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Sample records for chemotactic factors role

  1. Growth factors and chemotactic factors from parasitic helminths: molecular evidence for roles in host-parasite interactions versus parasite development.

    Science.gov (United States)

    Freitas, Tori C; Pearce, Edward J

    2010-06-01

    For decades molecular helminthologists have been interested in identifying proteins expressed by the parasite that have roles in modulating the host immune response. In some cases, the aim was targeting parasite-derived orthologues of mammalian cytokines and growth factors known to have functions in immune modulation. In others, novel proteins without homology to mammalian cytokines were isolated by investigating effects of purified worm extracts on various immunological processes. Often, the role parasite-derived growth factors play in worm development was ignored. Here, we review growth factors and chemotactic factors expressed by parasitic helminths and discuss their recognised and potential roles in immunomodulation and/or parasite development. (c) 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  2. Chemotactic and proangiogenic role of calcium sensing receptor is linked to secretion of multiple cytokines and growth factors in breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Hernández-Bedolla, Marco Antonio; Carretero-Ortega, Jorge; Valadez-Sánchez, Margarita; Vázquez-Prado, José; Reyes-Cruz, Guadalupe

    2015-01-01

    Breast cancer metastasis to the bone, potentially facilitated by chemotactic and angiogenic cytokines, contributes to a dramatic osteolytic effect associated with this invasive behavior. Based on the intrinsic ability of calcium sensing receptor (CaSR) to control hormonal secretion and considering its expression in the breast, we hypothesized that CaSR plays a chemotactic and proangiogenic role in highly invasive MDA-MB-231 breast cancer cells by promoting secretion of multiple cytokines. In this study, we show that MDA-MB-231 cells stimulated with R-568 calcimimetic and extracellular calcium secreted multiple cytokines and growth factors that induced endothelial cell migration and in vitro angiogenesis. These effects were dependent on the activity of CaSR as demonstrated by the inhibitory effect of either anti-CaSR blocking monoclonal antibodies or calcilytic NPS-2143. Moreover, CaSR knockdown prevented the proangiogenic effect of CaSR agonists. Importantly, CaSR promoted secretion of pleiotropic molecules like GM-CSF, EGF, MDC/CCL22, FGF-4 and IGFBP2, all known to be chemotactic mediators with putative angiogenic factor properties. In contrast, constitutive secretion of IL-6 and β-NGF was attenuated by CaSR. In the case of normal mammary cells, secretion of IL-6 was stimulated by CaSR, whereas a constitutive secretion of RANTES, Angiogenin and Oncostatin M was attenuated by this receptor. Taken together, our results indicate that an altered secretion of chemotactic and proangiogenic cytokines in breast cancer cells is modulated by CaSR, which can be considered a potential target in the therapy of metastatic breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Eosinophil chemotactic factors from cysticercoids of Hymenolepis nana.

    Science.gov (United States)

    Niwa, A; Asano, K; Ito, A

    1998-09-01

    A comparative study of eosinophil chemotactic factors was carried out using cysticercoids and oncospheres of Hymenolepis nana. Cysticercoids showed twice the chemotactic activity for eosinophils than the oncospheres. Eosinophilia induced by oncospheres and cysticercoids observed in secondary and primary infections, respectively, were discussed from the view point of the immunobiology of this parasite.

  4. Biological characterization of purified macrophage-derived neutrophil chemotactic factor

    Directory of Open Access Journals (Sweden)

    M. Dias-Baruffi

    1995-01-01

    Full Text Available We have recently described the purification of a 54 kDa acidic protein, identified as macrophage-derived neutrophil chemotactic factor (MNCF. This protein causes in vitro chemotaxis as well as in vivo neutrophil migration even in animals treated with dexamethasone. This in vivo chemotactic activity of MNCF in animals pretreated with dexamethasone is an uncommon characteristic which discriminates MNCF from known chemotactic cytokines. MNCF is released in the supernatant by macrophage monolayers stimulated with lipopolysaccharide (LPS. In the present study, we describe some biological characteristics of homogenous purified MNCF. When assayed in vitro, MNCF gave a bell-shaped dose–response curve. This in vitro activity was shown to be caused by haptotaxis. Unlike N-formyl-methionylleucyl- phenylalanine (FMLP or interleukin 8 (IL-8, the chemotactic activity of MNCF in vivo and in vitro, was inhibited by preincubation with D-galactose but not with D-mannose. In contrast with IL-8, MNCF did not bind to heparin and antiserum against IL-8 was ineffective in inhibiting its chemotactic activity. These data indicate that MNCF induces neutrophil migration through a carbohydrate recognition property, but by a mechanism different from that of the known chemokines. It is suggested that MNCF may be an important mediator in the recruitment of neutrophils via the formation of a substrate bound chemotactic gradient (haptotaxis in the inflamed tissues.

  5. Localization of monocyte chemotactic and activating factor (MCAF/MCP-1) in psoriasis

    DEFF Research Database (Denmark)

    Deleuran, M; Buhl, L; Ellingsen, T

    1996-01-01

    The monocyte chemotactic protein-1 (MCAF) also termed MCP-1, a strong chemotactic factor towards monocytes, is produced by several cell types present in the skin. The in situ presence of MCAF/MCP-1 protein in the skin has, however, not yet been established. Using immunohistochemical techniques we...

  6. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J.I.

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  7. Gaucher disease: chemotactic factors and immunological cell invasion in a mouse model.

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    Pandey, Manoj Kumar; Jabre, Nicholas A; Xu, You-Hai; Zhang, Wujuan; Setchell, Kenneth D R; Grabowski, Gregory A

    2014-02-01

    Gaucher disease results from mutations in GBA1 that cause functional disruption of the encoded lysosomal enzyme, acid β-glucosidase. The consequent excess accumulation of glucosylceramide and glucosylsphingosine in lysosomes is central to the disease pathogenesis with classical involvement of macrophage (Mфs) lineage cells of visceral organs, bone, or brain. Several studies have implicated the increased secretion of chemokines and infiltration of a variety of immunological cells into tissues of Gaucher disease patients. Trafficking of immunological cells to the sites of inflammation requires the presence of chemokines. Although increases of different immunological cells and several chemokines are present in Gaucher disease, the specific chemoattractants that cause the increased influx of immunological cells are not fully defined. Here, increased levels of I-309, MCP-5, CXCL-2, CXCL-9, CXCL-10, CXCL-11, CXCL-13, and their corresponding leukocytes, i.e., MOs (monocytes), Mфs, dendritic cells (DCs), polymorphonuclear neutrophils (PMNs), and T, and B cells were identified in the circulation of mice with Gba1 mutations (D409V/null). Sera from D409V/null mice contained chemoattractants for a variety of immunological cells as shown by ex vivo chemotaxis studies and by flow cytometry. Enhanced chemotaxis towards 9V/null sera was found for 9V/null lung-, spleen-, liver-, and bone marrow-derived Mфs (CD11b(+) F480(+)), PMNs (Gr1(high) CD11b(+)), DCs (CD11c(+) CD11b(+)), T lymphocytes (CD3(+) TCRB(+)), and B lymphocytes (B220(+) CD19(+)). These data support these chemotactic factors as causative to increased tissue infiltration of leukocytes in Gaucher disease. Published by Elsevier Inc.

  8. Migration of Chemotactic Bacteria in Soft Agar: Role of Gel Concentration

    Science.gov (United States)

    Croze, Ottavio A.; Ferguson, Gail P.; Cates, Michael E.; Poon, Wilson C.K.

    2011-01-01

    We study the migration of chemotactic wild-type Escherichia coli populations in semisolid (soft) agar in the concentration range C = 0.15–0.5% (w/v). For C≲0.35%, expanding bacterial colonies display characteristic chemotactic rings. At C = 0.35%, however, bacteria migrate as broad circular bands rather than sharp rings. These are growth/diffusion waves arising because of suppression of chemotaxis by the agar and have not been previously reported experimentally to our knowledge. For C = 0.4–0.5%, expanding colonies do not span the depth of the agar and develop pronounced front instabilities. The migration front speed is weakly dependent on agar concentration at C agar. The model makes it possible to fit the observed front speed decay in the range C = 0.15–0.35%, and its solutions qualitatively reproduce the observed transition from chemotactic to growth/diffusion bands. We discuss the implications of our results for the study of bacteria in porous media and for the design of improved bacteriological chemotaxis assays. PMID:21806920

  9. Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

    NARCIS (Netherlands)

    Verhoeckx, K.C.M.; Doornbos, R.P.; Witkamp, R.F.; Greef, de J.; Rodenburg, R.J.T.

    2006-01-01

    Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (ß2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents

  10. Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage-derived chemotactic factor with preferential activity for polymorphonuclear leukocytes.

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    Kazmierowski, J A; Gallin, J I; Reynolds, H Y

    1977-02-01

    Approximately 4 h after an initial bronchoalveolar lavage (BAL) of a primate's lung, an appreciable number of polymorphonuclear leukocytes (PMNs) were noted to accumulate in respiratory fluids when lavage was repeated. Whereas, alveolar macrophages (90%) and lymphocytes (7%) were the principal respiratory cells recovered initially from lavage fluid, later samples contained 45-90% PMNs To explain the observed ingress of PMNs into lung fluids, concentrated BAL fluid was tested for chemoattractant activity. Such fluid obtained 4 and 24 h after an initial lavage contained material that produced directed migration (chemotaxis) for PMNs and mononuclear cells isolated from peripheral blood of normal donors. Gel filtration chromatography of BAL disclosed two peaks of chemotactic activity in the effluent fractions. Material from the column with an estimated molecular weight of 15,000 daltons was chemotactic for both PMNs and mononuclear cells. Because it was susceptible to inactivation with antiserum against the fifth component of complement, resistant to heating, and unaffected by antiserum against C3, this factor was considered analogous to the cleavage product of the fifth component of complement. C5a. In addition chemotactic activity for PMNs only was contained in an effluent peak having a molecular weight of about 5,000 daltons. This material was heat labile but unaffected by antisera to complement components. To locate the possible source of these factors in respiratory fluid, in vitro cultures of alveolar macrophages were established. These cells, whether stimulated by phagocytosis of opsonized bacteria or merely by attachment to a glass surface, produced chemotactic material which had physical characteristics similar to the small molecular weight material in BAL. Moreover, it induced preferential chemotaxis for PMNs. Thus, in primate lungs, at least two chemotactic substances may generate an inflammatory response; one which is a fragment of the complement component

  11. Sequential and timely transfection of hepatocyte growth factor and monocyte chemotactic protein-1 ameliorates hyperkinetic pulmonary artery hypertension in rabbits.

    Science.gov (United States)

    Zhang, Yiqian; Zhang, Fang; Wang, Xiaoyu; Xie, Yue; Du, Junjie; Lu, Peng; Wang, Wei

    2015-09-01

    To investigate the effect of sequential and timely transfection of the recombinant human hepatocyte growth factor (hHGF) gene and human monocyte chemotactic protein-1 (hMCP-1) gene on hyperkinetic pulmonary artery hypertension in a rabbit model. The rabbits with pulmonary artery hypertension were randomly separated into 5 groups: control; hHGF; hMCP-1; hHGF/hMCP-1 simultaneous transfection; and hHGF/hMCP-1 sequential, timely transfection. Two weeks after the transfection, real-time polymerase chain reaction and immunohistochemistry examination were used to detect the expression of hHGF and hMCP-1. Four weeks later, the hemodynamic parameters were measured, and immunohistochemical and immunofluorescence staining were performed, to investigate microvascular density and arterialization. The final adenovirus coding with enhanced green fluorescent protein-hMCP-1 virus was 3 × 10(10) plaque-forming units/mL, and the purity of adenovirus coding with hHGF was 1.31. Three days after the transfection, enhance green fluorescent protein hMCP-1 green fluorescence was detected in the lung tissues and increased to its peak point in 1 week. Two weeks later, hHGF and hMCP-1 were expressed in all transfection groups. By the end of 4 weeks, the mean pulmonary artery pressure in the hHGF/hMCP-1 sequential and timely transfection group was lower than that in the other groups. Confirmed by immunohistochemical and immunofluorescence staining, the microvascular and arteriolar density in the lung tissues of the sequential and timely hHGF/hMCP-1 transfection group were higher than that in the other groups. Expression of hHGF and hMCP-1 were found in rabbit lung after gene transfection via an airway approach. By increasing the pulmonary microvascular density and promoting arterializations, sequential and timely hHGF/hMCP-1 transfection ameliorates the shunt flow-induced pulmonary artery hypertension. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier

  12. Polarised Clathrin-Mediated Endocytosis of EGFR During Chemotactic Invasion

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    Mutch, Laura Jane; Howden, Jake Davey; Jenner, Emma Poppy Louise; Poulter, Natalie Sarah; Rappoport, Joshua Zachary

    2014-01-01

    Directed cell migration is critical for numerous physiological processes including development and wound healing. However chemotaxis is also exploited during cancer progression. Recent reports have suggested links between vesicle trafficking pathways and directed cell migration. Very little is known about the potential roles of endocytosis pathways during metastasis. Therefore we performed a series of studies employing a previously characterised model for chemotactic invasion of cancer cells to assess specific hypotheses potentially linking endocytosis to directed cell migration. Our results demonstrate that clathrin-mediated endocytosis is indispensable for epidermal growth factor (EGF) directed chemotactic invasion of MDA-MB-231 cells. Conversely, caveolar endocytosis is not required in this mode of migration. We further found that chemoattractant receptor (EGFR) trafficking occurs by clathrin-mediated endocytosis and is polarised towards the front of migrating cells. However, we found no role for clathrin-mediated endocytosis in focal adhesion disassembly in this migration model. Thus, this study has characterised the role of endocytosis during chemotactic invasion and has identified functions mechanistically linking clathrin-mediated endocytosis to directed cell motility. PMID:24921075

  13. VEGF-A promotes IL-17A-producing γδ T cell accumulation in mouse skin and serves as a chemotactic factor for plasmacytoid dendritic cells.

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    Suzuki, Takahiro; Hirakawa, Satoshi; Shimauchi, Takatoshi; Ito, Taisuke; Sakabe, Jun-ichi; Detmar, Michael; Tokura, Yoshiki

    2014-05-01

    IL-17-producing CD4(+) T (Th17) cells and their cytokines, IL-17A and IL-22, are deeply involved in the pathogenesis of psoriasis by stimulating epidermal keratinocytes to proliferate and to produce cytokines/chemokines and vascular endothelial growth factor (VEGF)-A. Plasmacytoid dendritic cells (pDCs), infiltrating in psoriatic lesions, are known to exacerbate the Th17-mediated pathogenesis of psoriasis. To address the initiative role of VEGF-A in the development of psoriasis and the pDC accumulation. Numerical changes and VEGF receptor 1 (VEGFR1) and VEGFR2 expressions were investigated in skin-infiltrating T cells and pDCs of K14-VEGF-A transgenic (Tg) and wild type (WT) mice. The chemotactic properties of VEGF-A for purified splenic pDCs were also evaluated by real-time chemotaxis assay. By flow cytometry and immunohistochemistry, we observed that the number of dermal IL-17A(+) γδ T cells, but not CD4(+) T cells, was increased in VEGF-A Tg mice, suggesting that the main source of IL-17A was γδ T cells. Moreover, we identified pDCs as 440c(+) cells by immunohistochemistry and as PDCA-1(+)B220(+) cells by flow cytometry, and found that pDCs infiltrated at a higher frequency in VEGF-A Tg than WT mice. pDCs, but not γδ T cells, isolated from the skin expressed VEGFR1 and VEGFR2. Freshly isolated splenic pDCs expressed both receptors after 48-h cultivation. pDCs did not produce cytokines in response to VEGF-A, however, they had a strong velocity of chemotaxis toward VEGF-A at a comparable level to chemerin. These findings suggest that VEGF-A functions as not only a downstream enhancer but also an upstream initiator by chemoattracting pDCs in psoriatic lesions. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. Development of chemotactic smart scaffold for use in tissue regeneration.

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    Hokugo, Akishige; Li, Andrew; Segovia, Luis A; Yalom, Anisa; Rezzadeh, Kameron; Zhou, Situo; Zhang, Zheyu; Zuk, Patricia A; Jarrahy, Reza

    2015-05-01

    Regenerative medicine aims to obviate the need for autologous grafting through the use of bioengineered constructs that combine stem cells, growth factors, and biocompatible vehicles. Human mesenchymal stem cells and vascular endothelial growth factor (VEGF) have both shown promise for use in this context, the former because of their pluripotent capacity and the latter because of its chemotactic activity. The authors harnessed the regenerative potential of human mesenchymal stem cells and VEGF to develop a chemotactic scaffold for use in tissue engineering. Human mesenchymal stem cells were transduced with human VEGF via lentivirus particles to secrete VEGF. The chemotactic activity of the VEGF-transduced stem cells was evaluated via a trans-well assay. Migration through semipermeable membranes was significantly greater in chambers filled with medium conditioned by VEGF-transduced cells. VEGF-transduced cells were then seeded on apatite-coated poly(lactic-co-glycolic acid) scaffolds, thereby creating the Smart Scaffold. To determine in vivo angiogenesis, the Smart Scaffolds were implanted into subcutaneous pockets in the backs of nude mice. Significantly larger numbers of capillaries were observed in the Smart Scaffold compared with control implants on immunohistologic studies. For the chemotactic in vivo study, human mesenchymal stem cells tagged with a fluorescent dye (1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide) were injected intravenously via tail vein after the subcutaneous implantation of the Smart Scaffolds. In vivo fluorescent imaging revealed that fluorescent dye-tagged human mesenchymal stem cells successfully accumulated within the Smart Scaffolds. These observations suggest that VEGF may play a vital role in the design of clinically relevant tissue regeneration graft substitutes through its angiogenic effects and ability to chemoattract mesenchymal stem cells.

  15. Directed migration of human neural progenitor cells to interleukin-1β is promoted by chemokines stromal cell-derived factor-1 and monocyte chemotactic factor-1 in mouse brains

    Directory of Open Access Journals (Sweden)

    Wu Yumei

    2012-07-01

    Full Text Available Abstract Background Neurogenesis, including the proliferation, migration and differentiation of neural progenitor cells (NPCs, is impaired in HIV-1 associated dementia (HAD. We previously demonstrated HIV-1-infected macrophages (HIV-MDM regulate stromal cell-derived factor 1 (SDF-1 production in astrocytes through Interleukin-1β (IL-1β. Chemokines are known to induce NPC migration; however, it remains unclear how chemokines produced in inflammation regulate NPC migration. Methods The secretion of SDF-1 and Monocyte chemotactic preotein-1 (MCP-1 in astrocytes upon IL-1β stimulation was measured by ELISA assay. Human NPCs were injected parallel along with IL-1β, SDF-1 or MCP-1 intracranially into basal ganglion 1 mm apart in SCID mice, and immunofluorescent staining was used to study the survival and migration of injected human NPCs. Results SDF-1 and MCP-1 are secreted by astrocytes upon IL-1β stimulation in a time-dependent manner. Injected human NPCs survived in SCID mice and migrated towards sites of IL-1β, SDF-1 and MCP-1 injection. Conclusions In conclusion, chemokines SDF-1 or MCP-1 secreted by astrocytes in the presence of IL-1β injection are attractive to NPCs injected into SCID mouse brains, suggesting that SDF-1 and MCP-1 play important roles in NPC migration during neuroinflammation.

  16. Activation of TAK1 by Chemotactic and Growth Factors, and Its Impact on Human Neutrophil Signaling and Functional Responses.

    Science.gov (United States)

    Sylvain-Prévost, Stéphanie; Ear, Thornin; Simard, François A; Fortin, Carl F; Dubois, Claire M; Flamand, Nicolas; McDonald, Patrick P

    2015-12-01

    The MAP3 kinase, TAK1, is known to act upstream of IKK and MAPK cascades in several cell types, and is typically activated in response to cytokines (e.g., TNF, IL-1) and TLR ligands. In this article, we report that in human neutrophils, TAK1 can also be activated by different classes of inflammatory stimuli, namely, chemoattractants and growth factors. After stimulation with such agents, TAK1 becomes rapidly and transiently activated. Blocking TAK1 kinase activity with a highly selective inhibitor (5z-7-oxozeaenol) attenuated the inducible phosphorylation of ERK occurring in response to these stimuli but had little or no effect on that of p38 MAPK or PI3K. Inhibition of TAK1 also impaired MEKK3 (but not MEKK1) activation by fMLF. Moreover, both TAK1 and the MEK/ERK module were found to influence inflammatory cytokine expression and release in fMLF- and GM-CSF-activated neutrophils, whereas the PI3K pathway influenced this response independently of TAK1. Besides cytokine production, other responses were found to be under TAK1 control in neutrophils stimulated with chemoattractants and/or GM-CSF, namely, delayed apoptosis and leukotriene biosynthesis. Our data further emphasize the central role of TAK1 in controlling signaling cascades and functional responses in primary neutrophils, making it a promising target for therapeutic intervention in view of the foremost role of neutrophils in several chronic inflammatory conditions. Copyright © 2015 by The American Association of Immunologists, Inc.

  17. Identification of Monocyte Chemotactic Activity Produced by Malignant Cells

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    Graves, D. T.; Jiang, Y. L.; Williamson, M. J.; Valente, A. J.

    1989-09-01

    Human malignant cells secrete low molecular size proteins that attract peripheral blood monocytes and may be responsible for the accumulation of tumor-associated macrophages observed in vivo. Similar chemotactic proteins are secreted by cultured vascular smooth muscle cells. The predominant monocyte chemoattractants produced by tumor cells of differing origin were demonstrated to be related to smooth muscle cell-derived chemotactic factor. Thus, a single class of chemotactic proteins is produced by different cell types, which suggests a common mechanism for the recruitment of monocytes and macrophages. These results are significant in view of the potential of macrophages to affect tumor growth.

  18. Monocyte chemotactic protein-1, RANTES and macrophage migration inhibitory factor levels in gingival crevicular fluid of metabolic syndrome patients with gingivitis.

    Science.gov (United States)

    Gürkan, Ali; Eren, Gülnihal; Çetinkalp, Şevki; Akçay, Yasemin Delen; Emingil, Gülnur; Atilla, Gül

    2016-09-01

    The aim of the present study was to determine gingival crevicular fluid (GCF) levels of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted protein (RANTES) and macrophage migration inhibitory factor (MIF) in metabolic syndrome patients with gingivitis. Twenty metabolic syndrome patients with gingivitis (MSG), 20 MetS patients with clinically healthy periodontium (MSH), 20 systemically healthy subjects with gingivitis and 20 subjects who were both systemically and periodontally healthy were included. Periodontal and systemical parameters were recorded. GCF MCP-1, RANTES and MIF levels were assayed by enzyme-linked immunosorbent assay method. MSG and MSH groups had elevated blood pressure, triglyceride, waist circumference and fasting glucose values in comparison to gingivitis and healthy groups (Pgingivitis groups when compared to those of the MSH and healthy groups (Pgingivitis group had higher MCP-1, RANTES and MIF levels compared to the healthy group (P=0.011, P=0.0001, P=0.011 respectively). The RANTES level of MSG group was significantly higher than those of the gingivitis group (P=0.01), but MCP-1 and MIF levels were similar in the MSG and gingivitis groups (P>0.05). Elevated levels of GCF RANTES in MetS patients with gingivitis might associate with the presence of increased gingival inflammation by MetS. Low-grade systemic inflammation associated with MetS and adipose tissue-derived RANTES might lead to altered GCF RANTES levels in the presence of gingival inflammation. Copyright © 2016. Published by Elsevier Ltd.

  19. Differential roles of IL-16 and CD28/B7 costimulation in the generation of T-lymphocyte chemotactic activity in the bronchial mucosa of mild and moderate asthmatic individuals.

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    Dent, Gordon; Hosking, Lisa A; Lordan, James L; Steel, Mark D; Cruikshank, William W; Center, David M; Ellis, Jonathan H; Holgate, Stephen T; Davies, Donna E; Djukanović, Ratko

    2002-12-01

    IL-16 is an important T-cell chemotactic cytokine in asthmatic airways; its release from allergen-stimulated bronchial mucosa in mild asthma has been shown to be dependent on CD28/B7 costimulation. We have extended our previous studies to investigate the role of IL-16 and CD28/B7 costimulation in T-lymphocyte chemotactic activity (TLCA) released from the bronchial mucosa in more severe asthma. TLCA was determined in the supernatants of induced sputum and allergen-stimulated bronchial mucosal explants from healthy volunteers and volunteers with mild and moderately severe asthma by means of a Boyden chamber technique. The contribution of IL-16 to the activity was evaluated through use of a neutralizing monoclonal antibody; the contribution of CD28/B7 costimulation to allergen-induced release of TLCA was determined through use of CTLA4-Ig fusion protein and neutralizing monoclonal antibodies to CD80 (B7.1) and CD86 (B7.2). Induced sputum and unstimulated explants from asthmatic subjects generated significant spontaneous TLCA (P TLCA, but only in mild asthma could sputum and allergen-stimulated explant TLCA be inhibited by anti-IL-16 (median inhibition, 39% and 59%; P TLCA in mild asthmatic explants by 94% (P TLCA release from moderate asthmatic explants was unaffected by CTLA4-Ig. These results show that TLCA release in moderate asthmatic airways, in contrast to mild asthmatic airways, is not dependent on CD28/B7 costimulation and does not involve IL-16.

  20. The role of vascular endothelial growth factor in inflammatory processes

    Directory of Open Access Journals (Sweden)

    Ewa Koczy-Baron

    2014-01-01

    Full Text Available The vascular endothelial growth factor (VEGF is produced by different types of cells and has a major role in both, physiological and pathological angiogenesis. On the one hand VEGF is a strong mitotic and chemotactic factor for the endothelial cells, stimulating thus formation of new vessels, while on the other, it enhances the vascular endothelium permeability of the existing blood vessels which contributes to development and persistence of the inflammatory conditions. In the latter its activity is by 50 000 times higher than that of histamine. VEGF facilitates formation of oedema and leukocyte migration from the circulation to the site of inflammation. VEGF is also important in remodeling of the extracellular matrix. Moreover, it has an important significance in regulation of the immunological response, therefore plays a role in autoaggressive phenomena as well as immediate- and delayed-type hypersensitivity. Its role in the pathogenesis of immunological and inflammatory diseases, including allergy, asthma and different skin disorders has been indicated.

  1. Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration.

    Science.gov (United States)

    Ye, Baixin; Xiong, Xiaoxing; Deng, Xu; Gu, Lijuan; Wang, Qiongyu; Zeng, Zhi; Gao, Xiang; Gao, Qingping; Wang, Yueying

    2017-12-01

    Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.

  2. Critical involvement of the chemotactic axis CXCR4/stromal cell-derived factor-1 alpha in the inflammatory component of allergic airway disease.

    Science.gov (United States)

    Gonzalo, J A; Lloyd, C M; Peled, A; Delaney, T; Coyle, A J; Gutierrez-Ramos, J C

    2000-07-01

    Stromal cell-derived factor-1alpha/beta (SDF-1alpha/beta) is phylogenetically a primitive chemokine widely expressed in a variety of tissues and cell types. This expression is detectable in the absence of stimuli provided by bacterial or viral infections and allergic or autoimmune disorders. Based on these and other findings, SDF-1alpha has not been considered an inflammatory chemokine, but, rather, has been believed to be involved in certain homeostatic processes, such as leukocyte recirculation. SDF-1alpha is a potent chemoattractant for lymphocytes and monocytes that mediates its activity via the chemokine receptor CXCR4. Study of the role of SDF-1alpha/CXCR4 in vivo during inflammation has been limited by the fact that transgenic mice that have been made deficient in either molecule die early in life due to developmental defects. The present study was aimed at evaluating the functional relevance of the SDF-1alpha/CXCR4 axis during an inflammatory process. Neutralizing Abs to CXCR4 reduced lung eosinophilia (bronchoalveolar lavage fluid and interstitium) by half, indicating that CXCR4-mediated signals contribute to lung inflammation in a mouse model of allergic airway disease (AAD). This reduction in inflammation was accompanied by a significant decrease in airway hyper-responsiveness. SDF-1alpha neutralization resulted in similar reduction in both lung allergic inflammation and airway hyper-responsiveness. Retroviral delivery of a CXCR4 cDNA to leukocytes resulted in greater inflammation when transduced mice were subjected to a mouse model of AAD. These results highlight that, although considered a noninflammatory axis, the involvement of CXCR4 and SDF-1alpha is critical during AAD, and this receptor and its ligand are potentially relevant in other inflammatory processes.

  3. Spatial regulation of the cAMP-dependent protein kinase during chemotactic cell migration.

    Science.gov (United States)

    Howe, Alan K; Baldor, Linda C; Hogan, Brian P

    2005-10-04

    Historically, the cAMP-dependent protein kinase (PKA) has a paradoxical role in cell motility, having been shown to both facilitate and inhibit actin cytoskeletal dynamics and cell migration. In an effort to understand this dichotomy, we show here that PKA is regulated in subcellular space during cell migration. Immunofluorescence microscopy and biochemical enrichment of pseudopodia showed that type II regulatory subunits of PKA and PKA activity are enriched in protrusive cellular structures formed during chemotaxis. This enrichment correlates with increased phosphorylation of key cytoskeletal substrates for PKA, including the vasodilator-stimulated phosphoprotein (VASP) and the protein tyrosine phosphatase containing a PEST motif. Importantly, inhibition of PKA activity or its ability to interact with A kinase anchoring proteins inhibited the activity of the Rac GTPase within pseudopodia. This effect correlated with both decreased guanine nucleotide exchange factor activity and increased GTPase activating protein activity. Finally, inhibition of PKA anchoring, like inhibition of total PKA activity, inhibited pseudopod formation and chemotactic cell migration. These data demonstrate that spatial regulation of PKA via anchoring is an important facet of normal chemotactic cell movement.

  4. Spatiotemporal chemotactic model for ant foraging

    Science.gov (United States)

    Ramakrishnan, Subramanian; Laurent, Thomas; Kumar, Manish; Bertozzi, Andrea L.

    2014-12-01

    In this paper, we present a generic theoretical chemotactic model that accounts for certain emergent behaviors observed in ant foraging. The model does not have many of the constraints and limitations of existing models for ants colony dynamics and takes into account the distinctly different behaviors exhibited in nature by ant foragers in search of food and food ferrying ants. Numerical simulations based on the model show trail formation in foraging ant colonies to be an emergent phenomenon and, in particular, replicate behavior observed in experiments involving the species P. megacephala. The results have broader implications for the study of randomness in chemotactic models. Potential applications include the developments of novel algorithms for stochastic search in engineered complex systems such as robotic swarms.

  5. Psoriasin: a novel chemotactic protein

    DEFF Research Database (Denmark)

    Jinquan, T; Vorum, H; Larsen, C G

    1996-01-01

    Inflammatory skin disorders such as psoriasis show a preferential epidermal infiltration of neutrophils and T lymphocytes. This observation raises a question as to which factors determine the appearance and composition of leukocyte tissue infiltrations. Previously, we described a low molecular ma...

  6. Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3.

    Czech Academy of Sciences Publication Activity Database

    Potměšil, Petr; Holý, Antonín; Kmoníčková, Eva; Křížková, Jana; Zídek, Zdeněk

    2007-01-01

    Roč. 14, č. 1 (2007), s. 59-66 ISSN 1021-7770 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40550506 Keywords : Acyclic nucleoside phosponate * HIV * Monocyte chemotactic protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.024, year: 2007

  7. Chemotactic droplet swimmers in complex geometries

    Science.gov (United States)

    Jin, Chenyu; Hokmabad, Babak V.; Baldwin, Kyle A.; Maass, Corinna C.

    2018-02-01

    Chemotaxis1 and auto-chemotaxis are key mechanisms in the dynamics of micro-organisms, e.g. in the acquisition of nutrients and in the communication between individuals, influencing the collective behaviour. However, chemical signalling and the natural environment of biological swimmers are generally complex, making them hard to access analytically. We present a well-controlled, tunable artificial model to study chemotaxis and autochemotaxis in complex geometries, using microfluidic assays of self-propelling oil droplets in an aqueous surfactant solution (Herminghaus et al 2014 Soft Matter 10 7008–22 Krüger et al 2016 Phys. Rev. Lett. 117). Droplets propel via interfacial Marangoni stresses powered by micellar solubilisation. Moreover, filled micelles act as a chemical repellent by diffusive phoretic gradient forces. We have studied these chemotactic effects in a series of microfluidic geometries, as published in Jin et al (2017 Proc. Natl Acad. Sci. 114 5089–94): first, droplets are guided along the shortest path through a maze by surfactant diffusing into the maze from the exit. Second, we let auto-chemotactic droplet swimmers pass through bifurcating microfluidic channels and record anticorrelations between the branch choices of consecutive droplets. We present an analytical Langevin model matching the experimental data. In a previously unpublished experiment, pillar arrays of variable sizes and shapes provide a convex wall interacting with the swimmer and, in the case of attachment, bending its trajectory and forcing it to revert to its own trail. We observe different behaviours based on the interplay of wall curvature and negative autochemotaxis, i.e. no attachment for highly curved interfaces, stable trapping at large pillars, and a narrow transition region where negative autochemotaxis makes the swimmers detach after a single orbit.

  8. Dynamics of Chemotactic Droplets in Salt Concentration Gradients

    DEFF Research Database (Denmark)

    Cejkova, J.; Novak, M.; Stepanek, F.

    2014-01-01

    The chemotactic movement of decanol droplets in aqueous solutions of sodium decanoate in response to concentration gradients of NaCl has been investigated. Key parameters of the chemotactic response, namely the induction time and the migration velocity, have been evaluated as a function of the so...... of movement repeatedly, to carry and release a chemically reactive cargo, to select a stronger concentration gradient from two options, and to initiate chemotaxis by an external temperature stimulus have been demonstrated....

  9. Monocyte chemotactic protein-4: tissue-specific expression and signaling through CC chemokine receptor-2.

    Science.gov (United States)

    Godiska, R; Chantry, D; Raport, C J; Schweickart, V L; Trong, H L; Gray, P W

    1997-03-01

    Chemokines constitute a family of low-molecular-weight proteins that attract or activate a variety of cell types, including leukocytes, endothelial cells, and fibroblasts. An electronic search of the GenBank Expressed Sequence Tags database uncovered a partial cDNA sequence with homology to the chemokine monocyte chemotactic protein-1 (MCP-1). Isolation of the full-length clone revealed that it encodes the chemokine MCP-4, an eosinophil chemoattractant recently described by Uguccioni et al. [J. Exp. Med. 183, 2379-2384]. Recombinant MCP-4 was expressed in mammalian cells and purified by heparin-Sepharose chromatography. Sequencing the amino terminus of this protein corroborated the reported sequence of recombinant MCP-4 produced in insect cells. As shown by calcium flux assays, MCP-4 activated the cloned G protein-coupled receptor CCR-2, which also recognizes MCP-1 and MCP-3. Northern hybridization indicated that MCP-4 is constitutively expressed at high levels in the small intestine, colon, and lung. This expression profile is consistent with its role as a chemoattractant for eosinophils, which can be rapidly mobilized to the lung or intestine in response to invading pathogens. In marked contrast to MCP-1, MCP-4 was not induced in cell lines treated with pro-inflammatory stimuli such as lipopolysaccharide or tumor necrosis factor alpha.

  10. Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells.

    Science.gov (United States)

    Wang, J M; Sica, A; Peri, G; Walter, S; Padura, I M; Libby, P; Ceska, M; Lindley, I; Colotta, F; Mantovani, A

    1991-01-01

    The present study was designed to investigate the capacity of human vascular smooth muscle cells (SMCs) to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein [MCP]) and by way of comparison, a related polypeptide activator of neutrophils (known as interleukin-8 [IL-8] or neutrophil activating protein-1 [NAP-1]. On exposure to IL-1, SMCs released high levels of chemotactic activity for monocytes, which could be removed by absorption with anti-MCP antibodies. MCP production by activated SMCs was comparable to that of IL-1-stimulated umbilical vein endothelial cells. Activated SMCs released appreciable levels of IL-8, as determined by a specific enzyme-linked immunosorbent assay, but little chemotactic activity for neutrophils. IL-1-treated SMCs expressed high levels of both MCP and IL-8 mRNA transcripts, as assessed by Northern blot analysis. Tumor necrosis factor and bacterial lipopolysaccharide but not IL-6 also induced MCP and IL-8 gene expression in SMCs. Nuclear runoff analysis revealed that IL-1 augmented transcription of the MCP and IL-8 genes. The capacity of SMCs to produce a cytokine (MCP) that recruits and activates circulating mononuclear phagocytes may be of considerable importance in the pathogenesis of vascular diseases (e.g., vasculitis and atherosclerosis) that are characterized by monocyte infiltration of the vessel wall.

  11. Monocyte chemotactic protein-4 (MCP-4/CCL-13) and CC ...

    African Journals Online (AJOL)

    Background: Monocyte chemotactic protein-4 (MCP-4/CCL-13) is a potent chemoattractant to eosinophils, monocytes and lymphocytes. Objective: We aimed to investigate MCP-4 and its CC chemokine receptor 3 (CCR3) expression on cells of induced sputum during acute asthma exacerbation. Methods: ...

  12. Defect of netrophil chemotactic function is one of the etiology of aggressive periodontitis.

    Directory of Open Access Journals (Sweden)

    Yanti Rusyanti

    2016-06-01

    Full Text Available Characteristic of progressive destructive periodontal tissue in Aggressive Periodontitis is a features of disruption of the host-homeostasis as the results of imbalance between host response and specific bacterial pathogenic which presents at gingival sulcus. The objective of this study was to evaluate netrophil function of  Aggressive periodontitis molecularly by means of gen polimorphism of Formyl Peptide Receptor (FPR1 at the surface of netrophil cell, the level of IL-8 and netrophil chemotactic. The results of  the study  can be used as an early detection, prevention or to arrest tissue destruction and to restore a health-associated homeostasis in order to get better prognosis of Aggressive Periodontitis. The study was conducted during 20 months in Periodontic Clinic Dental Hospital, Faculty of Dentistry, Padjadjaran University, Genetica Moleculer Medical Laboratory of Research Institution Padjadjaran University Bandung. Research design used case control methode and sample selection is done in concecutive sampling of 32 aggressive periodontitis patients and 29 non aggressive periodontitis patients who were included in the inclusion criteria. Research materials were venous blood and gingival crevicular fluid. PCR-Sequensing methode was used to asses of gene FPR1 Polimorphism. ELISA methode was used to measure IL-8 level in gingival crevicular fluid, and Human CD66abce Microbead Kit by MACS Separation methode was used to asses netrophil chemotactic. Chi-square test, Fisher’s exact, unpaired t tests were employed to analyse the differences of  characteristic, allele frequencies and genotypic, bivariate analysis to analyse of risk factors and biserial point correlation to analyse correlation between risk factors. The results showed the existence of c576T>C>G gene FPR1 polymorphism 5.040 time-fold (p=0.006; OR=5.040 while the down regulation of IL-8( ≤0.064 pg/µl is 34.5 times-fold of having aggressive periodontitis (OR=34, and c576T

  13. Predicting Escherichia coli's chemotactic drift under exponential gradient

    Science.gov (United States)

    Samanta, Sibendu; Layek, Ritwik; Kar, Shantimoy; Raj, M. Kiran; Mukhopadhyay, Sudipta; Chakraborty, Suman

    2017-09-01

    Bacterial species are known to show chemotaxis, i.e., the directed motions in the presence of certain chemicals, whereas the motion is random in the absence of those chemicals. The bacteria modulate their run time to induce chemotactic drift towards the attractant chemicals and away from the repellent chemicals. However, the existing theoretical knowledge does not exhibit a proper match with experimental validation, and hence there is a need for developing alternate models and validating experimentally. In this paper a more robust theoretical model is proposed to investigate chemotactic drift of peritrichous Escherichia coli under an exponential nutrient gradient. An exponential gradient is used to understand the steady state behavior of drift because of the logarithmic functionality of the chemosensory receptors. Our theoretical estimations are validated through the experimentation and simulation results. Thus, the developed model successfully delineates the run time, run trajectory, and drift velocity as measured from the experiments.

  14. Misbalanced CXCL12 and CCL5 Chemotactic Signals in Vitiligo Onset and Progression.

    Science.gov (United States)

    Rezk, Ahmed F; Kemp, Daria Marley; El-Domyati, Moetaz; El-Din, Wael Hosam; Lee, Jason B; Uitto, Jouni; Igoucheva, Olga; Alexeev, Vitali

    2017-05-01

    Generalized nonsegmental vitiligo is often associated with the activation of melanocyte-specific autoimmunity. Because chemokines play an important role in the maintenance of immune responses, we examined chemotactic signatures in cultured vitiligo melanocytes and skin samples of early (≤2 months) and advanced (≥6 months) vitiligo. Analysis showed that melanocytes in early lesions have altered expression of several chemotaxis-associated molecules, including elevated secretion of CXCL12 and CCL5. Higher levels of these chemokines coincided with prominent infiltration of the skin with antigen presenting cells (APCs) and T cells. Most of the intralesional APCs expressed the CD86 maturation marker and co-localized with T cells, particularly in early vitiligo lesions. These observations were confirmed by in vivo animal studies showing preferential recruitment of APCs and T cells to CXCL12- and CCL5-expressing transplanted melanocytes, immunotargeting of the chemokine-positive cells, continuous loss of the pigment-producing cells from the epidermis, and development of vitiligo-like lesions. Taken together, our studies show that melanocyte-derived CXCL12 and CCL5 support APC and T-cell recruitment, antigen acquisition, and T-cell activation in early vitiligo and reinforce the role of melanocyte-derived CXCL12 and CCL5 in activation of melanocyte-specific immunity and suggest inhibition of these chemotactic axes as a strategy for vitiligo stabilization. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

    Directory of Open Access Journals (Sweden)

    Gomez-Lopez Nardhy

    2013-01-01

    Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

  16. Human skin melanocyte migration towards stromal cell-derived factor-1α demonstrated by optical real-time cell mobility assay: modulation of their chemotactic ability by α-melanocyte-stimulating hormone.

    Science.gov (United States)

    Yamauchi, Akira; Hadjur, Christophe; Takahashi, Tadahito; Suzuki, Itaru; Hirose, Kunitaka; Mahe, Yann F

    2013-10-01

    To identify potential regulators of normal human melanocyte behaviour, we have developed an in vitro human melanocyte migration assay, using the optically accessible, real-time cell motility assay device TAXIScan. Coating of the glass surface with an extracellular matrix that served as scaffolding molecule was essential to demonstrate efficient melanocyte migration. Among several chemokines tested, stromal cell-derived factor (SDF)-1α/CXCL12 was the most effective driver of human normal skin melanocytes. Incubation of melanocytes with α-melanocyte-stimulating hormone (MSH) before the assay specifically enhanced CXCR4 expression and consequently chemotaxis towards SDF-1α/CXCL12. These results suggest that α-MSH acts on melanocytes to produce melanin as well as stimulates the cells to migrate to the site where they work through CXCR4 up-regulation, which is a new dynamic mode of action of α-MSH on melanocyte physiology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Collective Chemotactic Cell Movement; a Key Mechanism of Development and Morphogenesis

    Science.gov (United States)

    Weijer, Cornelis

    2011-03-01

    We investigate the molecular mechanisms by which cells produce and detect chemotactic signals and translate this information in directed movement up or down chemical gradients in the social amoebae Dictyostelium discoideum, and during gastrulation in the chick embryo. Investigation of Dictyostelium mutants with changes in cAMP cell-cell signalling dynamics and chemotaxis, show how cellular heterogeneity in signalling dynamics and polarised activation of the actin-myosin cytoskeleton drive aggregation, cell sorting, slug formation and migration. Chemotactic cell movement also plays a critical role during gastrulation in the chick embryo a model for amniote development. We suggest that epiblast cell movement during the formation of the primitive streak as well as the movement of the mesoderm cells after their ingression through the streak is controlled by a combination of attractive and repulsive guidance cues. We use computer models explore signalling and cell movement interact to give rise to emergent phenomena at the tissue and organism level such as pattern formation and morphogenesis.

  18. The soluble form of urokinase receptor promotes angiogenesis through its Ser⁸⁸-Arg-Ser-Arg-Tyr⁹² chemotactic sequence.

    Science.gov (United States)

    Bifulco, K; Longanesi-Cattani, I; Gala, M; DI Carluccio, G; Masucci, M T; Pavone, V; Lista, L; Arra, C; Stoppelli, M P; Carriero, M V

    2010-12-01

    The urokinase plasminogen activator receptor (u-PAR) focuses the proteolytic activity of the urokinase plasminogen activator (u-PA) on the endothelial cell surface, thus promoting angiogenesis in a protease-dependent manner. The u-PAR may exist in a glycophosphatidylinositol-anchored and in a soluble form (soluble u-PAR [Su-PAR]), both including the chemotactic Ser⁸⁸ -Arg-Ser-Arg-Tyr⁹² internal sequence. To investigate whether Su-PAR may trigger endothelial cell signaling leading to new vessel formation through its chemotactic Ser⁸⁸ -Arg-Ser-Arg-Tyr⁹² sequence. In this study, the formation of vascular-like structures by human umbilical vein endothelial cells was assessed by using a matrigel basement membrane preparation. First, we found that Su-PAR protein promotes the formation of cord-like structures, and that this ability is retained by the isolated Ser(88) -Arg-Ser-Arg-Tyr⁹² chemotactic sequence, the maximal effect being reached at 10 nmol L⁻¹ SRSRY peptide (SRSRY). This effect is mediated by the α(v) β₃ vitronectin receptor, is independent of u-PA proteolytic activity, and involves the internalization of the G-protein-coupled formyl-peptide receptor in endothelial cells. Furthermore, exposure of human saphenous vein rings to Su-PAR or SRSRY leads to a remarkable degree of sprouting. Finally, we show that Su-PAR and SRSRY promote a marked response in angioreactors implanted into the dorsal flank of nude mice, retaining 91% and 66%, respectively, of the angiogenic response generated by a mixture of vascular endothelial growth factor and fibroblast growth factor type 2. Our results show a new protease-independent activity of Su-PAR that stimulates in vivo angiogenesis through its Ser⁸⁸ -Arg-Ser-Arg-Tyr⁹² chemotactic sequence. © 2010 International Society on Thrombosis and Haemostasis.

  19. Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance.

    LENUS (Irish Health Repository)

    Finucane, Orla M

    2012-11-01

    High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

  20. Bifurcation in the chemotactic behavior of Physarum plasmodium

    Science.gov (United States)

    Shirakawa, Tomohiro; Gunji, Yukio-Pegio; Sato, Hiroshi; Tsubakino, Hiroto

    2017-07-01

    The plasmodium of true slime mold Physarum polycephalum is a unicellular and multinuclear giant amoeba. Since the cellular organism has some computational abilities, it is attracting much attention in the field of information science. However, previous studies have mainly focused on the optimization behavior of the plasmodium for a single-modality stimulus, and there are few studies on how the organism adapts to multi-modal stimuli. We stimulated the plasmodium with mixture of attractant and repellent stimuli, and we observed bifurcation in the chemotactic behavior of the plasmodium.

  1. Phenomenological understanding of aggregation and dispersion of chemotactic cells

    CERN Document Server

    Iwasa, Masatomo

    2011-01-01

    We present a simple model that describes the motion of a single chemotactic cell exposed to a traveling wave of the chemoattractant. The model incorporates two types of responses to stimulation by the chemoattractant, i.e., change in polarity and change in motility of the cell. The periodic change in motility is assumed to be induced by the periodic stimulation by the chemoattractant on the basis of previous observations. Consequently, net migration of the cell occurs in a particular direction with respect to wave propagation, which explains the migration of Dictyostelium cells in aggregation processes. The difference between two time delays from the stimulation to the two responses and the wave frequency determined by the frequency of the secretion of the chemoattractant are important parameters that determine the direction of migration and the effective interaction between cells in a population. This result explains the dispersed state of a population of vegetative cells and cells in preaggregation without ...

  2. Substrate-driven chemotactic assembly in an enzyme cascade

    Science.gov (United States)

    Zhao, Xi; Palacci, Henri; Yadav, Vinita; Spiering, Michelle M.; Gilson, Michael K.; Butler, Peter J.; Hess, Henry; Benkovic, Stephen J.; Sen, Ayusman

    2018-03-01

    Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

  3. [The role of angiogenic factors in preeclampsia].

    Science.gov (United States)

    Alasztics, Bálint; Gullai, Nóra; Molvarec, Attila; Rigó, János

    2014-11-23

    Preeclampsia is one of the most common and most serious complications of pregnancy and the management of this condition still challenges obstetricians. Despite intensive research the etiology of preeclampsia still remains unclear. At the beginning of the 2000s preeclampsia-related research was directed towards factors that influence angiogenesis. Most studies have been carried out on the placental growth factor and soluble fms-like tyrosine kinase-1. Most publications confirm the increased concentrations of antiangiogenic factors and decreased concentrations of proangiogenic factors in maternal blood samples in preeclampsia even before the onset of clinical symptoms. According to our current knowledge antiangiogenic proteins are responsible for the endothelial dysfunction in the symptomatic stage of the disease. Placental growth factor and soluble fms-like tyrosine kinase-1 may have important roles in the prediction and treatment of the disease. The point of care detection of placental growth factor and soluble fms-like tyrosine kinase-1 may be used to predict preeclampsia. Rapid tests are available to determine the serum levels of the two proteins. Removal of soluble fms-like tyrosine kinase-1 from maternal circulation is a potential treatment option for early onset preeclampsia.

  4. Role of developmental factors in hypothalamic function

    Directory of Open Access Journals (Sweden)

    Jakob eBiran

    2015-04-01

    Full Text Available The hypothalamus is a brain region which regulates homeostasis by mediating endocrine, autonomic and behavioral functions. It is comprised of several nuclei containing distinct neuronal populations producing neuropeptides and neurotransmitters that regulate fundamental body functions including temperature and metabolic rate, thirst and hunger, sexual behavior and reproduction, circadian rhythm, and emotional responses. The identity, number and connectivity of these neuronal populations are established during the organism’s development and are of crucial importance for normal hypothalamic function. Studies have suggested that developmental abnormalities in specific hypothalamic circuits can lead to obesity, sleep disorders, anxiety, depression and autism. At the molecular level, the development of the hypothalamus is regulated by transcription factors, secreted growth factors, neuropeptides and their receptors. Recent studies in zebrafish and mouse have demonstrated that some of these molecules maintain their expression in the adult brain and subsequently play a role in the physiological functions that are regulated by hypothalamic neurons. Here, we summarize the involvement of some of the key developmental factors in hypothalamic development and function by focusing on the mouse and zebrafish genetic model organisms.

  5. Chemotactic Activity on Human Neutrophils to Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2013-07-01

    Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

  6. Growth-related gene product {alpha}: A chemotactic cytokine for neutrophils in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Koch, A.E.; Pope, R.M. [Northwestern Univ. Medical School, Chicago IL (United States)]|[Veteran`s Administration Lakeside Medical Center, Chicago, IL (United States); Shah, M.R.; Hosaka, S. [Northwestern Univ. Medical School, Chicago, IL (United States)] [and others

    1995-10-01

    Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product {alpha} (gro{alpha}) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro{alpha} (mean 5.3 {+-} 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro{alpha} (mean 4.3 {+-} 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10{sup 5}/cells/ml RPMI 1640/24 h) produced antigenic gro{alpha} (mean 0.2 {+-} 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-{alpha} (mean 1.3 {+-} 0.3 ng/ml) or IL-1{beta} (mean 2.3 {+-} 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro{alpha}: neutrophils (PMNs) (10{sup 7} cells/ml/24 h) produced 3.7 {+-} 0.7 ng/ml. RA SF mononuclear cells produced gro{alpha}, particularly upon incubation with LPS or PHA. Immunoreactive ST gro{alpha} was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro{alpha} for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro{alpha} plays an important role in the ingress of PMNs into the RA joint. 54 refs., 6 figs., 1 tab.

  7. Eosinophil recruitment and activation: the role of lipid mediators

    OpenAIRE

    Tatiana eLuna-Gomes; Patricia eBozza; Christianne eBandeira-Melo

    2013-01-01

    Eosinophils are effector cells that migrate toward several mediators released at inflammatory sites to perform their multiple functions. The mechanisms driving eosinophil selective accumulation in sites of allergic inflammation are well established and involve several steps controlled by adhesion molecules, priming agents, chemotactic and surviving factors. Even though the majority of studies focused on role of protein mediators like IL-5 and eotaxins, lipid mediators also participate in eosi...

  8. BUPRENORPHINE DECREASES THE CCL2-MEDIATED CHEMOTACTIC RESPONSE OF MONOCYTES

    Science.gov (United States)

    Carvallo, Loreto; Lopez, Lillie; Che, Fa-Yun; Lim, Jihyeon; Eugenin, Eliseo; Williams, Dionna W.; Nieves, Edward; Calderon, Tina M.; Madrid-Aliste, Carlos; Fiser, Andras; Weiss, Louis; Angeletti, Ruth Hogue; Berman, Joan W.

    2015-01-01

    Despite successful cART, approximately 60% of HIV infected people exhibit HIV associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9, were identified and had not been shown previously be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction. PMID:25716997

  9. Investigations into the design principles in the chemotactic behavior of Escherichia coli.

    Science.gov (United States)

    Kim, Tae-Hwan; Jung, Sung Hoon; Cho, Kwang-Hyun

    2008-01-01

    Inspired by the recent studies on the analysis of biased random walk behavior of Escherichia coli[Passino, K.M., 2002. Biomimicry of bacterial foraging for distributed optimization and control. IEEE Control Syst. Mag. 22 (3), 52-67; Passino, K.M., 2005. Biomimicry for Optimization, Control and Automation. Springer-Verlag, pp. 768-798; Liu, Y., Passino, K.M., 2002. Biomimicry of social foraging bacteria for distributed optimization: models, principles, and emergent behaviors. J. Optim. Theory Appl. 115 (3), 603-628], we have developed a model describing the motile behavior of E. coli by specifying some simple rules on the chemotaxis. Based on this model, we have analyzed the role of some key parameters involved in the chemotactic behavior to unravel the underlying design principles. By investigating the target tracking capability of E. coli in a maze through computer simulations, we found that E. coli clusters can be controlled as target trackers in a complex micro-scale-environment. In addition, we have explored the dynamical characteristics of this target tracking mechanism through perturbation of parameters under noisy environments. It turns out that the E. coli chemotaxis mechanism might be designed such that it is sensitive enough to efficiently track the target and also robust enough to overcome environmental noises.

  10. Squid-derived chitin oligosaccharides are a chemotactic signal during colonization by Vibrio fischeri.

    Science.gov (United States)

    Mandel, Mark J; Schaefer, Amy L; Brennan, Caitlin A; Heath-Heckman, Elizabeth A C; Deloney-Marino, Cindy R; McFall-Ngai, Margaret J; Ruby, Edward G

    2012-07-01

    Chitin, a polymer of N-acetylglucosamine (GlcNAc), is noted as the second most abundant biopolymer in nature. Chitin serves many functions for marine bacteria in the family Vibrionaceae ("vibrios"), in some instances providing a physical attachment site, inducing natural genetic competence, and serving as an attractant for chemotaxis. The marine luminous bacterium Vibrio fischeri is the specific symbiont in the light-emitting organ of the Hawaiian bobtail squid, Euprymna scolopes. The bacterium provides the squid with luminescence that the animal uses in an antipredatory defense, while the squid supports the symbiont's nutritional requirements. V. fischeri cells are harvested from seawater during each host generation, and V. fischeri is the only species that can complete this process in nature. Furthermore, chitin is located in squid hemocytes and plays a nutritional role in the symbiosis. We demonstrate here that chitin oligosaccharides produced by the squid host serve as a chemotactic signal for colonizing bacteria. V. fischeri uses the gradient of host chitin to enter the squid light organ duct and colonize the animal. We provide evidence that chitin serves a novel function in an animal-bacterial mutualism, as an animal-produced bacterium-attracting synomone.

  11. The stability of a homogeneous suspension of chemotactic bacteria

    Science.gov (United States)

    Subramanian, G.; Koch, Donald L.; Fitzgibbon, Sean R.

    2011-04-01

    The linear stability of a homogeneous dilute suspension of chemotactic bacteria in a constant chemoattractant gradient is analyzed. The bacteria execute a run-and-tumble motion, typified by the species E. coli, wherein periods of smooth swimming (runs) are interrupted by abrupt uncorrelated changes in swimming direction (tumbles). Bacteria tumble less frequently when swimming toward regions of higher chemoattractant concentration, leading to a mean bacterial orientation and velocity in the base state. The stability of an unbounded suspension, both with and without a chemoattractant, is controlled by coupled long wavelength perturbations of the fluid velocity and bacterial orientation fields. In the former case, the most unstable perturbations have their wave vector oriented along the chemoattractant gradient. Chemotaxis reduces the critical bacteria concentration, for the onset of collective swimming, compared with that predicted by Subramanian and Koch ["Critical bacterial concentration for the onset of collective swimming," J. Fluid Mech. 632, 359 (2009)] in the absence of a chemoattractant. A part of this decrease may be attributed to the increase in the mean tumbling time in the presence of a chemoattractant gradient. A second destabilizing influence comes from the ability of the shearing motion, associated with a velocity perturbation in which the velocity and chemical gradients are aligned, to sweep prealigned bacteria into the local extensional quadrant thereby creating a stronger destabilizing active stress than in an initially isotropic suspension. The chemoattractant gradient also fundamentally alters the unstable spectrum for any finite wavenumber. In suspensions of bacteria that do not tumble, Saintillan and Shelley ["Instabilities and pattern formation in active particle suspensions: Kinetic theory and continuum simulations," Phys. Rev. Lett. 100, 178103 (2008); "Instabilities, pattern formation and mixing in active suspensions," Phys. Fluids 20

  12. The Role of Psychological Factors in the Process of Reading

    Science.gov (United States)

    Habibian, Maryam; Roslan, Samsilah; Idris, Khairuddin; Othman, Jamilah

    2015-01-01

    In recent years, psychological factors have become vital factors in literacy education. Existing research has indicated that these factors haves received special attention in the comprehension process. Moreover, in reading process and teaching curriculum understanding, the role of these factors could be beneficial for the students. This paper…

  13. Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils.

    Science.gov (United States)

    Luu, N T; Rainger, G E; Nash, G B

    2000-06-01

    Neutrophils migrate through endothelium using an ordered sequence of adhesive interactions and activating signals. To investigate the consequences of disruption of this sequence, we characterized adhesion and migration of neutrophils perfused over HUVEC that had been treated with TNF-alpha for 4 h and evaluated changes caused by exogenously added chemotactic agents. When HUVEC were treated with 2 U/ml TNF, flowing neutrophils adhered, with the majority rolling and relatively few migrating through the monolayer. If fMLP, IL-8, zymosan-activated plasma (a source of activated complement factor C5a), epithelial cell-derived neutrophil-activating peptide (ENA-78), or growth-regulating oncogene, GRO-alpha, was perfused over these neutrophils, they stopped rolling and rapidly migrated over the monolayer, but did not penetrate it. When HUVEC were treated with 100 U/ml TNF, the majority of adherent neutrophils transmigrated. If neutrophils were treated with fMLP, IL-8, C5a, ENA-78, or GRO-alpha just before perfusion over this HUVEC, transmigration, but not adhesion, was abolished. However, when platelet-activating factor was used to activate neutrophils, migration through HUVEC treated with 100 U/ml TNF was not impaired, and migration through HUVEC treated with 2 U/ml TNF was actually increased. Transmigration required ligation of CXC chemokine receptor-2 on neutrophils, and differential desensitization of this receptor (e.g., by fMLP but not platelet-activating factor) may explain the pattern of disruption of migration. Thus, transmigration may require presentation of the correct activators in the correct sequence, and inappropriate activation (e.g., by systemic activators) could cause pathological accumulation of neutrophils in the vessel lumen.

  14. Neutrophil chemotactic activity in bronchoalveolar lavage fluid of patients with AIDS-associated Pneumocystis carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; Kharazmi, A; Larsen, C G

    1997-01-01

    been shown to confer a poor prognosis in PCP. We therefore investigated the potential of BAL fluid from 17 patients with PCP to induce neutrophil chemotaxis. BAL fluid from patients induced considerable neutrophil chemotactic activity compared to normal controls. Elevated levels of IL-8 were detected...... in patient samples as compared to controls. A specific anti-IL-8 antibody significantly reduced chemotactic activity of patient samples by more than 50%. In conclusion, IL-8 appears to be a significant participant of neutrophil chemotaxis in AIDS-associated PCP, and may participate in the recruitment...

  15. Chemotactic signal transduction and phosphate metabolism as adaptive strategies during citrus canker induction by Xanthomonas citri.

    Science.gov (United States)

    Moreira, Leandro Marcio; Facincani, Agda Paula; Ferreira, Cristiano Barbalho; Ferreira, Rafael Marine; Ferro, Maria Inês Tiraboshi; Gozzo, Fabio Cesar; de Oliveira, Julio Cezar Franco; Ferro, Jesus Aparecido; Soares, Márcia Regina

    2015-03-01

    The genome of Xanthomonas citri subsp. Citri strain 306 pathotype A (Xac) was completely sequenced more than 10 years; to date, few studies involving functional genomics Xac and its host compatible have been developed, specially related to adaptive events that allow the survival of Xac within the plant. Proteomic analysis of Xac showed that the processes of chemotactic signal transduction and phosphate metabolism are key adaptive strategies during the interaction of a pathogenic bacterium with its plant host. The results also indicate the importance of a group of proteins that may not be directly related to the classical virulence factors, but that are likely fundamental to the success of the initial stages of the infection, such as methyl-accepting chemotaxis protein (Mcp) and phosphate specific transport (Pst). Furthermore, the analysis of the mutant of the gene pstB which codifies to an ABC phosphate transporter subunit revealed a complete absence of citrus canker symptoms when inoculated in compatible hosts. We also conducted an in silico analysis which established the possible network of genes regulated by two-component systems PhoPQ and PhoBR (related to phosphate metabolism), and possible transcriptional factor binding site (TFBS) motifs of regulatory proteins PhoB and PhoP, detaching high degree of conservation of PhoB TFBS in 84 genes of Xac genome. This is the first time that chemotaxis signal transduction and phosphate metabolism were therefore indicated to be fundamental to the process of colonization of plant tissue during the induction of disease associated with Xanthomonas genus bacteria.

  16. Role of Psychological Factors on Advertising Effectiveness

    OpenAIRE

    Mohadese Ghayoomi Javinani; Shahab Alddin Shokri

    2014-01-01

    The main purpose of this research was to investigate effecting psychological factors on advertising effectiveness in case of Samsung Television. In this line, advertising attitude and advertising involvement were measured as indicators of effectiveness. This research is quantitative in its nature and applied in kind. The research population was consisted of 305 respondents who were selected by hazardous sampling. A questionnaire was developed as the research instrument and validity of it was ...

  17. Mixture Theory Study of Role of Growth Factor Gradients on Breast Cancer Chemotaxis

    Science.gov (United States)

    Chakraborty, Sreyashi; Schuff, Mary; Voigt, Elizabeth; Nauman, Eric; Rylander, Marissa; Vlachos, Pavlos

    2014-11-01

    The transport of chemotactic agents is strongly influenced by variation in interstitial flows in different types of tissue. The mixture theory model of the fluid and solute transport in the microvasculature of tissues accounts for transport in the vessel lumen, vessel wall and the interstitial space separately. In the present study we use this model to develop a three dimensional geometry of the tumor microenvironment platform incorporating a physiological concentration of growth factor protein through blood flow in an extracellular collagen matrix. We quantify chemotaxis in response to solute gradients of varying magnitude formed by diffusion of proteins into the surrounding collagen. The numerical analysis delineates the dependence of hydraulic permeability coefficient on solute concentration. The preliminary results show the existence of a linear concentration gradient in the central plane between the micro-channels and a strong nonlinear gradient at the remaining parts of the system.

  18. Characterization and reactivity of broiler chicken sera to selected recombinant Campylobacter jejuni chemotactic proteins.

    Science.gov (United States)

    Yeh, Hung-Yueh; Hiett, Kelli L; Line, John E; Seal, Bruce S

    2014-05-01

    Campylobacter jejuni, a Gram-negative rod bacterium, is the leading causative agent of human acute bacterial gastroenteritis worldwide. Consumption and handling of raw or undercooked poultry are regarded as a major source for human infection. Because bacterial chemotaxis guides microorganisms to colonization and invasion in the host cells, proteins involved in chemotactic processes can be novel targets for vaccine development. In this communication, we report amplification, cloning and expression of the C. jejuni chemotactic proteins in an Escherichia coli expression system. A total of 15 chemotactic protein genes were successfully expressed. These recombinant proteins were confirmed by nucleotide sequencing, SDS-PAGE analysis and immunoblot analysis of six-His and hemagglutinin tags. Twelve recombinant chemotactic proteins were further tested whether they were antigenic using sera from broiler chickens older than 4 weeks. The immunoblot results show that each chicken serum reacted to a variety of the recombinant proteins, but all sera reacted to the Cjj0473 gene product (annotated as a methyl-accepting chemotaxis protein), suggesting that anti-Campylobacter antibodies may be prevalent in the poultry population. These antibody screening results provide a rationale for further evaluation of the Cjj0473 protein as a potential vaccine for broilers to improve human food safety.

  19. Tolvaptan suppresses monocyte chemotactic protein-1 excretion in autosomal-dominant polycystic kidney disease

    NARCIS (Netherlands)

    Grantham, Jared J.; Chapman, Arlene B.; Blais, Jaime; Czerwiec, Frank S.; Devuyst, Olivier; Gansevoort, Ron T.; Higashihara, Eiji; Krasa, Holly; Zhou, Wen; Ouyang, John; Perrone, Ronald D.; Torres, Vicente E.

    2017-01-01

    Background: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by multitudes of expanding renal cysts associated with mononuclear interstitial infiltrates. Monocyte chemotactic protein-1 is produced in the kidneys and excreted in the urine (uMCP1) of these patients in increased

  20. Role of Growth Factors in the Development of Mandible

    Directory of Open Access Journals (Sweden)

    Deepu Leander

    2011-01-01

    Growth factors are a large family of polypeptide molecules that regulate cell division in many tissues by autocrine or paracrine mechanisms. Depending on what receptors are activated, growth factors can initiate mitogenic, antiproliferative or trophic effects, that is growth factors act as positive or negative modulators of cell proliferation. The synergistic and orchestrated influences of various growth factors and other regulatory factors that are endogenously expressed in the condyle have been well documented. Growth factors do not only play an important role in embryonic development and adult tissue homeostasis but also in pathological situations, like infection and wound healing. Consequently, the applications of growth factors have therapeutic applications.

  1. THE ROLE OF HUMAN FACTOR IN INNOVATION

    Directory of Open Access Journals (Sweden)

    Suzana DEMYEN

    2017-12-01

    Full Text Available Innovation is a concept that has attracted the attention of researchers increasingly intensely over the past ten years. We speak of innovation as a concept found in a great variety of research, both economic and social, or engineering. At present, Romania is one of the modest innovators with an innovation performance below 50% of the EU average. It is therefore an improvement in the overall situation, but a starting point would be to understand the link between innovation and human resource, that is, the role of the latest in the innovation process. We speak of innovation both at the organization level and at the national level, and it is a lasting process that can not be achieved in a short time. It presupposes dedication, resources and knowledge, many of which lead to the need for specialized centers. Research in Romania is mainly conducted in the university environment, but although the number of doctoral graduates is high, a major challenge at the general level remains the underfinancing of this sector.

  2. Elderly abuse: risk factors and nursing role.

    Science.gov (United States)

    Corbi, Graziamaria; Grattagliano, Ignazio; Ivshina, Evgeniya; Ferrara, Nicola; Solimeno Cipriano, Angela; Campobasso, Carlo Pietro

    2015-04-01

    Elderly abuse is still a hidden problem, often underestimated. It is much more common than the data available suggest. Unfortunately, the incidence is expected to grow with the progressive increase in the elderly population in the future. The aim was to examine the available literature in the last 5 years to define the state of art on this phenomenon, with particular regard to the nursing role in elderly abuse, focusing on the possible types of mistreatment, the motivations and preventive interventions. Articles published in the last 5 years regarding the mistreatment of the elderly were selected, by using scientifically recognized databases such as PubMed, Cochrane Library, Medline, Scopus, and Web of Knowledge. Several keywords were used for the query among which were: "elderly abuse" and "elderly abuse in nursing home". Moreover, to better understand the entity of the phenomenon, we also searched the corresponding keywords for child abuse. Considering the Scopus database, only 78 out of 1,342 published articles in the last 5 years deal with abuse of the elderly in relation to nursing, representing a very small part (5.81%) of the considered sample. Comparing the number of articles, the ratio child/elderly is equal to 1/0.04, underlying the poor interest of research on this phenomenon. Moreover, it was observed that elderly abuse in nursing homes is still underreported in both original articles and reviews. Despite the aging of the population, elderly abuse and neglect still remain hidden problems, overlooked and also underestimated in the literature.

  3. Factors Affecting Role Stress and Burnout among School Counselors

    Science.gov (United States)

    Willingham, Wendy Elizabeth

    2009-01-01

    The purpose of this study is to determine factors affecting role stress and burnout among practicing school counselors as measured by the Maslach Burnout Inventory-Educators Survey (MBI-ES) and the Role Conflict and Ambiguity Scale. The MBI-ES utilizes three subscales to measure burnout: emotional exhaustion, depersonalization, and personal…

  4. Emerging roles for MEF2 transcription factors in memory.

    Science.gov (United States)

    Rashid, A J; Cole, C J; Josselyn, S A

    2014-01-01

    In the brain, transcription factors are critical for linking external stimuli to protein production, enabling neurons and neuronal networks to adapt to the ever-changing landscape. Gene transcription and protein synthesis are also vital for the formation of long-term memory. Members of the myocyte enhancer factor-2 (MEF2) family of transcription factors have a well-characterized role in the development of a variety of tissues, but their role in the adult brain is only beginning to be understood. Recent evidence indicates that MEF2 regulates the structural and synaptic plasticity underlying memory formation. However, in stark contrast to most other transcription factors implicated in memory, MEF2-mediated transcription constrains (rather than promotes) memory formation. Here, we review recent data examining the role of MEF2 in adult memory formation in rodents. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  5. Common Factors' Role in Accredited MFT Training Programs.

    Science.gov (United States)

    D'Aniello, Carissa; Fife, Stephen T

    2017-10-01

    Common factors proponents discuss the benefits and methods of including common factors in marriage and family therapy (MFT) training; yet there are no empirical investigations of how common factors are incorporated into MFT curricula. The purpose of this study was to obtain a baseline understanding of common factors' role in MFT training. Thirty-one directors of COAMFTE- and CACREP-accredited MFT training programs responded to a survey about the inclusion of common factors in their training program, as well as the benefits, challenges, and students' reactions to common factors training. Findings show that common factors are regularly included in MFT training programs and have garnered largely positive responses. Additional results are discussed regarding the implications of common factors in MFT training. © 2017 American Association for Marriage and Family Therapy.

  6. Chemotactic movement in sperm of the oogamous brown algae, Saccharina japonica and Fucus distichus.

    Science.gov (United States)

    Kinoshita, Nana; Nagasato, Chikako; Motomura, Taizo

    2017-01-01

    In oogamous species of brown algae such as Saccharina japonica and Fucus distichus, the sperm possess an unusual long posterior flagellum, which oscillates actively and produces a propulsive force during swimming. In this study, we quantitatively analyzed the effect of chemotactic responses on sperm swimming and flagellar waveforms by high-speed video recordings. We found that the thigmotactic response to the chemo-attractant was not enhanced during chemotactic swimming and that the swimming velocity of sperm did not decrease. As concentration of the chemo-attractant decreased, the sperm performed drastic U-turn movements, which was caused by a rapid and large bend of the posterior flagellum. Unilateral bending of the posterior flagellum when sensing a decrease in the concentration of the chemo-attractant may be a common response in male gametes during fertilization of brown algae both oogamous and isogamous species.

  7. Chemoeffectors decrease the deposition of chemotactic bacteria during transport in porous media

    OpenAIRE

    Velasco Casal, P.; Wick, Lukas Y.; Ortega Calvo, J. J.

    2008-01-01

    Bacterial chemotaxis enables motile cells to move along chemical gradients and to swim toward optimal places for biodegradation. However, its potentially positive effects on subsurface remediation rely on the efficiency of bacterial movement in porous media, which is often restricted by high deposition rates and adhesion to soil surfaces. In well-controlled column systems, we assessed the influence of the chemoeffectors naphthalene, salicylate, fumarate, and acetate on deposition of chemotact...

  8. Chemotactic and hydrodynamic effects on collective dynamics of self-diffusiophoretic Janus motors

    Science.gov (United States)

    Huang, Mu-Jie; Schofield, Jeremy; Kapral, Raymond

    2017-12-01

    Collective motion in nonequilibrium steady state suspensions of self-propelled Janus motors driven by chemical reactions can arise due to interactions coming from direct intermolecular forces, hydrodynamic flow effects, or chemotactic effects mediated by chemical gradients. The relative importance of these interactions depends on the reactive characteristics of the motors, the way in which the system is maintained in a steady state, and properties of the suspension, such as the volume fraction. From simulations of a microscopic hard collision model for the interaction of fluid particles with the Janus motor we show that dynamic cluster states exist and determine the interaction mechanisms that are responsible for their formation. The relative importance of chemotactic and hydrodynamic effects is identified by considering a microscopic model in which chemotactic effects are turned off while the full hydrodynamic interactions are retained. The system is maintained in a steady state by means of a bulk reaction in which product particles are reconverted into fuel particles. The influence of the bulk reaction rate on the collective dynamics is also studied.

  9. Single amino acid substitutions in the chemotactic sequence of urokinase receptor modulate cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Katia Bifulco

    Full Text Available The receptor for urokinase-type plasminogen activator (uPAR plays an important role in controlling cell migration. uPAR binds urokinase and vitronectin extracellular ligands, and signals in complex with transmembrane receptors such as Formyl-peptide Receptors (FPRs and integrins. Previous work from this laboratory has shown that synthetic peptides, corresponding to the uPAR(88-92 chemotactic sequence, when carrying the S90P or S90E substitutions, up- or down-regulate cell migration, respectively. To gain mechanistic insights into these opposite cell responses, the functional consequences of S90P and S90E mutations in full-length uPAR were evaluated. First, (HEK-293 embryonic kidney cells expressing uPAR(S90P exhibit enhanced FPR activation, increased random and directional cell migration, long-lasting Akt phosphorylation, and increased adhesion to vitronectin, as well as uPAR/vitronectin receptor association. In contrast, the S90E substitution prevents agonist-triggered FPR activation and internalization, decreases binding and adhesion to vitronectin, and inhibits uPAR/vitronectin receptor association. Also, 293/uPAR(S90P cells appear quite elongated and their cytoskeleton well organized, whereas 293/uPAR(S90E cells assume a large flattened morphology, with random orientation of actin filaments. Interestingly, when HT1080 cells co-express wild type uPAR with uPAR S90E, the latter behaves as a dominant-negative, impairing uPAR-mediated signaling and reducing cell wound repair as well as lung metastasis in nude mice. In contrast, signaling, wound repair and in vivo lung metastasis of HT1080 cells bearing wild type uPAR are enhanced when they co-express uPAR(S90P. In conclusion, our findings indicate that Ser(90 is a critical residue for uPAR signaling and that the S90P and S90E exert opposite effects on uPAR activities. These findings may be accommodated in a molecular model, in which uPAR(S90E and uPAR(S90P are forced into inactive and active

  10. Noisy Oscillations in the Actin Cytoskeleton of Chemotactic Amoeba

    Science.gov (United States)

    Negrete, Jose; Pumir, Alain; Hsu, Hsin-Fang; Westendorf, Christian; Tarantola, Marco; Beta, Carsten; Bodenschatz, Eberhard

    2016-09-01

    Biological systems with their complex biochemical networks are known to be intrinsically noisy. Here we investigate the dynamics of actin polymerization of amoeboid cells, which are close to the onset of oscillations. We show that the large phenotypic variability in the polymerization dynamics can be accurately captured by a generic nonlinear oscillator model in the presence of noise. We determine the relative role of the noise with a single dimensionless, experimentally accessible parameter, thus providing a quantitative description of the variability in a population of cells. Our approach, which rests on a generic description of a system close to a Hopf bifurcation and includes the effect of noise, can characterize the dynamics of a large class of noisy systems close to an oscillatory instability.

  11. Differences in Attitudes toward Role Playing by Various Personality Factors.

    Science.gov (United States)

    Dixon, Paul N.; Elias, Susan F.

    1978-01-01

    The relationship between several personality variables, including locus of control and selected factors of the Sixteen P-F. (Adventurousness, Enthusiasm, Sociability, Apprehensiveness, Self-sufficiency, and Extraversion), and attitude toward role playing were examined. Differences by locus of control were nonsignificant, although significant…

  12. Transforming growth factor-beta: possible roles in Dupuytren's contracture

    NARCIS (Netherlands)

    Kloen, P.; Jennings, C. L.; Gebhardt, M. C.; Springfield, D. S.; Mankin, H. J.

    1995-01-01

    Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide that stimulates extracellular matrix deposition and fibroblast proliferation. Because both these features characterize Dupuytren's contracture, we investigated a possible role for TGF-beta in the etiology of this disorder.

  13. The role of tissue factor in colorectal cancer

    DEFF Research Database (Denmark)

    Lykke, J; Nielsen, Hans Jørgen

    2003-01-01

    The possible role of tissue factor (TF) in colorectal cancer (CRC) is reviewed. A correlation between TF expression and advanced stages of malignancy, and a correlation between TF expression and overall survival have been suggested in CRC. This is supported by experimental studies indicating...

  14. Role of psychosocial factors in the etiology of bruxism

    NARCIS (Netherlands)

    Manfredini, D.; Lobbezoo, F.

    2009-01-01

    AIMS: To summarize literature data about the role of psychosocial factors in the etiology of bruxism. METHODS: A systematic search in the National Library of Medicine's PubMed Database was performed to identify all peer-reviewed papers in the English literature dealing with the bruxism-psychosocial

  15. Role of Cognitive Factors and Distortions in Adolescent Suicides

    Directory of Open Access Journals (Sweden)

    Bedriye Oncu

    2013-06-01

    Full Text Available Suicide is one of the leading causes of adolescent death and is an important clinical problem. According to World Health Organization, it is the third most common cause of death for 15-44 age group worldwide and is the second most common cause of death for 15-24 age group in Turkey. The presence of a psychiatric disorder and previous suicidal acts, social, cultural and family related factors are well known predictors of suicide. However, cognitive developmental level and schemes are as important as the other factors. For prevention and treatment, it is essential to understand cognitive factors that lead adolescents to suicide. Cognitive factors and distortions that might have a role in adolescent suicides are hopelessness, problem solving deficits, cognitive rigidity, dichotomous thinking, perfectionism, personalizing, and catastrophising and time perspective. In this article, adolescent suicide and related cognitive factors are briefly reviewed.

  16. ROLE OF PAX-5 TRANSCRIPTION FACTOR IN IMMUNOLOGICAL PROCESSES

    Directory of Open Access Journals (Sweden)

    V. N. Mineev

    2011-01-01

    Full Text Available Abstract.  The  review  article  concerns  various  features  of  PAX-5  (paired  box  5  transcription  factor,  its structure, functions, regulation of activity, involvement into differentiation and activation of B lymphocytes, switching to IgE synthesis, its role in oncogenesis, and a putative role of this factor for development of bronchial asthma.Further  insight  into  specific  properties  of  PAX-5  factor  in  bronchial  asthma  may  provide  a  promising approach to studying mechanisms of this disorder. (Med. Immunol., 2011, vol. 13, N 6, pp 569-580

  17. [Role of nitric oxide and other endothelium-derived factors].

    Science.gov (United States)

    Stankevicius, Edgaras; Kevelaitis, Egidijus; Vainorius, Enrikas; Simonsen, Ulf

    2003-01-01

    The endothelial cell layer displays the features of a distributed organ and has a variety of biological functions such as keeping the balance between coagulation and fibrinolysis, expression of adhesion molecules for cells in the immune system, metabolism of noradrenaline and 5-hydroxytryptamine, and conversion of angiotensin I and bradykinin. The endothelium also regulates the underlying smooth muscle layer and vascular tone by release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) as well as vasoconstricting factors such as endothelin, superoxide (O(2)(-)), and thromboxane. We have reviewed the nature, mechanisms of action, and role of these factors in regulation of vascular tone, with special emphasis on NO. By a process catalyzed by NO synthase, NO and citrulline is formed from the substrates molecular O(2) and L-arginine. The main receptor for NO is guanylyl cyclase leading to formation of smooth muscle cyclic guanosinmonophosphate and relaxation. EDHF is an endothelium-derived factor causing vasorelaxation of the underlying smooth muscle layer by hyperpolarization. The nature of EDHF is still unknown, but several candidates for EDHF have been proposed such as potassium ions, hydrogen peroxide, and epoxyeicosatrienoic acids. Prostaglandins such as prostacyclin and prostaglandin E2 binds to specific receptors followed by increases in cyclic adenosinmonophosphate and vasorelaxation, while contractile prostaglandins constrict vessels by activation of thromboxane and endoperoxidase receptors. Superoxide anions induce contraction of vascular smooth muscles cells by scavenging NO. Endothelin is a potent endothelium-derived contractile factor. The synthesis of endothelin-1 is induced by hypoxia, thrombin, interleukin-1, transforming growth factor-beta1, vasopressin, and catecholamines. Cardiovascular risk factors like age, hypertension, and hyperlipidemia are associated with

  18. Roles of heat shock factors in gametogenesis and development.

    Science.gov (United States)

    Abane, Ryma; Mezger, Valérie

    2010-10-01

    Heat shock factors form a family of transcription factors (four in mammals), which were named according to the first discovery of their activation by heat shock. As a result of the universality and robustness of their response to heat shock, the stress-dependent activation of heat shock factor became a ‘paradigm’: by binding to conserved DNA sequences (heat shock elements), heat shock factors trigger the expression of genes encoding heat shock proteins that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stress and in several pathological conditions. Besides their roles in the stress response, heat shock factors perform crucial roles during gametogenesis and development in physiological conditions. First, during these process, in stress conditions, they are either proactive for survival or, conversely, for apoptotic process, allowing elimination or, inversely, protection of certain cell populations in a way that prevents the formation of damaged gametes and secure future reproductive success. Second, heat shock factors display subtle interplay in a tissue- and stage-specific manner, in regulating very specific sets of heat shock genes, but also many other genes encoding growth factors or involved in cytoskeletal dynamics. Third, they act not only by their classical transcription factor activities, but are necessary for the establishment of chromatin structure and, likely, genome stability. Finally, in contrast to the heat shock gene paradigm, heat shock elements bound by heat shock factors in developmental process turn out to be extremely dispersed in the genome, which is susceptible to lead to the future definition of ‘developmental heat shock element’.

  19. Acetylcholine stimulation of human neutrophil chemotactic activity is directly inhibited by tiotropium involving Gq and ERK-1/2 regulation

    Directory of Open Access Journals (Sweden)

    Kurai M

    2012-01-01

    Full Text Available Tiotropium, a long-acting anticholinergic, may improve chronic obstructive pulmonary disease (COPD by mechanisms beyond bronchodilatation. We tested the hypothesis that tiotropium may act as an anti-inflammatory mediator by directly acting on and inhibiting human neutrophil chemotactic activity (NCA that is promoted by acetylcholine (ACh exposure. ACh treatment increased NCA in a dose dependent manner (p < 0.001 and tiotropium pretreatment reduced ACh stimulation (dose effect; 0 to 1000 nM; p < 0.001. Selective muscarinic receptor inhibitors demonstrated that subtype-3 (M3 receptor plays a role in NCA regulation. In addition, NCA that was stimulated by cevimeline (M3 agonist and pasteurella multocida toxin (PMT, M3 coupled Gq agonist. However, the increased NCA to cevimeline and PMT was reduced by tiotropium pretreatment (p < 0.001. ACh treatment stimulated ERK-1/2 activation by promoting protein phosphorylation and tiotropium reduced this effect (p < 0.01. In addition, pretreatment of the cells with a specific MEK-1/2 kinase inhibitor reduced ACh stimulated NCA (p < 0.01. Together these results demonstrated that cholinergic stimulation of NCA is effectively inhibited by tiotropium and is governed by a mechanism involving M3 coupled Gq signaling and downstream ERK signaling. This study further demonstrates that tiotropium may act as an anti-inflammatory agent in lung disease.

  20. The role of tissue factor in colorectal cancer

    DEFF Research Database (Denmark)

    Lykke, J; Nielsen, Hans Jørgen

    2003-01-01

    The possible role of tissue factor (TF) in colorectal cancer (CRC) is reviewed. A correlation between TF expression and advanced stages of malignancy, and a correlation between TF expression and overall survival have been suggested in CRC. This is supported by experimental studies indicating...... that TF plays a key role in growth, invasion and dissemination of tumour cells, and in tumour related angiogenesis as well. In addition, the activation of TF in CRC patients in relation to the surgical trauma, perioperative blood transfusion and development of postoperative bacterial infectious...

  1. Role of environmental factors in the timing of puberty

    DEFF Research Database (Denmark)

    Euling, S.Y.; Selevan, S.G.; Pescovitz, O.H.

    2008-01-01

    Puberty-timing measures have historically been used as indicators of adequate nutrition and growth. More recently, these measures have been examined in relation to exposure to estrogenic or antiandrogenic agents, as well as other environmental factors. The scientific community has debated whether...... puberty timing is occurring earlier today than in the mid-1900s in the United States and, if so, whether environmental factors play a role; however, no one has asked a multidisciplinary panel to resolve this question. Thus, a multidisciplinary expert panel jointly sponsored by the US Environmental...... Protection Agency, the National Institute of Environmental Health Sciences, and Serono Symposia International was convened to examine the evidence of a secular trend, identify potential environmental factors of concern, and identify research needs regarding environmental factors and puberty timing at "The...

  2. Chemotactic activity of hemocytes derived from two marine neritid gastropod molluscs, Nerita albicilla and Heminerita japonica, to Vibrio parahaemolyticus and Escherichia coli strains.

    Science.gov (United States)

    Kumazawa, N H; Iwao, K; Morimoto, N

    1992-04-01

    Hemocytes of two marine neritid gastropods, Nerita albicilla and Heminerita japonica, were attracted chemotactically to live Vibrio parahaemolyticus and Escherichia coli strains. Chemotactic attraction of N. albicilla hemocytes was enhanced in the presence of N. albicilla plasma, while that of H. japonica hemocytes was not enhanced in the presence of H. japonica plasma. Chemotactic activity of the hemocytes seems to participate in the rapid elimination of V. parahaemolyticus from these gastropods.

  3. Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

    Science.gov (United States)

    Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

    2008-06-01

    Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

  4. Chemotactic Motility of Pseudomonas fluorescens F113 under Aerobic and Denitrification Conditions.

    Directory of Open Access Journals (Sweden)

    Candela Muriel

    Full Text Available The sequence of the genome of Pseudomonas fluorescens F113 has shown the presence of multiple traits relevant for rhizosphere colonization and plant growth promotion. Among these traits are denitrification and chemotactic motility. Besides aerobic growth, F113 is able to grow anaerobically using nitrate and nitrite as final electron acceptors. F113 is able to perform swimming motility under aerobic conditions and under anaerobic conditions when nitrate is used as the electron acceptor. However, nitrite can not support swimming motility. Regulation of swimming motility is similar under aerobic and anaerobic conditions, since mutants that are hypermotile under aerobic conditions, such as gacS, sadB, kinB, algU and wspR, are also hypermotile under anaerobic conditions. However, chemotactic behavior is different under aerobic and denitrification conditions. Unlike most pseudomonads, the F113 genome encode three complete chemotaxis systems, Che1, Che2 and Che3. Mutations in each of the cheA genes of the three Che systems has shown that the three systems are functional and independent. Mutation of the cheA1 gene completely abolished swimming motility both under aerobic and denitrification conditions. Mutation of the cheA2 gene, showed only a decrease in swimming motility under both conditions, indicating that this system is not essential for chemotactic motility but is necessary for optimal motility. Mutation of the cheA3 gene abolished motility under denitrification conditions but only produced a decrease in motility under aerobic conditions. The three Che systems proved to be implicated in competitive rhizosphere colonization, being the cheA1 mutant the most affected.

  5. The role of WRKY transcription factors in plant abiotic stresses.

    Science.gov (United States)

    Chen, Ligang; Song, Yu; Li, Shujia; Zhang, Liping; Zou, Changsong; Yu, Diqiu

    2012-02-01

    The WRKY gene family has been suggested to play important roles in the regulation of transcriptional reprogramming associated with plant stress responses. Modification of the expression patterns of WRKY genes and/or changes in their activity contribute to the elaboration of various signaling pathways and regulatory networks. Furthermore, a single WRKY gene often responds to several stress factors, and then their proteins may participate in the regulation of several seemingly disparate processes as negative or positive regulators. WRKY proteins also function via protein-protein interaction and autoregulation or cross-regulation is extensively recorded among WRKY genes, which help us understand the complex mechanisms of signaling and transcriptional reprogramming controlled by WRKY proteins. Here, we review recent progress made in starting to reveal the role of WRKY transcription factors in plant abiotic stresses. This article is part of a Special Issue entitled: Plant gene regulation in response to abiotic stress. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

    Science.gov (United States)

    Mori, Shogo; Williams, Howard; Cagle, Davey; Karanovich, Kristopher; Horgen, F. David; Smith, Roger; Watanabe, Coran M. H.

    2015-01-01

    A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue. PMID:26473885

  7. The role of human fatigue factor towards maritime casualties

    OpenAIRE

    Xhelilaj Ermal; Lapa Kristofor

    2010-01-01

    The international studies on maritime accidents has shown that fatigue is continuing to be either the main cause or a contributory factor in a considerable number of casualties at sea resulting in the loss of life and damage to the environment and property. In fact, fatigue??s detrimental role toward performance at work is leading to errors being made and consequently resulting in fatalities. In light of these considerations, fatigue issue is of great importance to seafarers, the shipping ind...

  8. The Role of Environmental Factors in Digestive Cancer

    Directory of Open Access Journals (Sweden)

    Rene Lambert

    2016-01-01

    Full Text Available The risk of digestive cancer in each country is analyzed in cancer registries for Incidence and Mortality. Survival is estimated from registries with a correct follow-up. Estimated values of Incidence and Mortality, expressed as an age standardized rate (ASR for 100 000 persons, for all the population of a country are also found in the WHO-IARC database Globocan, recently edited for the year 2008. At each site of digestive tumors, the variations between countries, in cancer incidence, mortality and survival, depend on the resources and the global health status of the country. Indeed environmental causal factors linked to lifestyle may have an increasing or decreasing impact on the risk of cancer. Such factors are classified on 3 categories: 1- nutrition plays a determinant role in colorectal cancer with a higher risk in countries with more resources and more calories in the diet. 2- Toxic agents like alcohol and tobacco increase the risk at all sites of digestive cancer; their role is preponderant in esophageal cancer. Aflatoxin, a food contaminant in tropical, less developed countries, increases the risk of liver cancer. 3 – Infectious agents play a major role with the Bacteria H.pylori for stomach cancer over the world, and the Hepatitis virus B and C for liver cancer in less developed countries of Africa and Asia. The control of carcinogenic causal environmental factors is included in the primary prevention of digestive cancer.

  9. Risk factors for psychosis: impaired social and role functioning.

    Science.gov (United States)

    Cornblatt, Barbara A; Carrión, Ricardo E; Addington, Jean; Seidman, Larry; Walker, Elaine F; Cannon, Tyronne D; Cadenhead, Kristin S; McGlashan, Thomas H; Perkins, Diana O; Tsuang, Ming T; Woods, Scott W; Heinssen, Robert; Lencz, Todd

    2012-11-01

    Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability.

  10. Effects of Garlic Oil on the Migration of Neutrophil-Like Cell Studied by Using a Chemotactic Gradient Labchip

    Directory of Open Access Journals (Sweden)

    Po-Chen Shih

    2010-01-01

    Full Text Available We have designed and fabricated a novel chemotactic gradient Labchip for studying cell migration quantitatively. Owing to the great potential of garlic and its preparations in developing antiinflammatory drugs, the aim of the present study is to investigate the effect of garlic oil on the locomotion of a neutrophil-like cell by measuring the dynamic features of cell migration including migration direction, average migration speed, chemotactic index (CI, and motility index (MI with the newly designed Labchip. We found that garlic oil treatment lowered the values of CI and MI and reduced the average speed of cell migration from 13 to 8 μm/min. The results indicate that garlic oil is a potential inhibitor for neutrophil-like cell migration and chemotactic responsiveness. By comparing with the effects of nocodazole and cytochalasin B, we also suggest that the antiinflammatory activity exhibited by garlic oil was mainly through inhibiting the assembly-disassembly processes of the cytoskeleton.

  11. Chemotactic behavior of deep subsurface bacteria toward carbohydrates, amino acids and a chlorinated alkene

    Energy Technology Data Exchange (ETDEWEB)

    Lopez de Victoria, G. (Puerto Rico Univ., Rio Piedras (Puerto Rico). Dept. of Biology)

    1989-02-01

    The chemotactic behavior of deep terrestrial subsurface bacteria toward amino acids, carbohydrates and trichloroethylene was assayed using a modification of the capillary method and bacterial enumeration by acridine orange direct counts. Eleven isolates of bacteria isolated from six different geological formations were investigated. A bimodal response rather than an absolute positive or negative response was observed in most assays. Most of the isolates were positively chemotactic to low concentrations of substrates and were repelled by high concentrations of the same substrate. However, this was not the case for trichloroethylene (TCE) which was mostly an attractant and elicited the highest responses in all the isolates when compared with amino acids and carbohydrates. The movement rates of these isolates in aseptic subsurface sediments in the absence and presence of TCE were also determined using a laboratory model. All of the isolates showed distinct response range, peak, and threshold concentrations when exposed to the same substrates suggesting that they are possibly different species as has been inferred from DNA homology studies. 101 refs., 4 figs., 57 tabs.

  12. Chemoeffectors decrease the deposition of chemotactic bacteria during transport in porous media.

    Science.gov (United States)

    Velasco-Casal, Patricia; Wick, Lukas Y; Ortega-Calvo, José-Julio

    2008-02-15

    Bacterial chemotaxis enables motile cells to move along chemical gradients and to swim toward optimal places for biodegradation. However, its potentially positive effects on subsurface remediation rely on the efficiency of bacterial movement in porous media, which is often restricted by high deposition rates and adhesion to soil surfaces. In well-controlled column systems, we assessed the influence of the chemo-effectors naphthalene, salicylate, fumarate, and acetate on deposition of chemotactic, naphthalene-degrading Pseudomonas putida G7 in selected porous environments (sand, forest soil, and clay aggregates). Our data showed that the presence of naphthalene in the pore water decreased deposition of strain 67 (but not of a derivative strain, P. putida 67.C1 (pHG100), nonchemotactic to naphthalene) by 50% in sand-filled columns, as calculated by the relative adhesion efficiency (at). Similar effects were observed with P. putida G7 strain for the other chemoeffectors. Deposition, however, depended on the chemoeffector's chemical structure, its interaction with the column packing material, and concomitantly its pore-water concentration. As the presence of the chemoeffectors had no influence on the physicochemical surface properties of the bacteria, we suggest that chemotactic sensing, combined with changed swimming modes, is likely to influence the deposition of bacteria in the subsurface, provided that the chemoeffector is dissolved at sufficient concentration in the pore water.

  13. Multi-phasic bi-directional chemotactic responses of the growth cone

    Science.gov (United States)

    Naoki, Honda; Nishiyama, Makoto; Togashi, Kazunobu; Igarashi, Yasunobu; Hong, Kyonsoo; Ishii, Shin

    2016-11-01

    The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue. With biologically realistic sigmoidal dose-responses, our model predicted tri-phasic turning response depending on intracellular Ca2+ level, which was then experimentally confirmed by growth cone turning assays and Ca2+ imaging. Furthermore, we took a reverse-engineering analysis to identify balanced regulation between CaMKII (activator) and PP1 (inhibitor) and then the model performance was validated by reproducing turning assays with inhibitions of CaMKII and PP1. Thus, our study implies that the balance between activator and inhibitor underlies the multi-phasic bi-directional turning response of the growth cone.

  14. A supplemented soft agar chemotaxis assay demonstrates the Helicobacter pylori chemotactic response to zinc and nickel

    Science.gov (United States)

    Sanders, Lisa; Andermann, Tessa M.

    2013-01-01

    Directed motility, or chemotaxis, is required for Helicobacter pylori to establish infection in the stomach, although the full repertoire of this bacterium’s chemotactic responses is not yet known. Here we report that H. pylori responds to zinc as an attractant and nickel as a repellent. To reach this conclusion, we employed both a temporal chemotaxis assay based on bacterial reversals and a supplemented soft agar spatial assay. We refined the temporal assay using a previously described chemorepellent, acid, and found that H. pylori requires rich media with serum to maintain optimal swimming motility. Surprisingly, we found that some strains respond to acid as an attractant, and that the TlpC chemoreceptor correlated with whether acid was sensed as an attractant or repellent. Using this same assay, we detected weak repellent responses to nickel and copper, and a varied response to zinc. We thus developed an alternative spatial chemotactic assay called the supplemented soft agar assay, which utilizes soft agar medium supplemented with the test compound. With Escherichia coli, the attractant serine slowed overall bacterial migration, while the repellent nickel increased the speed of overall migration. In H. pylori we detected slowed migration with doubled tryptone media, as well as zinc, consistent with an attractant response. In contrast, nickel increased migration, consistent with repulsion. PMID:23139399

  15. Role of Transcription Factors in Peripheral Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Smriti ePatodia

    2012-02-01

    Full Text Available Following axotomy, the activation of multiple intracellular signalling cascades causes the expression of a cocktail of regeneration-associated transcription factors which interact with each other and the extracellular environment to determine the fate of the injured neurons. The nerve injury response is channelled through manifold and parallel pathways, integrating diverse inputs and controlling a complex transcriptional output. Transcription factors form a vital link in the chain of regeneration, converting injury-induced stress signals into downstream protein expression via gene regulation. They can regulate the intrinsic ability of axons to grow, by controlling expression of whole cassettes of gene targets. In this review, we have investigated the functional role of a number of different transcription factors – c-jun, ATF3, CREB, STAT3, C/EBP β & δ, Oct-6, Sox11, p53, NFκB, and ELK3 – in peripheral nerve regeneration. Studies involving use of conditional mutants, microarrays, promoter region mapping and different injury paradigms, have enabled us to understand their distinct as well as overlapping roles in achieving functional and anatomical regeneration after peripheral nerve injury.

  16. Plant MYB Transcription Factors: Their Role in Drought Response Mechanisms

    Science.gov (United States)

    Baldoni, Elena; Genga, Annamaria; Cominelli, Eleonora

    2015-01-01

    Water scarcity is one of the major causes of poor plant performance and limited crop yields worldwide and it is the single most common cause of severe food shortage in developing countries. Several molecular networks involved in stress perception, signal transduction and stress responses in plants have been elucidated so far. Transcription factors are major players in water stress signaling. In recent years, different MYB transcription factors, mainly in Arabidopsis thaliana (L.) Heynh. but also in some crops, have been characterized for their involvement in drought response. For some of them there is evidence supporting a specific role in response to water stress, such as the regulation of stomatal movement, the control of suberin and cuticular waxes synthesis and the regulation of flower development. Moreover, some of these genes have also been characterized for their involvement in other abiotic or biotic stresses, an important feature considering that in nature, plants are often simultaneously subjected to multiple rather than single environmental perturbations. This review summarizes recent studies highlighting the role of the MYB family of transcription factors in the adaptive responses to drought stress. The practical application value of MYBs in crop improvement, such as stress tolerance engineering, is also discussed. PMID:26184177

  17. The Role of Emerging Risk Factors in Cardiovascular Outcomes.

    Science.gov (United States)

    Lacey, Ben; Herrington, William G; Preiss, David; Lewington, Sarah; Armitage, Jane

    2017-06-01

    This review discusses the recent evidence for a selection of blood-based emerging risk factors, with particular reference to their relation with coronary heart disease and stroke. For lipid-related emerging risk factors, recent findings indicate that increasing high-density lipoprotein cholesterol is unlikely to reduce cardiovascular risk, whereas reducing triglyceride-rich lipoproteins and lipoprotein(a) may be beneficial. For inflammatory and hemostatic biomarkers, genetic studies suggest that IL-6 (a pro-inflammatory cytokine) and several coagulation factors are causal for cardiovascular disease, but such studies do not support a causal role for C-reactive protein and fibrinogen. Patients with chronic kidney disease are at high cardiovascular risk with some of this risk not mediated by blood pressure. Randomized evidence (trials or Mendelian) suggests homocysteine and uric acid are unlikely to be key causal mediators of chronic kidney disease-associated risk and sufficiently large trials of interventions which modify mineral bone disease biomarkers are unavailable. Despite not being causally related to cardiovascular disease, there is some evidence that cardiac biomarkers (e.g. troponin) may usefully improve cardiovascular risk scores. Many blood-based factors are strongly associated with cardiovascular risk. Evidence is accumulating, mainly from genetic studies and clinical trials, on which of these associations are causal. Non-causal risk factors may still have value, however, when added to cardiovascular risk scores. Although much of the burden of vascular disease can be explained by 'classic' risk factors (e.g. smoking and blood pressure), studies of blood-based emerging factors have contributed importantly to our understanding of pathophysiological mechanisms of vascular disease, and new targets for potential therapies have been identified.

  18. The role of vascular endothelial growth factor in ossification

    Science.gov (United States)

    Yang, Yan-Qi; Tan, Ying-Ying; Wong, Ricky; Wenden, Alex; Zhang, Lin-Kun; Rabie, A Bakr M

    2012-01-01

    Osteogenesis and angiogenesis are two closely correlated processes during bone growth, development, remodelling and repair. Vascular endothelial growth factor (VEGF) is an essential mediator during the process of angiogenesis. Based on an extensive literature search, which was carried out using the PubMed database and the keywords of osteogenesis, VEGF, endochondral ossification and intramembranous ossification, this manuscript reviews the role of VEGF in ossification, with emphasis on its effect in endochondral and intramembranous ossification. Osteogenesis and angiogenesis are closely correlated processes. VEGF acts as an essential mediator during these processes. It not only functions in bone angiogenesis but also in various aspects of bone development. PMID:22722639

  19. Role of tumour necrosis factor in pathogenesis of radicular cyst.

    Science.gov (United States)

    Qureshi, Waqar-ur-Rehman; Idris, Muhammad; Khan, Shahbaz Ali

    2011-01-01

    The radicular cyst is very common odontogenic cyst of the jaws, which is usually associated with a tooth with necrotic pulp. The cyst formation requires proliferation of the epithelial rest cells of Malassez present in the periodontal ligament. Proliferation of epithelial rest cells of Malassez is an essential event in the Pathogenesis of radicular cyst. The wall of the cyst contains epithelial cells, macrophages, fibroblasts and other cells. TNF is one of inflammatory mediators, which is produced by macrophages and monocytes. This study was carried out to investigate the role of tumour necrosis factor in the pathogenesis of radicular cyst, which is by far the commonest cystic lesion of the jaws. Explants from 20 radicular cysts were cultured in vitro to grow the epithelial cells. However, the cultures were rapidly contaminated with fibroblasts and it was impossible to grow the epithelial cells separately. Therefore, the proliferative effect of Tumour Necrosis Factor (TNF) was studied on mammalian epithelial cells. TNF at low concentration had a proliferative effect on the epithelial cells, which may play some role in pathogenesis of radicular cyst. TNF stimulated the epithelial cell proliferation in low concentration and inhibit the proliferation in higher concentrations. These two effects may have some implications in the pathogenesis of radicular cyst.

  20. Role of genetic factors in the pathogenesis of aggressive periodontitis.

    Science.gov (United States)

    Vieira, Alexandre R; Albandar, Jasim M

    2014-06-01

    This article critically reviews the evidence for a role of genetic factors in the pathogenesis of aggressive periodontitis and discusses the study approaches commonly used to identify genetic risk factors of this disease. Available data suggest that aggressive periodontitis is caused by mutations in multiple genes, combined with environmental effects. Syndromic periodontal diseases include certain monogenic disorders that express phenotypes showing aggressive forms of periodontitis, and the genetic triggering factors of most of these syndromes have been identified. Other periodontal disease phenotypes seem to occur through different genetic predisposition patterns. Case-control and genome-wide studies have been used to investigate the association with gene polymorphisms. Association studies and the familial aggregation of aggressive periodontitis suggest a significant genetic component in the increased predisposition to this disease. There is evidence to support the contribution of a few major genes or of multiple small-effects genes. In addition, there is evidence of gene-gene and gene-environment interaction effects. Early studies suggested an X-linked mode of transmission of aggressive periodontitis, and subsequent studies support an autosomal mode. Genetic studies have the potential to improve the screening programs of subjects at risk for developing aggressive periodontitis and may enhance treatment outcome through gene therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Evaluation of the role of genetic factors in human radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Telnov, Vitaliy I.; Sotnik, Natalie V. [Southern Ural Biophysics Institute, Ozyorsk (Russian Federation)

    2002-07-01

    This study was focused on evaluation of the role of genetic factors in development of chronic radiation sickness (CRS) due to occupational exposure to external {gamma} -rays. This study was based on results of molecular-genetic studies for 985 nuclear workers of the Mayak Production Association. CRS occurrence was related to the genetic haptoglobin (Hp) system among a number of studied genetic markers. Excess risk of CRS was revealed at similar exposure doses for individuals-carriers of Hp 2-2 (1.96) versus lower risks for carriers of Hp 1-1 and 2-1 (0.64). The contribution of genetic factors to CRS development was implemented in a rather narrow dose range, i.e. it was of a relative nature. A scheme of the relationship of affecting factor and differences in genetic radioresistance was presented in terms of deterministic effects. The obtained data did not confirm the idea that A-bomb survivors were more radioresistant, thus being not representative for radiation risk estimation.

  2. Preeclampsia and ESRD: The Role of Shared Risk Factors.

    Science.gov (United States)

    Kattah, Andrea G; Scantlebury, Dawn C; Agarwal, Sanket; Mielke, Michelle M; Rocca, Walter A; Weaver, Amy L; Vaughan, Lisa E; Miller, Virginia M; Weissgerber, Tracey L; White, Wendy; Garovic, Vesna D

    2017-04-01

    Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors. Population-based nested case-control study. The US Renal Data System was used to identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was matched to 2 controls based on year of birth (±1 year), age at first pregnancy (±2 years), and parity (±1 or ≥4). Preeclamptic pregnancy, confirmed by medical record review. ESRD. Prepregnancy serum creatinine and urine protein measurements were recorded. Comorbid conditions existing prior to pregnancy were abstracted from medical records and included kidney disease, obesity, diabetes, and hypertension. There was evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases and 1 of 88 (preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  3. Boc SPPS of two hydrophobic peptides using a ''solubilising tail'' strategy : Dodecaalanine and chemotactic protein 10(42-55)

    NARCIS (Netherlands)

    Englebretsen, DR; Alewood, PF

    1996-01-01

    The solid phase syntheses of the hydrophobic peptides dodecaalanine and chemotactic protein-10(42-55) were achieved using a ''solubilising tail'' strategy. Peptide constructs of the form H-hydrophobic peptide-glycolamide ester-(Gly-Arg)(4)-Gly-OH were synthesised by Boc SPPS. The peptide-constructs

  4. Systemic Monocyte Chemotactic Protein-1 Inhibition Modifies Renal Macrophages and Restores Glomerular Endothelial Glycocalyx and Barrier Function in Diabetic Nephropathy

    NARCIS (Netherlands)

    Boels, M.G.; Koudijs, A.; Avramut, M.C.; Sol, W.; Wang, G.; Oeveren-Rietdijk, A.M. van; Zonneveld, A.J. van; Boer, H.C. de; Vlag, J. van der; Kooten, C. van; Eulberg, D.; Berg, B.M.; DHT, I.J.; Rabelink, T.J.

    2017-01-01

    Inhibition of monocyte chemotactic protein-1 (MCP-1) with the Spiegelmer emapticap pegol (NOX-E36) shows long-lasting albuminuria-reducing effects in diabetic nephropathy. MCP-1 regulates inflammatory cell recruitment and differentiation of macrophages. Because the endothelial glycocalyx is also

  5. Promotion of formyl peptide receptor 1-mediated neutrophil chemotactic migration by antimicrobial peptides isolated from the centipede Scolopendra subspinipes mutilans.

    Science.gov (United States)

    Park, Yoo Jung; Lee, Sung Kyun; Jung, Young Su; Lee, Mingyu; Lee, Ha Young; Kim, Sang Doo; Park, Joon Seong; Koo, JaeHyung; Hwang, Jae Sam; Bae, Yoe-Sik

    2016-09-01

    We investigated the effects of two antimicrobial peptides (AMPs) isolated from Scolopendra subspinipes mutilans on neutrophil activity. Stimulation of mouse neutrophils with the two AMPs elicited chemotactic migration of the cells in a pertussis toxin-sensitive manner. The two AMPs also stimulated activation of ERK and Akt, which contribute to chemotactic migration of neutrophils. We found that AMP-stimulated neutrophil chemotaxis was blocked by a formyl peptide receptor (FPR) 1 antagonist (cyclosporin H); moreover the two AMPs stimulated the chemotactic migration of FPR1-expressing RBL-2H3 cells but not of vector-expressing RBL-2H3 cells. We also found that the two AMPs stimulate neutrophil migration in vivo, and that this effect is blocked in FPR1-deficient mice. Taken together, our results suggest that the two AMPs stimulate neutrophils, leading to chemotactic migration through FPR1, and the two AMPs will be useful for the study of FPR1 signaling and neutrophil activation. [BMB Reports 2016; 49(9): 520-525].

  6. Biodegradation of naphthalene and anthracene by chemo-tactically active rhizobacteria of populus deltoides

    Science.gov (United States)

    Bisht, Sandeep; Pandey, Piyush; Sood, Anchal; Sharma, Shivesh; Bisht, N. S.

    2010-01-01

    Several naphthalene and anthracene degrading bacteria were isolated from rhizosphere of Populus deltoides, which were growing in non-contaminated soil. Among these, four isolates, i.e. Kurthia sp., Micrococcus varians, Deinococcus radiodurans and Bacillus circulans utilized chrysene, benzene, toluene and xylene, in addition to anthracene and naphthalene. Kurthia sp and B. circulans showed positive chemotactic response for naphthalene and anthracene. The mean growth rate constant (K) of isolates were found to increase with successive increase in substrate concentration (0.5 to 1.0 mg/50ml). B. circulans SBA12 and Kurthia SBA4 degraded 87.5% and 86.6% of anthracene while, Kurthia sp. SBA4, B. circulans SBA12, and M. varians SBA8 degraded 85.3 %, 95.8 % and 86.8 % of naphthalene respectively after 6 days of incubation as determined by HPLC analysis. PMID:24031572

  7. Biodegradation of naphthalene and anthracene by chemo-tactically active rhizobacteria of populus deltoides.

    Science.gov (United States)

    Bisht, Sandeep; Pandey, Piyush; Sood, Anchal; Sharma, Shivesh; Bisht, N S

    2010-10-01

    Several naphthalene and anthracene degrading bacteria were isolated from rhizosphere of Populus deltoides, which were growing in non-contaminated soil. Among these, four isolates, i.e. Kurthia sp., Micrococcus varians, Deinococcus radiodurans and Bacillus circulans utilized chrysene, benzene, toluene and xylene, in addition to anthracene and naphthalene. Kurthia sp and B. circulans showed positive chemotactic response for naphthalene and anthracene. The mean growth rate constant (K) of isolates were found to increase with successive increase in substrate concentration (0.5 to 1.0 mg/50ml). B. circulans SBA12 and Kurthia SBA4 degraded 87.5% and 86.6% of anthracene while, Kurthia sp. SBA4, B. circulans SBA12, and M. varians SBA8 degraded 85.3 %, 95.8 % and 86.8 % of naphthalene respectively after 6 days of incubation as determined by HPLC analysis.

  8. Biodegradation of naphthalene and anthracene by chemo-tactically active rhizobacteria of populus deltoides

    Directory of Open Access Journals (Sweden)

    Sandeep Bisht

    2010-12-01

    Full Text Available Several naphthalene and anthracene degrading bacteria were isolated from rhizosphere of Populus deltoides, which were growing in non-contaminated soil. Among these, four isolates, i.e. Kurthia sp., Micrococcus varians, Deinococcus radiodurans and Bacillus circulans utilized chrysene, benzene, toluene and xylene, in addition to anthracene and naphthalene. Kurthia sp and B. circulans showed positive chemotactic response for naphthalene and anthracene. The mean growth rate constant (K of isolates were found to increase with successive increase in substrate concentration (0.5 to 1.0 mg/50ml. B. circulans SBA12 and Kurthia SBA4 degraded 87.5% and 86.6% of anthracene while, Kurthia sp. SBA4, B. circulans SBA12, and M. varians SBA8 degraded 85.3 %, 95.8 % and 86.8 % of naphthalene respectively after 6 days of incubation as determined by HPLC analysis.

  9. Natural Killer (NK)/melanoma cell interaction induces NK-mediated release of chemotactic High Mobility Group Box-1 (HMGB1) capable of amplifying NK cell recruitment.

    Science.gov (United States)

    Parodi, Monica; Pedrazzi, Marco; Cantoni, Claudia; Averna, Monica; Patrone, Mauro; Cavaletto, Maria; Spertino, Stefano; Pende, Daniela; Balsamo, Mirna; Pietra, Gabriella; Sivori, Simona; Carlomagno, Simona; Mingari, Maria Cristina; Moretta, Lorenzo; Sparatore, Bianca; Vitale, Massimo

    2015-12-01

    In this study we characterize a new mechanism by which Natural Killer (NK) cells may amplify their recruitment to tumors. We show that NK cells, upon interaction with melanoma cells, can release a chemotactic form of High Mobility Group Box-1 (HMGB1) protein capable of attracting additional activated NK cells. We first demonstrate that the engagement of different activating NK cell receptors, including those mainly involved in tumor cell recognition can induce the active release of HMGB1. Then we show that during NK-mediated tumor cell killing two HMGB1 forms are released, each displaying a specific electrophoretic mobility possibly corresponding to a different redox status. By the comparison of normal and perforin-defective NK cells (which are unable to kill target cells) we demonstrate that, in NK/melanoma cell co-cultures, NK cells specifically release an HMGB1 form that acts as chemoattractant, while dying tumor cells passively release a non-chemotactic HMGB1. Finally, we show that Receptor for Advanced Glycation End products is expressed by NK cells and mediates HMGB1-induced NK cell chemotaxis. Proteomic analysis of NK cells exposed to recombinant HMGB1 revealed that this molecule, besides inducing immediate chemotaxis, also promotes changes in the expression of proteins involved in the regulation of the cytoskeletal network. Importantly, these modifications could be associated with an increased motility of NK cells. Thus, our findings allow the definition of a previously unidentified mechanism used by NK cells to amplify their response to tumors, and provide additional clues for the emerging role of HMGB1 in immunomodulation and tumor immunity.

  10. Cardioprotective Role of Tumor Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and Necroptosis.

    Science.gov (United States)

    Guo, Xiaoyun; Yin, Haifeng; Li, Lei; Chen, Yi; Li, Jing; Doan, Jessica; Steinmetz, Rachel; Liu, Qinghang

    2017-08-22

    Programmed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. We examined the role of tumor necrosis factor receptor-associated factor 2 (Traf2) in regulating myocardial necroptosis and remodeling using genetic mouse models. We also performed molecular and cellular biology studies to elucidate the mechanisms by which Traf2 regulates necroptosis signaling. We identified a critical role for Traf2 in myocardial survival and homeostasis by suppressing necroptosis. Cardiac-specific deletion of Traf2 in mice triggered necroptotic cardiac cell death, pathological remodeling, and heart failure. Plasma tumor necrosis factor α level was significantly elevated in Traf2-deficient mice, and genetic ablation of TNFR1 largely abrogated pathological cardiac remodeling and dysfunction associated with Traf2 deletion. Mechanistically, Traf2 critically regulates receptor-interacting proteins 1 and 3 and mixed lineage kinase domain-like protein necroptotic signaling with the adaptor protein tumor necrosis factor receptor-associated protein with death domain as an upstream regulator and transforming growth factor β-activated kinase 1 as a downstream effector. It is important to note that genetic deletion of RIP3 largely rescued the cardiac phenotype triggered by Traf2 deletion, validating a critical role of necroptosis in regulating pathological remodeling and heart failure propensity. These results identify an important Traf2-mediated, NFκB-independent, prosurvival pathway in the heart by suppressing necroptotic signaling, which may serve as a new therapeutic target for pathological remodeling and heart failure. © 2017 American Heart

  11. Role of Transforming Growth Factor β in Uterine Fibroid Biology

    Directory of Open Access Journals (Sweden)

    Michał Ciebiera

    2017-11-01

    Full Text Available Uterine fibroids (UFs are benign tumors of the female genital tract made of the smooth muscle of the uterus. UF growth depends mostly on the influence of the steroid hormones and selected growth factors. Transforming growth factor β (TGF-βs is a polypeptide that consists of three isoforms: TGF-β1, TGF-β2, and TGF-β3. At present, TGF-β is considered to be one of the key factors in the pathophysiology of UFs. It plays a major role in cellular migration within the tumor, stimulates tumor growth, and enhances tumor metabolism. As a consequence of various dependencies, the synthesis and release of TGF-β in a UF tumor is increased, which results in excessive extracellular matrix production and storage. High concentrations or overexpression of TGF-β mediators may be responsible for clinically symptomatic UFs. The aim of this review was to check the available evidence for the influence of the TGF-β family on UF biology. We conducted their search in PubMed of the National Library of Medicine with the use of the following selected keywords: “uterine fibroid”, “leiomyoma”, and “transforming growth factor β”. After reviewing the titles and abstracts, more than 115 full articles were evaluated. We focused on the TGF-β-related molecular aspects and their influence on the most common symptoms that are associated with UFs. Also, we described how the available data might implicate the current medical management of UFs.

  12. A role for the transcription factor HEY1 in glioblastoma

    DEFF Research Database (Denmark)

    Hulleman, Esther; Quarto, Micaela; Vernell, Richard

    2009-01-01

    Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes...... and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally......, we show that ectopic expression of HEY1 induces cell proliferation in neural stem cells, while depletion of HEY1 by RNA interference reduces proliferation of glioblastoma cells in tissue culture. Together, these data imply a role for HEY1 in the progression of GBM, and therefore we propose that HEY1...

  13. Prevention and schizophrenia--the role of dietary factors.

    Science.gov (United States)

    McGrath, John; Brown, Alan; St Clair, David

    2011-03-01

    Adequate prenatal nutrition is essential for optimal brain development. There is a growing body of evidence from epidemiology linking exposure to nutritional deprivation and increased risk of schizophrenia. Based on studies from the Netherlands and China, those exposed to macronutrient deficiencies during famine have an increased risk of schizophrenia. With respect to micronutrients, we focus on 3 candidates where there is biological plausibility for a role in this disorder and at least 1 study of an association with schizophrenia. These nutrients include vitamin D, folic acid, and iron. While the current evidence is incomplete, we discuss the potential implications of these findings for the prevention of schizophrenia. We argue that schizophrenia can draw inspiration from public health interventions related to prenatal nutrition and other outcomes and speculate on relevant factors that bear on the nature, risks, impact, and logistics of various nutritional strategies that may be employed to prevent this disorder.

  14. Prevention and Schizophrenia—The Role of Dietary Factors

    Science.gov (United States)

    McGrath, John; Brown, Alan; St Clair, David

    2011-01-01

    Adequate prenatal nutrition is essential for optimal brain development. There is a growing body of evidence from epidemiology linking exposure to nutritional deprivation and increased risk of schizophrenia. Based on studies from the Netherlands and China, those exposed to macronutrient deficiencies during famine have an increased risk of schizophrenia. With respect to micronutrients, we focus on 3 candidates where there is biological plausibility for a role in this disorder and at least 1 study of an association with schizophrenia. These nutrients include vitamin D, folic acid, and iron. While the current evidence is incomplete, we discuss the potential implications of these findings for the prevention of schizophrenia. We argue that schizophrenia can draw inspiration from public health interventions related to prenatal nutrition and other outcomes and speculate on relevant factors that bear on the nature, risks, impact, and logistics of various nutritional strategies that may be employed to prevent this disorder. PMID:20974747

  15. Role of hypoxia-inducible factors in acute kidney injury.

    Science.gov (United States)

    Andringa, Kelly K; Agarwal, Anupam

    2014-01-01

    Oxygen is vital to mammalian survival. Oxygen deprivation, defined as hypoxia, elicits adaptive responses in cells and tissues, a process regulated by proteins known as hypoxia-inducible factors (HIF). Animal studies have provided compelling data to demonstrate a pivotal role for the HIF pathway in the pathogenesis of acute kidney injury (AKI) that have led to initial human clinical trials examining this pathway in ischemia-reperfusion injury in various organ systems, including the kidney. HIF are master regulators and mediate adaptive responses to low oxygen in tissues and cells. This review will summarize recent key advances in the field highlighting preclinical and clinical studies relevant to the HIF pathway in the pathophysiology of AKI. 2014 S. Karger AG, Basel.

  16. The role of selected chemokines and their receptors in the pathogenesis and destabilisation of atheromatous plaques in the carotid arteries

    Directory of Open Access Journals (Sweden)

    Maria Konarska-Król

    2015-04-01

    Full Text Available Chemokines are cytokines that act selectively on cells and are capable of inducing selective migration of cells in vitro and in vivo. The term was first coined at the 3rd International Symposium on Chemotactic Cytokines in 1992. The name “chemokine” is a contraction of “chemotactic cytokine,” meaning that these molecules combine features of both cytokines and chemotactic factors. They are a family of low-molecular-mass proteins acting on specific membrane receptors. A cell’s overall sensitivity to chemotaxis depends on the expression profile of chemokine receptors. Atherosclerosis is essentially an excessive inflammatory and proliferative response to the damage of arterial walls. It takes place within the wall and leads to the formation of unstable atherosclerotic plaques. Many chemokines have been studied in terms of their role in the pathogenesis of an atheromatous plaque in the carotid arteries, both in animal models and with the use of human tissue. It  seems that molecules that are the most involved in the formation of atheromas in the carotid arteries include: CCL2, CCL3, CCL4 and CCL5. However, reports are sometimes contradictory, and more research is needed. Finding a marker that could help predict the destabilisation of an atheromatous plaque would be a valuable addition to the standard diagnostic panel of tests used in both the diagnosis and monitoring of vascular pathologies.

  17. Role of biochemical factors in the pathogenesis of keratoconus.

    Science.gov (United States)

    Wojcik, Katarzyna A; Blasiak, Janusz; Szaflik, Jerzy; Szaflik, Jacek P

    2014-01-01

    Keratoconus (KC) is a corneal disease associated with structural abnormalities in the corneal epithelium, Bowman's layer and stroma and altered concentration of tear components. KC corneas show a different pattern of collagen lamellae than their normal counterparts. Also, a reduction of several collagen types in KC epithelium and stroma was observed. Altered expression and/or activity of lysyl oxidase, a critical enzyme of the biogenesis of connective tissue detected in KC corneas, may weaken covalent bonds between collagen and elastin fibrils, what may lead to biomechanical deterioration of the cornea. Increased activity of matrix metalloproteinases observed in KC may induce the degradation of the extracellular matrix causing damage to the cornea. Oxidative and nitrative stress play an important role in KC pathogenesis and KC corneas are characterized by the disturbed lipid peroxidation and nitric oxide pathways. Malfunctioning of these pathways may lead to accumulation of their toxic by-products inducing several detrimental effects, along with apoptosis of the corneal cells, which may result from the loss of β-actin or increased levels of cytokines, including interleukin-1 and -6. Change in the expression of genes associated with wound healing, including the nerve growth factor and the visual system homeobox 1, may contribute to increased susceptibility of KC corneas to injury. Consequently, biochemical changes may play an important role in KC pathophysiology and, therefore, can be considered in prevention, diagnosis, prognosis and in the therapy of this disease as well.

  18. Improving English Speaking Fluency: The Role of Six Factors

    Directory of Open Access Journals (Sweden)

    Gholamhossein Shahini

    2017-12-01

    Full Text Available This qualitative study, using an open interview, set out to investigate the roles six factors, including age, university education, teachers of English Language institutes, teaching English, dictionary, and note-taking, played in improving English speaking fluency of seventeen fluent Iranian EFL speakers. The participants were chosen purposefully based on the speaking scale of Common European Framework of Reference for Languages (CEFRL. The findings indicated that early age had a great impact on the participants’ speaking fluency. They mentioned that they could not pick up fluency if they had started learning English at older ages. Moreover, university education had no effect on enhancing their fluency. They stated that not having enough opportunities to speak English in classrooms, being exposed to wrong amounts of input from their classmates or even from some university instructors, having no access to English native speakers in English Language Departments, professors’ talking in native language out of classes, in their offices or even sometimes in classes all led to their losing motivation after entering the university. In contrast, teachers in English language institutes had a supportive role in increasing the participants’ English learning. Although two participants quit teaching English since it had a negative influence on their speaking, it had a positive impact on improving speaking ability of the rest. And finally, fruitful strategies were suggested on how to use dictionaries and note-takings.

  19. Dynamic plasticity: the role of glucocorticoids, brain-derived neurotrophic factor and other trophic factors.

    Science.gov (United States)

    Gray, J D; Milner, T A; McEwen, B S

    2013-06-03

    Brain-derived neurotrophic factor (BDNF) is a secreted protein that has been linked to numerous aspects of plasticity in the central nervous system (CNS). Stress-induced remodeling of the hippocampus, prefrontal cortex and amygdala is coincident with changes in the levels of BDNF, which has been shown to act as a trophic factor facilitating the survival of existing and newly born neurons. Initially, hippocampal atrophy after chronic stress was associated with reduced BDNF, leading to the hypothesis that stress-related learning deficits resulted from suppressed hippocampal neurogenesis. However, recent evidence suggests that BDNF also plays a rapid and essential role in regulating synaptic plasticity, providing another mechanism through which BDNF can modulate learning and memory after a stressful event. Numerous reports have shown BDNF levels are highly dynamic in response to stress, and not only vary across brain regions but also fluctuate rapidly, both immediately after a stressor and over the course of a chronic stress paradigm. Yet, BDNF alone is not sufficient to effect many of the changes observed after stress. Glucocorticoids and other molecules have been shown to act in conjunction with BDNF to facilitate both the morphological and molecular changes that occur, particularly changes in spine density and gene expression. This review briefly summarizes the evidence supporting BDNF's role as a trophic factor modulating neuronal survival, and will primarily focus on the interactions between BDNF and other systems within the brain to facilitate synaptic plasticity. This growing body of evidence suggests a more nuanced role for BDNF in stress-related learning and memory, where it acts primarily as a facilitator of plasticity and is dependent upon the coactivation of glucocorticoids and other factors as the determinants of the final cellular response. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Epigallocatechin-3-Gallate Inhibits Matrix Metalloproteinase-9 and Monocyte Chemotactic Protein-1 Expression Through the 67-κDa Laminin Receptor and the TLR4/MAPK/NF-κB Signalling Pathway in Lipopolysaccharide-Induced Macrophages

    Directory of Open Access Journals (Sweden)

    Ya-Fei Li

    2017-09-01

    Full Text Available Background/Aims: Epigallocatechin-3-gallate (EGCG, a major catechin found in green tea, has been shown to prevent cardiovascular diseases. Previously, Matrix metalloproteinase-9 (MMP-9, monocyte chemotactic protein-1 (MCP-1 and toll-like receptor 4 (TLR4 were confirmed to play an important role in atherosclerosis and plaque instability. Both TLR4 and its negative regulator, Toll-interacting protein (Tollip, could be mediated by EGCG. The present study aimed to examine the effect of physiological concentration of EGCG (1 µM on the expression of MMP-9 and MCP-1 in lipopolysaccharide (LPS-induced macrophages and the potential mechanisms underlying its actions. Methods: The RAW264.7 cell line was used. Western blot was used to determine MCP-1, TLR4, Tollip, Mitogen-activated protein kinase (MAPK and Nuclear factor-κB (NF-κB protein expression. MMP-9 activity was assayed by gelatine zymography. The mRNA expression of MMP-9 and MCP-1 was measured by realtime polymerase chain reaction (RT-PCR. Results: EGCG (1 µM significantly suppressed the expression of MMP-9 and MCP-1 and inhibited MAPK and NF-κB in LPS-induced macrophages but was blocked by Tollip silencing. The expression of LPS-induced MMP-9 and MCP-1 and the phosphorylation of the ERK1/2, P38 and NF-κB pathway proteins decreased after TLR4 siRNA treatment. Furthermore, EGCG mediated TLR4 and Tollip expression through binding to 67-kDa laminin receptor (67LR. Conclusion: The results of our study suggested that EGCG (1 µM suppresses the TLR4/MAPK/NF-κB signalling pathway, decreases the expression of the plaque instability-mediating cytokines MMP-9 and MCP-1, and might prove to be effective in stabilizing atherosclerotic plaque.

  1. Brain-derived neurotrophic factor: role in depression and suicide

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2009-08-01

    Full Text Available Yogesh DwivediPsychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF, one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB and its splice variant (TrkB.T1 have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.Keywords: BDNF, neurotrophins, p75NTR, Trk receptor, depression, antidepressants, suicide, genetics, epigenetics

  2. The role of leukemia inhibitory factor in tubal ectopic pregnancy.

    Science.gov (United States)

    Krishnan, T; Winship, A; Sonderegger, S; Menkhorst, E; Horne, A W; Brown, J; Zhang, J-G; Nicola, N A; Tong, S; Dimitriadis, E

    2013-11-01

    Ectopic pregnancy is unique to humans and a leading cause of maternal morbidity and mortality. The etiology remains unknown however factors regulating embryo implantation likely contribute. Leukemia inhibitory factor (LIF) has roles in extravillous trophoblast adhesion and invasion and is present in ectopic implantation sites. We hypothesised that LIF facilitates blastocyst adhesion/invasion in the Fallopian tube, contributing to ectopic pregnancy. We immunolocalised LIF receptor (R) in tubal ectopic pregnancy (N = 5). We used an oviduct cell line (OE-E6/E7) to model Fallopian tube epithelial cells and a trophoblast spheroid co-culture model (HTR-8/SVneo cell line formed spheroids) to model blastocyst attachment to the Fallopian tube. We examined LIF signaling pathways in OE-E6/E7 cells by Western blot. The effect of LIF and LIF inhibition (using a novel LIF inhibitor, PEGLA) on first-trimester placental outgrowth was determined. LIFR localised to villous and extravillous trophoblast and Fallopian tube epithelium in ectopic pregnancy. LIF activated STAT3 but not the ERK pathway in OE-E6/E7 cells. LIF stimulated HTR-8/SVneo spheroid adhesion to OE-E6/E7 cells which was significantly reduced after PEGLA treatment. LIF promoted placental explants outgrowth, while co-treatment with PEGLA blocked outgrowth. Our data suggests LIF facilitates the development of ectopic pregnancy by stimulating blastocyst adhesion and trophoblast outgrowth from placental explants. Ectopic pregnancy is usually diagnosed after 6 weeks of pregnancy, therefore PEGLA may be useful in targeting trophoblast growth/invasion. LIF may contribute to the development of ectopic pregnancies and that pharmacologically targeting LIF-mediated trophoblast outgrowth may be useful as a treatment for ectopic pregnancy. Copyright © 2013. Published by Elsevier Ltd.

  3. Sex differences in human mortality: the role of genetic factors.

    Science.gov (United States)

    Waldron, I

    1983-01-01

    's endogenous sex hormones may reduce women's risk of ischemic heart disease. For both violent deaths and ischemic heart disease it appears that any genetic contributions to sex differences in mortality are strongly reinforced by the cultural influences that foster more risky behavior in males, including more use of weapons, employment in hazardous occupations, heavy alcohol consumption and cigarette smoking. It appears that these cultural influences on sex differences in behavior are widespread cross-culturally in part because of the effects of inherent sex differences in reproductive functions on the cultural evolution of sex roles. These examples illustrate the complexity and importance of interactions between genetic and environmental factors in determining sex differences in human mortality.

  4. Targeting cancer stem cells: emerging role of Nanog transcription factor

    Directory of Open Access Journals (Sweden)

    Wang ML

    2013-09-01

    Full Text Available Mong-Lien Wang,1 Shih-Hwa Chiou,2,3 Cheng-Wen Wu1,4–61Institute of Biochemistry and Molecular Biology, 2Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan; 3Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Microbiology and Immunology, 5Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; 6Institute of Biomedical Science, Academia Sinica, Taipei, TaiwanAbstract: The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the

  5. The role of fibroblast growth factor 21 in atherosclerosis.

    Science.gov (United States)

    Kokkinos, John; Tang, Shudi; Rye, Kerry-Anne; Ong, Kwok Leung

    2017-02-01

    The metabolic properties of the endocrine fibroblast growth factor 21 (FGF21) have been extensively studied in the past decade. Previous studies have demonstrated the lipid-lowering, anti-inflammatory and anti-oxidant properties of FGF21. FGF21 is mainly secreted in the liver and adipose tissue in response to a range of physiological and pathological stimuli. In animal and in vitro studies, FGF21 has been shown to improve lipid profiles and inhibit key processes in the pathogenesis of atherosclerosis. It exerts its effects on the cardiovascular system via adiponectin dependent and independent mechanisms. However, the signalling pathways by which FGF21 exerts its effects on endothelial cells remains unknown and needs to be further investigated. The elevation of circulating FGF21 levels in cardiovascular disease has also raised questions as to whether FGF21 can be used as a biomarker to predict subclinical atherosclerosis and cardiovascular events. Recent findings from population studies must be validated in independent cohorts before FGF21 can be used as a biomarker in the clinical setting. The anti-atherosclerotic effects of FGF21 have been investigated in two recent clinical trials, where treatment with an FGF21 analog significantly improved the cardiometabolic profile in obese patients with type 2 diabetes. This review will evaluate recent advances that suggest there may be a role for FGF21 in atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Accumulation of natural killer cells in ischemic brain tissues and the chemotactic effect of IP-10.

    Science.gov (United States)

    Zhang, Yao; Gao, Zhongming; Wang, Dandan; Zhang, Tongshuai; Sun, Bo; Mu, Lili; Wang, Jinghua; Liu, Yumei; Kong, Qingfei; Liu, Xijun; Zhang, Yue; Zhang, Haoqiang; He, Jiqing; Li, Hulun; Wang, Guangyou

    2014-04-17

    Stroke is accompanied by a distinguished inflammatory reaction that is initiated by the infiltration of immunocytes, expression of cytokines, and other inflammatory mediators. As natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system, we investigated the mechanism of NK cells-induced brain injuries after cerebral ischemia and the chemotactic effect of IP-10 simultaneously. NK cells infiltration, interferon-gamma (IFN-γ) and IP-10 expression were detected by immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence intensity of isolated NK cells was measured by flow cytometry. The neuronal injury made by NK cells was examined via apoptosis experiment. The chemotactic of IP-10 was detected by migration and permeability assays. In human ischemic brain tissue, infiltrations of NK cells were observed and reached a peak at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model, infiltration of NK cells into the ischemic infarct region reached their highest levels 12 hours after ischemia. IFN-γ-positive NK cells and levels of the chemokine IP-10 were also detected within the ischemic region, from 6 hours up to 4 days after pMCAO was performed, and IFN-γ levels decreased after NK cells depletion in vivo. Co-culture experiments of neural cells with NK cells also showed that neural necrosis was induced via IFN-γ. In parallel experiments with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10 via CXCR3, and the effect was dose-dependent. After IP-10 depletion in vivo, NK cells decreased. In migration assays and permeability experiments, disintegration of the blood-brain barrier (BBB) was observed following the addition of NK cells. Moreover, in the presence of IP-10 this injury was aggravated. All findings

  7. Functional role of hepatocyte growth factor receptor during sperm maturation.

    Science.gov (United States)

    Catizone, A; Ricci, G; Galdieri, M

    2002-01-01

    Mammalian spermatozoa acquire motility and fertilizing capacity during their transit through the epididymis. Hepatocyte growth factor (HGF) is a pleiotropic cytokine with potent motogenic capacities that has been identified in different organs, including the mammalian male genital tract. In mice, HGF is present in the testis and, in large amounts, in the distal part of the epididymis. In prepuberal rats, we have demonstrated that HGF is synthesized by the peritubular myoid cells and in men, HGF is present in significant quantities in seminal plasma. It has been suggested that in mice, HGF has a role in initiating sperm motility, whereas in men, no significant correlations between HGF concentration and sperm motility have been found. In the present paper we report that in rats, HGF receptor, c-met, is expressed in testicular and epididymal spermatozoa. Through immunocytochemistry, we have found that c-met is exclusively localized on the head in testicular sperm. A different localization of c-met has been found in sperm isolated from caput and cauda epididymidis. Cells isolated from epididymal caput show a c-met localization exclusively restricted to the head in most cells. In a minority of caput epididymis spermatozoa the receptor is localized both in the cell head and along the flagellum. Spermatozoa isolated from the epididymal cauda were quite homogeneous, showing the receptor localized along the entire cell surface. We also report that HGF is synthesized and secreted by the rat epididymis as indicated by the scatter effect of epididymal cell homogenate and culture medium on MDCK cells. To clarify whether HGF is involved in the acquisition of sperm motility in the epididymis, its maintenance, or both, spermatozoa isolated from caput epididymidis have been cultured in medium alone or supplemented with HGF. The results obtained indicated that HGF has a positive effect on the maintenance of sperm motility which, in the absence of HGF, significantly decreases during

  8. Chemokine Concentrations and Mast Cell Chemotactic Activity in BAL Fluid in Patients With Eosinophilic Bronchitis and Asthma, and in Normal Control Subjects

    National Research Council Canada - National Science Library

    Woodman, Lucy; Sutcliffe, Amanda; Kaur, Davinder; Berry, Mike; Bradding, Peter; Pavord, Ian D; Brightling, Christopher E

    2006-01-01

    ...: To investigate the concentration of chemokines in bronchial wash samples and BAL fluid, and the mast cell chemotactic activity in BAL fluid from subjects with asthma and eosinophilic bronchitis...

  9. Modification of β-Defensin-2 by Dicarbonyls Methylglyoxal and Glyoxal Inhibits Antibacterial and Chemotactic Function In Vitro.

    Directory of Open Access Journals (Sweden)

    Janna G Kiselar

    Full Text Available Beta-defensins (hBDs provide antimicrobial and chemotactic defense against bacterial, viral and fungal infections. Human β-defensin-2 (hBD-2 acts against gram-negative bacteria and chemoattracts immature dendritic cells, thus regulating innate and adaptive immunity. Immunosuppression due to hyperglycemia underlies chronic infection in Type 2 diabetes. Hyperglycemia also elevates production of dicarbonyls methylgloxal (MGO and glyoxal (GO.The effect of dicarbonyl on defensin peptide structure was tested by exposing recombinant hBD-2 (rhBD-2 to MGO or GO with subsequent analysis by MALDI-TOF MS and LC/MS/MS. Antimicrobial function of untreated rhBD-2 vs. rhBD-2 exposed to dicarbonyl against strains of both gram-negative and gram-positive bacteria in culture was determined by radial diffusion assay. The effect of dicarbonyl on rhBD-2 chemotactic function was determined by chemotaxis assay in CEM-SS cells.MGO or GO in vitro irreversibly adducts to the rhBD-2 peptide, and significantly reduces antimicrobial and chemotactic functions. Adducts derive from two arginine residues, Arg22 and Arg23 near the C-terminus, and the N-terminal glycine (Gly1. We show by radial diffusion testing on gram-negative E. coli and P. aeruginosa, and gram-positive S. aureus, and a chemotaxis assay for CEM-SS cells, that antimicrobial activity and chemotactic function of rhBD-2 are significantly reduced by MGO.Dicarbonyl modification of cationic antimicrobial peptides represents a potential link between hyperglycemia and the clinical manifestation of increased susceptibility to infection, protracted wound healing, and chronic inflammation in undiagnosed and uncontrolled Type 2 diabetes.

  10. Human papillomavirus deregulates the response of a cellular network comprising of chemotactic and proinflammatory genes.

    Directory of Open Access Journals (Sweden)

    Rezaul Karim

    Full Text Available Despite the presence of intracellular pathogen recognition receptors that allow infected cells to attract the immune system, undifferentiated keratinocytes (KCs are the main targets for latent infection with high-risk human papilloma viruses (hrHPVs. HPV infections are transient but on average last for more than one year suggesting that HPV has developed means to evade host immunity. To understand how HPV persists, we studied the innate immune response of undifferentiated human KCs harboring episomal copies of HPV16 and 18 by genome-wide expression profiling. Our data showed that the expression of the different virus-sensing receptors was not affected by the presence of HPV. Poly(I:C stimulation of the viral RNA receptors TLR3, PKR, MDA5 and RIG-I, the latter of which indirectly senses viral DNA through non-self RNA polymerase III transcripts, showed dampening in downstream signalling of these receptors by HPVs. Many of the genes downregulated in HPV-positive KCs involved components of the antigen presenting pathway, the inflammasome, the production of antivirals, pro-inflammatory and chemotactic cytokines, and components downstream of activated pathogen receptors. Notably, gene and/or protein interaction analysis revealed the downregulation of a network of genes that was strongly interconnected by IL-1β, a crucial cytokine to activate adaptive immunity. In summary, our comprehensive expression profiling approach revealed that HPV16 and 18 coordinate a broad deregulation of the keratinocyte's inflammatory response, and contributes to the understanding of virus persistence.

  11. Elevated acetoacetate and monocyte chemotactic protein-1 levels in cord blood of infants of diabetic mothers.

    Science.gov (United States)

    Kurepa, Dalibor; Pramanik, Arun K; Kakkilaya, Venkatakrishna; Caldito, Gloria; Groome, Lynn J; Bocchini, Joseph A; Jain, Sushil K

    2012-01-01

    Infants of diabetic mothers (IDMs) are at increased risk for metabolic complications. Type 1 and some type 2 diabetic patients have elevated levels of the ketone bodies acetoacetate (AA) and β-hydroxybutyrate (BHB). The aim of this study was to examine how hyperketonemia in diabetic mothers affects markers of inflammation and oxidative stress in their offspring. Blood was obtained from 23 diabetic mothers and 13 healthy mothers and their infants' umbilical cords at delivery. Interleukin-8, monocyte chemotactic protein-1 (MCP-1) and protein carbonyl (protein oxidation) levels were determined by ELISA. U937 human monocyte cell culture was used to examine the effect of AA and BHB on secretion of MCP-1. There was a significant increase in the levels of AA in cord blood of IDMs compared with cord blood of infants of healthy mothers. A significant increase in the levels of protein oxidation (p IDMs. The level of MCP-1 correlated significantly (r = 0.51, p = 0.01) with the concentration of AA in the IDMs. In further experiments with cultured monocytes treated with exogenous AA (0-4 mM), a significant increase in MCP-1 secretion was observed in AA- but not BHB-treated monocytes. Blood levels of AA and MCP-1 are elevated in IDMs, which may contribute to the development of the metabolic complications seen in IDMs. Copyright © 2012 S. Karger AG, Basel.

  12. The actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

    Science.gov (United States)

    Westendorf, Christian; Negrete, Jose, Jr.; Bae, Albert; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

    2013-03-01

    We report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. The averaged F-actin response of many cells to a short-time pulse of cAMP is reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. We systematically exposed a large number of cells to periodic pulse trains. The results indicate a resonance peak at periodic inputs of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the actin regulatory network. To quantitatively test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and Aip1. These served as markers of the F-actin disassembly process and thus allow us to estimate the delay time. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed experimentally. Financial support by the Max-Planck Society and the DFG (SFB 937).

  13. Plant-adapted Escherichia coli show increased lettuce colonizing ability, resistance to oxidative stress and chemotactic response.

    Directory of Open Access Journals (Sweden)

    Maria de los Angeles Dublan

    Full Text Available Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety.This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency.These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues.

  14. The Role of Factoring for Financing Small and Medium Enterprises

    OpenAIRE

    Klapper, Leora

    2005-01-01

    Around the world, factoring is a growing source of external financing for corporations and small and medium-size enterprises (SMEs). What is unique about factoring is that the credit provided by a lender is explicitly linked to the value of a supplier's accounts receivable and not the supplier's overall creditworthiness. Therefore, factoring allows high-risk suppliers to transfer their credit risk to their high-quality buyers. Factoring may be particularly useful in countries with weak judici...

  15. Eosinophil recruitment and activation: the role of lipid mediators.

    Science.gov (United States)

    Luna-Gomes, Tatiana; Bozza, Patrícia T; Bandeira-Melo, Christianne

    2013-01-01

    Eosinophils are effector cells that migrate toward several mediators released at inflammatory sites to perform their multiple functions. The mechanisms driving eosinophil selective accumulation in sites of allergic inflammation are well-established and involve several steps controlled by adhesion molecules, priming agents, chemotactic, and surviving factors. Even though the majority of studies focused on role of protein mediators like IL-5 and eotaxins, lipid mediators also participate in eosinophil recruitment and activation. Among the lipid mediators with distinguish eosinophil recruitment and activation capabilities are platelet activating factor and the eicosanoids, including leukotriene B4, cysteinyl leukotrienes, and prostaglandin D2. In this review, we focused on the role of these four lipid mediators in eosinophil recruitment and activation, since they are recognized as key mediators of eosinophilic inflammatory responses.

  16. Role of Transforming Growth Factor Beta in Human Cancer

    National Research Council Canada - National Science Library

    Rebecca L. Elliott; Gerard C. Blobe

    2005-01-01

    Transforming growth factor beta (TGF-beta) is a ubiquitous and essential regulator of cellular and physiologic processes including proliferation, differentiation, migration, cell survival, angiogenesis, and immunosurveillance...

  17. Mytilus galloprovincialis myticin C: a chemotactic molecule with antiviral activity and immunoregulatory properties.

    Directory of Open Access Journals (Sweden)

    Pablo Balseiro

    Full Text Available Previous research has shown that an antimicrobial peptide (AMP of the myticin class C (Myt C is the most abundantly expressed gene in cDNA and suppressive subtractive hybridization (SSH libraries after immune stimulation of mussel Mytilus galloprovincialis. However, to date, the expression pattern, the antimicrobial activities and the immunomodulatory properties of the Myt C peptide have not been determined. In contrast, it is known that Myt C mRNA presents an unusual and high level of polymorphism of unidentified biological significance. Therefore, to provide a better understanding of the features of this interesting molecule, we have investigated its function using four different cloned and expressed variants of Myt C cDNA and polyclonal anti-Myt C sera. The in vivo results suggest that this AMP, mainly present in hemocytes, could be acting as an immune system modulator molecule because its overexpression was able to alter the expression of mussel immune-related genes (as the antimicrobial peptides Myticin B and Mytilin B, the C1q domain-containing protein MgC1q, and lysozyme. Moreover, the in vitro results indicate that Myt C peptides have antimicrobial and chemotactic properties. Their recombinant expression in a fish cell line conferred protection against two different fish viruses (enveloped and non-enveloped. Cell extracts from Myt C expressing fish cells were also able to attract hemocytes. All together, these results suggest that Myt C should be considered not only as an AMP but also as the first chemokine/cytokine-like molecule identified in bivalves and one of the few examples in all of the invertebrates.

  18. Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.

    Directory of Open Access Journals (Sweden)

    Cheng-Yuk Lee

    Full Text Available Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis as well as upon contact (by serum-dependent adhesion and phagocytosis. This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

  19. Determination of factors affecting role performance of contact ...

    African Journals Online (AJOL)

    Result further indicated that major determinants of contact farmer's effectiveness in technology transfer included personal, motivational, endogenous environmental and exogenous environmental factors. The study recommends careful selection of contact farmers and adequate check to these factors to ensure positive effect ...

  20. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy

    African Journals Online (AJOL)

    elevation of hypoxia inducible factor (HIF), which in turn leads to increases in levels of VEGF and other angiogenic factors. This adaptive response delays progression from pathological cardiac hypertrophy to heart failure. In early cardiac hypertrophy, stability of HIF-1 promotes glycolysis, which improves glucose utilization ...

  1. Role of environmental and genetic factors in autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Zakia Sultana

    2017-05-01

    Full Text Available The aim of this study was to find out the environmental as well as genetic factors responsible for increasing the number of autism spectrum disorder (ASD patients in Bangladesh. A questionnaire was developed based on 12 environmental factors and genetic aspects. Sixty six patients of ASD and 66 non-ASD control were selected randomly. Among the environmental factors, the age of the mother, premature birth, air pollution, age of the father, hypoxia during childbirth and oral contraceptive came out as significant (p<0.05 factors for ASD incidence compared to the control. Association of multiple factors on an individual was found to be crucial to enhance the risk and exposure to five and six factors was statistically significant (p<0.05 for ASD development. Prospective parents should try to keep the number of risk factors as low as possible before 1-2 months of pregnancy, during pregnancy and 1-2 years after the child birth (for child only.

  2. The Role of Individual and Social Factors in Classroom Loneliness

    Science.gov (United States)

    Stoeckli, Georg

    2009-01-01

    The author investigated the role of individual characteristics (self-esteem, social anxiety, and self-reported classroom participation) and peer reactions (peer-perceived shyness, peer nominations) in classroom loneliness in a sample of 704 preadolescent boys (360) and girls (344). It was hypothesized that classroom participation functions as a…

  3. Organizational factors in fire prevention: roles, obstacles, and recommendations

    Science.gov (United States)

    John R. Christiansen; William S. Folkman; Keith W. Warner; Michael L. Woolcott

    1976-01-01

    Problems being encountered in implementing fire prevention programs were explored by studying the organization for fire prevention at the Fish Lake, Uinta, and Wasatch National Forests in Utah. The study focused on role congruency in fire prevention activities and on the social and organizational obstacles to effective programs. The problems identified included lack of...

  4. Role of GATA Transcription Factors in the T Cell Lineage

    NARCIS (Netherlands)

    J.P. van Hamburg (Jan Piet)

    2008-01-01

    textabstractT lymphocytes play a central role in the mammalian immune response against potentially hazardous pathogens, such as parasites, bacteria, viruses and fungi. These cells have the remarkable capacity to specifically recognize foreign substances, termed antigens, to which they respond by

  5. Molecular aspects of rheumatoid arthritis: role of environmental factors.

    Science.gov (United States)

    Kobayashi, Shu; Momohara, Shigeki; Kamatani, Naoyuki; Okamoto, Hiroshi

    2008-09-01

    Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease that affects 0.5-1% of the population. RA causes progressive joint destruction that leads to the restriction of activities of daily living and deterioration of quality of life. Although the pathogenesis of RA has not yet been fully elucidated, it is considered to be a complex, multifarious disease that is influenced by both genetic and environmental factors. Genetic influences that contribute to RA susceptibility have been demonstrated both in studies of twins and families, as well as in genome-wide linkage scans, and it is estimated that genetic factors are responsible for 50-60% of the risk of developing RA. Thus, environmental factors may explain the remaining risk of developing RA. A large variety of environmental factors such as infectious agents, smoking, sex hormones, pregnancy etc. have been extensively studied previously. Understanding of how these factors contribute to the development of RA may lead to the better understanding of pathogenesis of RA.

  6. The Role of Individual and Training Design Factors on Training Transfer

    Science.gov (United States)

    Bhatti, Muhammad Awais; Kaur, Sharan

    2010-01-01

    Purpose: The purpose of this study is to highlight the role of individual and training design factors on training transfer. Design/methodology/approach: A review of the literature is conducted, and this review highlights a dual role of perceived content validity in the form of increasing self-efficacy and the role of trainees' reaction. The study…

  7. The role of organisational factors in combating tacit knowledge loss ...

    African Journals Online (AJOL)

    2002) points out that “knowledge has become the most important factor in economic ... The importance of knowledge is emphasised by a European survey of 100 European business leaders, in which 89% considered “knowledge to be the key business power” ...... and antecedents', Journal of Business Ethics, 70: 411–428.

  8. The Role of WRKY Transcription Factors in Plant Immunity

    National Research Council Canada - National Science Library

    Shree P. Pandey; Imre E. Somssich

    2009-01-01

    ... variable environments, is mainly achieved by enforcement of a network of various transcription factors (TFs). WRKY TFs are a large family of regulatory proteins forming such a network (Eulgem and Somssich, 2007). They are involved in various plant processes but most notably in coping with diverse biotic and abiotic stresses. In this update, we will re...

  9. Perceived Role Of Dietary Factors In Cancer Causation And ...

    African Journals Online (AJOL)

    With the relatively high degree of awareness of cancer and acceptance of dietary factors as cancer risk determinants, campaigns which involve skill transfer and removal of barriers to change would enhance cancer preventive behaviour among university undergraduate. It is recommended that improvement in health ...

  10. The role of neoangiogenesis and vascular endothelial growth factor ...

    African Journals Online (AJOL)

    2015-10-28

    Oct 28, 2015 ... supply in the median nerve under transverse carpal ligament. Systemic factors facilitate the formation of the syndrome. ... of the wrist where the median nerve becomes compressed in the carpal tunnel. CTS symptoms include pain in the ..... mesangial expansion. As the disease progresses, the level of VEGF ...

  11. The role of organisational factors in combating tacit knowledge loss ...

    African Journals Online (AJOL)

    5Knowledge loss poses a challenge to organisations that wish to remain competitive. The meaning of knowledge that exists in the minds of people and its manifestation in organisations is examined to provide a framework for the investigation of organisational human input factors and strategic risks of knowledge loss.

  12. Readiness for College: The Role of Noncognitive Factors and Context

    Science.gov (United States)

    Nagaoka, Jenny; Farrington, Camille A.; Roderick, Melissa; Allensworth, Elaine; Keyes, Tasha Seneca; Johnson, David W.; Beechum, Nicole O.

    2013-01-01

    Research has shown that in addition to academic knowledge, a variety of noncognitive skills are essential to students' post-secondary success. This article summarizes a review by the University of Chicago Consortium on Chicago School Research (CCSR) that brought together hundreds of studies of factors that have been tied to academic success…

  13. Role of chromatin factors in Arabidopsis root stem cell maintenance

    NARCIS (Netherlands)

    Kornet, N.G.

    2008-01-01

    Stem cells replenish the cells present in an organism throughout its lifetime and sustain growth. They have unique characteristics: the capability to self-renew and the potential to differentiate into several cell types. Recently, it has become clear that chromatin factors support these unique

  14. Attitudinal and sociostructural factors and their role in dialect change

    DEFF Research Database (Denmark)

    Kammacher, Louise; Stæhr, Andreas; Jørgensen, J. Normann

    2011-01-01

    The causation of language change is a problem with a high profile in sociolinguistics. This paper presents two contrasting models of language change: one that is based on sociopsychological factors (Kristiansen & Jørgensen, 2005) and one that rejects them (the Napoleon Principle, Brink & Lund, 1979...

  15. Comprehending Expository Texts: The Role of Cognitive and Motivational Factors

    Science.gov (United States)

    Tarchi, Christian

    2017-01-01

    This study explored the differential contribution of cognitive and motivational factors on the comprehension of an expository text in secondary school students. One hundred and fifty-five 7th and 8th grade students were assessed in prior knowledge, inferences, metacognition, reading motivation, topic interest, and reading comprehension of history…

  16. Effect of heparin and related glycosaminoglycan on PDGF-induced lung fibroblast proliferation, chemotactic response and matrix metalloproteinases activity

    Directory of Open Access Journals (Sweden)

    Masahiro Sasaki

    2000-01-01

    Full Text Available Fibroblast migration, proliferation, extacellular matrix protein synthesis and degradation are the key events in various biological and pathological processes in pulmonary fibrosis. In addition, biopsy specimens from the lungs of patients with plumomary fibrosis show increased numbers of mast cells which have metachromatic granules containing heparin, histamin and proteases. Little is known about how these products influence pulmonary fibrosis. In the present study, we investigated the effect of heparin and related glycosaminoglycans on PDGF-induced lung fibroblast proliferation and chemotactic response in vitro. In addition, we examined the effect of heparin on both the induction of matorix metalloproteinases (MMPs and MMPs activity in lung fibroblasts in vitro.

  17. Quantitative modeling of Escherichia coli chemotactic motion in environments varying in space and time.

    Directory of Open Access Journals (Sweden)

    Lili Jiang

    2010-04-01

    Full Text Available Escherichia coli chemotactic motion in spatiotemporally varying environments is studied by using a computational model based on a coarse-grained description of the intracellular signaling pathway dynamics. We find that the cell's chemotaxis drift velocity v(d is a constant in an exponential attractant concentration gradient [L] proportional, variantexp(Gx. v(d depends linearly on the exponential gradient G before it saturates when G is larger than a critical value G(C. We find that G(C is determined by the intracellular adaptation rate k(R with a simple scaling law: G(C infinity k(1/2(R. The linear dependence of v(d on G = d(ln[L]/dx directly demonstrates E. coli's ability in sensing the derivative of the logarithmic attractant concentration. The existence of the limiting gradient G(C and its scaling with k(R are explained by the underlying intracellular adaptation dynamics and the flagellar motor response characteristics. For individual cells, we find that the overall average run length in an exponential gradient is longer than that in a homogeneous environment, which is caused by the constant kinase activity shift (decrease. The forward runs (up the gradient are longer than the backward runs, as expected; and depending on the exact gradient, the (shorter backward runs can be comparable to runs in a spatially homogeneous environment, consistent with previous experiments. In (spatial ligand gradients that also vary in time, the chemotaxis motion is damped as the frequency omega of the time-varying spatial gradient becomes faster than a critical value omega(c, which is controlled by the cell's chemotaxis adaptation rate k(R. Finally, our model, with no adjustable parameters, agrees quantitatively with the classical capillary assay experiments where the attractant concentration changes both in space and time. Our model can thus be used to study E. coli chemotaxis behavior in arbitrary spatiotemporally varying environments. Further experiments are

  18. Impact factor and its role in academic promotion

    Directory of Open Access Journals (Sweden)

    Richard Russell

    2009-07-01

    Full Text Available Richard Russell,1 Dave Singh21Wrexham Park Hospital, Berkshire, UK; 2Northwest Lung Research Centre, South Manchester University Hospitals Trust, Manchester, UKThis statement was adopted unanimously at the May 17, 2009 meeting of the International Respiratory Journal Editors Roundtable.In our collective experience as editors of international peer-reviewed journals, we propose that the impact factor calculated for individual journals should not be used as a basis for evaluating the significance of an individual scientist’s past performance or scientific potential. There are several reasons not to equate the impact factor of a journal in which the scientist publishes with the quality of the scientist’s research.

  19. Do intercultural factors play a role in exacerbating psychiatric symptoms?

    Science.gov (United States)

    Ong, Yong Lock; Yap, Hwa Ling

    2013-01-01

    We report the case of a 29-year-old mixed-race woman suffering from recurrent major depressive episodes, with suicidal ideation and risk, involving several inpatient admissions. A comorbid diagnosis of borderline personality disorder was also recorded in one of her previous inpatient admissions. During her last inpatient admission, a multidisciplinary case discussion and review of the patient's life highlighted several possible intercultural trigger factors that could have contributed to the exacerbation of her psychiatric illness. We emphasise the need to explore intercultural predisposing and precipitating factors for a more complete psychodynamic understanding of psychiatric illnesses among the multiracial population of Singapore. This also adds to the discussion on the management of such patients with the option of formal in-depth psychotherapy in adjunct to medication. This may prevent recurrent relapses, modify suicide intent and reduce the necessity for inpatient treatment, which will be cost-effective and result in efficacious treatment.

  20. Macroeconomic Adjustment in Armenia: The Role of External Factors

    Directory of Open Access Journals (Sweden)

    Bas van AARLE

    2010-05-01

    Full Text Available This paper develops a small macroeconomic model of the Armenian economy. After setting up the model and its estimation, a number of macroeconomic scenarios is analyzed in the form of out-of-sample simulations. We analyze the transmissions in the model of a number of macroeconomic shocks and policy scenarios to obtain a better understanding of their possible effects on the internal and external balance of the Armenian economy. A special focus is put on the role of exchange rate and monetary management and the inflow of remittances in the Armenian economy

  1. The role of factor Xa inhibitors in venous thromboembolism treatment

    Science.gov (United States)

    Cabral, Katherine P; Ansell, Jack E

    2015-01-01

    Three factor Xa inhibitors have been studied in the treatment of venous thromboembolism, both for acute therapy and as extended therapy to prevent recurrent events. Rivaroxaban, apixaban, and edoxaban have all proven to be effective in Phase III clinical trials for this indication when compared to current standard of therapy with similar or less bleeding. Nevertheless, the agents all offer different pharmacological profiles, which have an impact on patient selection and potential advantages in clinical practice. PMID:25673997

  2. Explaining Protectionism Support: The Role of Economic Factors

    OpenAIRE

    Melgar, Natalia; Milgram-Baleix, Juliette; Rossi, Máximo

    2013-01-01

    In this paper, we investigate some factors shaping individual support for protectionism that have not been studied previously. We examine a heterogeneous sample of thirty countries which includes both small and large and developed and developing countries using data from the 2003 International Social Survey Program (ISSP). We confirm the influence of social status, relative income, values and attachments on preferences for trade policies and the fact that skilled people are also more likely t...

  3. [The role of the therapist: the 'forgotten' factor in ROM].

    Science.gov (United States)

    de Jong, K

    2012-01-01

    Routine outcome monitoring (ROM) can only improve the quality of mental health care if the therapist is prepared to accept ROM-feedback. However, most implementation procedures tend to focus on the organisation of the measurements rather than on the role of the therapist. To obtain a better understanding of the characteristics of the therapist which influence his/her attitude to the use of the feedback that ROM generates. Therapists were asked to complete two questionnaires that measured their attitude to rom feedback. Six months later several therapists were asked to complete a questionnaire that measured the barriers of the use of ROM feedback. Therapists with a preference for external feedback and therapists who felt that the feedback was valuable had a positive attitude to ROM. Barriers that prevented therapists from using feedback included the need to attend to other pressing tasks and a lack of time. In ROM implementation procedures more attention needs to be given to the role of the therapist.

  4. Experiences of role model instructors and nursing students about facilitator factors of role-modeling process: A qualitative research.

    Science.gov (United States)

    Nouri, Jamileh Mokhtari; Ebadi, Abbas; Alhani, Fatemeh; Rejeh, Nahid

    2014-05-01

    One of the key strategies in students' learning is the influence of models on them. Understanding the factors affecting the implementation of role-modeling process in education will help to make greater use of this training strategy. This study aimed to understand the experiences of role model instructors and nursing students about the facilitator factors in the role-modeling process. This qualitative study was carried out by using thematic analysis method and purposeful sampling. Data were collected until saturation by using three focus group discussions (n = 20) and two individual interviews with nursing instructors, as well as six semi-structured face-to-face interviews with role model instructors from five nursing faculties of Tehran universities in 2011. Six themes, "effort for humanistic and professional growth of students," "individual and managerial empowerment of instructor," "instructor and student's modeling," "motivation and effort of student," "strategies governing the education system," and "appropriate facilities and equipment," were extracted as the facilitating factors. For development of role-modeling process in nursing education, paying attention to personal and environmental factors, especially effort for professional and humanistic growth of nursing students is necessary.

  5. Genetic and epigenetic factors: Role in male infertility

    Directory of Open Access Journals (Sweden)

    M B Shamsi

    2011-01-01

    Full Text Available Genetic factors contribute upto 15%-30% cases of male infertility. Formation of spermatozoa occurs in a sequential manner with mitotic, meiotic, and postmeiotic differentiation phases each of which is controlled by an intricate genetic program. Genes control a variety of physiologic processes, such as hypothalamus-pituitary-gonadal axis, germ cell development, and differentiation. In the era of assisted reproduction technology, it is important to understand the genetic basis of infertility to provide maximum adapted therapeutics and counseling to the couple.

  6. The role of eukaryotic translation initiation factor 6 in tumors

    OpenAIRE

    Zhu, Wei; Li, Gui Xian; Chen, Hong Lang; Liu, Xing Yan

    2017-01-01

    Eukaryotic translation initiation factor 6 (eIF6) affects the maturation of 60S ribosomal subunits. Found in yeast and mammalian cells, eIF6 is primarily located in the cytoplasm of mammalian cells. Emerging evidence has demonstrated that the dysregulated expression of eIF6 is important in several types of human cancer, including head and neck carcinoma, colorectal cancer, non-small cell lung cancer and ovarian serous adenocarcinoma. However, the molecular mechanisms by which eIF6 functions d...

  7. In vitro inhibitory effects of Moringa oleifera leaf extract and its major components on chemiluminescence and chemotactic activity of phagocytes.

    Science.gov (United States)

    Vongsak, Boonyadist; Gritsanapan, Wandee; Wongkrajang, Yuvadee; Jantan, Ibrahim

    2013-11-01

    The ethanol extract of Moringa oleifera Lam. leaves and its major constituents, crypto-chlorogenic acid, quercetin 3-O-glucoside and kaempferol 3-O-glucoside, were investigated on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using a luminol-based chemiluminescence assay. The chemotactic migration of PMNs was also investigated using the Boyden chamber technique. The ethanol extract demonstrated inhibitory activities on the oxidative burst and the chemotactic migration of PMNs. Quercetin 3-O-glucoside, crypto-chlorogenic acid, and kaempferol 3-O-glucoside, isolated from the extract, expressed relatively strong inhibitory activity on the oxidative burst of PMNs with IC50 values of 4.1, 6.7 and 7.0 microM, respectively, comparable with that of aspirin. They also demonstrated strong inhibition of chemotatic migration of PMNs with IC50 values of 9.5, 15.9 and 18.2 microM, respectively. The results suggest that M. oleifera leaves could modulate the immune response of human phagocytes, linking to its ethnopharmacological use as an anti-inflammatory agent. The immunomodulating activity of the plant was mainly due to its major components.

  8. The role of dispositional and situational factors in cognitive interference.

    Science.gov (United States)

    Pierce, G R; Ptacek, J T; Taylor, B; Yee, P L; Henderson, C A; Lauventi, H J; Bourdeau, C M

    1998-10-01

    Two studies investigated the cross-temporal stability and cross-situational consistency of cognitive interference. In Study 1, 70 college students reported on the intrusive thoughts they experienced during 2 course examinations and a self-reflective task. In Study 2, 55 college athletes reported on intrusive thoughts following 2 course examinations and 2 regular season football games. Major findings were (a) cognitive interference showed both cross-temporal stability and cross-situational consistency, (b) it was predicted by a measure of dispositional intrusive thinking, (c) the link between cognitive interference and dispositional intrusive thinking was not accounted for by indices of depressive symptomatology and trait anxiety, and (d) the degree of cross-situational consistency of cognitive interference and the content of these intrusive thoughts were influenced by situational factors.

  9. Epidemiology of Skin Cancer: Role of Some Environmental Factors

    Energy Technology Data Exchange (ETDEWEB)

    Fabbrocini, Gabriella, E-mail: gafabbro@unina.it [Department of Systematic Pathology, Division of Dermatology, University of Naples Federico II, Naples (Italy); Triassi, Maria [Department of Preventive Medical Sciences, Division of Hygiene, University of Naples Federico II Naples (Italy); Mauriello, Maria Chiara [Department of Systematic Pathology, Division of Dermatology, University of Naples Federico II, Naples (Italy); Torre, Guglielma [Department of Preventive Medical Sciences, Division of Hygiene, University of Naples Federico II Naples (Italy); Annunziata, Maria Carmela; Vita, Valerio De; Pastore, Francesco; D’Arco, Vincenza; Monfrecola, Giuseppe [Department of Systematic Pathology, Division of Dermatology, University of Naples Federico II, Naples (Italy)

    2010-11-24

    The incidence rate of melanoma and non-melanoma skin cancer entities is dramatically increasing worldwide. Exposure to UVB radiation is known to induce basal and squamous cell skin cancer in a dose-dependent way and the depletion of stratospheric ozone has implications for increases in biologically damaging solar UVB radiation reaching the earth’s surface. In humans, arsenic is known to cause cancer of the skin, as well as cancer of the lung, bladder, liver, and kidney. Exposure to high levels of arsenic in drinking water has been recognized in some regions of the world. SCC and BCC (squamous and basal cell carcinoma) have been reported to be associated with ingestion of arsenic alone or in combination with other risk factors. The impact of changes in ambient temperature will influence people’s behavior and the time they spend outdoors. Higher temperatures accompanying climate change may lead, among many other effects, to increasing incidence of skin cancer.

  10. The role of confounding factors in a radon epidemiological study

    Directory of Open Access Journals (Sweden)

    A. D. Onishchenko

    2017-01-01

    Full Text Available Objective: A simulation of a large-scale epidemiological case-control study to identify the relationship between exposure to radon and lung cancer in the presence of factors that distort the results of the assessment of exposure to radon in homes. Materials and Methods: Analysis of sources of uncertainties arising during radon epidemiologic case-control studies. Evaluation of the uncertainties caused by the errors of the measurements of the long-term variations in the radon concentration, exposure to radon in other places of the human habitat, except dwellings, etc. Simulation by Monte Carlo technique of radon epidemiologic study, comparable to the combined European radon study, and assessment of uncertainties, which affect the evaluation of dose-effect dependence. Results: The multiplicative error in the assessment of individual exposure based on the radon concentration is shown generally caused by the combined effect of long-term variations of the radon concentration and the differences in the levels of the radon concentration in living houses and other places of the human habitat. The logarithmic standard deviation of this errors σerr is from 0,70 to 0,90. The estimated value of this error is 2,0 times higher than the value used for correction of the results of the combined European radon study. It is shown that for the σerr <0,9 regression calibration technique, there is a possibility to make a full correction of uncertainty. Conclusion: Errors in the assessment of uncertainties of the radon exposure based on the radon concentration in the combine European radon case-control study has led to an underestimation of the relative risk of lung cancer incidence at least with a factor of 1,5.

  11. Role of biological factors in etiopathogenesis of borderline personality disorder

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    Jolanta Rabe-Jabłońska

    2012-09-01

    Full Text Available Emotionally labile personality of borderline type (borderline personality occurs in 1-2% of individuals from general population; 75% of this group are women. Similarly to most of the other mental disorders, the borderline personality results from a combination of biological, social and psychological factors. The subject of this study is a survey of the current knowledge on biological factors of borderline personality. Most researchers are of the opinion that these personality disorders are determined genetically, with such inherited temperamental traits as: dysregulation, impulsivity, and hypersensitivity. Perhaps hereditary is also a defect within the serotonergic system, endogenous opioid system and/or dopaminergic system related to the reward system. Many researchers have recently perceived the dysfunction of endogenous opioid system as an integral component of borderline personality. There is now a lot of evidence showing that this dysfunction as well as that of the reward system may account for most of the borderline personality symptoms which constitute an involuntary attempt of stimulating the inefficient systems. This is how e.g. the presence of reckless sexual behaviours, unstable interpersonal relationships and inability to delay the reward in borderline personality is accounted for. Such observations may in the future constitute an important indication for seeking a more effective pharmacotherapy for patients with borderline personality. It is possible that in some patients the described dysfunctions may be alleviated with time. This is implied by the results of comprehensive prospective studies which show a significant regression of symptoms and improvement in functioning of most patients with borderline personality after at least several years.

  12. Defining metabolically healthy obesity: role of dietary and lifestyle factors.

    Science.gov (United States)

    Phillips, Catherine M; Dillon, Christina; Harrington, Janas M; McCarthy, Vera J C; Kearney, Patricia M; Fitzgerald, Anthony P; Perry, Ivan J

    2013-01-01

    There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria. Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥ 30 kg/m(2)) and non-obese (BMI definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined. The prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006). A standard MHO definition is required. Moderate and high levels of physical activity and compliance with food pyramid recommendations increase the likelihood of MHO. Stratification of obese individuals based on their metabolic health phenotype may be important in ascertaining the appropriate therapeutic or intervention strategy.

  13. Defining metabolically healthy obesity: role of dietary and lifestyle factors.

    Directory of Open Access Journals (Sweden)

    Catherine M Phillips

    Full Text Available BACKGROUND: There is a current lack of consensus on defining metabolically healthy obesity (MHO. Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria. METHOD: Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥ 30 kg/m(2 and non-obese (BMI < 30 kg/m(2. Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined. RESULTS: The prevalence of MHO varied considerably between definitions (2.2% to 11.9%, was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model and non-obese subjects (OR 1.37-1.39 unadjusted model, respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006. CONCLUSION: A standard MHO definition is required. Moderate and high levels of physical activity and compliance with food pyramid recommendations increase the likelihood of MHO. Stratification of obese individuals based on their metabolic health phenotype may be important in ascertaining the appropriate

  14. Role of the Religious Factor in Expansion of Europe

    Directory of Open Access Journals (Sweden)

    Daniel Andrișan

    2008-06-01

    Full Text Available In the course of human communities priority was preservation of identity, sovereignty,independence and territorial integrity. States as the main framework of political organization, hadintended to build national security policy to protect and promote their interests. An increasing numberof conflicts have been caused or inflamed by cultural differences exacerbate, ethnic or religious.Therefore, religions and their associated phenomena have been given new relevant in the context ofsecurity, imposing civilization lately approach to security. This requires thorough research of cultural,religious phenomena and linguistic aspects, as Samuel Huntington did, who is the initiator of thismodel civilizational approach to security analysis. By applying this model the following conclusions:reality forces of integration in the world is exactly what generates forces of cultural claims,civilizational knowledge, in a sense the world is bipolar, but the main distinction is between the Westand as far dominant civilization and all others, however, share more than anything. In short, the worldis a world divided between Western and non-Western world more, nation states are and will remainthe most important actors in international affairs, but their interests, associations and conflictsbetween them are becoming more limited by factors culture and civilization, the world is indeedanarchic, punctuated by tribal and nationality conflicts, but conflicts that make the biggest threats tostability are those between states or groups from different civilizations.

  15. Role of Human Factors in Awareness Enhancing in Workplaces

    Directory of Open Access Journals (Sweden)

    F. Kiani

    2016-12-01

    Full Text Available Abstract Aims: Ability of employees to maintain awareness of the work situation, understand the information it holds, and predict how situations will develop are important factors in prevention of industrial accidents. The aim of current research was to investigate the relationship of safety climate and work overload with work situation awareness. Instrument & Methods: This cross sectional study was administrated between October and November 2015 in the National Petrochemical Company (NPC. 190 persons were selected by stratified random sampling method. Validated instruments were used for data collection on work situation awareness, safety climate and work overload. Data was analyzed by SPSS 15 software using Pearson correlation coefficient and stepwise regression analysis. Findings: Safety climate (68.67±7.13 had significant (p<0.01 correlations with work overload (16.17±3.21; r=0.26 and work situation awareness (65.55±6.22; r=0.5. Also, work overload and work situation awareness had a significant negative correlation (r=-0.39; p<0.01. Safety climate and work overload both predicted 33% of work situation awareness. Individually, safety climate predicted 21% (t=6.81; β=0.43 and work overload predicted 10% (t=- 4.43; β=-0.28 of the work situation awareness. Conclusion: Safety climate and work overload affect the work situation awareness among workers.

  16. [Promoting factors for breastfeeding: the role of health professionals].

    Science.gov (United States)

    Flores Quijano, María Eugenia

    2011-01-01

    By the end of their first year of life, infants are ready to sit at the dinner table, to eat the same food as their family and to accept a variety of foods in sufficient quantity to maintain adequate nutritional status. In this context, breastfeeding contributes through different mechanisms such as: self-regulation in milk consumption and exposure to different flavors to assure a good nutrition and to create adequate feeding habits. However, breastfeeding is one of several options available to feed a newborn and a behavior that women need to learn. Today, the responsibility to counsel and guide women and their families in breastfeeding falls upon health professionals, specifically the general practitioner. This paper discusses the characteristics and functioning of the mammary gland as well as anatomical and physiological bases of suction exerted by the baby on the breast, so the health professional can recognize the factors that promote successful breastfeeding and to solve the problems or difficulties that could arise. Also are discussed here the main elements of a practice and proper technique, which are essential to provide breastfeeding counseling.

  17. The role of heregulin-alpha as a motility factor and amphiregulin as a growth factor in wound healing.

    Science.gov (United States)

    Schelfhout, Vera R J; Coene, Elisabeth D; Delaey, Bernard; Waeytens, Anouk A T; De Rycke, Leen; Deleu, Mattias; De Potter, Christian R

    2002-12-01

    Wound healing is a complex process of which growth and motility are essential features. The aim of this study was to search for keratinocyte-derived secreted factors that may play a role in these mechanisms, and their corresponding receptors. Growth and motility factors were purified from conditioned medium from cultured primary keratinocytes. Receptor and growth factor expression profiles were investigated by immunohistochemical, western blotting, and in situ hybridization analysis on cultured keratinocytes and tissue sections derived from chronic wounds. The most potent autocrine growth factor for keratinocytes, which it was possible to purify and sequence from keratinocyte-conditioned medium, is amphiregulin. Its receptor HER-1 is up-regulated on the membranes of keratinocytes lining the edge of the wound. From the same keratinocyte-conditioned medium, heregulin-alpha was purified as a potent motility factor for keratinocytes. Its receptor is HER-3, which is up-regulated on the membranes of keratinocytes lining the edge of the wound and on keratinocytes that had migrated towards the centre of the wound. HER-4 - another receptor for heregulin-alpha - is weakly present in occasional cells near the edge of the wound. The co-receptor for HER-3 and HER-4 is HER-2/neu, which is also present in epidermal cells but not overexpressed. This study shows that heregulin-alpha is a potent motility factor for normal epithelial cells and that it plays a central role in the process of wound healing of stratified epithelia. Heregulin-alpha has already been shown to be the motility factor leading to migration of HER-2/neu-overexpressing breast cancer cells. The role of amphiregulin as a growth factor and of heregulin-alpha as a motility factor for keratinocytes in epidermal and mucosal wound healing parallels their motility and growth induction in carcinogenesis. Copyright 2002 John Wiley & Sons, Ltd.

  18. The Granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity

    Directory of Open Access Journals (Sweden)

    Stephanie eWallner

    2015-08-01

    Full Text Available Granulocyte-colony stimulating factor (G-CSF is a growth factor that has originally been identified several decades ago as a hematopoietic factor required mainly for the generation of neutrophilic granulocytes, and is in clinical use for that. More recently, it has been discovered that G-CSF also plays a role in the brain as a growth factor for neurons and neural stem cells, and as a factor involved in the plasticity of the vasculature. We review and discuss these dual properties in view of the neuroregenerative potential of this growth factor.

  19. The role of safe practices in hospitals’ total factor productivity

    Directory of Open Access Journals (Sweden)

    Timothy R Huerta

    2011-01-01

    Full Text Available Timothy R Huerta1, Mark A Thompson2, Eric W Ford31Center for Health Innovation, Education, and Research, 2Rawls College of Business, Texas Tech University, Lubbock, TX, USA; 3Forsyth Medical Center Distinguished Professor of Health Care, The University of North Carolina Greensboro, Greensboro, NC, USAAbstract: The dual aims of improving safety and productivity are a major part of the health care reform movement hospital leaders must manage. Studies exploring the two phenomena conjointly and over time are critical to understanding how change in one dimension influences the other over time. A Malmquist approach is used to assess hospitals’ relative productivity levels over time. Analysis of variance (ANOVA algorithms were executed to assess whether or not the Malmquist Indices (MIs correlate with the safe practices measure. The American Hospital Association’s annual survey and the Centers for Medicare and Medicaid Services’ Case Mix Index for fiscal years 2002–2006, along with Leapfrog Group’s annual survey for 2006 were used for this study. Leapfrog Group respondents have significantly higher technological change (TC and total factor productivity (TFP than nonrespondents without sacrificing technical efficiency changes. Of the three MIs, TC (P < 0.10 and TFP (P < 0.05 had significant relationships with the National Quality Forum’s Safe Practices score. The ANOVA also indicates that the mean differences of TFP measures progressed in a monotonic fashion up the Safe Practices scale. Adherence to the National Quality Forum’s Safe Practices recommendations had a major impact on hospitals’ operating processes and productivity. Specifically, there is evidence that hospitals reporting higher Safe Practices scores had above average levels of TC and TFP gains over the period assessed. Leaders should strive for increased transparency to promote both quality improvement and increased productivity.Keywords: safety, productivity, quality, safe

  20. Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors.

    Science.gov (United States)

    Kjøllesdal, M K R; Ariansen, I; Mortensen, L H; Davey Smith, G; Næss, Ø

    2016-12-01

    To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

  1. An Analysis of the Role of Service Specific Risk Factors in Active Duty Navy Suicides

    Science.gov (United States)

    2014-03-01

    risk among teenagers and older adults); furthermore, the age bracket results coincide with the crude suicide numbers in the dataset (the 17–19 age...ROLE OF SERVICE–SPECIFIC RISK FACTORS IN ACTIVE DUTY NAVY SUICIDES by James D. Golliday March 2014 Thesis Co-Advisors: Yu-Chu Shen...COVERED Master’s Thesis 4. TITLE AND SUBTITLE AN ANALYSIS OF THE ROLE OF SERVICE–SPECIFIC RISK FACTORS IN ACTIVE DUTY NAVY SUICIDES 5. FUNDING

  2. Integrating the ICF with positive psychology: Factors predicting role participation for mothers with multiple sclerosis.

    Science.gov (United States)

    Farber, Ruth S; Kern, Margaret L; Brusilovsky, Eugene

    2015-05-01

    Being a mother has become a realizable life role for women with disabilities and chronic illnesses, including multiple sclerosis (MS). Identifying psychosocial factors that facilitate participation in important life roles-including motherhood-is essential to help women have fuller lives despite the challenge of their illness. By integrating the International Classification of Functioning, Disability, and Health (ICF) and a positive psychology perspective, this study examined how environmental social factors and positive personal factors contribute to daily role participation and satisfaction with parental participation. One hundred and 11 community-dwelling mothers with MS completed Ryff's Psychological Well-Being Scales, the Medical Outcome Study Social Support Survey, the Short Form-36, and the Parental Participation Scale. Hierarchical regression analyses examined associations between social support and positive personal factors (environmental mastery, self-acceptance, purpose in life) with daily role participation (physical and emotional) and satisfaction with parental participation. One-way ANOVAs tested synergistic combinations of social support and positive personal factors. Social support predicted daily role participation (fewer limitations) and greater satisfaction with parental participation. Positive personal factors contributed additional unique variance. Positive personal factors and social support synergistically predicted better function and greater satisfaction than either alone. Integrating components of the ICF and positive psychology provides a useful model for understanding how mothers with MS can thrive despite challenge or impairment. Both positive personal factors and environmental social factors were important contributors to positive role functioning. Incorporating these paradigms into treatment may help mothers with MS participate more fully in meaningful life roles. (c) 2015 APA, all rights reserved).

  3. Factors Affecting the Transformational Leadership Role of Principals in Implementing ICT in Schools

    Science.gov (United States)

    Afshari, Mojgan; Bakar, Kamariah Abu; Luan, Wong Su; Siraj, Saedah

    2012-01-01

    Leadership is an important factor in the effective implementation of technology in schools. This study examines the transformational leadership role of principals to determine whether transformational leadership role of principals in ICT implementation in schools is influenced by the computer competence, level of computer use, and professional…

  4. Farm-Nonfarm Differentials in Fertility: The Effects of Compositional and Sex-Role Factors.

    Science.gov (United States)

    Johnson, Nan E.; And Others

    Data derived from the 1970 National Fertility Study (NFS II included post-married women, information on all compositional factors for each respondent, and an 18-item section on sex-role ideology) were used to test the following hypotheses: farm women are more traditional in sex-role ideology than nonfarm women; the higher the sex-role…

  5. Stressful Events and Depression among Chinese Adolescents: The Mitigating Role of Protective Factors

    Science.gov (United States)

    Zhang, Wenxin; Li, Hailei; Gong, Yanming; Ungar, Michael

    2013-01-01

    This study examines the role of salient external factors (family, peer and school caring relations) and internal factors (goals and aspirations, problem solving and self-efficacy, empathy, and self-awareness) in protecting adolescents experiencing interpersonal problems and academic pressure from depression. A total of 1,297 eighth and ninth grade…

  6. The Role of Socioeconomic Factors in the Prediction of Persistence in Puerto Rico

    Science.gov (United States)

    Dika, Sandra L.

    2014-01-01

    While research literature suggests that socioeconomic factors play a role in predicting educational attainment, very little research has been done to examine these relationships using data from Puerto Rico. A logistic regression approach was adopted to investigate the extent to which family and school socioeconomic factors predict retention from…

  7. The role of nurses in the prevention of cardiovascular risk factors

    Directory of Open Access Journals (Sweden)

    Azime KARAKOÇ KUMSAR

    2017-12-01

    Full Text Available Cardiovascular diseases are the causes of mortality and morbidity in the first ranks one of the major health problems in many countries all over the world. Race, age, gender and family history of cardiovascular disease are nonmodifiable risks factors. The majority of known risk factors for these diseases are modifiable by risk factors as hypertension, diabetes, hyperlipidaemia, smoking and alcohol use and obesity. Preventive measures as healthy diet, regular physical activity, effective stress management, non-use smoking and alcohol, hygienic measures and take responsibility for their own health are defined as healthy lifestyle may reduce the risk of cardiovascular diseases. In these direction health professionals especially nurses have an important role about control of preventable risk factors. Risk factors for cardiovascular disease, roles of the nurse about risk factors preventive strategies to gain and maintain healthy life-style behaviors were examined in this review article.

  8. Monocyte chemotactic protein-1 attenuates and high-fat diet exacerbates bone loss in mice with pulmonary metastasis of Lewis lung carcinoma

    Science.gov (United States)

    Bone can be adversely affected by obesity and cancer-associated complications including wasting. The objective of this study was to determine whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects found in male C57BL/6 mice with Lewis lung...

  9. Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco and Its Active Site for Chemotaxis

    Directory of Open Access Journals (Sweden)

    Farman Ullah Dawar

    2016-08-01

    Full Text Available Fish skin mucus is a dynamic barrier for invading pathogens with a variety of anti-microbial enzymes, including cyclophilin A (CypA, a multi-functional protein with peptidyl-prolyl cis/trans isomerase (PPIase activity. Beside various other immunological functions, CypA induces leucocytes migration in vitro in teleost. In the current study, we have discovered several novel immune-relevant proteins in yellow catfish skin mucus by mass spectrometry (MS. The CypA present among them was further detected by Western blot. Moreover, the CypA present in the skin mucus displayed strong chemotactic activity for yellow catfish leucocytes. Interestingly, asparagine (like arginine in mammals at position 69 was the critical site in yellow catfish CypA involved in leucocyte attraction. These novel efforts do not only highlight the enzymatic texture of skin mucus, but signify CypA to be targeted for anti-inflammatory therapeutics.

  10. Affect and Health Behavior Co-Occurrence: The Emerging Roles of Transdiagnostic Factors and Sociocultural Factors.

    Science.gov (United States)

    Zvolensky, Michael J; Leventhal, Adam M

    2016-01-01

    The majority of scientific work addressing relations among affective states and health correlates has focused primarily on their co-occurrence and a limited range of health conditions. We have developed a Special Issue to highlight recent advances in this emerging field of work that addresses the nature and interplay between affective states and disorders, in terms of their impact and consequences from health status and behavior. This Special Issue is organized into three parts classified as (a) co-occurrence and interplay between (b) transdiagnostic factors and (c) sociocultural factors. It is hoped that this issue will (a) alert readers to the significance of this work at different levels of analysis, (b) illustrate the many domains currently being explored via innovative approaches, and (c) identify fecund areas for future systematic study. © The Author(s) 2016.

  11. Agent-based model of human alveoli predicts chemotactic signaling by epithelial cells during early Aspergillus fumigatus infection.

    Directory of Open Access Journals (Sweden)

    Johannes Pollmächer

    Full Text Available Aspergillus fumigatus is one of the most important human fungal pathogens, causing life-threatening diseases. Since humans inhale hundreds to thousands of fungal conidia every day, the lower respiratory tract is the primary site of infection. Current interaction networks of the innate immune response attribute fungal recognition and detection to alveolar macrophages, which are thought to be the first cells to get in contact with the fungus. At present, these networks are derived from in vitro or in situ assays, as the peculiar physiology of the human lung makes in vivo experiments, including imaging on the cell-level, hard to realize. We implemented a spatio-temporal agent-based model of a human alveolus in order to perform in silico experiments of a virtual infection scenario, for an alveolus infected with A. fumigatus under physiological conditions. The virtual analog captures the three-dimensional alveolar morphology consisting of the two major alveolar epithelial cell types and the pores of Kohn as well as the dynamic process of respiration. To the best of our knowledge this is the first agent-based model of a dynamic human alveolus in the presence of respiration. A key readout of our simulations is the first-passage-time of alveolar macrophages, which is the period of time that elapses until the first physical macrophage-conidium contact is established. We tested for random and chemotactic migration modes of alveolar macrophages and varied their corresponding parameter sets. The resulting first-passage-time distributions imply that randomly migrating macrophages fail to find the conidium before the start of germination, whereas guidance by chemotactic signals derived from the alveolar epithelial cell associated with the fungus enables a secure and successful discovery of the pathogen in time.

  12. Migration of Chemotactic Bacteria Transverse to Flow in Response to a Benzoate Source Plume Created in a Saturated Sand-Packed Microcosm

    Science.gov (United States)

    Ford, R.; Boser, B.

    2012-12-01

    Bioremediation processes depend on contact between microbial populations and the groundwater contaminants that they biodegrade. Chemotaxis, the ability of bacteria to sense a chemical gradient and swim preferentially toward locations of higher concentration, can enhance the transport of bacteria toward contaminant sources that may not be readily accessible by advection and dispersion alone. A two-dimensional rectangular-shaped microcosm packed with quartz sand was used to quantify the effect of chemotaxis on the migration of bacteria within a saturated model aquifer system. Artificial groundwater was pumped through the microcosm at a rate of approximately 1 m/day. A plume of sodium benzoate was created by continuous injection into an upper port of the microcosm to generate a chemical gradient in the vertical direction transverse to flow. Chemotactic bacteria, Pseudomonas putida F1, or the nonchemotactic mutant, P. putida F1 CheA, were injected with a conservative tracer in a port several centimeters below the benzoate position. As the injectates traversed the one-meter length of the microcosm, samples were collected from a dozen effluent ports to determine vertical concentration distributions for the bacteria, benzoate and tracer. A moment analysis was implemented to estimate the center of mass, variance, and skewness of the concentration profiles. The transverse dispersion coefficient and the transverse dispersivity for chemotactic and nonchemotactic bacteria were also evaluated. Experiments performed with a continuous injection of bacteria showed that the center of mass for chemotactic bacteria was closer to the benzoate source on average than the nonchemotactic control (relative to the conservative tracer). These results demonstrated that chemotaxis can increase bacterial transport toward contaminants, potentially enhancing the effectiveness of in situ bioremediation. Experiments with 2 cm and 3 cm spacing between bacteria and benzoate injection locations were

  13. Dose-Response Analysis of Chemotactic Signaling Response in Salmonella typhimurium LT2 upon Exposure to Cysteine/Cystine Redox Pair.

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    Bob T Rosier

    Full Text Available The chemotaxis system enables motile bacteria to search for an optimum level of environmental factors. Salmonella typhimurium senses the amino acid cysteine as an attractant and its oxidized dimeric form, cystine, as a repellent. We investigated the dose-response dependence of changes in chemotactic signaling activity upon exposure to cysteine and cystine of S. typhimurium LT2 using in vivo fluorescence resonance energy transfer (FRET measurements. The dose-response curve of the attractant response to cysteine had a sigmoidal shape, typical for receptor-ligand interactions. However, in a knockout strain of the chemoreceptor genes tsr and tar, we detected a repellent response to cysteine solutions, scaling linearly with the logarithm of the cysteine concentration. Interestingly, the magnitude of the repellent response to cystine also showed linear dependence to the logarithm of the cystine concentration. This linear dependence was observed over more than four orders of magnitude, where detection started at nanomolar concentrations. Notably, low concentrations of another oxidized compound, benzoquinone, triggered similar responses. In contrast to S. typhimurium 14028, where no response to cystine was observed in a knockout strain of chemoreceptor genes mcpB and mcpC, here we showed that McpB/McpC-independent responses to cystine existed in the strain S. typhimurium LT2 even at nanomolar concentrations. Additionally, knocking out mcpB and mcpC did not affect the linear dose-response dependence, whereas enhanced responses were only observed to solutions that where not pH neutral (>100 μM cystine in the case of McpC overexpression. We discuss that the linear dependence of the response on the logarithm of cystine concentrations could be a result of a McpB/C-independent redox-sensing pathway that exists in S. typhimurium LT2. We supported this hypothesis with experiments with defined cysteine/cystine mixed solutions, where a transition from repellent

  14. A case study exploring employment factors affecting general practice nurse role development.

    Science.gov (United States)

    Crossman, Sue; Pfeil, Michael; Moore, Jennifer; Howe, Amanda

    2016-01-01

    The aim of this study was to explore the factors affecting role development in practice nursing in the United Kingdom. General practice is currently central to National Health Service reform, producing favourable conditions for the practice nurse role to be further strengthened and developed. However, the literature has continued to describe evidence that practice nurses are a disempowered, isolated group with many constraints reducing their ability to respond to opportunities to develop their role. The rationale for conducting the study was therefore to provide a greater understanding about the constraining factors and their influence on practice nurses wishing to develop their role. The method used to conduct the research followed a case approach, as the subject being investigated was complex with multiple inter-related factors and the approach was exploratory. The cases comprised six UK general practices and the participants within each case were a practice nurse, a GP and a practice manager. A combination of factors was found to contribute to the way the practice nurse role evolves. These are education, practice culture, practice nurse personal characteristics and empowerment. Empowerment holds the key to maximising the conditions favourable to practice nurse role evolution. This is not, however, a 'single' factor; it represents the combined synergistic effects of practice culture and practice nurse personal characteristics on creating an empowering environment. The inter-relationship between these was captured in a framework and given the title 'empowering employment principles'. The 'empowering employment principles' illustrate the features most conducive to role evolution, thus providing a tool for practice nurses and their employers to enhance opportunities for nurses to develop their role.

  15. Factors that facilitate registered nurses in their first-line nurse manager role.

    Science.gov (United States)

    Cziraki, Karen; McKey, Colleen; Peachey, Gladys; Baxter, Pamela; Flaherty, Brenda

    2014-11-01

    To determine the factors that attract and retain Registered Nurses in the first-line nurse manager role. The first-line nurse manger role is pivotal in health-care organisations. National demographics suggest that Canada will face a first-line nurse manager shortage because of retirement in the next decade. Determination of factors that attract and retain Registered Nurses will assist organisations and policy makers to employ strategies to address this shortage. The study used an exploratory, descriptive qualitative approach, consisting of semi-structured individual interviews with 11 Registered Nurses in first-line nurse manager roles. The findings revealed a discrepancy between the factors that attract and retain Registered Nurses in the first-line nurse manager role, underscored the importance of the mentor role and confirmed the challenges encountered by first-line nurse managers practicing in the current health-care environment. The first-line nurse manager role has been under studied. Further research is warranted to understand which strategies are most effective in supporting first-line nurse managers. Strategies to support nurses in the first-line nurse manager role are discussed for the individual, programme, organisation and health-care system/policy levels. © 2013 John Wiley & Sons Ltd.

  16. ATP-Dependent Chromatin Remodeling Factors and Their Roles in Affecting Nucleosome Fiber Composition

    Directory of Open Access Journals (Sweden)

    Alexandra Lusser

    2011-10-01

    Full Text Available ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties.

  17. 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.

  18. Multiple interactions of hazard exposures, role stressors and situational factors, and burnout among nurses.

    Science.gov (United States)

    Lu, Jinky Leilanie

    2007-01-01

    This was a cross-sectional study which looked into the interaction between situational factors, role stressors, hazard exposure and personal factors among 135 nurses in the Philippine General Hospital. More than half (58.5%) of the respondents reported being ill due to work in the past year, and 59.3% missed work because of an illness. Regression showed factors associated with burnout were organizational role stress, hazard exposure, self-efficacy, age, number of working years, illness in the past 12 months, migraine, dizziness, sleep disorder, cough and colds, and diarrhea. After multiple regression analysis, organizational role stress (p = .000), migraine (p = .001), age (p = .018) and illness in the past 12 months (p = .000) were found to be significant predictors of burnout. The contribution of the study is in advancing new concepts in the already existing framework of burnout, and thus, assisting nurses and hospital administration in on controlling this problem.

  19. Factors associated with occupational roles in older Brazilians: a cross-sectional pilot study

    Directory of Open Access Journals (Sweden)

    Carolina Rebellato

    2015-09-01

    Full Text Available Introduction: The Gerontology points out concerns in understanding aging and its consequences, in order to propose specific policies. Objective: Identify occupational roles of older Brazilians and the relationship of these roles to demographic, socioeconomic, and health factors. Method: Participants included 67 non-institutionalized individuals 70–84 years of age (33 men and 34 women; average age: 74.6 years. The roles performed in the Past, Present and Future were examined using the Role Checklist. Results: The occupational roles have changed over time, evidencing the loss of roles during the transition from Past to Present, although the participants stated that they intend to be engaged in a higher number of roles in the Future. The main roles performed in the Present are Hobbyist/Amateur, Home Maintainer and Family Member. In general, engaging in occupational roles was associated with higher education and income either in the Past, Present and Future. Conclusions: The study enabled to detect the diversity and complexity of older people’s participation in society, contributing to a further understanding of their occupational careers. The main limitation of this study concerns to the specific sample composition, with independent older people. Further studies are in need to obtain an in-depth theoretical and empirical understanding of the trends and trajectories of the roles of older people.

  20. Intellectual Leadership of Researchers in Higher Education: Relationship Between the Demographic Factors and Roles (Lithuanian Context

    Directory of Open Access Journals (Sweden)

    Žydžiūnaitė Vilma

    2016-12-01

    Full Text Available The intellectual leadership of educators or teachers represents a topic of a great interest for educational research and practice. Variety of variables or factors have been examined to find the most complete explanations for teachers’, professors’ and educators’ roles, for example, institutional, financial, gender, organizational, spiritual, and intellectual. No literature was found on the relationship between the demographic variables and researchers’ roles in higher education regarding intellectual leadership. But a lot of studies are focused on the relationship between demographic and other factors in education: job satisfaction, organizational justice, religion, gender, culture, personal and professional roles, stress, mental health, and mobility. The research issue in this study is related to researchers’/scientists’ work in higher education schools and is focused on intellectual leadership, which consists of different roles. It is worth to think about researchers as intellectual leaders and to discover how they recognize or identify their roles in higher education. In this study, findings answer the following research question: “What are the relationships between researchers’ roles and their gender, work experience, dissertation defence date, and research field?” The object of the research study is the researchers’ roles in higher education. The aim of the study was to reveal the relationship between demographic factors and researchers’ roles in higher education. Data were collected by performing a questioning survey and using a validated questionnaire with 116 statements in total. The sample consisted of 304 researchers working in higher education institutions. For data analysis, Cronbach’s alpha, Mean and ANOVA calculations were used. The research findings reported that the female-researchers’ evaluations were higher in all cases regarding their roles in higher education schools. The results of the study

  1. Dual role as a protective factor for burnout-related depersonalization in oncologists.

    Science.gov (United States)

    He, Yi; Pang, Ying; Zhang, Yening; Fielding, Richard; Tang, Lili

    2017-08-01

    This study compared self-reported burnout between dual-role oncologists (oncologists who also do psychosocial work) and single-role oncologists, to explore if dual role is protective against or a risk factor for burnout. Dual-role oncologists from across China (n = 131) were consecutively recruited via the Chinese Psychosocial Oncology Society and asked to identify single-role oncologist peers (n = 168) working in the same institution. Participants completed an anonymous online questionnaire, which included measures of demographic and work characteristics, Maslach Burnout Inventory-Human Services Survey, the Short Version Effort-Reward Inventory, the Job Demands-Resources (JD-R) Scales, and Work and Meaning Inventory. Fully adjusted multivariate analyses compared burnout scores for the 2 groups. Group analysis revealed single-role participants' scores indicated significantly poorer performance than dual-role participants for depersonalization (DP), work-family conflict (JD-R demands scale), and decision authority (JD-R scale). Single-role participants showed an increased risk of DP. Higher effort-reward imbalance ratio predicted greater DP in single-, dual-role and pooled participants, and emotional exhaustion (EE) in pooled- and dual-role participants. Overcommitment was independently associated with EE in all 3 groupings, with JD-R scores among pooled- and dual-role groups, while higher decision authority scores were associated with decreased EE. Work and Meaning Inventory was associated with a decreased risk of DP among pooled and dual-role participants. Differences in burnout-related DP scores between dual- and single-role oncologists are consistent with a protective effect from a psychosocial orientation in oncologists. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Directed melanocyte migration: the role of Stem cell factor, cytoskeleton and focal adhesions

    OpenAIRE

    Wehrle-Haller, Bernhard

    2002-01-01

    Cell adhesion and migration are critical for the development of multicellular organisms and the maintenance of tissue integrity. This thesis explores the roles of the growth factor "Stem Cell factor and its receptor c-kit, in the process of cell migration and developmental patterning. In addition changes of the cytoskeleton and adhesion receptors of the family of integrins were analysed by live cell imaging and quantitative dynamic analysis. The thesis focusses on the specific contributions o...

  3. The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review

    OpenAIRE

    Andreas Kronbichler; Julia Kerschbaum; Gert Mayer

    2015-01-01

    A better understanding of the pathophysiology of autoimmune disorders is desired to allow tailored interventions. Despite increased scientific interest a direct pathogenic factor in autoimmune renal disease has been described only in a minority like membranous nephropathy or ANCA-associated vasculitis. Nonetheless the initial step leading to the formation of these antibodies is still obscure. In this review we will focus on the possible role of microbial factors in this context. Staphylococcu...

  4. Perceptions of the worker role among people with psychiatric disabilities: description and investigation of associated factors.

    Science.gov (United States)

    Argentzell, Elisabeth; Eklund, Mona

    2013-01-01

    To investigate how subjective perceptions of everyday occupations, activity level, day centre attendance, social interaction, self-mastery and clinical factors were related to how unemployed people with psychiatric disabilities (PD) envision a future worker role, also controlling for socio-demographic variables. 175 people with PD; 93 attended a day centre and 82 did not. Of the 93 day centre attendees 39 visited meeting place-oriented day centres and 54 attended work-oriented ones. Self-ratings and interview-based instruments were used to assess the view of the worker role, social interaction, subjective perceptions of everyday occupations, activity level, self-mastery, and socio-demographic and clinical factors. Non-parametric statistics were used when analysing the data. A few aspects of the worker role seemed positively influenced by attending a day centre, in particular a work-oriented one. High levels of activity (p=0.009) and self-mastery (p=0.024), being younger (p=0.004) and having less depression (p=0.008) were also associated with a more positive view of the worker role. In order to enhance a future worker role the individual's feeling of control in the rehabilitation process should be highlighted and possibilities for general activity engagement be offered. Since the findings indicate that most aspects of the worker role were not enhanced by day centre attendance community-based care should further concentrate on promoting this future role for people with PD.

  5. Role of Risk Factors in the Incidence of Multidrug-Resistant Tuberculosis

    Directory of Open Access Journals (Sweden)

    Alya Putri Khairani

    2017-09-01

    Full Text Available Objective: To determine the risk factors that played roles in the incidence of multidrug-resistant tuberculosis (MDR-TB in such patients. Multidrug-Resistant Tuberculosis is a form of tuberculosis caused by Mycobacterium tuberculosis that is resistant to at least isoniazid and rifampicin. Methods: This was a case control study to compare MDR-TB to non-MDR-TB pulmonary tuberculosis outpatients in Dr. Hasan Sadikin General Hospital, Bandung on August–September 2014. Fifty MDR-TB outpatients were included as the cases and 50 non-MDR-TB outpatients as controls. Data was collected by questionnaires and patient’s registration forms. Bivariate and multivariate analyses were performed using chi-square test and multiple logistic regression test, with p<0.05 considered significant. Results: From bivariate analysis, number of previous tuberculosis treatments, regularity of previous treatment, and burden of cost were significant risk factors for developing MDR-TB (p<0.05; while from multivariate analysis, number of previous TB treatments was the only risk factor that played a significant role in the incidence of MDR-TB (OR 24.128 95% CI 6.771-85,976. Conclusions: Patients and medication factors are risk factors that play roles in the incidence of MDR-TB. The significant risk factor is the number of previous TB treatment.

  6. [Neurotrophic factors and their role in the pathogenesis of affective disorders].

    Science.gov (United States)

    Filuś, Jakub F; Rybakowski, Janusz

    2005-01-01

    Neurotrophic factors are a group of proteins with a similar structure (The regulation of neuronal plasticity and neuron protection are some of their biological functions). The group of neurotrophic factors consists of: growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin 4/5 (NT-4/5). BDNF is the most important neurotrophin from the affective disorders point of view. Preclinical and clinical studies of altered BDNF expression during chronic stress and increased BDNF activity during antidepressant treatment, confirm the role of BDNF in the pathogenesis of depression. Studies on animal models point to the antidepressant effect of BDNF, similar to long-term antidepressant treatment. The intracellular mechanisms mediated by this neurotrophic factor are connected with signal transduction pathways in cells (mainly mitogen-activated protein kinase cascade and cyclic adenosine 3',5'-monophosphate cascade). The BDNF serum level studies suggest a correlation between the BDNF expression in the central nervous system and its serum levels, what could make BDNF levels specific markers of depression. The molecular genetic studies focus on associations between BDNF gene polymorphisms and bipolar disorder or cognitive functioning disturbances. The novel pathogenetic theories of depression based on neuronal plasticity (Duman et al.) and disturbances in neurogenesis (Kempermann and Kronenberg) can be a kind of recapitulation of research on the role of neurotrophins in depression. However many issues related to the role of neurotrophic factors in affective disorders are still unclear and determine areas of future scientific interests in this field.

  7. Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

    Directory of Open Access Journals (Sweden)

    Neragi-Miandoab Siyamek

    2008-01-01

    Full Text Available Abstract Malignant pleural mesothelioma (MPM is a rare, aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. However, the late stage of MPM diagnosis and the long latency that exists between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects. In this review, we discuss the current molecular and genetic contributors in MPM pathogenesis and the risk factors associated with these carcinogenic processes.

  8. Roles of Municipal Councils in Poland and in the Czech Republic: Factors Shaping the Roles and the Dynamic of Change

    Directory of Open Access Journals (Sweden)

    Katarzyna Radzik-Maruszak

    2016-03-01

    Full Text Available Abstract: Research Question (RQ: After many years of not being in vogue, the issue of representative democracy at the local level has yet again caught the scholars’ attention. The interest is related both to falling turnout in local elections, disappointment in party politics as well as to the impact of the new trends such as the strengthening of the executive power or citizens’ more direct involvement in the decision-making process. Quite often the afore-mentioned trends force local councils to redefine their roles. Purpose: The main objective of the article is to investigate the factors that shape the roles of municipal councils in two CEE countries, Poland and the Czech Republic, and to track the possible dynamic of their change. Method: The analysis conducted in the paper is grounded mainly in institutional theory. The study is based on available statistic data, examination of legal regulations, documents and information included in the corpus of selected articles and books. Results: The outcome of the analysis conducted indicates that in both countries the basic roles of councils – representative, decision - making and administrative one – are being diminished. Nevertheless, the existing institutional framework as well as reforms implemented in recent years provide potential for the development of new roles, such as the facilitator of the governing process or a network coordinator. Organization: The paper may contribute to better organisation of local administration at the municipal level. Society: The study has an impact on the understanding of representative democracy in local self-governments. Originality: The paper elaborates on representative democracy at the municipal level in Poland and the Czech Republic, countries where the discussion over this issue is still much less visible than in Western Europe. Limitations / further research: The paper should be mainly perceived as a kind of theoretical introduction to further

  9. Autophagy and the hematopoietic niche: a regulatory role for the Forkhead-box transcription factors

    NARCIS (Netherlands)

    Gomez Puerto, MC

    2016-01-01

    Two main components of the hematopoietic niche are hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). FOXO transcription factors play a fundamental role in the maintenance of these cells through the regulation of cell cycle and oxidative stress. Other gene expression programs

  10. Structure and role of neutrophil cytosol factor 1 (NCF1) gene in ...

    African Journals Online (AJOL)

    Yomi

    2010-12-27

    Dec 27, 2010 ... in innate immunity and produce reactive oxygen species and reduce the severity and duration of parasitic infection and autoimmune disease. NCF1 also has a role in T cell activation. Key words: Neutrophil cytosol factor 1 (NCF1) gene, exons, T cell activation. INTRODUCTION. An immune system is a ...

  11. The Emerging Role of Guanine Exchange Factors in ALS and other neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Cristian eDroppelmann

    2014-09-01

    Full Text Available Small GTPases participate in a broad range of cellular processes such as proliferation, differentiation and migration. The exchange of GDP for GTP resulting in the activation of these GTPases is catalyzed by a group of enzymes called guanine nucleotide exchange factors (GEFs, of which two classes: Dbl-related exchange factors and the more recently described Dock family exchange factors. Increasingly, deregulation of normal GEF activity or function has been associated with a broad range of disease states, including neurodegeneration and neurodevelopmental disorders. In this review, we examine this evidence with special emphasis on the novel role of Rho guanine nucleotide exchange factor (RGNEF/p190RhoGEF in the pathogenesis of amyotrophic lateral sclerosis (ALS. RGNEF is the first neurodegeneration-linked GEF that regulates not only RhoA GTPase activation but also functions as an RNA binding protein that directly acts with low molecular weight neurofilament (NEFL mRNA 3’UTR to regulate its stability. This dual role for RGNEF, coupled with the increasing understanding of the key role for GEFs in modulating the GTPase function in cell survival suggests a prominent role for GEFs in mediating a critical balance between cytotoxicity and neuroprotection which, when disturbed, contributes to neuronal loss.

  12. The roles of the insulin-like growth factor system and leptin as ...

    African Journals Online (AJOL)

    The roles of the insulin-like growth factor system and leptin as possible mediators of the effects of nutritional restriction on age at puberty and compensatory growth in ... and IGFBP-3 are affected by nutritional restriction and repletion, and may contribute in some measure to the endocrine regulation of compensatory growth.

  13. Bullying and Victimization: Predictive Role of Individual, Parental, and Academic Factors

    Science.gov (United States)

    Atik, Gökhan; Güneri, Oya Yerin

    2013-01-01

    This study explored the roles of individual factors (age, gender, locus of control, self-esteem, and loneliness), parenting style, and academic achievement in discriminating students involved in bullying (as bullies, victims, and bully/victims) from those not involved. Participants comprised 742 middle school students (393 females, 349 males). The…

  14. The role of vascular endothelial growth factor in neurogenesis in adult brain.

    Science.gov (United States)

    Galvan, Veronica; Greenberg, David A; Jin, Kunlin

    2006-06-01

    VEGF is a canonical angiogenic factor. In addition, its role as a stimulator of neurogenesis was recently uncovered. Vascular and nervous networks share common molecular mechanisms underlying their morphogenesis. VEGF is likely to regulate both processes during development and in adult organisms.

  15. Contextual Predictive Factors of Child Sexual Abuse: The Role of Parent-Child Interaction

    Science.gov (United States)

    Ramirez, Clemencia; Pinzon-Rondon, Angela Maria; Botero, Juan Carlos

    2011-01-01

    Objectives: To determine the prevalence of child sexual abuse in the Colombian coasts, as well as to assess the role of parent-child interactions on its occurrence and to identify factors from different environmental levels that predict it. Methods: This cross-sectional study explores the results of 1,089 household interviews responded by mothers.…

  16. Data and hypotheses on the role of nerve growth factor and other neurotrophins in psychiatric disorders

    NARCIS (Netherlands)

    Bersani, G; Lannitelli, A; Fiore, M; Angelucci, F; Aloe, L

    Nerve growth factor (NGF) was discovered and characterized for its role on the growth, differentiation and maintenance of specific neurons of the peripheral nervous system. Subsequent studies revealed that NGF is synthesized and released within the central nervous system and exerts a trophic and

  17. Comparing Determinants of Perceived and Actual Recycling Skills: The Role of Motivational, Behavioral and Dispositional Factors

    Science.gov (United States)

    Passafaro, Paola; Livi, Stefano

    2017-01-01

    An empirical investigation assessed the role of different factors of motivational, behavioral, and dispositional nature in the prediction of both perceived and actual skills concerning household waste recycling. A structured questionnaire (measuring attitudes, social norms, perceived control, need for cognitive closure, self-reported household…

  18. Hypoxia-inducible factors - regulation, role and comparative aspects in tumourigenesis

    DEFF Research Database (Denmark)

    Hansen, A E; Kristensen, A T; Law, I

    2011-01-01

    Hypoxia-inducible factors (HIFs) play a key role in the cellular response experienced in hypoxic tumours, mediating adaptive responses that allow hypoxic cells to survive in the hostile environment. Identification and understanding of tumour hypoxia and the influence on cellular processes carries...

  19. Macrophage migration inhibitory factor: critical role in obesity, insulin resistance, and associated comorbidities.

    NARCIS (Netherlands)

    Kleemann, R.; Bucala, R.

    2010-01-01

    Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF) is an ubiquitously expressed protein that plays a crucial role in many

  20. Coping with chronic illness: the mediating role of biographic and illness-related factors.

    Science.gov (United States)

    Viney, L L; Westbrook, M T

    1982-01-01

    The aim of this research was to examine the mediating roles played by a range of biographic and illness-related factors in preferences for strategies for coping with chronic illness. Chronically-ill patients assessed their own coping strategy preference by ranking six clusters of strategies. Information was also obtained about their demographic characteristics, life styles, illness roles, the degree of their disability, their perceived handicaps and their perceived achievement of their rehabilitation goals. Multiple regression analyses of each of these six sets of variables on each coping strategy were carried out to identify patterns of association between them. (1) Preferences for action strategies were found to be associated with patient-related factors (demographic characteristics, life style and illness role). (2) Control strategies were associated with illness-related factors (illness role, degree of disability, perceived handicap and achievement of rehabilitation goals). (3) Escape strategies were ranked higher by women than by men, sex being their only significant predictor. (4) Preferences for fatalism, unlike those for action strategies, were associated with relatively low social status and relatively little interpersonal involvement or social commitment. (5) Preferences for optimism were related only to patients' perceptions of their handicaps. (6) Interpersonal coping was not found to be associated with any of this wide range of biographic illness-related factors.

  1. Exploring the Role of Motivational Factors in the Academic Achievement of EFL Learners

    Science.gov (United States)

    Solak, Ekrem

    2012-01-01

    The purpose of this research is to explore the role of motivational factors in the academic achievement of EFL learners. The research was conducted at a State University, Faculty of Education in Turkey. The participants were 230 freshman prospective teachers from four different academic majors taking English class. Attitude/Motivation Test Battery…

  2. Risk factors for admission and the role of respiratory syncytial virus ...

    African Journals Online (AJOL)

    Risk factors for admission and the role of respiratory syncytial virus-specific cytotoxic T-lymphocyte responses in children with acute bronchiolitis. ... CTL responses in peripheral blood of immunocompetent RSV-infected children suggest an alternative method of induction of immunity or compartmentalisation of immune cells.

  3. The Role of socioeconomic factors in fertility of Umuahia women in ...

    African Journals Online (AJOL)

    Rapid population growth arising from high fertility has been argued as being disadvantageous to the economic growth of countries especially the developing country like Nigeria. This paper examines the role of socioeconomic factors in fertility. The study elicited information from 500 women of the reproductive age of 15-49 ...

  4. Achieving Scientific Excellence: An Exploratory Study of the Role of Emotional and Motivational Factors

    Science.gov (United States)

    Araújo, Liliana S.; Cruz, José Fernando A.; Almeida, Leandro S.

    2017-01-01

    This study investigates the perceived role of psychological factors in achieving excellence in scientific research. Six outstanding scientists aged 33-42 were interviewed. Data were analyzed inductively resulting in three main dimensions: personality traits and characteristics, psychological skills and processes, and task-specific strategies.…

  5. Risk factors for admission and the role of respiratory syncytial virus ...

    African Journals Online (AJOL)

    (CTL) activity, enable respiratory syncytial virus (RSV)- specific CTL activity to be studied in infants with bronchiolitis for the first time. We evaluated risk factors for admission of children with acute bronchiolitis and determined the role of CTL responses in those infected with. RSV. Method. Children between 3 and 24 months ...

  6. Explaining Socioeconomic Inequalities In Student Achievement: The Role Of Home And School Factors

    Science.gov (United States)

    Marks, Gary; Cresswell, John; Ainley, John

    2006-01-01

    This paper examines the extent that material, social, and cultural resources and schools account for the relationship between socioeconomic background and student achievement among 15-year-olds in 30 countries. Generally, cultural factors play a more important role in most countries although in a small minority of countries, material resources…

  7. Potential roles of WRKY transcription factors in resistance to Aspergillus flavus colonization of immature maize kernels

    Science.gov (United States)

    Resistance to Aspergillus flavus by maize (Zea mays L.) is mediated by several defense proteins; however the mechanism regulating the expression of these defenses is poorly understood. This study examined the potential roles of six maize WRKY transcription factors, ZmWRKY19, ZmWRKY21, ZmWRKY53, ZmW...

  8. Role Performance of Community Health Volunteers and Its Associated Factors in Kuching District, Sarawak.

    Science.gov (United States)

    Chung, Melvin Hsien Liang; Hazmi, Helmy; Cheah, Whye Lian

    2017-01-01

    The objective of this study was to assess the role performance among KOSPEN community health volunteer in Kuching district and its associated factors. This was a cross-sectional study, conducted in 21 localities in Kuching with a total of 210 respondents. Data were collected using validated interviewer-administered questionnaires and analyzed using SPSS version 22.0. The respondents comprised 55.2% females, 81.9% married, and 41.4% aged above 45 and above and 72.4% completed their education up to secondary school. The result revealed that 59.0% of the respondents agreed and understood their role performances. Multiple Logistics analysis revealed that factors associated with role performance were age group (p = 0.003), education level (p performance of CHVs, commitment from the government, policy makers, stakeholders, and the communities is required.

  9. DMPD: The role of the interferon regulatory factor (IRF) family in dendritic celldevelopment and function. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17702640 The role of the interferon regulatory factor (IRF) family in dendritic cel...b 2007 Aug 16. (.png) (.svg) (.html) (.csml) Show The role of the interferon regulatory factor (IRF) family ...e interferon regulatory factor (IRF) family in dendritic celldevelopment and function. Authors Gabriele L, O

  10. Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Bhaskar Ponugoti

    2012-01-01

    Full Text Available Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response.

  11. Sedentary risk factors across genders and job roles within a university campus workplace: preliminary study.

    Science.gov (United States)

    Alkhatib, Ahmad

    2013-01-01

    The aim of this study was to investigate whether sedentary job role and gender are reflected by sedentary risk factors within a university campus. Following institutional ethical approval, 80 U.K. university campus employees were recruited, and 34 of them (age 47.8 ± 11.9 years, height 169 ± 1.0 cm, body mass 72.0 ± 14.1 kg) were measured for their systolic (SBP) and diastolic blood pressure (DBP), blood glucose (Glu), total serum blood cholesterol (Cho), dominant (DHG) and nondominant handgrip strength (NHG), body fat percentage (Fat%), trunk flexibility (Flex), peak cardiorespiratory capacity (V.O2max), and answered a physical activity questionnaire (IPAQ). The data were analyzed using two-way ANOVA with job role and gender as independent factors, and each measured risk as a dependent factor. Gender had significant effects (pworkplace.

  12. Role of milk fat globule-epidermal growth factor 8 in osteoimmunology.

    Science.gov (United States)

    Sinningen, Kathrin; Thiele, Sylvia; Hofbauer, Lorenz C; Rauner, Martina

    2016-01-01

    Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that is abundantly expressed in various tissues and has a pivotal role in the phagocytic clearance of apoptotic cells. However, MFG-E8 has also gained significant attention because of its wide range of functions in autoimmunity, inflammation and tissue homeostasis. More recently, MFG-E8 has been identified as a critical regulator of bone homeostasis, being expressed in both, osteoblasts and osteoclasts. In addition, it was shown that MFG-E8 fulfils an active role in modulating inflammatory processes, suggesting an anti-inflammatory role of MFG-E8 and proposing it as a novel therapeutic target for inflammatory diseases. This concise review focusses on the expression and regulation of MFG-E8 in the context of inflammatory bone diseases, highlights its role in the pathophysiology of osteoimmune diseases and discusses the therapeutic potential of MFG-E8.

  13. Factors that lead Generation Y nurses to consider or reject nurse leader roles

    Directory of Open Access Journals (Sweden)

    Rose O. Sherman

    Full Text Available Objective: This study examined factors that lead Generation Y nurses to consider or reject nursing leadership roles. Background: Almost half of the current nurse leaders in the country are expected to retire by the end of the decade. Generation Y will soon comprise 50% of the nursing workforce and organizations look to them to assume leadership roles. Learning how to effectively recruit, motivate and retain Generation Y nurse leaders will be critical to the future of nursing. Methods: This was a qualitative study that used a ConCensus™ process approach to collect the themes and factors of importance to participants related to nursing leadership roles. Three focus groups were conducted during 2013 and 2014 with 32 Generation Y Registered Nurses, not currently in leadership positions and born on or after January 1st, 1981. Key findings: Feedback from current nurse leaders about their roles is primarily negative. The strongest incentive for Generation Y nurses to seek leadership roles is the potential to create meaningful change in healthcare. Fear of failure in the role and lack of work-life balance are significant deterrents to accepting a leadership role. Conclusions: Generation Y nurses do see the value and importance of nursing leadership in making a difference in patient care but have concerns about the level of support that will be available to them as they assume these roles. Attention must be directed toward providing resources and strategies to develop skilled Generation Y nurse leaders in order to promote effective succession planning. Keywords: Generation Y, Millennials, Nursing leadership, Succession planning

  14. Expression and divalent cation binding properties of the novel chemotactic inflammatory protein psoriasin

    DEFF Research Database (Denmark)

    Vorum, H; Madsen, Peder; Rasmussen, H H

    1996-01-01

    -dimensional (2-D) gel electrophoresis and NH2-terminal sequencing. The ability of rh psoriasin to bind Ca2+, Zn2+, and Mg2+ was determined by dialysis experiments. We found that rh psoriasin may bind at least seven molecules of Ca2+ in KCl and several molecules in NaCl, with an affinity for the first bound...... in Escherichia coli as a fusion protein containing a hexa His tag and a factor Xa cleavage site in the NH2-terminus. The protein was purified by affinity chromatography on Ni(2+)-nitrilotriacetic acid agarose, digested with factor Xa, further purified by ion-exchange chromatography and characterized by two...

  15. The role of Anthropometric and Nutritional Factors on Breast Cancer Risk in African American Women

    Science.gov (United States)

    Chandran, Urmila; Hirshfield, Kim M.; Bandera, Elisa V.

    2013-01-01

    Objective While the role of nutrition, physical activity, and body size on breast cancer risk has been extensively investigated, most of these studies were conducted in Caucasian populations. However, there are well known differences in tumor biology and the prevalence of these factors between African American and Caucasian women. The objective of this paper was to conduct a review on the role of dietary factors, anthropometry, and physical activity on breast cancer risk in African American women. Design Twenty-six research articles that presented risk estimates on these factors in African American women and five articles involving non-US Black women were included in this review. Setting Racial disparities in the impact of anthropometric and nutritional factors on breast cancer risk Subjects African American and non-US Black women Results Based on the few studies that presented findings in African American women, an inverse association with physical activity was found for pre and postmenopausal African American women, while the association for anthropometric and other dietary factors, such as alcohol, was unclear. Studies assessing the effect by molecular subtypes in African American women were too few and based on sample sizes too small to provide definitive conclusions. Conclusions The effect of certain nutrition and lifestyle factors on breast cancer in African American is not starkly distinct from those observed in White women. However, there is an enormous need for further research on this minority group to obtain more confirmatory findings. PMID:22122844

  16. Human umbilical cord perivascular cells exhibited enhanced migration capacity towards hepatocellular carcinoma in comparison with bone marrow mesenchymal stromal cells: a role for autocrine motility factor receptor.

    Science.gov (United States)

    Bayo, Juan; Fiore, Esteban; Aquino, Jorge B; Malvicini, Mariana; Rizzo, Manglio; Peixoto, Estanislao; Alaniz, Laura; Piccioni, Flavia; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G; Mazzolini, Guillermo

    2014-01-01

    Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.

  17. Human Umbilical Cord Perivascular Cells Exhibited Enhanced Migration Capacity towards Hepatocellular Carcinoma in Comparison with Bone Marrow Mesenchymal Stromal Cells: A Role for Autocrine Motility Factor Receptor

    Directory of Open Access Journals (Sweden)

    Juan Bayo

    2014-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs and human umbilical cord perivascular cells (HUCPVCs towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2 and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.

  18. Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing

    Science.gov (United States)

    Pakyari, Mohammadreza; Farrokhi, Ali; Maharlooei, Mohsen Khosravi; Ghahary, Aziz

    2013-01-01

    Significance This review highlights the critical role of transforming growth factor beta (TGF-β)1–3 within different phases of wound healing, in particular, late-stage wound healing. It is also very important to identify the TGF-β1–controlling factors involved in slowing down the healing process upon wound epithelialization. Recent Advances TGF-β1, as a growth factor, is a known proponent of dermal fibrosis. Several strategies to modulate or regulate TGF's actions have been thoroughly investigated in an effort to create successful therapies. This study reviews current discourse regarding the many roles of TGF-β1 in wound healing by modulating infiltrated immune cells and the extracellular matrix. Critical Issues It is well established that TGF-β1 functions as a wound-healing promoting factor, and thereby if in excess it may lead to overhealing outcomes, such as hypertrophic scarring and keloid. Thus, the regulation of TGF-β1 in the later stages of the healing process remains as critical issue of which to better understand. Future Directions One hypothesis is that cell communication is the key to regulate later stages of wound healing. To elucidate the role of keratinocyte/fibroblast cross talk in controlling the later stages of wound healing we need to: (1) identify those keratinocyte-released factors which would function as wound-healing stop signals, (2) evaluate the functionality of these factors in controlling the outcome of the healing process, and (3) formulate topical vehicles for these antifibrogenic factors to improve or even prevent the development of hypertrophic scarring and keloids as a result of deep trauma, burn injuries, and any type of surgical incision. PMID:24527344

  19. A hybrid computational model to predict chemotactic guidance of growth cones

    OpenAIRE

    Roccasalvo, Iolanda Morana; Micera, Silvestro; Sergi, Pier Nicola

    2015-01-01

    The overall strategy used by growing axons to find their correct paths during the nervous system development is not yet completely understood. Indeed, some emergent and counterintuitive phenomena were recently described during axon pathfinding in presence of chemical gradients. Here, a novel computational model is presented together with its ability to reproduce both regular and counterintuitive axonal behaviours. In this model, the key role of intracellular calcium was phenomenologically mod...

  20. Hyaluronan’s Role in Fibrosis: A Pathogenic Factor or a Passive Player?

    Directory of Open Access Journals (Sweden)

    Sami Albeiroti

    2015-01-01

    Full Text Available Fibrosis is a debilitating condition that can lead to impairment of the affected organ’s function. Excessive deposition of extracellular matrix (ECM molecules is characteristic of most fibrotic tissues. Fibroblasts activated by cytokines or growth factors differentiate into myofibroblasts that drive fibrosis by depositing ECM molecules, such as collagen, fibronectin, and connective tissue growth factor. Transforming growth factor-β (TGF-β is one of the major profibrotic cytokines which promotes fibrosis by signaling abnormal ECM regulation. Hyaluronan (HA is a major ECM glycosaminoglycan that is regulated by TGF-β and whose role in fibrosis is emerging. Aside from its role as a hydrating, space filling polymer, HA regulates different cellular functions and is known to have a role in wound healing and inflammation. Importantly, HA deposition is increased in multiple fibrotic diseases. In this review we highlight studies that link HA to fibrosis and discuss what is known about the role of HA, its receptors, and its anabolic and catabolic enzymes in different fibrotic diseases.

  1. Impact of urbanization of the proteome of birch pollen and its chemotactic activity on human granulocytes

    NARCIS (Netherlands)

    Bryce, M.; Drews, O.; Schenk, M.F.; Menzel, A.; Estrella, N.; Weichenmeier, I.; Smulders, M.J.M.; Buters, J.; Ring, J.; Gorg, A.; Behrendt, H.; Traidl-Hoffmann, C.

    2010-01-01

    Background: Epidemiologic studies reveal a dramatic increase in allergies in the last decades. Air pollution is considered to be one of the factors responsible for this augmentation. The aim of this study was to analyze the impact of urbanization on birch pollen. The birch pollen proteome was

  2. Role of psychological factors in burning mouth syndrome: A systematic review and meta-analysis.

    Science.gov (United States)

    Galli, Federica; Lodi, Giovanni; Sardella, Andrea; Vegni, Elena

    2017-03-01

    Background Burning mouth syndrome (BMS) is a chronic medical condition characterised by hot, painful sensations in the lips, oral mucosa, and/or tongue mucosa. On examination, these appear healthy, and organic causes for the pain cannot be found. Several studies have yielded scant evidence of the involvement of psychological and/or psychopathological factors, and several have outlined a model for the classification of BMS. Aim This review aims to provide a systematic review of research examining the psychological, psychiatric, and/or personality factors linked to BMS. Findings Fourteen controlled studies conducted between 2000 and the present were selected based on stringent inclusion/exclusion criteria. All studies but one reported at least some evidence for the involvement of psychological factors in BMS. Anxiety and depression were the most common and the most frequently studied psychopathological disorders among BMS patients. Discussion and conclusion Anxiety and depression play critical roles in this condition. Evidence on the role of personality characteristics of BMS patients has also been produced by a few studies. Further studies on the role of specific psychological factors in BMS are warranted, but the importance of a multidisciplinary approach (medical and psychological) to BMS is no matter of discussion.

  3. The cis-acting phorbol ester "12-O-tetradecanoylphorbol 13-acetate"-responsive element is involved in shear stress-induced monocyte chemotactic protein 1 gene expression.

    OpenAIRE

    Shyy, J Y; Lin, M C; Han, J; Lu, Y; Petrime, M; Chien, S

    1995-01-01

    Vascular endothelial cells, serving as a barrier between vessel and blood, are exposed to shear stress in the body. Although endothelial responses to shear stress are important in physiological adaption to the hemodynamic environments, they can also contribute to pathological conditions--e.g., in atherosclerosis and reperfusion injury. We have previously shown that shear stress mediates a biphasic response of monocyte chemotactic protein 1 (MCP-1) gene expression in vascular endothelial cells...

  4. The directional response of chemotactic cells depends on a balance between cytoskeletal architecture and the external gradient.

    Science.gov (United States)

    Wang, Ming-Jie; Artemenko, Yulia; Cai, Wen-Jie; Iglesias, Pablo A; Devreotes, Peter N

    2014-11-06

    Polarized migrating cells display signal transduction events, such as activation of phosphatidylinositol 3-kinase (PI3K) and Scar/Wave, and respond more readily to chemotactic stimuli at the leading edge. We sought to determine the basis of this polarized sensitivity. Inhibiting actin polymerization leads to uniform sensitivity. However, when human neutrophils were "stalled" by simultaneously blocking actin and myosin dynamics, they maintained the gradient of responsiveness to chemoattractant and also displayed noise-driven PIP3 flashes on the basal membrane, localized toward the front. Thus, polarized sensitivity does not require migration or cytoskeletal dynamics. The threshold for response is correlated with the static F-actin distribution, but not cell shape or volume changes, membrane fluidity, or the preexisting distribution of PI3K. The kinetics of responses to temporal and spatial stimuli were consistent with the local excitation global inhibition model, but the overall direction of the response was biased by the internal axis of polarity. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma.

    Science.gov (United States)

    Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

    2017-04-04

    Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.

  6. Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro by the extracts of selected medicinal plants.

    Science.gov (United States)

    Jantan, Ibrahim; Harun, Nurul Hikmah; Septama, Abdi Wira; Murad, Shahnaz; Mesaik, M A

    2011-04-01

    The methanol extracts of 20 selected medicinal plants were investigated for their effects on the respiratory burst of human whole blood, isolated human polymorphonuclear leukocytes (PMNs) and isolated mice macrophages using a luminol/lucigenin-based chemiluminescence assay. We also tested the effect of the extracts on chemotactic migration of PMNs using the Boyden chamber technique. The extracts of Curcuma domestica L., Phyllanthus amarus Schum & Thonn and C. xanthorrhiza Roxb. were the samples producing the strongest oxidative burst of PMNs with luminol-based chemiluminescence, with IC(50) values ranging from 0.5 to 0.7 μg/ml. For macrophage cells, the extracts which showed strong suppressive activity for luminol-based chemiluminescence were C. xanthorrhiza and Garcinia mangostana L. Among the extracts studied, C. mangga Valton & Vazsjip, Piper nigrum L. and Labisia pumila var. alata showed strong inhibitory activity on lucigenin-amplified oxidative burst of PMNs, with IC(50) values ranging from 0.9 to 1.5 μg/ml. The extracts of Zingiber officinale Rosc., Alpinia galangal (L.) Willd and Averrhoa bilimbi Linn showed strong inhibition on the chemotaxic migration of cells, with IC(50) values comparable to that of ibuprofen (1.5 μg/ml). The results suggest that some of these plants were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.

  7. Factors That Play a Role in the Academic Resilience of Academicians

    Directory of Open Access Journals (Sweden)

    Ömer KUTLU

    2016-12-01

    Full Text Available In academic life, it is possible for all students to experience different obstacles, hardships and setbacks. While some students fail to negotiate their way through these difficulties, many are successful. In this context, the purpose of this study is to reveal the factors that play a role in the academic resilience of academicians. In this context, a qualitative study was employed, with semi-structured interviews conducted with 11 academicians from the Educational Sciences Faculty of Ankara University, Turkey. Eligibility criteria required academicians to have had a risk factor in their life. The academicians were also selected on the basis of their title and years of experience to sustain variety. In order to conduct interviews, an interview guide was prepared by the researchers. The questions in the interview guide for this study were linked to risk factors, and internal and external protective factors. Descriptive analysis was used to analyze collected data. According to the findings, mainly risk factors which academically resilient academicians had experienced were poverty, and negative environmental conditions. On the other hand, this study revealed that internal factors such as self-esteem, decisiveness, curiosity and external factors such as family support, qualified teachers, and peer relations helped them to overcome their risk factors.

  8. Role of the environmental factor in the competitiveness of the region

    Directory of Open Access Journals (Sweden)

    N. Ya. Kalyuzhnova

    2010-09-01

    Full Text Available The article shows the role of environmental factor in the competitiveness of the region. The issue of the country's image and the region is considered according to ecology and touristic appeal. We consider the modern role of botanical gardens and their transformation from scientific horticultural organizations to the objects of multi-use facilities type, for a regional multi-utility. The experience of an innovative project of creation of Russia's first environmental technological park and tourist-recreational zone on the basis of the university botanical garden in Irkutsk using the public-private partnership is stated.

  9. Macrophage Migration Inhibitory Factor: Critical Role in Obesity, Insulin Resistance, and Associated Comorbidities

    Directory of Open Access Journals (Sweden)

    Robert Kleemann

    2010-01-01

    Full Text Available Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF is an ubiquitously expressed protein that plays a crucial role in many inflammatory and autoimmune disorders. Increasing evidence suggests that MIF also controls metabolic and inflammatory processes underlying the development of metabolic pathologies associated with obesity. This is a comprehensive summary of our current knowledge on the role of MIF in obesity and obesity-associated comorbidities, based on human clinical data as well as animal models of disease.

  10. The Role of Social and Educational Factors in Oral Participation of ELT Students

    Directory of Open Access Journals (Sweden)

    Masoud Zoghi

    2013-11-01

    Full Text Available Oral participation (OP in class is an important factor contributing to the development of oral fluency. Recent studies in language learning have addressed the necessity of classroom interaction, or rather students’ oral participation in class. A correlational research study was drawn upon to measure the oral participation and factors affecting oral activities of the ELT students studying at the M.A. level at Islamic Azad University of Ardabil in Iran. An initial pool of 93 participants was selected through purposive sampling. The data analysis was conducted using structural equation modeling (SEM. The results obtained indicated that there is a significant relationship between social and educational factors relative to the oral activities of EFL learners. The findings also showed that in oral participation, educational factors play the most important role in controlling the OP content.

  11. An Empirical Investigation of the Role of Industry Factors in the Internationalization Patterns of Firms

    DEFF Research Database (Denmark)

    Grøgaard, Birgitte; Gioia, Carmine; Benito, Gabriel R. G.

    neglected as potential determinants of companies' internationalization. We argue that differences across industries with regard to competition level, research intensity, tangibility of the products, and the existence of clusters should influence the impetus and opportunities to internationalize. This study......Research on companies' internationalization has mainly focused on firm-level and country-level factors in order to explain firms' cross-border activities. With the exception of a limited number of studies emphasizing rivalistic behavior in oligopolistic industries, industry factors have been...... examines the role of such factors using data covering the internationalization patterns of the 100 largest non-financial Norwegian companies over the period 1990 to 2000. We find that industry factors contribute significantly to explaining the internationalization of these companies, and that the effects...

  12. Role of Factor Xa Inhibitors in Cancer-Associated Thrombosis: Any New Data?

    Directory of Open Access Journals (Sweden)

    Ali Zalpour

    2011-01-01

    Full Text Available The association between cancer and venous thromboembolism (VTE has been well documented in the literature. Prevention and treatment of VTE in cancer patients is imperative. Typically, the mainstay regimen for VTE prevention and treatment has been anticoagulation therapy, unless contraindicated. This therapy consists of unfractionated heparin (UFH, low-molecular-weight heparin (LMWH, factor Xa inhibitor, or vitamin K antagonist (VKA. Current guidelines recommend LMWH over VKA for the treatment of VTE in cancer patients. Factor-specific anticoagulants have been proven safe and effective, and recently factor Xa inhibitors have emerged as a treatment alternative to heparins and VKA. Currently, three factor Xa inhibitors have been identified: fondaparinux (the only one approved so far by the US Food and Drug Administration, idraparinux (in clinical trials, and idrabiotaparinux (in clinical trials. This paper will examine the role of these agents, focusing on fondaparinux, for the prevention and treatment of VTE in cancer patients.

  13. Exploring the chemotactic attraction of Campylobacter jejuni in chicken colonization

    DEFF Research Database (Denmark)

    Vegge, Christina Skovgaard; Brøndsted, Lone; Ingmer, Hanne

    are found to be colonized by C. jejuni, and the bacteria are expected to be attracted to this particular environment by chemotaxis. In order to explore the role of chemotaxis in C. jejuni colonization we are construction deletion mutants in the putative chemoreceptors of the sequenced strain NCTC11168....... These mutants will be analyzed for their chemotatic capacity in order to investigate the chemoreceptor function and to identify matching chemoeffectors. Furthermore, selected mutants will be investigated for their ability to colonize chickens with focus on establishment, level, and persistence. Special emphasis...

  14. Quinn’s Leadership Roles: A Confirmatory Factor Analysis Study in Portuguese Health Services

    Directory of Open Access Journals (Sweden)

    Pedro Parreira

    2015-08-01

    Full Text Available Purpose: To assess the psychometric properties of Quinn’s leadership questionnaire (CFV questionnaire; 1988 in Portuguese health services. Design: Cross-sectional study, using Quinn’s leadership questionnaire, administered to registered nurses and physicians in Portuguese health services (N = 687. Method: Self-administered survey applied to two samples. In the first sample (convenience; N = 249 Portuguese health professionals, exploratory factor and reliability analyses were performed to the CFV questionnaire. In the second sample (stratified; N = 50 surgical units of 33 Portuguese hospitals, confirmatory factor analyses were performed using LISREL 8.80. Findings: In the first sample, an eight-factor solution emerged accounting for 65.46% of the total variance, in an interpretable factor structure (loadings> .50, with Cronbach’s α greater than .79. This factor structure, replicated in the second sample, showed reasonable goodness-of-fit of the model to each of the leadership roles, that is, to the eight quadrants and global model. Overall, the models showed nomological validity, with scores between good and acceptable (.235 < x2/df < 2.055 and .00 < RMSEA < .077. Conclusions: Quinn’s leadership questionnaire showed good reliability and validity for the eight leadership roles, proving to be suitable for use in health care/hospital settings.

  15. Role of Environmental Factors in the Development of Pediatric Eosinophilic Esophagitis.

    Science.gov (United States)

    Slae, Mordechai; Persad, Rabin; Leung, Aldrich Jing-Tao; Gabr, Raniah; Brocks, Dion; Huynh, Hien Quoc

    2015-11-01

    Despite accumulating data on the pathogenesis of eosinophilic esophagitis, not much is known about risk factors for the development of the disease. The role of factors such as smoking, breastfeeding, early antibiotic exposure and other factors that have been associated with other allergic diseases has not been well studied in children with eosinophilic esophagitis. To explore the role of environmental and medication exposures in the development of pediatric eosinophilic esophagitis. We conducted a cross-sectional case-control study, utilizing a parent and child questionnaire and medical chart review. Urine cotinine levels, measured by high-performance liquid chromatography, were obtained as objective evidence for smoking exposure. One hundred and two children with eosinophilic esophagitis and 167 controls were recruited. The controls were mainly diagnosed with functional gastrointestinal disorders (33%) and gastroesophageal reflux disease (29%). Food allergy, specifically for peanuts and tree nuts, and allergy to pollen, tree, and grass were significantly higher among eosinophilic esophagitis children. Smoking exposure, both primary and secondary, was not associated with pediatric eosinophilic esophagitis when compared to controls (odds ratio 0.96, 95% confidence interval 0.58-1.59). Furthermore, early smoking exposure in the first year of life was higher among controls. Common accepted risk factors for allergy and atopy, such as breastfeeding practices, antibiotics exposure, animals' exposure, and others, were not found to be associated with eosinophilic esophagitis in our study. Common risk factors in other allergic and atopic conditions were not found to be associated with eosinophilic esophagitis.

  16. Relating Education, Brain Structure, and Cognition: The Role of Cardiovascular Disease Risk Factors

    Directory of Open Access Journals (Sweden)

    Moyra E. Mortby

    2014-01-01

    Full Text Available The protective effect of education on cognitive and brain health is well established. While the direct effects of individual cardiovascular disease (CVD risk factors (i.e., hypertension, smoking, diabetes, and obesity on cerebral structure have been investigated, little is understood about the possible interaction between the protective effect of education and the deleterious effects of CVD risk factors in predicting brain ageing and cognition. Using data from the PATH Through Life study (N=266, we investigated the protective effect of education on cerebral structure and function and tested a possible mediating role of CVD risk factors. Higher education was associated with larger regional grey/white matter volumes in the prefrontal cortex in men only. The association between education and cognition was mediated by brain volumes but only for grey matter and only in relation to information processing speed. CVD risk factors did not mediate the association between regional volumes and cognition. This study provides additional evidence in support for a protective effect of education on cerebral structures and cognition. However, it does not provide support for a mediating role of CVD risk factors in these associations.

  17. Etiopathogenesis of Sheehan’s Syndrome: Roles of Coagulation Factors and TNF-Alpha

    Directory of Open Access Journals (Sweden)

    Halit Diri

    2014-01-01

    Full Text Available Sheehan’s Syndrome (SS is defined as pituitary hormone deficiency due to ischemic infarction of the pituitary gland as a result of massive postpartum uterine hemorrhage. Herein, we aimed to investigate the roles of Factor II (G20210A, Factor V (G1691A, MTHFR (C677T and A1298C, PAI-1 4G/5G, and TNF-α (-308  G>A gene polymorphisms in the etiopathogenesis of SS. Venous blood samples were obtained from 53 cases with SS and 43 healthy women. Standard methods were used to extract the genomic DNAs. Factor II (G20210A, Factor V (G1691A, and MTHFR (C677T and A1298C polymorphisms were identified by real-time PCR. PAI-1 4G/5G and TNF-α (-308  G>A gene polymorphisms were detected with polymerase chain reaction (PCR and restriction fragment length polymorphism (RFLP methods. According to statistical analysis, none of the polymorphisms were found to be significantly higher in the SS group compared to the control group. Hence, we suggest that genetic factors other than Factor II, Factor V, MTHFR, PAI-1, and TNF-α gene polymorphisms should be researched in the etiopathogenesis of SS.

  18. Role of ciliary neurotrophic factor in the proliferation and differentiation of neural stem cells.

    Science.gov (United States)

    Ding, Jun; He, Zhili; Ruan, Juan; Ma, Zilong; Liu, Ying; Gong, Chengxin; Iqbal, Khalid; Sun, Shenggang; Chen, Honghui

    2013-01-01

    Ciliary neurotrophic factor (CNTF) is a pleiotropic cytokine that has been fully studied for its structure, receptor, and signaling pathways and its multiplex effects on neural system, skeletal muscle, and weight control. Recent research demonstrates that CNTF also plays an important role in neurogenesis and the differentiation of neural stem cells. In this article, we summarize the general characteristics of CNTF and its function on neural stem cells, which could be a valuable therapeutic strategy in treating neurological disorders.

  19. Factors of academic procrastination: The role of perfectionism, anxiety and depression

    OpenAIRE

    Eva Kranjec; Katja Košir; Luka Komidar

    2016-01-01

    This study investigated dimensions of perfectionism, anxiety, and depression as factors of academic procrastination. Our main research interest was to examine the role of specific dimensions of perfectionism as moderators in the relationship between anxiety and depression and academic procrastination. Four scales were administered on the sample of 403 students: perfectionism scale FMPS, academic procrastination scale APS-SI, depression scale CESD and anxiety scale STAI-X2. The results showed ...

  20. Vascular endothelial growth factor B-role in metabolism, lipotoxicity and disease

    OpenAIRE

    Mehlem, Annika

    2016-01-01

    Vascular Endothelial Growth Factor B (VEGF-B) was previously shown to control lipid uptake from the bloodstream via the endothelium into tissue cells, and when ablating Vegfb, intra-tissue lipid accumulation was reduced. However, very little is known regarding the metabolic role of VEGF-B in physiologic, or pathophysiologic conditions. In paper I, we characterized the upstream regulatory mechanism controlling VEGF-B expression. We showed in vitro and in vivo that peroxisome ...

  1. The Role Played by Socio-Cultural Factors in Sports Consumer Behavior

    OpenAIRE

    Hossein Abdolmaleki; Zahrasadat Mirzazadeh; Ebrahim Alidoust Ghahfarokhhi

    2016-01-01

    One common aspect of all human beings, regardless of education level, income level, location and so on, is that they are all consumers. The key of success in marketing strategy both in terms of local and global aspects is understanding consumer behavior. So aim of this study was to investigate the role of socio-cultural factors on sports consumer behavior. This research was survey- descriptive. The study population were included all sports consumers in Tehran. The sampling method was random. ...

  2. Role of hypoxia and hypoxia inducible factor in physiological and pathological conditions

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    Mozhgan Jahani

    2017-11-01

    Full Text Available Introduction: Organisms are exposed to oxygen deprivation (Hypoxia in various physiological and pathological conditions. There are different conserve evolutionary responses to counterview with this stress that primary transcriptional response to stress related to hypoxia is interceded by hypoxia-inducible factor (HIF-1 in mammals. This factor can regulate different genes that have essential roles in adaptation to this condition. In this review, the role of this factor in physiological and pathological conditions under hypoxic condition has been evaluated after examining structural features and regulation characteristics of HIF-1. Methods: First, articles related to the keywords of hypoxia and HIF-1 (from 1991-2016 were searched from valid databases such as Springer Link, Google Scholar, PubMed and Science direct. Then, the articles correlated with hypoxia, HIF-1 and their roles in physiological and pathological conditions (120 articles were searched and just 64 articles were selected for this study. Result: According to studies, there are different genes in cells and organs that can be regulated by HIF-1. Activation of genes expression by this protein occurs through its linkage to cis-acting of 50 base pair hypoxia response element (HRE region located in their promotor and enhancer. Depending on circumstances, activation of these genes can be beneficial or harmful. Conclusion: Activation of different genes in hypoxia by HIF-1 has different effects on physiological and pathological conditions. Therefore, HIF-1, as a hypoxia-inducible factor in hypoxic conditions, plays an essential role in the adaptation of cells and organs to changes related to the presence of oxygen.

  3. Factors That Play a Role in the Academic Resilience of Academicians

    OpenAIRE

    Ömer KUTLU; Hatice Çiğdem YAVUZ

    2016-01-01

    In academic life, it is possible for all students to experience different obstacles, hardships and setbacks. While some students fail to negotiate their way through these difficulties, many are successful. In this context, the purpose of this study is to reveal the factors that play a role in the academic resilience of academicians. In this context, a qualitative study was employed, with semi-structured interviews conducted with 11 academicians from the Educational Sciences Faculty of Ankara ...

  4. An investigation into the factors that influence the buying process of online role-playing gamers

    OpenAIRE

    Mifsud, Brian

    2016-01-01

    Massively multiplayer online role-playing games (MMORPGs) are the dominant form of online games. This study attempts to uncover what factors influence gamers when purchasing a MMORPG and renewing its monthly subscription. The results of this study confirm that MMORPGs are still male-dominated and gamers are likely to be single and have higher levels of education. A MMORPG should cost around €40 and a reasonable monthly subscription fee should be around €13. Gameplay videos and ...

  5. Sex roles and values of school children using self-esteem as a moderating factor.

    Science.gov (United States)

    Salminen, S

    1994-01-01

    This article consists of two studies. Study 1 compares the values of Finnish high school students with those of American students. The results show that Finnish adolescents value popularity more than academic or athletic success. Differences in values also reflect differences in the Finnish national character, school system, and sports organization. Study 2 investigated self-esteem as a moderating factor between the adolescents' values and their sex roles. Subjects were 743 school children who completed the Bem's Sex-Role Inventory and the Coopersmith's Self-esteem Inventory. The results showed that a traditional sex role was more prominent in the group of students with low self-esteem than in the group with high self-esteem.

  6. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis.

    Science.gov (United States)

    Gonzalo-Gil, Elena; Galindo-Izquierdo, María

    2014-01-01

    Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  7. Embryonic mouse testis development: role of platelet derived growth factor (PDGF-BB).

    Science.gov (United States)

    Ricci, G; Catizone, A; Galdieri, M

    2004-09-01

    Platelet-derived growth factors (PDGFs) are paracrine growth factors mediating epithelial-mesenchymal interactions and exerting multiple biological activities which include cell proliferation, motility, and differentiation. As previously demonstrated, PDGFs act during embryonic development and recently, by culturing male genital ridges, we have demonstrated that PDGF-BB is able to support in vitro testicular cord formation. In the present paper, we report that PDGF-BB is present during embryonic testis development and, in organ culture, induces cord formation although with reduced diameters compared with the cords formed in the genital ridges cultured in the presence of HGF. Moreover we have analyzed the roles exerted by this growth factor during the morphogenesis of the testis. We demonstrate by immunohistochemical experiments that PDGF-BB and its receptors are synthesized by the male UGRs isolated from 11.5 and 13.5 dpc embryos and by Western blot that the factor is secreted in a biologically active form by testicular cells isolated from 13.5 dpc embryos. The biological roles of the factor have also been studied and we demonstrate that PDGF-BB acts as a migratory factor for male mesonephric cells whose migration is a male specific event necessary for a normal testicular morphogenesis. In addition we demonstrate that during testicular development, PDGF-BB induces testicular cell proliferation being in this way responsible for the increase in size of the testis. Finally we demonstrate that PDGF-BB is able to reorganize dissociated testicular cells inducing the formation of large cellular aggregates. However the structures formed in vitro under PDGF-BB stimulation never had a cord-like morphology similar to the cord-like structures formed in the presence of HGF (Ricci et al., 2002, Mech Dev 118:19-28), suggesting that this factor does not act as a morphogenetic factor during testicular development. All together the data presented in this paper demonstrate that PDGF

  8. A systems biology perspective on the role of WRKY transcription factors in drought responses in plants.

    Science.gov (United States)

    Tripathi, Prateek; Rabara, Roel C; Rushton, Paul J

    2014-02-01

    Drought is one of the major challenges affecting crop productivity and yield. However, water stress responses are notoriously multigenic and quantitative with strong environmental effects on phenotypes. It is also clear that water stress often does not occur alone under field conditions but rather in conjunction with other abiotic stresses such as high temperature and high light intensities. A multidisciplinary approach with successful integration of a whole range of -omics technologies will not only define the system, but also provide new gene targets for both transgenic approaches and marker-assisted selection. Transcription factors are major players in water stress signaling and some constitute major hubs in the signaling webs. The main transcription factors in this network include MYB, bHLH, bZIP, ERF, NAC, and WRKY transcription factors. The role of WRKY transcription factors in abiotic stress signaling networks is just becoming apparent and systems biology approaches are starting to define their places in the signaling network. Using systems biology approaches, there are now many transcriptomic analyses and promoter analyses that concern WRKY transcription factors. In addition, reports on nuclear proteomics have identified WRKY proteins that are up-regulated at the protein level by water stress. Interactomics has started to identify different classes of WRKY-interacting proteins. What are often lacking are connections between metabolomics, WRKY transcription factors, promoters, biosynthetic pathways, fluxes and downstream responses. As more levels of the system are characterized, a more detailed understanding of the roles of WRKY transcription factors in drought responses in crops will be obtained.

  9. The role of dietary factors in prevention and progression of breast cancer.

    Science.gov (United States)

    Rossi, Roberta Elisa; Pericleous, Marinos; Mandair, Dalvinder; Whyand, Tara; Caplin, Martyn Evan

    2014-12-01

    Breast cancer (BC) is the leading global cause of cancer-related death in women. There is growing evidence for a role for dietary factors in BC pathophysiology. The aim of the present review was to evaluate the impact of dietary factors in BC risk. Bibliographical searches were performed in PubMed, using the following terms: "nutrition and breast cancer", "nutrition and breast carcinoma", "dietary factors and breast cancer", "risk factors and breast cancer", "diet and breast cancer, "breast cancer epidemiology", "breast cancer and prevention". Consumption of well-done red meat appears to be associated with increased risk of BC, whereas fish may be protective. Total cholesterol, triglyceride levels and glycaemic load should be monitored and controlled in at risk populations because they may be associated with increased risk of BC, although the exact mechanisms involved are not clear. Alcohol intake should be minimized since it is a risk factor for BC. High intake of polyphenol/phyto-oestrogen -rich food (i.e. flavonoids, soya products), as well as fibres, fruits and vegetables, may have potential protective effects against BC occurrence but the results might vary according to hormonal status. Vitamin D supplements appear protective against BC development and similarly other vitamins and oligo-elements might decrease BC risk, although further large prospective studies are required. There exist increasing evidence that dietary factors can play an important role in both the development and prevention of BC. Large randomized clinical and epidemiological studies are required but are difficult to design due to the number of variable factors. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer

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    Kristine von Maltzan

    2016-02-01

    Full Text Available The Slug transcription factor plays an important role in ultraviolet radiation (UVR-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2 pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results.

  11. NF-κB Transcription Factor Role in Consolidation and Reconsolidation of Persistent Memories

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    Verónica ede la Fuente

    2015-09-01

    Full Text Available Transcriptional regulation is an important molecular process required for long-term neural plasticity and long-term memory formation. Thus, one main interest in molecular neuroscience in the last decades has been the identification of transcription factors that are involved in memory processes. Among them, the NF-κB family of transcription factors has gained interest due to a significant body of evidence that supports a key role of these proteins in synaptic plasticity and memory. In recent years, the interest was particularly reinforced because NF-κB was characterized as an important regulator of synaptogenesis. This function may be explained by its participation in synapse to nucleus communication, as well as a possible local role at the synapse. This review provides an overview of experimental work obtained in the last years, showing the essential role of this transcription factor in memory processes in different learning tasks in mammals. We focus the review on the consolidation and reconsolidation memory phases as well as on the regulation of immediate-early and late genes by epigenetic mechanisms that determine enduring forms of memories.

  12. The role of psychological factors in the career of the independent dancer

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    Imogen eAujla

    2015-10-01

    Full Text Available Previous research indicates that psychological factors such as motivation and mental skills play an important role in relation to performance and to negotiating talent development stages. However, little is known about these factors in dance, particularly with regard to the independent dancer whose career may involve multiple roles, varied work patterns and periods of instability. The aim of this study was to explore dancers’ motivation to work in an independent capacity, and the extent to which dancers’ psychological characteristics and skills enabled them to navigate a career in this demanding sector. In-depth semi-structured interviews were conducted with 14 dancers at different stages of their careers. Interviews were transcribed verbatim and content analyzed. Analysis revealed that the dancers were intrinsically motivated and highly committed to the profession. Working in the independent sector offered dancers opportunities for growth and fulfillment; they appreciated the autonomy, flexibility and freedom that the independent career afforded, as well as working with new people across roles and disciplines. In order to overcome the various challenges associated with the independent role, optimism, self-belief, social support and career management skills were crucial. The mental skills reported by the participants had developed gradually in response to the demands that they faced. Therefore, mental skills training could be invaluable for dancers to help them successfully negotiate the independent sector.

  13. The role of psychological factors in the career of the independent dancer.

    Science.gov (United States)

    Aujla, Imogen; Farrer, Rachel

    2015-01-01

    Previous research indicates that psychological factors such as motivation and mental skills play an important role in relation to performance and to negotiating talent development stages. However, little is known about these factors in dance, particularly with regard to the independent dancer whose career may involve multiple roles, varied work patterns, and periods of instability. The aim of this study was to explore dancers' motivation to work in an independent capacity, and the extent to which dancers' psychological characteristics and skills enabled them to navigate a career in this demanding sector. In-depth semi-structured interviews were conducted with 14 dancers at different stages of their careers. Interviews were transcribed verbatim and content analyzed. Analysis revealed that the dancers were intrinsically motivated and highly committed to the profession. Working in the independent sector offered dancers opportunities for growth and fulfillment; they appreciated the autonomy, flexibility and freedom that the independent career afforded, as well as working with new people across roles and disciplines. In order to overcome the various challenges associated with the independent role, optimism, self-belief, social support, and career management skills were crucial. The mental skills reported by the participants had developed gradually in response to the demands that they faced. Therefore, mental skills training could be invaluable for dancers to help them successfully negotiate the independent sector.

  14. The role of psychological factors in oncology nurses' burnout and compassion fatigue symptoms.

    Science.gov (United States)

    Duarte, Joana; Pinto-Gouveia, José

    2017-06-01

    This study explored the role of several psychological factors in professional quality of life in nurses. Specifically, we tried to clarify the relationships between several dimensions of empathy, self-compassion, and psychological inflexibility, and positive (compassion satisfaction) and negative (burnout and compassion fatigue) domains of professional quality of life. Using a cross-sectional design, a convenience sample of 221 oncology nurses recruited from several public hospitals filling out a battery of self-report measures. Results suggested that nurses that benefit more from their work of helping and assisting others (compassion satisfaction) seem to have more empathic feelings and sensibility towards others in distress and make an effort to see things from others' perspective. Also, they are less disturbed by negative feelings associated with seeing others' suffering and are more self-compassionate. Nurses more prone to experience the negative consequences associated with care-providing (burnout and compassion fatigue) are more self-judgmental and have more psychological inflexibility. In addition, they experience more personal feelings of distress when seeing others in suffering and less feelings of empathy and sensibility to others' suffering. Psychological factors explained 26% of compassion satisfaction, 29% of burnout and 18% of compassion fatigue. We discuss the results in terms of the importance of taking into account the role of these psychological factors in oncology nurses' professional quality of life, and of designing nursing education training and interventions aimed at targeting such factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Transcription factor co-repressors in cancer biology: roles and targeting.

    Science.gov (United States)

    Battaglia, Sebastiano; Maguire, Orla; Campbell, Moray J

    2010-06-01

    Normal transcription displays a high degree of flexibility over the choice, timing and magnitude of mRNA expression levels that tend to oscillate and cycle. These processes allow for combinatorial actions, feedback control and fine-tuning. A central role has emerged for the transcriptional co-repressor proteins such as NCOR1, NCOR2/SMRT, CoREST and CTBPs, to control the actions of many transcriptional factors, in large part, by recruitment and activation of a range of chromatin remodeling enzymes. Thus, co-repressors and chromatin remodeling factors are recruited to transcription factors at specific promoter/enhancer regions and execute changes in the chromatin structure. The specificity of this recruitment is controlled in a spatial-temporal manner. By playing a central role in transcriptional control, as they move and target transcription factors, co-repressors act as a key driver in the epigenetic economy of the nucleus. Co-repressor functions are selectively distorted in malignancy, by both loss and gain of function and contribute to the generation of transcriptional rigidity. Features of transcriptional rigidity apparent in cancer cells include the distorted signaling of nuclear receptors and the WNTs/beta-catenin axis. Understanding and predicting the consequences of altered co-repressor expression patterns in cancer cells has diagnostic and prognostic significance, and also have the capacity to be targeted through selective epigenetic therapies.

  16. THE ROLE OF ADVERTISEMENT FACTORS IN DEVELOPMENT OF SPORT TOURISM INDUSTRY OF FARS PROVINCE

    Directory of Open Access Journals (Sweden)

    Fatemeh Eloon Kashkuli

    2014-06-01

    Full Text Available Purpose: The aim of this study is to investigate the role of advertisement factors in development of sport tourism industry of Fars province. Materials and methods : Present study is descriptive and functional. We used marketing indices questionnaire for collecting data. Statistical population was all the responsible managers and experts in tourism and sport which through purposeful non-random sampling method 170 of them were selected as samples. To calculate reliability by Cronbach's Alpha in a pilot study on a 40 people sample, marketing factors were alfa=0.82. Data were analyzed after collecting in respect of study hypotheses through Chi2 tests. Results: Study findings show that from managers and experts views the most effective advertisement factors to develop sport tourism industry are respectively: written activities, investigate and understand tourists motivations to provide their requirements, promote the province parks and green fields by making health stations, develop sport-cultural centers for doing creative plans related to native and regional culture; all of advertisement factors with significance level of 0.000 are effective in developing of Fars province sport tourism industry. Conclusions: Propaganda methods necessary for effective marketing for sports tourism. It should be noted that closely tied to tourism development and promotion each other in a specified process, Because the tourism development process, part of the production structure of the economy that can income generation and job creation in developing countries have a major role.

  17. Role of Growth Factors in Modulation of the Microvasculature in Adult Skeletal Muscle.

    Science.gov (United States)

    Smythe, Gayle

    2016-01-01

    Post-natal skeletal muscle is a highly plastic tissue that has the capacity to regenerate rapidly following injury, and to undergo significant modification in tissue mass (i.e. atrophy/hypertrophy) in response to global metabolic changes. These processes are reliant largely on soluble factors that directly modulate muscle regeneration and mass. However, skeletal muscle function also depends on an adequate blood supply. Thus muscle regeneration and changes in muscle mass, particularly hypertrophy, also demand rapid changes in the microvasculature. Recent evidence clearly demonstrates a critical role for soluble growth factors in the tight regulation of angiogenic expansion of the muscle microvasculature. Furthermore, exogenous modulation of these factors has the capacity to impact directly on angiogenesis and thus, indirectly, on muscle regeneration, growth and performance. This chapter reviews recent developments in understanding the role of growth factors in modulating the skeletal muscle microvasculature, and the potential therapeutic applications of exogenous angiogenic and anti-angiogenic mediators in promoting effective growth and regeneration, and ameliorating certain diseases, of skeletal muscle.

  18. THE ROLE OF ADVERTISEMENT FACTORS IN DEVELOPMENT OF SPORT TOURISM INDUSTRY OF FARS PROVINCE

    Directory of Open Access Journals (Sweden)

    Eloon Kashkuli Fatemeh

    2014-06-01

    Full Text Available Purpose: The aim of this study is to investigate the role of advertisement factors in development of sport tourism industry of Fars province. Materials and methods : Present study is descriptive and functional. We used marketing indices questionnaire for collecting data. Statistical population was all the responsible managers and experts in tourism and sport which through purposeful non-random sampling method 170 of them were selected as samples. To calculate reliability by Cronbach's Alpha in a pilot study on a 40 people sample, marketing factors were α=0.82. Data were analyzed after collecting in respect of study hypotheses through Chi 2 tests. Results: Study findings show that from managers and experts views the most effective advertisement factors to develop sport tourism industry are respectively: written activities, investigate and understand tourists motivations to provide their requirements, promote the province parks and green fields by making health stations, develop sport-cultural centers for doing creative plans related to native and regional culture; all of advertisement factors with significance level of 0.000 are effective in developing of Fars province sport tourism industry. Conclusions: Propaganda methods necessary for effective marketing for sports tourism. It should be noted that closely tied to tourism development and promotion each other in a specified process, Because the tourism development process, part of the production structure of the economy that can income generation and job creation in developing countries have a major role.

  19. The role of growth factors as a therapeutic approach to demyelinating disease

    Science.gov (United States)

    Huang, Yangyang; Dreyfus, Cheryl F.

    2016-01-01

    A variety of growth factors are being explored as therapeutic agents relevant to the axonal and oligodendroglial deficits that occur as a result of demyelinating lesions. This review focuses on five such proteins that are present in the lesion site and impact oligodendrocyte regeneration. It then presents approaches that are being exploited to manipulate the lesion environment affiliated with multiple neurodegenerative diseases and suggests that the utility of these approaches can extend to demyelination. Challenges are to further understand the roles of specific growth factors on a cellular and tissue level. Emerging technologies can then be employed to optimize the use of growth factors to ameliorate the deficits associated with demyelinating degenerative diseases. PMID:27016070

  20. The influence of gender on entrepreneurial intention: The mediating role of perceptual factors

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    Carmen Camelo-Ordaz

    2016-10-01

    Full Text Available The empirical evidence devoted to analyze the impact of perceptual factors in explaining the differences in the entrepreneurial intention of men and women is still limited and not entirely conclusive (Shinnar et al., 2012; Wilson et al., 2009. This non-conclusive research is significantly more noteworthy when the analysis is focused on the entrepreneurial intention of men and women once they become entrepreneurs. Drawing on this gap and taking as starting point the premises of Social Feminist Theory, our paper aims to examine the mediating role of perceptual factors on the relationship between gender and entrepreneurial intention of non-entrepreneurs and entrepreneurs. Drawing on a sample provided by the Global Entrepreneurship Monitor Project of 21,697 Spanish non-entrepreneurs and 2899 Spanish entrepreneurs, our results have shown that, in general terms, perceptual factor fully mediate the relationship between gender and the entrepreneurial intention of non-entrepreneurs, whereas such mediating impact disappears when people become entrepreneurs.

  1. The role of biomechanical factors in ankylosing spondylitis: the patient’s perspective

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    R.C. Ansell

    2016-02-01

    Full Text Available Biomechanical factors including occupational joint physical stressing and joint injury have been linked to spondyloarthritis. We explored such factors in ankylosing spondylitis (AS. A retrospective, online survey was developed alongside the UK National Ankylosing Spondylitis Society (NASS. Questions on early entheseal symptoms, potential precipitating trauma, sporting activity, and physiotherapy were asked. A total of 1026 patients responded with 44% recalling an instance of injury or trauma as a potential trigger for their AS. After symptom onset, 55% modified sporting activities and 28% reported that the initial AS recommended exercises exacerbated symptoms. Patients report physical trauma, exercise and physiotherapy as potential triggers for AS symptoms. These findings further support the experimental evidence for the role of biomechanical factors in disease.

  2. The role of growth factors as a therapeutic approach to demyelinating disease.

    Science.gov (United States)

    Huang, Yangyang; Dreyfus, Cheryl F

    2016-09-01

    A variety of growth factors are being explored as therapeutic agents relevant to the axonal and oligodendroglial deficits that occur as a result of demyelinating lesions such as are evident in Multiple Sclerosis (MS). This review focuses on five such proteins that are present in the lesion site and impact oligodendrocyte regeneration. It then presents approaches that are being exploited to manipulate the lesion environment affiliated with multiple neurodegenerative diseases and suggests that the utility of these approaches can extend to demyelination. Challenges are to further understand the roles of specific growth factors on a cellular and tissue level. Emerging technologies can then be employed to optimize the use of growth factors to ameliorate the deficits associated with demyelinating degenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Factors Associated With Tobacco Smoking Among Male Adolescents: the Role of Psychologic, Behavioral, and Demographic Risk Factors

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    Barati

    2015-02-01

    Full Text Available Background Tobacco smoking among adolescents has been a concern for researchers and health organizations in recent years. However, predisposing factors to smoking initiation among Iranian adolescents are not well recognized. Objectives This study aimed to determine the prevalence of tobacco smoking and to investigate the role of psychologic, behavioral, and demographic risk factors in adolescents' smoking status. Patients and Methods This cross-sectional study was performed on 810 male adolescents recruited through cluster random sampling method in Hamadan in 2014. The participants received a self-administered questionnaire that contained questions about tobacco smoking behavior and demographic, behavioral, and psychologic variables. Data were analyzed by SPSS16 through independent-samples t test, Chi square, and logistic regression. Results A total of 139 persons (17.1% were tobacco smoker and the mean (SD age at smoking initiation was 13.7 (2.2 years. Sense of need, decreasing stress, having a smoker friend, and inability to reject smoking suggestion were common reasons associated with tobacco smoking (P < 0.05. In addition, statistically significant differences between tobacco smokers and nonsmokers were found in the age, grade, mother's job, and education (P < 0.05. In comparison to non-smokers, tobacco smokers evaluated a typical smoker as less immature, more popular, more attractive, more self-confident, more independent, and less selfish person (P < 0.05. Conclusions The results showed that the effect of several psychosocial, behavioral, and demographic risk factors on adolescents' smoking status. Thus, design and implementation of interventions based on the results of the present study may be effective in preventing tobacco smoking among adolescents.

  4. Postoperative Changes in Aqueous Monocyte Chemotactic Protein-1 Levels and Bleb Morphology after Trabeculectomy vs. Ex-PRESS Shunt Surgery.

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    Kohei Shobayashi

    Full Text Available To evaluate the postoperative changes in blebs and levels of aqueous monocyte chemotactic protein-1 (MCP-1 after trabeculectomy vs. Ex-PRESS tube shunt surgery.Rabbits were subjected to trabeculectomy or Ex-PRESS tube shunt surgery and observed for up to 3 months. Intraocular pressure (IOP was measured using a rebound tonometer. The MCP-1 level was measured by enzyme-linked immunosorbent assay (ELISA. Bleb morphology was evaluated using photos and anterior-segment optical coherence tomography (OCT.There were no differences in bleb appearance or IOP at any time between the groups. Bleb wall density in the anterior-segment OCT image was significantly lower 1 week after surgery in the Ex-PRESS group than the trabeculectomy group. The MCP-1 level in control eyes was 304.1 ± 45.2 pg/mL. In the trabeculectomy group, the mean aqueous MCP-1 level was 1444.9, 1914.3, 1899.8, 516.4, 398.3, 427.3, 609.5, 1612.7, 386.2, and 167.9 pg/mL at 3, 6, and 12 h, and 1, 2, 5, 7, 14, 30, and 90 days after surgery, respectively. In the Ex-PRESS group, the corresponding values were 1744.0, 1372.0, 932.5, 711.7, 396.1, 487.3, 799.5, 1327.9, 293.6, and 184.0 pg/mL. There were no significant differences in the aqueous MCP-1 level between the groups at any time point.The postoperative changes were similar in the Ex-PRESS and trabeculectomy groups, except for bleb wall density in the anterior-segment OCT image. The postoperative aqueous MCP-1 level had bimodal peaks in both groups.

  5. A Gal-MµS Device to Evaluate Cell Migratory Response to Combined Galvano-Chemotactic Fields

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    Shawn Mishra

    2017-11-01

    Full Text Available Electric fields have been studied extensively in biomedical engineering (BME for numerous regenerative therapies. Recent studies have begun to examine the biological effects of electric fields in combination with other environmental cues, such as tissue-engineered extracellular matrices (ECM, chemical gradient profiles, and time-dependent temperature gradients. In the nervous system, cell migration driven by electrical fields, or galvanotaxis, has been most recently studied in transcranial direct stimulation (TCDS, spinal cord repair and tumor treating fields (TTF. The cell migratory response to galvano-combinatory fields, such as magnetic fields, chemical gradients, or heat shock, has only recently been explored. In the visual system, restoration of vision via cellular replacement therapies has been limited by low numbers of motile cells post-transplantation. Here, the combinatory application of electrical fields with other stimuli to direct cells within transplantable biomaterials and/or host tissues has been understudied. In this work, we developed the Gal-MµS device, a novel microfluidics device capable of examining cell migratory behavior in response to single and combinatory stimuli of electrical and chemical fields. The formation of steady-state, chemical concentration gradients and electrical fields within the Gal-MµS were modeled computationally and verified experimentally within devices fabricated via soft lithography. Further, we utilized real-time imaging within the device to capture cell trajectories in response to electric fields and chemical gradients, individually, as well as in combinatory fields of both. Our data demonstrated that neural cells migrated longer distances and with higher velocities in response to combined galvanic and chemical stimuli than to either field individually, implicating cooperative behavior. These results reveal a biological response to galvano-chemotactic fields that is only partially understood, as

  6. Roles of Arabidopsis WRKY3 and WRKY4 Transcription Factors in Plant Responses to Pathogens

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    Fan Baofang

    2008-06-01

    Full Text Available Abstract Background Plant WRKY DNA-binding transcription factors are involved in plant responses to biotic and abiotic responses. It has been previously shown that Arabidopsis WRKY3 and WRKY4, which encode two structurally similar WRKY transcription factors, are induced by pathogen infection and salicylic acid (SA. However, the role of the two WRKY transcription factors in plant disease resistance has not been directly analyzed. Results Both WRKY3 and WRKY4 are nuclear-localized and specifically recognize the TTGACC W-box sequences in vitro. Expression of WRKY3 and WRKY4 was induced rapidly by stress conditions generated by liquid infiltration or spraying. Stress-induced expression of WRKY4 was further elevated by pathogen infection and SA treatment. To determine directly their role in plant disease resistance, we have isolated T-DNA insertion mutants and generated transgenic overexpression lines for WRKY3 and WRKY4. Both the loss-of-function mutants and transgenic overexpression lines were examined for responses to the biotrophic bacterial pathogen Pseudomonas syringae and the necrotrophic fungal pathogen Botrytis cinerea. The wrky3 and wrky4 single and double mutants exhibited more severe disease symptoms and support higher fungal growth than wild-type plants after Botrytis infection. Although disruption of WRKY3 and WRKY4 did not have a major effect on plant response to P. syringae, overexpression of WRKY4 greatly enhanced plant susceptibility to the bacterial pathogen and suppressed pathogen-induced PR1 gene expression. Conclusion The nuclear localization and sequence-specific DNA-binding activity support that WRKY3 and WRKY4 function as transcription factors. Functional analysis based on T-DNA insertion mutants and transgenic overexpression lines indicates that WRKY3 and WRKY4 have a positive role in plant resistance to necrotrophic pathogens and WRKY4 has a negative effect on plant resistance to biotrophic pathogens.

  7. The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

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    Priscila Menezes Ferri

    2016-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.

  8. The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

    Science.gov (United States)

    Campos Silva, Soraya Luiza; Marques de Miranda, Débora; Ferreira, Alexandre Rodrigues

    2016-01-01

    Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients. PMID:27882046

  9. The Role of Checklists and Human Factors for Improved Patient Safety in Plastic Surgery.

    Science.gov (United States)

    Oppikofer, Claude; Schwappach, David

    2017-12-01

    After studying the article, participants should be able to: 1. Describe the role of human factors and nontechnical skills for patient safety and recognize the need for customization of surgical checklists. 2. Apply encouragement to speaking up and understand the importance of patient involvement for patient safety. 3. Recognize the potential for improvement regarding patient safety in their own environment and take a leading role in the patient safety process. 4. Assess their own safety status and develop measures to avoid unnecessary distraction in the operating room. Over the past 20 years, there has been increased attention to improving all aspects of patient safety and, in particular, the important role of checklists and human factors. This article gives a condensed overview of selected aspects of patient safety and aims to raise the awareness of the reader and encourage further study of referenced literature, with the goal of increased knowledge and use of proven safety methods. The CME questions should help indicate where there is still potential for improvement in patient safety, namely, in the field of nontechnical skills.

  10. Role Performance of Community Health Volunteers and Its Associated Factors in Kuching District, Sarawak

    Directory of Open Access Journals (Sweden)

    Melvin Hsien Liang Chung

    2017-01-01

    Full Text Available The objective of this study was to assess the role performance among KOSPEN community health volunteer in Kuching district and its associated factors. This was a cross-sectional study, conducted in 21 localities in Kuching with a total of 210 respondents. Data were collected using validated interviewer-administered questionnaires and analyzed using SPSS version 22.0. The respondents comprised 55.2% females, 81.9% married, and 41.4% aged above 45 and above and 72.4% completed their education up to secondary school. The result revealed that 59.0% of the respondents agreed and understood their role performances. Multiple Logistics analysis revealed that factors associated with role performance were age group (p=0.003, education level (p<0.001, marital status (p=0.025, prestige and respect (p=0.012, being seen as “doctor” in community (p=0.003, job aids (p=0.009, training location (p=0.001, and supervision by community (p<0.001. To increase and maintain the work performance of CHVs, commitment from the government, policy makers, stakeholders, and the communities is required.

  11. Nerve growth factor: role in growth, differentiation and controlling cancer cell development.

    Science.gov (United States)

    Aloe, Luigi; Rocco, Maria Luisa; Balzamino, Bijorn Omar; Micera, Alessandra

    2016-07-21

    Recent progress in the Nerve Growth Factor (NGF) research has shown that this factor acts not only outside its classical domain of the peripheral and central nervous system, but also on non-neuronal and cancer cells. This latter observation has led to divergent hypothesis about the role of NGF, its specific distribution pattern within the tissues and its implication in induction as well as progression of carcinogenesis. Moreover, other recent studies have shown that NGF has direct clinical relevance in certain human brain neuron degeneration and a number of human ocular disorders. These studies, by suggesting that NGF is involved in a plethora of physiological function in health and disease, warrant further investigation regarding the true role of NGF in carcinogenesis. Based on our long-lasting experience in the physiopathology of NGF, we aimed to review previous and recent in vivo and in vitro NGF studies on tumor cell induction, progression and arrest. Overall, these studies indicate that the only presence of NGF is unable to generate cell carcinogenesis, both in normal neuronal and non-neuronal cells/tissues. However, it cannot be excluded the possibility that the co-expression of NGF and pro-carcinogenic molecules might open to different consequence. Whether NGF plays a direct or an indirect role in cell proliferation during carcinogenesis remains to demonstrate.

  12. THE ROLE OF INTERPERSONAL AND FIRM FACTORS IN INTERNATIONAL BUSINESS RELATIONSHIPS

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    Farid Ahmed

    2010-01-01

    Full Text Available Managers have long known intuitively that relationships are important to business. In certain cultures, such as in the East, the emphasis on relationships may typically be more explicit, but a good salesperson knows that building trust and commitment with buyers are essential for long-term success. The role of interpersonal and firm factors on international business relationships are tested with data from 125 pairs of exporter-importer relationships. Drawing from relational exchange theory, personal (such as effective communication, cultural sensitivity and likability of partner and firm (such as reputation and competencies of partner factors are modeled as determinants of commitment and trust in such relationships. The findings support the overall model, highlighting the importance of interpersonal and firm factors to international business relationships. This research highlights the importance of personal and organisational factors that are linked to building trust and commitment. In particular, building, protecting and communicating a positive reputation, and ensuring strong marketing competencies, are important for building contractual and competence trust. The study highlights the importance of interpersonal factors and thus the need to have appropriate personnel involved in the developing and maintaining international business relationships.

  13. Connecting RNA Processing to Abiotic Environmental Response in Arabidopsis: the role of a polyadenylation factor

    Science.gov (United States)

    Li, Q. Q.; Xu, R.; Hunt, A. G.; Falcone, D. L.

    Plants are constantly challenged by numerous environmental stresses both biotic and abiotic It is clear that plants have evolved to counter these stresses using all but limited means We recently discovered the potential role of a messenger RNA processing factor namely the Arabidopsis cleavage and polyadenylation specificity factor 30 kDa subunit AtCPSF30 when a mutant deficient in this factor displayed altered responses to an array of abiotic stresses This AtCPSF30 mutant named oxt6 exhibited an elevated tolerance to oxidative stress Microarray experiments of oxt6 and its complemented lines revealed an altered gene expression profile among which were antioxidative defense genes Interestingly the same gene encoding AtCPSF30 can also be transcribed into a large transcript that codes for a potential splicing factor Both protein products have a domain for RNA binding and a calmodulin binding domain activities of which have been confirmed by biochemical assays Surprisingly binding of AtCPSF30 to calmodulin inhibits the RNA-binding activity of the protein Mutational analysis shows that a small part of the protein is responsible for calmodulin binding and point mutations in this region abolished both RNA binding activity and the inhibition of this activity by calmodulin Analyses of the potential splicing factor are on going and the results will be presented The interesting possibilities for both the interplay between splicing and polyadenylation and the regulation of these processes by stimuli that act through

  14. A systematic review of factors influencing knowledge management and the nurse leaders' role.

    Science.gov (United States)

    Lunden, Anne; Teräs, Marianne; Kvist, Tarja; Häggman-Laitila, Arja

    2017-09-01

    To describe factors facilitating or inhibiting the development of registered nurses' competency and nurse leader's role in knowledge management. Nurses' competency directly influences patient safety and the quality and effectiveness of patient care. Challenges of nurse leaders in knowledge management include acquiring, assessing and utilising current knowledge and assessing and enhancing competency. A systematic search was conducted in PubMed, CINAHL, SCOPUS and ERIC databases in April 2015. The search identified 18 relevant research articles published between 2009 and 2015. The quality of the studies was appraised in accordance with study designs. Knowledge management is facilitated by an organisation culture that supports learning, sharing of information and learning together. Leader commitment and competency were factors related to leadership facilitating knowledge management. Nurse leaders need evidence-based interventions to support shared learning and to create infrastructures that facilitate competence development. Future research is especially needed to evaluate connections between knowledge management and patient outcomes. The results of this review can be utilised in enhancing factors to facilitate knowledge management in clinical practice and identifying nurse leaders' role in strengthening nurses' competency. © 2017 John Wiley & Sons Ltd.

  15. Hepatocyte growth factor (HGF) receptor expression and role of HGF during embryonic mouse testis development.

    Science.gov (United States)

    Ricci, G; Catizone, A; Innocenzi, A; Galdieri, M

    1999-12-01

    The hepatocyte growth factor (HGF) receptor, c-met, transduces the HGF multiple biological activities. During embryonic development the system HGF/c-met regulates the morphogenesis of different organs and tissues. In this study we examined c-met gene expression during mouse testis development and, by means of Northern blot and in situ hybridization, we report the receptor expression pattern. C-met expression is not detectable in male genital ridges isolated from embryos at 11.5 days postcoitum (dpc). In testes isolated from 12.5 and 13.5 dpc, c-met expression is detectable and essentially localized in the developing cords. Male genital ducts do not express c-met at the reported ages, whereas female ducts appear c-met positive. Moreover, we report that HGF is able to induce testicular morphogenesis in vitro. Male genital ridges isolated from embryos at 11.5 dpc are morphologically nonorganized. Culturing 11.5 dpc urogenital ridges in the presence of HGF we obtained testis organization and testicular cord formation. Our data demonstrate that c-met is expressed during the beginning period of testis differentiation and that HGF is able to support testicular differentiation in vitro. All these data indicate that this growth factor, besides its role as mitogenic factor, plays a fundamental role during testicular cord formation probably inducing cell migration and/or cell differentiation. Copyright 1999 Academic Press.

  16. The transcription factor NFATp plays a key role in susceptibility to TB in mice.

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    Laura E Via

    Full Text Available In T cells, the transcription factor nuclear factor of activated T cells p (NFATp is a key regulator of the cytokine genes tumor necrosis factor (TNF and interferon-γ (IFN-γ. Here, we show that NFATp-deficient (NFATp(-/- mice have a dramatic and highly significant increase in mortality after Mycobacterium tuberculosis (MTb infection as compared to mortality of control animals after MTb infection. Animals deficient in NFATp have significantly impaired levels of TNF and IFN-γ transcription and protein expression in naïve or total CD4(+ T cells, but display wild-type levels of TNF mRNA or protein from MTb-stimulated dendritic cells (DC. The rapid mortality and disease severity observed in MTb-infected NFATp(-/- mice is associated with dysregulated production of TNF and IFN-γ in the lungs, as well as with increased levels of TNF, in their serum. Furthermore, global blocking of TNF production by injection of a TNF neutralizaing agent at 6 weeks, but not 12 weeks, post-MTb-infection further decreased the survival rate of both wild-type and NFATp(-/- mice, indicating an early role for TNF derived from cells from the monocyte lineage in containment of infection. These results thus demonstrate that NFATp plays a critical role in immune containment of TB disease in vivo, through the NFATp-dependent expression of TNF and IFN-γ in T cells.

  17. Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

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    Mi-Young Kim

    2012-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance.

  18. Essential role for the planarian intestinal GATA transcription factor in stem cells and regeneration.

    Science.gov (United States)

    Flores, Natasha M; Oviedo, Néstor J; Sage, Julien

    2016-10-01

    The cellular turnover of adult tissues and injury-induced repair proceed through an exquisite integration of proliferation, differentiation, and survival signals that involve stem/progenitor cell populations, their progeny, and differentiated tissues. GATA factors are DNA binding proteins that control stem cells and the development of tissues by activating or repressing transcription. Here we examined the role of GATA transcription factors in Schmidtea mediterranea, a freshwater planarian that provides an excellent model to investigate gene function in adult stem cells, regeneration, and differentiation. Smed-gata4/5/6, the homolog of the three mammalian GATA-4,-5,-6 factors is expressed at high levels in differentiated gut cells but also at lower levels in neoblast populations, the planarian stem cells. Smed-gata4/5/6 knock-down results in broad differentiation defects, especially in response to injury. These defects are not restricted to the intestinal lineage. In particular, at late time points during the response to injury, loss of Smed-gata4/5/6 leads to decreased neoblast proliferation and to gene expression changes in several neoblast subpopulations. Thus, Smed-gata4/5/6 plays a key evolutionary conserved role in intestinal differentiation in planarians. These data further support a model in which defects in the intestinal lineage can indirectly affect other differentiation pathways in planarians. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Role of Microvessel Density and Vascular Endothelial Growth Factor in Angiogenesis of Hematological Malignancies

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    Rashika Chand

    2016-01-01

    Full Text Available Angiogenesis plays an important role in progression of tumor with vascular endothelial growth factor (VEGF being key proangiogenic factor. It was intended to study angiogenesis in different hematological malignancies by quantifying expression of VEGF and MVD in bone marrow biopsy along with serum VEGF levels and observing its change following therapy. The study included 50 cases of hematological malignancies which were followed for one month after initial therapy along with 30 controls. All of them were subjected to immunostaining by anti-VEGF and factor VIII antibodies on bone marrow biopsy along with the measurement of serum VEGF levels. Significantly higher pretreatment VEGF scores, serum VEGF levels, and MVD were observed in cases as compared to controls (p<0.05. The highest VEGF score and serum VEGF were observed in chronic myeloid leukemia and maximum MVD in Non-Hodgkin’s Lymphoma. Significant decrease in serum VEGF levels after treatment was observed in all hematological malignancies except for AML. To conclude angiogenesis plays an important role in pathogenesis of all the hematological malignancies as reflected by increased VEGF expression and MVD in bone marrow biopsy along with increased serum VEGF level. The decrease in serum VEGF level after therapy further supports this view and also lays the importance of anti angiogenic therapy.

  20. The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

    Energy Technology Data Exchange (ETDEWEB)

    Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

    2006-01-13

    Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

  1. The role of Transposable Elements in shaping the combinatorial interaction of Transcription Factors

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    Testori Alessandro

    2012-08-01

    Full Text Available Abstract Background In the last few years several studies have shown that Transposable Elements (TEs in the human genome are significantly associated with Transcription Factor Binding Sites (TFBSs and that in several cases their expansion within the genome led to a substantial rewiring of the regulatory network. Another important feature of the regulatory network which has been thoroughly studied is the combinatorial organization of transcriptional regulation. In this paper we combine these two observations and suggest that TEs, besides rewiring the network, also played a central role in the evolution of particular patterns of combinatorial gene regulation. Results To address this issue we searched for TEs overlapping Estrogen Receptor α (ERα binding peaks in two publicly available ChIP-seq datasets from the MCF7 cell line corresponding to different modalities of exposure to estrogen. We found a remarkable enrichment of a few specific classes of Transposons. Among these a prominent role was played by MIR (Mammalian Interspersed Repeats transposons. These TEs underwent a dramatic expansion at the beginning of the mammalian radiation and then stabilized. We conjecture that the special affinity of ERα for the MIR class of TEs could be at the origin of the important role assumed by ERα in Mammalians. We then searched for TFBSs within the TEs overlapping ChIP-seq peaks. We found a strong enrichment of a few precise combinations of TFBS. In several cases the corresponding Transcription Factors (TFs were known cofactors of ERα, thus supporting the idea of a co-regulatory role of TFBS within the same TE. Moreover, most of these correlations turned out to be strictly associated to specific classes of TEs thus suggesting the presence of a well-defined "transposon code" within the regulatory network. Conclusions In this work we tried to shed light into the role of Transposable Elements (TEs in shaping the regulatory network of higher eukaryotes. To

  2. Role of glial-cell-derived neurotrophic factor in salivary gland stem cell response to irradiation

    DEFF Research Database (Denmark)

    Peng, Xiaohong; Varendi, Kärt; Maimets, Martti

    2017-01-01

    Background and purpose Recently, stem cell therapy has been proposed to allow regeneration of radiation damaged salivary glands. It has been suggested that glial-cell-derived neurotrophic factor (GDNF) promotes survival of mice salivary gland stem cells (mSGSCs). The purpose of this study...... was to investigate the role of GDNF in the modulation of mSGSC response to irradiation and subsequent salivary gland regeneration. Methods Salivary gland sphere derived cells of Gdnf hypermorphic (Gdnfwt/hyper) and wild type mice (Gdnfwt/wt) were irradiated (IR) with γ-rays at 0, 1, 2, 4 and 8 Gy. mSGSC survival...

  3. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    Science.gov (United States)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  4. Organizational citizenship behavior and social loafing: the role of personality, motives, and contextual factors.

    Science.gov (United States)

    Tan, Hwee Hoon; Tan, Min Li

    2008-01-01

    The present study integrates the literature on social loafing and organizational citizenship behavior (OCB). The authors examined the roles of personality, motives, and contextual factors in influencing the work behaviors of OCB and social loafing. In a sample of 341 individuals working in project groups, with data collected over 3 time periods, the authors found that conscientiousness was negatively related to social loafing. They also found the known positive relation of OCB with conscientiousness. Felt responsibility was negatively related to social loafing. The authors found no significant relations between social loafing and OCB motives.

  5. The role of diseases, risk factors and symptoms in the definition of multimorbidity

    DEFF Research Database (Denmark)

    Willadsen, Tora Grauers; Bebe, Anna; Køster-Rasmussen, Rasmus

    2016-01-01

    %). Sources of data were primarily self-reports (56 articles, 42%). Out of the 163 articles selected, 115 had individually constructed multimorbidity definitions, and in these articles diseases occurred in all definitions, with diabetes as the most frequent. Risk factors occurred in 98 (85%) and symptoms......Objective is to explore how multimorbidity is defined in the scientific literature, with a focus on the roles of diseases, risk factors, and symptoms in the definitions. DESIGN: Systematic review. METHODS: MEDLINE (PubMed), Embase, and The Cochrane Library were searched for relevant publications up...... until October 2013. One author extracted the information. Ambiguities were resolved, and consensus reached with one co-author. Outcome measures were: cut-off point for the number of conditions included in the definitions of multimorbidity; setting; data sources; number, kind, duration, and severity...

  6. Multiple regulatory roles of AP2/ERF transcription factor in angiosperm.

    Science.gov (United States)

    Gu, Chao; Guo, Zhi-Hua; Hao, Ping-Ping; Wang, Guo-Ming; Jin, Zi-Ming; Zhang, Shao-Ling

    2017-12-01

    APETALA2/ethylene response factor (AP2/ERF) transcription factor (TF) is a superfamily in plant kingdom, which has been reported to be involved in regulation of plant growth and development, fruit ripening, defense response, and metabolism. As the final response gene in ethylene signaling pathway, AP2/ERF TF could feedback modulate phytohormone biosynthesis, including ethylene, cytokinin, gibberellin, and abscisic acid. Moreover, AP2/ERF TF also participates in response to the signals of auxin, cytokinin, abscisic acid, and jasmonate. Thus, this superfamily is key regulator for connecting the phytohormonal signals. In this review, based on the evidence of structural and functional studies, we discussed the multiple regulator roles of AP2/ERF TF in angiosperm, and then constructed the network model of AP2/ERF TF in response to various phytohormonal signals and regulatory mechanism of the cross-talk.

  7. Exploring the roles of basal transcription factor 3 in eukaryotic growth and development.

    Science.gov (United States)

    Jamil, Muhammad; Wang, Wenyi; Xu, Mengyun; Tu, Jumin

    2015-01-01

    Basal transcription factor 3 (BTF3) has been reported to play a significant part in the transcriptional regulation linking with eukaryotes growth and development. Alteration in the BTF3 gene expression patterns or variation in their activities adds to the explanation of different signaling pathways and regulatory networks. Moreover, BTF3s often respond to numerous stresses, and subsequently they are involved in regulation of various mechanisms. BTF3 proteins also function through protein-protein contact, which can assist us to identify the multifaceted processes of signaling and transcriptional regulation controlled by BTF3 proteins. In this review, we discuss current advances made in starting to explore the roles of BTF3 transcription factors in eukaryotes especially in plant growth and development.

  8. Role of mechanical factors in the morphology of the primate cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Claus C Hilgetag

    2006-03-01

    Full Text Available The convoluted cortex of primates is instantly recognizable in its principal morphologic features, yet puzzling in its complex finer structure. Various hypotheses have been proposed about the mechanisms of its formation. Based on the analysis of databases of quantitative architectonic and connection data for primate prefrontal cortices, we offer support for the hypothesis that tension exerted by corticocortical connections is a significant factor in shaping the cerebral cortical landscape. Moreover, forces generated by cortical folding influence laminar morphology, and appear to have a previously unsuspected impact on cellular migration during cortical development. The evidence for a significant role of mechanical factors in cortical morphology opens the possibility of constructing computational models of cortical development based on physical principles. Such models are particularly relevant for understanding the relationship of cortical morphology to the connectivity of normal brains, and structurally altered brains in diseases of developmental origin, such as schizophrenia and autism.

  9. Therapeutic and pathological roles of fibroblast growth factors in pulmonary diseases.

    Science.gov (United States)

    El Agha, Elie; Seeger, Werner; Bellusci, Saverio

    2017-04-01

    Fibroblast growth factors (FGFs) constitute a large family of polypeptides that are involved in many biological processes, ranging from prenatal cell-fate specification and organogenesis to hormonal and metabolic regulation in postnatal life. During embryonic development, these growth factors are important mediators of the crosstalk among ectoderm-, mesoderm-, and endoderm-derived cells, and they instruct the spatial and temporal growth of organs and tissues such as the brain, bone, lung, gut, and others. The involvement of FGFs in postnatal lung homeostasis is a growing field, and there is emerging literature about their roles in lung pathophysiology. In this review, the involvement of FGF signaling in a wide array of lung diseases will be summarized. Developmental Dynamics 246:235-244, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis

    DEFF Research Database (Denmark)

    Sarusi Portuguez, Avital; Schwartz, Michal; Siersbaek, Rasmus

    2017-01-01

    The three dimensional folding of mammalian genomes is cell type specific and difficult to alter suggesting that it is an important component of gene regulation. However, given the multitude of chromatin-associating factors, the mechanisms driving the colocalization of active chromosomal domains...... and the role of this organization in regulating the transcription program in adipocytes are not clear. Analysis of genome-wide chromosomal associations revealed cell type-specific spatial clustering of adipogenic genes in 3T3-L1 cells. Time course analysis demonstrated that the adipogenic 'hub', sampled...... by PPARγ and Lpin1, undergoes orchestrated reorganization during adipogenesis. Coupling the dynamics of genome architecture with multiple chromatin datasets indicated that among all the transcription factors (TFs) tested, RXR is central to genome reorganization at the beginning of adipogenesis...

  11. Determining success factors for effective strategic change: Role of middle managers' strategic involvement

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    Minhajul Islam Ukil

    2017-05-01

    Full Text Available Middle managers are believed to play most crucial part in strategic change that in consequence leads to organizational success. The present study seeks to identify the underlying success factors for effective strategic change and, to investigate the relationship between middle management strategic involvement and effective strategic change. Data were collected following a survey administered among a group of mid-level managers (N=144 serving in twenty different private commercial banks in Bangladesh, and analyzed using various statistical tests including descriptive analysis, Pearson correlation, and simple and multiple regressions in STATA. Results uncovers that factors like relation with top management, strategy, role and skills are essential for effective strategic change. This study also reveals significant relationship between middle management strategic involvement and effective strategic change. Findings of this research suggest that organizations shall involve mid-level managers to formulate and implement strategy since middle mangers work as a bridge between top management and ground level workers.

  12. The Role of Atonal Factors in Mechanosensory Cell Specification and Function.

    Science.gov (United States)

    Cai, Tiantian; Groves, Andrew K

    2015-12-01

    Atonal genes are basic helix-loop-helix transcription factors that were first identified as regulating the formation of mechanoreceptors and photoreceptors in Drosophila. Isolation of vertebrate homologs of atonal genes has shown these transcription factors to play diverse roles in the development of neurons and their progenitors, gut epithelial cells, and mechanosensory cells in the inner ear and skin. In this article, we review the molecular function and regulation of atonal genes and their targets, with particular emphasis on the function of Atoh1 in the development, survival, and function of hair cells of the inner ear. We discuss cell-extrinsic signals that induce Atoh1 expression and the transcriptional networks that regulate its expression during development. Finally, we discuss recent work showing how identification of Atoh1 target genes in the cerebellum, spinal cord, and gut can be used to propose candidate Atoh1 targets in tissues such as the inner ear where cell numbers and biochemical material are limiting.

  13. The role of environmental factors in modulating immune responses in early life

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    Duncan Malcolm MacGillivray

    2014-09-01

    Full Text Available The concept of immunological memory stipulates that past exposures shape present immune function. These exposures include not only specific antigens impacting adaptive immune memory, but also conserved pathogen or danger associated molecular patterns that mold innate immune responses for prolonged periods of time. It should thus not come as a surprise that there is a vast range of external or environmental factors that impact immunity. The importance of environmental factors modulating immunity is most readily recognized in early life, a period of rapidly changing environments. We here summarize available data on the role of environment shaping immune development and from it derive an overarching hypothesis relating the underlying molecular mechanisms and evolutionary principles involved.

  14. The Role of Cytokines, Chemokines, and Growth Factors in the Pathogenesis of Pityriasis Rosea

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    Francesco Drago

    2015-01-01

    Full Text Available Introduction. Pityriasis rosea (PR is an exanthematous disease related to human herpesvirus- (HHV- 6/7 reactivation. The network of mediators involved in recruiting the infiltrating inflammatory cells has never been studied. Object. To investigate the levels of serum cytokines, growth factors, and chemokines in PR and healthy controls in order to elucidate the PR pathogenesis. Materials and Methods. Interleukin- (IL- 1, IL-6, IL-17, interferon- (IFN- γ, tumor necrosis factor- (TNF- α, vascular endothelial growth factor (VEGF, granulocyte colony stimulating factor (G-CSF, and chemokines, CXCL8 (IL-8 and CXCL10 (IP-10, were measured simultaneously by a multiplex assay in early acute PR patients’ sera and healthy controls. Subsequently, sera from PR patients were analysed at 3 different times (0, 15, and 30 days. Results and discussion. Serum levels of IL-17, IFN-γ, VEGF, and IP-10 resulted to be upregulated in PR patients compared to controls. IL-17 has a key role in host defense against pathogens stimulating the release of proinflammatory cytokines/chemokines. IFN-γ has a direct antiviral activity promoting NK cells and virus specific T cells cytotoxicity. VEGF stimulates vasculogenesis and angiogenesis. IP-10 can induce chemotaxis, apoptosis, cell growth, and angiogenesis. Conclusions. Our findings suggest that these inflammatory mediators may modulate PR pathogenesis in synergistic manner.

  15. The emerging role of cardiovascular risk factor-induced mitochondrial dysfunction in atherogenesis

    Directory of Open Access Journals (Sweden)

    De Pascalis Susanna

    2009-12-01

    Full Text Available Abstract An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells. Conversely, reactive oxygen species may favor the development of type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in addition to being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrial dysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally, other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associated with mitochondrial damage and an increased production of free radicals. So far clinical studies have been unable to demonstrate that antioxidants have any effect on human atherogenesis. Mitochondrial targeted antioxidants might provide more significant results.

  16. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

    DEFF Research Database (Denmark)

    Schmal, H; Shanley, T P; Jones, M L

    1996-01-01

    Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to th...... instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils....

  17. Factor Xa induces cytokine production and expression of adhesion molecules by human umbilical vein endothelial cells

    NARCIS (Netherlands)

    Senden, N. H.; Jeunhomme, T. M.; Heemskerk, J. W.; Wagenvoord, R.; van't Veer, C.; Hemker, H. C.; Buurman, W. A.

    1998-01-01

    Proinflammatory effects induced by the serine protease factor Xa were investigated in HUVEC. Exposure of cells to factor Xa (5-80 nM) concentration dependently stimulated the production of IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) and the expression of E-selectin, ICAM-1, and VCAM-1,

  18. [Effect of endogenous factors on the chemical perception of Grapholita molesta (Busck) (Lepidoptera: Tortricidae) to sex pheromone].

    Science.gov (United States)

    Altafini, Deisi L; Sant'Ana, Josué; Redaelli, Luiza R

    2010-01-01

    The oriental fruit moth, Grapholita molesta (Busck), stands out as one of the most important pest in Rosaceae orchards in Brazil. During feeding, caterpillars bore into shoots, branches and fruits, impairing the commercial production. This work aimed to study the effect of endogenous factors in the chemical perception and in the species chemotactic behavior, seeking to optimize monitoring and the behavioral control of this pest. We evaluated male electroantennographical (EAG) and chemotactical (olfactometry) responses to the synthetic sex pheromone in different ages, virgins or mated and fed or unfed. The EAG responses of males did not differ for all evaluated factors. Nevertheless, the chemotactical behavior of males seems to decrease with age, not varying as a function of mating or feeding conditions. The knowledge about the interference of these factors in G. molesta may help with the interpretation of field results, allowing the development of suitable and reliable control measures based on infochemicals for behavioral control.

  19. Premorbid adjustment profiles in psychosis and the role of familial factors.

    Science.gov (United States)

    Quee, Piotr J; Meijer, Julia H; Islam, Md Atiqul; Aleman, André; Alizadeh, Behrooz Z; Meijer, Carin J; van den Heuvel, Edwin R

    2014-08-01

    Disease heterogeneity in patients with psychotic disorder may be explained by distinct profiles of premorbid adjustment. The current study explored premorbid adjustment profiles in patients with psychotic disorders, associations with cognitive and clinical characteristics after disease onset, and the role of familial factors. A total of 666 patients with psychosis (predominantly schizophrenia), 673 siblings, 575 parents, and 585 controls were included in this study. Cluster analyses were performed on the patients' scores of the Premorbid Adjustment Scale (PAS), using information on domains (social, academic) and age epochs (childhood, early adolescence, late adolescence). Resulting profiles were compared with characteristics in patients and their unaffected relatives. Six clusters, labeled normal, social intermediate, academic decline, overall decline, overall intermediate, and overall impaired adjustment, were identified in patients. Patients in different clusters differed from each other on cognitive, clinical, and functional characteristics after disease onset. Heterogeneity in the patient population may be explained in part by the adjustment profile prior to disease onset. This is in line with theories that propose different etiologies in the development of psychosis. Patient profiles were expressed in unaffected siblings, suggesting a role for familial factors. (c) 2014 APA, all rights reserved.

  20. Role of cellular caspases, nuclear factor-kappa B and interferon regulatory factors in Bluetongue virus infection and cell fate

    Directory of Open Access Journals (Sweden)

    Roy Polly

    2010-12-01

    Full Text Available Abstract Background Bluetongue virus (BTV infection causes haemorrhagic disease in ruminants and induces cell death. The pathogenesis in animals and in cell culture has been linked to BTV-induced apoptosis. Results In this report, we investigated BTV-induced apoptosis in cell culture in depth and show that both extrinsic (caspase-8 activation and intrinsic (caspase-9 activation pathways play roles in BTV apoptosis. Further, by using chemical inhibitors and knock-out cell lines, we show that these pathways act independently of each other in BTV infected cells. In addition to activation of caspase-8, -9 and executioner caspase-3, we also identified that BTV infection causes the activation of caspase-7, which results in the cleavage of poly (ADP-ribose polymerase (PARP. BTV-induced cell death appears to be due to apoptosis rather than necrosis, as the HMBG-1 was not translocated from the nucleus. We also examined if NF-κB response is related to BTV-induced apoptosis as in reovirus. Our data suggests that NF-κB response is not linked to the induction of apoptosis. It is controlled by the degradation of only IκBα but not IκBβ, resulting in a rapid transient response during BTV infection. This was supported using an NF-κB dependent luciferase reporter gene assay, which demonstrated early response, that appeared to be suppressed by the late stage of BTV replication. Furthermore, virus titres were higher in the presence of NF-κB inhibitor (SN50, indicating that NF-κB has a role in initiating an antiviral environment. In addition, we show that BTV infection induces the translocation of interferon regulatory factors (IRF-3 and IRF-7 into the nucleus. The induction of IRF responses, when measured by IRF dependent luciferase reporter gene assay, revealed that the IRF responses, like NF-κB response, were also at early stage of infection and mirrored the timing of NF-κB induction. Conclusion BTV triggers a wide range of caspase activities resulting

  1. Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.

    Science.gov (United States)

    Askmyr, Maria; White, Kirby E; Jovic, Tanja; King, Hannah A; Quach, Julie M; Maluenda, Ana C; Baker, Emma K; Smeets, Monique F; Walkley, Carl R; Purton, Louise E

    2015-10-21

    The gp130 receptor and its binding partners play a central role in cytokine signalling. Ciliary neurotrophic factor (CNTF) is one of the cytokines that signals through the gp130 receptor complex. CNTF has previously been shown to be a negative regulator of trabecular bone remodelling and important for motor neuron development. Since haematopoietic cell maintenance and differentiation is dependent on the bone marrow (BM) microenvironment, where cells of the osteoblastic lineage are important regulators, we hypothesised that CNTF may also have important roles in regulating haematopoiesis. Analysis of haematopoietic parameters in male and female Cntf(-/-) mice at 12 and 24 weeks of age revealed altered B lymphopoiesis. Strikingly, the B lymphocyte phenotype differed based on sex, age and also the BM microenvironment in which the B cells develop. When BM cells from wildtype mice were transplanted into Cntf(-/-) mice, there were minimal effects on B lymphopoiesis or bone parameters. However, when Cntf(-/-) BM cells were transplanted into a wildtype BM microenvironment, there were changes in both haematopoiesis and bone parameters. Our data reveal that haematopoietic cell-derived CNTF has roles in regulating BM B cell lymphopoiesis and both trabecular and cortical bone, the latter in a sex-dependent manner.

  2. THE ROLE OF FAMILY FACTORS IN THE DEVELOPMENT OF ADAPTIVE ABILITIES OF THE GRADUATE SCHOOL

    Directory of Open Access Journals (Sweden)

    Альфия Равилевна Вагапова

    2014-06-01

    Full Text Available Discusses the problem of development of adaptive abilities of graduates of schools. This paper discusses theoretical approaches to understanding the role of parental family in adaptation process. It is shown that the integral indicators of social and psychological adaptation depends on understanding of parental attitudes high school students , and the acceptability of the parental model determined by the level of conflict in the family. The use of complex techniques allowed us to study possible options for child-parent interaction (n = 40. In the case of identical types of parental behavior at display positive interest increase the values and adaptation possibilities. Ways of understanding of parental attitudes as a guideline, inconsistent, contradictory lead to reduction in integrative indicators of social and psychological adaptation. Also identified by sex - differences, it is shown that the most important for high school students has a positive perception of the father's position, as in the case of deviations difficult adaptation process, there is a trend toward a closed position to face interpersonal interaction. In the event of heightened conflict in parent-child relationship is noted difficult and unacceptable understanding of the parental role . The author comes to the conclusion that family factors play a significant role in the development of adaptive abilities. Applied aspect of research problem can be implemented in practice of psychological counseling services, and to develop programs to optimize the adaptation process.DOI: http://dx.doi.org/10.12731/2218-7405-2013-12-7

  3. Measured and modeled humidification factors of fresh smoke particles from biomass burning: role of inorganic constituents

    Directory of Open Access Journals (Sweden)

    J. L. Hand

    2010-07-01

    Full Text Available During the 2006 FLAME study (Fire Laboratory at Missoula Experiment, laboratory burns of biomass fuels were performed to investigate the physico-chemical, optical, and hygroscopic properties of fresh biomass smoke. As part of the experiment, two nephelometers simultaneously measured dry and humidified light scattering coefficients (bsp(dry and bsp(RH, respectively in order to explore the role of relative humidity (RH on the optical properties of biomass smoke aerosols. Results from burns of several biomass fuels from the west and southeast United States showed large variability in the humidification factor (f(RH=bsp(RH/bsp(dry. Values of f(RH at RH=80–85% ranged from 0.99 to 1.81 depending on fuel type. We incorporated measured chemical composition and size distribution data to model the smoke hygroscopic growth to investigate the role of inorganic compounds on water uptake for these aerosols. By assuming only inorganic constituents were hygroscopic, we were able to model the water uptake within experimental uncertainty, suggesting that inorganic species were responsible for most of the hygroscopic growth. In addition, humidification factors at 80–85% RH increased for smoke with increasing inorganic salt to carbon ratios. Particle morphology as observed from scanning electron microscopy revealed that samples of hygroscopic particles contained soot chains either internally or externally mixed with inorganic potassium salts, while samples of weak to non-hygroscopic particles were dominated by soot and organic constituents. This study provides further understanding of the compounds responsible for water uptake by young biomass smoke, and is important for accurately assessing the role of smoke in climate change studies and visibility regulatory efforts.

  4. [Potential role of the angiogenic factor "EG-VEGF" in gestational trophoblastic diseases].

    Science.gov (United States)

    Boufettal, H; Feige, J-J; Benharouga, M; Aboussaouira, T; Nadifi, S; Mahdaoui, S; Samouh, N; Alfaidy, N

    2013-10-01

    Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. The political elite recruitment in the Baltic: the role of the ethnic factor

    Directory of Open Access Journals (Sweden)

    Smirnov Vadim

    2013-11-01

    Full Text Available The role of the ethnic factor in political processes in Lithuania, Latvia, and Estonia has been rather significant since these countries’ independence. The author investigates the assumption that after the completion of major Eurointegration procedures, the ethnic factor — which became especially important in the Baltics after independence — relegated to the periphery of political life. After a period of ‘independence-induced euphoria’ faded, Lithuanian, Latvian, and Estonian power groups had to tackle the problem of civil society formation and the development of a political regime based on democratic procedures. In these countries the processes of elite recruitment were largely affected by the factor of ethic homogeneity of the social structure. This article analyses the process of elite group formation in the Baltics through the lens of the ethnic factor. By applying the ethnopolitical approach, the author concludes that the de facto barriers to non-titular population groups entering power structures, which exist in Latvia and Estonia, “freeze” the system of elite recruitment. In the conditions of increasing social unrest, it may have an adverse effect on the overall political stability in these countries. The results obtained can be used for research, educational, and practical purposes. In the field of research and education, they can be employed in further research on the transformation of the elite structure in the Baltics in view of the ethnopolitical factor, including comparative analysis of the elite re-grouping processes, as well as in developing corresponding university courses. As to the practical aspect, the results obtained can be used by the authorities of the Russian Federation in making decisions regarding interaction with the representatives of Lithuanian, Latvian, and Estonian political elites.

  6. The political elite recruitment in the Baltic: the role of the ethnic factor

    Directory of Open Access Journals (Sweden)

    Smirnov Vadim

    2013-01-01

    Full Text Available The role of the ethnic factor in political processes in Lithuania, Latvia, and Estonia has been rather significant since these countries’ independence. The author investigates the assumption that after the completion of major Eurointegration procedures, the ethnic factor — which became especially important in the Baltics after independence — relegated to the periphery of political life. After a period of ‘independence-induced euphoria’ faded, Lithuanian, Latvian, and Estonian power groups had to tackle the problem of civil society formation and the development of a political regime based on democratic procedures. In these countries the processes of elite recruitment were largely affected by the factor of ethic homogeneity of the social structure. This article analyses the process of elite group formation in the Baltics through the lens of the ethnic factor. By applying the ethnopolitical approach, the author concludes that the de facto barriers to non-titular population groups entering power structures, which exist in Latvia and Estonia, “freeze” the system of elite recruitment. In the conditions of increasing social unrest, it may have an adverse effect on the overall political stability in these countries. The results obtained can be used for research, educational, and practical purposes. In the field of research and education, they can be employed in further research on the transformation of the elite structure in the Baltics in view of the ethnopolitical factor, including comparative analysis of the elite re-grouping processes, as well as in developing corresponding university courses. As to the practical aspect, the results obtained can be used by the authorities of the Russian Federation in making decisions regarding interaction with the representatives of Lithuanian, Latvian, and Estonian political elites.

  7. Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals.

    Science.gov (United States)

    Singh, S P; Hasker, E; Picado, A; Gidwani, K; Malaviya, P; Singh, R P; Boelaert, M; Sundar, S

    2010-07-01

    Studies investigating risk factors for visceral leishmaniasis (VL) on the Indian Subcontinent have shown contradictory results related to the role of domestic animals. In some studies having animals in or around the house was a risk factor, in others it was protective. We investigated the specific hypothesis that keeping domestic animals inside the house at night is a risk factor for VL. Individually matched case-control study. All patients with VL diagnosed in the study area in Bihar, India between March 1st, 2007 and December 1st, 2008 were eligible. For each case, we selected two random controls, with no history of previous VL; matched on sex, age group and neighbourhood. Patients and controls were subjected to a structured interview on the main exposure of interest and potential confounders; a conditional logistic regression model was used to analyse the data. We enrolled 141 patients and 282 controls. We found no significant associations between VL and keeping domestic animals inside the house (OR of 0.88 for bovines and 1.00 for 'any animal') or ownership of domestic animals (OR of 0.97 for bovines and 1.02 for 'any animal'). VL was associated with housing conditions. Living in a thatched house (OR 2.60, 95% CI 1.50-4.48) or in a house with damp floors (OR 2.60, 95% CI 1.25-5.41) were risk factors, independently from socio economic status. Keeping animals inside the house is not a risk factor for VL in Bihar, India. Improving housing conditions for the poor has the potential to reduce VL incidence.

  8. A reappraisal of the role of 'mindbody' factors in chronic urticaria.

    Science.gov (United States)

    Broom, Brian C

    2010-06-01

    Chronic spontaneous urticaria (CSU) is a very common skin condition that causes considerable suffering and is often poorly responsive to drug treatment regimens. Most clinicians accept that multiple factors play a role in the aetiology of CSU, but there is a widespread reluctance to accept a significant role for 'mindbody' factors, despite a large number of clinical reports and studies over many decades suggesting their relevance. This reluctance has multiple origins. A primary influence is the flawed dualistic model of mind and body relatedness underpinning much of modern medical care. In this view, if a pathophysiological mechanism can be discerned, then 'mind' factors can be largely ignored. Recent evidence demonstrating intimate structural and functional relations between peripheral nerves and mast cells, and local skin secretion of mast cell-influencing neuropeptides by nerves, provides an argument for discarding old 'organic' and dualistic conceptualisations of CSU. A sound, integrative, multifactorial approach requires a unitive 'mindbody' model in which physical and subjective dimensions of personhood are seen as coexisting and equally deserving of exploration and management. Another influence is the tendency for 'psychosomatic' research studies in CSU to focus on patient experience using broad group-based diagnostic categories, such as anxiety and depressive disorders, and generic measures of stress. Two case examples are given, illustrating that CSU arises in relation to highly individual and relevant 'stories', which would not usually be picked up by these generic measures. It is suggested that an appropriate 'mindbody' management programme leading to good clinical outcomes for CSU is dependent on clinicians discerning unique patient 'stories'. Finally, a lack of formal studies comparing drug and 'mindbody' treatment outcomes will continue to negatively influence the adoption of 'mindbody' approaches in CSU. There is an urgent need for properly

  9. Diet, Cardiometabolic Factors and Type-2 Diabetes Mellitus: The Role of Genetics.

    Science.gov (United States)

    Marcadenti, Aline

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is a highly prevalent condition and is associated with a number of metabolic risk factors such as excess of weight, impaired lipid profile and higher levels of blood pressure. As other complex diseases, it is strongly related to an environmental component such as sedentarism and unhealthy diet, and also to a genetic component. A cluster of variants (polymorphisms) in a large number of genes seem to interact with nutrients/dietary factors in modulating cardiometabolic parameters in healthy individuals. The role of total calories intake and also different kind of carbohydrates and dietary fats in worsening the excess of weight and/or metabolic profile in patients with diabetes is well known, but the extent to which genetic factors can modify these associations is not yet fully understood. Therefore, the aim of this mini-review is to discuss the interaction of genetics and diet in the T2DM setting, since both are strongly involved in the genesis and development of the disease.

  10. Roles of hypoxia inducible factor-1α in the temporomandibular joint.

    Science.gov (United States)

    Mino-Oka, Akiko; Izawa, Takashi; Shinohara, Takehiro; Mori, Hiroki; Yasue, Akihiro; Tomita, Shuhei; Tanaka, Eiji

    2017-01-01

    Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease characterized by permanent cartilage loss. Articular cartilage is maintained in a low-oxygen environment. The chondrocyte response to hypoxic conditions involves expression of hypoxia inducible factor 1α (HIF-1α), which induces chondrocytes to increase expression of vascular endothelial growth factor (VEGF). Here, we investigated the role of HIF-1α in mechanical load effects on condylar cartilage and subchondral bone in heterozygous HIF-1α-deficient mice (HIF-1α+/-). Mechanical stress was applied to the TMJ of C57BL/6NCr wild-type (WT) and HIF-1α+/- mice with a sliding plate for 10 days. Histological analysis was performed by HE staining, Safranin-O/Fast green staining, and immunostaining specific for articular cartilage homeostasis. HIF-1α+/- mice had thinner cartilage and smaller areas of proteoglycan than WT controls, without and with mechanical stress. Mechanical stress resulted in prominent degenerative changes with increased expression of HIF-1α, VEGF, and the apoptosis factor cleaved Caspase-3 in condylar cartilage. Our results indicate that HIF-1α may be important for articular cartilage homeostasis and protective against articular cartilage degradation in the TMJ under mechanical stress condition, therefore HIF-1α could be an important new therapeutic target in TMJ-OA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Cartilage Tissue Regeneration: The Roles of Cells, Stimulating Factors and Scaffolds.

    Science.gov (United States)

    Huang, Kui; Li, Qing; Li, Yong; Yao, Zhihao; Luo, Daowen; Rao, Pengcheng; Xiao, Jingang

    2017-06-07

    Cartilage tissue engineering is an emerging technique for the regeneration of cartilage tissue damaged as a result of trauma or disease. As the propensity for healing and regenerative capabilities of articular cartilage are limited, its repair remains one of the most challenging issues of musculoskeletal medicine. Clinical treatments intended to promote the success and complete repair of partial- and full-thickness articular cartilage defects are still unpredictable. However, one of the most exciting theories is that treatment of damaged articular cartilage can be realized with cartilage tissue engineering. This notion has prompted tissue engineering research involving cells, stimulating factors and scaffolds, either alone or in combination. With these perspectives, this review aims to present a summary of cartilage tissue engineering including development, recent progress, and major steps taken toward the regeneration of functional cartilage tissue. In addition, we discussed the role of stimulating factors, including growth factors, gene therapies, biophysical stimuli, and bioreactors, as well as scaffolds, including natural, synthetic, and nanostructured scaffolds, in cartilage tissue regeneration. Special emphasis was placed on cell source, including chondrocytes, fibroblasts, and stem cells, as an important component of cartilage tissue engineering techniques. In conclusion, continued development of cartilage tissue engineering will support future applications for patients suffering from diseased cartilage tissue problems and osteoarthritis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Impact of skeletal unloading on bone formation: Role of systemic and local factors

    Science.gov (United States)

    Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

    We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

  13. Thyroid Transcription Factor-1 in Orbital Adipose Tissues: Potential Role in Orbital Thyrotropin Receptor Expression

    Science.gov (United States)

    Bhattacharyya, Kalyan K.; Coenen, Michael J.; Bahn, Rebecca S.

    2005-01-01

    Thyroid transcription factor-1 (TTF-1) is required for maximal expression of thyrotropin receptor (TSHR) in the thyroid. Extrathyroidal TSHR expression is detectable in normal orbital adipose tissues, with increased levels found in orbital tissues from patients with Graves’ ophthalmopathy (GO), and in orbital preadipocyte cultures following differentiation. In order to determine whether TTF-1 might be involved in orbital TSHR expression, we used quantitative real-time polymerase chain reaction (PCR) to assess relative expression of this and other thyroid-associated transcription factors (TTF-2 and Pax-8) in GO orbital tissue specimens (n = 28) and cultures (n = 3), and in normal orbital tissues (n = 19) and cultures (n = 3). We detected TTF-1 and TTF-2 mRNA in GO and normal orbital tissue samples, with no difference in levels noted between the tissues. In the GO orbital cultures, TTF-1 mRNA was higher in differentiated than in control (undifferentiated) cultures (p < 0.05), while TTF-2 was unchanged. In the normal cultures, neither TTF-1 nor TTF-2 mRNA levels increased in differentiated cultures. Pax8 was undetectable in all orbital tissues and cell cultures. The presence of mRNA encoding TTF-1 in orbital tissues and cultures suggest that this transcription factor may play an important role in extrathyroidal, as it does in thyroidal, TSHR expression. PMID:15929662

  14. The Role of Vascular Endothelial Growth Factor Receptor-1 Signaling in the Recovery from Ischemia.

    Science.gov (United States)

    Amano, Hideki; Kato, Shintaro; Ito, Yoshiya; Eshima, Koji; Ogawa, Fumihiro; Takahashi, Ryo; Sekiguchi, Kazuki; Tamaki, Hideaki; Sakagami, Hiroyuki; Shibuya, Masabumi; Majima, Masataka

    2015-01-01

    Vascular endothelial growth factor (VEGF) is one of the most potent angiogenesis stimulators. VEGF binds to VEGF receptor 1 (VEGFR1), inducing angiogenesis through the receptor's tyrosine kinase domain (TK), but the mechanism is not well understood. We investigated the role of VEGFR1 tyrosine kinase signaling in angiogenesis using the ischemic hind limb model. Relative to control mice, blood flow recovery was significantly impaired in mice treated with VEGFA-neutralizing antibody. VEGFR1 tyrosine kinase knockout mice (TK-/-) had delayed blood flow recovery from ischemia and impaired angiogenesis, and this phenotype was unaffected by treatment with a VEGFR2 inhibitor. Compared to wild type mice (WT), TK-/- mice had no change in the plasma level of VEGF, but the plasma levels of stromal-derived cell factor 1 (SDF-1) and stem cell factor, as well as the bone marrow (BM) level of pro-matrix metalloproteinase-9 (pro-MMP-9), were significantly reduced. The recruitment of cells expressing VEGFR1 and C-X-C chemokine receptor type 4 (CXCR4) into peripheral blood and ischemic muscles was also suppressed. Furthermore, WT transplanted with TK-/- BM significantly impaired blood flow recovery more than WT transplanted with WT BM. These results suggest that VEGFR1-TK signaling facilitates angiogenesis by recruiting CXCR4+VEGFR1+ cells from BM.

  15. The role of psychological and physiological factors in decision making under risk and in a dilemma

    Directory of Open Access Journals (Sweden)

    Jonas eFooken

    2016-01-01

    Full Text Available Different methods to elicit risk attitudes of individuals often provide differing results despite a common theory. Reasons for such inconsistencies may be the different influence of underlying factors in risk-taking decisions. In order to evaluate this conjecture, a better understanding of underlying factors across methods and decision contexts is desirable. In this paper we study the difference in result of two different risk elicitation methods by linking estimates of risk attitudes to gender, age and personality traits, which have been shown to be related. We also investigate the role of these factors during decision-making in a dilemma situation. For these two decision contexts we also investigate the decision-maker's physiological state during the decision, measured by heart rate variability (HRV, which we use as an indicator of emotional involvement. We found that the two elicitation methods provide different individual risk attitude measures which is partly reflected in a different gender effect between the methods. Personality traits explain only relatively little in terms of driving risk attitudes and the difference between methods. We also found that risk taking and the physiological state are related for one of the methods, suggesting that more emotionally involved individuals are more risk averse in the experiment. Finally, we found evidence that personality traits are connected to whether individuals made a decision in the dilemma situation, but risk attitudes and the physiological state were not indicative for the ability to decide in this decision context.

  16. Body Dissatisfaction in Early Adolescence: The Coactive Roles of Cognitive and Sociocultural Factors.

    Science.gov (United States)

    Saunders, Jessica F; Frazier, Leslie D

    2017-06-01

    The sociocultural influences of the media, friends, and family on body dissatisfaction in young girls are well documented, yet further increasing our comprehension of the coaction of cognitive processes with sociocultural factors is crucial to understanding the dynamic emergence of body dissatisfaction in early adolescence. The current study examined the roles of appearance related messages and expectations from friends and family and selective attention biases in the development of body dissatisfaction. An ethnically and racially diverse sample of girls (72 % Hispanic White, 17.8 % African-American, 8.5 % non-Hispanic White, and 1.7 % Asian-American) between the ages of 9 and 13 (N = 118) completed multiple measures of attention, sociocultural attitudes toward weight and shape, and body dissatisfaction. The data from these measures were examined using path analysis. The final model fit well, and demonstrated the coactive effect of selective attention and sociocultural factors on body dissatisfaction. These findings will be instrumental in designing future body dissatisfaction intervention and prevention programs that incorporate cognitive factors, augmenting the existing sociocultural and psycho-educational frameworks.

  17. Potential role for plasma placental growth factor in predicting coronary heart disease risk in women.

    Science.gov (United States)

    Cassidy, Aedín; Chiuve, Stephanie E; Manson, JoAnn E; Rexrode, Kathyrn M; Girman, Cynthia J; Rimm, Eric B

    2009-01-01

    The purpose of this study was to examine placental growth factor's (PlGF) predictive value in relation to coronary heart disease (CHD) risk in healthy women. Among 32 826 women from the Nurses' Health Study who provided blood samples at baseline, 453 CHD events were documented during 14 years of follow-up. Controls were matched to cases (2:1) for age, smoking, fasting status, and date of blood sampling. PlGF was inversely correlated with HDL-cholesterol (HDL-C), and positively correlated with several coronary risk factors. In multivariate models, women in the highest versus lowest quintile of PlGF had a greater risk of CHD (RR: 1.58; 95% CI: 1.03 to 2.41). Additional adjustment for many coronary risk factors did not substantively alter this relationship, but HDL-C attenuated the association (RR: 1.25; 95% CI: 0.81 to 1.94). In exploratory time to event analysis, higher PlGF levels, measured >10 years before CHD event, but not prediction of CHD, consistent with a potential role in early plaque formation and growth.

  18. The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review.

    Science.gov (United States)

    Kronbichler, Andreas; Kerschbaum, Julia; Mayer, Gert

    2015-01-01

    A better understanding of the pathophysiology of autoimmune disorders is desired to allow tailored interventions. Despite increased scientific interest a direct pathogenic factor in autoimmune renal disease has been described only in a minority like membranous nephropathy or ANCA-associated vasculitis. Nonetheless the initial step leading to the formation of these antibodies is still obscure. In this review we will focus on the possible role of microbial factors in this context. Staphylococcus aureus may be a direct pathogenetic factor in granulomatosis with polyangiitis (GPA). Chronic bacterial colonization or chronic infections of the upper respiratory tract have been proposed as trigger of IgA vasculitis and IgA nephropathy. Interventions to remove major lymphoid organs, such as tonsillectomy, have shown conflicting results but may be an option in IgA vasculitis. Interestingly no clear clinical benefit despite similar local colonization with bacterial strains has been detected in patients with IgA nephropathy. In systemic lupus erythematosus injection of bacterial lipopolysaccharide induced progressive lupus nephritis in mouse models. The aim of this review is to discuss and summarize the knowledge of microbial antigens in autoimmune renal disease. Novel methods may provide insight into the involvement of microbial antigens in the onset, progression, and prognosis of autoimmune kidney disorders.

  19. The Relationship between Demographic Factors and Gender Role Attitudes in Women Referring to Mashhad Health Care Centers in 2014

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    Elham Fazeli

    2015-01-01

    Full Text Available Background & aim:  Gender roles are affected by biosocial and cultural factors. These roles have significant impacts on one’s professional, social, and family life. Therefore, given the recent changes in gender roles in Iran, we aimed to determine the relationship between demographic factors and gender role attitudes among women. Methods:This cross-sectional study was conducted on 712 females, selected via stratified sampling. Data were collected using a demographic checklist and a gender role questionnaire including 2 sections: gender role stereotypes and gender egalitarianism. The validity of this questionnaire was confirmed by content validity and its reliability was verified by internal consistency (α=0.77. For data analysis, ANOVA and correlation coefficient tests were performed, using SPSS version16. Results: The mean scores of gender role stereotypes and egalitarianism were 29.55±4.33 and 112.55±14.64, respectively. Stereotypic and egalitarian attitudes were significantly correlated with age, family size, duration of marriage, women’s age at first childbirth, educational level, intentions to pursue education in future, and occupational status. Conclusion: As to the finding, gender role attitudes were influenced by social, economic, and demographic factors in Iran. By paying attention to these factors, we can implement proper interventions in order to promote personal and social health among women.

  20. The role of tissue factor in normal pregnancy and in the development of preeclampsia: A review.

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    Prochazkova, Jana; Slavik, Ludek; Ulehlova, Jana; Prochazka, Martin

    2015-06-01

    Tissue factor (TF) is a key element for normal gestation, especially in the first trimester. TF levels are hence raised in pregnancy, producing an adaptive hypercoagulable state. Potentiated hypercoagulability however, is associated with disorders of pregnancy such as pre-eclampsia but the results of TF and its inhibitor, tissue factor pathway inhibitor (TFPI), measurement, in pre eclampsic women are ambiguous and the data conflicting. This review covers the current knowledge status of the role of TF assessment in pregnancy with a focus on its diagnostic utility. A review of the literature using the following key words: tissue factor, thrombosis, inflammation, pregnancy, preeclampsia. The published literature shows raised and unchanged TF levels in various studies of pre-eclampsia along with equally conflicting data for TFPI. The various study designs and methods used in these studies makes valid comparison difficult. Meta analysis of 34 randomized trials showed that low-dose aspirin in early phases of gravidity (starting from the 16th week or earlier) significantly reduces the incidence of preeclampsia. Overall, the results of the literature search together with knowledge of the structure and biological effects of TF, suggest that measuring the level of plasma TF/TFPI is not ideal for determining the actual levels of TF in the uteroplacental circulation. The current view that endothelial dysfunction is the trigger for preeclampsia, suggests that aspirin may be an effective prophylaxis. Further research will be necessary: measuring the expression of tissue factor on monocytes using flowcytometry and comparing the development of this expression during normal pregnancy and pregnancy complicated by preeclampsia, for example. Another possibility is immunohistochemical determination of the level of TF expression directly in placental tissue.

  1. Role of Dicer1-Dependent Factors in the Paracrine Regulation of Epididymal Gene Expression.

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    Olivia Jerczynski

    Full Text Available Dicer1 is an endoribonuclease involved in the biogenesis of functional molecules such as microRNAs (miRNAs and endogenous small interfering RNAs (endo-siRNAs. These small non-coding RNAs are important regulators of post-transcriptional gene expression and participate in the control of male fertility. With the knowledge that 1 Dicer1-dependent factors are required for proper sperm maturation in the epididymis, and that 2 miRNAs are potent mediators of intercellular communication in most biological systems, we investigated the role of Dicer1-dependent factors produced by the proximal epididymis (initial segment/caput- including miRNAs- on the regulation of epididymal gene expression in the distal epididymis regions (i.e. corpus and cauda. To this end, we performed comparative microarray and ANOVA analyses on control vs. Defb41iCre/wt;Dicer1fl/fl mice in which functional Dicer1 is absent from the principal cells of the proximal epididymis. We identified 35 and 33 transcripts that displayed significant expression level changes in the corpus and cauda regions (Fold change > 2 or 2 or < -2; p < 0.01. These miRNAs are secreted via extracellular vesicles (EVs derived from the DC2 epididymal principal cell line, and their expression correlates with target transcripts involved in distinct biological pathways, as evidenced by in silico analysis. Albeit correlative and based on in silico approach, our study proposes that Dicer1-dependent factors trigger- directly or not-significant genes expression changes in distinct regions of this organ. The paracrine control of functions important to post-testicular sperm maturation by Dicer1-dependent factors may open new avenues for the identification of molecular targets important to male fertility control.

  2. The role of psychosocial factors in exclusive breastfeeding to six months postpartum.

    Science.gov (United States)

    de Jager, Emily; Broadbent, Jaclyn; Fuller-Tyszkiewicz, Matthew; Skouteris, Helen

    2014-06-01

    intention and duration. psychosocial factors are likely to play a significant role in the maintenance of exclusive breastfeeding for six months post-birth. Future research should adopt a prospective study design to examine the influence of psychosocial factors systematically and rigorously. longitudinal, prospective studies are needed to further examine the role of psychosocial factors on exclusive breastfeeding outcomes. Interventions, which involve improving psychosocial factors such as breastfeeding self-efficacy, may improve exclusive breastfeeding outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Irrepressible, truncated auxin response factors: natural roles and applications in dissecting auxin gene regulation pathways.

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    Ckurshumova, Wenzislava; Krogan, Naden T; Marcos, Danielle; Caragea, Adriana E; Berleth, Thomas

    2012-08-01

    The molecularly well-characterized auxin signal transduction pathway involves two evolutionarily conserved families interacting through their C-terminal domains III and IV: the Auxin Response Factors (ARFs) and their repressors the Aux/IAAs, to control auxin-responsive genes, among them genes involved in auxin transport. ( 1) (,) ( 2) We have developed a new genetic tool to study ARF function. Using MONOPTEROS (MP)/ARF5, we have generated a truncated version of MP (MPΔ), ( 3) which has lost the target domains for repression by Aux/IAA proteins. Besides exploring genetic interactions between MP and Aux/IAAs, we used this construct to trace MP's role in vascular patterning, a previously characterized auxin dependent process. ( 4) (,) ( 5) Here we summarize examples of naturally occurring truncated ARFs and summarize potential applications of truncated ARFs as analytical tools.

  4. Divestments in Banking. Preliminary Evidence on the Role of External Factors

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    Krzysztof Jackowicz

    2011-06-01

    Full Text Available Divestment constitutes an important method of corporate restructuring. Despite this fact, the banking literature on divestment is very limited. In this text, we try to remediate partially to the shortcomings of the existing literature by examining empirically the role of external factors. Using a large sample of 313 transactions, we have established that parent companies originate from countries with relatively high accumulated wealth, slow GDP growth, stable macroeconomic situation and dominant bank intermediation in financial system. The acquirers in turn come from poorer countries with faster economic growth and relatively more market-oriented financial systems. Those results broadly conform with the predictions of three hypotheses formulated in the text, namely the weak performance hypothesis, the corporate governance hypothesis and the rebalancing hypothesis.

  5. Emerging role of transcription factor-microRNA-target gene feed-forward loops in cancer.

    Science.gov (United States)

    Wu, Qian; Qin, Hua; Zhao, Qiu; He, Xing-Xing

    2015-09-01

    Transcriptional regulatory networks are biological network motifs that act in accordance with each other to play decisive roles in the pathological processes of cancer. One of the most common types, the feed-forward loop (FFL), has recently attracted interest. Three connected deregulated nodes, a transcription factor (TF), its downstream microRNA (miRNA) and their shared target gene can make up a class of cancer-involved FFLs as ≥1 of the 3 can act individually as a bona fide oncogene or a tumor suppressor. Numerous notable elements, such as p53, miR-17-92 cluster and cyclins, are proven members of their respective FFLs. Databases of interaction prediction, verification of experimental methods and confirmation of loops have been continually emerging during recent years. Development of TF-miRNA-target loops may help understand the mechanism of tumorgenesis at a higher level and explain the discovery and screening of the therapeutic target for drug exploitation.

  6. Role of Eosinophils and Tumor Necrosis Factor Alpha in Interleukin-25-Mediated Protection from Amebic Colitis

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    Zannatun Noor

    2017-02-01

    Full Text Available The parasite Entamoeba histolytica is a cause of diarrhea in infants in low-income countries. Previously, it was shown that tumor necrosis factor alpha (TNF-α production was associated with increased risk of E. histolytica diarrhea in children. Interleukin-25 (IL-25 is a cytokine that is produced by intestinal epithelial cells that has a role in maintenance of gut barrier function and inhibition of TNF-α production. IL-25 expression was decreased in humans and in the mouse model of amebic colitis. Repletion of IL-25 blocked E. histolytica infection and barrier disruption in mice, increased gut eosinophils, and suppressed colonic TNF-α. Depletion of eosinophils with anti-Siglec-F antibody prevented IL-25-mediated protection. In contrast, depletion of TNF-α resulted in resistance to amebic infection. We concluded that IL-25 provides protection from amebiasis, which is dependent upon intestinal eosinophils and suppression of TNF-α.

  7. Role of Host Genetic Factors in the Outcome of Hepatitis C Virus Infection

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    Hubert E. Blum

    2009-08-01

    Full Text Available The natural history of hepatitis C virus (HCV infection is determined by a complex interplay between host genetic, immunological and viral factors. This review highlights genes involved in innate and adaptive immune responses associated with different outcomes of HCV infection. For example, an association of HCV clearance with certain HLA alleles has been demonstrated. The mechanisms responsible for these associations have been linked to specific T cell responses for some particular alleles (e.g., HLA-B27. Genetic associations involved in T cell regulation and function further underline the role of the adaptive immune response in the natural history of HCV infection. In addition, some genes involved in innate NK cell responses demonstrate the complex interplay between components of the immune system necessary for a successful host response to HCV infection.

  8. THE ROLE OF THE HYDROLOGICAL FACTOR IN HABITAT DYNAMICS WITHIN THE FLUVIAL CORRIDOR OF DANUBE

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    GH. CLOŢĂ

    2012-03-01

    Full Text Available The role of the hydrological factor in habitat dynamics within the fluvial corridor of Danube. This paper had explored the connections between river hydrology with its changes and habitat dynamics. The fluvial corridor integrates spatially the channel and parts of its floodplain affected by periodical flooding and could be considered as an ecological corridor because of the size of the hydrosystem. The river and its ecosystems depend on geomorphogenetic and biological function and, thus creating a inter-dependence transposed into a concept, namely the fluvial hydrosystem, proposed firstly by Roux 1982, Amoros 1987. The hydrosystem is an ecological complex system constituted of biotopes and specific biocenoses of stream waters, stagnant water bodies, semi-aquatic, terrestrial ecosystems localized in the space of floodplain modeled directly and indirectly by river’s active force.

  9. The Possible Role of Tumor Necrosis Factor-α in Diabetic Polyneuropathy

    Science.gov (United States)

    Yagihashi, Soroku; Toyota, Takayoshi

    2003-01-01

    In this review, the authors provide evidences that imply the role of tumor necrosis factor-α (TNF-α) in the pathogenesis of diabetic complications, especially diabetic polyneuropathy. Under chronic hyperglycemia, endogenous TNF-α production is accelerated in microvascular and neural tissues, which may undergo an increased microvascular permeability, hypercoagulability, and nerve damage, thus initiating and promoting the development of characteristic lesions of diabetic microangiopathy and polyneuropathy. Enhanced TNF-α production may also promote atherosclerosis due to increased insulin resistance and the expression of adhesion molecules. Clinical application of specific agents that suppress production and/or activity of TNF-α may inhibit the development and exacerbation of chronic diabetic complications. PMID:14630568

  10. The possible role of tumor necrosis factor-alpha in diabetic polyneuropathy.

    Science.gov (United States)

    Satoh, Jo; Yagihashi, Soroku; Toyota, Takayoshi

    2003-01-01

    In this review, the authors provide evidences that imply the role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of diabetic complications, especially diabetic polyneuropathy. Under chronic hyperglycemia, endogenous TNF-alpha production is accelerated in microvascular and neural tissues, which may undergo an increased microvascular permeability, hypercoagulability, and nerve damage, thus initiating and promoting the development of characteristic lesions of diabetic microangiopathy and polyneuropathy. Enhanced TNF-alpha production may also promote atherosclerosis due to increased insulin resistance and the expression of adhesion molecules. Clinical application of specific agents that suppress production and/or activity of TNF-alpha may inhibit the development and exacerbation of chronic diabetic complications.

  11. The role of hypoxia-inducible factor-2 in digestive system cancers.

    Science.gov (United States)

    Zhao, J; Du, F; Shen, G; Zheng, F; Xu, B

    2015-01-15

    Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIF-1α and HIF-2α, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIF-2α in digestive system cancers. Indeed, HIF-2α has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIF-2α a critical regulator of this malignant phenotype. Here we summarize the function of HIF-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies.

  12. Role of Sociocultural Factors in Depression among Elderly of Twin Cities (Rawalpindi and Islamabad of Pakistan

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    Saira Javed

    2014-01-01

    Full Text Available This research was conducted to examine the role of sociocultural factors on depression among elderly of twin cities (Rawalpindi and Islamabad of Pakistan. 310 older adults participated in the present study. Through convenient sampling technique, face to face interview was carried out for data collection. Urdu translated Geriatric Depression Scale Short Form and demographic sheet were used to test hypotheses. Descriptive statistics and t-test were used for data analysis. Results showed significant mean differences among gender, marital status, family system, and status of employment on depression. Financial crisis, feeling of dejection because of isolation, and trend of nuclear family system have been observed as strong predictors of depression in older adults.

  13. Factors influencing residents' evaluations of clinical faculty member teaching qualities and role model status.

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    Arah, Onyebuchi A; Heineman, Maas J; Lombarts, Kiki M J M H

    2012-04-01

      Evaluations of faculty members are widely used to identify excellent or substandard teaching performance. In order to enable such evaluations to be properly interpreted and used in faculty development, it is essential to understand the factors that influence resident doctors' (residents) evaluations of the teaching qualities of faculty members and their perceptions of faculty members as role-model specialists.   We carried out a cross-sectional survey within a longitudinal study of the System for Evaluation of Teaching Qualities (SETQ) of clinical teachers. The study sample included 889 residents and 1014 faculty members in 61 teaching programmes spanning 22 specialties in 20 hospitals in the Netherlands. Main outcome measures included residents' (i) global and (ii) specific ratings of faculty member teaching qualities, and (iii) global ratings of faculty members as role-model specialists. Statistical analysis was conducted using adjusted multivariable logistic generalised estimating equations.   In total, 690 residents (77.6%) completed 6485 evaluations of 962 faculty members, 848 (83.6%) of whom also self-evaluated. More recently certified faculty members, those who had attended a teacher training programme, and those who spent more time teaching than seeing patients or conducting research were more likely to score highly on most teaching qualities. However, faculty members who had undergone teacher training were less likely to be seen as role models (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.59-0.88). In addition, faculty members were evaluated slightly higher by male than female residents on core teaching domains and overall teaching quality, but were less likely to be seen as role models by male residents (OR 0.80, 95% CI 0.67-0.97). Lastly, faculty members had higher odds of receiving top scores in specific teaching domains from residents in the first 4 years of residency and were less likely to be considered as role models by more

  14. Using multistate observational studies to determine role of hypertension and diabetes as risk factors for dementia

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    Mitasha Singh

    2016-01-01

    Full Text Available Background: Evidence suggests that modifiable risk factors which can be targeted by prevention are vascular diseases, such as diabetes, midlife hypertension (HTN, midlife obesity, midlife cholesterol, mid- and late-life depression as well as lifestyle factors such as smoking, physical inactivity, and poor diet. Methods: A comprehensive search of the National Library of Medicine's PubMed database and Google Scholar was conducted. A combinations of medical subject headings and free text words that included search terms related to the exposure (e.g., prevalence, HTN, raised BP, high BP, diabetes, high blood sugar, DM, India, state, were combined with search terms related to the outcomes (e.g., prevalence, disease burden, estimate, dementia, India. The filters included were English for the language category and humans for the study category. Results: The PubMed search initially identified 269 references, and a total of 204 abstracts were screened by inclusion criteria. Full-text assessment of 136 articles on prevalence of dementia resulted in 20 relevant articles from which the different regions of the country were identified. Based on the search conducted according to the regions; 287abstracts of the prevalence of HTN and 577 on the prevalence of diabetes mellitus were screened. There were 43 full-text articles on the prevalence of HTN and diabetes from the regions where the prevalence of dementia was available. Of these potentially relevant articles were 14 in number. Conclusion: Despite the uncertainty in the role, the data analysis, therefore, points to a role in the prevention of HTN and diabetes to prevent dementia.

  15. The gut microbiota composition in dichorionic triplet sets suggests a role for host genetic factors.

    Science.gov (United States)

    Murphy, Kiera; O' Shea, Carol Anne; Ryan, C Anthony; Dempsey, Eugene M; O' Toole, Paul W; Stanton, Catherine; Ross, R Paul

    2015-01-01

    Monozygotic and dizygotic twin studies investigating the relative roles of host genetics and environmental factors in shaping gut microbiota composition have produced conflicting results. In this study, we investigated the gut microbiota composition of a healthy dichorionic triplet set. The dichorionic triplet set contained a pair of monozygotic twins and a fraternal sibling, with similar pre- and post-natal environmental conditions including feeding regime. V4 16S rRNA and rpoB amplicon pyrosequencing was employed to investigate microbiota composition, and the species and strain diversity of the culturable bifidobacterial population was also examined. At month 1, the monozygotic pair shared a similar microbiota distinct to the fraternal sibling. By month 12 however, the profile was more uniform between the three infants. Principal coordinate analysis (PCoA) of the microbiota composition revealed strong clustering of the monozygotic pair at month 1 and a separation of the fraternal infant. At months 2 and 3 the phylogenetic distance between the monozygotic pair and the fraternal sibling has greatly reduced and by month 12 the monozygotic pair no longer clustered separately from the fraternal infant. Pulse field gel electrophoresis (PFGE) analysis of the bifidobacterial population revealed a lack of strain diversity, with identical strains identified in all three infants at month 1 and 12. The microbiota of two antibiotic-treated dichorionic triplet sets was also investigated. Not surprisingly, in both triplet sets early life antibiotic administration appeared to be a major determinant of microbiota composition at month 1, irrespective of zygosity. By month 12, early antibiotic administration appeared to no longer exert such a strong influence on gut microbiota composition. We hypothesize that initially host genetics play a significant role in the composition of an individual's gut microbiota, unless an antibiotic intervention is given, but by month 12 environmental

  16. Factor analysis as a tool for survey analysis using a professional role orientation inventory as an example.

    Science.gov (United States)

    Swisher, Laura L; Beckstead, Jason W; Bebeau, Muriel J

    2004-09-01

    The purpose of this article is to illustrate how confirmatory factor analysis can be used to extend and clarify a researcher's insight into a survey instrument beyond that afforded through the typical exploratory factor analytic approach. The authors use as an example a survey instrument developed to measure individual differences in professional role orientation among physical therapists, the Professional Role Orientation Inventory for Physical Therapists (PROI-PT). Five hundred three physical therapists responded to a mail survey instrument that was sent to a random sample of 2,000 American Physical Therapy Association members. An adapted version of the Professional Role Orientation Inventory, a 40-item Likert-scale instrument developed to assess professional role orientation on 4 dimensions (authority, responsibility, agency, and autonomy), was used. Exploratory and confirmatory factor analyses were used to examine the factorial validity of the PROI-PT. Exploratory factor analysis served as a starting point for examining the factor structure of the instrument. Confirmatory factor analysis then was used to test the hypothesized factor structure and to suggest refinements to the PROI-PT that would improve a psychometric property (internal consistency). Although further refinement of the PROI-PT is needed, an instrument that yields valid and reliable measurements of individual differences in professionalism among physical therapists could further our understanding of the psychosocial aspects of physical therapist practice. Exploratory and confirmatory factor analyses can be used by researchers who study various psychosocial constructs in physical therapy.

  17. Moderating role of entrepreneurial orientation on the relationship between entrepreneurial skills, environmental factors and entrepreneurial intention: A PLS approach

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    Najafi Auwalu Ibrahim; Abdulsalam Mas’ud

    2016-01-01

    For decades, entrepreneurship has become a major concern to both scholars and policymakers because of its significant role in economic and social transformation. This paper modeled the direct effects of entrepreneurial skill, environmental factors and entrepreneurial orientation on entrepreneurial intention as well as the indirect (moderating) effect of entrepreneurial orientation on the relationship of entrepreneurial skill and environmental factors with entrepreneurial intention. Quantitati...

  18. Novel aspects of human infertility: the role of the male factor

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    Anna Havrylyuk

    2015-11-01

    Full Text Available In the article new aspects of the ‘male factor’ and its role in early stages of pregnancy are described. Among others, genetic and immunogenetic (KIR/KAR, HLA factors are underlined as well as immunological ones (e.g. microchimerism. A significant part of this review is dedicated to infectious agents and semen inflammation as well as to the TORCH syndrome and chlamydiosis, concentrating on the male part, in which there are a lot of unclarified consequences. The problem of somatic diseases and general homeostasis of the male and its influence on pregnancy with particular emphasis on previous cryptorchidism is also discussed. The role of sperm DNA integrity in the fertilization process as well as genetic polymorphisms on the male side is emphasised. Particularly, molecular aspects of HLA-G and HLA-C in developmental biology are raised. There is a discussion of the individual approach to assisted reproductive techniques, which cannot be treated as a panacea for infertility treatment, particularly considering early stages of embryonal and fetal development.

  19. Role of environmental factors and history of low back pain in sciatica symptoms among Finnish adolescents.

    Science.gov (United States)

    Karjalainen, Ulla; Paananen, Markus; Okuloff, Annaleena; Taimela, Simo; Auvinen, Juha; Männikkö, Minna; Karppinen, Jaro

    2013-06-01

    Cross-sectional study in a subcohort of the 1986 Northern Finland Birth Cohort (n = 1987). To investigate the role of environmental factors and LBP history in sciatica symptoms among Finnish young adults. History of low back pain (LBP), smoking, and male sex are associated with sciatica in adult populations. The role of the environmental determinants of sciatica has not been evaluated in populations consisting of only adolescents. Sciatic symptoms and environmental exposures were elicited by a mailed questionnaire and the associations were analyzed using multinomial logistic regression. Female sex was associated with severe sciatica at 18 years (OR, 3.9; 95% confidence interval (CI), 1.6-9.3). Both reported LBP at 16 years and LBP requiring consultation of a health care professional were associated with mild sciatica at 18 years (OR, 2.5; 95% CI, 1.3-4.9; and OR, 3.8; 95% CI, 1.2-11.9). In addition, LBP at 16 years requiring consultation of a health care professional was associated with severe sciatica at 18 years (OR, 5.0; 95% CI, 1.7-15.3). Smoking, obesity, physical workload, and level of physical activity were not associated with sciatica. Females reported sciatic pain more often than males. LBP at 16 years predicted sciatica at 18 years. 2.

  20. Ciliary neurotrophic factor role in myelin oligodendrocyte glycoprotein expression in Cuprizone-induced multiple sclerosis mice.

    Science.gov (United States)

    Salehi, Zivar; Hadiyan, Sara Pishgah; Navidi, Reza

    2013-05-01

    Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. Myelin oligodendrocyte glycoprotein (MOG) is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of MS. Ciliary neurotrophic factor (CNTF) has been shown to enhance the generation, maturation, and survival of oligodendrocytes in culture medium. The aim of this study was to demonstrate the role of CNTF on MOG expression in the cerebral cortex of Cuprizone-induced MS mice. The mice were treated by Cuprizone for five weeks in order to induce MS. The mice were then divided into 3 groups. The first group was injected subcutaneously (SC) by CNTF in the amount of 250 μg/kg BW per day. The second group (SHAM) was injected SC by normal saline and the third group was left without injection as the control group. After four weeks the mice were killed and the cerebral cortex was harvested and the expression of MOG was studied by Western blotting. The data from this study show that the MOG expression was significantly increased in the CNTF-injected group as compared to the other groups. It is concluded that CNTF increases the MOG expression and may be important in the pathophysiology of MS. It is also concluded that CNTF may play a role in the process of remyelination by inducing the MOG expression.

  1. Mechanical factors play an important role in pectus excavatum with thoracic scoliosis

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    Wang Yuncang

    2012-11-01

    Full Text Available Abstract Background This study investigated the incidence, imaging characteristics and mechanical factors in scoliotic patients with pectus excavatum. Methods A total of 142 scoliostic patients with pectus excavatum were evaluated prior to operation. The evaluation included a complete physical exam, phenotype and severity of the pectus excavatum, incidence and severity of scoliosis, and analysis of radiological images, including calculation of the Haller index. Results Twenty five out of 142 patients (17.61% with pectus excavatum had scoliosis with a Cobb angle >10 degrees, and in 80.00% of the cases the spinal column was bent to the right. Seventeen patients had bent-to-the-right spines that involved the 6th to 10 th thoracic vertebrae. We found that 23 out of 25 patients with a Cobb angle more than 10° were teenagers and adults. The incidence of scoliosis was only 6.06% in the children under 11 years whereas it was 21.79% in the teenage group. Conclusions Mechanical forces appear to play a role in the coexistence of pectus excavatum and scoliosis. There is a relationship between age, severity (Haller index, asymmetry and scoliosis. The heart and mediastinum play a role in providing an outward force to the left of the sternum which may be an important reason for the coexistence of pectus excavatum and scoliosis, but the correlation needs further proof.

  2. Mechanical factors play an important role in pectus excavatum with thoracic scoliosis.

    Science.gov (United States)

    Wang, Yuncang; Chen, Gang; Xie, Liang; Tang, Jiming; Ben, Xiaosong; Zhang, Dongkun; Xiao, Pu; Zhou, Haiyu; Zhou, Zihao; Ye, Xiong

    2012-11-12

    This study investigated the incidence, imaging characteristics and mechanical factors in scoliotic patients with pectus excavatum. A total of 142 scoliostic patients with pectus excavatum were evaluated prior to operation. The evaluation included a complete physical exam, phenotype and severity of the pectus excavatum, incidence and severity of scoliosis, and analysis of radiological images, including calculation of the Haller index. Twenty five out of 142 patients (17.61%) with pectus excavatum had scoliosis with a Cobb angle >10 degrees, and in 80.00% of the cases the spinal column was bent to the right. Seventeen patients had bent-to-the-right spines that involved the 6th to 10 th thoracic vertebrae. We found that 23 out of 25 patients with a Cobb angle more than 10° were teenagers and adults. The incidence of scoliosis was only 6.06% in the children under 11 years whereas it was 21.79% in the teenage group. Mechanical forces appear to play a role in the coexistence of pectus excavatum and scoliosis. There is a relationship between age, severity (Haller index), asymmetry and scoliosis. The heart and mediastinum play a role in providing an outward force to the left of the sternum which may be an important reason for the coexistence of pectus excavatum and scoliosis, but the correlation needs further proof.

  3. The role of platelet activating factor in a neonatal piglet model of necrotising enterocolitis.

    Science.gov (United States)

    Ewer, A K; Al-Salti, W; Coney, A M; Marshall, J M; Ramani, P; Booth, I W

    2004-02-01

    Necrotising enterocolitis (NEC) is a potentially devastating disorder of preterm infants but its aetiology remains unclear. The aim of these studies was to develop a neonatal piglet model for NEC and to then use the model to investigate the role of platelet activating factor (PAF) in its pathogenesis. Anaesthetised newborn piglets were divided into six groups: (i) controls, and groups subjected to (ii) hypoxia, (iii) lipopolysaccharide (LPS), (iv) hypoxia+LPS, (v) hypoxia+LPS and the PAF antagonist WEB 2170, and (vi) PAF. Arterial blood pressure (ABP), superior mesenteric artery blood flow (MBF), mesenteric vascular conductance (MVC), and arterial blood gases were recorded, and intestinal histology was evaluated. Exposure to LPS, hypoxia+LPS, or PAF all caused haemorrhagic intestinal lesions associated with varying degrees of intestinal injury. PAF caused a significant initial decrease in both MVC and MBF whereas hypoxia+LPS caused a significant late reduction in ABP and MBF with a trend towards a decrease in MVC. The effects of hypoxia+LPS on both haemodynamic changes and intestinal injury were ameliorated by WEB 2170. Administration of hypoxia and LPS or of PAF in the neonatal piglet induces haemodynamic changes and intestinal lesions that are consistent with NEC. These effects are ameliorated by prior administration of WEB 2170, indicating an important role for PAF in the pathogenesis of NEC.

  4. Role of the colony-stimulating factor (CSF)/CSF-1 receptor axis in cancer.

    Science.gov (United States)

    Achkova, Daniela; Maher, John

    2016-04-15

    Cancer cells employ a variety of mechanisms to evade apoptosis and senescence. Pre-eminent among these is the aberrant co-expression of growth factors and their ligands, forming an autocrine growth loop that promotes tumour formation and progression. One growth loop whose transforming potential has been repeatedly demonstrated is the CSF-1/CSF-1R axis. Expression of CSF-1 and/or CSF-1R has been documented in a number of human malignancies, including breast, prostate and ovarian cancer and classical Hodgkin's lymphoma (cHL). This review summarizes the large body of work undertaken to study the role of this cytokine receptor system in malignant transformation. These studies have attributed a key role to the CSF-1/CSF-1R axis in supporting tumour cell survival, proliferation and enhanced motility. Moreover, increasing evidence implicates paracrine interactions between CSF-1 and its receptor in defining a tumour-permissive and immunosuppressive tumour-associated stroma. Against this background, we briefly consider the prospects for therapeutic targeting of this system in malignant disease. © 2016 Authors; published by Portland Press Limited.

  5. Role of apoptosis-inducing factor (AIF in programmed nuclear death during conjugation in Tetrahymena thermophila

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    Endoh Hiroshi

    2010-02-01

    Full Text Available Abstract Background Programmed nuclear death (PND, which is also referred to as nuclear apoptosis, is a remarkable process that occurs in ciliates during sexual reproduction (conjugation. In Tetrahymena thermophila, when the new macronucleus differentiates, the parental macronucleus is selectively eliminated from the cytoplasm of the progeny, concomitant with apoptotic nuclear events. However, the molecular mechanisms underlying these events are not well understood. The parental macronucleus is engulfed by a large autophagosome, which contains numerous mitochondria that have lost their membrane potential. In animals, mitochondrial depolarization precedes apoptotic cell death, which involves DNA fragmentation and subsequent nuclear degradation. Results We focused on the role of mitochondrial apoptosis-inducing factor (AIF during PND in Tetrahymena. The disruption of AIF delays the normal progression of PND, specifically, nuclear condensation and kilobase-size DNA fragmentation. AIF is localized in Tetrahymena mitochondria and is released into the macronucleus prior to nuclear condensation. In addition, AIF associates and co-operates with the mitochondrial DNase to facilitate the degradation of kilobase-size DNA, which is followed by oligonucleosome-size DNA laddering. Conclusions Our results suggest that Tetrahymena AIF plays an important role in the degradation of DNA at an early stage of PND, which supports the notion that the mitochondrion-initiated apoptotic DNA degradation pathway is widely conserved among eukaryotes.

  6. Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes.

    Science.gov (United States)

    Gorbet, Maud B; Sefton, Michael V

    2004-11-01

    Our failure to produce truly non-thrombogenic materials may reflect a failure to fully understand the mechanisms of biomaterial-associated thrombosis. The community has focused on minimizing coagulation or minimizing platelet adhesion and activation. We have infrequently considered the interactions between the two although we are generally familiar with these interactions. However, we have rarely considered in the context of biomaterial-associated thrombosis the other major players in blood: complement and leukocytes. Biomaterials are known agonists of complement and leukocyte activation, but this is frequently studied only in the context of inflammation. For us, thrombosis is a special case of inflammation. Here we summarize current perspectives on all four of these components in thrombosis and with biomaterials and cardiovascular devices. We also briefly highlight a few features of biomaterial-associated thrombosis that are not often considered in the biomaterials literature: The importance of tissue factor and the extrinsic coagulation system. Complement activation as a prelude to platelet activation and its role in thrombosis. The role of leukocytes in thrombin formation. The differing time scales of these contributions.

  7. Specific Roles of MicroRNAs in Their Interactions with Environmental Factors

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    Juan Wang

    2012-01-01

    Full Text Available MicroRNAs (miRNAs have emerged as critical regulators of gene expression by modulating numerous target mRNAs expression at posttranscriptional level. Extensive studies have shown that miRNAs are critical in various important biological processes, including cell growth, proliferation, differentiation, development, and apoptosis. In terms of their importance, miRNA dysfunction has been associated with a broad range of diseases. Increased number of studies have shown that miRNAs can functionally interact with a wide spectrum of environmental factors (EFs including drugs, industrial materials, virus and bacterial pathogens, cigarette smoking, alcohol, nutrition, sleep, exercise, stress, and radiation. More importantly, the interactions between miRNAs and EFs have been shown to play critical roles in determining abnormal phenotypes and diseases. In this paper, we propose an outline of the current knowledge about specific roles of miRNAs in their interactions with various EFs and analyze the literatures detailing miRNAs-EFs interactions in the context of various of diseases.

  8. The role of the transcription factor SIM2 in prostate cancer.

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    Bin Lu

    Full Text Available Recent reports have suggested a possible involvement of Single-minded homolog 2 (SIM2 in human solid cancers, including prostate cancer. However, the exact role of SIM2 in cancer in general, and in prostate cancer in particular, remains largely unknown. This study was designed to elucidate the role of SIM2 in prostate cancer using a shRNA-based approach in the PC3 prostate cancer cell line.Lentiviral shRNAs were used to inhibit SIM2 gene and protein levels in PC3 cells. Quantitative RT-PCR and branched DNA were performed to evaluate transcript expression. SIM2 protein expression level was measured by western blot. Profiling of gene expression spanning the whole genome, as well as polar metabolomics of several major metabolic pathways was performed to identify major pathway dysregulations.SIM2 gene and protein products were significantly downregulated by lenti-shRNA in PC3 cell line. This low expression of SIM2 affected gene expression profile, revealing significant changes in major signaling pathways, networks and functions. In addition, major metabolic pathways were affected.Taken together, our results suggest an involvement of SIM2 in key traits of prostate tumor cell biology and might underlie a contribution of this transcription factor to prostate cancer onset and progression.

  9. Dysregulation of the homeobox transcription factor gene HOXB13: role in prostate cancer.

    Science.gov (United States)

    Decker, Brennan; Ostrander, Elaine A

    2014-01-01

    Prostate cancer (PC) is the most common noncutaneous cancer in men, and epidemiological studies suggest that about 40% of PC risk is heritable. Linkage analyses in hereditary PC families have identified multiple putative loci. However, until recently, identification of specific risk alleles has proven elusive. Cooney et al used linkage mapping and segregation analysis to identify a putative risk locus on chromosome 17q21-22. In search of causative variant(s) in genes from the candidate region, a novel, potentially deleterious G84E substitution in homeobox transcription factor gene HOXB13 was observed in multiple hereditary PC families. In follow-up testing, the G84E allele was enriched in cases, especially those with an early diagnosis or positive family history of disease. This finding was replicated by others, confirming HOXB13 as a PC risk gene. The HOXB13 protein plays diverse biological roles in embryonic development and terminally differentiated tissue. In tumor cell lines, HOXB13 participates in a number of biological functions, including coactivation and localization of the androgen receptor and FOXA1. However, no consensus role has emerged and many questions remain. All HOXB13 variants with a proposed role in PC risk are predicted to damage the protein and lie in domains that are highly conserved across species. The G84E variant has the strongest epidemiological support and lies in a highly conserved MEIS protein-binding domain, which binds cofactors required for activation. On the basis of epidemiological and biological data, the G84E variant likely modulates the interaction between the HOXB13 protein and the androgen receptor, as well as affecting FOXA1-mediated transcriptional programming. However, further studies of the mutated protein are required to clarify the mechanisms by which this translates into PC risk.

  10. An investigation into vocal expressions of emotions: the roles of valence, culture, and acoustic factors

    Science.gov (United States)

    Sauter, Disa

    This PhD is an investigation of vocal expressions of emotions, mainly focusing on non-verbal sounds such as laughter, cries and sighs. The research examines the roles of categorical and dimensional factors, the contributions of a number of acoustic cues, and the influence of culture. A series of studies established that naive listeners can reliably identify non-verbal vocalisations of positive and negative emotions in forced-choice and rating tasks. Some evidence for underlying dimensions of arousal and valence is found, although each emotion had a discrete expression. The role of acoustic characteristics of the sounds is investigated experimentally and analytically. This work shows that the cues used to identify different emotions vary, although pitch and pitch variation play a central role. The cues used to identify emotions in non-verbal vocalisations differ from the cues used when comprehending speech. An additional set of studies using stimuli consisting of emotional speech demonstrates that these sounds can also be reliably identified, and rely on similar acoustic cues. A series of studies with a pre-literate Namibian tribe shows that non-verbal vocalisations can be recognized across cultures. An fMRI study carried out to investigate the neural processing of non-verbal vocalisations of emotions is presented. The results show activation in pre-motor regions arising from passive listening to non-verbal emotional vocalisations, suggesting neural auditory-motor interactions in the perception of these sounds. In sum, this thesis demonstrates that non-verbal vocalisations of emotions are reliably identifiable tokens of information that belong to discrete categories. These vocalisations are recognisable across vastly different cultures and thus seem to, like facial expressions of emotions, comprise human universals. Listeners rely mainly on pitch and pitch variation to identify emotions in non verbal vocalisations, which differs with the cues used to comprehend

  11. The role of phosphoinositide 3-kinases in neutrophil migration in 3D collagen gels.

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    Kayleigh J S Martin

    Full Text Available The entry of neutrophils into tissue has been well characterised; however the fate of these cells once inside the tissue microenvironment is not fully understood. A variety of signal transduction pathways including those involving class I PI3 Kinases have been suggested to be involved in neutrophil migration. This study aims to determine the involvement of PI3 Kinases in chemokinetic and chemotactic neutrophil migration in response to CXCL8 and GM-CSF in a three-dimensional collagen gel, as a model of tissue. Using a three-dimensional collagen assay chemokinetic and chemotactic migration induced by CXCL8 was inhibited with the pan PI3 Kinase inhibitor wortmannin. Analysis of the specific Class I PI3 Kinase catalytic isoforms alpha, delta and gamma using the inhibitors PIK-75, PIK-294 and AS-605240 respectively indicated differential roles in CXCL8-induced neutrophil migration. PIK-294 inhibited both chemokinetic and chemotactic CXCL8-induced migration. AS-605240 markedly reduced CXCL8 induced chemokinetic migration but had no effect on CXCL8 induced chemotactic migration. In contrast PIK-75 inhibited chemotactic migration but not chemokinetic migration. At optimal concentrations of GM-CSF the inhibitors had no effect on the percentage of neutrophil migration in comparison to the control however at suboptimal concentrations wortmannin, AS-605240 and PIK-294 inhibited chemokinesis. This study suggests that PI3 Kinase is necessary for CXCL8 induced migration in a 3D tissue environment but that chemokinetic and chemotactic migration may be controlled by different isoforms with gamma shown to be important in chemokinesis and alpha important in chemotaxis. Neutrophil migration in response to suboptimal concentrations of GM-CSF is dependent on PI3 Kinase, particularly the gamma and delta catalytic isoforms.

  12. Stress-Related Growth among Suicide Survivors: The Role of Interpersonal and Cognitive Factors.

    Science.gov (United States)

    Levi-Belz, Yossi

    2015-01-01

    Although stress-related growth had been documented in bereaved individuals, it is still not clear to what extent it can be experienced by suicide survivors or which psychological processes facilitate it. The current study examined the role of interpersonal factors-self disclosure and social supports as well as cognitive coping strategies in stress-related growth among suicide survivors. The sample consisted of 135 suicide survivors (104 women and 31 men) aged 18-70. All participants completed the stress-related growth questionnaire as well as instruments measuring interpersonal activities, cognitive strategies, and demographic characteristics concerning the bereavement. The findings showed significant positive correlations between time elapsed since death, self-disclosure, social support, adaptive cognitive strategies, and stress-related growth. Furthermore, hierarchical regression analysis revealed that together these variables accounted for over 38% of the variance in stress-related growth. Interpersonal activities such as talking and interacting with others, as well as a cognitive focus on planning for the future emerged as important factors in personal transformation after suicide loss.

  13. The Role of Vascular Endothelial Growth Factor in Metastatic Prostate Cancer to the Skeleton

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    Emma Roberts

    2013-01-01

    Full Text Available Despite the clinical implication and high incidence of bone and spinal metastases, the molecular mechanisms behind prostate cancer metastasis to bone and spine are not well understood. In this review the molecular mechanisms that may contribute to the highly metastatic phenotype of prostate cancer are discussed. Proangiogenic factors such as vascular endothelial growth factor (VEGF have been shown to not only aid in the metastatic capabilities of prostate cancer but also encourage the colonization and growth of prostate tumour cells in the skeleton. The importance of VEGF in the complex process of prostate cancer dissemination to the skeleton is discussed, including its role in the development of the bone premetastatic niche, metastatic tumour cell recognition of bone, and bone remodeling. The expression of VEGF has also been shown to be upregulated in prostate cancer and is associated with clinical stage, Gleason score, tumour stage, progression, metastasis, and survival. Due to the multifaceted effect VEGF has on tumour angiogenesis, tumour cell proliferation, and bone destruction, therapies targeting the VEGF pathways have shown promising clinical application and are being investigated in clinical trials.

  14. Opposing roles for interferon regulatory factor-3 (IRF-3 and type I interferon signaling during plague.

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    Ami A Patel

    Full Text Available Type I interferons (IFN-I broadly control innate immunity and are typically transcriptionally induced by Interferon Regulatory Factors (IRFs following stimulation of pattern recognition receptors within the cytosol of host cells. For bacterial infection, IFN-I signaling can result in widely variant responses, in some cases contributing to the pathogenesis of disease while in others contributing to host defense. In this work, we addressed the role of type I IFN during Yersinia pestis infection in a murine model of septicemic plague. Transcription of IFN-β was induced in vitro and in vivo and contributed to pathogenesis. Mice lacking the IFN-I receptor, Ifnar, were less sensitive to disease and harbored more neutrophils in the later stage of infection which correlated with protection from lethality. In contrast, IRF-3, a transcription factor commonly involved in inducing IFN-β following bacterial infection, was not necessary for IFN production but instead contributed to host defense. In vitro, phagocytosis of Y. pestis by macrophages and neutrophils was more effective in the presence of IRF-3 and was not affected by IFN-β signaling. This activity correlated with limited bacterial growth in vivo in the presence of IRF-3. Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-β production.

  15. [Role of genetic and environmental factors in the development of polycystic ovary syndrome].

    Science.gov (United States)

    Ságodi, László; Kiss-Tóth, Emőke; Barkai, László

    2013-04-28

    Polycystic ovary syndrome is the most common heterogeneous endocrine abnormality in women in the reproductive age. The syndrome remains an enigmatic disorder because the aetiology is still unclear. Familial aggreagation is relatively common among patients with polycystic ovary syndrome suggesting a significant genetic component, although the way of inheritance has not been established firmly. The authors review the relevant medical literature and suggest that genetic and environmental factors play a role in the development of polycystic ovary syndrome. To date, no gene has been identified that causes or contributes substantially to the development of a polycystic ovary syndrome phenotype. Polycystic ovarian syndrome is considered to be an oligogenic disorder in which the interaction of a number of genetic and environmental factors determines the heterogeneous clinical and biochemical phenotype. To summarize current evidence the authors conclude, that when we are able to identify and then modify environmental determinants, then we will be able to safeguard better the health of those patients who are predisposed to disease development due to genotype or previous environmental effects.

  16. Role of HPF (hibernation promoting factor) in translational activity in Escherichia coli.

    Science.gov (United States)

    Ueta, Masami; Ohniwa, Ryosuke L; Yoshida, Hideji; Maki, Yasushi; Wada, Chieko; Wada, Akira

    2008-03-01

    During the stationary phase of growth in Escherichia coli, ribosome modulation factor (RMF) and hibernation promoting factor (HPF) dimerize most 70S ribosomes to form 100S ribosomes. The process of 100S formation has been termed 'ribosomal hibernation'. Here, the contributions of HPF to 100S formation and translation were analysed in vitro. HPF bound to, but did not dimerize the 70S ribosome. RMF dimerized and formed immature 90S ribosomes. Binding of both HPF and RMF converted 90S ribosomes to mature 100S ribosomes, which is consistent with the in vivo data. The role of HPF in in vitro translation also was investigated. In an artificial mRNA poly (U)-dependent phenylalanine incorporation assay, HPF bound to ribosomal particles and inhibited translation. In contrast, in a natural MS2 mRNA-dependent leucine incorporation assay, bound HPF was removed and hardly inhibited normal translation. Multiple alignment and phylogenetic analyses indicates that the hibernation system mediated by the HPF homologue, RMF and 100S ribosome formation may be specific to the proteobacteria gamma group. In contrast, most bacteria have at least one HPF homologue, and these homologues can be classified into three types, long HPF, short HPF and YfiA.

  17. The role of stem cell factor in mobilization of peripheral blood progenitor cells.

    Science.gov (United States)

    McNiece, I K; Briddell, R A; Yan, X Q; Hartley, C A; Gringeri, A; Foote, M A; Andrews, R G

    1994-11-01

    Stem cell factor (SCF) is a hematopoietic growth factor which acts on both primitive and mature progenitors cells. In animals, high doses of SCF alone stimulate increases in cells of multiple lineages and mobilize peripheral blood progenitor cells (PBPC). Phase I studies of rhSCF have demonstrated dose related side effects which are consistent with mast cell activation. Based upon in vitro synergy between SCF and G-CSF we have demonstrated the potential of low doses of SCF to synergize with G-CSF to give enhanced mobilization of PBPC. These PBPC have increased potential for both short and long term engraftment in lethally irradiated mice and lead to more rapid recovery of platelets. On going Phase I/II studies with rhSCF plus rhG-CSF for mobilization of PBPC, demonstrated similar increases in PBPC compared to rhG-CSF alone. These data suggest a clinical role of rhSCF in combination with rhG-CSF for optimal mobilization of PBPC.

  18. Evaluation the role of nutritional and individual factors in colorectal cancer

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    Kamran Moshfeghi

    2011-09-01

    Full Text Available Background: Colorectal cancer is one of the most common cancers worldwide including 38% of gastrointestinal cancers. Colorectal cancer is the third type of Iranian men and fourth in women in ranking. The purpose of this study was to determine the role of environmental risk factors in colorectal cancer.Materials and Method: In this case-control study, the authors selected cases from colorectal cancer patients in Arak and controls were selected from Arak hospitals in proportion to the number of cases. Data collected by using a structured questionnaire and based on interviews with patients and their medical records. We used chi-squared and independent t-tests to analyze data. Logistic regression applies to eliminate the effect of possible confounding variables.Results: From all participants 55.7% were male and 90% got married. 33.6% were overweight and/or obese. Mean ± SD of age and BMI was 54.41±14.88 yr and 24.42±4.58, respectively. Regression model showed that fatty food intake, high education and positive family history are the predictor risk factors of colorectal cancer. Conclusion: Due to preventable colorectal cancer and increased global incidence of disease, educational intervention about the importance of disease, methods of screening and diagnosis, treatment and rehabilitation of patients are necessary

  19. The role of psychological factors in the development of burning mouth syndrome.

    Science.gov (United States)

    Yoo, H S; Jin, S H; Lee, Y J; Song, C M; Ji, Y B; Tae, K

    2018-03-01

    The psychiatric profiles of 50 patients diagnosed with burning mouth syndrome (BMS) were compared to those of 50 age- and sex-matched individuals as the control group. The Symptom Checklist-90-Revised (SCL-90-R) questionnaire was used to evaluate the role of psychological factors in the development of BMS. Somatization, obsessive-compulsive, depression, anxiety, hostility, phobic anxiety, psychoticism, global severity index (GSI), positive symptom total (PST), and positive symptom distress index (PSDI) scores were significantly higher in the patients with BMS than in the control group. In a subgroup analysis according to sex, women with BMS had higher T-scores for somatization, obsessive-compulsive, paranoid ideation, GSI, PST, and PSDI than women in the control group. In contrast, only the PSDI score was significantly higher in men with BMS compared to men in the control group. There was a significant difference in the T-scores for somatization, psychoticism, and GSI between the three age subgroups (≤50, 51-65, and ≥66 years). The obsessive-compulsive and PSDI scores were significantly higher in patients with BMS who also had at least one chronic disease than in patients with BMS who had no chronic disease. In conclusion, psychological factors are correlated with BMS. Copyright © 2017. Published by Elsevier Ltd.

  20. Prognostic role of epidermal growth factor receptor in nasopharyngeal carcinoma: a meta-analysis.

    Science.gov (United States)

    Sun, Wei; Long, Guoxian; Wang, Junfeng; Mei, Qi; Liu, Dongbo; Hu, Guoqing

    2014-10-01

    Various studies have assessed the prognostic value of epidermal growth factor receptor (EGFR) overexpression in nasopharyngeal carcinoma (NPC), but their results remain controversial. Studies published up to January 2013 were collected. A total of 16 studies involving 1179 patients were reviewed. A meta-analysis was performed to clarify the prognostic role of EGFR in patients with NPC. The combined hazard ratio (HR) and 95% confidence interval (CI) were estimated using fixed-effects or random-effects models. EGFR overexpression had significantly poor effect on overall survival (OS; HR, 1.86; 95% CI, 1.25-2.77), disease-free survival (DFS; HR, 2.25; 95% CI, 1.66-3.04) and locoregional control (HR, 2.93; 95% CI, 1.71-5.02). However, the association between EGFR overexpression and distant metastasis-free survival was not statistically significant (HR, 1.39; 95% CI, 0.72-2.67). EGFR overexpression can be a prognostic factor for patients with NPC. © 2013 Wiley Periodicals, Inc.

  1. Work-related factors of presenteeism: The mediating role of mental and physical health.

    Science.gov (United States)

    Pohling, Rico; Buruck, Gabriele; Jungbauer, Kevin-Lim; Leiter, Michael P

    2016-04-01

    Even though work-related factors have been found to play a crucial role in predicting presenteeism, studies investigating established theoretical frameworks of job design features and, in particular, underlying mechanisms are still very scarce. The objective of this study was to investigate the influence of the areas of work life according to the Areas of Worklife Scale (AWS; Leiter & Maslach, 2004) on presenteeism. We examined mental and physical health as the underlying process of this relationship and assessed 2 presenteeism outcome measures and their relationship to each other-that is, the frequency of acts of presenteeism and work productivity. Using a cross-sectional design, the study was conducted in a sample of 885 employees from German public service. Results showed that the influence of some, but not all, areas of work life (workload, control, reward, and values) on both acts of presenteeism and health-related lost productivity was mediated by health indicators (well-being and musculoskeletal complaints). Moreover, we found a relationship between health-related lost productivity and acts of presenteeism. The present research clarifies the importance of work-related factors as antecedents of sickness presenteeism. The findings of our study also emphasize the necessity to include both acts of presenteeism and health-related lost productivity in presenteeism research and prevention. Presenteeism should be included as a measure in health prevention interventions because it reflects a crucial part of employee health that is not covered by other measures. (c) 2016 APA, all rights reserved).

  2. Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle.

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    William Hartman

    Full Text Available Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF, can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs.48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia.Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy.

  3. The role of nuclear factor κB in the cellular response to different radiation qualities

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Kristina

    2013-04-11

    Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

  4. Two MYB-related transcription factors play opposite roles in sugar signaling in Arabidopsis.

    Science.gov (United States)

    Chen, Yi-Shih; Chao, Yi-Chi; Tseng, Tzu-Wei; Huang, Chun-Kai; Lo, Pei-Ching; Lu, Chung-An

    2017-02-01

    Sugar regulation of gene expression has profound effects at all stages of the plant life cycle. Although regulation at the transcriptional level is one of the most prominent mechanisms by which gene expression is regulated, only a few transcription factors have been identified and demonstrated to be involved in the regulation of sugar-regulated gene expression. OsMYBS1, an R1/2-type MYB transcription factor, has been demonstrated to be involved in sugar- and hormone-regulated α-amylase gene expression in rice. Arabidopsis contains two OsMYBS1 homologs. In the present study, we investigate MYBS1 and MYBS2 in sugar signaling in Arabidopsis. Our results indicate that MYBS1 and MYBS2 play opposite roles in regulating glucose and ABA signaling in Arabidopsis during seed germination and early seedling development. MYB proteins have been classified into four subfamilies: R2R3-MYB, R1/2-MYB, 3R-MYB, and 4R-MYB. An R1/2-type MYB transcription factor, OsMYBS1, has been demonstrated to be involved in sugar- and hormone-regulated α-amylase genes expression in rice. In this study, two genes homologous to OsMYBS1, MYBS1 and MYBS2, were investigated in Arabidopsis. Subcellular localization analysis showed that MYBS1 and MYBS2 were localized in the nucleus. Rice embryo transient expression assays indicated that both MYBS1 and MYBS2 could recognize the sugar response element, TA-box, in the promoter and induced promoter activity. mybs1 mutant exhibited hypersensitivity to glucose, whereas mybs2 seedlings were hyposensitive to it. MYBS1 and MYBS2 are involved in the control of glucose-responsive gene expression, as the mybs1 mutant displayed increased expression of a hexokinase gene (HXK1), chlorophyll a/b-binding protein gene (CAB1), ADP-glucose pyrophosphorylase gene (APL3), and chalcone synthase gene (CHS), whereas the mybs2 mutant exhibited decreased expression of these genes. mybs1 also showed an enhanced response to abscisic acid (ABA) in the seed germination and seedling

  5. Nurses' perceived and actual caregiving roles: identifying factors that can contribute to job satisfaction.

    Science.gov (United States)

    Morrison, Kelsey B; Korol, Susan A

    2014-12-01

    To compare nurses' caring expectations with their caregiving experiences and to identify factors that could potentially be included in a preliminary conceptual model of job satisfaction and compassion fatigue. Nurses often report emotional reward and satisfaction in their profession from compassionately caring for sick and injured patients. However, being in close proximity to trauma can eventually deplete a nurse's compassion and empathy for the patients they care for. This loss of compassion is further exacerbated by demanding work environments that involve administrative duties, attending to patients' psychosocial needs and interacting with patients' families. To date, the literature has tended to focus on pathology of compassion fatigue, rather than identifying its contributing factors. A grounded theory approach was used to identify emerging themes in nurses' accounts of their caregiving roles. Open-ended interviews were conducted with nurses (n = 9) who were employed by a maritime district health authority for a minimum of five years. Interviews focused on beliefs of how to provide care, perceived caregiving responsibilities and perceived challenges in the provision of care. Emerging from the data is a proposed model of job satisfaction. The concepts of monitoring and patient advocacy appeared to be key components in reported satisfaction or alienation. Discrepancies were found between care expectations outlined by management and nurses' perceptions of care provision. Additionally, type of nursing education was related to nurses' confidence in applying nursing skills. These findings have implications for training programmes, hospital management and quality of patient care. It is important to identify factors that could explain resilience to compassion fatigue because compassion fatigue has negative consequences not only for nurses themselves but for the patients in their care. © 2014 John Wiley & Sons Ltd.

  6. The role of Ikaros transcriptional factor in normal hematopoiesis and leukemogenesis: biological and clinical aspects

    Directory of Open Access Journals (Sweden)

    V. S. Vshivkoo

    2015-01-01

    Full Text Available Investigation of the pathogenesis and factors effecting recurrence, progression and drug resistance in acute leukemia (AL remains a major challenge for hematology and other related areas. The role of more than 50 genes and proteins in the AL pathogenesis has been shown, including the well-studied tumor suppressor (CDKN2A/CDKN2B, RB1, PTEN, p53, and classical fusion genes (BCR/ABL1, TEL/AML1, E2A/PBX, MLL translocations. In addition, high frequency of aberrations in genes responsible for lymphoid differentiation have been identified such as transcription factors (PAX5, IKZF1 and EBF1, transcriptional regulation of the genes (ETV6, ERG, and signaling pathways of antigen receptors (BTLA, CD200, TOX, BLNK, VPREB1, as well as genes involved in chemoresistance of leukemia cells (NR3C1. In recent studies, Ikaros abnormalities have been reported to be frequently associated with AL. Ikaros is a member of a Kruppel-like family of zinc finger transcription factors that also includes IKZF2 (Helios, IKZF3 (Aiolos, Eos and Pegasus, and encoded by the IKZF1 gene. In hematopoietic cells Ikaros functions as a transcription factor, a key protein controlling T-, B-, NK-, and dendritic cells early differentiation. At the early hematopoiesis stages, it represses the myeloid and erythroid lineages, and stimulates the lymphoid differentiation. Ikaros also normally modulates immune response and plays role of a tumor suppressor in lymphoid malignances. Data from numerous clinical studies confirmed an association between the presence of IKZF1 aberrations and B-cell and, to a lesser extent, T-cell acute lymphoblastic leukemia (ALL development. Besides, loss of Ikaros function was associated with progression of myeloproliferative diseases to acute myeloid leukemia (AML in children. From clinical point of view, particular intragenic IKZF1 deletions and a short (non-functional protein Ikaros isoforms, which may occur as a result of intragenic deletions or aberrant splicing

  7. Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin.

    Science.gov (United States)

    Dixit, V M; Green, S; Sarma, V; Holzman, L B; Wolf, F W; O'Rourke, K; Ward, P A; Prochownik, E V; Marks, R M

    1990-02-15

    Cytokines such as tumor necrosis factor alpha (TNF) profoundly affect endothelial cell function, promoting for example interaction with leukocytes and inducing a procoagulant phenotype. Changes of this nature are likely to be central to the proinflammatory effects of TNF. In order to elucidate molecular mechanisms by which TNF alters endothelial cell function we utilized differential plaque hybridization to identify TNF-responsive genes. Forty TNF-inducible cDNAs were identified which on cross-hybridization were found to arise from six unique genes. DNA sequencing of these cDNAs revealed two encoded known cytokine-induced genes, endothelial leukocyte adhesion molecule 1 and neutrophil chemotactic factor. One of the cDNAs encodes a recently described monocyte-specific chemotactic factor not previously associated with endothelium. The production of a monocyte chemotaxin by cytokine-activated endothelium has important implications for understanding the role of the vessel wall in disease states such as atherosclerosis and may also in part explain the indirect angiogenic activity of TNF. The three other cDNAs are completely novel as judged by data bank searches of partial DNA sequences and remain unidentified. On exposure of endothelial cells to TNF there is a rapid and substantial increase in levels of mRNA encoding the six genes, which are further superinduced by cycloheximide. Thus these represent primary response genes as their induction does not depend on protein synthesis. Interleukin-1 beta and lipopolysaccharide are also potent inducers. Nuclear run-on studies revealed that in most cases induction by TNF is mediated largely at the transcriptional level.

  8. Brain-derived neurotrophic factor is increased in atopic dermatitis and modulates eosinophil functions compared with that seen in nonatopic subjects.

    Science.gov (United States)

    Raap, Ulrike; Goltz, Christine; Deneka, Nicole; Bruder, Manuela; Renz, Harald; Kapp, Alexander; Wedi, Bettina

    2005-06-01

    Recently, the pivotal role of brain-derived neurotrophic factor (BDNF) has been described in allergic asthma. However, the role of this neurotrophin in atopic dermatitis (AD) still remains unknown. The aim of this study was to investigate the functional role of BDNF on eosinophils and to assess BDNF levels in patients with AD and nonatopic control subjects. Methods p75 Neurotrophin receptor and tyrosine kinase B receptor expression was demonstrated by using FACS analysis and immunohistochemistry. BDNF levels were assessed with ELISA and FACS analysis. Chemotactic activity (modified Boyden chamber assay), eosinophil cationic protein release (fluoroenzyme immunoassay), respiratory burst (lucigenin-dependent chemiluminescence), and apoptosis (Nicoletti protocol and Annexin-V method) assays were used to assess BDNF functional activity. BDNF levels were increased in serum, plasma, eosinophils, and supernatants of stimulated eosinophils from patients with AD compared with levels seen in nonatopic control subjects ( P neurotrophin receptor and tyrosine kinase B expression was higher on eosinophils from patients with AD compared with that seen on eosinophils from nonatopic control subjects ( P < .05-.001). Eosinophil apoptosis was inhibited by BDNF ( P < .05-.01) and chemotactic index was increased ( P < .001) in BDNF-stimulated eosinophils from patients with AD, whereas this effect was not shown in eosinophils from nonatopic control subjects. However, no response of BDNF through the release of eosinophil cationic protein or reactive oxygen species was found. This study provides the first evidence for a functional role of BDNF on eosinophils from patients with AD, probably mediated by an increased expression of BDNF receptors compared with that seen in nonatopic control subjects. In addition, higher intracellular, serum, and plasma BDNF levels, as well as the release of BDNF by eosinophils, underline the particular importance of BDNF in patients with AD, pointing to new

  9. The Anthropological Implications of Sex Role Differences: Class and Ethnic Factors.

    Science.gov (United States)

    Wright, Jerome W.

    The implications of physical and biological sex differences on sex role behavior cannot be understood without analyzing the complementary role of the sociocultural meaning of sex roles. The normative aspect of gender role behavior is fluid and can be affected by culture, class, and ethnicity. All societies recognize differences between the sexes.…

  10. Rice NAC transcription factor ONAC095 plays opposite roles in drought and cold stress tolerance.

    Science.gov (United States)

    Huang, Lei; Hong, Yongbo; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2016-09-20

    The NAC (NAM, ATAF and CUC) transcriptional factors constitute a large family with more than 150 members in rice and some of them have been demonstrated to play crucial roles in plant abiotic stress response. Here, we report the characterization of a rice stress-responsive NAC gene, ONAC095, and the exploration of its function in drought and cold stress tolerance. Expression of ONAC095 was up-regulated by drought stress and abscisic acid (ABA) but down-regulated by cold stress. ONAC095 protein had transactivation activity and the C2 domain in C-terminal was found to be critical for transactivation activity. Transgenic rice lines with overexpression of ONAC095 (ONAC095-OE) and dominant chimeric repressor-mediated suppression of ONAC095 (ONAC095-SRDX) were generated. The ONAC095-OE plants showed comparable phenotype to wild type under drought and cold stress conditions. However, the ONAC095-SRDX plants displayed an improved drought tolerance but exhibited an attenuated cold tolerance. The ONAC095-SRDX plants had decreased water loss rate, increased proline and soluble sugar contents, and up-regulated expression of drought-responsive genes under drought condition, whereas the ONAC095-SRDX plants accumulated excess reactive oxygen species, increased malondialdehyde content and down-regulated expression of cold-responsive genes under cold condition. Furthermore, ONAC095-SRDX plants showed an increased ABA sensitivity, contained an elevated ABA level, and displayed altered expression of ABA biosynthetic and metabolic genes as well as some ABA signaling-related genes. Functional analyses through dominant chimeric repressor-mediated suppression of ONAC095 demonstrate that ONAC095 plays opposite roles in drought and cold stress tolerance, acting as a negative regulator of drought response but as a positive regulator of cold response in rice.

  11. 6-gingerol ameliorated doxorubicin-induced cardiotoxicity: role of nuclear factor kappa B and protein glycation.

    Science.gov (United States)

    El-Bakly, Wesam M; Louka, Manal L; El-Halawany, Ali M; Schaalan, Mona F

    2012-12-01

    Doxorubicin is a widely used antitumour drug. Cardiotoxicity is considered a major limitation for its clinical use. The present study was designed to assess the possible antioxidant and antiapoptotic effects of 6-gingerol in attenuating doxorubicin-induced cardiac damage. Male albino rats were treated with either intraperitoneal doxorubicin (18 mg/kg divided into six equal doses for 2 weeks) and/or oral 6-gingerol (10 mg/kg starting 5 days before and continued till the end of the experiment). 6-gingerol significantly ameliorated the doxorubicin-induced elevation in the cardiac enzymes. The stimulation of oxidative stress by doxorubicin was evidenced by the significant decrease in the serum soluble receptor for advanced glycation endproduct allowing unopposed serum advanced glycation endproduct availability. Moreover, doxorubicin activated nuclear factor kappa B (NF-κB) which was indicated by an increase in its immunohistochemical staining in the nucleus. In addition, doxorubicin-induced cardiotoxicity was accompanied by elevation of cardiac caspase-3. Notably, pretreatment with 6-gingerol significantly ameliorated the changes in sRAGE, NF-κB and cardiac caspase-3. Cardiac enzymes showed significant positive correlation with NF-κB and caspase-3 but negative with serum sRAGE, suggesting their role in doxorubicin-induced cardiac injury. These findings were confirmed by cardiac tissue histopathology. 6-gingerol, a known single compound from ginger with anticancer activity, was shown to have a promising role in cardioprotection against doxorubicin-induced cardiotoxicity. This study suggested a novel mechanism for 6-gingerol cardioprotection, which might be mediated through its antioxidative effect and modulation of NF-κB as well as apoptosis.

  12. Role of information sources and socio-demographic factors on knowledge about AIDS in female adolescents.

    Science.gov (United States)

    Farid, Rakshanda

    2005-01-01

    To assess the role of information sources and socio-demographic factors on knowledge about AIDS in female adolescents. Cross-sectional survey. Three different girls colleges of Lahore. Study was conducted from September 1999 to November 1999. The sample of 600 students was divided into various colleges according to the total strength of students in the college. The students filled a semi structured questionnaire anonymously. To assess the overall knowledge of students a scale with a range of 0-49 score was developed for 49 items inquired to assess knowledge about AIDS. On the basis of this score students were divided into satisfactory and unsatisfactory knowledge groups by using the 50th percentile as the cut off point. Eighty percent of those students whose mothers and 58% of those students whose fathers had postgraduate qualifications had satisfactory knowledge of AIDS as compared to those students whose parents were graduate and undergraduate (p political and sports section of the newspapers. Access to television, satellite channels and Internet had a statistically significant effect on knowledge about AIDS (p<0.0001). Significant higher knowledge of AIDS was observed among those students who discussed AIDS with their sisters and friends (p <0.05) as compared to those students who discussed AIDS with their parents and teachers. Those students who belonged to higher socioeconomic group and had educated parents had satisfactory knowledge about AIDS. The newspaper and electronic media also have an important role in transmitting knowledge about AIDS. Family members, friends and teachers can prove to be a potential source for dissemination of information about AIDS.

  13. Histamine-Induced Dilation of Isolated Porcine Retinal Arterioles: Role of Endothelium-Derived Hyperpolarizing Factor.

    Science.gov (United States)

    Otani, Shinichi; Nagaoka, Taiji; Omae, Tsuneaki; Tanano, Ichiro; Kamiya, Takayuki; Ono, Shinji; Hein, Travis W; Kuo, Lih; Yoshida, Akitoshi

    2016-09-01

    Although endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles has been well described, the role of endothelium-derived hyperpolarizing factor (EDHF) in the retinal arteriolar response remains unclear. In the current study, we examined the contribution of EDHF to the retinal arteriolar dilation to the inflammatory agent histamine and investigated the signaling mechanisms underlying this vasomotor activity. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for functional study by using video microscopic techniques. The immunohistochemical staining was performed to determine histamine receptor subtypes. Histamine (0.1-30 μM) produced concentration-dependent dilation of retinal arterioles in a manner sensitive to H1- and H2-receptor antagonists chlorpheniramine and famotidine, respectively. Histamine-induced vasodilation was almost abolished after endothelial removal. In the intact vessels, vasodilation to histamine was partially inhibited by the inhibitors of cyclooxygenase (indomethacin), NO synthase (NG-nitro-L-arginine methyl ester, L-NAME), or Ca2+ -activated K+ (KCa) channels (apamin plus charybdotoxin). Combination of the above inhibitors abolished histamine-induced vasodilation. Residual vasodilation in the presence of indomethacin and L-NAME was further reduced by the cytochrome P450 enzyme inhibitor sulfaphenazole but not by the gap junction inhibitor carbenoxolone or the hydrogen peroxide scavenger catalase. Immunohistochemical signals for H1- and H2-receptor expression were found only in the endothelium. The endothelium plays an essential role in the dilation of porcine retinal arterioles to histamine via H1- and H2-receptor activation. The EDHF derived from cytochrome P450 contributed in part to this vasodilation via KCa channel activation, in addition to the endothelial release of NO and prostanoids.

  14. Oncogenic role of fibroblast growth factor receptor 3 in tumorigenesis of urinary bladder cancer.

    Science.gov (United States)

    Pandith, Arshad A; Shah, Zafar A; Siddiqi, Mushtaq A

    2013-05-01

    Bladder cancer is the second most common genitourinary tumor and constitutes a very heterogeneous disease. Molecular and pathologic studies suggest that low-grade noninvasive and high-grade invasive urothelial cell carcinoma (UCC) arise via distinct pathways. Low-grade noninvasive UCC represent the majority of tumors at presentation. A high proportion of patients with low-grade UCC develop recurrences but usually with no progression to invasive disease. At presentation, a majority of the bladder tumors (70%-80%) are low-grade noninvasive (pTa). Several genetic changes may occur in bladder cancer, but activating mutations in the fibroblast growth factor receptor 3 (FGFR3) genes are the most common and most specific genetic abnormality in bladder cancer. Interestingly, these mutations are associated with bladder tumors of low stage and grade, which makes the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive bladder tumors. Since the first report of FGFR3 involvement in bladder tumors, numerous studies have been conducted to understand its function and thereby confirm the oncogenic role of this receptor particularly in noninvasive groups. Efforts are on to exploit this receptor as a therapeutic target, which holds much promise in the treatment of bladder cancer, particularly low-grade noninvasive tumors. Further studies need to explore the potential use of FGFR3 mutations in bladder cancer diagnosis, prognosis, and in surveillance of patients with bladder cancer. This review focuses on the role of FGFR3 in bladder tumors in the backdrop of various studies published. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Expression and prognostic role of ubiquitination factor E4B in primary hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Xiao-Fei; Pan, Qiu-Zhong; Pan, Ke; Weng, De-Sheng; Wang, Qi-Jing; Zhao, Jing-Jing; He, Jia; Liu, Qing; Wang, Dan-Dan; Jiang, Shan-Shan; Zheng, Hai-Xia; Lv, Lin; Chen, Chang-Long; Zhang, Hong-Xia; Xia, Jian-Chuan

    2016-01-01

    Ubiquitination factor E4B (UBE4B) has been speculated to have contradictory functions upon tumorigenesis as an oncogene or tumor suppressor in different types of cancers. We investigated the expression and prognostic role of UBE4B in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples. Correlation between the functions of UBE4B in HCC was also explored. We used human HCC cell lines (HepG2, Hep3B, SK-Hep1, Huh7, SMMC-7721, BEL-7402) and a normal hepatocyte cell line (LO2) along with HCC samples from patients who had undergone resection for HCC previously at our hospital. A battery of methods (real-time quantitative polymerase chain reaction; Western blotting; immunohistochjemical analyses; cell proliferation and colony formation assays; cell migration and cell invasion assays) were employed to assess various aspects of UBE4B.We found that UBE4B expression was upregulated aberrantly at mRNA and protein levels in human primary HCC tissues. Amplified expression of UBE4B was highly correlated with poor outcome. Silencing of UBE4B expression by siRNA inhibited the proliferation, colony formation, migration and invasion of HCC cells in vitro, and resulted in significant apoptosis that was associated with downregulation of expression of Bcl-2 and upregulation of expression of total p53, p-p53, Bax and Cleaved-Caspase3 in HCC cells. Our findings suggested that UBE4B might have an oncogenic role in human primary HCC, and that it could be used as a prognostic marker (as well as a potential molecular target) for the treatment of HCC. © 2015 Wiley Periodicals, Inc.

  16. Role of eukaryotic translation initiation factor 3a in bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Li, Xian-Wei; Wu, Yue-Han; Li, Xiao-Hui; Li, Dai; Du, Jie; Hu, Chang-Ping; Li, Yuan-Jian

    2015-02-15

    Eukaryotic translation initiation factor 3a (eIF3a) is a multifunctional protein and plays an important role in regulation of cellular function including proliferation and differentiation. In the present study, we tested the function of eIF3a in pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Primary pulmonary fibroblasts were cultured for proliferation investigation by BrdU incorporation method and flow cytometry. The expression/level of eIF3a, TGF-β1, ERK1/2 and α-SMA were analyzed by ELISA, real-time PCR or western blot. Results showed that the expression of eIF3a was obviously increased in lungs of pulmonary fibrosis rats accompanied by up-regulation of α-SMA and collagens. In cultured pulmonary fibroblasts, application of exogenous TGF-β1 induced cell proliferation and differentiation concomitantly with up-regulation of eIF3a expression and ERK1/2 phosphorylation. The effects of TGF-β1-induced proliferation of fibroblasts and up-regulation of α-SMA were abolished by eIF3a siRNA. TGF-β1-induced eIF3a expression was reversed in the presence of PD98059, an inhibitor of ERK1/2. These findings suggest that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis by regulating pulmonary fibroblasts׳ function, and up-regulation of eIF3a induced by TGF-β1 is mediated via the ERK1/2 pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Ren HY

    2016-03-01

    Full Text Available Hai-Yong Ren,1 Yin-Hua Zhang,1,2 Heng-Yuan Li,1 Tao Xie,1 Ling-Ling Sun,1 Ting Zhu,1 Sheng-Dong Wang,1 Zhao-Ming Ye1 1Department of Orthopaedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 2The First Department of Orthopaedics, Hospital of Zhejiang General Corps of Armed Police Forces, Jiaxing, People’s Republic of China Background: Hypoxia-inducible factor-1α (HIF-1α plays an important role in tumor progression and metastasis. A number of studies have investigated the association of HIF-1α with prognosis and clinicopathological characteristics of osteosarcoma but yielded inconsistent results.  Method: Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs and odds ratios (ORs with corresponding confidence intervals (CIs were calculated to assess the prognostic value of HIF-1α expression. The standard mean difference was used to analyze the continuous variable.  Results: Finally, nine studies comprising 486 patients were subjected to final analysis. Protein expression level of HIF-1α was found to be significantly related to overall survival (HR =3.0; 95% CI: 1.46–6.15, disease-free survival (HR =2.23; 95% CI: 1.26–3.92, pathologic grade (OR =21.33; 95% CI: 4.60–98.88, tumor stage (OR =10.29; 95% CI: 3.55–29.82, chemotherapy response (OR =9.68; 95% CI: 1.87–50.18, metastasis (OR =5.06; 95% CI: 2.87–8.92, and microvessel density (standard mean difference =2.83; 95% CI: 2.28–3.39.  Conclusion: This meta-analysis revealed that overexpression of HIF-1α is a predictive factor of poor outcomes for osteosarcoma. HIF-1α appeared to play an important role in prognostic evaluation and may be a potential target in antitumoral therapy. Keywords: HIF-1α, osteosarcoma, prognosis, meta-analysis

  18. Personality Correlates of Midlife Cardiometabolic Risk: The Explanatory Role of Higher-Order Factors of the Five-Factor Model.

    Science.gov (United States)

    Dermody, Sarah S; Wright, Aidan G C; Cheong, JeeWon; Miller, Karissa G; Muldoon, Matthew F; Flory, Janine D; Gianaros, Peter J; Marsland, Anna L; Manuck, Stephen B

    2016-12-01

    Varying associations are reported between Five-Factor Model (FFM) personality traits and cardiovascular disease risk. Here, we further examine dispositional correlates of cardiometabolic risk within a hierarchical model of personality that proposes higher-order traits of Stability (shared variance of Agreeableness, Conscientiousness, inverse Neuroticism) and Plasticity (Extraversion, Openness), and we test hypothesized mediation via biological and behavioral factors. In an observational study of 856 community volunteers aged 30-54 years (46% male, 86% Caucasian), latent variable FFM traits (using multiple-informant reports) and aggregated cardiometabolic risk (indicators: insulin resistance, dyslipidemia, blood pressure, adiposity) were estimated using confirmatory factor analysis (CFA). The cardiometabolic factor was regressed on each personality factor or higher-order trait. Cross-sectional indirect effects via systemic inflammation, cardiac autonomic control, and physical activity were tested. CFA models confirmed the Stability "meta-trait," but not Plasticity. Lower Stability was associated with heightened cardiometabolic risk. This association was accounted for by inflammation, autonomic function, and physical activity. Among FFM traits, only Openness was associated with risk over and above Stability, and, unlike Stability, this relationship was unexplained by the intervening variables. A Stability meta-trait covaries with midlife cardiometabolic risk, and this association is accounted for by three candidate biological and behavioral factors. © 2015 Wiley Periodicals, Inc.

  19. Dysregulation of the homeobox transcription factor gene HOXB13: role in prostate cancer

    Directory of Open Access Journals (Sweden)

    Decker B

    2014-08-01

    Full Text Available Brennan Decker1,2, Elaine A Ostrander1 1Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; 2Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK Abstract: Prostate cancer (PC is the most common noncutaneous cancer in men, and epidemiological studies suggest that about 40% of PC risk is heritable. Linkage analyses in hereditary PC families have identified multiple putative loci. However, until recently, identification of specific risk alleles has proven elusive. Cooney et al used linkage mapping and segregation analysis to identify a putative risk locus on chromosome 17q21-22. In search of causative variant(s in genes from the candidate region, a novel, potentially deleterious G84E substitution in homeobox transcription factor gene HOXB13 was observed in multiple hereditary PC families. In follow-up testing, the G84E allele was enriched in cases, especially those with an early diagnosis or positive family history of disease. This finding was replicated by others, confirming HOXB13 as a PC risk gene. The HOXB13 protein plays diverse biological roles in embryonic development and terminally differentiated tissue. In tumor cell lines, HOXB13 participates in a number of biological functions, including coactivation and localization of the androgen receptor and FOXA1. However, no consensus role has emerged and many questions remain. All HOXB13 variants with a proposed role in PC risk are predicted to damage the protein and lie in domains that are highly conserved across species. The G84E variant has the strongest epidemiological support and lies in a highly conserved MEIS protein-binding domain, which binds cofactors required for activation. On the basis of epidemiological and biological data, the G84E variant likely modulates the interaction between the HOXB13

  20. Critical role of serum response factor in pulmonary myofibroblast differentiation induced by TGF-beta.

    Science.gov (United States)

    Sandbo, Nathan; Kregel, Steven; Taurin, Sebastien; Bhorade, Sangeeta; Dulin, Nickolai O

    2009-09-01

    Transforming growth factor-beta (TGF-beta) is a cytokine implicated in wound healing and in the pathogenesis of pulmonary fibrosis. TGF-beta stimulates myofibroblast differentiation characterized by expression of contractile smooth muscle (SM)-specific proteins such as SM-alpha-actin. In the present study, we examined the role of serum response factor (SRF) in the mechanism of TGF-beta-induced pulmonary myofibroblast differentiation of human lung fibroblasts (HLF). TGF-beta stimulated SM-alpha-actin expression in HLF, which paralleled with a profound induction of SRF expression and activity. Inhibition of SRF by the pharmacologic SRF inhibitor (CCG-1423), or via adenovirus-mediated transduction of SRF short hairpin RNA (shSRF), blocked the expression of both SRF and SM-alpha-actin in response to TGF-beta without affecting Smad-mediated signaling of TGF-beta. However, forced expression of SRF on its own did not promote SM-alpha-actin expression, whereas expression of the constitutively transactivated SRF fusion protein (SRF-VP16) was sufficient to induce SM-alpha-actin expression, suggesting that both expression and transactivation of SRF are important. Activation of protein kinase A (PKA) by forskolin or iloprost resulted in a significant inhibition of SM-alpha-actin expression induced by TGF-beta, and this was associated with inhibition of both SRF expression and activity, but not of Smad-mediated gene transcription. In summary, this is the first direct demonstration that TGF-beta-induced pulmonary myofibroblast differentiation is mediated by SRF, and that inhibition of myofibroblast differentiation by PKA occurs through down-regulation of SRF expression levels and SRF activity, independent of Smad signaling.

  1. Critical Role of Serum Response Factor in Pulmonary Myofibroblast Differentiation Induced by TGF-β

    Science.gov (United States)

    Sandbo, Nathan; Kregel, Steven; Taurin, Sebastien; Bhorade, Sangeeta; Dulin, Nickolai O.

    2009-01-01

    Transforming growth factor-β (TGF-β) is a cytokine implicated in wound healing and in the pathogenesis of pulmonary fibrosis. TGF-β stimulates myofibroblast differentiation characterized by expression of contractile smooth muscle (SM)-specific proteins such as SM–α-actin. In the present study, we examined the role of serum response factor (SRF) in the mechanism of TGF-β–induced pulmonary myofibroblast differentiation of human lung fibroblasts (HLF). TGF-β stimulated SM–α-actin expression in HLF, which paralleled with a profound induction of SRF expression and activity. Inhibition of SRF by the pharmacologic SRF inhibitor (CCG-1423), or via adenovirus-mediated transduction of SRF short hairpin RNA (shSRF), blocked the expression of both SRF and SM–α-actin in response to TGF-β without affecting Smad-mediated signaling of TGF-β. However, forced expression of SRF on its own did not promote SM–α-actin expression, whereas expression of the constitutively transactivated SRF fusion protein (SRF-VP16) was sufficient to induce SM–α-actin expression, suggesting that both expression and transactivation of SRF are important. Activation of protein kinase A (PKA) by forskolin or iloprost resulted in a significant inhibition of SM–α-actin expression induced by TGF-β, and this was associated with inhibition of both SRF expression and activity, but not of Smad-mediated gene transcription. In summary, this is the first direct demonstration that TGF-β–induced pulmonary myofibroblast differentiation is mediated by SRF, and that inhibition of myofibroblast differentiation by PKA occurs through down-regulation of SRF expression levels and SRF activity, independent of Smad signaling. PMID:19151320

  2. Role of OCB and demographic factors in the relationship of motivation and employee performance

    Directory of Open Access Journals (Sweden)

    Yew Huei Tan

    2014-05-01

    Full Text Available Purpose: This research seeks to broaden the study by investigating the interplay of organizational citizenship behaviour (OCB and demographic factor (gender and organizational tenure on the motivation and employee performance relationship.Design/methodology/approach: Multiple linear regression was used to test the relationship between motivation (intrinsic and extrinsic and employee performance among (n=368 lecturers in Malaysia. To test the mediating effect of OCB, path analysis was employed. Furthermore, the demographic factors (gender and organizational tenure was tested using the moderated multiple regression analysis.Findings: Significant differences in explaining the variance of employee\tperformance was found between intrinsic motivation and extrinsic motivation. In addition, OCB was found perfectly mediating the relationship of extrinsic motivation and employee performance, however, OCB was found partially mediating the relationship between intrinsic motivation and employee performance. Furthermore, gender and organizational tenure do not show any moderate results in the relationship between OCB and employee performance.Research limitations: Study limitations (e.g. cross-sectional research design and biasness and future opportunities are outlined.Practical implications: Argues that the suitable type of motivation in explaining the variances of employee performance. Also, identifies the important of OCB between the motivation and employee performance relationship, thus gender and organizational tenure were not significant to OCB and employee performance relationship.Social implications: HR can help an organization to succeed, provided that the suitable motivations are adopted to monitor lecturer performance and helping behavior. In addition, HR should not emphasize too much of gender and organizational tenure to justify the lecturer performance as the findings show insignificant relationship.Originality/value: This paper identifies and

  3. Role of allatostatin-like factors from the brain of Tenebrio molitor females.

    Science.gov (United States)

    Wasielewski, O; Skonieczna, M; Kodrík, D

    2009-08-01

    The effect of brain extract from females of freshly emerged Tenebrio molitor on ovary, oocyte development, total protein content of hemolymph, and ovary was studied in 4-day-old adult mealworm females. Injections of extracts of 2-brain equivalents into intact (unligatured) Tenebrio females did not affect ovarian and oocyte development. Injections of ligated females, however, with 2-brain equivalents on day 1 and 2 after adult emergence strongly inhibited ovarian growth and oocyte development. At day 4, ligated and injected females did not develop their ovaries and pre-vitellogenic oocytes were not found. The changes in ovarian development correlated with an increase in the concentration of soluble proteins in the hemolymph as compared with the saline-injected controls. Additionally, a strong reduction of total protein content in ovarian tissue was observed. Reverse phase HPLC separation of a methanolic brain extract of T. molitor females showed that fraction 5 has a similar retention time to synthetic cockroach allatostatin. Fraction 5 was eluted at 12.88 min, which was closest to the internal standard Dippu-AST I, which eluted at 12.77 min. An ELISA of fraction 5 from the methanolic brain extract using antibodies against allatostatins Grybi-AST A1 and Grybi-AST B1 from cricket Gryllus bimaculatus showed that fraction 5 cross-reacted with Grybi-AST A1 antibodies. The cross-reactivity was similar to the synthetic allatostatin from D. punctata, which was used as a positive control. These observations demonstrate a possible role for allatostatin-like brain factor(s) in regulating the reproductive cycle of Tenebrio molitor.

  4. A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.

    Science.gov (United States)

    Seto, Danielle N; Kandarian, Susan C; Jackman, Robert W

    2015-08-07

    Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Role of socio-demographical factors on tuberculosis outcome in Yemen

    Directory of Open Access Journals (Sweden)

    Ammar Ali Saleh Jaber

    2016-01-01

    and health care providers can optimize and indicate the factors which play a role in successful and unsuccessful treatment outcome.

  6. NSAID-induced small intestinal damage--roles of various pathogenic factors.

    Science.gov (United States)

    Takeuchi, Koji; Satoh, Hiroshi

    2015-01-01

    NSAID-induced enteropathy has been the focus of recent basic and clinical research subsequent to the development of the capsule endoscope and double-balloon endoscope. We review the possible pathogenic mechanisms underlying NSAID-induced enteropathy and discuss the role of the inhibition of COX-1/COX-2 and the influences of food as well as various prophylactic treatments on these lesions. Studies were performed in experimental animals. Multiple factors, such as intestinal hypermotility, decreased mucus secretion, enterobacteria, and upregulation of iNOS/NO expression, are involved in the pathogenesis of NSAID-induced enteropathy, in addition to the decreased production of PGs due to the inhibition of COX. Enterobacterial invasion is the most important pathogenic event, and intestinal hypermotility, which was associated with this event, is essential for the development of these lesions. NSAIDs also upregulate the expression of COX-2, and the inhibition of both COX-1 and COX-2 is required for the intestinal ulcerogenic properties of NSAIDs to manifest. NSAID-induced enteropathy is prevented by PGE2, atropine, ampicillin, and aminoguanidine as well as soluble dietary fiber, and exacerbated by antisecretory drugs such as proton pump inhibitors. These findings on the pathogenesis of NSAID-induced enteropathy will be useful for the future development of intestinal-sparing alternatives to standard NSAIDs. © 2015 S. Karger AG, Basel.

  7. The role of the transcription factor Rbpj in the development of dorsal root ganglia

    Directory of Open Access Journals (Sweden)

    Chen Jia-Yin

    2011-04-01

    Full Text Available Abstract Background The dorsal root ganglion (DRG is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs, and is a good system to study the mechanisms of neurogenesis and gliogenesis. Notch signaling is known to play important roles in DRG development, but the full scope of Notch functions in mammalian DRG development remains poorly understood. Results In the present study, we used Wnt1-Cre to conditionally inactivate the transcription factor Rbpj, a critical integrator of activation signals from all Notch receptors, in NCCs and their derived cells. Deletion of Rbpj caused the up-regulation of NeuroD1 and precocious neurogenesis in DRG early development but led to an eventual deficit of sensory neurons at later stages, due to reduced cell proliferation and abnormal cell death. In addition, gliogenesis was delayed initially, but a near-complete loss of glia was observed finally in Rbpj-deficient DRG. Furthermore, we found P75 and Sox10, which are normally expressed exclusively in neuronal and glial progenitors of the DRG after the NCCs have completed their migration, were co-expressed in many cells of the DRG of Rbpj conditional knock-out mice. Conclusions Our data indicate that Rbpj-mediated canonical Notch signaling inhibits DRG neuronal differentiation, possibly by regulating NeuroD1 expression, and is required for DRG gliogenesis in vivo.

  8. The Role of Environmental Factors in the Development of Celiac Disease: What Is New?

    Science.gov (United States)

    Lionetti, Elena; Catassi, Carlo

    2015-01-01

    Celiac disease (CD) is a systemic immune-mediated disorder caused by the ingestion of gluten-containing grains in genetically susceptible persons. It is one of the most common lifelong disorders, affecting approximately 1% of the general population. The prevalence of CD has increased in developed countries over recent decades, pointing to the role of additional environmental triggers other than gluten. It has been hypothesized that intestinal infections, the amount and quality of gluten, the intestinal microbiota, and early nutrition are all possible triggers of the switch from tolerance to an immune response to gluten. Two recent randomized controlled trials have been performed to clarify the relationship between the age at which gluten is introduced to a child’s diet and the risk of CD, showing that timing of gluten introduction does not modify the risk of CD. Both trials also showed that breastfeeding compared with no breastfeeding or breastfeeding duration or breastfeeding during gluten introduction have no effect on the risk of CD. The two trials, although not designed to address this issue, have shown that intestinal infections seem not to influence the risk of CD. Further studies are still needed to explore the missing environmental factors of CD for future prevention. PMID:28943625

  9. Role of socio-economic factors in cataract surgery utilization in JIPMER Pondicherry

    Directory of Open Access Journals (Sweden)

    Prasanna T

    2007-01-01

    Full Text Available Background : This study was conducted in JIPMER & Kurusukuppam, Pondicherry. Objectives : To identify the socioeconomic factors influencing the utilization of cataract surgery & to identify the persons motivating the patients to utilize these services. This was a case-control study; cases were patients (age group 50-70 years who were operated in JIPMER for senile cataract without complications and one control was selected for each case. Controls were also of the same age group residing at Kurusukuppam with complaints of dimness of vision and who had not undergone cataract surgery, selected by random sampling. Both the groups were interviewed using a pretested interview schedule. Results : Subjects who were literate and with high school education and more and with income more than Rs.1050 (class III utilized the cataract surgery services more. In majority of cases, motivation for getting operated comes from relatives. Peer groups who have undergone the surgery before, were the predominant sources of health information about the surgery. Higher income & higher education affect the utilization significantly. Relatives & Previously operated peers play an important role.

  10. The role of macrophage migration inhibitory factor in obesity-associated type 2 diabetes in mice

    Directory of Open Access Journals (Sweden)

    Saksida Tamara

    2013-01-01

    Full Text Available Macrophage migration inhibitory factor (MIF is implicated in the pathogenesis of several inflammationrelated diseases, including obesity and type 2 diabetes (T2D. However, MIF deficiency itself promotes obesity and glucose intolerance in mice. Here we show that the introduction of a high-fat diet (HFD further aggravates the parameters of obesity-associated T2D: weight gain and glucose intolerance. Furthermore, in contrast to MIF-KO mice on standard chow, HFD-fed MIF-KO mice develop insulin resistance. Although the clinical signs of obesity-associated T2D are upgraded, inflammation in MIF-deficient mice on HFD is significantly lower. These results imply that MIF possesses a complex role in glucose metabolism and the development of obesity-related T2D. However, the downregulation of inflammation upon MIF inhibition could be a useful tool in short-term T2D therapy for preventing pancreatic islet deterioration. [Projekat Ministarstva nauke Republike Srbije, br. 173013

  11. The role of pre-oedipal and oedipal factors in psychic life.

    Science.gov (United States)

    Kancyper, Luis

    2006-02-01

    The Oedipus complex, a basic concept in Freudian theory, is an essential factor in the constitution of the human subject. It plays a key role in the structuring of the personality and in the orientation of desire. It is the oedipal triangular structure that precedes the pre-oedipal situation (in a logical, not chronological, order), and not vice versa. The oedipal structure exists before the infant's biological birth. It is present in the parents' desires and identifications, which inexorably fall upon each subject. That is why the author believes that it is necessary to leave behind a solipsistic reading of the nuclear complex of neuroses--a reading that is based solely on Oedipus's drive nucleus--and take a joint and comprehensive view of Laius's and Jocasta's histories and traumatic experiences, which were invested in their son. Among these three vertices, a dynamic set of forces emerges whereby a basic, original unconscious field phantasy is created that bears a unique narrative and an invisible and hermetic web made of passions and beliefs, scandals and secrets. This phantasy gives shape to an unrepeatable oedipal structure in each subject, a structure that articulates with the effects of the narcissistic and fraternal dynamic and may determine the subject's fate. This paper develops the following issues: 1) Oedipus, victimizer or victim?; 2) the generational confrontation as dynamic field; and 3) neuroses with a preponderance of dualistic relationships.

  12. A Role for APETALA1/FRUITFULL Transcription Factors in Tomato Leaf Development[C][W

    Science.gov (United States)

    Burko, Yogev; Shleizer-Burko, Sharona; Yanai, Osnat; Shwartz, Ido; Zelnik, Iris Daphne; Jacob-Hirsch, Jasmine; Kela, Itai; Eshed-Williams, Leor; Ori, Naomi

    2013-01-01

    Flexible maturation rates underlie part of the diversity of leaf shape, and tomato (Solanum lycopersicum) leaves are compound due to prolonged organogenic activity of the leaf margin. The CINCINNATA -TEOSINTE BRANCHED1, CYCLOIDEA, PCF (CIN-TCP) transcription factor LANCEOLATE (LA) restricts this organogenic activity and promotes maturation. Here, we show that tomato APETALA1/FRUITFULL (AP1/FUL) MADS box genes are involved in tomato leaf development and are repressed by LA. AP1/FUL expression is correlated negatively with LA activity and positively with the organogenic activity of the leaf margin. LA binds to the promoters of the AP1/FUL genes MBP20 and TM4. Overexpression of MBP20 suppressed the simple-leaf phenotype resulting from upregulation of LA activity or from downregulation of class I knotted like homeobox (KNOXI) activity. Overexpression of a dominant-negative form of MBP20 led to leaf simplification and partly suppressed the increased leaf complexity of plants with reduced LA activity or increased KNOXI activity. Tomato plants overexpressing miR319, a negative regulator of several CIN-TCP genes including LA, flower with fewer leaves via an SFT-dependent pathway, suggesting that miR319-sensitive CIN-TCPs delay flowering in tomato. These results identify a role for AP1/FUL genes in vegetative development and show that leaf and plant maturation are regulated via partially independent mechanisms. PMID:23771895

  13. A multifaceted role for MOF histone modifying factor in genome maintenance.

    Science.gov (United States)

    Mujoo, Kalpana; Hunt, Clayton R; Horikoshi, Nobuo; Pandita, Tej K

    2017-01-01

    MOF (males absent on the first) was initially identified as a dosage compensation factor in Drosophila that acetylates lysine 16 of histone H4 (H4K16ac) and increased gene transcription from the single copy male X-chromosome. In humans, however, the ortholog of Drosophila MOF has been shown to interact with a range of proteins that extend its potential significance well beyond transcription. For example, recent results indicate MOF is an upstream regulator of the ATM (ataxia-telangiectasia mutated) protein, the loss of which is responsible for ataxia telangiectasia (AT). ATM is a key regulatory kinase that interacts with and phosphorylates multiple substrates that influence critical, cell-cycle control and DNA damage repair pathways in addition to other pathways. Thus, directly or indirectly, MOF may be involved in a wide range of cellular functions. This review will focus on the contribution of MOF to cellular DNA repair and new results that are beginning to examine the in vivo physiological role of MOF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Pathogenic Roles of Macrophage Migration Inhibitory Factor during Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Yung-Chun Chuang

    2015-01-01

    Full Text Available Dengue virus (DENV infection is the most common cause of viral hemorrhagic fever, which can lead to life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS. Hemorrhage and plasma leakage are two major hallmarks of DHF/DSS. Because the mechanisms causing these pathogenic changes are unclear, there is no effective therapy against DHF/DSS. In this review, we focus on the possible pathogenic effects of a pleiotropic cytokine, macrophage migration inhibitory factor (MIF, on the pathogenesis of DENV infection. MIF is a critical mediator of the host immune response and inflammation, and there is a correlation between the serum levels of MIF and disease severity in dengue patients. Furthermore, MIF knock-out mice exhibit less severe clinical disease and lethality. However, the role of MIF in the pathogenesis of DHF/DSS is not limited to immune cell recruitment. Recent evidence indicates that DENV infection induced MIF production and may contribute to vascular hyperpermeability and viral replication during DENV infection. The expression of both adhesion and coagulation molecules on MIF-stimulated monocytes and endothelial cells is also increased, which may contribute to inflammatory and anticoagulatory states during DHF/DSS. Therefore, blocking MIF production or its function may provide a solution for the treatment and prevention of DHF/DSS.

  15. Role expectations in pedagogical communication of coach and athlete as a factor of athletic performance

    Directory of Open Access Journals (Sweden)

    A.A. Svetlova

    2013-07-01

    Full Text Available The article presents the results of theoretical and empirical research on the socio-psychological factors of the effectiveness of training young athletes. We show the relationship between effectiveness of training young players and the nature of its relationship with the coach. The study involved 187 fencing athletes (101 females and 86 males aged 16-20 years and their trainers (46 people with professional experience of 13 to 17 years. The methods used were observation, survey, document analysis, C. Zamfir "The motivation of professional activity" questionnaire, "MUN" questionnaire (A.A. Rean, a technique to study the relationship between the athlete and the coach (Y.L. Khanin, A.V. Stambulov, and author's method "Identifying the profile of the real and the ideal coach". The study confirmed the assumption that the more successful athlete, the greater the extent of his role expectations from the interaction with the trainer coincide with the views of the effective work of the coach with the athlete. In addition, juniors, occupying higher places in the ranking of the All-Russian athletes have the best motivational complex personality and motivation of the most pronounced success.

  16. Geoethics and philosophy of Earth sciences: the role of geophysical factors in human evolution

    Directory of Open Access Journals (Sweden)

    Telmo Pievani

    2012-07-01

    Full Text Available This article explores the role of philosophy of the Earth sciences in the foundation of the principles of ‘geoethics’. In particular, the focus is on two different examples of philosophical analysis in the field of geosciences: the first is the trial against the Italian National Commission for Forecasting and Predicting Great Risks, which was charged with negligence in communication and prediction on the occasion of the earthquake that almost destroyed the city of L’Aquila on the night of April 6, 2009; the second is related to the scientific and theoretical consequences of the updated geographical scenario of the human global populating of the Earth, based on archeological, paleontological and genetic data. Our concept of ‘scientific prediction’ in the case of geophysical phenomena and the new ways to see human evolution that depend on geophysical factors have ethical and philosophical implications that are crucial for the foundations of geoethics. The tentative conclusion is that we need an evolutionary sense of belonging to our Planet, and a concept of ‘natural’ phenomena and ‘natural’ disasters that should not be an alibi for the underestimation of our political and ethical responsibilities.

  17. A novel ethylene responsive factor CitERF13 plays a role in photosynthesis regulation.

    Science.gov (United States)

    Xie, Xiu-Lan; Xia, Xiao-Jian; Kuang, Sheng; Zhang, Xi-Li; Yin, Xue-Ren; Yu, Jing-Quan; Chen, Kun-Song

    2017-03-01

    Ethylene responsive factors (ERFs) act as critical downstream components of the ethylene signalling pathway in regulating plant development and stress responses. However little is known about its role in regulation of photosynthesis. Here, we identified an ethylene-inducible ERF gene in citrus, CitERF13. Transient over-expression of CitERF13 in N. tabacum leaves, resulted in a significant decrease in net photosynthetic rate. Closer examination of photosynthetic activity of PSII and PSI indicated that CitERF13 overexpression led to declines of Fv/Fm, Y(II) and Y(I). However, change in NPQ was less pronounced. CitERF13 overexpression also significantly reduced Vc,max, Jmax and AQY, indicating inhibition of the Calvin cycle. The expression of photosynthesis-related genes was suppressed to a variable extent in leaf blades transiently over-expressing CitERF13. CitERF13 transient overexpression in tobacco or citrus both resulted in a decline of Chlorophyll content and CitERF13 overexpressing tobacco leaf disc was more susceptible to chlorosis in response to MV-mediated oxidative stress. The results suggest that CitERF13 is potentially involved in suppressing photosynthesis through multiple pathways, for instance, inhibiting photochemical activity of photosynthesis, CO2 carboxylation capacity and chlorophyll metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. The Role of Forkhead Box Q1 Transcription Factor in Ovarian Epithelial Carcinomas

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    Tian-Li Wang

    2012-10-01

    Full Text Available The role of the forkhead box Q1 (FOXQ1 transcription factor in cancer pathogenesis has recently emerged. Overexpression of FOXQ1 has been found in a variety of human cancers, and its upregulation has been associated with poor prognosis in colorectal, breast, and non-small cell lung carcinomas. However, the molecular mechanism underlying how FOXQ1 contributes to ovarian epithelial carcinomas remains unclear. To this end, we analyzed gene expression levels in ovarian cancer tissues and cell lines and demonstrated a higher expression level of FOXQ1 in epithelial ovarian cancer cells than that in normal epithelial cells. We then used a human ovarian cancer cell line, SKOV3, which expressed a higher level of FOXQ1, as a cell model to investigate the biological effects of FOXQ1 by using RNA interference. Silencing of FOXQ1 expression using a shRNA knockdown approach affected the expression of several cell cycle regulators, leading to suppressed cell proliferation, reduced cell motility/invasion, and upregulation of epithelial cell markers and the downregulation of mesenchymal cell markers. Taken together, these results suggest that FOXQ1 expression is essential to maintain cell proliferation, motility/invasion, and epithelial-mesenchymal transition phenotypes in ovarian cancer cells.

  19. Organochlorine pollution in tropical rivers (Guadeloupe): Role of ecological factors in food web bioaccumulation

    Energy Technology Data Exchange (ETDEWEB)

    Coat, Sophie, E-mail: coatsophie@gmail.com [EA 926 DYNECAR, Laboratoire de Biologie Marine, UFR Sciences, Universite des Antilles et de la Guyane, BP592, 97159 Pointe-a-Pitre Cedex (France); Monti, Dominique, E-mail: dominique.monti@univ-ag.fr [EA 926 DYNECAR, Laboratoire de Biologie Marine, UFR Sciences, Universite des Antilles et de la Guyane, BP592, 97159 Pointe-a-Pitre Cedex (France); Legendre, Pierre, E-mail: pierre.legendre@umontreal.ca [Departement de Sciences Biologique, Universite de Montreal, C.P. 6128, succursale A, Montreal, Quebec H3C 3J7 (Canada); Bouchon, Claude, E-mail: claude.bouchon@univ-ag.fr [EA 926 DYNECAR, Laboratoire de Biologie Marine, UFR Sciences, Universite des Antilles et de la Guyane, BP592, 97159 Pointe-a-Pitre Cedex (France); Massat, Felix, E-mail: fmassat@ladrome.fr [LDA26, laboratoire Departemental d' Analyses de la Drome, 27 avenue Lautagne, 26000 Valence (France); Lepoint, Gilles, E-mail: g.lepoint@ulg.ac.be [MARE Centre, Laboratoire d' Oceanologie, Universite de Liege, Bat. B6, 4000 Sart Tilman, Belgique (Belgium)

    2011-06-15

    Concentrations of organochlorine pesticides and stable isotope ratios of nitrogen and carbon were measured in a tropical freshwater ecosystem to evaluate the contamination level of biota and examine the bioaccumulation patterns of pollutants through the food web. Chemical analyses showed a general and heavy contamination of the entire food web. They revealed the strong accumulation of pollutants by juveniles of diadromous fishes and shrimps, as they re-enter the river. The role of ecological factors in the bioaccumulation of pesticides was evaluated. Whereas the most persistent pollutants (chlordecone and monohydro-chlordecone) were related to the organisms diet and habitat, bioaccumulation of {beta}-HCH was only influenced by animal lipid content. The biomagnification potential of chlordecone through the food chain has been demonstrated. It highlighted the importance of trophic transfer in this compound bioaccumulation process. In contrast, bioconcentration by passive diffusion from water seemed to be the main exposure route of biota to {beta}-HCH. - Highlights: > We measured OC pesticides and stable isotope ratios in a tropical stream. > Results showed a strong and ubiquitous contamination of the entire food web. > Diadromous juveniles strongly accumulated pollutants when they re-enter the river. > The most persistent pollutant (chlordecone) was related to species diet and habitat. > {beta}-HCH was only influenced by animal lipid content. - This paper determines the bioaccumulation and transfer processes of organochlorine pesticides within the stream food web in Guadeloupe (Caribbean).

  20. Organochlorine pollution in tropical rivers (Guadeloupe): role of ecological factors in food web bioaccumulation.

    Science.gov (United States)

    Coat, Sophie; Monti, Dominique; Legendre, Pierre; Bouchon, Claude; Massat, Félix; Lepoint, Gilles

    2011-06-01

    Concentrations of organochlorine pesticides and stable isotope ratios of nitrogen and carbon were measured in a tropical freshwater ecosystem to evaluate the contamination level of biota and examine the bioaccumulation patterns of pollutants through the food web. Chemical analyses showed a general and heavy contamination of the entire food web. They revealed the strong accumulation of pollutants by juveniles of diadromous fishes and shrimps, as they re-enter the river. The role of ecological factors in the bioaccumulation of pesticides was evaluated. Whereas the most persistent pollutants (chlordecone and monohydro-chlordecone) were related to the organisms diet and habitat, bioaccumulation of β-HCH was only influenced by animal lipid content. The biomagnification potential of chlordecone through the food chain has been demonstrated. It highlighted the importance of trophic transfer in this compound bioaccumulation process. In contrast, bioconcentration by passive diffusion from water seemed to be the main exposure route of biota to β-HCH. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety.

    Science.gov (United States)

    Shekhar, Anantha; Truitt, William; Rainnie, Donald; Sajdyk, Tammy

    2005-12-01

    Stress initiates a series of neuronal responses that prepare an organism to adapt to new environmental challenges. However, chronic stress may lead to maladaptive responses that can result in psychiatric syndromes such as anxiety and depressive disorders. Corticotropin-releasing factor (CRF) has been identified as a key neuropeptide responsible for initiating many of the endocrine, autonomic and behavioral responses to stress. The amygdala expresses high concentrations of CRF receptors and is itself a major extrahypothalamic source of CRF containing neurons. Within the amygdala, the basolateral nucleus (BLA) has an important role in regulating anxiety and affective responses. During periods of stress, CRF is released into the amygdala and local CRF receptor activation has been postulated as a substrate for stress-induced alterations in affective behavior. Previous studies have suggested that synaptic plasticity in the BLA contributes to mechanisms underlying long-term changes in the regulation of affective behaviors. Several studies have shown that acute glutamate receptor-mediated activation, by either GABA-mediated disinhibition or CRF-mediated excitation, induces long-term synaptic plasticity and increases the excitability of BLA neurons. This review summarizes some of the data supporting the hypotheses that stress induced plasticity within the amygdala may be a critical step in the pathophysiology of the development of chronic anxiety states. It is further proposed that such a change in the limbic neural circuitry is involved in the transition from normal vigilance responses to pathological anxiety, leading to syndromes such as panic and post-traumatic stress disorders.

  2. Factors of academic procrastination: The role of perfectionism, anxiety and depression

    Directory of Open Access Journals (Sweden)

    Eva Kranjec

    2016-06-01

    Full Text Available This study investigated dimensions of perfectionism, anxiety, and depression as factors of academic procrastination. Our main research interest was to examine the role of specific dimensions of perfectionism as moderators in the relationship between anxiety and depression and academic procrastination. Four scales were administered on the sample of 403 students: perfectionism scale FMPS, academic procrastination scale APS-SI, depression scale CESD and anxiety scale STAI-X2. The results showed significant positive relationships between maladaptive dimensions of perfectionism, anxiety, depression, and academic procrastination. In addition, results showed significant negative associations between adaptive dimensions of perfectionism and academic procrastination. Certain dimensions of perfectionism, anxiety, and depression proved to be significant predictors of academic procrastination. The dimensions of perfectionism and academic procrastination were also significantly related to anxiety and depression, which both predicted academic procrastination. The relationship between anxiety levels and academic procrastination was moderated by personal standards (as adaptive dimension of perfectionism, while the relationship between depression levels and academic procrastination was moderated by the maladaptive dimension of parents’ expectations.

  3. The role of historical and ecological factors on initial survival of Copaifera langsdorffii Desf. (Fabaceae

    Directory of Open Access Journals (Sweden)

    Marcílio Fagundes

    2013-12-01

    Full Text Available The plant population dynamic is affected by ecological and evolutionary processes that operate at all stages of the plant life cycle. The aim of this study was to characterize the seed and seedling performance of Copaifera langsdorffii by testing four hypotheses: the resource concentration hypothesis; the relationship between seed size and germinability hypothesis; the relationship between seed size and seedling vigor hypothesis; and the intraspecific seedling competition hypothesis. All seeds used in the experiments were collected from 35 C. langsdorffii plants located in a fragment of the Brazilian cerrado (savanna. The number of fruits per plant negatively affected Rhinochenus brevicollis attacks on C. langsdorffii seeds. Therefore, this result does not support the resource concentration hypothesis, and predator satiation was used in order to explain the observed result. In general, seed germinability (percentage and time to emergence was not influenced by seed size. The homogeneity of the experimental design, together with an abundant water supply, may have masked the effects of seed size on germinability. Seed size positively affected seedling development, corroborating the expected relationship between seed size and seedling vigor. The number of seedling per plastic bags negatively affected the growth of C. langsdorffii. The nutrient-limited soil probably promoted the below-ground competition for nutrients among seedlings. Finally, the role of evolutionary and ecological factors on C. langsdorffii population dynamics is discussed.

  4. The Role of Environmental Factors in the Development of Celiac Disease: What Is New?

    Directory of Open Access Journals (Sweden)

    Elena Lionetti

    2015-10-01

    Full Text Available Celiac disease (CD is a systemic immune-mediated disorder caused by the ingestion of gluten-containing grains in genetically susceptible persons. It is one of the most common lifelong disorders, affecting approximately 1% of the general population. The prevalence of CD has increased in developed countries over recent decades, pointing to the role of additional environmental triggers other than gluten. It has been hypothesized that intestinal infections, the amount and quality of gluten, the intestinal microbiota, and early nutrition are all possible triggers of the switch from tolerance to an immune response to gluten. Two recent randomized controlled trials have been performed to clarify the relationship between the age at which gluten is introduced to a child’s diet and the risk of CD, showing that timing of gluten introduction does not modify the risk of CD. Both trials also showed that breastfeeding compared with no breastfeeding or breastfeeding duration or breastfeeding during gluten introduction have no effect on the risk of CD. The two trials, although not designed to address this issue, have shown that intestinal infections seem not to influence the risk of CD. Further studies are still needed to explore the missing environmental factors of CD for future prevention.

  5. The Study of the Role of Contributor Factors in Addiction Withdrawal

    Directory of Open Access Journals (Sweden)

    Omar Kianipour

    2012-08-01

    Full Text Available Introduction: The present paper investigated the factors contributing to addiction withdrawal so as to it would be possible to set preventive and rehabilitative programs for addicts. Method: The study was ex-post facto and causal-comparative one. Population included all addicts referred to addiction withdrawal centers of Kahnouj city and the sample was selected of addicts of Yaran addiction withdrawal Center by voluntary sampling. Bar-on emotional intelligence inventory, family boundary questionnaire and demographic information were administered among selected sample. Results: The results showed that normal family boundaries, higher emotional intelligence and opium use in comparison of crack and crystal glass are effective on addiction withdrawal. But disengaged family boundaries, crack and crystal glass use can be led to addiction recursion. Age, addiction duration, marital status, and education level are not effective on addiction withdrawal. Conclusion: Altogether, the results represented the role and importance of variables namely: family, emotional intelligence, and the kind of used material in addiction withdrawal.

  6. Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

    Directory of Open Access Journals (Sweden)

    Loft Steffen

    2006-02-01

    Full Text Available Abstract Background Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs. Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6 and the chemokines, monocyte chemoattractant protein (Mcp-1, macrophage inflammatory protein-2 (Mip-2 and keratinocyte derived chemokine (Kc in the lung tissue at different time points after exposure. Results Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. Conclusion Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1.

  7. Dual role of the p75 tumor necrosis factor (TNF) receptor in TNF cytotoxicity

    DEFF Research Database (Denmark)

    Bigda, J; Beletsky, I; Brakebusch, C

    1994-01-01

    Whereas there is ample evidence for involvement of the p55 tumor necrosis factor (TNF) receptor (p55-R) in the cytocidal effect of TNF, the role of the p75 TNF receptor (p75-R) in this effect is a matter of debate. In this study, we probed the function of p75-R in cells sensitive...... to the cytotoxicity of TNF using a wide panel of antibodies (Abs) against the receptor's extracellular domain. Two distinct Ab effects were observed. The Abs triggered signaling for cytotoxicity. This effect: (a) was correlated with the extent of p75-R expression by the cells; (b) was dependent on receptor cross...... against p55-R. Moreover, it seemed to reverse induced desensitization to the cytocidal effect of anti p55-R Abs, suggesting that it involves mechanisms different from those of the signaling by the p55 TNF-R. In addition, the Abs affected the response to TNF in a way that does not involve the signaling...

  8. An Essential Role for the Transcription Factor Runx1 in T Cell Maturation.

    Science.gov (United States)

    Hsu, Fan-Chi; Shapiro, Michael J; Dash, Barsha; Chen, Chien-Chang; Constans, Megan M; Chung, Ji Young; Romero Arocha, Sinibaldo R; Belmonte, Paul J; Chen, Meibo W; McWilliams, Douglas C; Shapiro, Virginia Smith

    2016-03-29

    The transcription factor Runx1 has essential roles throughout hematopoiesis. Here, we demonstrate that Runx1 is critical for T cell maturation. Peripheral naïve CD4(+) T cells from CD4-cre Runx1 cKO mice are phenotypically and functionally immature as shown by decreased production of TNF-α upon TCR stimulation. The loss of peripheral CD4(+) T cells in CD4-cre Runx1 cKO mice is not due to defects in homeostasis or decreased expression of IL-7Rα, as transgenic expression of IL-7Rα does not rescue the loss of CD4(+) T cells. Rather, immature Runx1-deficient CD4(+) T cells are eliminated in the periphery by the activation and fixation of the classical complement pathway. In the thymus, there is a severe block in all aspects of intrathymic T cell maturation, although both positive and negative selection are unaltered. Thus, loss of Runx1 leads to the earliest characterized block in post-positive selection intrathymic maturation of CD4 T cells.

  9. Molecular factors in cell (and tumor) response to photodynamic therapy: the role of Bid

    Science.gov (United States)

    Chiu, Song-mao; Xue, Liang-yan; Lam, Minh; Rodriguez, Myriam E.; Zhang, Ping; Kenney, Malcolm E.; Nieminen, Anna-Liisa; Oleinick, Nancy L.

    2010-02-01

    The phthalocyanine photosensitizer Pc 4 binds preferentially to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components, including Bcl-2, are photodamaged and apoptosis is triggered. We recently prepared analogues of Pc 4 containing two axial ligands, one identical to the single ligand in Pc 4, and the other containing one or two hydroxyl groups on a dimethylsiloxy alkyl chain. Pc 181 is representative of this group of photosensitizers. In MCF-7 human breast cancer cells, the new analogues preferentially localized in lysosomes and were highly efficient in inducing apoptosis and overall cell death. The Bcl-2 family member Bid is required for signaling to mitochondria for apoptosis in response to primary lysosomal photodamage. To further evaluate the role of Bid, we compared the effects of PDT with Pc 4 or Pc 181 in wild-type murine embryonic fibroblasts and those knocked out for Bid. We find that the two cell lines are equally sensitive to killing by Pc 4-PDT, but the Bid-/- cells are significantly more resistant to killing and apoptosis induction by Pc 181-PDT than are the Bid+/+ cells. The data show that low levels of lysosomal photodamage are not alone lethal and that a specific defect in a factor required for apoptosis can severely compromise cell response to PDT.

  10. Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2.

    Science.gov (United States)

    Furue, Masutaka; Uchi, Hiroshi; Mitoma, Chikage; Hashimoto-Hachiya, Akiko; Chiba, Takahito; Ito, Takamichi; Nakahara, Takeshi; Tsuji, Gaku

    2017-03-03

    Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are abundantly expressed in epidermal keratinocytes and mediate the production of reactive oxygen species. To neutralize or minimize oxidative stress, the keratinocytes also express nuclear factor-erythroid 2-related factor-2 (NRF2), which is a master switch for antioxidant signaling. Notably, there is fine-tuned crosstalk between AHR and NRF2, which mutually increase or decrease their activation states. Many NRF2-mediated antioxidant phytochemicals are capable of up- and downmodulating AHR signaling. The precise mechanisms by which these phytochemicals differentially affect the AHR and NRF2 system remain largely unknown and warrant future investigation.

  11. Role of the factor V Leiden mutation in septic peritonitis assessed in factor V Leiden transgenic mice

    NARCIS (Netherlands)

    Brüggemann, Lois W.; Schoenmakers, Saskia H. H. F.; Groot, Angelique P.; Reitsma, Pieter H.; Spek, C. Arnold

    2006-01-01

    OBJECTIVE: The factor V Leiden (FVL) mutation (Arg506Glu) results in the production of an FV protein that when activated is relatively resistant to inactivation by activated protein C and thereby leads to predisposition to thrombosis. The rather high prevalence of the FVL mutation in the general

  12. The role of abiotic factors modulating the plant-microbe-soil interactions: toward sustainable agriculture. A review

    OpenAIRE

    Gustavo Santoyo; Claudia Hernández-Pacheco; Julie Hernández-Salmerón; Rocio Hernández-León

    2017-01-01

    Microbial soil communities are active players in the biogeochemical cycles, impacting soil fertility and interacting with aboveground organisms. Although soil microbial diversity has been studied in good detail, the factors that modulate its structure are still relatively unclear, especially the environmental factors. Several abiotic elements may play a key role in modulating the diversity of soil microbes, including those inhabiting the rhizosphere (known as the rhizosphere microbiome). This...

  13. High concentrations of circulating interleukin-6 and monocyte chemotactic protein-1 with low concentrations of interleukin-8 were associated with severe chikungunya fever during the 2009-2010 outbreak in Thailand.

    Science.gov (United States)

    Lohachanakul, Jindarat; Phuklia, Weerawat; Thannagith, Montri; Thonsakulprasert, Tipparat; Ubol, Sukathida

    2012-02-01

    The recent outbreak of Chikungunya virus in Thailand caused a rheumatic fever associated with considerable morbidity and fatalities. Thus, it is important to identify biomarker(s) of severe disease induced by this threatening arbovirus. Putative biomarkers in cases of chikungunya fever during an outbreak in the southern part of Thailand in 2009-2010 were identified. Sixty-two patients who had developed fever and myalgia, with or without arthralgia/arthritis, were enrolled and grouped into severe chikungunya fever (CHIKF) (n= 15), mild CHIKF (n= 20) and non-CHIKF (n= 27) to investigate circulating immunological mediators that might serve as markers of severity. Blood samples were taken at presentation (day 1) and 30 days later (day 30) and plasma concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase-1 and viral load were measured by ELISA. On day 1, severe CHIKF and mild CHIKF groups had viral loads of 10(8.5) and 10(8.3) of RNA copies/mL, respectively. At presentation, all CHIKF patients had circulating concentrations of IL-6 and MCP-1 higher than did non-CHIKF patients, whereas amongst the CHKF patients, the severe CHIKF patients had higher IL-6 concentrations than did mild CHIKF patients. Interestingly, severe CHIKF patients had significantly lower concentrations of circulating IL-8 than the other groups of patients, suggesting that high concentrations of IL-6 and MCP-1 with low concentrations of IL-8 may be a determinant of severe chikungunya virus infection. © 2012 The Societies and Blackwell Publishing Asia Pty Ltd.

  14. Gender Role and Social Identifications: The Two Major Factors to Shape Turkish Women

    Science.gov (United States)

    Erden-Imamoglu, Seval

    2013-01-01

    The process of being a woman starts with biological gender but it is shaped by learning the social gender roles. Besides social gender role; age, education, marriage, and motherhood supply social roles and attributions and they have an impact on women identification and their interpersonal relationships. The aim of the study is to investigate…

  15. The role of big five factors on predicting job crafting propensities amongst administrative employees in a South African tertiary institution

    Directory of Open Access Journals (Sweden)

    Clement Bell

    2016-02-01

    Full Text Available Orientation: Personality provides a foundation for understanding employee job behaviours. It determines and reflects how they respond to their work situations. There is a shortage of previous researches that have specifically dealt with the predictive role of personality on job crafting. Job crafting is also a significantly new concept in the South African work context. It has both positive and negative consequences on employee job behaviours.Research purpose: The present study investigated the role of big five factors on predicting job crafting propensities amongst administrative employees in Alice, South Africa.Motivation for the study: The present study aimed to determine the role of big five factors on predicting job crafting propensities amongst administrative employees. It was premised on previous research that the big five factors are associated with many employee job behaviours.Research approach, design and method: The present study employed a quantitative, crosssectional research design with a sample of 246 administrative employees in Alice, South Africa. A biographical questionnaire, a Big Five Inventory, and a job crafting questionnaire were used to collect data.Main findings: The findings showed that big five factors of Conscientiousness, Extraversion, Agreeableness, Openness to experience and Neuroticism play a significant role in predicting job crafting propensities.Practical implications: The present study suggests that big five factors of Conscientiousness, Extraversion, Agreeableness, Openness to experience and Neuroticism have a predictive role on job crafting behaviours. Managers of tertiary institutions can therefore consider these big five personalities to understand and predict the impacts of their job design strategies on administrative employees’ behaviours.Contribution: The contribution of the study was significant in that it contributed to research literature representing the influence of the big five factors in

  16. PHASER 2.10 methodology for dependence, importance, and sensitivity: The role of scale factors, confidence factors, and extremes

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, J.A. [Sandia National Labs., Albuquerque, NM (United States). System Studies Dept.

    1996-09-01

    PHASER (Probabilistic Hybrid Analytical System Evaluation Routine) is a software tool that has the capability of incorporating subjective expert judgment into probabilistic safety analysis (PSA) along with conventional data inputs. An earlier report described the PHASER methodology, but only gave a cursory explanation about how dependence was incorporated in Version 1.10 and about how ``Importance`` and ``Sensitivity`` measures were to be incorporated in Version 2.00. A more detailed description is given in this report. The basic concepts involve scale factors and confidence factors that are associated with the stochastic variability and subjective uncertainty (which are common adjuncts used in PSA), and the safety risk extremes that are crucial to safety assessment. These are all utilized to illustrate methodology for incorporating dependence among analysis variables in generating PSA results, and for Importance and Sensitivity measures associated with the results that help point out where any major sources of safety concern arise and where any major sources of uncertainty reside, respectively.

  17. Obesity: The role of desynchronosis and genetic factors in mechanisms of its development

    Directory of Open Access Journals (Sweden)

    M. O. Ryznychuk

    2017-02-01

    Full Text Available The article highlights the role of desynchronosis and certain genetic factors in the development of obesity. Some pathogenetic links of obesity and the influence of melatonin on them are analyzed.Desynchronosis is one of the causes of obesity as a result of dysregulatory changes in the chronoperiodic system – between suprachiasmatic nuclei of the hypothalamus and secretory activity of the pineal gland.In obesity there are some changes in circadian patterns of important physiological parameters. These include acrophases of blood pressure; rhythm of hormone secretion, including insulin; electrolytes; sleep-wake cycle displaced for a period of a day, which is a deviation from the normal course. Phase discrepancies of established circadian oscillations of physiological processes arise. Preconditions of fat metabolism imbalance, particularly visfatin, apelin and vaspin – components of atherosclerotic lesions, gradually emerge.There is abundant evidence for close relationships between metabolism and circadian mechanisms. It is proved, that there is a strong direct impact of endogenous circadian rhythms on the metabolic pathways that do not depend on food intake or sleep. A potential low molecular weight of biomarkers of human circadian phases has been identified. A number of key metabolic enzymes in tissues such as the liver, adipose tissue or the pancreas are chronodependent. Desynchronosis phenomena caused by genetic or environmental factors can lead to serious metabolic disorders, including obesity, insulin resistance and metabolic syndrome.Genesis of pineal removal-induced insulin resistance and reduced glucose tolerance in cells is related to the consequences of melatonin absence, which leads to abnormalities in insulin signaling pathways and reduced GLUT4 gene expression and protein content.Insulin-sensitive tissues (white and brown adipose tissue, skeletal and heart muscles after pineal removal are characterized by a significant reduction

  18. Exploring the role of sigma factor gene expression on production by Corynebacterium glutamicum: sigma factor H and FMN as example

    Directory of Open Access Journals (Sweden)

    Hironori eTaniguchi

    2015-07-01

    Full Text Available Bacteria are known to cope with environmental changes by using alternative sigma factors binding to RNA polymerase core enzyme. Sigma factor is one of the targets to modify transcription regulation in bacteria and to influence production capacities. In this study, the effect of overexpressing each annotated sigma factor gene in C. glutamicum WT was assayed using an IPTG inducible plasmid system and different IPTG concentrations. It was revealed that growth was severely decreased when sigD or sigH were overexpressed with IPTG concentrations higher than 50 μM. Overexpression of sigH led to an obvious phenotypic change, a yellow-colored supernatant. HPLC analysis revealed that riboflavin was excreted to the medium when sigH was overexpressed and DNA microarray analysis confirmed increased expression of riboflavin biosynthesis genes. In addition, genes for enzymes related to the pentose phosphate pathway and for enzymes dependent on FMN, FAD or NADPH as cofactor were upregulated when sigH was overexpressed. To test if sigH overexpression can be exploited for production of riboflavin-derived FMN or FAD, the endogenous gene for bifunctional riboflavin kinase/FMN adenyltransferase was co-expressed with sigH from a plasmid. Balanced expression of sigH and ribF improved accumulation of riboflavin (19.8 ± 0.3 μM and allowed for its conversion to FMN (33.1 ± 1.8 μM in the supernatant. While a proof-of-concept was reached, conversion was not complete and titers were not high. This study revealed that inducible and gradable overexpression of sigma factor genes is an interesting approach to switch gene expression profiles and to discover untapped potential of bacteria for chemical production.

  19. The Role of Genome Accessibility in Transcription Factor Binding in Bacteria.

    Science.gov (United States)

    Gomes, Antonio L C; Wang, Harris H

    2016-04-01

    ChIP-seq enables genome-scale identification of regulatory regions that govern gene expression. However, the biological insights generated from ChIP-seq analysis have been limited to predictions of binding sites and cooperative interactions. Furthermore, ChIP-seq data often poorly correlate with in vitro measurements or predicted motifs, highlighting that binding affinity alone is insufficient to explain transcription factor (TF)-binding in vivo. One possibility is that binding sites are not equally accessible across the genome. A more comprehensive biophysical representation of TF-binding is required to improve our ability to understand, predict, and alter gene expression. Here, we show that genome accessibility is a key parameter that impacts TF-binding in bacteria. We developed a thermodynamic model that parameterizes ChIP-seq coverage in terms of genome accessibility and binding affinity. The role of genome accessibility is validated using a large-scale ChIP-seq dataset of the M. tuberculosis regulatory network. We find that accounting for genome accessibility led to a model that explains 63% of the ChIP-seq profile variance, while a model based in motif score alone explains only 35% of the variance. Moreover, our framework enables de novo ChIP-seq peak prediction and is useful for inferring TF-binding peaks in new experimental conditions by reducing the need for additional experiments. We observe that the genome is more accessible in intergenic regions, and that increased accessibility is positively correlated with gene expression and anti-correlated with distance to the origin of replication. Our biophysically motivated model provides a more comprehensive description of TF-binding in vivo from first principles towards a better representation of gene regulation in silico, with promising applications in systems biology.

  20. The Role of Genome Accessibility in Transcription Factor Binding in Bacteria.

    Directory of Open Access Journals (Sweden)

    Antonio L C Gomes

    2016-04-01

    Full Text Available ChIP-seq enables genome-scale identification of regulatory regions that govern gene expression. However, the biological insights generated from ChIP-seq analysis have been limited to predictions of binding sites and cooperative interactions. Furthermore, ChIP-seq data often poorly correlate with in vitro measurements or predicted motifs, highlighting that binding affinity alone is insufficient to explain transcription factor (TF-binding in vivo. One possibility is that binding sites are not equally accessible across the genome. A more comprehensive biophysical representation of TF-binding is required to improve our ability to understand, predict, and alter gene expression. Here, we show that genome accessibility is a key parameter that impacts TF-binding in bacteria. We developed a thermodynamic model that parameterizes ChIP-seq coverage in terms of genome accessibility and binding affinity. The role of genome accessibility is validated using a large-scale ChIP-seq dataset of the M. tuberculosis regulatory network. We find that accounting for genome accessibility led to a model that explains 63% of the ChIP-seq profile variance, while a model based in motif score alone explains only 35% of the variance. Moreover, our framework enables de novo ChIP-seq peak prediction and is useful for inferring TF-binding peaks in new experimental conditions by reducing the need for additional experiments. We observe that the genome is more accessible in intergenic regions, and that increased accessibility is positively correlated with gene expression and anti-correlated with distance to the origin of replication. Our biophysically motivated model provides a more comprehensive description of TF-binding in vivo from first principles towards a better representation of gene regulation in silico, with promising applications in systems biology.

  1. Role of the tumor necrosis factor family member LIGHT in the pathogenesis of atopic dermatitis.

    Science.gov (United States)

    Seifeldin, Neveen Salah; El Sayed, Shereen Bendary; Asaad, Marwa Kamal; Aly, Alaa Ahmed

    2015-10-01

    LIGHT (the name of which is derived from "homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator, and expressed by T lymphocytes"), is a member of the tumor necrosis factor superfamily that is involved in various inflammatory diseases. To assess serum LIGHT levels in patients with atopic dermatitis (AD) before and after treatment and compare it with controls. To correlate serum LIGHT with the severity scoring of AD (SCORAD) index. Another objective is to compare LIGHT levels between lesional skin in patients with AD and controls. Twenty patients with AD and 20 healthy controls were enrolled in the study. Serum LIGHT levels were examined using an enzyme immunoassay technique. Serum total IgE levels, absolute eosinophil count, and eosinophil percentage were also done for both patients and controls. The SCORAD index was done for every patient before and after treatment. Skin LIGHT levels were analyzed using enzyme-linked immunosorbent assay kit and compared with control skin. Serum LIGHT levels in patients with AD were significantly higher than that of healthy controls and correlated positively with SCORAD index. LIGHT concentrations decreased as the symptoms were improved by treatment. A significant correlation was found on comparing the LIGHT serum levels and other established markers of disease severity. LIGHT levels in lesional skin in these patients were markedly higher than LIGHT levels in normal skin. LIGHT may play an important role in the pathogenesis of AD. This may presumably have possible future implications on the treatment of this chronic disease. © 2015 The International Society of Dermatology.

  2. Prognostic factors in breast cancer with extracranial oligometastases and the appropriate role of radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Gyu Sang; Yu, Jeong Il; Park, Won; Huh, Seung Jae; Choi, Doo Ho [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-12-15

    To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (> or =50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (< or =1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

  3. The Role of Individual Traits and Environmental Factors for Diet Composition of Sheep.

    Directory of Open Access Journals (Sweden)

    Atle Mysterud

    Full Text Available Large herbivore consumption of forage is known to affect vegetation composition and thereby ecosystem functions. It is thus important to understand how diet composition arises as a mixture of individual variation in preferences and environmental drivers of availability, but few studies have quantified both. Based on 10 years of data on diet composition by aid of microhistological analysis for sheep kept at high and low population density, we analysed how both individual traits (sex, age, body mass, litter size linked to preference and environmental variation (density, climate proxies linked to forage availability affected proportional intake of herbs (high quality/low availability and Avenella flexuosa (lower quality/high availability. Environmental factors affecting current forage availability such as population density and seasonal and annual variation in diet had the most marked impact on diet composition. Previous environment of sheep (switch between high and low population density had no impact on diet, suggesting a comparably minor role of learning for density dependent diet selection. For individual traits, only the difference between lambs and ewes affected proportion of A. flexuosa, while body mass better predicted proportion of herbs in diet. Neither sex, body mass, litter size, ewe age nor mass of ewe affected diet composition of lambs, and there was no effect of age, body mass or litter size on diet composition of ewes. Our study highlights that diet composition arises from a combination of preferences being predicted by lamb and ewes' age and/or body mass differences, and the immediate environment in terms of population density and proxies for vegetation development.

  4. Environmental factors and teenagers' personalities: The role of personal and familial Socio-Cultural Level.

    Science.gov (United States)

    Menardo, Elisa; Balboni, Giulia; Cubelli, Roberto

    2017-05-15

    Environmental (e.g., socio-cultural context), individual (e.g., genetic makeup), and interpersonal (e.g., caregiver-children relationships) factors can play a crucial role in shaping the development of the teenagers' personality. In this study, we focused on the Socio-Cultural Level that designates the set of preferences, knowledge, and behaviors that characterize an individual's way of life and depend on his or her cultural, social, and economic resources. We studied the relationship between Socio-Cultural Level (personal, maternal, and paternal) and Big Five personality traits of 191 teenagers living in the same geographical area. Results showed that Socioeconomic Status (i.e., parental education level and occupational prestige), which is the only dimension generally measured in investigations on Socio-Cultural Level, was not related with personality. In contrast, Cultural Capital and Social Capital were associated with different personality traits. Personal Cultural Capital was related to Openness to experience of boys and girls and to Extraversion of girls; personal Social Capital was related to Extraversion of girls, Emotional stability of boys, and Agreeableness of both boys and girls; maternal Cultural Capital was associated with Openness to experience of daughters. Overall, the personality of teenagers was more related to their own Cultural and Social Capital than to the Cultural and Social Capital of their parents. Moreover, the relationship between Cultural Capital and Social Capital of boys/girls and of fathers/mothers was moderate in strength. It seems that parents influence the development of personality of their teenagers indirectly, their Socio-Cultural Level shaping the Socio-Cultural Level of their sons and daughters. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The Role of Individual Traits and Environmental Factors for Diet Composition of Sheep.

    Science.gov (United States)

    Mysterud, Atle; Austrheim, Gunnar

    2016-01-01

    Large herbivore consumption of forage is known to affect vegetation composition and thereby ecosystem functions. It is thus important to understand how diet composition arises as a mixture of individual variation in preferences and environmental drivers of availability, but few studies have quantified both. Based on 10 years of data on diet composition by aid of microhistological analysis for sheep kept at high and low population density, we analysed how both individual traits (sex, age, body mass, litter size) linked to preference and environmental variation (density, climate proxies) linked to forage availability affected proportional intake of herbs (high quality/low availability) and Avenella flexuosa (lower quality/high availability). Environmental factors affecting current forage availability such as population density and seasonal and annual variation in diet had the most marked impact on diet composition. Previous environment of sheep (switch between high and low population density) had no impact on diet, suggesting a comparably minor role of learning for density dependent diet selection. For individual traits, only the difference between lambs and ewes affected proportion of A. flexuosa, while body mass better predicted proportion of herbs in diet. Neither sex, body mass, litter size, ewe age nor mass of ewe affected diet composition of lambs, and there was no effect of age, body mass or litter size on diet composition of ewes. Our study highlights that diet composition arises from a combination of preferences being predicted by lamb and ewes' age and/or body mass differences, and the immediate environment in terms of population density and proxies for vegetation development.

  6. [The role of psychic factors in the pathogenesis of bronchial asthma].

    Science.gov (United States)

    Vucević, Danijela; Radosavljević, Tatjana; Mladenović, Dusan; Todorović, Vera

    2011-01-01

    Bronchial asthma is a chronic inflammatory disorder of the airways in which many cells play a role, in particular mast cells, eosinophils, neutrophils, T-lymphocytes and epithelial cells. In susceptible individuals this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and cough, particularly at night and/or in the early morning. These symptoms are usually associated with variable and extensive limitations of airflow in the bronchi reversible spontaneously or by treatment. It has been shown that restrain of the effectors of stress response participate in the pathogenesis of bronchial asthma. Anger that is not expressed and frustrations may activate the limbic stress pathway. Thus, the released neurotransmitters followed by excitation thus causing psychogenic (mental or emotional) stress. It is also known that emotional stress may be responsible for the exacerbation of asthma. Namely, pronounced emotions cause hyperventilation and hypocapnia inducing bronchospasm. Certain psychological personality features are related to adaptive or inadequate body response to numerous life events. Thus, until the beginning of the last century, bronchial asthma was referred to as asthma nervosa, because clinicians clearly observed the psychological profile of patients with predominant fear of asphyxia and recurrent attacks of paroxysmal dyspnoea. Besides, increased sensitivity, repression of aggressive feelings and expressive empathy have been identified as the most frequent psychological characteristics of asthmatic patients. However, scientists are still far from a full understanding of bronchial asthma pathogenesis. The contribution of psychic factors has become meaningful in the understanding of the development of bronchial asthma. Having in mind that in the majority of patients asthma is a lifelong condition, there is a hope that further investigations of bronchial asthma psychogenesis will improve prevention and treatment of this disease.

  7. The role of psychic factors in the pathogenesis of bronchial asthma

    Directory of Open Access Journals (Sweden)

    Vučević Danijela

    2011-01-01

    Full Text Available Bronchial asthma is a chronic inflammatory disorder of the airways in which many cells play a role, in particular mast cells, eosinophils, neutrophils, T-lymphocytes and epithelial cells. In susceptible individuals this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and cough, particularly at night and/or in the early morning. These symptoms are usually associated with variable and extensive limitations of airflow in the bronchi reversible spontaneously or by treatment. It has been shown that restrain of the effectors of stress response participate in the pathogenesis of bronchial asthma. Anger that is not expressed and frustrations may activate the limbic stress pathway. Thus, the released neurotransmitters followed by excitation thus causing psychogenic (mental or emotional stress. It is also known that emotional stress may be responsible for the exacerbation of asthma. Namely, pronounced emotions cause hyperventilation and hypocapnia inducing bronchospasm. Certain psychological personality features are related to adaptive or inadequate body response to numerous life events. Thus, until the beginning of the last century, bronchial asthma was referred to as asthma nervosa, because clinicians clearly observed the psychological profile of patients with predominant fear of asphyxia and recurrent attacks of paroxysmal dyspnoea. Besides, increased sensitivity, repression of aggressive feelings and expressive empathy have been identified as the most frequent psychological characteristics of asthmatic patients. However, scientists are still far from a full understanding of bronchial asthma pathogenesis. The contribution of psychic factors has become meaningful in the understanding of the development of bronchial asthma. Having in mind that in the majority of patients asthma is a lifelong condition, there is a hope that further investigations of bronchial asthma psychogenesis will improve prevention and treatment of

  8. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables?

    Science.gov (United States)

    Linos, A; Kaklamani, V G; Kaklamani, E; Koumantaki, Y; Giziaki, E; Papazoglou, S; Mantzoros, C S

    1999-12-01

    Although several studies showed that risk of rheumatoid arthritis (RA) is inversely associated with consumption of n-3 fatty acids, the one study showing that olive oil may have a protective role has not yet been confirmed. We examined the relation between dietary factors and risk of RA in persons from southern Greece. We studied 145 RA patients and 188 control subjects who provided information on demographic and socioeconomic variables, prior medical and family history, and present disease status. Subjects responded to an interviewer-administered, validated, food-frequency questionnaire that assessed the consumption of >100 food items. We calculated chi-square statistics for linear trend and odds ratios (ORs) for the development of RA in relation to the consumption of olive oil, fish, vegetables, and a series of food groups classified in quartiles. Risk of developing RA was inversely and significantly associated only with cooked vegetables (OR: 0.39) and olive oil (OR: 0.39) by univariate analysis. A significant trend was observed with increasing olive oil (chi-square: 4.28; P = 0.03) and cooked vegetable (chi-square: 10. 48; P = 0.001) consumption. Multiple logistic regression analysis models confirmed the independent and inverse association between olive oil or cooked vegetable consumption and risk of RA (OR: 0.38 and 0.24, respectively). Consumption of both cooked vegetables and olive oil was inversely and independently associated with risk of RA in this population. Further research is needed to elucidate the underlying mechanisms of this finding, which may include the antioxidant properties or the high n-9 fatty acid content of the olive oil.

  9. Potential role of growth factors with particular focus on growth hormone and insulin-like growth factor-1 in the management of chronic kidney disease

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Bo; El Nahas, Meguid

    2009-01-01

    Prevention and treatment of chronic kidney disease (CKD) so far primarily has been based on early and aggressive treatment of hypertension. A number of other therapeutic approaches have the potential of being translated to the clinical area within the foreseeable future. In this review, we focus...... administration on the nutritional parameters of patients on renal replacement therapy. More recently, a larger randomized, double-blind, placebo-controlled, 26-week, proof-of-concept clinical study was conducted to investigate the effect of GH (Norditropin; Novo Nordisk, Bagsvaerd, Denmark) in adult chronic...... on growth factors and, in particular, on the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in the treatment of CKD and the management of its complications. Disturbances of the GH-IGF-1 axis in CKD have suggested therapeutic roles for both the inhibition, as well as the stimulation...

  10. Effect of endogenous factors on the chemical perception of Grapholita molesta (Busck) (Lepidoptera: Tortricidae) to sex pheromone; Efeito de fatores endogenos na percepcao quimica de Grapholita molesta(Busck) (Lepidoptera: Tortricidae) ao feromonio sexual

    Energy Technology Data Exchange (ETDEWEB)

    Altafini, Deisi L.; Sant' Ana, Josue; Redaelli, Luiza R., E-mail: deisila@gmail.co [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Dept. de Fitossanidade. Programa de Pos-Graduacao em Fitotecnia

    2010-06-15

    The oriental fruit moth, Grapholita molesta (Busck), stands out as one of the most important pest in Rosaceae orchards in Brazil. During feeding, caterpillars bore into shoots, branches and fruits, impairing the commercial production. This work aimed to study the effect of endogenous factors in the chemical perception and in the species chemotactic behavior, seeking to optimize monitoring and the behavioral control of this pest. We evaluated male electroantennographical (EAG) and chemotactical (olfactometry) responses to the synthetic sex pheromone in different ages, virgins or mated and fed or unfed. The EAG responses of males did not differ for all evaluated factors. Nevertheless, the chemotactical behavior of males seems to decrease with age, not varying as a function of mating or feeding conditions. The knowledge about the interference of these factors in G. molesta may help with the interpretation of fi eld results, allowing the development of suitable and reliable control measures based on infochemicals for behavioral control. (author)

  11. TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle

    NARCIS (Netherlands)

    Pera, Tonio; Sami, Riham; Zaagsma, Johan; Meurs, Herman

    2011-01-01

    Pera T, Sami R, Zaagsma J, Meurs H. TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 301: L822-L828, 2011. First published August 26, 2011; doi:10.1152/ajplung.00017.2011.-Increased airway smooth muscle (ASM) mass is a

  12. Socioemotional and Academic Adjustment Among Children with Learning Disorders: The Mediational Role of Attachment-Based Factors

    Science.gov (United States)

    Al-Yagon, Michal; Mikulincer, Mario

    2004-01-01

    This study examined the role of attachment-based factors (children's attachment style, children's appraisal of teacher as a secure base, and teacher's feelings of closeness to child) in explaining differences in Israeli children's socioemotional adjustment (self-rated sense of coherence, loneliness) and academic functioning (teacher-rated). The…

  13. Explaining Gender Gaps in English Composition and College Algebra in College: The Mediating Role of Psychosocial Factors

    Science.gov (United States)

    Ndum, Edwin; Allen, Jeff; Way, Jason; Casillas, Alex

    2018-01-01

    We examined the role of six psychosocial factors (PSFs) in explaining gender gaps in English Composition (n = 8,633) and College Algebra (n = 2,261) using data of first-year female (55%) and male students from 42 colleges. Using a multilevel model and controlling for prior achievement, we found that PSFs mediated between 3% and 41% of the gender…

  14. 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...

  15. Mediating Role of Self-Determination Constructs in Explaining the Relationship between School Factors and Postschool Outcomes

    Science.gov (United States)

    Shogren, Karrie A.; Garnier Villarreal, Mauricio; Lang, Kyle; Seo, Hyojeong

    2017-01-01

    Secondary data analysis using the National Longitudinal Transition Study-2 data set was conducted to examine the degree to which autonomy, psychological empowerment, and self-realization (3 of 4 essential characteristics of self-determination) play a mediating role in the relationship between school-based factors and postschool outcomes. The…

  16. Factors Impacting Job Performance and Role Attractiveness in Academic Directors and Their Implications for Policy and Practice in Higher Education

    Science.gov (United States)

    Vilkinas, Tricia; Ladyshewsky, Richard K.

    2014-01-01

    The purpose of this study was to identify factors that impacted on the performance and attractiveness of the Academic Director's role. Academic Directors are responsible for leading and managing an academic qualification. Academic Directors (n = 101) participating in a leadership development programme were invited to respond to an online 360…

  17. Clues from Crouzon: Insights into the potential role of growth factors in the pathogenesis of myelinated retinal nerve fibers

    Directory of Open Access Journals (Sweden)

    Giancarlo A. Garcia

    2016-12-01

    Conclusions: This association of Crouzon syndrome with bilateral peripapillary MRNF may lend insight into the developmental control of optic nerve myelination, the pathogenesis of MRNF, and the potential role of growth factors in these processes. Further, OCT angiography allowed for excellent blood vessel visualization in this case of MRNF.

  18. The role of tumour necrosis factor alpha and soluble tumour necrosis factor alpha receptors in the symptomatology of schizophrenia.

    Science.gov (United States)

    Turhan, Levent; Batmaz, Sedat; Kocbiyik, Sibel; Soygur, Arif Haldun

    2016-07-01

    Background Immunological mechanisms may be responsible for the development and maintenance of schizophrenia symptoms. Aim The aim of this study is to measure tumour necrosis factor-alpha (TNF-α), soluble tumour necrosis factor-alpha receptor I (sTNF-αRI), and soluble tumour necrosis factor-alpha receptor II (sTNF-αRII) levels in patients with schizophrenia and healthy individuals, and to determine their relationship with the symptoms of schizophrenia. Methods Serum TNF-α, sTNF-αRI and sTNF-αRII levels were measured. The Positive and Negative Syndrome Scale (PANSS) was administered for patients with schizophrenia (n = 35), and the results were compared with healthy controls (n = 30). Hierarchical regression analyses were undertaken to predict the levels of TNF-α, sTNF-αRI and sTNF-αRII. Results No significant difference was observed in TNF-α levels, but sTNF-αRI and sTNF-αRII levels were lower in patients with schizophrenia. Serum sTNF-αRI and sTNF-αRII levels were found to be negatively correlated with the negative subscale score of the PANSS, and sTNF-αRI levels were also negatively correlated with the total score of the PANSS. Smoking, gender, body mass index were not correlated with TNF-α and sTNF-α receptor levels. Conclusions These results suggest that there may be a change in anti-inflammatory response in patients with schizophrenia due to sTNF-αRI and sTNF-αRII levels. The study also supports low levels of TNF activity in schizophrenia patients with negative symptoms.

  19. The role of sialoadenectomy and epıdermal growth factor (EGF) in ...

    African Journals Online (AJOL)

    USER

    2010-05-17

    May 17, 2010 ... Epidermal growth factor (EGF), which was first isolated from submandibular .... The stimulation of epidermal keratinization by a a protein isolated from ... growth factor on skin and oral mucosa in neonatal mice. Arch. Oral. Biol.

  20. Factors Associated with Colorectal Cancer Risk Perception: The Role of Polyps and Family History

    Science.gov (United States)

    Stark, Jennifer Rider; Bertone-Johnson, Elizabeth R.; Costanza, Mary E.; Stoddard, Anne M.

    2006-01-01

    It is unclear how objective risk factors influence the factors associated with colorectal cancer (CRC) risk perception. The goals of this study were to investigate factors associated with perceived risk of CRC and to explore how these relationships were modified by personal history of polyps or family history of CRC. The study involved a mailed…

  1. A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor β receptor signaling.

    Science.gov (United States)

    Gu, Ai-Di; Zhang, Song; Wang, Yunqi; Xiong, Hui; Curtis, Thomas A; Wan, Yisong Y

    2015-01-20

    Transforming growth factor-beta (TGF-β) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-β signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-βR) deletion and compromised T-cell-mediated tumor rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and effector function, it was essential for T cell proliferation after activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-βR-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Incorporation of stromal cell-derived factor-1 alpha in PCL/gelatin electrospun membranes for guided bone regeneration

    NARCIS (Netherlands)

    Ji, W.; Yang, F.; Ma, J.L.; Bouma, M.J.; Boerman, O.C.; Chen, Z.; Beucken, J.J.J.P van den; Jansen, J.B.M.J.

    2013-01-01

    The goal of this work was to evaluate the effect of membrane functionalization with a chemotactic factor on cell recruitment and bone formation in order to develop a bioactive membrane for guided bone regeneration (GBR) applications. To this end. GBR membranes were prepared by electrospinning using

  3. The Relationship of Secondary Special Education Teachers' Roles and Factors that Lead to Professional Burnout.

    Science.gov (United States)

    Embich, Jeanne L.

    2001-01-01

    A survey of 300 learning disability teachers in middle and high schools found teachers were experiencing high levels of emotional exhaustion, specifically those who team teach with a general educator. Role conflict, role ambiguity, perceived workload, and lack of principal support contributed to the teachers' feelings of emotional exhaustion.…

  4. Socio-economic factors affecting the role of local leaders in rural ...

    African Journals Online (AJOL)

    Findings also revealed that local leaders play active roles in community and rural development. The study recommended that the socio-economic conditions of women leaders be further enhanced to increase their role in rural and community development. International Journal of Agriculture and Rural Development Vol.

  5. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency

    Science.gov (United States)

    Mukhopadhyay, C. K.; Mazumder, B.; Fox, P. L.

    2000-01-01

    A role of the copper protein ceruloplasmin (Cp) in iron metabolism is suggested by its ferroxidase activity and by the tissue iron overload in hereditary Cp deficiency patients. In addition, plasma Cp increases markedly in several conditions of anemia, e.g. iron deficiency, hemorrhage, renal failure, sickle cell disease, pregnancy, and inflammation. However, little is known about the cellular and molecular mechanism(s) involved. We have reported that iron chelators increase Cp mRNA expression and protein synthesis in human hepatocarcinoma HepG2 cells. Furthermore, we have shown that the increase in Cp mRNA is due to increased rate of transcription. We here report the results of new studies designed to elucidate the molecular mechanism underlying transcriptional activation of Cp by iron deficiency. The 5'-flanking region of the Cp gene was cloned from a human genomic library. A 4774-base pair segment of the Cp promoter/enhancer driving a luciferase reporter was transfected into HepG2 or Hep3B cells. Iron deficiency or hypoxia increased luciferase activity by 5-10-fold compared with untreated cells. Examination of the sequence showed three pairs of consensus hypoxia-responsive elements (HREs). Deletion and mutation analysis showed that a single HRE was necessary and sufficient for gene activation. The involvement of hypoxia-inducible factor-1 (HIF-1) was shown by gel-shift and supershift experiments that showed HIF-1alpha and HIF-1beta binding to a radiolabeled oligonucleotide containing the Cp promoter HRE. Furthermore, iron deficiency (and hypoxia) did not activate Cp gene expression in Hepa c4 hepatoma cells deficient in HIF-1beta, as shown functionally by the inactivity of a transfected Cp promoter-luciferase construct and by the failure of HIF-1 to bind the Cp HRE in nuclear extracts from these cells. These results are consistent with in vivo findings that iron deficiency increases plasma Cp and provides a molecular mechanism that may help to understand these

  6. Inactivation of factor VIIa by antithrombin in vitro, ex vivo and in vivo: role of tissue factor and endothelial cell protein C receptor.

    Directory of Open Access Journals (Sweden)

    Rit Vatsyayan

    Full Text Available Recent studies have suggested that antithrombin (AT could act as a significant physiologic regulator of FVIIa. However, in vitro studies showed that AT could inhibit FVIIa effectively only when it was bound to tissue factor (TF. Circulating blood is known to contain only traces of TF, at best. FVIIa also binds endothelial cell protein C receptor (EPCR, but the role of EPCR on FVIIa inactivation by AT is unknown. The present study was designed to investigate the role of TF and EPCR in inactivation of FVIIa by AT in vivo. Low human TF mice (low TF, ∼ 1% expression of the mouse TF level and high human TF mice (HTF, ∼ 100% of the mouse TF level were injected with human rFVIIa (120 µg kg(-1 body weight via the tail vein. At varying time intervals following rFVIIa administration, blood was collected to measure FVIIa-AT complex and rFVIIa antigen levels in the plasma. Despite the large difference in TF expression in the mice, HTF mice generated only 40-50% more of FVIIa-AT complex as compared to low TF mice. Increasing the concentration of TF in vivo in HTF mice by LPS injection increased the levels of FVIIa-AT complexes by about 25%. No significant differences were found in FVIIa-AT levels among wild-type, EPCR-deficient, and EPCR-overexpressing mice. The levels of FVIIa-AT complex formed in vitro and ex vivo were much lower than that was found in vivo. In summary, our results suggest that traces of TF that may be present in circulating blood or extravascular TF that is transiently exposed during normal vessel damage contributes to inactivation of FVIIa by AT in circulation. However, TF's role in AT inactivation of FVIIa appears to be minor and other factor(s present in plasma, on blood cells or vascular endothelium may play a predominant role in this process.

  7. THE ROLE OF BACTERIAL FACTOR AND IMMUNOLOGICAL СHANGES IN NONINFECTIOUS DISEASES OF MICROBIAL ORIGIN

    Directory of Open Access Journals (Sweden)

    Korniychuk O.P.

    2015-05-01

    Full Text Available Introduction. Today during the study of the development mechanisms of any somatic disease possible participation of the microorganism as trigger factor or its influence on the course of the disease or development of complications is considered. Microflora participation in the etiopathogenesis of noninfectious diseases allows to divide the latest into the following groups: Naturally, the first aspects of the study of the role of microorganisms in the development of noninfectious diseases are pathological processes developing in the organs and systems of the body, which are natural biotope, particularly gastrointestinal tract. The imbalance in the functioning of the macroorganism (stress, poor diet causes changes in the composition of endogenous microcenosis and therefore dysbiosis. Thus changes in the hormonal homeostasis, immunoreactivity, in the hypothalamic-adrenal system, speed of peristalsis of the intestines are observed, the overgrowth syndrome in the small intestine developes. A classic disease of a group of diseases that are accompanied by the development of erosive conditions are Helicobacter pylori - associated ulcerous disease of 12 duodenal ulcer. Diseases of the colon digestive canal can be divided into 2 groups - ulcerative colitis and tumors. Escherichia are the main representatives of facultative anaerobic microflora of the colon and are involved in the pathogenesis of both ulcerative colitis and cancer. Material and methods. A study in order to compare the inducing impact of Escherichia lipopolysaccharide isolated from patients with nonspecific ulcerative colitis (NUC, N =38, Crohn's disease (CD, N =30 and colon cancer (CC, N =38, on the humoral and cellular (cytokine links of immunity in ulcerative colitis and colon cancer. From the patients in both study groups and individuals from the control group E. coli were isolated from fecal for obtainining LPS. Synthesis induction of TNFα, IL.-8 and IL.-10 was conducted by

  8. Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells

    Directory of Open Access Journals (Sweden)

    R. Dong

    2007-08-01

    Full Text Available The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-a (TNF-a. To evaluate the role of TNF-a in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-a -treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-a treatment. These results showed that TNF-a can promote epithelial-mesenchymal transition (EMT of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB inhibitor aspirin while not affected by the reactive oxygen species (ROS scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBa also blocked the TNF-a-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-a-induced EMT. ROS caused by TNF-a seemed to play a minor role in the TNF-a-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-a - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

  9. Role of hemostatic factors on the risk of venous thrombosis in people with impaired kidney function.

    Science.gov (United States)

    Ocak, Gürbey; Vossen, Carla Y; Lijfering, Willem M; Verduijn, Marion; Dekker, Friedo W; Rosendaal, Frits R; Cannegieter, Suzanne C

    2014-02-11

    Factors explaining the association between impaired kidney function and venous thrombosis have not been identified so far. The aim of our study was to determine whether the association between impaired kidney function and venous thrombosis can be explained by the concurrent presence of genetic or acquired venous thrombosis risk factors. The glomerular filtration rate was estimated (eGFR) in 2473 venous thrombosis patients and 2936 controls from a population-based case-control study. Kidney function was grouped into 6 categories based on percentiles of the eGFR in the controls (>50th [reference], 10th-50th, 5th-10th, 2.5th-5th, 1st-2.5th, and percentile). Several hemostatic factors showed a procoagulant shift with decreasing kidney function in controls, most notably factor VIII and von Willebrand factor. Compared with eGFR >50th percentile, factor VIII levels (adjusted mean difference, 60 IU/dL for the percentile category) and von Willebrand factor levels (adjusted mean difference, 60 IU/dL for the percentile category) increased with each percentile category. The odds ratios for venous thrombosis similarly increased across the categories from 1.1 (95% confidence interval, 0.9-1.3) for the 10th to 50th percentile to 3.7 (95% confidence interval, 2.4-5.7) for the percentile category. Adjustment for factor VIII or von Willebrand factor attenuated these odds ratios, indicating an effect of eGFR on thrombosis through these factors. Adjustments for other risk factors for venous thrombosis did not affect the odds ratios. Impaired kidney function affects venous thrombosis risk via concurrently raised factor VIII and von Willebrand factor levels.

  10. Factors behind Leisure-Time Physical Activity Behavior Based on Finnish Twin Studies: The Role of Genetic and Environmental Influences and the Role of Motives

    Directory of Open Access Journals (Sweden)

    Sari Aaltonen

    2014-01-01

    Full Text Available Different approaches are being taken to clarify the role of various factors in the development of physical activity behaviors. Genetic studies are a new area of physical activity research and also the motives for physical activity have been widely studied. The purpose of this paper is to review the findings emerging from the longitudinal genetic studies on leisure-time physical activity and to evaluate the associations between motivational factors and leisure-time physical activity. The focus is to review recent findings of longitudinal Finnish twin studies. The results of the latest longitudinal Finnish twin studies point to the existence of age-specific genetic and environmental influences on leisure-time physical activity. Variations in environmental factors seem to explain the observed deterioration in leisure-time physical activity levels. A decline in genetic influences is seen first from adolescence to young adulthood and again from the age of thirty to the mid-thirties. In the Finnish twin participants, mastery, physical fitness, and psychological state were the major motivation factors associated with consistent leisure-time physical activity behavior. The results also indicate that intrinsic motivation factors may be important for engagement in leisure-time physical activity.

  11. Factors behind leisure-time physical activity behavior based on Finnish twin studies: the role of genetic and environmental influences and the role of motives.

    Science.gov (United States)

    Aaltonen, Sari; Kujala, Urho M; Kaprio, Jaakko

    2014-01-01

    Different approaches are being taken to clarify the role of various factors in the development of physical activity behaviors. Genetic studies are a new area of physical activity research and also the motives for physical activity have been widely studied. The purpose of this paper is to review the findings emerging from the longitudinal genetic studies on leisure-time physical activity and to evaluate the associations between motivational factors and leisure-time physical activity. The focus is to review recent findings of longitudinal Finnish twin studies. The results of the latest longitudinal Finnish twin studies point to the existence of age-specific genetic and environmental influences on leisure-time physical activity. Variations in environmental factors seem to explain the observed deterioration in leisure-time physical activity levels. A decline in genetic influences is seen first from adolescence to young adulthood and again from the age of thirty to the mid-thirties. In the Finnish twin participants, mastery, physical fitness, and psychological state were the major motivation factors associated with consistent leisure-time physical activity behavior. The results also indicate that intrinsic motivation factors may be important for engagement in leisure-time physical activity.

  12. Ciliary neurotrophic factor inhibits bone formation and plays a sex-specific role in bone growth and remodeling.

    Science.gov (United States)

    McGregor, Narelle E; Poulton, Ingrid J; Walker, Emma C; Pompolo, Sueli; Quinn, Julian M W; Martin, T John; Sims, Natalie A

    2010-03-01

    Ciliary neurotrophic factor (CNTF) receptor (CNTFR) expression has been described in osteoblast-like cells, suggesting a role for CNTF in bone metabolism. When bound to CNTF, neuropoietin (NP), or cardiotrophin-like-cytokine (CLC), CNTFR forms a signaling complex with gp130 and the leukemia inhibitory factor receptor, which both play critical roles in bone cell biology. This study aimed to determine the role of CNTFR-signaling cytokines in bone. Immunohistochemistry detected CNTF in osteoblasts, osteocytes, osteoclasts, and proliferating chondrocytes. CNTFR mRNA was detected in primary calvarial osteoblasts and was upregulated during osteoblast differentiation. Treatment of osteoblasts with CNTF or CLC, but not NP, significantly inhibited mineralization and osterix mRNA levels. Twelve-week-old male CNTF ( -/- ) mice demonstrated reduced femoral length, cortical thickness, and periosteal circumference; but femoral trabecular bone mineral density (Tb.BMD) and tibial trabecular bone volume (BV/TV) were not significantly different from wild-type, indicating a unique role for CNTF in bone growth in male mice. In contrast, female CNTF ( -/- ) femora were of normal width, but femoral Tb.BMD, tibial BV/TV, trabecular number, and trabecular thickness were all increased. Female CNTF ( -/- ) tibiae also demonstrated high osteoblast number and mineral apposition rate compared to wild-type littermates, and this was intrinsic to the osteoblast lineage. CNTF is expressed locally in bone and plays a unique role in female mice as an inhibitor of trabecular bone formation and in male mice as a stimulus of cortical growth.

  13. Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress.

    Science.gov (United States)

    Xiao, Weihua; Liu, Yu; Chen, Peijie

    2016-12-01

    Muscle contusion is one of the most common muscle injuries in sports medicine. Macrophages play complex roles in the regeneration of skeletal muscle. However, the roles of macrophages, especially the mechanisms involved, in the regeneration of muscle contusion are still not fully understood. We hypothesize that the depletion of macrophages impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may be involved in the process. To test these hypotheses, we constructed a muscle contusion injury and a macrophage depletion model and followed it up with morphological and gene expression analyses. The data showed that fibrotic scars were formed in the muscle of contusion injury, and they deteriorated in the mice of macrophage depletion. Furthermore, the sizes of regenerating myofibers were significantly reduced by macrophage depletion. Pro-fibrotic factors, inflammatory cytokines, chemokines, and oxidative stress-related enzymes increased significantly after muscle injury. Moreover, the expression of these factors was delayed by macrophage depletion. Most of them were still significantly higher in the later stage of regeneration. These results suggest that macrophage depletion impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may play important roles in the process.

  14. [Factors influencing juvenile alcohol consumption: the role of gene-environment interactions].

    Science.gov (United States)

    Hinckers, Anne S; Frank, Josef; Heinz, Andreas; Schumann, Gunter; Schmidt, Martin H; Laucht, Manfred

    2006-09-01

    Excessive alcohol consumption in youth increases the risk of subsequent alcohol use disorders. Despite the recognition of genetic and environmental factors, an appropriate aetiological model is needed to take adequate preventative steps. This is in part due to the complex interactions between genotype and environment. In this article we review research on factors determining alcohol use by adolescents and on the development of an unifying model. The data bank Medline Advanced was searched for topical articles that were then checked for relevance and sorted according to genetic factors, environmental factors, and their interactions. Many factors, alone and in combination with others, influence juvenile alcohol consumption. Each single variable, however, can explain only a small part of the variation in consumption behaviour. The manifold possibilities of interactions between these factors become clear. There is a strong need for comprehensive models of juvenile alcohol use and the integration of current results into these models.

  15. Endoplasmic Reticulum-Associated Degradation Factor ERLIN2: Oncogenic Roles and Molecular Targeting of Breast Cancer

    Science.gov (United States)

    2013-06-01

    factor-independent proliferation in insulin-like growth factor-deficient media . To further examine the effects of ERLIN2 in a context that more... media . Oncogenesis-associated conditions, such as nutrient or growth factor depletion, can cause pathophysiologic ER stress [22,23]. When MCF10A cells...activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae . Mol Cancer Res 2005; 3

  16. Physiological role of growth factors and bone morphogenetic proteins in osteogenesis and bone fracture healing: а review

    Directory of Open Access Journals (Sweden)

    S. Sagalovsky

    2015-01-01

    Full Text Available The repair of large bone defects remains a major clinical orthopedic challenge. Bone regeneration and fracture healing is a complex physiological mechanisms regulated by a large number of biologically active molecules. Multiple factors regulate this cascade of molecular events, which affects different stages in the osteoblast and chondroblast lineage during such processes as migration, proliferation, chemotaxis, differentiation, inhibition, and extracellular protein synthesis. A recent review has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to identification of many signaling molecules associated with formation of skeletal tissues, including a large family of growth factors (transforming growth factor-β and bone morphogenetic proteins, fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, platelet-derived growth factor, cytokines and interleukins. There is increasing evidence indicating that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and bone mineralization. A clear understanding of cellular and molecular pathways involved in fracture healing is not only critical for improvement of fracture treatments, but it may also enhance further our knowledge of mechanisms involved in skeletal growth and repair, as well as mechanisms of aging. This suggests that, in the future, they may play a major role in the treatment of bone disease and fracture repair.

  17. Role of behavioural factors in green supply chain management implementation in Indian mining industries

    DEFF Research Database (Denmark)

    Muduli, Kamalakanta; Govindan, Kannan; Barve, Akhilesh

    2013-01-01

    factors which are influenced by human behaviours. Human behaviour is dynamic in nature and the relationships between them continuously evolve and change. In this ever-changing context, therefore, identifying and ranking the behavioural factors that affect GSCM implementation becomes essential. This can...... be taken as a reference by the decision makers while deciding the hierarchy of action necessary for effective implementation of green practices in mining supply chains. The present research attempts to explore various behavioural factors affecting GCSM practices and their interactions which help to attain...... green-enabled needs. Interpretive structural modelling (ISM) is employed in this research to extract the interrelationships among the identified behavioural factors....

  18. The Possible Role of Dentin as a Piezoelectric Signal Generator by Determining the Elec-tromechanical Coupling Factor of Dentin

    Directory of Open Access Journals (Sweden)

    Atabak Shahidi

    2011-08-01

    Full Text Available Introduction: This article aimed at calculation of the electromechanical coupling factor of dentin which is an indicator of the effectiveness with which a piezoelectric material converts electrical en-ergy into mechanical energy, or vice versa. The hypothesis: The electro-mechanical coupling factor of dentin was determined in mode 11 and 33 by calculating the ratio of the produced electrical energy to the stored elastic energy in dentin under applied pressure. This study showed that the electromechanical coupling factor of dentin was affected by the direction of the applied force and the moisture content of dentin. Also dentin was a weak electromechanical energy converter which might be categorized as a piezoelectric pressure sensor.Evaluation of the hypothesis: Determination of the electrome-chanical coupling factor of dentin and its other piezoelectric constants is essential to investigate the biologic role of piezoelectricity in tooth.

  19. Direct and indirect radioiodination of protein: comparative study of chemotactic peptide labeling; Radioiodacao de proteina por via direta e indireta: estudo comparativo da marcacao de peptideo quimiotatico

    Energy Technology Data Exchange (ETDEWEB)

    Lavinas, Tatiana

    2004-07-01

    The development of simple methods for protein radioiodination have stimulated the use of radioiodinated peptides in vivo. There are two basic methods for labeling proteins with radioiodine: direct labeling, reaction of an electrophilic radioiodine with functional activated groups on protein, like the phenol ring in the tyrosine residue, and the conjugation of a previously radioiodinated molecule to the protein, referred as indirect method. The great problem related to the direct radioiodination of proteins is the in vivo dehalogenation. This problem can be minimized if a non-phenolic prosthetic group is used in the indirect radioiodination of the peptide. The ATE prosthetic group, N-succinimidyl 3-(tri-n-butylstannyl) benzoate, when radioiodinated by electrophilic iododestannilation produces N-succinimidyl 3-[{sup 123}l/{sup 131}l] iodine benzoate (SIB) that is subsequently conjugated to the protein by the acylation of the lysine group. There are many radiopharmaceuticals employed in scintigraphic images of infection and inflammation used with some limitations. These limitations stimulated the improvement of a new class of radiopharmaceuticals, the receptor-specific related labeled peptides, as the mediators of the inflammatory response, that presents high affinity by receptors expressed in the inflammation process, and fast clearance from blood and non-target tissues. One of these molecules is the synthetic chemotactic peptide fNleLFNIeYK that presents potent chemotaxis for leukocytes, with high affinity by the receptors presented in polymorphonuclear leukocytes and mononuclear phagocytes. The objective of this work included the synthesis of ATE prosthetic group and comparative radioiodination of the chemotactic peptide fNleLFNIeYK by direct and indirect methods, with radiochemical purity determination and evaluation of in vivo and in vitro stability of the compounds. This work presented an original contribution in the comparative biological distribution studies

  20. Factor analysis in the identification of dietary patterns and their predictive role in morbid and fatal events.

    Science.gov (United States)

    Menotti, Alessandro; Alberti-Fidanza, Adalberta; Fidanza, Flaminio; Lanti, Mariapaola; Fruttini, Daniela

    2012-07-01

    The purpose was to examine the role of dietary patterns derived from factor analysis and their association with health and disease. Longitudinal population study, with measurement of diet (dietary history method), cardiovascular risk factors and a follow-up of 20 years for CHD incidence and 40 years for mortality. Two population samples in rural villages in northern and central Italy. Men (n 1221) aged 45-64 years were examined and followed up. One of the factors identified with factor analysis, run on seventeen food groups, was converted into a factor score (Factor 2 score) and used as a possible predictor of morbid and fatal events. High values of Factor 2 score were characterized by higher consumption of bread, cereals (pasta), potatoes, vegetables, fish and oil and by lower consumption of milk, sugar, fruit and alcoholic beverages. In multivariate analysis, Factor 2 score (mean 0·0061; sd 1·3750) was inversely and significantly associated (hazard ratio for a 1 sd increase; 95% CI) with 20-year CHD incidence (0·88; 0·73, 0·96) and 40-year mortality from CHD (0·79; 0·66, 0·95), CVD (0·87; 0·78, 0·96), cancer (0·84; 0·74, 0·96) and all causes (0·89; 0·83, 0·96), after adjustment for five other risk factors. Men in quintile 5 of Factor 2 score had a 4·1 years longer life expectancy compared with men in quintile 1. A dietary pattern derived from factor analysis, and resembling the characteristics of the Mediterranean diet, was protective for the occurrence of various morbid and fatal events during 40 years of follow-up.

  1. Overweight at age two years in a multi-ethnic cohort (ABCD study): the role of prenatal factors, birth outcomes and postnatal factors

    Science.gov (United States)

    2011-01-01

    Background Childhood overweight/obesity is a major public health problem worldwide which disproportionally affects specific ethnic groups. Little is known about whether such differences already exist at an early age and which factors contribute to these ethnic differences. Therefore, the present study assessed possible ethnic differences in overweight at age 2 years, and the potential explanatory role of prenatal factors, birth outcomes and postnatal factors. Methods Data were derived from a multi-ethnic cohort in the Netherlands (the ABCD study). Weight and height data of 3,156 singleton infants at age 2 years were used. Five ethnic populations were distinguished: Dutch native (n = 1,718), African descent (n = 238), Turkish (n = 162), Moroccan (n = 245) and other non-Dutch (n = 793). Overweight status was defined by the International Obesity Task Force guidelines. The explanatory role of prenatal factors, birth outcomes and postnatal factors in ethnic disparities in overweight (including obesity) was assessed by logistic regression analysis. Results Compared to the native Dutch (7.1%), prevalence of overweight was higher in the Turkish (19.8%) and Moroccan (16.7%) group, whereas the prevalence was not increased in the African descent (9.2%) and other non-Dutch (8.8%) group. Although maternal pre-pregnancy body mass index partly explained the ethnic differences, the odds ratio (OR) of being overweight remained higher in the Turkish (OR: 2.66; 95%CI: 1.56-4.53) and Moroccan (OR: 2.11; 95%CI: 1.31-3.38) groups after adjusting for prenatal factors. The remaining differences were largely accounted for by weight gain during the first 6 months of life (postnatal factor). Maternal height, birth weight and gender were independent predictors for overweight at age 2 years, but did not explain the ethnic differences. Conclusion Turkish and Moroccan children in the Netherlands have 2- to 3-fold higher odds for being overweight at age 2 years, which is largely attributed to

  2. Problem-Solving Test: The Role of Ubiquitination in Epidermal Growth Factor Receptor Trafficking

    Science.gov (United States)

    Szeberenyi, Jozsef

    2012-01-01

    Terms to be familiar with before you start to solve the test: growth factor signaling, epidermal growth factor, tyrosine protein kinase, tyrosine phosphorylation, ubiquitin, monoubiquitination, polyubiquitination, site-directed mutagenesis, transfection, expression vector, cDNA, immunoprecipitation, SDS-polyacrylamide gel electrophoresis, Western…

  3. Frequent respiratory tract infections in children. The role of environmental and genetic factors.

    NARCIS (Netherlands)

    Ruskamp, J.M.

    2009-01-01

    Respiratory tract infections (RTI), presenting as common cold, pharyngitis, tonsillitis, acute otitis media, bronchitis or pneumonia are a major health problem in children. In this thesis common environmental and host factors, as well as plausible genetic factors were evaluated in a large birth

  4. Head circumference and height abnormalities in autism revisited: the role of pre- and perinatal risk factors

    NARCIS (Netherlands)

    Schrieken, M.; Visser, J.C.; Oosterling, I.J.; Steijn, D.J. van; Bons, D.M.A.; Draaisma, J.M.; Gaag, R.J. van der; Buitelaar, J.K.; Donders, R.; Rommelse, N.N.

    2013-01-01

    Pre/perinatal risk factors and body growth abnormalities have been studied frequently as early risk markers in autism spectrum disorder (ASD), yet their interrelatedness in ASD has received very little research attention. This is surprising, given that pre/perinatal risk factors can have a

  5. The Role of Environmental Factors in Beginning Teachers' Professional Learning Related to Differentiated Instruction

    Science.gov (United States)

    De Neve, Debbie; Devos, Geert

    2016-01-01

    Little research has investigated factors that facilitate beginning teachers' participation in professional learning activities related to differentiated instruction (DI). This study examines environmental factors for DI learning activities in a sample of 272 beginning teachers from 72 primary schools. Multilevel analyses show that teacher…

  6. The Role of Human Factors/Ergonomics in the Science of Security: Decision Making and Action Selection in Cyberspace.

    Science.gov (United States)

    Proctor, Robert W; Chen, Jing

    2015-08-01

    The overarching goal is to convey the concept of science of security and the contributions that a scientifically based, human factors approach can make to this interdisciplinary field. Rather than a piecemeal approach to solving cybersecurity problems as they arise, the U.S. government is mounting a systematic effort to develop an approach grounded in science. Because humans play a central role in security measures, research on security-related decisions and actions grounded in principles of human information-processing and decision-making is crucial to this interdisciplinary effort. We describe the science of security and the role that human factors can play in it, and use two examples of research in cybersecurity--detection of phishing attacks and selection of mobile applications--to illustrate the contribution of a scientific, human factors approach. In these research areas, we show that systematic information-processing analyses of the decisions that users make and the actions they take provide a basis for integrating the human component of security science. Human factors specialists should utilize their foundation in the science of applied information processing and decision making to contribute to the science of cybersecurity. © 2015, Human Factors and Ergonomics Society.

  7. Climate factors play a limited role for past adaptation strategies in West Africa

    DEFF Research Database (Denmark)

    Mertz, Ole; Mbow, Cheikh; Nielsen, Jonas Østergaard

    2010-01-01

    The Sudano-Sahelian zone of West Africa has experienced recurrent droughts since the mid-1970s and today there is considerable concern for how this region will be able to adapt to future climate change. To develop well targeted adaptation strategies, the relative importance of climate factors...... as drivers of land use and livelihood change need to be better understood. Based on the perceptions of 1249 households in five countries across an annual rainfall gradient of 400-900 mm, we provide an estimate of the relative weight of climate factors as drivers of changes in rural households during the past...... 20 years. Climate factors, mainly inadequate rainfall, are perceived by 30-50% of households to be a cause of decreasing rainfed crop production, whereas a wide range of other factors explains the remaining 50-70%. Climate factors are much less important for decreasing livestock production...

  8. Roles of SigB and SigF in the Mycobacterium tuberculosis Sigma Factor Network▿ †

    OpenAIRE

    Lee, Jong-Hee; Karakousis, Petros C.; Bishai, William R.

    2007-01-01

    To characterize the roles of SigB and SigF in sigma factor regulation in Mycobacterium tuberculosis, we used chemically inducible recombinant strains to conditionally overexpress sigB and sigF. Using whole genomic microarray analysis and quantitative reverse transcription-PCR, we investigated the resulting global transcriptional changes after sigB induction, and we specifically tested the relative expression of other sigma factor genes after knock-in expression of sigB and sigF. Overexpressio...

  9. Factors affecting productivity and the role of customer relationship management: A case study of home appliance manufacturing

    Directory of Open Access Journals (Sweden)

    Saeed Mirzamohammadi

    2012-01-01

    Full Text Available In today's competitive world, productivity- as a core source of production - is the most important target of the organization. Experimental studies in developed industrial countries prove that productivity improvements resulted from development of management systems play a more important role in production than physical increases in labor and capital factors. This paper, while focusing on productivity from a CRM perspective, employs a European Organizational Excellence Model framework to identify factors affecting productivity and the role of CRM systems. We perform an empirical study for a case study of home appliance manufacturing and using a questionnaire computed present status and compared with desired status of CRM components such as customer leadership, strategy, skill and motivation of labor work, effective use of information technology and process management.

  10. Assembly of Saccharomyces cerevisiae 60S ribosomal subunits: role of factors required for 27S pre-rRNA processing

    Science.gov (United States)

    Sahasranaman, Aarti; Dembowski, Jill; Strahler, John; Andrews, Philip; Maddock, Janine; Woolford, John L

    2011-01-01

    The precise functions of most of the ∼200 assembly factors and 79 ribosomal proteins required to construct yeast ribosomes in vivo remain largely unexplored. To better understand the roles of these proteins and the mechanisms driving ribosome biogenesis, we examined in detail one step in 60S ribosomal subunit assembly—processing of 27SA3 pre-rRNA. Six of seven assembly factors required for this step (A3 factors) are mutually interdependent for association with preribosomes. These A3 factors are required to recruit Rrp17, one of three exonucleases required for this processing step. In the absence of A3 factors, four ribosomal proteins adjacent to each other, rpL17, rpL26, rpL35, and rpL37, fail to assemble, and preribosomes are turned over by Rat1. We conclude that formation of a neighbourhood in preribosomes containing the A3 factors establishes and maintains stability of functional preribosomes containing 27S pre-rRNAs. In the absence of these assembly factors, at least one exonuclease can switch from processing to turnover of pre-rRNA. PMID:21926967

  11. Epithelial-mesenchymal interactions and lung branching morphogenesis. Role of polyamines and transforming growth factor ß1

    Directory of Open Access Journals (Sweden)

    G Stabellini

    2009-12-01

    Full Text Available Lung branching morphogenesis is a result of epithelial-mesenchymal interactions, which are in turn dependent on extracellular matrix composition and cytokine regulation. Polyamines have recently been demonstrated as able to modify chick embryo skin differentiation. In this work we have examined the effects of putrescine and spermidine during chick embryo lung morphogenesis in organotypic cultures by morphological, histochemical and biochemical examination. To verify the role of polyamines, we used specific inhibitors, such as bis-cyclohexylammonium sulphate and alfa-difluoromethylornithine, and transforming growth factor ß1, an ornithine decarboxylase and polyamine stimulator. Our data show that lung morphogenesis is significantly altered following the induced mesenchymal glycosaminoglycan changes. The increase of mesenchymal glycosaminoglycans is correlated with a stimulation of lung development in the presence of polyamines, and with its inhibition when transforming growth factor ß1 is added to the culture medium. The morphometric data show a uniform increase of both the mesenchyme and epithelial branching with spermidine and putrescine stimulus, whereas the mesenchymal substance alone is significantly increased in apical-median lung sections with transforming growth factor ß1 and transforming growth factor ß1 + spermidine lung cultures. Transforming growth factor ß1 and transforming growth factor ß1 + spermidine confirm the blocking of epithelial branching formations and fibroblast activation, and show that polyamines are unable to prevent the blocking of epithelial cells due to the inhibitory effect of transforming growth factor ß1.

  12. Exploring the Risk Factors for Sudden Infant Deaths and Their Role in Inflammatory Responses to Infection

    Science.gov (United States)

    Blackwell, Caroline; Moscovis, Sophia; Hall, Sharron; Burns, Christine; Scott, Rodney J.

    2015-01-01

    The risk factors for sudden infant death syndrome (SIDS) parallel those associated with susceptibility to or severity of infectious diseases. There is no evidence that a single infectious agent is associated with SIDS; the common thread appears to be induction of inflammatory responses to infections. In this review, interactions between genetic and environmental risk factors for SIDS are assessed in relation to the hypothesis that many infant deaths result from dysregulation of inflammatory responses to “minor” infections. Risk factors are assessed in relation to three important stages of infection: (1) bacterial colonization (frequency or density); (2) induction of temperature-dependent toxins; (3) induction or control of inflammatory responses. In this article, we review the interactions among risk factors for SIDS for their effects on induction or control of inflammatory responses. The risk factors studied are genetic factors (sex, cytokine gene polymorphisms among ethnic groups at high or low risk of SIDS); developmental stage (changes in cortisol and testosterone levels associated with 2- to 4-month age range); environmental factors (virus infection, exposure to cigarette smoke). These interactions help to explain differences in the incidences of SIDS observed between ethnic groups prior to public health campaigns to reduce these infant deaths. PMID:25798137

  13. [The role of some psychological, psychosocial and obstetrical factors in the intensity of postpartum blues].

    Science.gov (United States)

    Séjourné, N; Denis, A; Theux, G; Chabrol, H

    2008-04-01

    Within days following birth, most women show signs of mood changes, commonly named baby blues. Baby blues can result in postpartum depression. Hence it appears important to explore in more details the clinical background related to the intensity of postpartum blues. The aim of this study is to investigate the contribution of psychological, psychosocial and obstetrical factors to the intensity of postpartum blues. One hundred and forty-eight women participated in the study and completed questionnaires three days after delivery. A questionnaire was built to collect information on psychosocial and obstetrical factors. The Maternity Blues (Kennerley and Gath, 1989) was used to assess postpartum blues. Psychological factors were measured with the Maternal Self-Report Inventory (Shea et Tronick, 1988), the Perceived Stress Scale (Cohen, Kamarch et Mermelstein, 1983) and the Sarason's Social Support Questionnaire (1983). Four multiple regression analyses were conducted to predict the intensity of postpartum blues by entering psychosocial factors, history of depression, obstetrical factors and psychological and relational factors. Significant predictors (maternal self-esteem, marital status, previous psychotherapeutic treatment, previous antidepressant treatment) were entered in a multiple regression analysis predicting the intensity of postpartum blues. This model accounted for 31% of the variance in the intensity of postpartum blues (F(4, 143)=17.9; Pblues and may be used in order to detect women who exhibit risk factors.

  14. [The role of environmental factors in Parkinson's disease may depend on disease onset age].

    Science.gov (United States)

    Kłodowska-Duda, Gabriela; Jasińska-Myga, Barbara; Safranow, Krzysztof; Boczarska-Jedynak, Magdalena; Opala, Grzegorz

    2005-01-01

    Various factors are suspected to participate in PD onset and include environment-related factors and workplace exposure to pesticides, metals and hydrocarbons. Nevertheless, results of epidemiological research are inconsistent. Some authors emphasize hydrocarbons exposure to younger patients. Our aim was to compare PD risk factors to onset age. Of 174 patients with idiopathic PD, without dementia, two subgroups were isolated: 65 patients with early onset PD (EOPD) below 50 (n=65, age 52.8+/-7.6 years, onset 42.8+/-5.3 years) and 109 patients with late onset (LOPD) above 50 (n=109, age 67.8+/-7.0, onset 60.8+/-6.7 years). Various environmental factors reported in literature were analyzed. The univariate analysis showed that factors significantly predisposing to EOPD are vocational education (OR 3.24, 95%CI 1.50-7.00, prisk factors are smoking (OR 2.20, 95%CI 1.07-4.53, prisk of PD onset at younger ages. Presumably, some of the observed differences in the results of research of various authors into PD risk factors may be caused by ignoring onset age within the researched patients.

  15. Role of platelet activating factor in the intestinal epithelial secretory and Chinese hamster ovary cell cytoskeletal responses to cholera toxin.

    OpenAIRE

    Guerrant, R L; Fang, G D; Thielman, N M; Fonteles, M C

    1994-01-01

    With the recent heightened concern about cholera around the world come new questions about the mechanism by which cholera toxin causes diarrhea. Peterson and Ochoa have suggested that prostaglandin synthesis is key to both the intestinal epithelial secretory and the CHO cell responses to cholera toxin [Peterson, J. W. and Ochoa, G. (1989) Science 245, 857-859]. Because platelet activating factor (PAF) can be a potent stimulus for prostaglandin synthesis, we examined its role in the intestinal...

  16. Splenic embolization in a Jehovah's Witness: role of recombinant human factor VIIa.

    Science.gov (United States)

    Mindikoglu, Ayse L; Anantharaju, Abhinandana; George, Magdalene; Leone, Nancy; Bejna, Judy; Van Thiel, David H

    2003-01-01

    A case of a 50-year-old Jehovah's Witness with cryptogenic cirrhosis, severe portal hypertension and a coagulopathy, who underwent splenic embolization to improve the platelet count after receiving recombinant human Factor VIIa, is reported. Following the infusion of recombinant human Factor VIIa, the coagulopathy was rapidly corrected and it became possible to safely embolize her spleen. The changes in prothrombin time, international normalized ratio and activated partial thromboplastin time as well as thrombomodulin, tissue factor and plasminogen activator inhibitor after the infusion are presented. As a result of the splenic embolization, her platelet count normalized and she has been listed for liver transplantation.

  17. The Multifaceted Effects of Granulocyte Colony-Stimulating Factor in Immunomodulation and Potential Roles in Intestinal Immune Homeostasis

    Science.gov (United States)

    Martins, Andrew; Han, Jiahuai; Kim, Sung O.

    2010-01-01

    Summary The three colony-stimulating factors, GM-CSF, M-CSF and G-CSF, have been regarded as immunostimulators due to their role in granulocyte and myeloid hematopoiesis and immune function. However, unlike GM-CSF and M-CSF, G-CSF possesses immunosuppressive effects on other immune cells including monocytes/macrophages, dendritic cells and T lymphocytes when exogenously administered. Given the immunomodulatory effects of exogenous G-CSF, endogenous G-CSF may also play an important role in maintaining local immune homeostasis in tissue where it is highly and constitutively produced. This review highlights the potential role of G-CSF in immunomodulation and intestinal immune homeostasis. PMID:20681025

  18. In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1

    Directory of Open Access Journals (Sweden)

    Zannini Mariastella

    2011-02-01

    Full Text Available Abstract Background The transcription factor Nkx2-1 (also known as TTF-1, Titf1 or T/EBP contains two apparently redundant activation domains and is post-translationally modified by phosphorylation. We have generated mouse mutant strains to assess the roles of the two activation domains and of phosphorylation in mouse development and differentiation. Results Mouse strains expressing variants of the transcription factor Nkx2-1 deleted of either activation domain have been constructed. Phenotypic analysis shows for each mutant a distinct set of defects demonstrating that distinct portions of the protein endow diverse developmental functions of Nkx2-1. Furthermore, a mouse strain expressing a Nkx2-1 protein mutated in the phosphorylation sites shows a thyroid gland with deranged follicular organization and gene expression profile demonstrating the functional role of phosphorylation in Nkx2-1. Conclusions The pleiotropic functions of Nkx2-1 are not all due to the protein as a whole since some of them can be assigned to separate domains of the protein or to specific post-translational modifications. These results have implication for the evolutionary role of mutations in transcription factors.

  19. The affect of vision and compassion upon role factors in physician leadership.

    Science.gov (United States)

    Quinn, Joann F

    2015-01-01

    The career path for many professionals is often into a leadership role, yet many professionals do not have the competencies or inclination to lead. This study explores physician leaders as a representative group of professionals. While there have been many efforts at understanding the characteristics of effective physician leaders, a greater understanding is needed on the nature of physician leadership. The largest healthcare organization for physician leaders in the United States was surveyed to gain a greater understanding of the nature of leadership. Partial Lease Squares (PLS) was used to analyze results from 677 online surveys to understand the causal relationship of role conflict and role endorsement to participation. The findings reveal the mediating influence that positivity exerts upon participation, and offers health care leaders an opportunity to increase understanding of the social identification process that leads a higher level of professional participation, which may increase effectiveness for physicians in leadership.

  20. Prevention of relapse in patients with congestive heart failure: the role of precipitating factors

    NARCIS (Netherlands)

    J. Feenstra; D.E. Grobbee (Diederick); F.A.M. Jonkman (Fokke); A.W. Hoes (Arno); B.H.Ch. Stricker (Bruno)

    1998-01-01

    textabstractRelapse of congestive heart failure (CHF) frequently occurs and has serious consequences in terms of morbidity, mortality, and health care expenditure. Many studies have investigated the aetiological and prognostic factors of CHF, but there are only