(?udx??among functions??u:O?Rsuch?that???????u|?O=0??and??u=F??a.e. for a given function F?C2(O¯,F|?O<0 and a bounded Lipschitz domain O in Rn. The growth properties of the convex integrand G are described in terms of a N-function A:[0,8?[0,8 with limt?8¯A(tt-2<8. If n=3, we prove, under certain assumptions on G,C1,8-partial regularity for the solution to the above obstacle problem. For the special case where A(t=tln(1+t we obtain C1,a-partial regularity when n=4. One of the main features of the paper is that we do not require any power growth of G.

  13. Growth hormone deficiency - children

    Science.gov (United States)

    ... childhood. The pediatrician will most often draw the child's growth curve on a growth chart . Children with growth ... Most cases are not preventable. Review your child's growth chart ... child's growth rate, evaluation by a specialist is recommended.

  14. [Effects of silencing Smad ubiquitination regulatory factor 2 on the function of human hypertrophic scar-derived fibroblasts].

    Science.gov (United States)

    Zhang, Z; Kuang, F; Liu, C L; Chen, B; Tang, W B; Li, X J

    2017-03-20

    Objective: To explore the effects of silencing Smad ubiquitination regulatory factor 2 (Smurf2) on the secretion of transforming growth factor beta 1 (TGF-β(1)), alpha-smooth muscle actin (α-SMA), and collagen type Ⅰ by human hypertrophic scar-derived fibroblasts. Methods: The human normal skin-derived fibroblasts and hypertrophic scar-derived fibroblasts were cultured with explant culture technique from the normal skin and hypertrophic scar tissue, which was obtained from 9 patients with hypertrophic scars after burn. Two kinds of fibroblasts of the third passage were both divided into 6 groups according to the random number table, with 9 wells in each group. Fibroblasts in blank control group were cultured for 72 h without transfection of any small interfering RNA (siRNA), fibroblasts in negative control group were for cultured for 72 h after transfected with non-target siRNA, fibroblasts in Smurf2 siRNA group were cultured for 72 h after transfected with 100 nmol/L Smurf2 siRNA, fibroblasts in blank control+ TGF-β(1) group were cultured for 72 h without transfection of any siRNA and then treated with 10 ng/mL TGF-β(1) for 6 h, fibroblasts in negative control+ TGF-β(1) group were cultured for 72 h after transfected with non-target siRNA and then treated with 10 ng/mL TGF-β(1) for 6 h, fibroblasts in Smurf2 siRNA+ TGF-β(1) group were cultured for 72 h after transfected with Smurf2 siRNA and then treated with 10 ng/mL TGF-β(1) for 6 h. (1) The protein and mRNA expression levels of Smurf2 of the two kinds of cells in blank control group, negative control group, and Smurf2 siRNA group were assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively. (2) The content of TGF-β(1) in the cell culture supernatant of the two kinds of cells in blank control group and Smurf2 siRNA group was determined by enzyme-linked immunosorbent assay (ELISA). (3) The protein expression levels of α-SMA of the two kinds of cells in

  15. 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

  16. 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

  17. Correlation of astrocyte elevated gene‑1, basic‑fibroblast growth ...

    African Journals Online (AJOL)

    2015-02-03

    . Hu G, Wei Y, Kang Y. The multifaceted role of MTDH/AEG‑1 in cancer progression. Clin Cancer Res 2009;15:5615‑20. 10. Dow JK, deVere White RW. Fibroblast growth factor 2: Its structure and property, paracrine function ...

  18. Growth factor transgenes interactively regulate articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2013-04-01

    Adult articular chondrocytes lack an effective repair response to correct damage from injury or osteoarthritis. Polypeptide growth factors that stimulate articular chondrocyte proliferation and cartilage matrix synthesis may augment this response. Gene transfer is a promising approach to delivering such factors. Multiple growth factor genes regulate these cell functions, but multiple growth factor gene transfer remains unexplored. We tested the hypothesis that multiple growth factor gene transfer selectively modulates articular chondrocyte proliferation and matrix synthesis. We tested the hypothesis by delivering combinations of the transgenes encoding insulin-like growth factor I (IGF-I), fibroblast growth factor-2 (FGF-2), transforming growth factor beta1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), and bone morphogenetic protien-7 (BMP-7) to articular chondrocytes and measured changes in the production of DNA, glycosaminoglycan, and collagen. The transgenes differentially regulated all these chondrocyte activities. In concert, the transgenes interacted to generate widely divergent responses from the cells. These interactions ranged from inhibitory to synergistic. The transgene pair encoding IGF-I and FGF-2 maximized cell proliferation. The three-transgene group encoding IGF-I, BMP-2, and BMP-7 maximized matrix production and also optimized the balance between cell proliferation and matrix production. These data demonstrate an approach to articular chondrocyte regulation that may be tailored to stimulate specific cell functions, and suggest that certain growth factor gene combinations have potential value for cell-based articular cartilage repair. Copyright © 2012 Wiley Periodicals, Inc.

  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. Translation initiation requires cell division cycle 123 (Cdc123) to facilitate biogenesis of the eukaryotic initiation factor 2 (eIF2).

    Science.gov (United States)

    Perzlmaier, Angelika F; Richter, Frank; Seufert, Wolfgang

    2013-07-26

    The eukaryotic translation initiation factor 2 (eIF2) is central to the onset of protein synthesis and its modulation in response to physiological demands. eIF2, a heterotrimeric G-protein, is activated by guanine nucleotide exchange to deliver the initiator methionyl-tRNA to the ribosome. Here we report that assembly of the eIF2 complex in vivo depends on Cdc123, a cell proliferation protein conserved among eukaryotes. Mutations of CDC123 in budding yeast reduced the association of eIF2 subunits, diminished polysome levels, and increased GCN4 expression indicating that Cdc123 is critical for eIF2 activity. Cdc123 bound the unassembled eIF2γ subunit, but not the eIF2 complex, and the C-terminal domain III region of eIF2γ was both necessary and sufficient for Cdc123 binding. Alterations of the binding site revealed a strict correlation between Cdc123 binding, the biological function of eIF2γ, and its ability to assemble with eIF2α and eIF2β. Interestingly, high levels of Cdc123 neutralized the assembly defect and restored the biological function of an eIF2γ mutant. Moreover, the combined overexpression of eIF2 subunits rescued an otherwise inviable cdc123 deletion mutant. Thus, Cdc123 is a specific eIF2 assembly factor indispensable for the onset of protein synthesis. Human Cdc123 is encoded by a disease risk locus, and, therefore, eIF2 biogenesis control by Cdc123 may prove relevant for normal cell physiology and human health. This work identifies a novel step in the eukaryotic translation initiation pathway and assigns a biochemical function to a protein that is essential for growth and viability of eukaryotic cells.

  1. Initiation factor 2, tRNA, and 50S subunits cooperatively stabilize mRNAs on the ribosome during initiation

    Science.gov (United States)

    Masuda, Tomoaki; Petrov, Alexey N.; Iizuka, Ryo; Funatsu, Takashi; Puglisi, Joseph D.; Uemura, Sotaro

    2012-01-01

    Initiation factor 2 (IF2) is a key factor in initiation of bacterial protein synthesis. It recruits initiator tRNA to the small ribosomal subunit and facilitates joining of the large ribosomal subunit. Using reconstituted translation system of Escherichia coli and optical tweezers, we directly measure the rupture force between single ribosomal complexes and mRNAs for initiation complexes in the presence and the absence of IF2. We demonstrate that IF2 together with codon recognition by initiator tRNA increases the force required to dislocate mRNA from the ribosome complexes; mRNA stabilization by IF2 required the presence of a joined 50S subunit, and was independent of bound guanine nucleotide. IF2 thus helps lock the 70S ribosome over the start codon during initiation, thus maintaining reading frame. Our results show how mRNA is progressively stabilized on the ribosome through distinct steps of initiation. PMID:22411833

  2. Effect of ten weeks of combined exercise on growth hormone, insulin ...

    African Journals Online (AJOL)

    The purpose of the present study was to examine the effect of 10 weeks of combined exercise on growth hormone (GH), insulin-like growth factor-2 (IGF-2) and myostatin levels in elderly Korean women. Subjects were randomly assigned to the combined exercise group (CEG; n=17) or the control group (CG; n=17).

  3. α-synuclein aggregation reduces nigral myocyte enhancer factor-2D in idiopathic and experimental Parkinson's disease.

    Science.gov (United States)

    Chu, Yaping; Mickiewicz, Amanda L; Kordower, Jeffrey H

    2011-01-01

    α-Synuclein is an abundant neuronal protein that has been linked to both normal synaptic function and neurodegenerative disease, in particular, Parkinson's disease (PD). Evidence from both in vitro and in vivo studies indicate that increased wild type or mutant α-synuclein can cause PD, but the molecular mechanisms that underlie α-synuclein-mediated neurotoxicity remain poorly understood. We reported here that myocyte enhancer factor 2D (MEF2D), a nuclear transcription factor known to promote neuronal survival, is down regulated in response α-synuclein accumulation and aggregation. Our data demonstrated that levels of cytoplasmic and nuclear MEF2D were significantly decreased in PD nigral neurons when compared to the nigra of age-matched controls and Alzheimer's disease (AD) cases. This decrease was significantly greater in the nigral neurons with α-synuclein inclusions. Viral vector-mediated overexpression of human α-synuclein in rats resulted in significantly decreased MEF2D in nigral neurons similar to what was seen in PD. The decline of MEF2D-immunoreactivity was associated with a reduction in TH-immunoreactivity. These results indicate that the neuronal survival factor MEF2D is decreased in human and experimental PD, and this decrease is specifically associated with α-synuclein accumulation and aggregation. Copyright © 2010. Published by Elsevier Inc.

  4. The Drosophila Transcription Factors Tinman and Pannier Activate and Collaborate with Myocyte Enhancer Factor-2 to Promote Heart Cell Fate.

    Directory of Open Access Journals (Sweden)

    TyAnna L Lovato

    Full Text Available Expression of the MADS domain transcription factor Myocyte Enhancer Factor 2 (MEF2 is regulated by numerous and overlapping enhancers which tightly control its transcription in the mesoderm. To understand how Mef2 expression is controlled in the heart, we identified a late stage Mef2 cardiac enhancer that is active in all heart cells beginning at stage 14 of embryonic development. This enhancer is regulated by the NK-homeodomain transcription factor Tinman, and the GATA transcription factor Pannier through both direct and indirect interactions with the enhancer. Since Tinman, Pannier and MEF2 are evolutionarily conserved from Drosophila to vertebrates, and since their vertebrate homologs can convert mouse fibroblast cells to cardiomyocytes in different activator cocktails, we tested whether over-expression of these three factors in vivo could ectopically activate known cardiac marker genes. We found that mesodermal over-expression of Tinman and Pannier resulted in approximately 20% of embryos with ectopic Hand and Sulphonylurea receptor (Sur expression. By adding MEF2 alongside Tinman and Pannier, a dramatic expansion in the expression of Hand and Sur was observed in almost all embryos analyzed. Two additional cardiac markers were also expanded in their expression. Our results demonstrate the ability to initiate ectopic cardiac fate in vivo by the combination of only three members of the conserved Drosophila cardiac transcription network, and provide an opportunity for this genetic model system to be used to dissect the mechanisms of cardiac specification.

  5. 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.

  6. 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.

  7. 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.

  8. A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B.

    Science.gov (United States)

    Klein, U; Ramirez, M T; Kobilka, B K; von Zastrow, M

    1997-08-01

    The alpha-subunit of eukaryotic initiation factor 2B (eIF-2B), a guanine nucleotide exchange protein that functions in regulation of translation, was observed to associate with the carboxyl-terminal cytoplasmic domains of the alpha2A- and alpha2B-adrenergic receptors in a yeast two-hybrid screen of a cDNA library prepared from 293 cells. This protein association was confirmed in vitro by affinity chromatography and was shown to be specific for a subset of G protein-coupled receptors, including the alpha2A-, alpha2B-, alpha2C-, and beta2-adrenergic receptors, but not the vasopressin (V2) receptor. Association of these proteins in vivo was confirmed by specific co-immunoprecipitation of eIF-2Balpha with full-length beta2-adrenergic receptors expressed in transfected 293 cells and by fluorescence microscopy showing co-localization of these proteins in intact cells. Remarkably, eIF-2Balpha co-localized with receptors exclusively in regions of the plasma membrane that are in contact with the extracellular medium, but failed to associate with membranes making cell-cell contacts. Overexpression of eIF-2Balpha in 293 cells caused a small (approximately 15%) but significant enhancement of beta2-adrenergic receptor-mediated activation of adenylyl cyclase, without affecting forskolin or V2 receptor-mediated activation. These observations suggest a new role for a previously identified guanine nucleotide exchange protein in membrane biology and cell signaling.

  9. Genetic effects analysis of myeloid leukemia factor 2 and T cell receptor-beta on resistance to coccidiosis in chickens.

    Science.gov (United States)

    Kim, E-S; Hong, Y H; Lillehoj, H S

    2010-01-01

    Associations between the parameters of resistance to coccidiosis and SNP in 3 candidate genes located on chromosome 1 [T cell receptor-beta (TCR-beta), myeloid leukemia factor 2 (MLF2), and lymphotactin] were determined. Single nucleotide polymorphisms were genotyped in 24 F1 generation and 290 F2 generation birds. Four SNP were identified in the lymphotactin gene, 12 were located in the TCR-beta gene, and 4 in the MLF2 gene. At various times after experimental infection of the F2 generation with Eimeria maxima, BW, fecal oocyst shedding, and biochemical parameters were measured as parameters of coccidiosis resistance. Single marker association test was applied to determine the associations between the 20 SNP and the parameters of coccidiosis resistance. The maximum additive genetic effect on disease resistance of an SNP in MLF2 was explained by BW (P = 0.0002). The SNP in MLF2 significantly associated with BW was also associated with fecal oocyst shedding (P = 0.001). Four SNP associated with oocyst shedding were found within the coding region of TCR-beta (P coccidiosis resistance in chickens.

  10. 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.

  11. 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

  12. Mapping Gray's BIS and BAS Constructs onto Factor 1 and Factor 2 of Hare's Psychopathy Checklist - Revised.

    Science.gov (United States)

    Wallace, John F; Malterer, Melanie B; Newman, Joseph P

    2009-12-01

    Reinforcement Sensitivity Theory (RST; Gray, 1987; Gray & McNaughton, 2000) has proven to be a valuable tool for understanding psychopathy (e.g., Fowles, 1980, 1988; Newman & Malterer, 2009; Poythress, Edens, Landfield, Lilienfeld, Skeem, & Douglas, 2008). Recent research has linked two RST constructs, the Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS), to individuals with primary psychopathy and secondary psychopathy (Lykken, 1995; Newman, MacCoon, Vaughn, & Sadeh, 2005): Primary psychopaths manifest low BIS reactivity and secondary psychopaths manifest high BAS reactivity. In the present study, we examine the relationships between the BIS/BAS constructs and Factors 1 and 2 of the Psychopathy Checklist - Revised (PCL-R) in a sample of 472 incarcerated male offenders. Paralleling their relationships with primary and secondary psychopathy, the BIS/BAS constructs were differentially related to the two PCL-R factors. Specifically, the influence of the BIS was found to be more prominent than the influence of the BAS for Factor 1, and the influence of the BAS was more prominent than that of the BIS for Factor 2.

  13. DNA ligase 1 deficient plants display severe growth defects and delayed repair of both DNA single and double strand breaks

    Directory of Open Access Journals (Sweden)

    Bray Clifford M

    2009-06-01

    Full Text Available Abstract Background DNA ligase enzymes catalyse the joining of adjacent polynucleotides and as such play important roles in DNA replication and repair pathways. Eukaryotes possess multiple DNA ligases with distinct roles in DNA metabolism, with clear differences in the functions of DNA ligase orthologues between animals, yeast and plants. DNA ligase 1, present in all eukaryotes, plays critical roles in both DNA repair and replication and is indispensable for cell viability. Results Knockout mutants of atlig1 are lethal. Therefore, RNAi lines with reduced levels of AtLIG1 were generated to allow the roles and importance of Arabidopsis DNA ligase 1 in DNA metabolism to be elucidated. Viable plants were fertile but displayed a severely stunted and stressed growth phenotype. Cell size was reduced in the silenced lines, whilst flow cytometry analysis revealed an increase of cells in S-phase in atlig1-RNAi lines relative to wild type plants. Comet assay analysis of isolated nuclei showed atlig1-RNAi lines displayed slower repair of single strand breaks (SSBs and also double strand breaks (DSBs, implicating AtLIG1 in repair of both these lesions. Conclusion Reduced levels of Arabidopsis DNA ligase 1 in the silenced lines are sufficient to support plant development but result in retarded growth and reduced cell size, which may reflect roles for AtLIG1 in both replication and repair. The finding that DNA ligase 1 plays an important role in DSB repair in addition to its known function in SSB repair, demonstrates the existence of a previously uncharacterised novel pathway, independent of the conserved NHEJ. These results indicate that DNA ligase 1 functions in both DNA replication and in repair of both ss and dsDNA strand breaks in higher plants.

  14. THE INDIAN GROWTH MIRACLE AND ENDOGENOUS GROWTH

    OpenAIRE

    Jakob B. Madsen; Shishir Saxena; James B. Ang

    2008-01-01

    Using over half a century of R&D data for India, this paper examines the extent to which India's recent growth experience can be explained by R&D, international R&D spillovers, catch-up to the technology frontier and financial liberalization. Furthermore, the paper also tests whether any of the competing second-generation endogenous growth theories can explain India's growth experience. The findings provide support for Schumpeterian growth theory and indicate that the recent high growth rates...

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

    Science.gov (United States)

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

    2010-11-05

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

  16. Endothelial Myocyte Enhancer Factor 2c Inhibits Migration of Smooth Muscle Cells Through Fenestrations in the Internal Elastic Lamina.

    Science.gov (United States)

    Lu, Yao Wei; Lowery, Anthony M; Sun, Li-Yan; Singer, Harold A; Dai, Guohao; Adam, Alejandro P; Vincent, Peter A; Schwarz, John J

    2017-07-01

    Laminar flow activates myocyte enhancer factor 2 (MEF2) transcription factors in vitro to induce expression of atheroprotective genes in the endothelium. Here we sought to establish the role of Mef2c in the vascular endothelium in vivo. To study endothelial Mef2c, we generated endothelial-specific deletion of Mef2c using Tie2-Cre or Cdh5-Cre-ER T2 and examined aortas and carotid arteries by en face immunofluorescence. We observed enhanced actin stress fiber formation in the Mef2c-deleted thoracic aortic endothelium (laminar flow region), similar to those observed in normal aortic inner curvature (disturbed flow region). Furthermore, Mef2c deletion resulted in the de novo formation of subendothelial intimal cells expressing markers of differentiated smooth muscle in the thoracic aortas and carotids. Lineage tracing showed that these cells were not of endothelial origin. To define early events in intimal development, we induced endothelial deletion of Mef2c and examined aortas at 4 and 12 weeks postinduction. The number of intimal cell clusters increased from 4 to 12 weeks, but the number of cells within a cluster peaked at 2 cells in both cases, suggesting ongoing migration but minimal proliferation. Moreover, we identified cells extending from the media through fenestrations in the internal elastic lamina into the intima, indicating transfenestral smooth muscle migration. Similar transfenestral migration was observed in wild-type carotid arteries ligated to induce neointimal formation. These results indicate that endothelial Mef2c regulates the endothelial actin cytoskeleton and inhibits smooth muscle cell migration into the intima. © 2017 American Heart Association, Inc.

  17. 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.

  18. Expression of rat oligodendrocyte transcription factor 2 in COS-7 cells following its eukaryotic expression vector construction.

    Science.gov (United States)

    Qu, D-W; Han, X-J; Wang, Y-L; Xu, H-S

    2014-08-01

    The basic HLH transcription factor Olig is a key regulator for differentiating the oligodendrocyte lineage cells during development. Oligodendrocyte transcription factor 2 (Olig2) plays a crucial role in differentiating the oligodendrocytes in the spinal cord. We aimed to construct and investigate the eukaryotic expression recombinant plasmid in the rat Olig2. The experiment was performed at the Laboratory of Neurobiology, Xuzhou Medical College from October 2011 to March 2012. The pEGFP-N1 vector was purchased from Invitrogen. JM101 competent cells and COS-7 cells were preserved at the Laboratory of Neurobiology, Xuzhou Medical College, China. The Olig2 cDNA fragment was cloned by RT-PCR with the total RNA from the neonatal rat spinal cord, and subsequently cloned into pGEM-T vector. The confirmed Olig2 fragment was then cloned into the pEGFP-N1 vector. The right recombinant was transfected into COS-7 cells by lipofectamine 2000. The expression of the Olig2 in COS-7 cells was detected by RT-PCR and immunoblot analysis. Enzyme digestion and sequencing of the recombinant plasmid; and expression of the Olig2 were analyzed by fluorescence microscope and western blot. The correct pEGFP-N1-Olig2 cloning was verified by restriction endonuclease digestion and sequencing. The western blot analysis indicated that the Olig2-GFP fusion protein was expressed in the COS-7/pEGFP-N1-Olig2 cells at 72 h. The pEGFP-N1-Olig2 vector was constructed successfully. The Olig2-GFP fusion protein was expressed in the COS-7/pEGFP-N1-Olig2 cells. This study lays the foundation for further research in gene therapy for central nervous system demyelinating diseases.

  19. Dynamic Phosphorylation of the Myocyte Enhancer Factor 2Cα1 Splice Variant Promotes Skeletal Muscle Regeneration and Hypertrophy.

    Science.gov (United States)

    Baruffaldi, Fiorenza; Montarras, Didier; Basile, Valentina; De Feo, Luca; Badodi, Sara; Ganassi, Massimo; Battini, Renata; Nicoletti, Carmine; Imbriano, Carol; Musarò, Antonio; Molinari, Susanna

    2017-03-01

    The transcription factor MEF2C (Myocyte Enhancer Factor 2C) plays an established role in the early steps of myogenic differentiation. However, the involvement of MEF2C in adult myogenesis and in muscle regeneration has not yet been systematically investigated. Alternative splicing of mammalian MEF2C transcripts gives rise to two mutually exclusive protein variants: MEF2Cα2 which exerts a positive control of myogenic differentiation, and MEF2Cα1, in which the α1 domain acts as trans-repressor of the MEF2C pro-differentiation activity itself. However, MEF2Cα1 variants are persistently expressed in differentiating cultured myocytes, suggesting a role in adult myogenesis. We found that overexpression of both MEF2Cα1/α2 proteins in a mouse model of muscle injury promotes muscle regeneration and hypertrophy, with each isoform promoting different stages of myogenesis. Besides the ability of MEF2Cα2 to increase differentiation, we found that overexpressed MEF2Cα1 enhances both proliferation and differentiation of primary myoblasts, and activates the AKT/mTOR/S6K anabolic signaling pathway in newly formed myofibers. The multiple activities of MEF2Cα1 are modulated by phosphorylation of Ser98 and Ser110, two amino acid residues located in the α1 domain of MEF2Cα1. These specific phosphorylations allow the interaction of MEF2Cα1 with the peptidyl-prolyl isomerase PIN1, a regulator of MEF2C functions. Overall, in this study we established a novel regulatory mechanism in which the expression and the phosphorylation of MEF2Cα1 are critically required to sustain the adult myogenesis. The described molecular mechanism will represent a new potential target for the development of therapeutical strategies to treat muscle-wasting diseases. Stem Cells 2017;35:725-738. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  20. Participation of nuclear factor (erythroid 2-related), factor 2 in ameliorating lithocholic acid-induced cholestatic liver injury in mice.

    Science.gov (United States)

    Tan, K P; Wood, G A; Yang, M; Ito, S

    2010-11-01

    Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. We previously showed that LCA activates the oxidative stress-responsive nuclear factor (erythroid-2 like), factor 2 (Nrf2) in cultured liver cells, triggering adaptive responses that reduce cell injury. In this study, we determined whether Nrf2 protects the liver against LCA-induced toxicity in vivo. Nrf2 disrupted (Nrf2(-/-) ) and wild-type mice were treated with LCA (125 mg·kg(-1) body weight) to induce liver injury. Levels of mRNA, protein and function of important Nrf2 target genes coupled with liver histology and injury biomarkers of mice were examined. In 4 day LCA treatments, we observed a significantly higher hepatic induction of Nrf2 target, cytoprotective genes including thioredoxin reductase 1, glutamate cysteine ligase subunits, glutathione S-transferases, haeme oxygenase-1 and multidrug resistance-associated proteins 3 and 4 in the wild type as compared with the Nrf2(-/-) mice. Moreover, basal and LCA-induced hepatic glutathione and activities of glutathione S-transferases and thioredoxin reductases were higher in wild-type than in Nrf2(-/-) mice. This reduced production of cytoprotective genes against LCA toxicity rendered Nrf2(-/-) mice more susceptible to severe liver damage with the presence of multifocal liver necrosis, inflamed bile ducts and elevation of lipid peroxidation and liver injury biomarkers, such as alanine aminotransferase and alkaline phosphatase. Nrf2 plays a crucial cytoprotective role against LCA-induced liver injury by orchestrating adaptive responses. The pharmacological potential of targeting liver Nrf2 in the management of cholestatic liver diseases is proposed. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

  1. 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.

  2. Autophosphorylation of heme-regulated eukaryotic initiation factor 2α kinase and the role of the modification in catalysis.

    Science.gov (United States)

    Igarashi, Jotaro; Sasaki, Takehiko; Kobayashi, Noriko; Yoshioka, Shinji; Matsushita, Miyuki; Shimizu, Toru

    2011-04-01

    Heme-regulated eukaryotic initiation factor 2α (eIF2α) kinase (HRI), functions in response to heme shortage in reticulocytes and aids in the maintenance of a heme:globin ratio of 1:1. Under normal conditions, heme binds to HRI and blocks its function. However, during heme shortage, heme dissociates from the protein and autophosphorylation subsequently occurs. Autophosphorylation comprises a preliminary critical step before the execution of the intrinsic function of HRI; specifically, phosphorylation of Ser-51 of eIF2α to inhibit translation of the globin protein. The present study indicates that dephosphorylated mouse HRI exhibits strong intramolecular interactions (between the N-terminal and C-terminal domains) compared to phosphorylated HRI. It is therefore suggested that autophosphorylation reduces the intramolecular interaction, which induces irreversible catalytic flow to the intrinsic eIF2α kinase activity after heme dissociates from the protein. With the aid of MS, we identified 33 phosphorylated sites in mouse HRI overexpressed in Escherichia coli. Phosphorylated sites at Ser, Thr and Tyr were predominantly localized within the kinase insertion region (16 sites) and kinase domain (12 sites), whereas the N-terminal domain contained five sites. We further generated 30 enzymes with mutations at the phosphorylated residues and examined their catalytic activities. The activities of Y193F, T485A and T490A mutants were significantly lower than that of wild-type protein, whereas the other mutant proteins displayed essentially similar activity. Accordingly, we suggest that Tyr193, Thr485 and Thr490 are essential residues in the catalysis. © 2011 The Authors Journal compilation © 2011 FEBS.

  3. Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin- like growth factor 2 expression

    NARCIS (Netherlands)

    A.W. Langerak (Anton); K.A. Williamson (K.); K. Miyagawa (K.); A. Hagemeijer (Anne); M.A. Versnel (Marjan); N. Hastie (Nick)

    1995-01-01

    textabstractMutations in the WT1 tumor suppressor gene are known to contribute to the development of Wilms' tumor (WT) and associated gonadal abnormalities. WT1 is expressed principally in the fetal kidney, developing gonads, and spleen and also in the mesothelium, which lines the coelomic cavities.

  4. Step-Growth Polymerization.

    Science.gov (United States)

    Stille, J. K.

    1981-01-01

    Following a comparison of chain-growth and step-growth polymerization, focuses on the latter process by describing requirements for high molecular weight, step-growth polymerization kinetics, synthesis and molecular weight distribution of some linear step-growth polymers, and three-dimensional network step-growth polymers. (JN)

  5. Multiphasic growth curve analysis.

    NARCIS (Netherlands)

    Koops, W.J.

    1986-01-01

    Application of a multiphasic growth curve is demonstrated with 4 data sets, adopted from literature. The growth curve used is a summation of n logistic growth functions. Human height growth curves of this type are known as "double logistic" (n = 2) and "triple logistic" (n = 3) growth curves (Bock

  6. 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.

  7. The effects of myocyte enhancer factor 2A gene on the proliferation, migration and phenotype of vascular smooth muscle cells.

    Science.gov (United States)

    Zhao, Wang; Zhao, Shui-ping; Peng, Dao-quan

    2012-03-01

    The genetic basis for the phenotypic switching of vascular smooth muscle cells (VSMCs) is unclear in atherosclerosis. Recent studies showed that the 21-base pair deletion mutation (Δ21) in myocyte enhancer factor 2A (MEF2A) gene could be an inherited marker for coronary artery disease. MEF2A mutation may affect the phenotypic switching of VSMCs. Human aortic VSMCs were used. Four groups of VSMCs transfected with green fluorescent protein plasmid (control group), MEF2A wild-type (WT) plasmid (WT group), MEF2A Δ21 plasmid (Δ21 group) or MEF2A siRNA (siRNA group) were studied. The proliferation of VSMCs was determined by methylthiazolyldiphenyl-tetrazolium bromide, and the migration of VSMCs was measured by Millicell chamber. The protein expressions of MEF2A, smooth muscle α-actin, SM22α, osteopontin and p38 mitogen-activated protein kinase signaling pathway were detected by Western blotting. MEF2A protein expression was knockdown by siRNA transfection. MEF2A protein was overexpressed in WT and Δ21 groups. Δ21 and siRNA groups obviously showed more proliferation (methylthiazolyldiphenyl-tetrazolium bromide, 0.63 vs 0.66 vs 0.31, P < 0.01) and migration (52.6 vs 58.0 vs 21.2, P < 0.01) of VSMCs as compared with the WT group. In addition, the transfection of Δ21 and siRNA could induce the down-regulation of smooth muscle α-actin and SM22α (P < 0.01) and the up-regulation of osteopontin (P < 0.01) in VSMCs. The phosphorylated p38 signaling pathway expression was significantly enhanced in the Δ21 and siRNA groups as compared with that of the WT group (P < 0.01). These results suggest that MEF2A dominant negative mutation and RNA silence could induce the phenotypic switching of VSMCs, leading to its increased proliferation and migration, and p38 mitogen-activated protein kinase signaling pathway may participate in it. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Atypical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress.

    Science.gov (United States)

    Numazawa, Satoshi; Ishikawa, Makie; Yoshida, Aya; Tanaka, Sachiko; Yoshida, Takemi

    2003-08-01

    Transcription factor NF-E2-related factor 2 (Nrf2) regulates the induction of antioxidative proteins, including heme oxygenase-1 (HO-1). Nrf2 is sequestered in the cytoplasm by Keap1 under unstimulated conditions but translocates into the nucleus and transactivates the antioxidant responsive element (ARE) upon exposure to oxidative insults. It has recently been demonstrated that in vitro phosphorylation of Nrf2 on Ser40 by protein kinase C (PKC) facilitates the dissociation of Nrf2 from the Keap1 complex (Huang HC, Nguyen T, and Pickett CB. J Biol Chem 277: 42769-42774, 2002). The present study was designed to examine whether PKC is involved in oxidative stress-mediated nuclear translocation of Nrf2 in vivo and, if so, which PKC isoforms are involved. Induction of HO-1 gene expression by phorone, a glutathione depletor, and 4-hydroxy-2,3-nonenal (4-HNE), an end product of lipid peroxidation, was suppressed by a specific PKC inhibitor, Ro-31-8220, at concentrations that inhibit all isoforms in WI-38 cells. The induction of HO-1 was not affected by prolonged exposure of the cells to 12-O-tetradecanoylphorbol-13 acetate (TPA), suggesting that TPA-insensitive atypical PKC (aPKC) isoforms are involved. An immunocomplex kinase assay revealed that phorone and 4-HNE increased aPKCiota activity. In COS-7 cells, 4-HNE induced nuclear translocation of the Nrf2-green fluorescent protein (GFP) fusion protein, but not the Nrf2(S40A)-GFP mutant. In the absence of oxidative insults, the Nrf2(S40E)-GFP mutant was distributed in the nucleus. The Nrf2-GFP accumulation in the nucleus was induced by coexpression of aPKCiota, but not by a kinase inactive mutant aPKCiota(K274W). The activity of an ARE-driven reporter was increased by coexpression of aPKCiota, and this effect was eliminated by Ro-31-8220 in HepG2 cells. The reporter activity induced by 4-HNE was inhibited by coexpression of aPKCiota(K274W). These results suggest that phosphorylation of Nrf2 Ser40 by aPKC(s) is involved in

  9. Role for Runt-related Transcription Factor 2 in Proliferative and Calcified Vascular Lesions in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Ruffenach, Grégoire; Chabot, Sophie; Tanguay, Virginie F; Courboulin, Audrey; Boucherat, Olivier; Potus, Francois; Meloche, Jolyane; Pflieger, Aude; Breuils-Bonnet, Sandra; Nadeau, Valérie; Paradis, Renée; Tremblay, Eve; Girerd, Barbara; Hautefort, Aurélie; Montani, David; Fadel, Elie; Dorfmuller, Peter; Humbert, Marc; Perros, Frédéric; Paulin, Roxane; Provencher, Steeve; Bonnet, Sébastien

    2016-11-15

    Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This is sustained in time by the down-regulation of microRNA (miR)-204. In systemic vascular diseases, reduced miR-204 expression promotes vascular biomineralization by augmenting the expression of the transcription factor Runt-related transcription factor 2 (RUNX2). Implication of RUNX2 in PAH-related vascular remodeling and presence of calcified lesions in PAH remain unexplored. We hypothesized that RUNX2 is up-regulated in lungs of patients with PAH, contributing to vascular remodeling and calcium-related biomineralization. We harvested human lung tissues in which we assessed calcification lesions and RUNX2 expression. We also isolated PASMCs from these tissues for in vitro analyses. Using a bidirectional approach, we investigated the role for RUNX2 in cell proliferation, apoptosis, and calcification capacity. Ectopic delivery of small interfering RNA against RUNX2 was used in an animal model of PAH to evaluate the therapeutic potential of RUNX2 inhibition in this disease. Patients with PAH display features of calcified lesions within the distal pulmonary arteries (PAs). We show that RUNX2 is up-regulated in lungs, distal PAs, and primary cultured human PASMCs isolated from PAH and compared with patients without PAH. RUNX2 expression histologically correlates with vascular remodeling and calcification. Using in vitro gain- and loss-of-function approaches, we mechanistically demonstrate that miR-204 diminution promotes RUNX2 up-regulation and that sustained RUNX2 expression activates hypoxia-inducible factor-1α, leading to aberrant proliferation, resistance to apoptosis, and subsequent transdifferentiation of PAH-PASMCs into osteoblast-like cells. In the PAH Sugen/hypoxia rat model, molecular RUNX2 inhibition reduces PA remodeling and prevents calcification, thus improving pulmonary hemodynamic parameters and right ventricular

  10. Genomic growth hormone, growth hormone receptor and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-20

    Jul 20, 2009 ... Genomic growth hormone, growth hormone receptor and transforming growth factor β-3 gene polymorphism in breeder hens of Mazandaran native fowls. Babak Enayati and Ghodrat Rahimi-Mianji*. Laboratory for Molecular Genetics and Animal Biotechnology, Department of Animal Sciences, Faculty of ...

  11. Growth hormone suppression test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  12. Growth factors and kinases in glioblastoma growth

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Peña-Ortiz

    2016-10-01

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive type of brain cancer, having the highest invasion, migration, proliferation, and angiogenesis rates. Several signaling pathways are involved in the regulation of these processes including growth factors and their tyrosine kinase receptors, such as vascular endothelial growth factor (VEGF, transforming growth factor beta (TGFβ, fibroblast growth factor (FGF, platelet-derived growth factor (PDGF, and insulin-like growth factor–I (IGF–I. Different kinases and regulators also participate in signaling pathways initiated by growth factors, such as mitogen-activated kinases (MAPK, protein kinases C (PKC, phosphatidylinositol-3 kinases (PI3K, protein kinase B (PKB or Akt, glycogen synthase kinase 3β (GSK3β, the mTOR complex, and Bcl-2. In this review, we will focus on the role of these proteins as possible therapeutic targets in GBM.

  13. The Cytoprotective Effect of Petalonia binghamiae Methanol Extract against Oxidative Stress in C2C12 Myoblasts: Mediation by Upregulation of Heme Oxygenase-1 and Nuclear Factor-Erythroid 2 Related Factor 2

    Directory of Open Access Journals (Sweden)

    Ji Sook Kang

    2015-04-01

    Full Text Available This study was designed to examine the protective effects of the marine brown algae Petalonia binghamiae against oxidative stress-induced cellular damage and to elucidate the underlying mechanisms. P. binghamiae methanol extract (PBME prevented hydrogen peroxide (H2O2-induced growth inhibition and exhibited scavenging activity against intracellular reactive oxygen species (ROS induced by H2O2 in mouse-derived C2C12 myoblasts. PBME also significantly attenuated H2O2-induced comet tail formation in a comet assay, histone γH2A.X phosphorylation, and annexin V-positive cells, suggesting that PBME prevented H2O2-induced cellular DNA damage and apoptotic cell death. Furthermore, PBME increased the levels of heme oxygenase-1 (HO-1, a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2 related factor 2 (Nrf2. However, zinc protoporphyrin IX, a HO-1 competitive inhibitor, significantly abolished the protective effects of PBME on H2O2-induced ROS generation, growth inhibition, and apoptosis. Collectively, these results demonstrate that PBME augments the antioxidant defense capacity through activation of the Nrf2/HO-1 pathway.

  14. Fibroblast growth factor signaling in embryonic and cancer stem cells

    Czech Academy of Sciences Publication Activity Database

    Dvořák, Petr; Dvořáková, D.; Hampl, Aleš

    2006-01-01

    Roč. 580, - (2006), s. 2869-2874 ISSN 0014-5793 R&D Projects: GA MŠk 1M0538; GA ČR GA301/03/1122 Institutional research plan: CEZ:AV0Z50390512 Keywords : Fibroblast growth factor 2 * Embryonic stem cell * Hematopoietic progenitor cell Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.372, year: 2006

  15. 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

  16. Development and melt growth of novel scintillating halide crystals

    Czech Academy of Sciences Publication Activity Database

    Yoshikawa, A.; Yokota, Y.; Shoji, Y.; Král, Robert; Kamada, K.; Kurosawa, S.; Ohashi, Y.; Arakawa, M.; Chani, V.I.; Kochurikhin, V.V.; Yamaji, A.; Medvedev, A.; Nikl, Martin

    2017-01-01

    Roč. 74, Dec (2017), s. 109-119 ISSN 0925- 3467 Institutional support: RVO:68378271 Keywords : scintillator * halide * crystal growth from the melt * Bridgman method * Czochralski method * edge-defined film-fed method * micro-pulling-down method Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 2.238, year: 2016

  17. Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders

    NARCIS (Netherlands)

    Zhang, Z.; Suzuki, Y.; Shimozawa, N.; Fukuda, S.; Imamura, A.; Tsukamoto, T.; Osumi, T.; Fujiki, Y.; Orii, T.; Wanders, R. J.; Barth, P. G.; Moser, H. W.; Paton, B. C.; Besley, G. T.; Kondo, N.

    1999-01-01

    The PEX6 (peroxisome assembly factor-2, PAF-2) gene encodes a member of the AAA protein (ATPases associated with diverse cellular activities) family and restores peroxisome assembly in fibroblasts from peroxisome biogenesis disorder patients belonging to complementation group C (group 4 in the

  18. Population growth and economic growth: a reconsideration.

    Science.gov (United States)

    Yip, C K; Zhang, J

    1996-01-01

    The relationship between population growth and development has long been a controversial topic in the economic development literature. Early work by Hoover and Coale and more recent work by Blanchet suggest that high fertility suppresses per capita income growth. However, recent work by Kelley and Srinivasan are ambivalent about such a neo-Malthusian relationship between population growth and economic growth. The authors examine these conflicting positions. They emphasize that the rates of both population growth and income growth are endogenous variables within a general equilibrium framework. An endogenous growth model with endogenous fertility is then developed. It is found that when all exogenous variables are controlled for, there exists an inverse relation between population growth and economic growth. However, when some exogenous factors change, such as an improvement in technological progress, the relation becomes ambiguous. This suggests that the conflicting findings in the literature may be because of the presence of substantial heterogeneity in unobserved variables across countries and over time in cross-country panel data sets.

  19. Identification of singles bar as a direct transcriptional target of Drosophila Myocyte enhancer factor-2 and a regulator of adult myoblast fusion

    OpenAIRE

    Brunetti, Tonya M.; Fremin, Brayon J.; Cripps, Richard M.

    2015-01-01

    In Drosophila, myoblast fusion is a conserved process in which founder cells (FCs) and fusion competent myoblasts (FCMs) fuse to form a syncytial muscle fiber. Mutants for the myogenic regulator Myocyte enhancer factor-2 (MEF2) show a failure of myoblast fusion, indicating that MEF2 regulates the fusion process. Indeed, chromatin immunoprecipitation studies show that several genes involved in myoblast fusion are bound by MEF2 during embryogenesis. Of these, the MARVEL domain gene singles bar ...

  20. 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

  1. Influence of surface wave plasma deposition conditions on diamond growth regime

    Czech Academy of Sciences Publication Activity Database

    Babchenko, Oleg; Potocký, Štěpán; Ižák, Tibor; Hruška, Karel; Bryknar, Z.; Kromka, Alexander

    2015-01-01

    Roč. 271, Jun (2015), s. 74-79 ISSN 0257-8972 R&D Projects: GA ČR(CZ) GA14-05053S Institutional support: RVO:68378271 Keywords : surface wave plasma * diamond thin films * growth kinetics * scanning electron microscopy * Raman spectroscopy * optical emission spectroscopy Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.139, year: 2015

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Crystal growth and scintillation properties of Nd:CaF.sub.2./sub..

    Czech Academy of Sciences Publication Activity Database

    Tanaka, H.; Kawaguchi, N.; Abe, N.; Furuya, Y.; Yokota, Y.; Yanagida, T.; Pejchal, Jan; Nikl, Martin; Kawazoe, Y.; Yoshikawa, A.

    2011-01-01

    Roč. 33, č. 3 (2011), 284-287 ISSN 0925- 3467 Institutional research plan: CEZ:AV0Z10100521 Keywords : fluoride * single crystal * crystal growth from the melt * Nd 3+ 5d-4f * radiation * scintillator Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.023, year: 2011

  11. 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

  12. 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

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

    DEFF Research Database (Denmark)

    Hawkins, Clare Louise; Davies, Michael Jonathan

    2002-01-01

    Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is a key bactericidal agent, but can also damage host tissue. As there is a strong link between chronic inflammation and some cancers, we have investigated H...

  14. 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,

  15. Growth hormone stimulation test

    Science.gov (United States)

    ... 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 the ...

  16. 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

  17. 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...

  18. Toddler Growth and Development

    Science.gov (United States)

    ... time, his or her physical growth and motor development will slow, but you can expect to see ... Schedule of Well-Child Care Visits . ​​ Toddler Growth & Development Physical Skills Walks alone Pulls toys behind when ...

  19. Growth uncertainty and risksharing

    OpenAIRE

    Stefano Athanasoulis; Eric Van Wincoop

    1997-01-01

    How large are potential benefits from global risksharing? In order to answer this question we propose a new methodology that is closely connected with the empirical growth literature. We obtain estimates of residual risk (growth uncertainty) at various horizons from regressions of country-specific growth in deviation from world growth on a wide set of variables in the information set. Since this residual risk can be entirely hedged through risksharing, we use it to obtain a measure of the pot...

  20. Growth of Nd doped (Lu, Gd).sub.3./sub.(Ga, Al).sub.5./sub.O.sub.12./sub. single crystal by the micro pulling down method and their scintillation properties

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

    Roč. 41, Mar (2015), s. 32-35 ISSN 0925- 3467 Institutional support: RVO:68378271 Keywords : single crystal growth * scintillator * garnet * neodymium Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.183, year: 2015

  1. [Population Growth and Development].

    Science.gov (United States)

    Clausen, A. W.

    Rapid population growth as a central development problem, the proper domain of government in reducing population growth, and effective measures which can be taken to reduce fertility are examined. Rapid population growth puts a brake on development because it exacerbates the difficult choice between higher consumption now and the investment needed…

  2. 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...

  3. Corrupt Bureaucracy and Growth

    OpenAIRE

    Djumashev, Ratbek

    2006-01-01

    In this paper, we analyze 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.

  4. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    IAS Admin

    Plant Growth Promoting Rhizobacteria (PGPR) are a group of bacteria that enhances plant growth and yield via various plant growth promoting substances as well as biofertilizers. Given the negative environmental impact of artificial fertiliz- ers and their increasing costs, the use of beneficial soil micro- organisms such as ...

  5. 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...

  6. 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...... 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......, investing in the rebuilding of fish stocks and a coordinated regulation of marine activities that interact with fisheries. Incentive-based regulation of fisheries that counterbalances services of the ecosystems is an important instrument to achieve green growth....

  7. 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.

  8. Growth rates made easy.

    Science.gov (United States)

    Hall, Barry G; Acar, Hande; Nandipati, Anna; Barlow, Miriam

    2014-01-01

    In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux. We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates.

  9. 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)....

  10. New thrombopoietic growth factors

    OpenAIRE

    Kuter, David J.

    2007-01-01

    Although development of first-generation thrombopoietic growth factors (recombinant human thrombopoietin [TPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) was stopped due to development of antibodies to PEG-rHuMGDF, nonimmunogenic second-generation thrombopoietic growth factors with unique pharmacologic properties have been developed. TPO peptide mimetics contain TPO receptor-activating peptides inserted into complementarity-determining regions o...

  11. 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....

  12. 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....

  13. Optimising growth in phenylketonuria

    DEFF Research Database (Denmark)

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

    2012-01-01

    . 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...... 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...

  14. 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.

  15. Deregulation, economic growth and growth acceleration

    Czech Academy of Sciences Publication Activity Database

    Stankov, Petar

    -, č. 424 (2010), s. 1-42 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : deregulation * economic growth * origins of institutional change Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp424.pdf

  16. Governance and growth revisited

    NARCIS (Netherlands)

    Seldadyo, H.; de Haan, J.; Pandu Nugroho, E.

    2007-01-01

    Recent studies yield diverging outcomes on the governance-growth relationship. In this paper we construct a new index of governance using a latent variable approach and test whether this index is related to growth with varying samples of countries and different conditioning variables. The results

  17. 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.

  18. Employment without Growth

    DEFF Research Database (Denmark)

    Nørgaard, Jørgen

    Employment is a central argument for economic growth in the Western world. But environmental problems like global warming points towards limits to growth. The presentation outlines the history of what has lead to this dilemma. Fortunately citizens attitudes now points towards a preference for less...

  19. 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

  20. Pubertal growth in diabetics.

    OpenAIRE

    Stewart-Brown, S L; Lee, T J; Savage, D C

    1985-01-01

    Mean values for two variables of the pubertal growth spurt, peak height velocity and age at peak velocity, of children attending the diabetic clinic in Bristol are reported. The growth spurt was normal both in timing and intensity in boys, but the peak velocity was reduced and age at peak velocity more variable among girls.

  1. Globalization, Growth and Poverty

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

    research. Older and Poorer? How sharing among generations could improve wellbeing. TOWARD INCLUSIVE GROWTH. Around the world, the age of the entire population is changing. These changes will affect economic growth and equity across generations. In. 190 countries, the fastest-growing age group is working-age ...

  2. Synthetic growth reference charts

    NARCIS (Netherlands)

    Hermanussen, Michael; Stec, Karol; Aßmann, Christian; Meigen, Christof; Van Buuren, Stef

    2016-01-01

    Objectives: To reanalyze the between-population variance in height, weight, and body mass index (BMI), and to provide a globally applicable technique for generating synthetic growth reference charts. Methods: Using a baseline set of 196 female and 197 male growth studies published since 1831, common

  3. 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.

  4. Globalization, Growth and Poverty

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

    supply foreign-owned firms have gained in productivity as foreign firms made efforts to increase supplier efficiency. Also, they find that local firms, especially in Brazil, have positive (but small) vertical spillovers as they have turned to export markets. TOWARD INCLUSIVE GROWTH. Since the 1990s, growth in Argentina and ...

  5. Growth Plate Injuries

    Science.gov (United States)

    ... cause any lasting problems for your child or teen. Growth plates are areas of growing tissues that cause ... are replaced by solid bone. Who gets them? Growth plate injuries happen to children and teens. This injury happens twice as often in boys ...

  6. Growth hormone test

    Science.gov (United States)

    ... children it is called gigantism . Too little growth hormone can cause a slow or flat rate of growth in children . In adults it can cause changes in energy, muscle mass, cholesterol levels, and bone strength. The GH test may also be used ...

  7. 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.

  8. 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....

  9. Cavitation cloud growth

    International Nuclear Information System (INIS)

    Bonnin, J.

    1977-01-01

    The cavitation cloud growth in a pipeline submitted to a steep pressure drop (passage of a negative surge) is due to the simultaneous growth of a great number of homogeneous nuclei, thus producing a cloud of cavitation bubbles whose diameters become rapidly of the same order as their distances. Though their growth are independent at the beginning of the phenomenon, interactions take place when they become relatively close, due either to a change in the system planimetry, or to the interlocking of mass diffusion (gaseous cavitation) or heat (vaporous cavitation) boundary layers. After having examined known solutions to the problem of an unique bubble growth, and their possible use in case of interaction, the limits of the unique bubble growth are pointed out to conclude in favour of a preferential geometric limit, occuring near the minimum of the perturbation celerity in the mixture [fr

  10. Aid and Growth

    DEFF Research Database (Denmark)

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

    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......, 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...... 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....

  11. 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

  12. Silencing of EEF2K (eukaryotic elongation factor-2 kinase) reveals AMPK-ULK1-dependent autophagy in colon cancer cells.

    Science.gov (United States)

    Xie, Chuan-Ming; Liu, Xiao-Yu; Sham, Kathy W Y; Lai, Josie M Y; Cheng, Christopher H K

    2014-09-01

    EEF2K (eukaryotic elongation factor-2 kinase), also known as Ca (2+)/calmodulin-dependent protein kinase III, functions in downregulating peptide chain elongation through inactivation of EEF2 (eukaryotic translation elongation factor 2). Currently, there is a limited amount of information on the promotion of autophagic survival by EEF2K in breast and glioblastoma cell lines. However, the precise role of EEF2K in carcinogenesis as well as the underlying mechanism involved is still poorly understood. In this study, contrary to the reported autophagy-promoting activity of EEF2K in certain cancer cells, EEF2K is shown to negatively regulate autophagy in human colon cancer cells as indicated by the increase of LC3-II levels, the accumulation of LC3 dots per cell, and the promotion of autophagic flux in EEF2K knockdown cells. EEF2K negatively regulates cell viability, clonogenicity, cell proliferation, and cell size in colon cancer cells. Autophagy induced by EEF2K silencing promotes cell survival and does not potentiate the anticancer efficacy of the AKT inhibitor MK-2206. In addition, autophagy induced by silencing of EEF2K is attributed to induction of protein synthesis and activation of the AMPK-ULK1 pathway, independent of the suppression of MTOR activity and ROS generation. Knockdown of AMPK or ULK1 significantly abrogates EEF2K silencing-induced increase of LC3-II levels, accumulation of LC3 dots per cell as well as cell proliferation in colon cancer cells. In conclusion, silencing of EEF2K promotes autophagic survival via activation of the AMPK-ULK1 pathway in colon cancer cells. This finding suggests that upregulation of EEF2K activity may constitute a novel approach for the treatment of human colon cancer.

  13. 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

    OpenAIRE

    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

    2014-01-01

    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. ...

  14. 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

    Purpose: To investigate long-term functional and anatomical outcomes, discontinuation patterns, drug switching and rates of nonimprovement in patients treated with ranibizumab pro re nata (PRN) regimen for diabetic macular oedema (DME) according to the Danish national guidelines. Methods......: 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.......5, +2.7, +1.8, +2.3 letters and -97.4, -102.6, -106.9, -105.9, -131.6 μm, respectively. Mean number of injections was 6.1 in year 1 and 1.8 in year 4. In 93 patients, drug switching to aflibercept showed no difference between the two drugs on BCVA or CST. In 79 patients, CST decreased

  15. 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

  16. Growth in pinnipeds.

    Science.gov (United States)

    McLaren, I A

    1993-02-01

    This review presents summary figures of, and fits growth curves to, data on body lengths (as standard length, SL, whenever possible) of pinnipeds at ages estimated to O.I y. (1) Generalized von Bertalanffy (vB) growth curves are fitted to most data: Lx = L infinity (I - ea(x-x0)b, Lx is length at age x, x0 is the origin of the curve (here chosen a priori as time of initiation of embryonic growth), L infinity is asymptotic length, a (which is negative) determines rate of approach to the asymptote, and b influences the 'shape' of the approach. (2) No single monotonic growth equation suffices for growth in length, which is linear before birth and remains so during early life. The vB equation is only suitable to describe mean lengths of newborns, and animals one or more years old. (3) Also, for males of polygynous species, two functions are needed to account for accelerated growth at puberty. Generally a Gompertz equation is adequate for adult males of these species. (4) The fitted growth equations permit statistical comparisons of sizes and growth rates, as well as of individual variability (as growth-curve residuals), among populations and species. (5) For the following species (including different populations when available), the reliability of data is assessed and parameters of growth curves are presented (with sexes separated where significantly different): walrus, California and Steller sea lions, Antarctic, subantarctic and northern fur seals, Hawaiian monk seal, crabeater, Weddell and Leopard seals, southern and northern elephant seals, bearded, hooded, ringed, Baikal, Caspian, spotted, harbour, harp, ribbon and grey seals. (6) Some novel findings pertain to individual species as follows. Although the Pacific walrus is generally stated to be the larger subspecies, females from Hudson Bay and males from Foxe Basin, in the eastern Canadian Arctic, may be as long as those from the Bering Sea. Although female Weddell seals have been assumed to grow larger than

  17. 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....

  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. Biofuels, poverty, and growth

    DEFF Research Database (Denmark)

    Arndt, Channing; Benfica, Rui; Tarp, Finn

    2010-01-01

    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......This paper assesses the implications of large-scale investments in biofuels for growth and income distribution. We find that biofuels investment enhances growth and poverty reduction despite some displacement of food crops by biofuels. Overall, the biofuel investment trajectory analyzed increases...

  1. Modeling Urban Fire Growth,

    Science.gov (United States)

    Nuclear explosion damage, *Explosion effects, *Fires, *Flame propagation, Growth (General), Area coverage, Ignition, Combustion, Casualties...Computerized simulation, Predictions, Countermeasures, Fire suppression, Damage assessment, Urban areas, Vulnerability, Data acquisition, Methodology, Symposia

  2. Normal growth and development

    Science.gov (United States)

    A child's growth and development can be divided into four periods: Infancy Preschool years Middle childhood years Adolescence Soon after birth, an infant normally loses about 5% to 10% of their birth weight. By about age ...

  3. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    IAS Admin

    PGPR genera exhibiting plant growth promoting activity are: Pseudomonas, Azospirillum, Azotobacter, Bacillus, Burkholdaria,. Enterobacter, Rhizobium, Erwinia, Mycobacterium, Mesorhizo- bium, Flavobacterium, etc. This article presents perspectives on the role of PGPR in agriculture sustainability. Jay Shankar Singh is an.

  4. 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.

  5. 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.

  6. 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.

  7. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 3. Plant Growth Promoting Rhizobacteria - Potential Microbes for Sustainable Agriculture. Jay Shankar Singh. General Article Volume 18 Issue 3 March 2013 pp 275-281 ...

  8. 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.

  9. Mapping Inclusive Growth

    OpenAIRE

    Raquel Almeida Ramos; Rafael Ranieri; Jan-Willem Lammes

    2013-01-01

    Since its emergence around the turn of the century the concept of inclusive growth has been substantially debated by researchers and practitioners, has increasingly gained space in domestic and international political circles, has inspired the design of and generated projects and policies, and has impacted the views and the lives of many people. While the conceptual debate and the practical application of various definitions of inclusive growth have taken place simultaneously, they have recen...

  10. ECONOMIC GROWTH AND POVERTY,

    Science.gov (United States)

    The problems of poverty in the United States, and their resolution, are inextricably connected with the nature of the economic growth process and its...economic deprivation, but the adjustments required by growth have left in their wake new pockets of poverty . In the future, one of the key variables...that will determine how rapidly we can eliminate poverty in the United States will be the rate of increase in average incomes. And one of the key

  11. 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 ...

  12. Inflation, volatility and growth

    OpenAIRE

    Ruth Judson; Athanasios Orphanides

    1996-01-01

    This paper re-examines the relationship between inflation, inflation volatility and growth using cross-country panel data for the past 30 years. With regard to the level of inflation, we find that in contrast to current findings which are based on cross-sectional time-average regression comparisons, exploiting the time dimension of the data reveals a strong negative correlation between inflation and income growth for all but very low inflation countries. To examine the role of inflation uncer...

  13. FGF growth factor analogs

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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

  15. 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

  16. Entrepreneurship, Information, and Growth.

    Science.gov (United States)

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

    2015-09-01

    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.

  17. 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

  18. 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

  19. 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.

  20. Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation.

    Science.gov (United States)

    Barhwal, K; Hota, S K; Jain, V; Prasad, D; Singh, S B; Ilavazhagan, G

    2009-06-30

    Exposure to hypobaric hypoxia, a condition involving decreased availability of oxygen is known to be associated with oxidative stress, neurodegeneration and memory impairment. The multifactorial response of the brain and the complex signaling pathways involved therewith limits the therapeutic efficacy of several antioxidants in ameliorating hypobaric hypoxia-induced memory impairment. The present study was therefore aimed at investigating the potential of acetyl-l-carnitine (ALCAR), a known antioxidant that has been reported to augment neurotrophin-mediated survival mechanisms, in ameliorating hypoxia-induced neurodegeneration and memory impairment. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor involved in the cellular defense mechanism against oxidative stress related to brain injury and neurological disorders. The study was designed to understand the mechanisms involving Nrf2 stabilization following exposure to hypobaric hypoxia. The results displayed reference memory impairment in Sprague-Dawley rats exposed to hypobaric hypoxia (7620 m) for 14 consecutive days which however improved on administration of ALCAR during hypoxic exposure. The study also revealed Nrf2 regulated augmented antioxidant response on administration of ALCAR which was through a novel tyrosine kinase A (TrkA) receptor-mediated mechanism. A decrease in free radical generation, lipid peroxidation and protein oxidation was also observed along with a concomitant increase in thioredoxin and reduced glutathione levels on administration of ALCAR during exposure to hypobaric hypoxia. The present study therefore reveals the therapeutic potential of ALCAR under conditions of hypobaric hypoxia and elucidates a novel mechanism of action of the drug.

  1. A p38 Mitogen-Activated Protein Kinase-Regulated Myocyte Enhancer Factor 2–β-Catenin Interaction Enhances Canonical Wnt Signaling

    Science.gov (United States)

    Ehyai, Saviz; Dionyssiou, Mathew G.; Gordon, Joseph W.; Williams, Declan; Siu, K. W. Michael

    2015-01-01

    Canonical Wnt/β-catenin signaling plays a major role in various biological contexts, such as embryonic development, cell proliferation, and cancer progression. Previously, a connection between p38 mitogen-activated protein kinase (MAPK) signaling and Wnt-mediated activation of β-catenin was implied but poorly understood. In the present study, we investigated potential cross talk between p38 MAPK and Wnt/β-catenin signaling. Here we show that a loss of p38 MAPK α/β function reduces β-catenin nuclear accumulation in Wnt3a-stimulated primary vascular smooth muscle cells (VSMCs). Conversely, active p38 MAPK signaling increases β-catenin nuclear localization and target gene activity in multiple cell types. Furthermore, the effect of p38 MAPK α/β on β-catenin activity is mediated through phosphorylation of a key p38 MAPK target, myocyte enhancer factor 2 (MEF2). Here we report a p38 MAPK-mediated, phosphorylation-dependent interaction between MEF2 and β-catenin in multiple cell types and primary VSMCs that results in (i) increased β-catenin nuclear retention, which is reversed by small interfering RNA (siRNA)-mediated MEF2 gene silencing; (ii) increased activation of MEF2 and Wnt/β-catenin target genes; and (iii) increased Wnt-stimulated cell proliferation. These observations provide mechanistic insight into a fundamental level of cross talk between p38 MAPK/MEF2 signaling and canonical Wnt signaling. PMID:26552705

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5.

    Science.gov (United States)

    Ashino, Takashi; Ohkubo-Morita, Haruyo; Yamamoto, Masayuki; Yoshida, Takemi; Numazawa, Satoshi

    2014-01-01

    Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)-deficient (Nrf2(-⧸-)) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2(-⧸-) mouse livers were lower than that in wild-type mouse livers. Nrf2(-⧸-) mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression.

  7. Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5☆

    Science.gov (United States)

    Ashino, Takashi; Ohkubo-Morita, Haruyo; Yamamoto, Masayuki; Yoshida, Takemi; Numazawa, Satoshi

    2014-01-01

    Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)–deficient (Nrf2−⧸−) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2−⧸− mouse livers were lower than that in wild-type mouse livers. Nrf2−⧸− mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression. PMID:24494203

  8. Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5

    Directory of Open Access Journals (Sweden)

    Takashi Ashino

    2014-01-01

    Full Text Available Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2–deficient (Nrf2−⧸− mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(PH-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2−⧸− mouse livers were lower than that in wild-type mouse livers. Nrf2−⧸− mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression.

  9. Attenuation of β-Amyloid-Induced Oxidative Cell Death by Sulforaphane via Activation of NF-E2-Related Factor 2

    Directory of Open Access Journals (Sweden)

    Chan Lee

    2013-01-01

    Full Text Available β-amyloid peptide (Aβ, a major component of senile plaques, plays important roles in neuropathology of Alzheimer's disease (AD. An array of in vitro and in vivo data indicates that Aβ-induced neuronal death is mediated by oxidative stress. In this study, we aimed to investigate effects of sulforaphane (SUL, an isothiocyanate in cruciferous vegetables, on Aβ-induced oxidative cell death in SH-SY5Y cells. Cells treated with Aβ25–35 exhibited decreased cell viability and underwent apoptosis as determined by MTT assay and TUNEL, respectively. Aβ25–35-induced cytotoxicity and apoptotic characteristics such as activation of c-JNK, dissipation of mitochondrial membrane potential, altered expression of Bcl-2 family proteins, and DNA fragmentation were effectively attenuated by SUL pretreatment. The antiapoptotic activity of SUL seemed to be mediated by inhibition of intracellular accumulation of reactive oxygen species and oxidative damages. SUL exerted antioxidant potential by upregulating expression of antioxidant enzymes including γ-glutamylcysteine ligase, NAD(PH:quinone oxidoreductase-1, and heme oxygenase-1 via activation of NF-E2-related factor 2(Nrf2. The protective effect of SUL against Aβ25–35-induced apoptotic cell death was abolished by siRNA of Nrf2. Taken together, the results suggest that pharmacologic activation of Nrf2 signaling pathway by SUL might be a practical prevention and/or protective treatment for the management of AD.

  10. Nuclear factor erythroid 2-related factor 2 antibody attenuates thermal hyperalgesia in the dorsal root ganglion: Neurochemical changes and behavioral studies after sciatic nerve-pinch injury.

    Science.gov (United States)

    Xiang, Qiong; Yu, Chao; Zhu, Yao-Feng; Li, Chun-Yan; Tian, Rong-Bo; Li, Xian-Hui

    2016-08-01

    Oxidative stress is generated in several peripheral nerve injury models.Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated to have a role in antioxidant effect. After nerve injury, the severely painful behavior is also performed. However, little has been explored regarding the function of Nrf2 in this painful process. Therefore, in this study, we compared the effects of Nrf2 antibody administration following sciatic nerve-pinch injury on painful behavior induced in young mice and neurochemical changes in dorsal root ganglion neurons. After pinch nerve injury, we found that the magnitude of the thermal allodynia was significantly decreased after application of Nrf2 antibody (5ul, 1mg/ml) in such injured animals and phosphorylated ERK(p-ERK) as well as the apoptotic protein (i.e., Bcl-6) in DRG neurons were also down-regulated in the anti-Nrf2-treated injured groups compared to the saline-treated groups. Taken collectively, these data suggested that the Nrf2 antibody reduced thermal hyperalgesia via ERK pathway and the down regulation of Bcl-6 protein from the apoptosis pathway might be protecting against the protein deletions caused by anti-Nrf2 effect and suggested the new therapeutic strategy with Nrf2 inhibitor following nerve injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Mutation of a nuclear respiratory factor 2 binding site in the 5' untranslated region of the ADSL gene in three patients with adenylosuccinate lyase deficiency.

    Science.gov (United States)

    Marie, S; Race, V; Nassogne, M-C; Vincent, M-F; Van den Berghe, G

    2002-07-01

    Adenylosuccinate lyase (ADSL; also called "adenylosuccinase") catalyzes two steps in the synthesis of purine nucleotides: (1) the conversion of succinylaminoimidazolecarboxamide ribotide into aminoimidazolecarboxamide ribotide and (2) the conversion of adenylosuccinate into adenosine monophosphate. ADSL deficiency, a recessively inherited disorder, causes variable-but most often severe-mental retardation, frequently accompanied by epilepsy and/or autism. It is characterized by the accumulation, in body fluids, of succinylaminoimidazolecarboxamide riboside and succinyladenosine, the dephosphorylated derivatives of the two substrates of the enzyme. Analysis of the ADSL gene of three unrelated patients with ADSL deficiency, in whom one of the ADSL alleles displayed a normal coding sequence, revealed a -49T-->C mutation in the 5' untranslated region of this allele. Measurements of the amount of mRNA transcribed from the latter allele showed that it was reduced to approximately 33% of that transcribed from the alleles mutated in their coding sequence. Further investigations showed that the -49T-->C mutation provokes a reduction to 25% of wild-type control of promoter function, as evaluated by luciferase activity and mRNA level in transfection experiments. The mutation also affects the binding of nuclear respiratory factor 2 (NRF-2), a known activator of transcription, as assessed by gel-shift studies. Our findings indicate that a mutation of a regulatory region of the ADSL gene might be an unusually frequent cause of ADSL deficiency, and they suggest a role for NRF-2 in the gene regulation of the purine biosynthetic pathway.

  12. 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.

  13. 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.

  14. Tools for measuring academic growth.

    Science.gov (United States)

    Kingsbury, G Gage; McCall, Martha; Hauser, Carl

    2009-01-01

    Growth measurement and growth modeling have gained substantial interest in the last few years with the development of new statistical procedures and policy decisions such as the incorporation of growth into No Child Left Behind. The current study investigates the following four aspects of growth measurement: a) issues in the development of vertical scales to measure growth; b) design of instruments to measure academic growth; c) techniques for modeling individual student growth, and d) uses of growth information in a classroom. Measuring growth has always been a daunting task, but the development of measurement tools such as the Rasch model and computerized adaptive testing position us well to obtain high-quality data with which to measure and model the growth of an individual student across a course of study. This growth information, in norm-referenced and standards-referenced form, should enhance educators' ability to enrich student learning.

  15. 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......Although it has been widely recognized that the growth of women-owned businesses is central to wealth creation, innovation and economic development; limited attention has been devoted to understanding small business growth from a female perspective.This research seeks to develop an understanding....... 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....

  16. Urban growth management

    DEFF Research Database (Denmark)

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

    2011-01-01

    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......, 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...

  17. Unsustainable growth, unsustainable capitalism

    DEFF Research Database (Denmark)

    Næss, Petter

    2006-01-01

    This article argues that there is a fundamental contradiction between a profit-oriented economic system and long-term environmental sustainability. The 'solutions' that are proposed by mainstream environmental economists as well as their 'ecological economy' colleagues do not solve the central...... 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......-coupling of economic growth from resource depletion and environmental degradation is possible only within certain sectors or product types and within relatively short time perspectives. The assumptions of mainstream economists about infinite economic growth (and infinite dematerialisation) represent a false ontology...

  18. Secular trends in growth.

    Science.gov (United States)

    Fudvoye, Julie; Parent, Anne-Simone

    2017-06-01

    Human adult height has been increasing world-wide for a century and a half. The rate of increase depends on time and place of measurement. Final height appears to have reached a plateau in Northern European countries but it is still increasing in southern European countries as well as Japan. While mean birth length has not changed recently in industrialized countries, the secular trend finally observed in adult height mostly originates during the first 2 years of life. Secular trend in growth is a marker of public health and provides insights into the interaction between growth and environment. It has been shown to be affected by income, social status, infections and nutrition. While genetic factors cannot explain such rapid changes in average population height, epigenetic factors could be the link between growth and environment. Copyright © 2017. Published by Elsevier Masson SAS.

  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. 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.

  1. Transforming growth factor-beta1 inhibits all-trans retinoic acid-induced apoptosis

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Pacherník, Jiří; Kubala, Lukáš; Vondráček, Jan; Hofmanová, Jiřina; Kozubík, Alois

    2006-01-01

    Roč. 30, č. 5 (2006), s. 607-623 ISSN 0145-2126 R&D Projects: GA ČR(CZ) GA524/03/0766; GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507 Keywords : transforming growth factor - beta * retinoic acid * myeloid leukemia Subject RIV: BO - Biophysics Impact factor: 2.483, year: 2006

  2. 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

  3. Growth and optical properties of RE-doped ternary rubidium lead chloride single crystals

    Czech Academy of Sciences Publication Activity Database

    Král, Robert; Nitsch, Karel; Babin, Vladimir; Šulc, J.; Jelínková, H.; Yokota, Y.; Yoshikawa, A.; Nikl, Martin

    2013-01-01

    Roč. 36, č. 2 (2013), s. 214-220 ISSN 0925- 3467 R&D Projects: GA MŠk LH12150 Institutional support: RVO:68378271 Keywords : rubidium lead chloride * crystal growth * micro-pulling-down method * rare earth doping * luminescence Subject RIV: BH - Optics, Masers, Lasers Impact factor: 2.075, year: 2013 http://www.sciencedirect.com/science/article/pii/S0925346713004710

  4. 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

  5. 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

  6. 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 inequali...... 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....

  7. 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 inequali...... 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....

  8. 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.

  9. Insulin-like growth factors in endometrioid adenocarcinoma: Correlation with clinico-pathological features and estrogen receptor expression

    International Nuclear Information System (INIS)

    Liang, Yuan-Jiao; Hao, Qun; Zhang, Hui-Ming; Wu, Yuan-Zhe; Wang, Jian-Dong

    2012-01-01

    Endometrial carcinoma is a common malignancy of female genital tract. Insulin-like growth factor is known to elicit estrogen-induced mitogenic activity and anti-apoptotic effect in endometrial tissues. The retrospective study investigated the expression of insulin-like growth factors, estrogen receptors and their associations in endometrioid adenocarcinoma (EAC) from 80 EAC patients in immunohistochemistry, and 58 EAC patients and 42 control patients in quantitative RT-PCR. The Pearson correlation analysis was used to analyze their correlations with clinic-pathological parameters. Our results showed that insulin-like growth factor-1 and insulin-like growth factor-2 mRNA levels were higher in tumor tissues and tumor-adjacent tissues than those in control cells, and were inversely correlated with the malignancy of the tumor with a positive correlation with ERα and ERβ expression. Insulin-like growth factor-1R protein expression was correlated with clinical stage, and insulin-like growth factor-2R protein expression was inversely correlated with histological grade. Insulin-like growth factor system plays an important role in estrogen-induced endometrial carcinogenesis, and overexpression of insulin-like growth factor-1R in the advanced endometrioid adenocarcinoma is not estrogen-dependent

  10. Theoretical Grounds of Economic Growth

    Directory of Open Access Journals (Sweden)

    Hasan Alp ÖZEL

    2012-06-01

    Full Text Available Economic growth bears importance for any country with different levels of development. It is seen that various theories of economic growth give a different importance to technological development and human capital. Theories of economic growth referred to as exogenous economic growth theories, which assume technological development and human capital as determinants of economic growth and propose that they are not affected by economic variables, consider them as the main determinants of economic growth in the long run While these models support technological development as the main source of economic growth in the long run, they have deficiencies in explaining the sources of technological development. These deficiencies are overcome by endogenous growth theories. Endogenous growth theories consider technological development as a variable that is affected by the decisions of economic units and internalize them. The aim of this study is to explain the thoretical grounds of exogenous and endogenous economic growth theories and stress the differences based on their nature.

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

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    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.

  12. Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma

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    Xiang Lei

    2012-03-01

    Full Text Available Abstract Background Breast cancer is the most common cancer and the leading cause of cancer mortality in women worldwide. Hypoxia is an important factor involved in the progression of solid tumors and has been associated with various indicators of tumor metabolism, angiogenesis and metastasis. But little is known about the contribution of Hypoxia-Inducible Factor-2a (HIF-2a to the drug resistance and the clinicopathological characteristics in breast cancer. Methods Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 invasive breast cancer patients with clinicopathological data. The correlations between the expression of HIF-2a and ABCG2 as well as other patients' clinicopathological data were investigated. Results The results showed that HIF-2a was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive staining for HIF-2a was defined as a brown staining observed mainly in the nucleus. A statistically significant correlation was demonstrated between HIF-2a expression and ABCG2 expression (p = 0.001, histology-grade (p = 0.029, and Ki67 (p = 0. 043 respectively. Conclusion HIF-2a was correlated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma. HIF-2a could regulate ABCG2 in breast cancer cells, and could be a novel potential bio-marker to predict chemotherapy effectiveness. The hypoxia/HIF-2a/ABCG2 pathway could be a new mechanism of breast cancer multidrug-resistance. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2965948166714795

  13. Human nuclear respiratory factor 2 alpha subunit cDNA: isolation, subcloning, sequencing, and in situ hybridization of transcripts in normal and monocularly deprived macaque visual system.

    Science.gov (United States)

    Guo, A; Nie, F; Wong-Riley, M

    2000-02-07

    Nuclear respiratory factor 2 (NRF-2) has been shown to contribute to the transcriptional regulation of a number of subunits of respiratory chain enzymes, including cytochrome c oxidase (CO). Our recent study demonstrated a parallel distribution of the alpha subunit proteins of NRF-2 (NRF-2 alpha) with CO in the monkey striate cortex, and that it can be regulated by neuronal activity. To determine whether this regulation is at the transcriptional level, the present study examined the expression of NRF-2 alpha mRNA in normal and monocularly deprived adult monkeys. A partial NRF-2 alpha cDNA was isolated from a human brain cDNA library. Sequence analysis revealed that it shared 99% identity with the published sequence from human HeLa cells. Riboprobes of NRF-2 alpha was generated and labeled with digoxigenin-11-UTP for in situ hybridization. The expression pattern of NRF-2 alpha mRNA in the normal striate cortex paralleled that of CO activity. It was highly expressed in layers IVC and VI, which contained high levels of CO, and more densely expressed in puffs of layers II and III than in interpuffs. In monkeys monocularly treated with tetrodotoxin for 1 day to 2 weeks, both NRF-2 alpha expression and CO activity were reduced in deprived ocular dominance columns of the visual cortex and in deprived layers of the lateral geniculate nucleus. These data indicate that, in the normal and visually deprived adult monkeys, NRF-2 alpha is regulated by neuronal activity at the transcriptional level.

  14. Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Tang, Chun-Mei; Liu, Fang-Zhou; Zhu, Jie-Ning; Fu, Yong-Heng; Lin, Qiu-Xiong; Deng, Chun-Yu; Hu, Zhi-Qin; Yang, Hui; Zheng, Xi-Long; Cheng, Jian-Ding; Wu, Shu-Lin; Shan, Zhi-Xin

    2016-10-31

    The role of microRNA-214-3p (miR-214-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. In mice with either Ang-II infusion or transverse aortic constriction (TAC) model, miR-214-3p expression was markedly decreased in the hypertrophic myocardium. Down-regulation of miR-214-3p was observed in the myocardium of patients with cardiac hypertrophy. Expression of miR-214-3p was upregulated in Ang-II-induced hypertrophic neonatal mouse ventricular cardiomyocytes. Cardiac hypertrophy was attenuated in Ang-II-infused mice by tail vein injection of miR-214-3p. Moreover, miR-214-3p inhibited the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC) in Ang-II-treated mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2C (MEF2C), which was increased in Ang-II-induced hypertrophic mouse myocardium and cardiomyocytes, was identified as a target gene of miR-214-3p. Functionally, miR-214-3p mimic, consistent with MEF2C siRNA, inhibited cell size increase and protein expression of ANP and β-MHC in Ang-II-treated mouse cardiomyocytes. The NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in cardiomyocytes. Taken together, our results revealed that MEF2C is a novel target of miR-214-3p, and attenuation of miR-214-3p expression may contribute to MEF2Cexpressionin cardiac hypertrophy.

  15. Genetic variants and effects on milk traits of the caprine paired-like homeodomain transcription factor 2 (PITX2) gene in dairy goats.

    Science.gov (United States)

    Zhao, Haiyu; Wu, Xianfeng; Cai, Hanfang; Pan, Chuanying; Lei, Chuzhao; Chen, Hong; Lan, Xianyong

    2013-12-15

    The paired-like homeodomain transcription factor 2 (PITX2) gene plays a critical role in cell proliferation, differentiation, hematopoiesis and organogenesis. This gene regulates several genes' expressions in the Wnt/beta-catenin and POU1F1 pathways, thereby probably affecting milk performance. The goal of this study was to characterize the genetic variants of the PITX2 gene and test their associations with milk traits in dairy goats. Herein, four novel single nucleotide polymorphisms (SNPs), AC_000163:g.18117T>C, g.18161C>G, g.18322C>A and g.18353T>C, within the caprine PITX2 gene, were found in two famous Chinese dairy goat breeds. These SNPs mapping at Cys28Arg, Pro42Pro, IVS1+79C>A and IVS1+110T>C, were genotyped by the MvaI, SmaI, MspI and RsaI aCRS-RFLP or PCR-RFLP methods, respectively. Accordingly, two main haplotypes (CGCT and CGCC) were identified among the specimens. Association testing revealed that the SmaI and RsaI polymorphisms were significantly associated with the milk fat content, milk lactose content and milk density (PPITX2 gene had the significant effects on milk traits. Hence, the RsaI and SmaI loci could be regarded as two DNA markers for selecting superior milk performance in dairy goats. These preliminary findings not only would extend the spectrum of genetic variation of the goat PITX2 gene, but also would contribute to implementing marker-assisted selection (MAS) in breeding and genetics in dairy goats. © 2013.

  16. 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.

  17. Role of nuclear factor erythroid 2-related factor 2 in the oxidative stress-dependent hypertension associated with the depletion of DJ-1.

    Science.gov (United States)

    Cuevas, Santiago; Yang, Yu; Konkalmatt, Prasad; Asico, Laureano D; Feranil, Jun; Jones, John; Villar, Van Anthony; Armando, Ines; Jose, Pedro A

    2015-06-01

    Renal dopamine 2 receptor dysfunction is associated with oxidative stress and high blood pressure (BP). We have reported that DJ-1, an oxidative stress response protein, is positively regulated by dopamine 2 receptor in the kidney. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of several antioxidant genes. We tested the hypothesis that Nrf2 is involved in the renal DJ-1-mediated inhibition of reactive oxygen species production. We have reported that silencing dopamine 2 receptor in mouse renal proximal tubule cells decreases the expression of DJ-1. We now report that silencing DJ-1 or dopamine 2 receptor in mouse proximal tubule cells and mouse kidneys decreases Nrf2 expression and activity and increases reactive oxygen species production; BP is also increased in mice in which renal DJ-1 or dopamine 2 receptor is silenced. DJ-1(-/-) mice have decreased renal Nrf2 expression and activity and increased nitro-tyrosine levels and BP. Silencing Nrf2 in mouse proximal tubule cells does not alter the expression of DJ-1 or dopamine 2 receptor, indicating that Nrf2 is downstream of dopamine 2 receptor and DJ-1. An Nrf2 inducer, bardoxolone, normalizes the systolic BP and renal malondialdehyde levels in DJ-1(-/-) mice without affecting them in their wild-type littermates. Because Nrf2 ubiquitination is increased in DJ-1(-/-) mice, we conclude that the protective effect of DJ-1 on renal oxidative stress is mediated, in part, by preventing Nrf2 degradation. Moreover, renal dopamine 2 receptor and DJ-1 are necessary for normal Nrf2 activity to keep a normal redox balance and BP. © 2015 American Heart Association, Inc.

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

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    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.

  19. Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2 in burn patient immune cells and monocytes.

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    Timothy K Eitas

    Full Text Available Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA injury have elevated levels of the innate immune cytokines Interleukin-6 (IL-6 and Monocyte Chemoattractant Protein-1 (MCP-1/CC-motif Chemokine Ligand 2(CCL2 early after hospital admission (0-48 Hours Post-hospital Admission (HPA. Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs revealed that burn shock patients (≥15% TBSA produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2 agonist, CDDO-Me(bardoxolone methyl, reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10 secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA. Hence, our findings with CDDO-Me(bardoxolone methyl and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.

  20. Treatment with a corticotrophin releasing factor 2 receptor agonist modulates skeletal muscle mass and force production in aged and chronically ill animals

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    Ferreira Leonardo F

    2011-01-01

    Full Text Available Abstract Background Muscle weakness is associated with a variety of chronic disorders such as emphysema (EMP and congestive heart failure (CHF as well as aging. Therapies to treat muscle weakness associated with chronic disease or aging are lacking. Corticotrophin releasing factor 2 receptor (CRF2R agonists have been shown to maintain skeletal muscle mass and force production in a variety of acute conditions that lead to skeletal muscle wasting. Hypothesis We hypothesize that treating animals with a CRF2R agonist will maintain skeletal muscle mass and force production in animals with chronic disease and in aged animals. Methods We utilized animal models of aging, CHF and EMP to evaluate the potential of CRF2R agonist treatment to maintain skeletal muscle mass and force production in aged animals and animals with CHF and EMP. Results In aged rats, we demonstrate that treatment with a CRF2R agonist for up to 3 months results in greater extensor digitorum longus (EDL force production, EDL mass, soleus mass and soleus force production compared to age matched untreated animals. In the hamster EMP model, we demonstrate that treatment with a CRF2R agonist for up to 5 months results in greater EDL force production in EMP hamsters when compared to vehicle treated EMP hamsters and greater EDL mass and force in normal hamsters when compared to vehicle treated normal hamsters. In the rat CHF model, we demonstrate that treatment with a CRF2R agonist for up to 3 months results in greater EDL and soleus muscle mass and force production in CHF rats and normal rats when compared to the corresponding vehicle treated animals. Conclusions These data demonstrate that the underlying physiological conditions associated with chronic diseases such as CHF and emphysema in addition to aging do not reduce the potential of CRF2R agonists to maintain skeletal muscle mass and force production.

  1. Identification of singles bar as a direct transcriptional target of Drosophila Myocyte enhancer factor-2 and a regulator of adult myoblast fusion.

    Science.gov (United States)

    Brunetti, Tonya M; Fremin, Brayon J; Cripps, Richard M

    2015-05-15

    In Drosophila, myoblast fusion is a conserved process in which founder cells (FCs) and fusion competent myoblasts (FCMs) fuse to form a syncytial muscle fiber. Mutants for the myogenic regulator Myocyte enhancer factor-2 (MEF2) show a failure of myoblast fusion, indicating that MEF2 regulates the fusion process. Indeed, chromatin immunoprecipitation studies show that several genes involved in myoblast fusion are bound by MEF2 during embryogenesis. Of these, the MARVEL domain gene singles bar (sing), is down-regulated in MEF2 knockdown pupae, and has five consensus MEF2 binding sites within a 9000-bp region. To determine if MEF2 is an essential and direct regulator of sing during pupal muscle development, we identified a 315-bp myoblast enhancer of sing. This enhancer was active during myoblast fusion, and mutation of two MEF2 sites significantly decreased enhancer activity. We show that lack of sing expression resulted in adult lethality and muscle loss, due to a failure of fusion during the pupal stage. Additionally, we sought to determine if sing was required in either FCs or FCMs to support fusion. Interestingly, knockdown of sing in either population did not significantly affect fusion, however, knockdown in both FCs and FCMs resulted in muscles with significantly reduced nuclei numbers, provisionally indicating that sing function is required in either cell type, but not both. Finally, we found that MEF2 regulated sing expression at the embryonic stage through the same 315-bp enhancer, indicating that sing is a MEF2 target at both critical stages of myoblast fusion. Our studies define for the first time how MEF2 directly controls fusion at multiple stages of the life cycle, and provide further evidence that the mechanisms of fusion characterized in Drosophila embryos is also used in the formation of the more complex adult muscles. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. 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.

  3. Nuclear Factor E2-Related Factor-2 Negatively Regulates NLRP3 Inflammasome Activity by Inhibiting Reactive Oxygen Species-Induced NLRP3 Priming.

    Science.gov (United States)

    Liu, Xiuting; Zhang, Xin; Ding, Yang; Zhou, Wei; Tao, Lei; Lu, Ping; Wang, Yajing; Hu, Rong

    2017-01-01

    The NLRP3 inflammasome is a multiprotein complex that protects hosts against a variety of pathogens. However, the molecular mechanisms of modulating NLRP3 inflammasome activation, especially at the priming step, are still poorly understood. This study was designed to elucidate the negative regulation of nuclear factor E2-related factor-2 (Nrf2) on the activation of NLRP3 inflammasome. We reported that Nrf2 activation inhibited NLRP3 expression, caspase-1 cleavage, and subsequent IL-1β generation. Compared with normal cells, Nrf2-deficient cells showed upregulated cleaved caspase-1, which were attributed to the increased transcription of NLRP3 caused by excess reactive oxygen species (ROS). Furthermore, priming of the NLRP3 inflammasome was sensitive to the exogenous ROS levels induced by H 2 O 2 or rotenone. Combined with adenosine triphosphate, rotenone triggered higher activity of the NLRP3 inflammasome compared with lipopolysaccharide, suggesting that ROS promoted the priming step. In addition, Nrf2-induced NQO1 was involved in the inhibition of the NLRP3 inflammasome. In an in vivo alum-induced peritonitis mouse model, Nrf2 activation suppressed typical IL-1 signaling-dependent inflammation, whereas Nrf2 -/- mice exhibited a significant increase in the recruitment of immune cell and the generation of IL-1β compared with wild-type mice. We elucidated the effects and possible mechanisms of Nrf2 activation-induced NQO1 expression on NLRP3 inflammasome inactivation and established a novel regulatory role of the Nrf2 pathway in ROS-induced NLRP3 priming. We demonstrated Nrf2 negatively regulating NLRP3 inflammasome activity by inhibiting the priming step and suggested that Nrf2 could be a potential target for some uncontrolled inflammasome activation-associated diseases. Antioxid. Redox Signal. 26, 28-43.

  4. Haploinsufficiency of NADPH Oxidase Subunit Neutrophil Cytosolic Factor 2 Is Sufficient to Accelerate Full-Blown Lupus in NZM 2328 Mice.

    Science.gov (United States)

    Jacob, Chaim O; Yu, Ning; Yoo, Dae-Goon; Perez-Zapata, Lizet J; Barbu, Emilia Alina; Kaplan, Mariana J; Purmalek, Monica; Pingel, Jeanette T; Idol, Rachel A; Dinauer, Mary C

    2017-08-01

    We have previously established that the gene for neutrophil cytosolic factor 2 (NCF-2) predisposes to lupus, and we have identified lupus patients with point mutations that are predicted to cause reduced NADPH oxidase activity. We undertook this study to investigate the relationship between reduced leukocyte NADPH oxidase activity and immune dysregulation associated with systemic lupus erythematosus (SLE). We generated NCF-2-null mice, in which NADPH oxidase activity is absent, on the nonautoimmune C57BL/6 (B6) mouse background and on the NZM 2328 mouse background, a polygenic model in which mice spontaneously develop lupus. Clinical disease, serology, and immunopathology were evaluated. NCF-2-null mice on the B6 background were susceptible to Aspergillus fumigatus pneumonia characteristic of chronic granulomatous disease, but did not develop systemic lupus disease. In contrast, NCF-2-null and even NCF-2-haploinsufficient mice on the NZM 2328 background developed accelerated full-blown lupus with significantly accelerated lupus kidney disease. This was characterized by more rapid development of hyperactive B cell and T cell immune compartments, increased expression of type I interferon-responsive genes, and generation of neutrophil extracellular traps, which were observed even in the absence of NADPH oxidase activity. Just as patients with chronic granulomatous disease who lack NADPH oxidase rarely develop SLE, NCF-2-null mice on a nonautoimmune background were susceptible to a chronic granulomatous disease-like opportunistic infection but did not develop lupus. In contrast, on a lupus-prone background, even haploinsufficiency of NCF-2 accelerated the development of full-blown lupus disease. This establishes an interaction between reduced oxidase activity and other lupus-predisposing genes, paralleling human SLE-associated variants predicted to have only reduced NADPH oxidase activity. © 2017, American College of Rheumatology.

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

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    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.

  6. Mutation of a Nuclear Respiratory Factor 2 Binding Site in the 5′ Untranslated Region of the ADSL Gene in Three Patients with Adenylosuccinate Lyase Deficiency

    Science.gov (United States)

    Marie, S.; Race, V.; Nassogne, M.-C.; Vincent, M.-F.; Van den Berghe, G.

    2002-01-01

    Adenylosuccinate lyase (ADSL; also called “adenylosuccinase”) catalyzes two steps in the synthesis of purine nucleotides: (1) the conversion of succinylaminoimidazolecarboxamide ribotide into aminoimidazolecarboxamide ribotide and (2) the conversion of adenylosuccinate into adenosine monophosphate. ADSL deficiency, a recessively inherited disorder, causes variable—but most often severe—mental retardation, frequently accompanied by epilepsy and/or autism. It is characterized by the accumulation, in body fluids, of succinylaminoimidazolecarboxamide riboside and succinyladenosine, the dephosphorylated derivatives of the two substrates of the enzyme. Analysis of the ADSL gene of three unrelated patients with ADSL deficiency, in whom one of the ADSL alleles displayed a normal coding sequence, revealed a −49T→C mutation in the 5′ untranslated region of this allele. Measurements of the amount of mRNA transcribed from the latter allele showed that it was reduced to ∼33% of that transcribed from the alleles mutated in their coding sequence. Further investigations showed that the −49T→C mutation provokes a reduction to 25% of wild-type control of promoter function, as evaluated by luciferase activity and mRNA level in transfection experiments. The mutation also affects the binding of nuclear respiratory factor 2 (NRF-2), a known activator of transcription, as assessed by gel-shift studies. Our findings indicate that a mutation of a regulatory region of the ADSL gene might be an unusually frequent cause of ADSL deficiency, and they suggest a role for NRF-2 in the gene regulation of the purine biosynthetic pathway. PMID:12016589

  7. 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.

  8. 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

  9. Nuclear factor E2-related factor 2’s activation in transgenic mice fed with high dosage of fish oil.

    Directory of Open Access Journals (Sweden)

    Elena Mariani

    2016-06-01

    Full Text Available Some fatty acids, such as CLA (conjugated linoleic acid and n-3 fatty acids modulate immune and inflammatory response in ruminants and monogastrics; their supplementation alters fatty acids profile of meat and milk, enhancing their nutritional quality. However, it is still unclear if their addition causes oxidative damage to animals. Nuclear factor E2-related factor 2 (Nrf2 plays an important role in cellular defenses against oxidative stress, indeed it produces a rapid induction of its target genes involved in antioxidant response. The aim of the project is to investigate the activation of Nrf2 in luciferase reporter mice fed different amount of n-3 PUFA in the diet (7,5% lard, 7,5% tuna oil, 20 % lard and 20%tuna oil. Forty-eight reporter mice are divided into three groups: male, intact female and ovariectomized female. Each group is split in four subgroups fed different diets. Oxidative status will be studied monitoring Nrf2’s activation with in vivo bioluminescent imaging. The inflammatory and immune response will be assessed using calprotectin and lactoferrin levels in faecal samples that are non-invasive techniques. The trial is still in progress: on the 62nd day, animals will be sacrificed after a challenge in order to measure the different effects of diets and +/- oestrogen on stress response. Finally, the post mortem analysis will be carried on extract organs. Data obtained will be analysed using statistical procedures and results will improve the knowledge about interaction between omega-3 fatty acids and animals’ oxidative status.

  10. The brain-specific neural zinc finger transcription factor 2b (NZF-2b/7ZFMyt1 suppresses cocaine self-administration in rats

    Directory of Open Access Journals (Sweden)

    Vijay Chandrasekar

    2010-04-01

    Full Text Available Brain-specific neural-zinc-finger transcription factor-2b (NZF2b/7ZFMyt1 is induced in the mesolimbic dopaminergic region after chronic cocaine exposure and lentiviral-mediated expression of NZF2b/7ZFMyt1 in the nucleus accumbens results in decreased locomotor activity (Chandrasekar and Dreyer, 2009. In this study the role of NZF2b/7ZFMyt1 in active cocaine seeking and of its interaction with histone deacetylase on the altered behavior has been observed. Localized expression of NZF2b/7ZFMyt1 in the nucleus accumbens resulted in attenuated cocaine self-administration, whereas silencing this transcription factor with lentiviruses expressing siRNAs increased the animal′s motivation to self-infuse cocaine. Low doses of sodium butyrate, a potent inhibitor of histone deacetylase, were sufficient to reverse the NZF2b/7ZFMyt1-mediated decrease in cocaine self-administration. NZF2b/7ZFMyt1 expression resulted in strong induction of transcription factors REST1 and NAC1 and of the dopamine D2 receptor, with concomitant inhibition of BDNF and its receptor TrkB. We show that NZF2b/7ZFMyt1 colocalizes with histone deacetylase-2 (HDAC2, probably overcoming the suppression of transcriptional activity caused by Lingo1. These findings show that molecular adaptations mediated by NZF2b/7ZFMyt1 expression possibly lead to decreased responsiveness to the reinforcing properties of cocaine and play a prominent role in affecting the behavioral changes induced by the drug.

  11. Dynamic Urban Growth Models

    Science.gov (United States)

    1979-12-01

    In the report the concept of 'order by fluctuation,' that has appeared recently in physico-chemical and biological systems, is applied to the description of urban growth. It is shown that fluctuations play a vital role in the evolutionary process of ...

  12. The Bacterial Growth Curve.

    Science.gov (United States)

    Paulton, Richard J. L.

    1991-01-01

    A procedure that allows students to view an entire bacterial growth curve during a two- to three-hour student laboratory period is described. Observations of the lag phase, logarithmic phase, maximum stationary phase, and phase of decline are possible. A nonpathogenic, marine bacterium is used in the investigation. (KR)

  13. Betting on Growth.

    Science.gov (United States)

    Spoor, Dana L.

    1997-01-01

    Discusses how the Clark County School District (Las Vegas) is able to successfully manage approximately 8% student enrollment growth per year along with one new building opening on an average of every 15 days. Examines managing new facility construction, making provisions for new technology, and using portable buildings to accommodate student…

  14. 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

  15. From Dormancy to Growth.

    Science.gov (United States)

    Malan, Riki

    Inhibitors of growth in education and training in South Africa include the past isolation from the rest of the world, failure to keep up with the rapid development of explosion of knowledge, compulsory dependency on bureaucracy, and disregard of the diverse needs of learners. Various initiatives have been undertaken that reflect the enormous need…

  16. Crystal growth and crystallography

    Science.gov (United States)

    Chernov, A. A.

    1998-01-01

    Selected topics that may be of interest for both crystal-structure and crystal-growth communities are overviewed. The growth of protein crystals, along with that of some other compounds, is one of the topics, and recent insights into related phenomena are considered as examples of applications of general principles. The relationship between crystal growth shape and structure is reviewed and an attempt to introduce semiquantitative characterization of binding for proteins is made. The concept of kinks for complex structures is briefly discussed. Even at sufficiently low supersaturations, the fluctuation of steps may not be sufficient to implement the Gibbs-Thomson law if the kink density is low enough. Subsurface ordering of liquids and growth of rough interfaces from melts is discussed. Crystals growing in microgravity from solution should be more perfect if they preferentially trap stress-inducing impurities, thus creating an impurity-depleted zone around themselves. Evidently, such a zone is developed only around the crystals growing in the absence of convection. Under terrestrial conditions, the self-purified depleted zone is destroyed by convection, the crystal traps more impurity and grows stressed. The stress relief causes mosaicity. In systems containing stress-inducing but poorly trapped impurities, the crystals grown in the absence of convection should be worse than those of their terrestrial counterparts.

  17. 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 GGP -supported projects referenced in the footnotes. The authors of the work cited are not responsible for the contents of GGP One-pagers. This One-pager was prepared by Edgard Rodriguez.

  18. 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 deriv...

  19. Growth and Environmental Quality

    Science.gov (United States)

    Gordon, Larry J.

    1976-01-01

    The author suggests that numbers and distribution of people should be given highest priority in dealing with environmental quality. If population problems are solved, then other environmental problems will be prevented or solved. New Mexico, contends the author, must determine the balance between growth and quality of life. (MR)

  20. Coordinate green growth

    NARCIS (Netherlands)

    Alkemade, F.; Hekkert, M.P.

    2010-01-01

    Green economic growth needs a shared sense of direction if it is to lead to a more sustainable future under climate change. Studies on green innovation and societal transformation show that uncoordinated initiatives are unlikely to be an effective way “to get the ball rolling and to ‘learn

  1. Plant growth promoting rhizobacterium

    Science.gov (United States)

    Doktycz, Mitchel John; Pelletier, Dale A.; Schadt, Christopher Warren; Tuskan, Gerald A.; Weston, David

    2015-08-11

    The present invention is directed to the Pseudomonas fluorescens strain GM30 deposited under ATCC Accession No. PTA-13340, compositions containing the GM30 strain, and methods of using the GM30 strain to enhance plant growth and/or enhance plant resistance to pathogens.

  2. 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...

  3. 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) sign...

  4. 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 GGP-supported projects referenced in the footnotes. Readers are encouraged to consult the Project output cited. The authors of the work cited are not responsible for the contents of GGP ...

  5. Supporting Inclusive Growth

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

    msandilands

    2010-10-27

    Oct 27, 2010 ... United Nations Development Programme. WRC. Women's Rights and Citizenship ... The goal of the Supporting Inclusive Growth (SIG) program is to support rigorous and policy-oriented research that ... Exploring synergies with IDRC's Environmental Economics program and other lead players outside the ...

  6. Economic growth, globalization and trade

    OpenAIRE

    Leitão, Nuno Carlos

    2012-01-01

    The purpose of this article is to investigate the relationship between economic growth, globalization and trade. The manuscript uses the assumptions of the economic growth exogenous and endogenous models. It introduces new proxies for explain the economic growth as in intra-industry trade, foreign direct investment and globalization index. The results indicate that economic growth is a dynamic process. The intra-industry has a positive impact on economic growth. This paper confirms relevant t...

  7. 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......Transforming growth factor-betas are members of a superfamily of multifunctional cytokines regulating cell growth and differentiation. Their functions in neural and endocrine cells are not well understood. We show here that transforming growth factor-betas are synthesized, stored and released...... 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...

  8. 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

  9. Myocyte Enhancer Factor 2A Regulates Hydrogen Peroxide-Induced Senescence of Vascular Smooth Muscle Cells Via microRNA-143.

    Science.gov (United States)

    Zhao, Wang; Zheng, Xi-Long; Peng, Dao-Quan; Zhao, Shui-Ping

    2015-09-01

    Myocyte enhancer factor 2A (MEF2A) is involved in vascular smooth muscle cell (VSMC) proliferation, migration, and senescence. MicroRNA-143/145 (miR-143/145), which may be regulated by MEF2A, is known to promote cellular senescence. We hypothesized that MEF2A may promote VSMC senescence via miR-143/145. VSMC senescence was induced by hydrogen peroxide (H(2)O(2)), followed by detection using a senescence-associated β-galactosidase staining kit. The MEF2A protein, mRNA, and miR-143/145 levels in VSMCs were detected using Western blot analysis and SYBR green real-time quantitative PCR, respectively. We further manipulated the expression levels of MEF2A and miR-143 through viral or transient transfection. VSMC proliferation and migration were determined by methylthiazolyldiphenyl-tetrazolium bromide and Millicell chamber, respectively. Both MEF2A and miR-143, but not miRNA-145, were up-regulated in senescent VSMCs. Overexpression of either MEF2A or miR-143 significantly enhanced VSMC senescence, but reduced proliferation and migration. MEF2A knockdown or miR-143 inhibitor suppressed cellular senescence and increased proliferation and migration. We further revealed AKT signaling as a potential miR-143 target, and an induction of miR-143 expression by MEF2A via KLF2. Additionally, overexpression of MEF2A and miR-143 resulted in synergistic effects on promotion of senescence, and MEF2A knockdown and miR-143 reduction by inhibitor had synergistic inhibitory effects. Finally, MEF2A barely promoted VSMC senescence when miR-143 was inhibited, and miR-143 overexpression antagonized the inhibitory effect of MEF2A knockdown on VSMC senescence. Our results revealed a link and interaction between MEF2A and miR-143 and suggested a potential mechanism for MEF2A to regulate H(2)O(2) -induced VSMC senescence. © 2015 Wiley Periodicals, Inc.

  10. Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex.

    Science.gov (United States)

    Okamoto, Naoki; Mizote, Keisuke; Honda, Hiroe; Saeki, Akinori; Watanabe, Yasuharu; Yamaguchi-Miyamoto, Tomomi; Fukui, Ryutaro; Tanimura, Natsuko; Motoi, Yuji; Akashi-Takamura, Sachiko; Kato, Tatsuhisa; Fujishita, Shigeto; Kimura, Takahito; Ohto, Umeharu; Shimizu, Toshiyuki; Hirokawa, Takatsugu; Miyake, Kensuke; Fukase, Koichi; Fujimoto, Yukari; Nagai, Yoshinori; Takatsu, Kiyoshi

    2017-09-15

    The Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) complex is essential for LPS recognition and induces innate immune responses against Gram-negative bacteria. As activation of TLR4/MD-2 is also critical for the induction of adaptive immune responses, TLR4/MD-2 agonists have been developed as vaccine adjuvants, but their efficacy has not yet been ascertained. Here, we demonstrate that a funiculosin (FNC) variant, FNC-RED, and FNC-RED and FNC derivatives are agonists for both murine and human TLR4/MD-2. FNC-RED induced nuclear factor-κB (NF-κB) activation via murine TLR4/MD-2, whereas FNC had no TLR4/MD-2 stimulatory activity. Biacore analysis revealed that FNC-RED binds to murine TLR4/MD-2 but not murine radioprotective 105 (RP105)/myeloid differentiation factor-1 (MD-1), another LPS sensor. FNC-RED induced CD14-independent expressions of pro-inflammatory cytokines and co-stimulatory molecules in murine macrophages and dendritic cells. In contrast, FNC-RED stimulation was reduced in CD14-dependent LPS responses, including dimerization and internalization of TLR4/MD-2 and IFN-β expression. FNC-RED-induced IL-12p40 production from murine dendritic cells was dependent on NF-κB but not MAPK pathway. In addition, fetal bovine serum augmented lipid A-induced NF-κB activation but blocked FNC-RED-mediated responses. Two synthetic phosphate group-containing FNC-RED and FNC derivatives, FNC-RED-P01 and FNC-P01, respectively, activated human TLR4/MD-2, unlike FNC-RED. Finally, computational analysis revealed that this species-specific activation by FNC-RED and FNC-RED-P01 resulted from differences in electrostatic surface potentials between murine and human TLR4/MD-2. We conclude that FNC-RED and its synthetic derivative represent a novel category of murine and human TLR4/MD-2 agonist. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. The effect of ex vivo CDDO-Me activation on nuclear factor erythroid 2-related factor 2 pathway in white blood cells from patients with septic shock.

    Science.gov (United States)

    Noel, Sanjeev; Zheng, Laura; Navas-Acien, Ana; Fuchs, Ralph J

    2014-11-01

    Nuclear factor erythroid 2-related factor 2 (NRF2) has been shown to protect against experimental sepsis in mice and lipopolysaccharide (LPS)-induced inflammation in ex vivo white blood cells from healthy subjects by upregulating cellular antioxidant genes. The objective of this study was to test the hypothesis that ex vivo methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate (CDDO-Me) activates NRF2-regulated antioxidant genes in white blood cells from patients with septic shock and protects against LPS-induced inflammation and reactive oxidative species production. Peripheral blood was collected from 18 patients with septic shock who were being treated in medical and surgical intensive care units. Real-time polymerase chain reaction was used to quantify the expression of NRF2 target genes (NQO1, HO-1, GCLM, and FTL) and IL-6 in peripheral blood mononuclear cells (PBMCs), monocytes, and neutrophils after CDDO-Me treatment alone or after subsequent LPS exposure. Superoxide anion (O2) was measured to assess the effect of CDDO-Me pretreatment on subsequent LPS exposure. Treatment with CDDO-Me increased the gene expression of NQO1 (P = 0.04) and decreased the expression of HO-1 (P = 0.03) in PBMCs from patients with septic shock. Purified monocytes exhibited significant increases in the expression of NQO1 (P = 0.01) and GCLM (P = 0.003) after CDDO-Me treatment. Levels of other NRF2 target genes (HO-1 and FTL) remained similar to those of vehicle-treated cells. Peripheral blood mononuclear cells showed a trend toward increased IL-6 gene expression after CDDO-Me treatment, whereas purified monocytes showed a trend toward decreased IL-6. There was no discernible trend in the IL-6 expression subsequent to LPS treatment in either vehicle-treated or CDDO-Me-treated PBMCs and monocytes. Treatment with CDDO-Me significantly increased O2 production in PBMCs (P = 0.04). Although CDDO-Me pretreatment significantly attenuated O2 production to subsequent LPS exposure (P = 0.03), the

  12. 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

  13. 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.

  14. 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.

  15. Impaired nuclear factor erythroid 2-related factor 2 expression increases apoptosis of airway epithelial cells in patients with chronic obstructive pulmonary disease due to cigarette smoking.

    Science.gov (United States)

    Yamada, Kazuhiro; Asai, Kazuhisa; Nagayasu, Fumihiro; Sato, Kanako; Ijiri, Naoki; Yoshii, Naoko; Imahashi, Yumiko; Watanabe, Tetsuya; Tochino, Yoshihiro; Kanazawa, Hiroshi; Hirata, Kazuto

    2016-02-09

    Cigarette smoking-induced oxidative stress is known to be a key mechanism in COPD pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a central transcription factor that regulates the antioxidant defense system. The aim of this study was to compare Nrf2 expression in COPD subjects and control subjects, and to determine the role of Nrf2 in protecting against oxidative stress-induced apoptosis. We enrolled 8 COPD subjects and 7 control subjects in this study. We performed bronchial brushing by bronchoscopy and obtained bronchial epithelial cells from the airways. Nrf2 expression in bronchial epithelial cells was evaluated by real-time PCR and Western blotting. We examined the effect of 10 or 15 % cigarette smoke extract (CSE) induced A549 cells apoptosis using a time-lapse cell imaging assay with caspase-3/7 activation detecting reagent and performed Terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling assay for confirming A549 cells apoptosis. We also examined the effects of Nrf2 knockdown and, 0.1, 0.5, and 1.0 mM N-acetyl cysteine on CSE-induced apoptosis. Statistical analyses were performed using t-test, paired t-test or an analysis of variance followed by the Tukey-Kramer method. Nrf2 mRNA expression in COPD subjects was significantly lower than that in control subjects and Nrf2 mRNA were negatively correlated with pack year. Nrf2 protein in COPD subjects was significantly lower than that in control subjects. CSE-induced A549 cells apoptosis was increased in a time-, concentration-dependent manner, and was significantly increased by Nrf2 knockdown. N-acetyl cysteine significantly ameliorated CSE-induced apoptosis. Nrf2 expression was lower in COPD patients than in control subjects. Nrf2 might have a protective role against apoptosis caused by CSE-induced oxidative stress. These results suggest an involvement of Nrf2 in COPD and administration of antioxidants to patients with COPD might be a basic therapeutic option.

  16. On Growth and Form

    Science.gov (United States)

    Maartens, Aidan

    2017-12-01

    D'Arcy Thompson was born in 1860, trained in Edinburgh and Cambridge, and held positions in Dundee and St Andrews, where he worked until his death in 1948. On Growth and Form , his classic work on the mathematical patterns and physical rules underlying biological forms, was first published in 1917. To learn more about the book's context, we met Matthew Jarron, Curator of Museum Services at the University of Dundee, in the University's D'Arcy Thompson Zoology Museum. Surrounded by specimens, many of which were collected by Thompson himself, we discussed the legacy of On Growth and Form and the life of the man behind it. © 2017. Published by The Company of Biologists Ltd.

  17. 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...

  18. 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....

  19. 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

  20. Growth Hormone and Aging

    Science.gov (United States)

    2000-08-01

    given to children or Growth hormone (GH) is a peptide containing adolescents as substitution therapy to treat is 191 aminoacids that is secreted by the...thyroid hormones and sexual hormones time on an evident beneficial action of GH together with an appropiate nutrition , therapy has been obtained in...of GH (Tresguerres 1996) reduction in muscular and bone mass together IGFI is a peptide of 70 aminoacids that shows with an increase in body fat

  1. 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

  2. Aid, Growth, and Development

    DEFF Research Database (Denmark)

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

    This paper uses a unique panel dataset on firm-level corruption. It contains quantitative information on bribe payments by a sample of formal and informal Vietnamese firms. We show that bribe incidence is highly associated with firm-level differences in (i) visibility, (ii) sunk costs, (iii......, this premium outweighs the additional bribe cost of formalization. Formalization embodies net benefits in spite of the growth hampering effects of bribes....

  3. 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.

  4. Technology diffusion and growth

    OpenAIRE

    Erzo G. J. Luttmer

    2009-01-01

    Suppose firms are subject to decreasing returns and permanent idiosyncratic productivity shocks. Suppose also firms can only stay in business by continuously paying a fixed cost. New firms can enter. Firms with a history of relatively good productivity shocks tend to survive and others are forced to exit. This paper identifies assumptions about entry that guarantee a stationary firm size distribution and lead to balanced growth. The range of technology diffusion mechanisms that can be conside...

  5. 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...

  6. Geography, depreciation, and growth

    OpenAIRE

    Hsiang, SM; Jina, AS

    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...

  7. Aid and growth regressions

    DEFF Research Database (Denmark)

    Hansen, Henrik; Tarp, Finn

    2001-01-01

    . There are, however, decreasing returns to aid, and the estimated effectiveness of aid is highly sensitive to the choice of estimator and the set of control variables. When investment and human capital are controlled for, no positive effect of aid is found. Yet, aid continues to impact on growth via...... investment. We conclude by stressing the need for more theoretical work before this kind of cross-country regressions are used for policy purposes....

  8. 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.

  9. [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.

  10. 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.

  11. Influence of root canal disinfectants on growth factor release from dentin.

    Science.gov (United States)

    Galler, Kerstin M; Buchalla, Wolfgang; Hiller, Karl-Anton; Federlin, Marianne; Eidt, Andreas; Schiefersteiner, Mona; Schmalz, Gottfried

    2015-03-01

    During dentinogenesis, growth factors become entrapped in the dentin matrix that can later be released by demineralization. Their effect on pulpal stem cell migration, proliferation, and differentiation could be beneficial for regenerative endodontic therapies. However, precondition for success, as for conventional root canal treatment, will be sufficient disinfection of the root canal system. Various irrigation solutions and intracanal dressings are available for clinical use. The aim of this study was 2-fold: to identify a demineralizing solution suitable for growth factor release directly from dentin and to evaluate whether commonly used disinfectants for endodontic treatment will compromise this effect. Dentin disks were prepared from extracted human teeth and treated with EDTA or citric acid at different concentrations or pH for different exposure periods. The amount of transforming growth factor-β1 (TGF-β1), fibroblast growth factor 2, and vascular endothelial growth factor were quantified via enzyme-linked immunosorbent assay and visualized by gold labeling. Subsequently, different irrigation solutions (5.25% sodium hypochloride, 0.12% chlorhexidine digluconate) and intracanal dressings (corticoid-antibiotic paste, calcium hydroxide: water-based and oil-based, triple antibiotic paste, chlorhexidine gel) were tested, and the release of TGF-β1 was measured after a subsequent conditioning step with EDTA. Conditioning with 10% EDTA at pH 7 rendered the highest amounts of TGF-β1 among all test solutions. Fibroblast growth factor 2 and vascular endothelial growth factor were detected after EDTA conditioning at minute concentrations. Irrigation with chlorhexidine before EDTA conditioning increased TGF-β1 release; sodium hypochloride had the opposite effect. All tested intracanal dressings interfered with TGF-β1 release except water-based calcium hydroxide. Growth factors can be released directly from dentin via EDTA conditioning. The use of disinfecting

  12. 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

  13. Cheiradone: a vascular endothelial cell growth factor receptor antagonist

    Directory of Open Access Journals (Sweden)

    Ahmed Nessar

    2008-01-01

    Full Text Available Abstract Background Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing and pathological conditions (tumour development. Vascular endothelial growth factor (VEGF, fibroblast growth factor-2 (FGF-2 and epidermal growth factor (EGF are the major angiogenic regulators. We have identified a natural product (cheiradone isolated from a Euphorbia species which inhibited in vivo and in vitro VEGF- stimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in in vitro (proliferation, wound healing, invasion in Matrigel and tube formation and in vivo (the chick chorioallantoic membrane models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC50 was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated. Results Cheiradone inhibited all stages of VEGF-induced angiogenesis with IC50 values in the range 5.20–7.50 μM but did not inhibit FGF-2 or EGF-induced angiogenesis. It also inhibited VEGF binding to VEGF receptor-1 and 2 with IC50 values of 2.9 and 0.61 μM respectively. Conclusion Cheiradone inhibited VEGF-induced angiogenesis by binding to VEGF receptors -1 and -2 and may be a useful investigative tool to study the specific contribution of VEGF to angiogenesis and may have therapeutic potential.

  14. 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

  15. 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

  16. 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

  17. 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

  18. The ZBED6-IGF2 axis has a major effect on growth of skeletal muscle and internal organs in placental mammals

    DEFF Research Database (Denmark)

    Younis, Shady; Schönke, Milena; Massart, Julie

    2018-01-01

    A single nucleotide substitution in the third intron of insulin-like growth factor 2 (IGF2) is associated with increased muscle mass and reduced subcutaneous fat in domestic pigs. This mutation disrupts the binding of the ZBED6 transcription factor and leads to a threefold up-regulation ofIGF2exp...

  19. Extraradical mycelium of arbuscular mycorrhizal fungi radiating from large plants depresses the growth of nearby seedlings in a nutrient deficient substrate

    Czech Academy of Sciences Publication Activity Database

    Janoušková, Martina; Rydlová, Jana; Püschel, David; Száková, J.; Vosátka, Miroslav

    2011-01-01

    Roč. 21, č. 7 (2011), s. 641-650 ISSN 0940-6360 R&D Projects: GA MŠk 1M0571; GA ČR GA526/09/0838 Institutional research plan: CEZ:AV0Z60050516 Keywords : mycorrhiza * nitrogen * growth response Subject RIV: EF - Botanics Impact factor: 2.630, year: 2011

  20. Crystal growth and scintillation characteristics of the Nd.sup.3+./sup. doped LiLuF.sub.4./sub. single crystals

    Czech Academy of Sciences Publication Activity Database

    Fukuda, K.; Kawaguchi, N.; Ishizu, S.; Nagami, T.; Suyama, T.; Yanagida, T.; Yokota, Y.; Nikl, Martin; Yoshikawa, A.

    2011-01-01

    Roč. 33, č. 6 (2011), s. 924-927 ISSN 0925- 3467 Grant - others:AV ČR(CZ) M100100910 Institutional research plan: CEZ:AV0Z10100521 Keywords : fluoride * single crystal * VUV Nd 3 + 5d–4f * crystal growth from the melt Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.023, year: 2011

  1. Your Baby's Growth: 3 Months

    Science.gov (United States)

    ... on a standardized growth chart (there are different charts for boys and girls). Whether your baby is large, small, or medium-sized, as long as this growth pattern stays consistent over time, chances are everything is ...

  2. 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.

  3. Cultural Globalization and Economic Growth

    Directory of Open Access Journals (Sweden)

    Nuno Carlos Leitão

    2013-03-01

    Full Text Available This article investigates the relationship between cultural globalization and economic growth for the Portuguese experience for the period 1995-2011. In this research we apply a static and dynamic panel data. The initial GDP per capita is negatively correlated with economic growth. This result is according to theoretical and empirical studies. This paper shows that international trade and cultural globalization promote the economic growth. As we expected the inflation has a negative impact on economic growth.

  4. Dumb Growth and the Biosphere

    OpenAIRE

    Cairns, John

    2011-01-01

    Dumb growth is defined as any growth that is unsustainable on a finite planet. Growth in population and consumption of finite resources are not sustainable practices and have already damaged the biospheric life support system in a way that is difficult to eradicate. In fact, all eight interactive global crises (human economy, climate change, exponential human population growth, ecological overshoot, biotic impoverishment and reduction of biodiversity, renewable resources depletion, energy al...

  5. Governance, Growth and Poverty Reduction

    OpenAIRE

    Mushtaq H. Khan

    2009-01-01

    Poverty reduction is a function of economic growth, income distribution and distribution changes. Governance can impact both growth and income distribution. The dominant market-enhancing governance paradigm seeks to enhance the efficiency of markets through ‘good governance’ reforms, ostensibly to trigger or sustain growth. ‘Pro-poor’ good governance reforms purport to enhance the scale and efficiency of service delivery to the poor. The good governance approach to enhancing growth is dispute...

  6. 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

  7. Research Award: Employment and Growth

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

    Office 2004 Test Drive User

    IDRC's Employment and Growth program supports policy-oriented research that generates new insights and options for promoting policies that facilitate inclusive growth. This is growth that enhances access of the poor to opportunities and reduces inequalities. Women's economic empowerment and youth employment are ...

  8. 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

  9. Mobilizing investors for blue growth

    NARCIS (Netherlands)

    Burg, van den Sander W.K.; Stuiver, Marian; Bolman, Bas C.; Wijnen, Roland; Selnes, Trond; Dalton, Gordon

    2017-01-01

    The European Union's Blue Growth Strategy is a long term strategy to support sustainable growth in the marine and maritime sectors, aiming to contribute to innovation and economic growth (European Commission, 2012). The EU sees the financial sector as a key partner to bring about transition to

  10. Growth Hormone: Use and Abuse

    Science.gov (United States)

    ... is huma n gr owth hormone? Human growth hormone (GH) is a substance that controls your body’s growth. ... little GH, they may have health problems. Growth hormone deficiency (too little GH) and some other health problems can be treated ...

  11. 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.

  12. Protein crystal growth - Growth kinetics for tetragonal lysozyme crystals

    Science.gov (United States)

    Pusey, M. L.; Snyder, R. S.; Naumann, R.

    1986-01-01

    Results are reported from theoretical and experimental studies of the growth rate of lysozyme as a function of diffusion in earth-gravity conditions. The investigations were carried out to form a comparison database for future studies of protein crystal growth in the microgravity environment of space. A diffusion-convection model is presented for predicting crystal growth rates in the presence of solutal concentration gradients. Techniques used to grow and monitor the growth of hen egg white lysozyme are detailed. The model calculations and experiment data are employed to discuss the effects of transport and interfacial kinetics in the growth of the crystals, which gradually diminished the free energy in the growth solution. Density gradient-driven convection, caused by presence of the gravity field, was a limiting factor in the growth rate.

  13. Monitoring urban growth

    DEFF Research Database (Denmark)

    Møller-Jensen, Lasse; Kofie, Richard; Yankson, Paul

    2007-01-01

    is occurring at a pace that has increased from 10 km2 per year for the period 1985-1991 to 25 km2 per year for the period 1991-2002. This development is subsequently discussed with focus on the unplanned and haphazard nature of the growth and the corresponding absence of adequate infrastructure and service......The extent of the urbanized areas of Accra is assessed from Landsat-TM satellite images for the year 2002 and compared to similar information for the years 1985 and 1991. A texture-based classification method is applied. The results show that the urbanization of the fringe areas of Accra...

  14. Translation, Quality and Growth

    DEFF Research Database (Denmark)

    Petersen, Margrethe

    The paper investigates the feasibility and some of the possible consequences of applying quality management to translation. It first gives an introduction to two different schools of translation and to (total) quality management. It then examines whether quality management may, in theory......, be applied to translation and goes on to present a case study which involves a firm in the translation industry and which illustrates quality management in practice. The paper shows that applying quality management to translation is feasible and that doing so may translate into sustained growth....

  15. Helicopter Reliability Growth Evaluation

    Science.gov (United States)

    1976-04-01

    a)A LO 44LA N4 r1i H-P 1)H CD 0 4 4J ~4J N4 N t40 4-) 1 P4 t41 0 0 0 u z 0 UN 0 010 ON r- UN 0 z 4-) o 0 N O LA 0 N- mA kID - Ln W r- 0 m 1 Y L rdO Ln...growth-c~urves. Reliability gkowth measuremenht define~d by RPM :is not sutbefor ’helicopter$. When.pgrh intensity is dha ~iged. to Alter the qrdwth ratd

  16. 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

    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......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...

  17. Carbon nanotube growth density control

    Science.gov (United States)

    Delzeit, Lance D. (Inventor); Schipper, John F. (Inventor)

    2010-01-01

    Method and system for combined coarse scale control and fine scale control of growth density of a carbon nanotube (CNT) array on a substrate, using a selected electrical field adjacent to a substrate surface for coarse scale density control (by one or more orders of magnitude) and a selected CNT growth temperature range for fine scale density control (by multiplicative factors of less than an order of magnitude) of CNT growth density. Two spaced apart regions on a substrate may have different CNT growth densities and/or may use different feed gases for CNT growth.

  18. 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

  19. Silencing of a lipase maturation factor 2-like gene by wheat-mediated RNAi reduces the survivability and reproductive capacity of the grain aphid, Sitobion avenae.

    Science.gov (United States)

    Xu, Lanjie; Hou, Qiling; Zhao, Yanjie; Lu, Lihua; Li, Baoyun; Ni, Zhongfu; Liang, Rongqi

    2017-07-01

    Lipase maturation factor (LMF) family proteins are required for the maturation and transport of active lipoprotein lipases. However, the specific roles of LMF2 remain unknown. In this study, a grain aphid lmf2-like gene fragment was cloned and was highly similar in sequence to a homologous gene in the pea aphid, Acyrthosiphon pisum. An RNAi vector was constructed with this fragment and used for wheat transformation. The expression of the lmf2-like gene in aphid, as well as the growth and reproduction of the aphids, was analyzed after feeding on the transgenic wheat. There were no significant differences in the expression of the lmf2-like gene over development. The expression of the lmf2-like gene was significantly reduced by 27.6% on the fifth day, and 57.6% on the 10th day after feeding. The total number of aphids produced on the transgenic plants was less than the number produced on control plants, and the difference became significant or after 2 weeks. The molting numbers were also reduced in the aphids reared on the transgenic plants. Our findings indicate that lmf2-like genes may have potential as a target gene for the control of grain aphids and show that feeding aphids with wheat expressing lmf2-like RNAi resulted in significant reductions in survival and reproduction. © 2017 Wiley Periodicals, Inc.

  20. Sex dimorphism in growth.

    Science.gov (United States)

    Gasser, T; Sheehy, A; Molinari, L; Largo, R H

    2000-01-01

    While there is agreement that sex differences in height are small up to the onset of the pubertal spurt in girls, there has been some debate about the question of which, and to what extent, various growth phases contribute to the average adult sex difference of about 13 cm. There has been no consistent agreement between authors as to what extent this difference is due to the late onset of the pubertal spurt (PS) for boys and to what extent it is due to their more intense PS. In this paper, we investigate this question for the variables height, sitting and leg height, arm length, bihumeral and biiliac width. Biiliac width is a special case since both sexes have roughly the same adult size, but girls still have a shorter growing period. The gains for boys, when compared to girls, show a very different pattern across variables: for the legs, the additional growth due to the later spurt is responsible for most of the adult sex difference (64%). On the other hand, for bihumeral width and sitting height, the more intense PS contributes almost 50% to the adult sex difference. An analysis across variables indicates that increments from 1.5 to 6 years largely compensate for deviations in infant morphology from adult morphology.

  1. 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.

  2. 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...

  3. 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

    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...... 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...... 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...

  4. How nations govern growth.

    Science.gov (United States)

    1984-03-02

    Officials in China admit that the killing or abondoning of baby girls stems from a government policy limiting couples to 1 child combined with an ancient preference for sons. At the same time leaders maintain that population growth is an national emergency and must be checked. And the 1-child policy remains. To enforce the policy, sterilization is compulsory for 1 parent in a 2-child family. Other reports claim that pregnant women face severe government and social pressure to have an abortion. Comunist governments are not alone in taking a forceful role in population control. In 1975 thousands of people in India were pressured to undergo "voluntary" sterilization. In many places, police and tax collectors, money in hand, "convinced" people to get sterilized. Critics recognize a horribla abuse of government powers in these population control efforts. Recognizing that the populations of the poorest nations will double in 20-30 years, 59 countries responded with some kind of population policy by 1980. These countries are spending an average of US$4.60 on population programs for each US$1 they received in UN aid. In many places, the effort is beginning to show results. A 1982 survey found that 35 countries -- with 88% of the 3rd world population -- had cut the growth of their birthrates by 5-34%. Generally, governments have chosen any of 3 ways to attack the problem: cash payments for sterilization or contraceptive use; penalties for big families; and "delayed incentives." At least 20 governments use money to convince people to have fewer babies. Some programs pay for sterilization,other for contraceptive use. All payments are low. Some governments personalize those who exceed a recommended family size. Other nations have adopted variations of the idea. Some governments, instead of paying up front cash, offer pension plans or bank accounts to limit family size. Almost all population experts believe that the mot successful programs are those which are not imposed from

  5. 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.

  6. 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

  7. 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

  8. Nanowire Growth for Photovoltaics

    DEFF Research Database (Denmark)

    Holm, Jeppe Vilstrup

    consisting of a single, vertical, gallium arsenide(GaAs) nanowire grown on silicon with a radial p-i-n-junction. The average concentration was ~8, and the peak concentration was ~12. By increasing the number of junctions in solar cells, they can extract more energy per absorbed photon. In ideal multi...... of the nanowires, some of which were removed from their growth substrate and turned into single nanowire solar cells (SNWSC). The best device showed a conversion efficiency of 6.8% under 1.5AMG 1-sun illumination. In order to improve the efficiency a surface passivating shell consisting of highly doped, wide......Solar cells commercial success is based on an efficiency/cost calculation. Nanowire solar cells is one of the foremost candidates to implement third generation photo voltaics, which are both very efficient and cheap to produce. This thesis is about our progress towards commercial nanowire solar...

  9. 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.

  10. 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

  11. 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).

  12. Brown growth, green growth, and the efficiency of urbanization

    OpenAIRE

    Quaas, Martin F.; Smulders, Sjak

    2012-01-01

    We analyze the efficiency of urbanization patterns in a stylized dynamic model of urban growth with three sectors of production. Pollution, as a force that discourages agglomeration, is caused by domestic production. We show that cities are too large and too few in number in uncoordinated equilibrium if economic growth implies increasing pollution (‘brown growth’). If, however, production becomes cleaner over time (‘green growth’) the equilibrium urbanization path reaches the efficien...

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Farnesol inhibits translation to limit growth and filamentation in C. albicans and S. cerevisiae

    Directory of Open Access Journals (Sweden)

    Nkechi E. Egbe

    2017-09-01

    Full Text Available Candida albicans is a polymorphic yeast where the capacity to switch between yeast and filamentous growth is critical for pathogenicity. Farnesol is a quorum-sensing sesquiterpene alcohol that, via regulation of specific signalling and transcription components, inhibits filamentous growth in C. albicans. Here we show that farnesol also inhibits translation at the initiation step in both C. albicans and S. cerevisiae. In contrast to fusel alcohols, that target the eukaryotic initiation factor 2B (eIF2B, farnesol affects the interaction of the mRNA with the small ribosomal subunit leading to reduced levels of the 48S preinitiation ribosomal complex in S. cerevisiae. Therefore, farnesol targets a different step in the translation pathway than fusel alcohols to elicit a completely opposite physiological outcome by negating filamentous growth.

  18. 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....

  19. Growth and photosynthesis of lettuce

    OpenAIRE

    Holsteijn, van, H.M.C.

    1981-01-01

    Butterhead lettuce is an important glass-house crop in the poor light period in The Netherlands. Fundamental data about the influence of temperature, light and CO 2 on growth and photosynthesis are important e.g. to facilitate selection criteria for new cultivars. In this study on lettuce emphasis has been given to light interception in the poor light period, the relationship of growth rate and relative growth rate with time, dry weight and soil cover, and to ...

  20. 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 example, the influence of prevailing ethical norms on the aggregate elasticity of substitution and, therefore, total factor productivity and growth....