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Sample records for laminin receptor carries

  1. Laminin binding protein, 34/67 laminin receptor, carries stage-specific embryonic antigen-4 epitope defined by monoclonal antibody Raft.2

    International Nuclear Information System (INIS)

    Katagiri, Yohko U.; Kiyokawa, Nobutaka; Nakamura, Kyoko; Takenouchi, Hisami; Taguchi, Tomoko; Okita, Hajime; Umezawa, Akihiro; Fujimoto, Junichiro

    2005-01-01

    We previously produced monoclonal antibodies against the detergent-insoluble microdomain, i.e., the raft microdomain, of the human renal cancer cell line ACHN. Raft.2, one of these monoclonal antibodies, recognizes sialosyl globopentaosylceramide, which has the stage-specific embryonic antigen (SSEA)-4 epitope. Although the mouse embryonal carcinoma (EC) cell line F9 does not express SSEA-4, some F9 cells stained with Raft.2. Western analysis and matrix-assisted laser desorption ionization-time of flight mass spectrometry identified the Raft.2 binding molecule as laminin binding protein (LBP), i.e., 34/67 laminin receptor. Weak acid treatment or digestion with Clostridium perfringens sialidase reduced Raft.2 binding to LBP on nitrocellulose sheets and [ 14 C]galactose was incorporated into LBP, indicating LBP to have a sialylated carbohydrate moiety. Subcellular localization analysis by sucrose density-gradient centrifugation and examination by confocal microscopy revealed LBP to be localized on the outer surface of the plasma membrane. An SSEA-4-positive human EC cell line, NCR-G3 cells, also expressed Raft.2-binding LBP

  2. Role of laminin receptor in tumor cell migration

    DEFF Research Database (Denmark)

    Wewer, U M; Taraboletti, G; Sobel, M E

    1987-01-01

    Polyclonal antisera were made against biochemically purified laminin receptor protein as well as against synthetic peptides deduced from a complementary DNA clone corresponding to the COOH-terminal end of the laminin receptor (U.M. Wewer et al., Proc. Natl. Acad. Sci. USA, 83: 7137-7141, 1986......). These antisera were used to study the potential role of laminin receptor in laminin-mediated attachment and haptotactic migration of human A2058 melanoma cells. The anti-laminin receptor antisera reacted with the surface of suspended, nonpermeabilized melanoma and carcinoma cells. The anti-laminin receptor...... antisera blocked the surface interaction of A2058 cells with endogenous laminin, resulting in the inhibition of laminin-mediated cell attachment. The A2058 melanoma cells migrated toward a gradient of solid phase laminin or fibronectin (haptotaxis). Anti-laminin antiserum abolished haptotaxis on laminin...

  3. Laminins

    DEFF Research Database (Denmark)

    Rasmussen, Daniel Guldager Kring; Karsdal, Morten Asser

    2016-01-01

    Laminins are a major constituent of the basement membrane which is an intricate meshwork of proteins separating the epithelium, mesothelium and endothelium from connective tissue. There are 15 different laminins each consisting of a unique combination of 3 subchains. The combination of chains con...

  4. Crystal Structure of the Human Laminin Receptor Precursor

    Energy Technology Data Exchange (ETDEWEB)

    Jamieson,K.; Wu, J.; Hubbard, S.; Meruelo, D.

    2008-01-01

    The human laminin receptor (LamR) interacts with many ligands, including laminin, prions, Sindbis virus, and the polyphenol (-)-epigallocatechin-3-gallate (EGCG), and has been implicated in a number of diseases. LamR is overexpressed on tumor cells, and targeting LamR elicits anti-cancer effects. Here, we report the crystal structure of human LamR, which provides insights into its function and should facilitate the design of novel therapeutics targeting LamR.

  5. Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle cell adhesion to laminin.

    Science.gov (United States)

    Udani, M; Zen, Q; Cottman, M; Leonard, N; Jefferson, S; Daymont, C; Truskey, G; Telen, M J

    1998-01-01

    Sickle red cells bind significant amounts of soluble laminin, whereas normal red cells do not. Solid phase assays demonstrate that B-CAM/LU binds laminin on intact sickle red cells and that red cell B-CAM/LU binds immobilized laminin, whereas another putative laminin binding protein, CD44, does not. Ligand blots also identify B-CAM/LU as the only erythrocyte membrane protein(s) that binds laminin. Finally, transfection of murine erythroleukemia cells with human B-CAM cDNA induces binding of both soluble and immobilized laminin. Thus, B-CAM/LU appears to be the major laminin-binding protein of sickle red cells. Previously reported overexpression of B-CAM/LU by epithelial cancer cells suggests that this protein may also serve as a laminin receptor in malignant tumors. PMID:9616226

  6. Intestinal epithelial restitution. Involvement of specific laminin isoforms and integrin laminin receptors in wound closure of a transformed model epithelium

    DEFF Research Database (Denmark)

    Lotz, M M; Nusrat, A; Madara, J L

    1997-01-01

    laminins 5, 6, and 7 as indicated by immunostaining using laminin subunit-specific monoclonal antibodies (MAbs). A MAb (BM2) specific for the laminin alpha 3 subunit, a component of laminins 5, 6, and 7, completely inhibited the closure of mechanical wounds in T84 monolayers. Confocal microscopy using MAbs...... BM2 (laminin alpha 3 subunit) and 6F12 (laminin beta 3 subunit) revealed that laminin-5 is deposited in a basal matrix that extends into the wound. The MAbs 4E10 (laminin beta 1 subunit) and C4 (laminin beta 2 subunit) stained the lateral membranes between T84 cells. This staining was enhanced...

  7. Formation of the 67-kDa laminin receptor by acylation of the precursor.

    Science.gov (United States)

    Butò, S; Tagliabue, E; Ardini, E; Magnifico, A; Ghirelli, C; van den Brûle, F; Castronovo, V; Colnaghi, M I; Sobel, M E; Ménard, S

    1998-06-01

    Even though the involvement of the 67-kDa laminin receptor (67LR) in tumor invasiveness has been clearly demonstrated, its molecular structure remains an open problem, since only a full-length gene encoding a 37-kDa precursor protein (37LRP) has been isolated so far. A pool of recently obtained monoclonal antibodies directed against the recombinant 37LRP molecule was used to investigate the processing that leads to the formation of the 67-kDa molecule. In soluble extracts of A431 human carcinoma cells, these reagents recognize the precursor molecule as well as the mature 67LR and a 120-kDa molecule. The recovery of these proteins was found to be strikingly dependent upon the cell solubilization conditions: the 67LR is soluble in NP-40-lysis buffer whereas the 37LRP is NP-40-insoluble. Inhibition of 67LR formation by cerulenin indicates that acylation is involved in the processing of the receptor. It is likely a palmitoylation process, as indicated by sensitivity of NP-40-soluble extracts to hydroxylamine treatment. Immunoblotting assays performed with a polyclonal serum directed against galectin3 showed that both the 67- and the 120-kDa proteins carry galectin3 epitopes whereas the 37LRP does not. These data suggest that the 67LR is a heterodimer stabilized by strong intramolecular hydrophobic interactions, carried by fatty acids bound to the 37LRP and to a galectin3 cross-reacting molecule.

  8. Disruption of the 37-kDa/67-kDa laminin receptor gene in bovine ...

    African Journals Online (AJOL)

    ... gene encoding for the prion binding site in bovine fetal fibroblasts. The heterozygous BFF are ready to be used in producing homozygous cattle, which will be applied to study the interaction between prion and the 37-kDa/67-kDa LRP/LR. Key words: Prion, PrPC, PrPSc, 37-kDa/67-kDa laminin receptor, gene targeting.

  9. Downregulation of the non-integrin laminin receptor reduces cellular viability by inducing apoptosis in lung and cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Kiashanee Moodley

    Full Text Available The non-integrin laminin receptor, here designated the 37-kDa/67-kDa laminin receptor (LRP/LR, is involved in many physiologically relevant processes, as well as numerous pathological conditions. The overexpression of LRP/LR on various cancerous cell lines plays critical roles in tumour metastasis and angiogenesis. This study investigated whether LRP/LR is implicated in the maintenance of cellular viability in lung and cervical cancer cell lines. Here we show a significant reduction in cellular viability in the aforementioned cell lines as a result of the siRNA-mediated downregulation of LRP. This reduction in cellular viability is due to increased apoptotic processes, reflected by the loss of nuclear integrity and the significant increase in the activity of caspase-3. These results indicate that LRP/LR is involved in the maintenance of cellular viability in tumorigenic lung and cervix uteri cells through the blockage of apoptosis. Knockdown of LRP/LR by siRNA might represent an alternative therapeutic strategy for the treatment of lung and cervical cancer.

  10. Seventeen copies of the human 37 kDa laminin receptor precursor/p40 ribosome-associated protein gene are processed pseudogenes arisen from retropositional events

    DEFF Research Database (Denmark)

    Jackers, P; Clausse, N; Fernandez, M

    1996-01-01

    A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40). Interestingly, increased expression of this polypeptide (37LRP/p40) is consistently observed...

  11. Key region of laminin receptor 1 for interaction with human period 1

    African Journals Online (AJOL)

    GREGORY

    2010-09-20

    Sep 20, 2010 ... acids) through yeast two-hybrid system in the present study. And we identified the ... the cell surface and functions as a membrane receptor for the adhesive ..... Circadian modulation of dopamine receptor responsiveness in ...

  12. A simplified laminin nomenclature

    DEFF Research Database (Denmark)

    Aumailley, Monique; Bruckner-Tudermann, Leena; Carter, William G.

    2005-01-01

    A simplification of the laminin nomenclature is presented. Laminins are multidomain heterotrimers composed of alpha, beta and gamma chains. Previously, laminin trimers were numbered with Arabic numerals in the order discovered, that is laminins-1 to -5. We introduce a new identification system fo...

  13. Carry

    DEFF Research Database (Denmark)

    Koijen, Ralph S.J.; Moskowitz, Tobias J.; Heje Pedersen, Lasse

    that include global equities, global bonds, currencies, commodities, US Treasuries, credit, and equity index options. This predictability underlies the strong returns to "carry trades" that go long high-carry and short low-carry securities, applied almost exclusively to currencies, but shown here...

  14. Oxygen partial pressure modulates 67-kDa laminin receptor expression, leading to altered activity of the green tea polyphenol, EGCG.

    Science.gov (United States)

    Tsukamoto, Shuntaro; Yamashita, Shuya; Kim, Yoon Hee; Kumazoe, Motofumi; Huang, Yuhui; Yamada, Koji; Tachibana, Hirofumi

    2012-09-21

    (-)-Epigallocatechin-3-O-gallate (EGCG) exhibits anti-tumor activity mediated via the 67-kDa laminin receptor (67LR). In this study, we found that 67LR protein levels are reduced by exposure to low O(2) levels (5%), without affecting the expression of HIF-1α. We also found that EGCG-induced anti-cancer activity is abrogated under low O(2) levels (5%) in various cancer cells. Notably, treatment with the proteasome inhibitor, prevented down-regulation of 67LR and restored sensitivity to EGCG under 5% O(2). In summary, 67LR expression is highly sensitive to O(2) partial pressure, and the activity of EGCG can be regulated in cancer cells by O(2) partial pressure. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. Carry

    DEFF Research Database (Denmark)

    Koijen, Ralph S.J.; Moskowitz, Tobias; Pedersen, Lasse Heje

    2018-01-01

    -sectionally and in time series for a host of different asset classes, including global equities, global bonds, commodities, US Treasuries, credit, and options. Carry is not explained by known predictors of returns from these asset classes, and it captures many of these predictors, providing a unifying framework...... for return predictability. We reject a generalized version of Uncovered Interest Parity and the Expectations Hypothesis in favor of models with varying risk premia, in which carry strategies are commonly exposed to global recession, liquidity, and volatility risks, though none fully explains carry’s premium....

  16. Laminin-dependent and laminin-independent adhesion of human melanoma cells to sulfatides

    DEFF Research Database (Denmark)

    Roberts, D D; Wewer, U M; Liotta, L A

    1988-01-01

    Sulfatides (galactosylceramide-I3-sulfate) but not neutral glycolipids or gangliosides adsorbed on plastic promote adhesion of the human melanoma cell line G361. Direct adhesion of G361 cells requires densities of sulfatide greater than 1 pmol/mm2. In the presence of laminin, however, specific...... adhesion of G361 cells to sulfatide or seminolipid (galactosylalkylacyl-glycerol-I3-sulfate) but not to other lipids is strongly stimulated and requires only 25 fmol/mm2 of adsorbed lipid. The effects of laminin and sulfatide on adhesion are synergistic, suggesting that laminin is mediating adhesion...... by cross-linking receptors on the melanoma cell surface to sulfatide adsorbed on the plastic. Although thrombospondin binds to sulfatides and G361 cells, it does not enhance, but rather inhibits direct and laminin-dependent G361 cell adhesion to sulfatide. In contrast, C32 melanoma cells also adhere...

  17. Green tea polyphenol epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor on lipopolysaccharide-stimulated dendritic cells

    International Nuclear Information System (INIS)

    Byun, Eui-Baek; Choi, Han-Gyu; Sung, Nak-Yun; Byun, Eui-Hong

    2012-01-01

    Highlights: ► Expressions of CD80, CD86, and MHC class I/II were inhibited by EGCG via 67LR. ► EGCG-treated DCs inhibited LPS-induced pro-inflammatory cytokines via 67LR. ► EGCG-treated DCs inhibited MAPKs activation and NF-κB p65 translocation via 67LR. ► EGCG elevated the expression of the Tollip protein through 67LR in DCs. -- Abstract: Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to down-regulate inflammatory responses in dendritic cells (DCs); however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor. In this study, we showed the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by EGCG in DCs. The expressions of CD80, CD86, and MHC class I and II, which are molecules essential for antigen presentation by DCs, were inhibited by EGCG via 67LR. In addition, EGCG-treated DCs inhibited lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) and activation of mitogen-activated protein kinases (MAPKs), e.g., extracellular signal-regulated kinase 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and nuclear factor κB (NF-κB) p65 translocation through 67LR. Interestingly, we also found that EGCG markedly elevated the expression of the Tollip protein, a negative regulator of TLR signaling, through 67LR. These novel findings provide new insight into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and consequent inflammatory responses that are implicated in the development and progression of many chronic diseases.

  18. Green tea polyphenol epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor on lipopolysaccharide-stimulated dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Eui-Baek [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Choi, Han-Gyu [Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Nak-Yun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Hong, E-mail: ehbyun80@gmail.com [Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of)

    2012-10-05

    Highlights: Black-Right-Pointing-Pointer Expressions of CD80, CD86, and MHC class I/II were inhibited by EGCG via 67LR. Black-Right-Pointing-Pointer EGCG-treated DCs inhibited LPS-induced pro-inflammatory cytokines via 67LR. Black-Right-Pointing-Pointer EGCG-treated DCs inhibited MAPKs activation and NF-{kappa}B p65 translocation via 67LR. Black-Right-Pointing-Pointer EGCG elevated the expression of the Tollip protein through 67LR in DCs. -- Abstract: Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to down-regulate inflammatory responses in dendritic cells (DCs); however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor. In this study, we showed the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by EGCG in DCs. The expressions of CD80, CD86, and MHC class I and II, which are molecules essential for antigen presentation by DCs, were inhibited by EGCG via 67LR. In addition, EGCG-treated DCs inhibited lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-{alpha}, interleukin [IL]-1{beta}, and IL-6) and activation of mitogen-activated protein kinases (MAPKs), e.g., extracellular signal-regulated kinase 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and nuclear factor {kappa}B (NF-{kappa}B) p65 translocation through 67LR. Interestingly, we also found that EGCG markedly elevated the expression of the Tollip protein, a negative regulator of TLR signaling, through 67LR. These novel findings provide new insight into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and consequent inflammatory responses that are implicated in the development and progression of many chronic diseases.

  19. Synergetic downregulation of 67 kDa laminin receptor by the green tea (Camellia sinensis secondary plant compound epigallocatechin gallate: a new gateway in metastasis prevention?

    Directory of Open Access Journals (Sweden)

    Müller Jakob

    2012-12-01

    Full Text Available Abstract Background In traditional Chinese medicine, green tea is considered to have a life-prolonging effect, possibly as a result of its rich content of antioxidant tea polyphenols, and hence has the potential to prevent cancer. This study investigated the role of the major tea secondary plant compound epigallocatechin gallate (EGCG for its inhibitory effects on the metastasis-associated 67 kDa laminin receptor (67LR. Methods To clarify the impact of EGCG on siRNA-silenced expression of 67LR, we applied an adenoviral-based intestinal in vitro knockdown model, porcine IPEC-J2 cells. Quantitative real-time polymerase chain reaction was performed to analyze 67LR gene expression following treatment with physiological and pharmacological concentrations of EGCG (1.0 g/l, 0.1 g/l, 0.02 g/l and 0.002 g/l. Results We report co-regulation of EGCG and 67LR, which is known to be an EGCG receptor. siRNA selectively and highly significantly suppressed expression of 67LR under the impact of EGCG in a synergetic manner. Conclusions Our findings suggest that 67LR expression is regulated by EGCG via a negative feedback loop. The explicit occurrence of this effect in synergy with a small RNA pathway and a plant-derived drug reveals a new mode of action. Our findings may help to provide insights into the many unsolved health-promoting activities of other natural pharmaceuticals.

  20. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages.

    Science.gov (United States)

    Wang, Qi-Ming; Wang, Hao; Li, Ya-Fei; Xie, Zhi-Yong; Ma, Yao; Yan, Jian-Jun; Gao, Yi Fan Wei; Wang, Ze-Mu; Wang, Lian-Sheng

    2016-01-01

    It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque. © 2016 The Author(s) Published by S. Karger AG, Basel.

  1. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages

    Directory of Open Access Journals (Sweden)

    Qi-Ming Wang

    2016-11-01

    Full Text Available Background/Aims: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer and MMPs (matrix metalloproteinases by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA. Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. Results: We showed that EGCG (10-50µmol/L significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2, p38 and c-Jun N-terminal kinase (JNK in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Conclusion: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.

  2. Dystroglycan loss disrupts polarity and beta-casein induction inmammary epithelial cells by perturbing laminin anchoring

    Energy Technology Data Exchange (ETDEWEB)

    Weir, M. Lynn; Oppizzi, Maria Luisa; Henry, Michael D.; Onishi,Akiko; Campbell, Kevin P.; Bissell, Mina J.; Muschler, John L.

    2006-02-17

    Precise contact between epithelial cells and their underlying basement membrane is critical to the maintenance of tissue architecture and function. To understand the role that the laminin receptor dystroglycan (DG) plays in these processes, we assayed cell responses to laminin-111 following conditional ablation of DG expression in cultured mammary epithelial cells (MECs). Strikingly, DG loss disrupted laminin-111-induced polarity and {beta}-casein production, and abolished laminin assembly at the step of laminin binding to the cell surface. DG re-expression restored these deficiencies. Investigations of mechanism revealed that DG cytoplasmic sequences were not necessary for laminin assembly and signaling, and only when the entire mucin domain of extracellular DG was deleted did laminin assembly not occur. These results demonstrate that DG is essential as a laminin-111 co-receptor in MECs that functions by mediating laminin anchoring to the cell surface, a process that allows laminin polymerization, tissue polarity, and {beta}-casein induction. The observed loss of laminin-111 assembly and signaling in DG-/-MECs provides insights into the signaling changes occurring in breast carcinomas and other cancers, where DG's laminin-binding function is frequently defective.

  3. Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization

    DEFF Research Database (Denmark)

    Henry, M D; Satz, J S; Brakebusch, C

    2001-01-01

    Dystroglycan (DG) is a cell surface receptor for several extracellular matrix (ECM) molecules including laminins, agrin and perlecan. Recent data indicate that DG function is required for the formation of basement membranes in early development and the organization of laminin on the cell surface...... integrin-deficient ES cells, laminin-1 binds to the cell surface, but fails to organize into more morphologically complex structures. This result indicates that beta1 integrin function is required after DG function in the cell surface-mediated laminin assembly process. In perlecan-deficient ES cells......, the formation of complex laminin-1 structures is defective, implicating perlecan in the laminin matrix assembly process. Moreover, laminin and perlecan reciprocally modulate the organization of the other on the cell surface. Taken together, the data support a model whereby DG serves as a receptor essential...

  4. Interaction of human laminin receptor with Sup35, the [PSI⁺] prion-forming protein from S. cerevisiae: a yeast model for studies of LamR interactions with amyloidogenic proteins.

    Directory of Open Access Journals (Sweden)

    Christine Pampeno

    Full Text Available The laminin receptor (LamR is a cell surface receptor for extracellular matrix laminin, whereas the same protein within the cell interacts with ribosomes, nuclear proteins and cytoskeletal fibers. LamR has been shown to be a receptor for several bacteria and viruses. Furthermore, LamR interacts with both cellular and infectious forms of the prion protein, PrP(C and PrP(Sc. Indeed, LamR is a receptor for PrP(C. Whether LamR interacts with PrP(Sc exclusively in a capacity of the PrP receptor, or LamR specifically recognizes prion determinants of PrP(Sc, is unclear. In order to explore whether LamR has a propensity to interact with prions and amyloids, we examined LamR interaction with the yeast prion-forming protein, Sup35. Sup35 is a translation termination factor with no homology or functional relationship to PrP. Plasmids expressing LamR or LamR fused with the green fluorescent protein (GFP were transformed into yeast strain variants differing by the presence or absence of the prion conformation of Sup35, respectively [PSI⁺] and [psi⁻]. Analyses by immunoprecipitation, centrifugal fractionation and fluorescent microscopy reveal interaction between LamR and Sup35 in [PSI⁺] strains. The presence of [PSI⁺] promotes LamR co-precipitation with Sup35 as well as LamR aggregation. In [PSI⁺] cells, LamR tagged with GFP or mCherry forms bright fluorescent aggregates that co-localize with visible [PSI⁺] foci. The yeast prion model will facilitate studying the interaction of LamR with amyloidogenic prions in a safe and easily manipulated system that may lead to a better understanding and treatment of amyloid diseases.

  5. Intrathymic laminin-mediated interactions: role in T cell migration and development

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    Wilson eSavino

    2015-11-01

    Full Text Available Intrathymic T cell differentiation is a key process for the development and maintenance of cell-mediated immunity, and occurs concomitantly to highly regulated migratory events. We have proposed a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comprises interactions mediated by laminins, a heterotrimeric protein family of the extracellular matrix. Several laminins are expressed in the thymus, being produced by microenvironmental cells, particularly thymic epithelial cells. Also, thymocytes and epithelial cells express integrin-type laminin receptors. Functionally, it has been reported that the dy/dy mutant mouse (lacking the laminin isoform 211 exhibits defective thymocyte differentiation. Several data show haptotactic effects of laminins upon thymocytes, as well as their adhesion on thymic epithelial cells; both effects being prevented by anti-laminin or anti-laminin receptor antibodies. Interestingly, laminin synergizes with chemokines to enhance thymocyte migration, whereas classe-3 semaphorins and B ephrins, which exhibit chemorepulsive effects in the thymus, downregulate laminin-mediated migratory responses of thymocytes. More recently, we showed that knocking down the ITGA6 gene (which encodes the α6 integrin chain of laminin receptors in human thymic epithelial cells, modulates a large number of cell-migration related genes, and results in changes of adhesion pattern of thymocytes onto the thymic epithelium. Overall, laminin-mediated interactions can be placed at the cross-road of the multivectorial process of thymocyte migration, with a direct influence per se, as well as by modulating other molecular interactions associated with the intrathymic trafficking events.

  6. Laminin isoforms differentially regulate adhesion, spreading, proliferation, and ERK activation of β1 integrin-null cells

    International Nuclear Information System (INIS)

    Kikkawa, Yamato; Yu, Hao; Genersch, Elke; Sanzen, Noriko; Sekiguchi, Kiyotoshi; Faessler, Reinhard; Campbell, Kevin P.; Talts, Jan F.; Ekblom, Peter

    2004-01-01

    The presence of many laminin receptors of the β1 integrin family on most cells makes it difficult to define the biological functions of other major laminin receptors such as integrin α6β4 and dystroglycan. We therefore tested the binding of a β1 integrin-null cell line GD25 to four different laminin variants. The cells were shown to produce dystroglycan, which based on affinity chromatography bound to laminin-1, -2/4, and -10/11, but not to laminin-5. The cells also expressed the integrin α6Aβ4A variant. GD25 β1 integrin-null cells are known to bind poorly to laminin-1, but we demonstrate here that these cells bind avidly to laminin-2/4, -5, and -10/11. The initial binding at 20 min to each of these laminins could be inhibited by an integrin α6 antibody, but not by a dystroglycan antibody. Hence, integrin α6Aβ4A of GD25 cells was identified as a major receptor for initial GD25 cell adhesion to three out of four tested laminin isoforms. Remarkably, cell adhesion to laminin-5 failed to promote cell spreading, proliferation, and extracellular signal-regulated kinase (ERK) activation, whereas all these responses occurred in response to adhesion to laminin-2/4 or -10/11. The data establish GD25 cells as useful tools to define the role integrin α6Aβ4A and suggest that laminin isoforms have distinctly different capacities to promote cell adhesion and signaling via integrin α6Aβ4A

  7. Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets

    Science.gov (United States)

    Stipp, Christopher S.

    2010-01-01

    Within the integrin family of cell adhesion receptors, integrins α3β1, α6β1, α6β4 and α7β1 make up a laminin-binding subfamily. The literature is divided on the role of these laminin-binding integrins in metastasis, with different studies indicating either pro- or antimetastatic functions. The opposing roles of the laminin-binding integrins in different settings might derive in part from their unusually robust associations with tetraspanin proteins. Tetraspanins organise integrins into multiprotein complexes within discrete plasma membrane domains termed tetraspanin-enriched microdomains (TEMs). TEM association is crucial to the strikingly rapid cell migration mediated by some of the laminin-binding integrins. However, emerging data suggest that laminin-binding integrins also promote the stability of E-cadherin-based cell–cell junctions, and that tetraspanins are essential for this function as well. Thus, TEM association endows the laminin-binding integrins with both pro-invasive functions (rapid migration) and anti-invasive functions (stable cell junctions), and the composition of TEMs in different cell types might help determine the balance between these opposing activities. Unravelling the tetraspanin control mechanisms that regulate laminin-binding integrins will help to define the settings where inhibiting the function of these integrins would be helpful rather than harmful, and may create opportunities to modulate integrin activity in more sophisticated ways than simple functional blockade. PMID:20078909

  8. Merosin/laminin-2 and muscular dystrophy

    DEFF Research Database (Denmark)

    Wewer, U M; Engvall, E

    1996-01-01

    structural organization of domains, some of which have been assigned biological activities, including self-assembly and interactions with other proteins. The particular importance of laminins for the formation and stability of cell adhesion complexes is highlighted in severe inherited diseases of muscle...... and skin. Merosin is the collective name for laminins that share a common subunit, the laminin alpha 2 chain. Merosin-deficient congenital muscular dystrophy (CMD) is caused by mutations in the laminin alpha 2 chain gene. The skin disease Herlitz junctional epidermolysis bullosa is caused by mutations...

  9. Skeletal muscle laminin and MDC1A: pathogenesis and treatment strategies

    Directory of Open Access Journals (Sweden)

    Gawlik Kinga I

    2011-03-01

    Full Text Available Abstract Laminin-211 is a cell-adhesion molecule that is strongly expressed in the basement membrane of skeletal muscle. By binding to the cell surface receptors dystroglycan and integrin α7β1, laminin-211 is believed to protect the muscle fiber from damage under the constant stress of contractions, and to influence signal transmission events. The importance of laminin-211 in skeletal muscle is evident from merosin-deficient congenital muscular dystrophy type 1A (MDC1A, in which absence of the α2 chain of laminin-211 leads to skeletal muscle dysfunction. MDC1A is the commonest form of congenital muscular dystrophy in the European population. Severe hypotonia, progressive muscle weakness and wasting, joint contractures and consequent impeded motion characterize this incurable disorder, which causes great difficulty in daily life and often leads to premature death. Mice with laminin α2 chain deficiency have analogous phenotypes, and are reliable models for studies of disease mechanisms and potential therapeutic approaches. In this review, we introduce laminin-211 and describe its structure, expression pattern in developing and adult muscle and its receptor interactions. We will also discuss the molecular pathogenesis of MDC1A and advances toward the development of treatment.

  10. Sensitivity of C6 Glioma Cells Carrying the Human Poliovirus Receptor to Oncolytic Polioviruses.

    Science.gov (United States)

    Sosnovtseva, A O; Lipatova, A V; Grinenko, N F; Baklaushev, V P; Chumakov, P M; Chekhonin, V P

    2016-10-01

    A humanized line of rat C6 glioma cells expressing human poliovirus receptor was obtained and tested for the sensitivity to oncolytic effects of vaccine strains of type 1, 2, and 3 polioviruses. Presentation of the poliovirus receptor on the surface of C6 glioma cells was shown to be a necessary condition for the interaction of cells with polioviruses, but insufficient for complete poliovirus oncolysis.

  11. Differential expression of integrins and laminin-5 in normal oral epithelia

    DEFF Research Database (Denmark)

    Thorup, A K; Dabelsteen, Erik; Schou, S

    1997-01-01

    beta 1 and beta 4 integrins are receptors on epithelial cells mediating cell-extracellular matrix adhesion. Furthermore, alpha 2 beta 1 and alpha 3 beta 1 contribute to cell-cell adhesion. Laminin-5 in epithelial basement membranes (BMs) is a ligand for alpha 6 beta 4 and alpha 3 beta 1. Expressi...

  12. Template Based Design of Anti-Metastatic Drugs from the Active Conformation of Laminin Peptide II

    Science.gov (United States)

    2001-01-01

    affords lactam 10 as a 7 X=OH, Y=H Ph2BuSiO HH separable mixture of diastereomers rather 8 x = CI, Y NO2 9 10 than tricycle 11. Treatment of 10 with base...of mimotopes. explain the fact that pre- treatment of laminin with Amongst the phage that mimic the LBP൜ 9 peptide G in solution increases its...of ca6 - Colnagi, M. I. (1994). The simultaneous expression of integrin receptors and of mRNA encoding the puta- c-erbB-2 oncoprotein and laminin

  13. Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function.

    Directory of Open Access Journals (Sweden)

    Kihoon Nam

    Full Text Available Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration.

  14. Relationship between laminin binding capacity and laminin expression on tumor cells sensitive or resistant to natural cell-mediated cytotoxicity

    International Nuclear Information System (INIS)

    Laybourn, K.A.; Varani, J.; Fligiel, S.E.G.; Hiserodt, J.C.

    1986-01-01

    Previous studies have identified the presence of laminin binding sites on murine NK and NC sensitive tumor cells by 125 I-laminin binding and laminin induced cell-cell aggregation. The finding that the addition of exogenous laminin inhibits NK/NC binding to sensitive tumor cells suggests laminin binding sites may serve as target antigens for NK cells. The present study extends earlier reports by analyzing a large panel of tumor cells for laminin binding capacity, laminin expression and sensitivity to NK/NC killing. The data indicate that all tumor cells which bind to NK/NC cells (8 lines tested) express laminin binding sites. All of these tumor cells were capable of competing for NK lysis of YAC-1 cells in cold target competition assays, and all bound enriched NK cells in direct single cell binding assays. In contrast, tumor cells expressing high levels of surface laminin (B16 melanomas, C57B1/6 fibrosarcomas, and RAS transfected 3T3 fibroblasts) but low levels of laminin binding capacity did not bind NK/NC cells and were resistant to lysis. These data support the hypothesis that expression of laminin/laminin binding sites may contribute to tumor cell sensitivity to NK/NC binding and/or killing

  15. Distinct antigenic characteristics of murine parietal yolk sac laminin

    DEFF Research Database (Denmark)

    Wewer, U M; Tichy, D; Damjanov, A

    1987-01-01

    Two monoclonal antibodies (LAM-A and LAM-B) specific for laminin from normal and neoplastic parietal yolk sac (PYS) cells were produced in rats immunized with a mouse yolk sac carcinoma cell line. Both antibodies immunoprecipitated the 400,000- and 200,000-Da chains of laminin and reacted...... with purified PYS laminin in ELISA. LAM-A reacted with mouse and rat PYS laminin, whereas LAM-B reacted only with mouse PYS laminin. Formaldehyde- and methanol-fixed adult and fetal somatic tissues were immunohistochemically unreactive with either of the two antibodies. In acetone-fixed tissue sections, both...

  16. A fractal nature for polymerized laminin.

    Directory of Open Access Journals (Sweden)

    Camila Hochman-Mendez

    Full Text Available Polylaminin (polyLM is a non-covalent acid-induced nano- and micro-structured polymer of the protein laminin displaying distinguished biological properties. Polylaminin stimulates neuritogenesis beyond the levels achieved by ordinary laminin and has been shown to promote axonal regeneration in animal models of spinal cord injury. Here we used confocal fluorescence microscopy (CFM, scanning electron microscopy (SEM and atomic force microscopy (AFM to characterize its three-dimensional structure. Renderization of confocal optical slices of immunostained polyLM revealed the aspect of a loose flocculated meshwork, which was homogeneously stained by the antibody. On the other hand, an ordinary matrix obtained upon adsorption of laminin in neutral pH (LM was constituted of bulky protein aggregates whose interior was not accessible to the same anti-laminin antibody. SEM and AFM analyses revealed that the seed unit of polyLM was a flat polygon formed in solution whereas the seed structure of LM was highly heterogeneous, intercalating rod-like, spherical and thin spread lamellar deposits. As polyLM was visualized at progressively increasing magnifications, we observed that the morphology of the polymer was alike independently of the magnification used for the observation. A search for the Hausdorff dimension in images of the two matrices showed that polyLM, but not LM, presented fractal dimensions of 1.55, 1.62 and 1.70 after 1, 8 and 12 hours of adsorption, respectively. Data in the present work suggest that the intrinsic fractal nature of polymerized laminin can be the structural basis for the fractal-like organization of basement membranes in the neurogenic niches of the central nervous system.

  17. A fractal nature for polymerized laminin.

    Science.gov (United States)

    Hochman-Mendez, Camila; Cantini, Marco; Moratal, David; Salmeron-Sanchez, Manuel; Coelho-Sampaio, Tatiana

    2014-01-01

    Polylaminin (polyLM) is a non-covalent acid-induced nano- and micro-structured polymer of the protein laminin displaying distinguished biological properties. Polylaminin stimulates neuritogenesis beyond the levels achieved by ordinary laminin and has been shown to promote axonal regeneration in animal models of spinal cord injury. Here we used confocal fluorescence microscopy (CFM), scanning electron microscopy (SEM) and atomic force microscopy (AFM) to characterize its three-dimensional structure. Renderization of confocal optical slices of immunostained polyLM revealed the aspect of a loose flocculated meshwork, which was homogeneously stained by the antibody. On the other hand, an ordinary matrix obtained upon adsorption of laminin in neutral pH (LM) was constituted of bulky protein aggregates whose interior was not accessible to the same anti-laminin antibody. SEM and AFM analyses revealed that the seed unit of polyLM was a flat polygon formed in solution whereas the seed structure of LM was highly heterogeneous, intercalating rod-like, spherical and thin spread lamellar deposits. As polyLM was visualized at progressively increasing magnifications, we observed that the morphology of the polymer was alike independently of the magnification used for the observation. A search for the Hausdorff dimension in images of the two matrices showed that polyLM, but not LM, presented fractal dimensions of 1.55, 1.62 and 1.70 after 1, 8 and 12 hours of adsorption, respectively. Data in the present work suggest that the intrinsic fractal nature of polymerized laminin can be the structural basis for the fractal-like organization of basement membranes in the neurogenic niches of the central nervous system.

  18. Forced expression of laminin β1 in podocytes prevents nephrotic syndrome in mice lacking laminin β2, a model for Pierson syndrome

    Science.gov (United States)

    Suh, Jung Hee; Jarad, George; VanDeVoorde, Rene G.; Miner, Jeffrey H.

    2011-01-01

    Pierson syndrome is a congenital nephrotic syndrome with ocular and neurological defects caused by mutations in LAMB2, the gene encoding the basement membrane protein laminin β2 (Lamβ2). It is the kidney glomerular basement membrane (GBM) that is defective in Pierson syndrome, as Lamβ2 is a component of laminin-521 (LM-521; α5β2γ1), the major laminin in the mature GBM. In both Pierson syndrome and the Lamb2−/− mouse model for this disease, laminin β1 (Lamβ1), a structurally similar homolog of Lamβ2, is marginally increased in the GBM, but it fails to fully compensate for the loss of Lamβ2, leading to the filtration barrier defects and nephrotic syndrome. Here we generated several lines of Lamβ1 transgenic mice and used them to show that podocyte-specific Lamβ1 expression in Lamb2−/− mice abrogates the development of nephrotic syndrome, correlating with a greatly extended lifespan. In addition, the more Lamβ1 was expressed, the less urinary albumin was excreted. Transgenic Lamβ1 expression increased the level of Lamα5 in the GBM of rescued mice, consistent with the desired increased deposition of laminin-511 (α5β1γ1) trimers. Ultrastructural analysis revealed occasional knob-like subepithelial GBM thickening but intact podocyte foot processes in aged rescued mice. These results suggest the possibility that up-regulation of LAMB1 in podocytes, should it become achievable, would likely lessen the severity of nephrotic syndrome in patients carrying LAMB2 mutations. PMID:21876163

  19. Forced expression of laminin beta1 in podocytes prevents nephrotic syndrome in mice lacking laminin beta2, a model for Pierson syndrome.

    Science.gov (United States)

    Suh, Jung Hee; Jarad, George; VanDeVoorde, Rene G; Miner, Jeffrey H

    2011-09-13

    Pierson syndrome is a congenital nephrotic syndrome with ocular and neurological defects caused by mutations in LAMB2, the gene encoding the basement membrane protein laminin β2 (Lamβ2). It is the kidney glomerular basement membrane (GBM) that is defective in Pierson syndrome, as Lamβ2 is a component of laminin-521 (LM-521; α5β2γ1), the major laminin in the mature GBM. In both Pierson syndrome and the Lamb2(-/-) mouse model for this disease, laminin β1 (Lamβ1), a structurally similar homolog of Lamβ2, is marginally increased in the GBM, but it fails to fully compensate for the loss of Lamβ2, leading to the filtration barrier defects and nephrotic syndrome. Here we generated several lines of Lamβ1 transgenic mice and used them to show that podocyte-specific Lamβ1 expression in Lamb2(-/-) mice abrogates the development of nephrotic syndrome, correlating with a greatly extended lifespan. In addition, the more Lamβ1 was expressed, the less urinary albumin was excreted. Transgenic Lamβ1 expression increased the level of Lamα5 in the GBM of rescued mice, consistent with the desired increased deposition of laminin-511 (α5β1γ1) trimers. Ultrastructural analysis revealed occasional knob-like subepithelial GBM thickening but intact podocyte foot processes in aged rescued mice. These results suggest the possibility that up-regulation of LAMB1 in podocytes, should it become achievable, would likely lessen the severity of nephrotic syndrome in patients carrying LAMB2 mutations.

  20. Human umbilical cord mesenchymal stromal cells exhibit immature nucleus pulposus cell phenotype in a laminin-rich pseudo-three-dimensional culture system.

    Science.gov (United States)

    Chon, Brian H; Lee, Esther J; Jing, Liufang; Setton, Lori A; Chen, Jun

    2013-10-02

    Cell supplementation to the herniated or degenerated intervertebral disc (IVD) is a potential strategy to promote tissue regeneration and slow disc pathology. Human umbilical cord mesenchymal stromal cells (HUCMSCs) - originating from the Wharton's jelly - remain an attractive candidate for such endeavors with their ability to differentiate into multiple lineages. Previously, mesenchymal stem cells (MSCs) have been studied as a potential source for disc tissue regeneration. However, no studies have demonstrated that MSCs can regenerate matrix with unique characteristics matching that of immature nucleus pulposus (NP) tissues of the IVD. In our prior work, immature NP cells were found to express specific laminin isoforms and laminin-binding receptors that may serve as phenotypic markers for evaluating MSC differentiation to NP-like cells. The goal of this study is to evaluate these markers and matrix synthesis for HUCMSCs cultured in a laminin-rich pseudo-three-dimensional culture system. HUCMSCs were seeded on top of Transwell inserts pre-coated with Matrigel™, which contained mainly laminin-111. Cells were cultured under hypoxia environment with three differentiation conditions: NP differentiation media (containing 2.5% Matrigel™ solution to provide for a pseudo-three-dimensional laminin culture system) with no serum, or the same media supplemented with either insulin-like growth factor-1 (IGF-1) or transforming growth factor-β1 (TGF-β1). Cell clustering behavior, matrix production and the expression of NP-specific laminin and laminin-receptors were evaluated at days 1, 7, 13 and 21 of culture. Data show that a pseudo-three-dimensional culture condition (laminin-1 rich) promoted HUCMSC differentiation under no serum conditions. Starting at day 1, HUCMSCs demonstrated a cell clustering morphology similar to that of immature NP cells in situ and that observed for primary immature NP cells within the similar laminin-rich culture system (prior study

  1. Lysophosphatidic Acid Upregulates Laminin-332 Expression during A431 Cell Colony Dispersal

    Directory of Open Access Journals (Sweden)

    Hironobu Yamashita

    2010-01-01

    Full Text Available Lysophosphatidic acid (LPA is a bioactive phospholipid that affects various biological functions, such as cell proliferation, migration, survival, wound healing, and tumor invasion through LPA receptors. Previously, we reported that LPA induces A431 colony dispersal, accompanied by disruption of cell-cell contacts and cell migration. However, it remains unclear how LPA affects cell migration and gene expression during A431 colony dispersal. In this paper, we performed cDNA microarray analysis to investigate this question by comparing gene expression between untreated and LPA-treated A431 cells. Interestingly, these results revealed that LPA treatment upregulates several TGF-β1 target genes, including laminin-332 (Ln-332 components (α3, β3, and γ2 chains. Western blot analysis also showed that LPA increased phosphorylation of Smad2, an event that is carried out by TGF-β1 interactions. Among the genes upregulated, we further addressed the role of Ln-332. Real-time PCR analysis confirmed the transcriptional upregulation of all α3, β3, and γ2 chains of Ln-332 by LPA, corresponding to the protein level increases revealed by western blot. Further, the addition of anti-Ln-332 antibody prevented LPA-treated A431 colonies from dispersing. Taken together, our results suggest that LPA-induced Ln-332 plays a significant role in migration of individual cells from A431 colonies.

  2. Anti-laminin-1 Autoantibodies, Pregnancy Loss and Endometriosis

    Directory of Open Access Journals (Sweden)

    Junko Inagaki

    2004-01-01

    Full Text Available Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, α1, β1 and γ1 chains. It is the earliest synthesized network-forming protein during embryogenesis and plays an important role in embryonic development, embryonic implantation and placentation. We have recently shown that IgG anti-laminin-1 antibodies were significantly associated with recurrent first-trimester miscarriages and with subsequent pregnancy outcome. Interestingly, these antibodies were also observed in patients with endometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterine abnormalities. Laminin-α1, -β1 and -γ1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-α1, -β1 and -γ1 chains were localized in the basement membranes of glandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodies from those patients reacted with all laminin-1's chains. ELISA also confirmed that one of the target epitopes for these antibodies was located in a particular region of the laminin-1 molecule, i.e. the carboxyl-terminal globular G domain of α1 chain. IgM monoclonal anti-laminin-1 autoantibody, that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunized with –mouse— laminin-1, caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 antibodies may be important in development of autoimmune-mediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.

  3. Can alterations in integrin and laminin-5 expression be used as markers of malignancy?

    DEFF Research Database (Denmark)

    Thorup, Alis Karabulut; Reibel, J.; Schjødt, Morten

    1998-01-01

    Integrins, laminin-5, cell adhesion molecules, oral, leukoplakia, premalignant, squamous cell carcinomas......Integrins, laminin-5, cell adhesion molecules, oral, leukoplakia, premalignant, squamous cell carcinomas...

  4. Further biochemical characterization of Mycobacterium leprae laminin-binding proteins

    Directory of Open Access Journals (Sweden)

    M.A.M. Marques

    2001-04-01

    Full Text Available It has been demonstrated that the alpha2 chain of laminin-2 present on the surface of Schwann cells is involved in the process of attachment of Mycobacterium leprae to these cells. Searching for M. leprae laminin-binding molecules, in a previous study we isolated and characterized the cationic proteins histone-like protein (Hlp and ribosomal proteins S4 and S5 as potential adhesins involved in M. leprae-Schwann cell interaction. Hlp was shown to bind alpha2-laminins and to greatly enhance the attachment of mycobacteria to ST88-14 Schwann cells. In the present study, we investigated the laminin-binding capacity of the ribosomal proteins S4 and S5. The genes coding for these proteins were PCR amplified and their recombinant products were shown to bind alpha2-laminins in overlay assays. However, when tested in ELISA-based assays and in adhesion assays with ST88-14 cells, in contrast to Hlp, S4 and S5 failed to bind laminin and act as adhesins. The laminin-binding property and adhesin capacity of two basic host-derived proteins were also tested, and only histones, but not cytochrome c, were able to increase bacterial attachment to ST88-14 cells. Our data suggest that the alanine/lysine-rich sequences shared by Hlp and eukaryotic H1 histones might be involved in the binding of these cationic proteins to laminin.

  5. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions.

    Directory of Open Access Journals (Sweden)

    Melanie A Samuel

    Full Text Available As synapses form and mature the synaptic partners produce organizing molecules that regulate each other's differentiation and ensure precise apposition of pre- and post-synaptic specializations. At the skeletal neuromuscular junction (NMJ, these molecules include agrin, a nerve-derived organizer of postsynaptic differentiation, and synaptic laminins, muscle-derived organizers of presynaptic differentiation. Both become concentrated in the synaptic cleft as the NMJ develops and are retained in adulthood. Here, we used mutant mice to ask whether these organizers are also required for synaptic maintenance. Deletion of agrin from a subset of adult motor neurons resulted in the loss of acetylcholine receptors and other components of the postsynaptic apparatus and synaptic cleft. Nerve terminals also atrophied and eventually withdrew from muscle fibers. On the other hand, mice lacking the presynaptic organizer laminin-α4 retained most of the synaptic cleft components but exhibited synaptic alterations reminiscent of those observed in aged animals. Although we detected no marked decrease in laminin or agrin levels at aged NMJs, we observed alterations in the distribution and organization of these synaptic cleft components suggesting that such changes could contribute to age-related synaptic disassembly. Together, these results demonstrate that pre- and post-synaptic organizers actively function to maintain the structure and function of adult NMJs.

  6. The Effect of Laminin-1-Doped Nanoroughened Implant Surfaces: Gene Expression and Morphological Evaluation

    Directory of Open Access Journals (Sweden)

    Humberto Osvaldo Schwartz-Filho

    2012-01-01

    Full Text Available Aim. This study aimed to observe the morphological and molecular effect of laminin-1 doping to nanostructured implant surfaces in a rabbit model. Materials and Methods. Nanostructured implants were coated with laminin-1 (test; dilution, 100 μg/mL and inserted into the rabbit tibiae. Noncoated implants were used as controls. After 2 weeks of healing, the implants were removed and subjected to morphological analysis using scanning electron microscopy (SEM and gene expression analysis using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR. Results. SEM revealed bony tissue attachment for both control and test implants. Real-time RT-PCR analysis showed that the expression of osteoblast markers RUNX-2, osteocalcin, alkaline phosphatase, and collagen I was higher (1.62-fold, 1.53-fold, 1.97-fold, and 1.04-fold, resp. for the implants modified by laminin-1 relative to the control. All osteoclast markers investigated in the study presented higher expression on the test implants than controls as follows: tartrate-resistant acid phosphatase (1.67-fold, calcitonin receptor (1.35-fold, and ATPase (1.25-fold. The test implants demonstrated higher expression of inflammatory markers interleukin-10 (1.53-fold and tumour necrosis factor-α (1.61-fold relative to controls. Conclusion. The protein-doped surface showed higher gene expression of typical genes involved in the osseointegration cascade than the control surface.

  7. An adhesome comprising laminin, dystroglycan and myosin IIA is required during notochord development in Xenopus laevis.

    Science.gov (United States)

    Buisson, Nicolas; Sirour, Cathy; Moreau, Nicole; Denker, Elsa; Le Bouffant, Ronan; Goullancourt, Aline; Darribère, Thierry; Bello, Valérie

    2014-12-01

    Dystroglycan (Dg) is a transmembrane receptor for laminin that must be expressed at the right time and place in order to be involved in notochord morphogenesis. The function of Dg was examined in Xenopus laevis embryos by knockdown of Dg and overexpression and replacement of the endogenous Dg with a mutated form of the protein. This analysis revealed that Dg is required for correct laminin assembly, for cell polarization during mediolateral intercalation and for proper differentiation of vacuoles. Using mutations in the cytoplasmic domain, we identified two sites that are involved in cell polarization and are required for mediolateral cell intercalation, and a site that is required for vacuolation. Furthermore, using a proteomic analysis, the cytoskeletal non-muscle myosin IIA has been identified for the first time as a molecular link between the Dg-cytoplasmic domain and cortical actin. The data allowed us to identify the adhesome laminin-Dg-myosin IIA as being required to maintain the cortical actin cytoskeleton network during vacuolation, which is crucial to maintain the shape of notochordal cells. © 2014. Published by The Company of Biologists Ltd.

  8. Increased Expression of Laminin Subunit Alpha 1 Chain by dCas9-VP160

    OpenAIRE

    Perrin, Arnaud; Rousseau, Jo?l; Tremblay, Jacques P.

    2016-01-01

    Laminin-111 protein complex links the extracellular matrix to integrin α7β1 in sarcolemma, thus replacing in dystrophic muscles links normally insured by the dystrophin complex. Laminin-111 injection in mdx mouse stabilized sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscles from exercised-induced damages. These results suggested that increased laminin-111 is a potential therapy for DMD. Laminin subunit beta 1 and laminin subunit gamma 1 are expressed in adul...

  9. Targeting the Immune System to Fight Cancer Using Chemical Receptor Homing Vectors Carrying Polyinosine/Cytosine (PolyIC)

    International Nuclear Information System (INIS)

    Levitzki, Alexander

    2012-01-01

    Cancer researchers have been looking for ways to harness the immune system and to reinstate immune surveillance, to kill cancer cells without collateral damage. Here we scan current approaches to targeting the immune system against cancer, and emphasize our own approach. We are using chemical vectors attached to a specific ligand, to introduce synthetic dsRNA, polyinosine/cytosine (polyIC), into tumors. The ligand binds to a receptor protein that is overexpressed on the surface of the tumor cells. Upon ligand binding, the receptor complex is internalized, introducing the polyIC into the cell. In this fashion a large amount of synthetic dsRNA can be internalized, leading to the activation of dsRNA-binding proteins, such as dsRNA dependent protein kinase (PKR), Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-1), and melanoma differentiation-associated gene 5 (MDA5). The simultaneous activation of these signaling proteins leads to the rapid demise of the targeted cell and to cytokine secretion. The cytokines lead to a strong bystander effect and to the recruitment of immune cells that converge upon the targeted cells. The bystander effects lead to the destruction of neighboring tumor cells not targeted themselves by the vector. Normal cells, being more robust than tumor cells, survive. This strategy has several advantages: (1) recruitment of the immune system is localized to the tumor. (2) The response is rapid, leading to fast tumor eradication. (3) The bystander effects lead to the eradication of tumor cells not harboring the target. (4) The multiplicity of pro-death signaling pathways elicited by PolyIC minimizes the likelihood of the emergence of resistance. In this chapter we focus on EGFR as the targeted receptor, which is overexpressed in many tumors. In principle, the strategy can be extended to other tumors that overexpress a protein that can be internalized by a ligand, which can be a small molecule, a single chain antibody, or an affibody.

  10. Targeting the immune system to fight cancer using chemical receptor homing vectors carrying Poly Inosine/Cytosine (PolyIC

    Directory of Open Access Journals (Sweden)

    Alexander eLevitzki

    2012-02-01

    Full Text Available Cancer researchers have been looking for ways to harness the immune system and to reinstate immune surveillance, to kill cancer cells without collateral damage. Here we scan current approaches to targeting the immune system against cancer, and emphasize our own approach. We are using chemical vectors attached to a specific ligand, to introduce synthetic dsRNA, poly Inosine/Cytosine (polyIC, into tumors. The ligand binds to a receptor protein that is overexpressed on the surface of the tumor cells. Upon ligand binding, the receptor complex is internalized, introducing the polyIC into the cell. In this fashion a large amount of synthetic dsRNA can be internalized, leading to the activation of dsRNA binding proteins, such as dsRNA dependent protein kinase (PKR, Toll-3 receptor (TLR3, retinoic acid–inducible gene I (RIG-1 and melanoma differentiation–associated gene 5 (MDA5. The simultaneous activation of these signaling proteins leads to the rapid demise of the targeted cell and to cytokine secretion. The cytokines lead to a strong bystander effect and to the recruitment of immune cells that converge upon the targeted cells. The bystander effects lead to the destruction of neighboring tumor cells not targeted themselves by the vector. Normal cells, being more robust than tumor cells, survive. This strategy has several advantages: (1 Recruitment of the immune system is localized to the tumor. (2 The response is rapid, leading to fast tumor eradication. (3 The bystander effects lead to the eradication of tumor cells not harboring the target. (4 The multiplicity of pro-death signaling pathways elicited by PolyIC minimizes the likelihood of the emergence of resistance. In this chapter we focus on EGFR as the targeted receptor, which is overexpressed in many tumors. In principle, the strategy can be extended to other tumors that overexpress a protein that can be internalized by a ligand, which be a small molecule, a single chain antibody or an

  11. Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy.

    Science.gov (United States)

    Tsai, Y-S; Shiau, A-L; Chen, Y-F; Tsai, H-T; Tzai, T-S; Wu, C-L

    2010-01-01

    The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope-modified ones had extended viral tropism to human HER2-expressing bladder cancer cell lines, induced apoptosis, and affected cell cycle progression despite lower viral titers. Moreover, animal studies showed that envelope-modified gammaretroviruses carrying IL-12 gene exerted higher antitumor activity in terms of retarding tumor growth and prolonging the survival of tumor-bearing mice than unmodified ones, which were associated with enhanced tumor cell apoptosis as well as increased intratumoral levels of IL-12, interferon-gamma, IL-1beta, and tumor necrosis factor-alpha proteins. Therefore, the antitumor activity of gammaretroviruses carrying the IL-12 gene was enhanced through genetic modification of the envelope targeting HER2 receptor, which may be a promising strategy for bladder cancer therapy.

  12. Sarcospan integration into laminin-binding adhesion complexes that ameliorate muscular dystrophy requires utrophin and α7 integrin

    Science.gov (United States)

    Marshall, Jamie L.; Oh, Jennifer; Chou, Eric; Lee, Joy A.; Holmberg, Johan; Burkin, Dean J.; Crosbie-Watson, Rachelle H.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene that result in loss of the dystrophin–glycoprotein complex, a laminin receptor that connects the myofiber to its surrounding extracellular matrix. Utrophin, a dystrophin ortholog that is normally localized to the neuromuscular junction, is naturally upregulated in DMD muscle, which partially compensates for the loss of dystrophin. Transgenic overexpression of utrophin causes broad sarcolemma localization of utrophin, restoration of laminin binding and amelioration of disease in the mdx mouse model of DMD. We previously demonstrated that overexpression of sarcospan, a dystrophin- and utrophin-binding protein, ameliorates mdx muscular dystrophy. Sarcospan boosts levels of utrophin to therapeutic levels at the sarcolemma, where attachment to laminin is restored. However, understanding the compensatory mechanism is complicated by concomitant upregulation of α7β1 integrin, which also binds laminin. Similar to the effects of utrophin, transgenic overexpression of α7 integrin prevents DMD disease in mice and is accompanied by increased abundance of utrophin around the extra-synaptic sarcolemma. In order to investigate the mechanisms underlying sarcospan ‘rescue’ of muscular dystrophy, we created double-knockout mice to test the contributions of utrophin or α7 integrin. We show that sarcospan-mediated amelioration of muscular dystrophy in DMD mice is dependent on the presence of both utrophin and α7β1 integrin, even when they are individually expressed at therapeutic levels. Furthermore, we found that association of sarcospan into laminin-binding complexes is dependent on utrophin and α7β1 integrin. PMID:25504048

  13. Solid lipid nanoparticles carrying chemotherapeutic drug across the blood-brain barrier through insulin receptor-mediated pathway.

    Science.gov (United States)

    Kuo, Yung-Chih; Shih-Huang, Chun-Yuan

    2013-09-01

    Carmustine (BCNU)-loaded solid lipid nanoparticles (SLNs) were grafted with 83-14 monoclonal antibody (MAb) (83-14 MAb/BCNU-SLNs) and applied to the brain-targeting delivery. Human brain-microvascular endothelial cells (HBMECs) incubated with 83-14 MAb/BCNU-SLNs were stained to demonstrate the interaction between the nanocarriers and expressed insulin receptors (IRs). The results revealed that the particle size of 83-14 MAb/BCNU-SLNs decreased with an increasing weight percentage of Dynasan 114 (DYN). Storage at 4 °C for 6 weeks slightly deformed the colloidal morphology. In addition, poloxamer 407 on 83-14 MAb/BCNU-SLNs induced cytotoxicity to RAW264.7 cells and inhibited phagocytosis by RAW264.7 cells. An increase in the weight percentage of DYN from 0% to 67% slightly reduced the viability of RAW264.7 cells and promoted phagocytosis. Moreover, the transport ability of 83-14 MAb/BCNU-SLNs across the blood-brain barrier (BBB) in vitro enhanced with an increasing weight percentage of Tween 80. 83-14 MAb on MAb/BCNU-SLNs stimulated endocytosis by HBMECs via IRs and enhanced the permeability of BCNU across the BBB. 83-14 MAb/BCNU-SLNs can be a promising antitumor drug delivery system for transporting BCNU to the brain.

  14. Clinical and functional characterization of a patient carrying a compound heterozygous pericentrin mutation and a heterozygous IGF1 receptor mutation.

    Directory of Open Access Journals (Sweden)

    Eva Müller

    Full Text Available Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X] were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration.

  15. Clinical and functional characterization of a patient carrying a compound heterozygous pericentrin mutation and a heterozygous IGF1 receptor mutation.

    Science.gov (United States)

    Müller, Eva; Dunstheimer, Desiree; Klammt, Jürgen; Friebe, Daniela; Kiess, Wieland; Kratzsch, Jürgen; Kruis, Tassilo; Laue, Sandy; Pfäffle, Roland; Wallborn, Tillmann; Heidemann, Peter H

    2012-01-01

    Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA) with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X]) were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration.

  16. Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor

    Directory of Open Access Journals (Sweden)

    Dokter Wim

    2010-06-01

    Full Text Available Abstract Background Glucocorticoids (GCs control expression of a large number of genes via binding to the GC receptor (GR. Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in the regulation of gene expression, we performed gene expression profiling of livers of prednisolone-treated wild type (WT and mice that have lost the ability to form GR dimers (GRdim. Results The GR target genes identified in WT mice were predominantly related to glucose metabolism, the cell cycle, apoptosis and inflammation. In GRdim mice, the level of prednisolone-induced gene expression was significantly reduced compared to WT, but not completely absent. Interestingly, for a set of genes, involved in cell cycle and apoptosis processes and strongly related to Foxo3a and p53, induction by prednisolone was completely abolished in GRdim mice. In contrast, glucose metabolism-related genes were still modestly upregulated in GRdim mice upon prednisolone treatment. Finally, we identified several novel GC-inducible genes from which Fam107a, a putative histone acetyltransferase complex interacting protein, was most strongly dependent on GR dimerization. Conclusions This study on prednisolone-induced effects in livers of WT and GRdim mice identified a number of interesting candidate genes and pathways regulated by GR dimers and sheds new light onto the complex transcriptional regulation of liver function by GCs.

  17. Characterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells†

    Science.gov (United States)

    Das, Lipsa; Anderson, Todd A.; Gard, Jaime M.C.; Sroka, Isis C.; Strautman, Stephanie R.; Nagle, Raymond B.; Morrissey, Colm; Knudsen, Beatrice S.; Cress, Anne E.

    2017-01-01

    Laminin binding integrins α6 (CD49f) and α3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modelling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, α6 integrin internalized with a rate constant (kactual) of 3.25min−1, 3-fold faster than α3 integrin (1.0 min−1), 1.5-fold faster than the vitronectin binding αv integrin (CD51) (2.2 min−1), and significantly slower than the unrelated transferrin receptor (CD71) (15 min−1). Silencing of α3 integrin protein expression in DU145, PC3 and PC3B1 cells resulted in up to a 1.71-fold increase in kactual for α6 integrin. The internalized α6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of α3 integrin expression resulted in redistribution of α6β4 integrin to an observed cell-cell staining pattern that is consistent with a suprabasal distribution observed in epidermis and early PIN lesions in PCa. Depletion of α3 integrin increased cell migration by 1.8 fold, which was dependent on α6β1 integrin. Silencing of α6 integrin expression however, had no significant effect on the kactual of α3 integrin or its distribution in early endosomes. These results indicate that α3 and α6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. This article is protected by copyright. All rights reserved PMID:27509031

  18. Characterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells.

    Science.gov (United States)

    Das, Lipsa; Anderson, Todd A; Gard, Jaime M C; Sroka, Isis C; Strautman, Stephanie R; Nagle, Raymond B; Morrissey, Colm; Knudsen, Beatrice S; Cress, Anne E

    2017-05-01

    Laminin binding integrins α6 (CD49f) and α3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modeling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, α6 integrin internalized with a rate constant (k actual ) of 3.25 min -1 , threefold faster than α3 integrin (1.0 min -1 ), 1.5-fold faster than the vitronectin binding αv integrin (CD51) (2.2 min -1 ), and significantly slower than the unrelated transferrin receptor (CD71) (15 min -1 ). Silencing of α3 integrin protein expression in DU145, PC3, and PC3B1 cells resulted in up to a 1.71-fold increase in k actual for α6 integrin. The internalized α6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of α3 integrin expression resulted in redistribution of α6β4 integrin to an observed cell-cell staining pattern that is consistent with a suprabasal distribution observed in epidermis and early PIN lesions in PCa. Depletion of α3 integrin increased cell migration by 1.8-fold, which was dependent on α6β1 integrin. Silencing of α6 integrin expression however, had no significant effect on the k actual of α3 integrin or its distribution in early endosomes. These results indicate that α3 and α6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. J. Cell. Biochem. 118: 1038-1049, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Laminins and cancer stem cells: Partners in crime?

    Science.gov (United States)

    Qin, Yan; Rodin, Sergey; Simonson, Oscar E; Hollande, Frédéric

    2017-08-01

    As one of the predominant protein families within the extracellular matrix both structurally and functionally, laminins have been shown to be heavily involved in tumor progression and drug resistance. Laminins participate in key cellular events for tumor angiogenesis, cell invasion and metastasis development, including the regulation of epithelial-mesenchymal transition and basement membrane remodeling, which are tightly associated with the phenotypic characteristics of stem-like cells, particularly in the context of cancer. In addition, a great deal of studies and reports has highlighted the critical roles of laminins in modulating stem cell phenotype and differentiation, as part of the stem cell niche. Stemming from these discoveries a growing body of literature suggests that laminins may act as regulators of cancer stem cells, a tumor cell subpopulation that plays an instrumental role in long-term cancer maintenance, metastasis development and therapeutic resistance. The accumulating evidence in this emerging research area suggests that laminins represent potential therapeutic targets for anti-cancer treatments against cancer stem cells, and that they may be used as predictive and prognostic markers to inform clinical management and improve patient survival. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Laminin-Coated Poly(Methyl Methacrylate (PMMA Nanofiber Scaffold Facilitates the Enrichment of Skeletal Muscle Myoblast Population

    Directory of Open Access Journals (Sweden)

    Nor Kamalia Zahari

    2017-10-01

    Full Text Available Myoblasts, the contractile cells of skeletal muscle, have been invaluable for fundamental studies of muscle development and clinical applications for muscle loss. A major limitation to the myoblast-based therapeutic approach is contamination with non-contractile fibroblasts, which overgrow during cell expansion. To overcome these limitations, this study was carried out to establish a 3D culture environment using nanofiber scaffolds to enrich the myoblast population during construct formation. Poly(methyl methacrylate (PMMA nanofiber (PM scaffolds were fabricated using electrospinning techniques and coated with extracellular matrix (ECM proteins, such as collagen or laminin, in the presence or absence of genipin. A mixed population of myoblasts and fibroblasts was isolated from human skeletal muscle tissues and cultured on plain surfaces, as well as coated and non-coated PM scaffolds. PMMA can produce smooth fibers with an average diameter of 360 ± 50 nm. Adsorption of collagen and laminin on PM scaffolds is significantly enhanced in the presence of genipin, which introduces roughness to the nanofiber surface without affecting fiber diameter and mechanical properties. It was also demonstrated that laminin-coated PM scaffolds significantly enhance myoblast proliferation (0.0081 ± 0.0007 h−1 and migration (0.26 ± 0.04 μm/min, while collagen-coated PM scaffolds favors fibroblasts proliferation (0.0097 ± 0.0009 h−1 and migration (0.23 ± 0.03 μm/min. Consequently, the myoblast population was enriched on laminin-coated PM scaffolds throughout the culture process. Therefore, laminin coating of nanofiber scaffolds could be a potential scaffold for the development of a tissue-engineered muscle substitute.

  1. Laminin-Coated Poly(Methyl Methacrylate) (PMMA) Nanofiber Scaffold Facilitates the Enrichment of Skeletal Muscle Myoblast Population.

    Science.gov (United States)

    Zahari, Nor Kamalia; Idrus, Ruszymah Binti Haji; Chowdhury, Shiplu Roy

    2017-10-30

    Myoblasts, the contractile cells of skeletal muscle, have been invaluable for fundamental studies of muscle development and clinical applications for muscle loss. A major limitation to the myoblast-based therapeutic approach is contamination with non-contractile fibroblasts, which overgrow during cell expansion. To overcome these limitations, this study was carried out to establish a 3D culture environment using nanofiber scaffolds to enrich the myoblast population during construct formation. Poly(methyl methacrylate) (PMMA) nanofiber (PM) scaffolds were fabricated using electrospinning techniques and coated with extracellular matrix (ECM) proteins, such as collagen or laminin, in the presence or absence of genipin. A mixed population of myoblasts and fibroblasts was isolated from human skeletal muscle tissues and cultured on plain surfaces, as well as coated and non-coated PM scaffolds. PMMA can produce smooth fibers with an average diameter of 360 ± 50 nm. Adsorption of collagen and laminin on PM scaffolds is significantly enhanced in the presence of genipin, which introduces roughness to the nanofiber surface without affecting fiber diameter and mechanical properties. It was also demonstrated that laminin-coated PM scaffolds significantly enhance myoblast proliferation (0.0081 ± 0.0007 h -1 ) and migration (0.26 ± 0.04 μm/min), while collagen-coated PM scaffolds favors fibroblasts proliferation (0.0097 ± 0.0009 h -1 ) and migration (0.23 ± 0.03 μm/min). Consequently, the myoblast population was enriched on laminin-coated PM scaffolds throughout the culture process. Therefore, laminin coating of nanofiber scaffolds could be a potential scaffold for the development of a tissue-engineered muscle substitute.

  2. Laminin-5 Degradation Due to Mustard in Cultured Normal Human Epidermal Keratinocytes (NHEK)

    National Research Council Canada - National Science Library

    Ray, Prabhati; Jin, Xiannu; Leng, Yan; Li, Zhuangwu; Ray, Radharaman

    2003-01-01

    .... We observed that in NHEK, mustards degrade laminin-5. Calmodulin antagonist, W7 or the serine protease inhibitor, TLCK prior to mustard exposure prevented mustard-induced degradation of laminin-5...

  3. Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jong Hyuk; Kim, Jaeyoon; Lee, Hyeongjoo [NovaCell Technology Inc., Pohang, Kyungbuk 790-784 (Korea, Republic of); Kim, So Young [Department of Dermatology, Chung-Ang University College of Medicine, Seoul 156-756 (Korea, Republic of); Department of Convergence Medicine and Pharmaceutical Biosciences, Graduate School, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Jang, Hwan-Hee [Functional Food and Nutrition Division, Department of Agrofood Resources, Rural Development Administration, Suwon 441-853 (Korea, Republic of); Ryu, Sung Ho [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk 790-784 (Korea, Republic of); Kim, Beom Joon [Department of Dermatology, Chung-Ang University College of Medicine, Seoul 156-756 (Korea, Republic of); Department of Convergence Medicine and Pharmaceutical Biosciences, Graduate School, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Taehoon G., E-mail: taehoon@novacelltech.com [NovaCell Technology Inc., Pohang, Kyungbuk 790-784 (Korea, Republic of)

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer We identify a function of the YIGSR peptide to enhance collagen synthesis in Hs27. Black-Right-Pointing-Pointer YIGSR peptide enhanced collagen type 1 synthesis both of gene and protein levels. Black-Right-Pointing-Pointer There were no changes in cell proliferation and MMP-1 level in YIGSR treatment. Black-Right-Pointing-Pointer The YIGSR effect on collagen synthesis mediated activation of FAK, pyk2 and ERK. Black-Right-Pointing-Pointer The YIGSR-induced FAK and ERK activation was modulated by FAK and MEK inhibitors. -- Abstract: The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the {beta}1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67 kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate

  4. Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts

    International Nuclear Information System (INIS)

    Yoon, Jong Hyuk; Kim, Jaeyoon; Lee, Hyeongjoo; Kim, So Young; Jang, Hwan-Hee; Ryu, Sung Ho; Kim, Beom Joon; Lee, Taehoon G.

    2012-01-01

    Highlights: ► We identify a function of the YIGSR peptide to enhance collagen synthesis in Hs27. ► YIGSR peptide enhanced collagen type 1 synthesis both of gene and protein levels. ► There were no changes in cell proliferation and MMP-1 level in YIGSR treatment. ► The YIGSR effect on collagen synthesis mediated activation of FAK, pyk2 and ERK. ► The YIGSR-induced FAK and ERK activation was modulated by FAK and MEK inhibitors. -- Abstract: The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929–933 sequence of the β1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67 kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate peptide for the treatment of skin aging and wrinkles.

  5. Carcinoma-associated perisinusoidal laminin may signal tumour cell metastasis to the liver

    DEFF Research Database (Denmark)

    Wewer, U M; Albrechtsen, R

    1992-01-01

    using chain-specific monoclonal antibodies against B2 laminin. In an ex vivo assay, viable tumour cells (Panc-1 and clone A) were found to bind with remarkable specificity to frozen sections of liver tissue containing perisinusoidal laminin as opposed to liver tissues without laminin. We suggest...

  6. Laminin in the anterior pituitary gland of the rat. Laminin in the gonadotrophic cells correlates with their functional state

    DEFF Research Database (Denmark)

    Holck, S; Albrechtsen, R; Wewer, U M

    1987-01-01

    The distribution pattern of laminin in the rat anterior pituitary gland under physiological and hormonally altered conditions was studied immunohistochemically. Intense immunoreactivity of the capillaries and of the basement membranes surrounding parenchymal cells was found. Five to 10......% of the parenchymal cells of normal adult rat pituitary gland exhibited also intense positive cytoplasmic staining. These were identified as gonadotrophic cells on the basis of their topographic distribution and typical 700-nm light bodies. By immunoelectron microscopy it was shown that the light bodies contain...... laminin and the number of light bodies reflects the hormonal activity of the gonadotrophic cells of the rat pituitary gland....

  7. Platelet-derived growth factor receptor-β, carrying the activating mutation D849N, accelerates the establishment of B16 melanoma

    International Nuclear Information System (INIS)

    Suzuki, Shioto; Heldin, Carl-Henrik; Heuchel, Rainer Lothar

    2007-01-01

    Platelet-derived growth factor (PDGF)-BB and PDGF receptor (PDGFR)-β are mainly expressed in the developing vasculature, where PDGF-BB is produced by endothelial cells and PDGFR-β is expressed by mural cells, including pericytes. PDGF-BB is produced by most types of solid tumors, and PDGF receptor signaling participates in various processes, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. Furthermore, PDGF-BB-producing tumors are characterized by increased pericyte abundance and accelerated tumor growth. Thus, there is a growing interest in the development of tumor treatment strategies by blocking PDGF/PDGFR function. We have recently generated a mouse model carrying an activated PDGFR-β by replacing the highly conserved aspartic acid residue (D) 849 in the activating loop with asparagine (N). This allowed us to investigate, in an orthotopic tumor model, the role of increased stromal PDGFR-β signaling in tumor-stroma interactions. B16 melanoma cells lacking PDGFR-β expression and either mock-transfected or engineered to express PDGF-BB, were injected alone or in combination with matrigel into mice carrying the activated PDGFR-β (D849N) and into wild type mice. The tumor growth rate was followed and the vessel status of tumors, i.e. total vessel area/tumor, average vessel surface and pericyte density of vessels, was analyzed after resection. Tumors grown in mice carrying an activated PDGFR-β were established earlier than those in wild-type mice. In this early phase, the total vessel area and the average vessel surface were higher in tumors grown in mice carrying the activated PDGFR-β (D849N) compared to wild-type mice, whereas we did not find a significant difference in the number of tumor vessels and the pericyte abundance around tumor vessels between wild type and mutant mice. At later phases of tumor progression, no significant difference in tumor growth rate was

  8. Carrying Capacity

    DEFF Research Database (Denmark)

    Schroll, Henning; Andersen, Jan; Kjærgård, Bente

    2012-01-01

    A spatial planning act was introduced inIndonesia 1992 and renewed in 2008. It emphasised the planning role of decentralised authorities. The spatial planning act covers both spatial and environmental issues. It defines the concept of carrying capacity and includes definitions of supportive....../cities. Four different sectors (water, food production, waste, and forests) were selected as core areas for decentralised spatial planning. Indicators for SCC and ACC were identified and assessed with regard to relevance and quantifiability. For each of the indicators selected, a legal threshold or guiding...... was introduced inIndonesia 1992 and renewed in 2008. It emphasised the planning role of decentralised authorities. The spatial planning act covers both spatial and environmental issues. It defines the concept of carrying capacity and includes definitions of supportive carrying capacity (SCC) and assimilative...

  9. The role of laminins in cartilaginous tissues: from development to regeneration.

    Science.gov (United States)

    Sun, Y; Wang, T L; Toh, W S; Pei, M

    2017-07-21

    As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells) could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus) throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells' proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

  10. The role of laminins in cartilaginous tissues: from development to regeneration

    Directory of Open Access Journals (Sweden)

    Y Sun

    2017-07-01

    Full Text Available As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells’ proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

  11. LAMININS IN COLORECTAL CANCER: EXPRESSION, FUNCTION, PROGNOSTIC POWER AND MOLECULAR MECHANISMS

    Directory of Open Access Journals (Sweden)

    S. A. Rodin

    2017-01-01

    Full Text Available Extracellular matrix (ECM proteins are a major component of the tumor stroma. Laminins emerge as one of the main families of ECM proteins with signaling properties. Apart from the structural function, laminins and products of their degradation affect survival and differentiation of cancer cells, motility of cancer and stromal cells, angiogenesis, invasion into distant organs, and other aspects of cancer development. Here, we discus expression of laminins in colorectal cancer (CRC, studying of laminin functions in in vitro and in vivo models of CRC, and using laminins as prognostic markers of CRC. Recently, we have reported a new approach to assessing prognostic power using classifiers constructed from sets of laminin genes. The method allows for accurate prognosis of CRC and provides additional information that may suggest possible molecular mechanisms of laminin function in CRC progression.

  12. Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

    International Nuclear Information System (INIS)

    Fujita, Manabu; Khazenzon, Natalya M; Bose, Shikha; Sekiguchi, Kiyotoshi; Sasaki, Takako; Carter, William G; Ljubimov, Alexander V; Black, Keith L; Ljubimova, Julia Y

    2005-01-01

    Laminins are the major components of vascular and parenchymal basement membranes. We previously documented a switch in the expression of vascular laminins containing the α4 chain from predominantly laminin-9 (α4β2γ1) to predominantly laminin-8 (α4β1γ1) during progression of human brain gliomas to high-grade glioblastoma multiforme. Here, differential expression of laminins was studied in blood vessels and ductal epithelium of the breast. In the present study the expressions of laminin isoforms α1–α5, β1–β3, γ1, and γ2 were examined during progression of breast cancer. Forty-five clinical samples of breast tissues including normal breast, ductal carcinomas in situ, invasive ductal carcinomas, and their metastases to the brain were compared using Western blot analysis and immunohistochemistry for various chains of laminin, in particular laminin-8 and laminin-9. Laminin α4 chain was observed in vascular basement membranes of most studied tissues, with the highest expression in metastases. At the same time, the expression of laminin β2 chain (a constituent of laminin-9) was mostly seen in normal breast and carcinomas in situ but not in invasive carcinomas or metastases. In contrast, laminin β1 chain (a constituent of laminin-8) was typically found in vessel walls of carcinomas and their metastases but not in those of normal breast. The expression of laminin-8 increased in a progression-dependent manner. A similar change was observed from laminin-11 (α5β2γ1) to laminin-10 (α5β1γ1) during breast tumor progression. Additionally, laminin-2 (α2β1γ1) appeared in vascular basement membranes of invasive carcinomas and metastases. Chains of laminin-5 (α3β3γ2) were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression. These results suggest that laminin-2, laminin-8, and laminin-10 are important components of tumor microvessels and may associate with breast tumor progression. Angiogenic switch

  13. Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

    Science.gov (United States)

    Fujita, Manabu; Khazenzon, Natalya M; Bose, Shikha; Sekiguchi, Kiyotoshi; Sasaki, Takako; Carter, William G; Ljubimov, Alexander V; Black, Keith L; Ljubimova, Julia Y

    2005-01-01

    Introduction Laminins are the major components of vascular and parenchymal basement membranes. We previously documented a switch in the expression of vascular laminins containing the α4 chain from predominantly laminin-9 (α4β2γ1) to predominantly laminin-8 (α4β1γ1) during progression of human brain gliomas to high-grade glioblastoma multiforme. Here, differential expression of laminins was studied in blood vessels and ductal epithelium of the breast. Method In the present study the expressions of laminin isoforms α1–α5, β1–β3, γ1, and γ2 were examined during progression of breast cancer. Forty-five clinical samples of breast tissues including normal breast, ductal carcinomas in situ, invasive ductal carcinomas, and their metastases to the brain were compared using Western blot analysis and immunohistochemistry for various chains of laminin, in particular laminin-8 and laminin-9. Results Laminin α4 chain was observed in vascular basement membranes of most studied tissues, with the highest expression in metastases. At the same time, the expression of laminin β2 chain (a constituent of laminin-9) was mostly seen in normal breast and carcinomas in situ but not in invasive carcinomas or metastases. In contrast, laminin β1 chain (a constituent of laminin-8) was typically found in vessel walls of carcinomas and their metastases but not in those of normal breast. The expression of laminin-8 increased in a progression-dependent manner. A similar change was observed from laminin-11 (α5β2γ1) to laminin-10 (α5β1γ1) during breast tumor progression. Additionally, laminin-2 (α2β1γ1) appeared in vascular basement membranes of invasive carcinomas and metastases. Chains of laminin-5 (α3β3γ2) were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression. Conclusion These results suggest that laminin-2, laminin-8, and laminin-10 are important components of tumor microvessels and may associate with breast

  14. Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer’s Disease Patients Carrying the APOE Epsilon 4 Allele

    Directory of Open Access Journals (Sweden)

    Alen Zollo

    2017-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4 allele. Changes in amyloid precursor protein (APP binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1 as an important factor in APP trafficking and processing. Recent in vitro evidence has associated the APOE4 allele and alterations in the SORL1 pathway with AD development and progression. Here, we analyzed SORL1 expression in neural stem cells (NSCs from AD patients carrying null, one, or two copies of the APOE4 allele. We show reduced SORL1 expression only in NSCs of a patient carrying two copies of APOE4 allele with increased Aβ/SORL1 localization along the degenerated neurites. Interestingly, SORL1 binding to APP was largely compromised; this could be almost completely reversed by γ-secretase (but not β-secretase inhibitor treatment. These findings may yield new insights into the complex interplay of SORL1 and AD pathology and point to NSCs as a valuable tool to address unsolved AD-related questions in vitro.

  15. Single-cell force spectroscopy as a technique to quantify human red blood cell adhesion to subendothelial laminin.

    Science.gov (United States)

    Maciaszek, Jamie L; Partola, Kostyantyn; Zhang, Jing; Andemariam, Biree; Lykotrafitis, George

    2014-12-18

    Single-cell force spectroscopy (SCFS), an atomic force microscopy (AFM)-based assay, enables quantitative study of cell adhesion while maintaining the native state of surface receptors in physiological conditions. Human healthy and pathological red blood cells (RBCs) express a large number of surface proteins which mediate cell-cell interactions, or cell adhesion to the extracellular matrix. In particular, RBCs adhere with high affinity to subendothelial matrix laminin via the basal cell adhesion molecule and Lutheran protein (BCAM/Lu). Here, we established SCFS as an in vitro technique to study human RBC adhesion at baseline and following biochemical treatment. Using blood obtained from healthy human subjects, we recorded adhesion forces from single RBCs attached to AFM cantilevers as the cell was pulled-off of substrates coated with laminin protein. We found that an increase in the overall cell adhesion measured via SCFS is correlated with an increase in the resultant total force measured on 1 µm(2) areas of the RBC membrane. Further, we showed that SCFS can detect significant changes in the adhesive response of RBCs to modulation of the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) pathway. Lastly, we identified variability in the RBC adhesion force to laminin amongst the human subjects, suggesting that RBCs maintain diverse levels of active BCAM/Lu adhesion receptors. By using single-cell measurements, we established a powerful new method for the quantitative measurement of single RBC adhesion with specific receptor-mediated binding. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin

    DEFF Research Database (Denmark)

    Goldfinger, L E; Hopkinson, S B; deHart, G W

    1999-01-01

    Previously, we demonstrated that proteolytic processing within the globular domain of the alpha3 subunit of laminin-5 (LN5) converts LN5 from a cell motility-inducing factor to a protein complex that can trigger the formation of hemidesmosomes, certain cell-matrix attachment sites found in epithe......-inhibiting antibodies, we provide evidence that LN5 and its two integrin receptors (alpha6beta4 and alpha3beta1) appear necessary for wound healing to occur in MCF-10A cell culture wounds. We propose a model for healing of wounded epithelial tissues based on these results....... in epithelial cells. We have prepared a monoclonal antibody (12C4) whose epitope is located toward the carboxy terminus of the globular domain of the alpha3 laminin subunit. This epitope is lost from the alpha3 subunit as a consequence of proteolytic processing. Antibody 12C4 stains throughout the matrix...... the wound site. A similar phenomenon is observed in human skin wounds, since we also detect expression of the unprocessed alpha3 laminin subunit at the leading tip of the sheet of epidermal cells that epithelializes skin wounds in vivo. In addition, using alpha3 laminin subunit and integrin function...

  17. The Laminin 511/521 Binding Site on the Lutheran Blood Group Glycoprotein is Located at theFlexible Junction of Ig Domains 2 and 3

    Energy Technology Data Exchange (ETDEWEB)

    Mankelow, Tosti J.; Burton, Nicholas; Stedansdottir, Fanney O.; Spring, Frances A.; Parsons, Stephen F.; Pesersen, Jan S.; Oliveira, Cristiano L.P.; Lammie, Donna; Wess, Timothy; Mohandas, Narla; Chasis, Joel A.; Brady, R. Leo; Anstee, David J.

    2007-07-01

    The Lutheran blood group glycoprotein, first discovered on erythrocytes, is widely expressed in human tissues. It is a ligand for the {alpha}5 subunit of Laminin 511/521, an extracellular matrix protein. This interaction may contribute to vasocclusive events that are an important cause of morbidity in sickle cell disease. Using X-ray crystallography, small angle X-ray scattering and site directed mutagenesis we show that the extracellular region of Lutheran forms an extended structure with a distinctive bend between the second and third immunoglobulin-like domains. The linker between domains 2 and 3 appears to be flexible and is a critical determinant in maintaining an overall conformation for Lutheran that is capable of binding to Laminin. Mutagenesis studies indicate that Asp312 of Lutheran and the surrounding cluster of negatively charged residues in this linker region form the Laminin binding site. Unusually, receptor binding is therefore not a function of the domains expected to be furthermost from the plasma membrane. These studies imply that structural flexibility of Lutheran may be essential for its interaction with Laminin and present a novel opportunity for the development of therapeutics for sickle cell disease.

  18. Laminin promotes vascular network formation in 3D in vitro collagen scaffolds by regulating VEGF uptake.

    Science.gov (United States)

    Stamati, Katerina; Priestley, John V; Mudera, Vivek; Cheema, Umber

    2014-09-10

    Angiogenesis is an essential neovascularisation process, which if recapitulated in 3D in vitro, will provide better understanding of endothelial cell (EC) behaviour. Various cell types and growth factors are involved, with vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 key components. We were able to control the aggregation pattern of ECs in 3D collagen hydrogels, by varying the matrix composition and/or having a source of cells signalling angiogenic proteins. These aggregation patterns reflect the different developmental pathways that ECs take to form different sized tubular structures. Cultures with added laminin and thus increased expression of α6 integrin showed a significant increase (p3D. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  19. An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model

    International Nuclear Information System (INIS)

    Ma Jun; Tian Weiming; Hou Shaoping; Xu Qunyuan; Spector, Myron; Cui Fuzhai

    2007-01-01

    The objective of the study was to determine the effects of a hyaluronic-acid-based (HA-based) hydrogel implant, carrying a polyclonal antibody to the Nogo-66 receptor (NgR), on adult rats that underwent middle cerebral artery occlusion (MCAO). Behavioral tests of a forelimb-reaching task suggested that the disabled function of the impaired forelimb in this stroke model was ameliorated by the implant to a certain extent. These behavioral findings were correlated with immunohistochemical results of investigating the distribution of NgR antibody, neurofilaments (NF) and neuron-specific class III β-tubulin (TuJ1) in the brain sections. The porous hydrogel functioned as a scaffold to deliver the NgR antibody, support cell migration and development. In addition, it was found NF-positive and TuJ1-positive expressions were distributed in the implanted hydrogel. Collectively, the results demonstrate the promise of the HA hydrogel as a scaffold material and the delivery vehicle of the NgR antibody for the repair of defects and the support of neural regeneration in the brain

  20. An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Ma Jun [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Tian Weiming [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Hou Shaoping [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing 100054 (China); Xu Qunyuan [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing 100054 (China); Spector, Myron [Tissue Engineering, VA Boston Healthcare System, Harvard Medical School, Boston, MA (United States); Cui Fuzhai [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2007-12-15

    The objective of the study was to determine the effects of a hyaluronic-acid-based (HA-based) hydrogel implant, carrying a polyclonal antibody to the Nogo-66 receptor (NgR), on adult rats that underwent middle cerebral artery occlusion (MCAO). Behavioral tests of a forelimb-reaching task suggested that the disabled function of the impaired forelimb in this stroke model was ameliorated by the implant to a certain extent. These behavioral findings were correlated with immunohistochemical results of investigating the distribution of NgR antibody, neurofilaments (NF) and neuron-specific class III {beta}-tubulin (TuJ1) in the brain sections. The porous hydrogel functioned as a scaffold to deliver the NgR antibody, support cell migration and development. In addition, it was found NF-positive and TuJ1-positive expressions were distributed in the implanted hydrogel. Collectively, the results demonstrate the promise of the HA hydrogel as a scaffold material and the delivery vehicle of the NgR antibody for the repair of defects and the support of neural regeneration in the brain.

  1. Secondary reduction of alpha7B integrin in laminin alpha2 deficient congenital muscular dystrophy supports an additional transmembrane link in skeletal muscle.

    Science.gov (United States)

    Cohn, R D; Mayer, U; Saher, G; Herrmann, R; van der Flier, A; Sonnenberg, A; Sorokin, L; Voit, T

    1999-03-01

    The integrins are a large family of heterodimeric transmembrane cellular receptors which mediate the association between the extracellular matrix (ECM) and cytoskeletal proteins. The alpha7beta1 integrin is a major laminin binding integrin in skeletal and cardiac muscle and is thought to be involved in myogenic differentiation and migration processes. The main binding partners of the alpha7 integrin are laminin-1 (alpha1-beta1-gamma1), laminin-2 (alpha2-beta1-gamma1) and laminin-4 (alpha2-beta2-gamma1). Targeted deletion of the gene for the alpha7 integrin subunit (ITGA7) in mice leads to a novel form of muscular dystrophy. In the present study we have investigated the expression of two alternative splice variants, the alpha7B and beta1D integrin subunits, in normal human skeletal muscle, as well as in various forms of muscular dystrophy. In normal human skeletal muscle the expression of the alpha7 integrin subunit appeared to be developmentally regulated: it was first detected at 2 years of age. In contrast, the beta1D integrin could be detected in immature and mature muscle in the sarcolemma of normal fetal skeletal muscle at 18 weeks gestation. The expression of alpha7B integrin was significantly reduced at the sarcolemma in six patients with laminin alpha2 chain deficient congenital muscular dystrophy (CMD) (age >2 years). However, this reduction was not correlated with the amount of laminin alpha2 chain expressed. In contrast, the expression of the laminin alpha2 chain was not altered in the skeletal muscle of the alpha7 knock-out mice. These data argue in favor that there is not a tight correlation between the expression of the alpha7 integrin subunit and that of the laminin alpha2 chain in either human or murine dystrophic muscle. Interestingly, in dystrophinopathies (Duchenne and Becker muscular dystrophy; DMD/BMD) expression of alpha7B was upregulated irrespective of the level of dystrophin expression as shown by a strong sarcolemmal staining pattern even

  2. Laminin, a noncollagenous component of epithelial basement membranes synthesized by a rat yolk sac tumor

    DEFF Research Database (Denmark)

    Wewer, U; Albrechtsen, R; Ruoslahti, E

    1981-01-01

    Laminin, a glycoprotein antigenically similar or identical to a component of epithelial basement membranes, was identified as a major component of the abundant extracellular matrix synthesized by an experimentally induced rat yolk sac tumor. Immunocytochemical staining revealed laminin in cultured...... polypeptides with molecular weights of approximately 200,000 and 400,000. These comigrated with the polypeptides of mouse laminin isolated previously. The yolk sac tumor tissue grown in vivo contained laminin in the tumor cells and in the extracellular material as evidenced by immunofluorescence...... membranes in rat tissues in a manner indistinguishable from antilaminin. The presence of laminin in rat yolk sac cells, the presumed origin of our yolk sac tumor, was studied in some detail. Laminin was found to be present in normal cells of the visceral as well as the parietal yolk sac layer...

  3. Changes of laminin beta 2 chain expression in congenital muscular dystrophy

    DEFF Research Database (Denmark)

    Cohn, R D; Herrmann, R; Wewer, U M

    1997-01-01

    We studied the distribution of laminin beta 2 chain in the skeletal muscle basement membrane of 16 patients with congenital muscular dystrophy (CMD) by immunohistochemistry. A dramatic reduction in the laminin beta 2 staining was observed in four patients with classical merosin-negative CMD....... A moderate reduction of laminin beta 2 labelling was observed in four patients with partial merosin deficiency and two patients with merosin-positive CMD. Two patients with merosin-positive CMD had no apparent changes in the expression of laminin beta 2. In three patients and one fetus diagnosed as Walker...

  4. Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice

    DEFF Research Database (Denmark)

    Guo, L T; Zhang, X U; Kuang, W

    2003-01-01

    2, lacking domain VI. Interestingly, all mutants lack laminin alpha2 in peripheral nerve. We have demonstrated previously, that overexpression of the human laminin alpha2 in skeletal muscle in dy(2J)/dy(2J) and dy(W)/dy(W) mice under the control of a striated muscle-specific creatine kinase promoter......Deficiency of laminin alpha2 is the cause of one of the most severe muscular dystrophies in humans and other species. It is not yet clear how particular mutations in the laminin alpha2 chain gene affect protein expression, and how abnormal levels or structure of the protein affect disease. Animal...

  5. IFN-Alpha receptor-1 upregulation in PBMC from HCV naïve patients carrying cc genotype. possible role of IFN-lambda.

    Directory of Open Access Journals (Sweden)

    Eleonora Lalle

    Full Text Available IL-28B gene polymorphisms predict better therapeutic response and spontaneous clearance of HCV. Moreover, higher expression of IFN-lambda has been reported in patients with the rs12979860 CC favourable genotype. The study aim was to establish possible relationships between IL-28B rs12979860 genotypes and expression of IFN-alpha receptor-1 (IFNAR-1 in naïve HCV patients, and to explore the possible role of IFN-lambda.IFNAR-1 mRNA levels were measured in PBMC from naïve patients with chronic hepatitis C with different IL-28 genotypes. The ability of IFN-lambda to up-regulate the expression of IFNAR-1 was established in PBMC from healthy donors carrying different IL-28B genotypes.Lower IFNAR-1 mRNA levels were observed in PBMC from HCV-infected naïve patients as compared to healthy donors. In healthy donors, IFNAR-1 mRNA levels were independent from IL-28B genotype, while in HCV patients, an increasing gradient was observed in TT vs CT vs CC carriers. In the latter group, a direct correlation between IFNAR-1 and endogenous IL-28B expression was observed. Moreover, IFN-lambda up-regulated IFNAR-1 expression in normal PBMC in a time-and dose-dependent manner, with a more effective response in CC vs TT carriers.Endogenous levels of IFN-lambda may be responsible for partial restoration of IFNAR-1 expression in HCV patients with favourable IL-28 genotype. This, in turn, may confer to CC carriers a response advantage to either endogenous or exogenous IFN-alpha, representing the biological basis for the observed association between CC genotype and favourable outcome of either natural infection (clearance vs chronicization or IFN therapy.

  6. Endogenous laminin is required for human airway smooth muscle cell maturation

    Directory of Open Access Journals (Sweden)

    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  7. Rethinking Molecular Mimicry in Rheumatic Heart Disease andAutoimmune Myocarditis: Laminin, Collagen IV, CAR and B1AR as Initial Targets of Disease

    Directory of Open Access Journals (Sweden)

    Robert eRoot-Bernstein

    2014-08-01

    Full Text Available Rationale: Molecular mimicry theory (MMT suggests that epitope mimicry between pathogens and human proteins can activate autoimmune disease. Group A streptococci (GAS mimics human cardiac myosin in rheumatic heart disease (RHD and coxsackie viruses (CX mimic actin in autoimmune myocarditis (AM. But myosin and actin are immunologically inaccessible and unlikely initial targets. Extracellular cardiac proteins that mimic GAS and CX would be more likely.Objectives: To determine whether extracellular cardiac proteins such as coxsackie and adenovirus receptor (CAR, beta 1 adrenergic receptor (B1AR, CD55/DAF, laminin, and collagen IV mimic GAS, CX and/or cardiac myosin or actin. Methods: BLAST 2.0 and LALIGN searches of the UniProt protein database were employed to identify potential molecular mimics. Quantitative ELISA was used to measure antibody cross-reactivity. Measurements: Similarities were considered to be significant if a sequence contained at least 5 identical amino acids in 10. Antibodies were considered to be cross-reactive if the binding constant had a Kd less than 10-9 M. Main Results: GAS mimics laminin, CAR and myosin. CX mimics actin and collagen IV and B1AR. The similarity search results are mirrored by antibody cross-reactivities. Additionally, antibodies against laminin recognize antibodies against collagen IV; antibodies against actin recognize antibodies against myosin, and antibodies against GAS recognize antibodies against CX. Thus, there is both mimicry of extracellular proteins and antigenic complementarity between GAS-CX in RHD/AM.Conclusions: RHD/AM may be due to combined infections of GAS with CX localize at cardiomyocytes may produce a synergistic, hyperinflammatory response that cross-reacts with laminin, collagen IV, CAR and/or B1AR. Epitope drift shifts the immune response to myosin and actin after cardiomyocytes become damaged.

  8. Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle

    DEFF Research Database (Denmark)

    Wewer, U M; Thornell, L E; Loechel, F

    1997-01-01

    and Becker muscular dystrophy. Immunoaffinity chromatography of muscle extracts with a monoclonal antibody to the laminin alpha 2 chain followed by immunoblotting with various antibodies to the beta 2 chain demonstrated the presence of the laminin-4 (alpha 2-beta 2-gamma 1) isoform. Together the present...

  9. Construction of a fucoidan/laminin functional multilayer to direction vascular cell fate and promotion hemocompatibility

    International Nuclear Information System (INIS)

    Ye, Changrong; Wang, Yan; Su, Hong; Yang, Ping; Huang, Nan; Maitz, Manfred F.; Zhao, Anshan

    2016-01-01

    Surface biofunctional modification of cardiovascular stents is a versatile approach to reduce the adverse effects after implantation. In this work, a novel multifunctional coating was fabricated by coimmobilization of the sulfated polysaccharide of brown algae fucoidan and laminin to biomimic the vascular intimal conditions in order to support rapid endothelialization, prevent restenosis and improve hemocompatibility. The surface properties of the coating such as hydrophilicity, bonding density of biomolecules and stability were evaluated and optimized. According to the biocompatibility tests, the fucoidan/laminin multilayer coated surface displayed less platelet adhesion with favorable anticoagulant property. In addition, the fucoidan/laminin complex showed function to selectively regulate vascular cells growth behavior. The proliferation of endothelial cells (ECs) on the fucoidan/laminin biofunctional coating was significantly promoted. For the smooth muscle cells (SMCs), inhibitory effects on cell adhesion and proliferation were observed. In conclusion, the fucoidan/laminin biofunctional coating was successfully fabricated with desirable anticoagulant and endothelialization properties which show a promising application in the vascular devices such as vascular stents or grafts surface modification. - Highlights: • Construction of fucoidan/laminin functional multilayer to biomimic the basement membrane of vascular • The fucoidan/laminin complex demonstrates anti-coagulation property. • The fucoidan/laminin complex can selectively regulate EC and SMC growth behavior to prevent restenosis.

  10. Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin

    DEFF Research Database (Denmark)

    Albrechtsen, R; Nielsen, M; Wewer, U

    1981-01-01

    The distribution of the basement membrane glycoprotein laminin was studied by the immunoperoxidase technique in benign and malignant human breast tissue and in axillary lymph nodes from patients with breast cancer. An antiserum prepared against rat laminin was used. The specificity...

  11. Construction of a fucoidan/laminin functional multilayer to direction vascular cell fate and promotion hemocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Changrong; Wang, Yan; Su, Hong; Yang, Ping; Huang, Nan [Key Laboratory of Advanced Materials Technology of Ministry of Education, Department of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Maitz, Manfred F. [Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Dresden 01069 (Germany); Zhao, Anshan [Key Laboratory of Advanced Materials Technology of Ministry of Education, Department of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2016-07-01

    Surface biofunctional modification of cardiovascular stents is a versatile approach to reduce the adverse effects after implantation. In this work, a novel multifunctional coating was fabricated by coimmobilization of the sulfated polysaccharide of brown algae fucoidan and laminin to biomimic the vascular intimal conditions in order to support rapid endothelialization, prevent restenosis and improve hemocompatibility. The surface properties of the coating such as hydrophilicity, bonding density of biomolecules and stability were evaluated and optimized. According to the biocompatibility tests, the fucoidan/laminin multilayer coated surface displayed less platelet adhesion with favorable anticoagulant property. In addition, the fucoidan/laminin complex showed function to selectively regulate vascular cells growth behavior. The proliferation of endothelial cells (ECs) on the fucoidan/laminin biofunctional coating was significantly promoted. For the smooth muscle cells (SMCs), inhibitory effects on cell adhesion and proliferation were observed. In conclusion, the fucoidan/laminin biofunctional coating was successfully fabricated with desirable anticoagulant and endothelialization properties which show a promising application in the vascular devices such as vascular stents or grafts surface modification. - Highlights: • Construction of fucoidan/laminin functional multilayer to biomimic the basement membrane of vascular • The fucoidan/laminin complex demonstrates anti-coagulation property. • The fucoidan/laminin complex can selectively regulate EC and SMC growth behavior to prevent restenosis.

  12. Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene

    DEFF Research Database (Denmark)

    Xu, H; Wu, X R; Wewer, U M

    1994-01-01

    The classic murine muscular dystrophy strain, dy, was first described almost 40 years ago. We have identified the molecular basis of an allele of dy, called dy2J, by detecting a mutation in the laminin alpha 2 chain gene--the first identified mutation in laminin-2. The G to A mutation in a splice...

  13. Purification, crystallization and preliminary crystallographic analysis of Streptococcus pyogenes laminin-binding protein Lbp

    International Nuclear Information System (INIS)

    Linke, Christian; Caradoc-Davies, Tom T.; Proft, Thomas; Baker, Edward N.

    2008-01-01

    The S. pyogenes laminin-binding protein Lbp, which is essential for adhesion to human laminin, has been expressed, purified and crystallized. The laminin-binding protein Lbp (Spy2007) from Streptococcus pyogenes (a group A streptococcus) mediates adhesion to the human basal lamina glycoprotein laminin. Accordingly, Lbp is essential in in vitro models of cell adhesion and invasion. However, the molecular and structural basis of laminin binding by bacteria remains unknown. Therefore, the lbp gene has been cloned for recombinant expression in Escherichia coli. Lbp has been purified and crystallized from 30%(w/v) PEG 1500 by the sitting-drop vapour-diffusion method. The crystals belonged to the monoclinic space group P2 1 , with unit-cell parameters a = 42.62, b = 92.16, c = 70.61 Å, β = 106.27°, and diffracted to 2.5 Å resolution

  14. Purification, crystallization and preliminary crystallographic analysis of Streptococcus pyogenes laminin-binding protein Lbp

    Energy Technology Data Exchange (ETDEWEB)

    Linke, Christian, E-mail: clin180@ec.auckland.ac.nz [School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland (New Zealand); Caradoc-Davies, Tom T. [School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland (New Zealand); Australian Synchrotron, Clayton, Victoria 3168 (Australia); Proft, Thomas [School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland (New Zealand); Baker, Edward N. [School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland (New Zealand)

    2008-02-01

    The S. pyogenes laminin-binding protein Lbp, which is essential for adhesion to human laminin, has been expressed, purified and crystallized. The laminin-binding protein Lbp (Spy2007) from Streptococcus pyogenes (a group A streptococcus) mediates adhesion to the human basal lamina glycoprotein laminin. Accordingly, Lbp is essential in in vitro models of cell adhesion and invasion. However, the molecular and structural basis of laminin binding by bacteria remains unknown. Therefore, the lbp gene has been cloned for recombinant expression in Escherichia coli. Lbp has been purified and crystallized from 30%(w/v) PEG 1500 by the sitting-drop vapour-diffusion method. The crystals belonged to the monoclinic space group P2{sub 1}, with unit-cell parameters a = 42.62, b = 92.16, c = 70.61 Å, β = 106.27°, and diffracted to 2.5 Å resolution.

  15. Folliculostellate Cells Are Required for Laminin Release from Gonadotrophs in Rat Anterior Pituitary

    International Nuclear Information System (INIS)

    Tsukada, Takehiro; Fujiwara, Ken; Horiguchi, Kotaro; Azuma, Morio; Ramadhani, Dini; Tofrizal, Alimuddin; Batchuluun, Khongorzul; Maliza, Rita; Syaidah, Rahimi; Kikuchi, Motoshi; Yashiro, Takashi

    2014-01-01

    The anterior pituitary gland is organized tissue comprising hormone-producing cells and folliculostellate (FS) cells. FS cells interconnect to form a meshwork, and their cytoplasmic processes are anchored by a basement membrane containing laminin. Recently, we developed a three-dimensional (3D) cell culture that reproduces this FS cell architecture. In this study of the novel function of FS cells, we used transgenic rats that express green fluorescent protein in FS cells for the 3D culture. Anterior pituitary cells were cultured with different proportions of FS cells (0%, 5%, 10%, and 20%). Anterior pituitary cells containing 5–20% FS cells formed round/oval cell aggregates, whereas amorphous cell aggregates were formed in the absence of FS cells. Interestingly, immunohistochemistry showed laminin-immunopositive cells instead of extracellular laminin deposition in FS cell-deficient cell aggregates. Double-immunostaining revealed that these laminin-immunopositive cells were gonadotrophs. Laminin mRNA expression did not differ in relation to the presence or absence of FS cells. When anterior pituitary cells with no FS cells were cultured with FS cell-conditioned medium, the proportion of laminin-immunopositive cells was lower than in control. These results suggest that a humoral factor from FS cells is required for laminin release from gonadotrophs

  16. Cellular Interaction of Integrin α3β1 with Laminin 5 Promotes Gap Junctional Communication

    Science.gov (United States)

    Lampe, Paul D.; Nguyen, Beth P.; Gil, Susana; Usui, Marcia; Olerud, John; Takada, Yoshikazu; Carter, William G.

    1998-01-01

    Wounding of skin activates epidermal cell migration over exposed dermal collagen and fibronectin and over laminin 5 secreted into the provisional basement membrane. Gap junctional intercellular communication (GJIC) has been proposed to integrate the individual motile cells into a synchronized colony. We found that outgrowths of human keratinocytes in wounds or epibole cultures display parallel changes in the expression of laminin 5, integrin α3β1, E-cadherin, and the gap junctional protein connexin 43. Adhesion of keratinocytes on laminin 5, collagen, and fibronectin was found to differentially regulate GJIC. When keratinocytes were adhered on laminin 5, both structural (assembly of connexin 43 in gap junctions) and functional (dye transfer) assays showed a two- to threefold increase compared with collagen and five- to eightfold over fibronectin. Based on studies with immobilized integrin antibody and integrin-transfected Chinese hamster ovary cells, the interaction of integrin α3β1 with laminin 5 was sufficient to promote GJIC. Mapping of intermediate steps in the pathway linking α3β1–laminin 5 interactions to GJIC indicated that protein trafficking and Rho signaling were both required. We suggest that adhesion of epithelial cells to laminin 5 in the basement membrane via α3β1 promotes GJIC that integrates individual cells into synchronized epiboles. PMID:9852164

  17. Laminin isoforms: biological roles and effects on the intracellular distribution of nuclear proteins in intestinal epithelial cells

    International Nuclear Information System (INIS)

    Turck, Natacha; Gross, Isabelle; Gendry, Patrick; Stutzmann, Jeanne; Freund, Jean-Noel; Kedinger, Michele; Simon-Assmann, Patricia; Launay, Jean-Francois

    2005-01-01

    Laminins are structurally and functionally major components of the extracellular matrix. Four isoforms of laminins (laminin-1, -2, -5 and -10) are expressed in a specific pattern along the crypt-villus axis of the intestine. Previous works indicated that expression of these isoforms is developmentally regulated and that laminins could modulate the behaviour of intestinal cells, but the exact role of each isoform remained unclear. Here, we report the first systematic analysis of the cellular functions of the four isoforms using the human colon adenocarcinoma Caco2/TC7 cell line as a model. We compared the respective abilities of each isoform to modulate adhesion, proliferation and differentiation of intestinal epithelial cells. We found that the isoforms were functionally distinct, with laminin-10 being the most adhesive substratum, laminin-2, laminin-5 and laminin-10 enhancing cellular proliferation and at the opposite, laminin-1 stimulating intestinal cell differentiation. To begin to characterise the molecular events induced by the different isoforms, we examined by immunofluorescence the intracellular distribution of several nuclear proteins, recently highlighted by a nuclear proteomic approach. We observed clear nucleocytoplasmic redistribution of these proteins, which depended on the laminin isoform. These results provide evidence for a distinct functional role of laminins in intestinal cell functions characterised by specific localisation of nuclear proteins

  18. Structural requirement of carboxyl-terminal globular domains of laminin alpha 3 chain for promotion of rapid cell adhesion and migration by laminin-5.

    Science.gov (United States)

    Hirosaki, T; Mizushima, H; Tsubota, Y; Moriyama, K; Miyazaki, K

    2000-07-21

    The basement membrane protein laminin-5, a heterotrimer of laminin alpha3, beta3, and gamma2 chains, potently promotes cellular adhesion and motility. It has been supposed that the carboxyl-terminal globular region of the alpha3 chain consisting of five distinct domains (G1 to G5) is important for its interaction with integrins. To clarify the function of each G domain, we transfected cDNAs for the full-length (wild type (WT)) and five deletion derivatives (DeltaGs) of the alpha3 chain into human fibrosarcoma cell line HT1080, which expressed and secreted the laminin beta3 and gamma2 chains but not the alpha3 chain. The transfectants with the alpha3 chain cDNAs lacking G5 (DeltaG(5)), G4-5 (DeltaG(4-5)), G3-5 (DeltaG(3-5)), and G2-5 (DeltaG(2-5)) secreted laminin-5 variants at levels comparable to that with WT cDNA. However, the transfectant with the cDNA without any G domains (DeltaG(1-5)) secreted little laminin-5, suggesting that the G domains are essential for the efficient assembly and secretion of the heterotrimer alpha3beta3gamma2. The transfectants with WT, DeltaG(5), and DeltaG(4-5) cDNAs survived in serum-free medium longer than those with DeltaG(3-5), DeltaG(2-5), and DeltaG(1-5) cDNAs. The transfectants with WT, DeltaG(5), and DeltaG(4-5) cDNAs secreted apparently the same size of laminin-5, which lacked G4 and G5 due to proteolytic cleavage between G3 and G4, and these laminin-5 forms potently promoted integrin alpha(3)beta(1)-dependent cell adhesion and migration. However, the laminin-5 forms of DeltaG(3-5) and DeltaG(2-5) hardly promoted the cell adhesion and motility. These findings demonstrate that the G3 domain, but not the G4 and G5 domains, of the alpha3 chain is essential for the potent promotion of cell adhesion and motility by laminin-5.

  19. Expression, purification, crystallization and preliminary crystallographic analysis of laminin-binding protein (Lmb) from Streptococcus agalactiae

    International Nuclear Information System (INIS)

    Ragunathan, Preethi; Spellerberg, Barbara; Ponnuraj, Karthe

    2009-01-01

    Laminin-binding protein from S. agalactiae was expressed, purified and crystallized and X-ray diffraction data were collected to 2.5 Å resolution. Laminin-binding protein (Lmb), a surface-exposed lipoprotein from Streptococcus agalactiae (group B streptococcus), mediates attachment to human laminin and plays a crucial role in the adhesion/invasion of eukaryotic host cells. However, the structural basis of laminin binding still remains unclear. In the context of detailed structural analysis, the lmb gene has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals diffracted to a resolution of 2.5 Å and belonged to the monoclinic space group P2 1 , with unit-cell parameters a = 56.63, b = 70.60, c = 75.37 Å, β = 96.77°

  20. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

    Science.gov (United States)

    Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

    2014-04-01

    The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins

  1. Regulation of laminin beta2 chain gene expression in human cancer cell lines

    DEFF Research Database (Denmark)

    Durkin, M E; Nielsen, F C; Loechel, F

    2001-01-01

    of the human laminin beta2 chain gene generates two isoforms of the 5' untranslated region of the beta2 chain mRNA. The translational efficiencies of the two laminin beta2 chain leaders did not differ significantly, when assayed by polysome profile analysis of endogenous clone A cell beta2 chain m......RNA, transient transfection of chimeric beta2 chain leader/luciferase expression plasmids in clone A cells, and translation of in vitro synthesized RNAs in rabbit reticulocyte lysates....

  2. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

    Science.gov (United States)

    Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

    2014-01-01

    Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional

  3. Noninvasive imaging of malignant tumors using laminin peptide fragments YIGSR labeled with Technetium-99m

    International Nuclear Information System (INIS)

    Qin, G.M.; Zhang, Y.X.; Hu, J.; An, R.; Gao, Z.R.; Cao, G.X.; Hnatowich, D.J.

    2002-01-01

    The radiopharmaceuticals that localize specifically at certain sites (such as peptides directed against receptors expressed on tumor cells or antibodies with high binding affinities for bacterial determinants) may be expected to display greater specificity of localization. Peptides, which diffuse rapidly into target lesions and clear rapidly elsewhere, may be expected to enjoy a pharmacokinetic advantage over those, such as antibodies, which accumulate and clear more slowly. The laminin peptide fragments YIGSR is known to bind to a 67-kDa laminin receptor. This receptor is understood to be expressed at higher than normal levels in malignant tumor cells, particularly those of breast and colon carcinomas. Methods 1 peptide conjugation and labeling A 2.5 mg/mL solution of YIGSR in 0.1 M N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer, pH8.0, and a fresh 10mg/mL solution of NHS-S-acetyl-MAG 3 in dimethylformamide dried over molecular sieve were prepared. 2 biodistribution and imaging studies A colony of KM mice (15-20g) were inoculated with 1x10 6 Ehrlich (breast) carcinoma tumor cells in the right thigh, and the tumors were allowed to grow for 6-7 days to a size of 1.0-1.5 cm in diameter. Biodistribution studies were performed in 40 KM mice after 50 μCi per mouse of 99m Tc-labeled YIGSR were injected intravenously. A total of 10 mice were injected intravenously in the tail vein with 1-2 mCi of 99m Tc-labeled YIGSR, immobilized with ketamine hydrochloride and imaged periodically from 0.5 hr to 24 hr with a gamma camera. The identical imaging procedure was also performed in mice with sterile infection/inflammation lesions to evaluate the specificity. Results Essentially complete conjugation was achieved by reverse-phase Sep-Pak C18 chromatography analysis. The highest accumulation of label was in the kidney first, with the liver and small bowel next. The injected activity localized in the lesion as early as 15 min and reached a saturation value at 3

  4. Laminin enhances the growth of human neural stem cells in defined culture media

    Directory of Open Access Journals (Sweden)

    Lathia Justin D

    2008-07-01

    Full Text Available Abstract Background Human neural stem cells (hNSC have the potential to provide novel cell-based therapies for neurodegenerative conditions such as multiple sclerosis and Parkinson's disease. In order to realise this goal, protocols need to be developed that allow for large quantities of hNSC to be cultured efficiently. As such, it is important to identify factors which enhance the growth of hNSC. In vivo, stem cells reside in distinct microenvironments or niches that are responsible for the maintenance of stem cell populations. A common feature of niches is the presence of the extracellular matrix molecule, laminin. Therefore, this study investigated the effect of exogenous laminin on hNSC growth. Results To measure hNSC growth, we established culture conditions using B27-supplemented medium that enable neurospheres to grow from human neural cells plated at clonal densities. Limiting dilution assays confirmed that neurospheres were derived from single cells at these densities. Laminin was found to increase hNSC numbers as measured by this neurosphere formation. The effect of laminin was to augment the proliferation/survival of the hNSC, rather than promoting the undifferentiated state. In agreement, apoptosis was reduced in dissociated neurospheres by laminin in an integrin β1-dependent manner. Conclusion The addition of laminin to the culture medium enhances the growth of hNSC, and may therefore aid their large-scale production.

  5. Interdependence of laminin-mediated clustering of lipid rafts and the dystrophin complex in astrocytes.

    Science.gov (United States)

    Noël, Geoffroy; Tham, Daniel Kai Long; Moukhles, Hakima

    2009-07-17

    Astrocyte endfeet surrounding blood vessels are active domains involved in water and potassium ion transport crucial to the maintenance of water and potassium ion homeostasis in brain. A growing body of evidence points to a role for dystroglycan and its interaction with perivascular laminin in the targeting of the dystrophin complex and the water-permeable channel, aquaporin 4 (AQP4), at astrocyte endfeet. However, the mechanisms underlying such compartmentalization remain poorly understood. In the present study we found that AQP4 resided in Triton X-100-insoluble fraction, whereas dystroglycan was recovered in the soluble fraction in astrocytes. Cholesterol depletion resulted in the translocation of a pool of AQP4 to the soluble fraction indicating that its distribution is indeed associated with cholesterol-rich membrane domains. Upon laminin treatment AQP4 and the dystrophin complex, including dystroglycan, reorganized into laminin-associated clusters enriched for the lipid raft markers GM1 and flotillin-1 but not caveolin-1. Reduced diffusion rates of GM1 in the laminin-induced clusters were indicative of the reorganization of raft components in these domains. In addition, both cholesterol depletion and dystroglycan silencing reduced the number and area of laminin-induced clusters of GM1, AQP4, and dystroglycan. These findings demonstrate the interdependence between laminin binding to dystroglycan and GM1-containing lipid raft reorganization and provide novel insight into the dystrophin complex regulation of AQP4 polarization in astrocytes.

  6. Changes in Laminin Chain Expression in Pre- and Postnatal Rat Pituitary Gland

    International Nuclear Information System (INIS)

    Ramadhani, Dini; Tsukada, Takehiro; Fujiwara, Ken; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2014-01-01

    Cell–matrix interaction is required for tissue development. Laminin, a major constituent of the basement membrane, is important for structural support and as a ligand in tissue development. Laminin has 19 isoforms, which are determined by combinational assembly of five α, three β, and three γ chains (eg, laminin 121 is α1, β2, and γ1). However, no report has identified the laminin isoforms expressed during pituitary development. We used in situ hybridization to investigate all laminin chains expressed during rat anterior pituitary development. The α5 chain was expressed during early pituitary development (embryonic day 12.5–15.5). Expression of α1 and α4 chains was noted in vasculature cells at embryonic day 19.5, but later diminished. The α1 chain was re-expressed in parenchymal cells of anterior lobe from postnatal day 10 (P10), while the α4 chain was present in vasculature cells from P30. The α2 and α3 chains were transiently expressed in vasculature cells and anterior lobe, respectively, only at P30. Widespread distribution of β and γ chains was also observed during development. These findings suggest that numerous laminin isoforms are involved in anterior pituitary gland development and that alteration of the expression pattern is required for proper development of the gland

  7. Integrin β4 Regulates Migratory Behavior of Keratinocytes by Determining Laminin-332 Organization*s

    Science.gov (United States)

    Sehgal, Bernd U.; DeBiase, Phillip J.; Matzno, Sumio; Chew, Teng-Leong; Claiborne, Jessica N.; Hopkinson, Susan B.; Russell, Alan; Marinkovich, M. Peter; Jones, Jonathan C. R.

    2010-01-01

    Whether α6β4 integrin regulates migration remains controversial. β4 integrin-deficient (JEB) keratinocytes display aberrant migration in that they move in circles, a behavior that mirrors the circular arrays of laminin (LM)-332 in their matrix. In contrast, wild-type keratinocytes and JEB keratinocytes, induced to express β4 integrin, assemble laminin-332 in linear tracks over which they migrate. Moreover, laminin-332-dependent migration of JEB keratinocytes along linear tracks is restored when cells are plated on wild-type keratinocyte matrix, whereas wild-type keratinocytes show rotation over circular arrays of laminn-332 in JEB keratinocyte matrix. The activities of Rac1 and the actin cytoskeleton-severing protein cofilin are low in JEB keratinocytes compared with wild-type cells but are rescued following expression of wild-type β4 integrin in JEB cells. Additionally, in wild-type keratinocytes Rac1 is complexed with α6β4 integrin. Moreover, Rac1 or cofilin inactivation induces wild-type keratinocytes to move in circles over rings of laminin-332 in their matrix. Together these data indicate that laminin-332 matrix organization is determined by the α6β4 integrin/actin cytoskeleton via Rac1/cofilin signaling. Furthermore, our results imply that the organizational state of laminin-332 is a key determinant of the motility behavior of keratinocytes, an essential element of skin wound healing and the successful invasion of epidermal-derived tumor cells. PMID:16973601

  8. Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse

    DEFF Research Database (Denmark)

    Xu, H; Christmas, P; Wu, X R

    1994-01-01

    -linked Duchenne and Becker muscular dystrophies. We have examined M-laminin expression in mice with autosomal recessive muscular dystrophy caused by the mutation dy. The heavy chain of M-laminin was undetectable in skeletal muscle, heart muscle, and peripheral nerve by immunofluorescence and immunoblotting......M-laminin is a major member of the laminin family of basement membrane proteins. It is prominently expressed in striated muscle and peripheral nerve. M-laminin is deficient in patients with the autosomal recessive Fukuyama congenital muscular dystrophy but is normal in patients with the sex...... tissue from dy/dy mice, suggesting that M-laminin heavy-chain mRNA may be produced at very low levels or is unstable. Information about the chromosomal localization of the M heavy-chain in human and mouse suggests that a mutation in the M-chain gene causes the muscular dystrophy in dy/dy mice. The dy...

  9. De novo deposition of laminin-positive basement membrane in vitro by normal hepatocytes and during hepatocarcinogenesis

    DEFF Research Database (Denmark)

    Albrechtsen, R; Wewer, U M; Thorgeirsson, S S

    1988-01-01

    De novo formation of laminin-positive basement membranes was found to be a distinct morphologic feature of diethylnitrosamine/phenobarbital-induced hepatocellular carcinomas of the rat. The first appearance of extracellularly located laminin occurred in the preneoplastic liver lesions...... (corresponding to neoplastic nodules), and this feature became successively more prominent during the course of hepatocellular carcinoma development. Most groups of tumor cells were surrounded by laminin-positive basement membrane material. The laminin-positive material was also deposited along the sinusoids......, a location where no laminin was seen in normal rat liver. The amount of extractable laminin from hepatocellular carcinomas was significantly higher (approximately 100 ng per mg tissue) than that of normal liver tissue (less than 20 ng per mg). In vitro experiments demonstrated that normal and preneoplastic...

  10. Generation and characterization of recombinant human antibodies specific for native laminin epitopes. Potential application in cancer therapy. Cancer Immunol. Immunother

    DEFF Research Database (Denmark)

    Sanz, Laura; Kristensen, Peter; Russell, Stephen J.

    2001-01-01

    of human-derived antibody fragments able to modulate laminin-regulated biological functions would allow the development of new strategies to improve treatment of cancer patients. In this report, we explore the use of phage display technology to isolate human anti-laminin antibody fragments. A library...... to mouse, rat and human laminin. and show strong immunohistochemical reactivity with basement membranes in human and murine tissue sections. Their properties make them ideal candidates for in vivo applications....

  11. Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Morales-Nebreda, Luisa I; Rogel, Micah R; Eisenberg, Jessica L; Hamill, Kevin J; Soberanes, Saul; Nigdelioglu, Recep; Chi, Monica; Cho, Takugo; Radigan, Kathryn A; Ridge, Karen M; Misharin, Alexander V; Woychek, Alex; Hopkinson, Susan; Perlman, Harris; Mutlu, Gokhan M; Pardo, Annie; Selman, Moises; Jones, Jonathan C R; Budinger, G R Scott

    2015-04-01

    Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the α3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the α3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-β was worse in mice deficient in α3 laminin in the lung. Taken together, our results suggest that the loss of α3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-β. Thus, we speculate that the loss of the normal basement membrane organization of α3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression.

  12. Increased Expression of Laminin Subunit Alpha 1 Chain by dCas9-VP160

    Directory of Open Access Journals (Sweden)

    Arnaud Perrin

    2017-03-01

    Full Text Available Laminin-111 protein complex links the extracellular matrix to integrin α7β1 in sarcolemma, thus replacing in dystrophic muscles links normally insured by the dystrophin complex. Laminin-111 injection in mdx mouse stabilized sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscles from exercised-induced damages. These results suggested that increased laminin-111 is a potential therapy for DMD. Laminin subunit beta 1 and laminin subunit gamma 1 are expressed in adult human muscle, but laminin subunit alpha 1 (LAMA1 gene is expressed only during embryogenesis. We thus developed an alternative method to laminin-111 protein repeated administration by inducing expression of the endogenous mouse Lama1 gene. This was done with the CRSPR/Cas9 system, i.e., by targeting the Lama1 promoter with one or several gRNAs and a dCas9 coupled with the VP160 transcription activation domain. Lama1 mRNA (qRT-PCR and proteins (immunohistochemistry and western blot were not detected in the control C2C12 myoblasts and in control muscles. However, significant expression was observed in cells transfected and in mouse muscles electroporated with plasmids coding for dCas9-VP160 and a gRNA. Larger synergic increases were observed by using two or three gRNAs. The increased Lama1 expression did not modify the expression of the α7 and β1 integrins. Increased expression of Lama1 by the CRISPR/Cas9 system will have to be further investigated by systemic delivery of the CRISPR/Cas9 components to verify whether this could be a treatment for several myopathies.

  13. Increased Expression of Laminin Subunit Alpha 1 Chain by dCas9-VP160.

    Science.gov (United States)

    Perrin, Arnaud; Rousseau, Joël; Tremblay, Jacques P

    2017-03-17

    Laminin-111 protein complex links the extracellular matrix to integrin α7β1 in sarcolemma, thus replacing in dystrophic muscles links normally insured by the dystrophin complex. Laminin-111 injection in mdx mouse stabilized sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscles from exercised-induced damages. These results suggested that increased laminin-111 is a potential therapy for DMD. Laminin subunit beta 1 and laminin subunit gamma 1 are expressed in adult human muscle, but laminin subunit alpha 1 (LAMA1) gene is expressed only during embryogenesis. We thus developed an alternative method to laminin-111 protein repeated administration by inducing expression of the endogenous mouse Lama1 gene. This was done with the CRSPR/Cas9 system, i.e., by targeting the Lama1 promoter with one or several gRNAs and a dCas9 coupled with the VP160 transcription activation domain. Lama1 mRNA (qRT-PCR) and proteins (immunohistochemistry and western blot) were not detected in the control C2C12 myoblasts and in control muscles. However, significant expression was observed in cells transfected and in mouse muscles electroporated with plasmids coding for dCas9-VP160 and a gRNA. Larger synergic increases were observed by using two or three gRNAs. The increased Lama1 expression did not modify the expression of the α7 and β1 integrins. Increased expression of Lama1 by the CRISPR/Cas9 system will have to be further investigated by systemic delivery of the CRISPR/Cas9 components to verify whether this could be a treatment for several myopathies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. The diagnostic and biological implications of laminin expression in serous tubal intraepithelial carcinoma.

    Science.gov (United States)

    Kuhn, Elisabetta; Kurman, Robert J; Soslow, Robert A; Han, Guangming; Sehdev, Ann Smith; Morin, Patrick J; Wang, Tian-Li; Shih, Ie-Ming

    2012-12-01

    There is compelling evidence to suggest that serous tubal intraepithelial carcinoma (STIC) is the likely primary site for the development of many pelvic high-grade serous carcinomas (HGSCs). Identifying molecules that are upregulated in STIC is important not only to provide biomarkers to assist in the diagnosis of STIC but also to elucidate our understanding of the pathogenesis of HGSC. In this study, we performed RNA sequencing to compare transcriptomes between HGSC and normal fallopian tube epithelium (FTE), and we identified LAMC1 encoding laminin γ1 as one of the preferentially upregulated genes associated with HGSC. Reverse transcription polymerase chain reaction further validated LAMC1 upregulation in HGSC as compared with normal FTE. Immunohistochemical analysis was performed on 32 cases of concurrent HGSC and STIC. The latter was diagnosed on the basis of morphology, TP53 mutations, and p53 and Ki-67 immunohistochemical patterns. Laminin γ1 immunostaining intensity was found to be significantly higher in STIC and HGSC compared with adjacent FTE in all cases (PSTIC and HGSC cells, laminin γ1 staining was diffuse and intense throughout the cytoplasm. More importantly, strong laminin γ1 staining was detected in all 13 STICs, which lacked p53 immunoreactivity because of null mutations. These findings suggest that the overexpression of laminin γ1 immunoreactivity and alteration of its staining pattern in STICs can serve as a useful tissue biomarker, especially for those STICs that are negative for p53 and have a low Ki-67 labeling index.

  15. Keratinocyte-derived laminin-332 protein promotes melanin synthesis via regulation of tyrosine uptake.

    Science.gov (United States)

    Chung, Heesung; Jung, Hyejung; Lee, Jung-Hyun; Oh, Hye Yun; Kim, Ok Bin; Han, Inn-Oc; Oh, Eok-Soo

    2014-08-01

    Melanocytes, which produce the pigment melanin, are known to be closely regulated by neighboring keratinocytes. However, how keratinocytes regulate melanin production is unclear. Here we report that melanin production in melanoma cells (B16F10 and MNT-1) was increased markedly on a keratinocyte-derived extracellular matrix compared with a melanoma cell-derived extracellular matrix. siRNA-mediated reduction of keratinocyte-derived laminin-332 expression decreased melanin synthesis in melanoma cells, and laminin-332, but not fibronectin, enhanced melanin content and α-melanocyte-stimulating hormone-regulated melanin production in melanoma cells. Similar effects were observed in human melanocytes. Interestingly, however, laminin-332 did not affect the expression or activity of tyrosinase. Instead, laminin-332 promoted the uptake of extracellular tyrosine and, subsequently, increased intracellular levels of tyrosine in both melanocytes and melanoma cells. Taken together, these data strongly suggest that keratinocyte-derived laminin-332 contributes to melanin production by regulating tyrosine uptake. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Laminin and Matrix metalloproteinase 11 regulate Fibronectin levels in the zebrafish myotendinous junction.

    Science.gov (United States)

    Jenkins, Molly H; Alrowaished, Sarah S; Goody, Michelle F; Crawford, Bryan D; Henry, Clarissa A

    2016-01-01

    Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition. We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture. These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.

  17. Effects of laminin blended with chitosan on axon guidance on patterned substrates

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, N; Guan, Y J; Chen, X B [Division of Biomedical Engineering, University of Saskatchewan, Saskatoon S7N 5A9 (Canada); Li, M G [Department of Mechanical Engineering, University of Saskatchewan, Saskatoon S7N 5A9 (Canada); Schreyer, D J, E-mail: niz504@mail.usask.c [Department of Anatomy and Cell Biology, Cameco MS Neuroscience Research Center, University of Saskatchewan, Saskatoon, S7K 0M7 (Canada)

    2010-12-15

    Axon guidance is a crucial consideration in the design of tissue scaffolds used to promote nerve regeneration. Here we investigate the combined use of laminin (a putative axon adhesion and guidance molecule) and chitosan (a leading candidate base material for the construction of scaffolds) for promoting axon guidance in cultured adult dorsal root ganglion (DRG) neurons. Using a dispensing-based rapid prototyping (DBRP) technique, two-dimensional grid patterns were created by dispensing chitosan or laminin-blended chitosan substrate strands oriented in orthogonal directions. In vitro experiments illustrated DRG neurites on these patterns preferentially grew upon and followed the laminin-blended chitosan pathways. These results suggest that an orientation of neurite growth can be achieved in an artificially patterned substrate by creating selectively biofunctional pathways. The DBRP technique may provide improved strategies for the use of biofunctional pathways in the design of three-dimensional scaffolds for guidance of nerve repair.

  18. Effects of laminin blended with chitosan on axon guidance on patterned substrates

    International Nuclear Information System (INIS)

    Zhu, N; Guan, Y J; Chen, X B; Li, M G; Schreyer, D J

    2010-01-01

    Axon guidance is a crucial consideration in the design of tissue scaffolds used to promote nerve regeneration. Here we investigate the combined use of laminin (a putative axon adhesion and guidance molecule) and chitosan (a leading candidate base material for the construction of scaffolds) for promoting axon guidance in cultured adult dorsal root ganglion (DRG) neurons. Using a dispensing-based rapid prototyping (DBRP) technique, two-dimensional grid patterns were created by dispensing chitosan or laminin-blended chitosan substrate strands oriented in orthogonal directions. In vitro experiments illustrated DRG neurites on these patterns preferentially grew upon and followed the laminin-blended chitosan pathways. These results suggest that an orientation of neurite growth can be achieved in an artificially patterned substrate by creating selectively biofunctional pathways. The DBRP technique may provide improved strategies for the use of biofunctional pathways in the design of three-dimensional scaffolds for guidance of nerve repair.

  19. A novel biomarker of laminin turnover is associated with mortality and disease progression in chronic kidney disease

    DEFF Research Database (Denmark)

    Nielsen, Signe Holm; Guldager Kring Rasmussen, Daniel; Fenton, Anthony

    2017-01-01

    matrix (ECM) remodeling. The laminin γ1 (LAMC1) chain is a constituent of the laminin types present in the glomerular basement membrane (GBM), and its turnover may be altered in CKD. Fragments of LAMC1 could quantify GBM turnover in human CKD and reflect pathological tissue changes. We developed...

  20. The pattern of distribution of laminin in neurogenic tumors, granular cell tumors, and nevi of the oral mucosa

    DEFF Research Database (Denmark)

    Reibel, J; Wewer, U; Albrechtsen, R

    1985-01-01

    . Accentuated staining was seen in Verocay bodies. In granular cell myoblastomas (GCM), small groups of tumor cells were encircled by laminin-positive material, whereas individual tumor cells were unstained. In nevi, diffusely spread nevus cells were surrounded by a rim of laminin, whereas when arranged...

  1. Laminin-411 Is a Vascular Ligand for MCAM and Facilitates TH17 Cell Entry into the CNS

    Science.gov (United States)

    Flanagan, Ken; Fitzgerald, Kent; Baker, Jeanne; Regnstrom, Karin; Gardai, Shyra; Bard, Frederique; Mocci, Simonetta; Seto, Pui; You, Monica; Larochelle, Catherine; Prat, Alexandre; Chow, Samuel; Li, Lauri; Vandevert, Chris; Zago, Wagner; Lorenzana, Carlos; Nishioka, Christopher; Hoffman, Jennifer; Botelho, Raquel; Willits, Christopher; Tanaka, Kevin; Johnston, Jennifer; Yednock, Ted

    2012-01-01

    TH17 cells enter tissues to facilitate pathogenic autoimmune responses, including multiple sclerosis (MS). However, the adhesion molecules involved in the unique migratory capacity of TH17 cells, into both inflamed and uninflamed tissues remain unclear. Herein, we characterize MCAM (CD146) as an adhesion molecule that defines human TH17 cells in the circulation; following in vitro restimulation of human memory T cells, nearly all of the capacity to secrete IL-17 is contained within the population of cells expressing MCAM. Furthermore, we identify the MCAM ligand as laminin 411, an isoform of laminin expressed within the vascular endothelial basement membranes under inflammatory as well as homeotstatic conditions. Purified MCAM-Fc binds to laminin 411 with an affinity of 27 nM, and recognizes vascular basement membranes in mouse and human tissue. MCAM-Fc binding was undetectable in tissue from mice with targeted deletion of laminin 411, indicating that laminin 411 is a major tissue ligand for MCAM. An anti-MCAM monoclonal antibody, selected for inhibition of laminin binding, as well as soluble MCAM-Fc, inhibited T cell adhesion to laminin 411 in vitro. When administered in vivo, the antibody reduced TH17 cell infiltration into the CNS and ameliorated disease in an animal model of MS. Our data suggest that MCAM and laminin 411 interact to facilitate TH17 cell entry into tissues and promote inflammation. PMID:22792325

  2. Laminin-10 and Its Receptors in Breast Carcinoma: Cooperation of Alpha6Beta4 and Alpha3Beta1 Integrin Laminin Receptors in Breast Carcinoma

    National Research Council Canada - National Science Library

    Awwad, Rana

    2003-01-01

    .... In fact, IRS-1 function might reduce the efficacy of IRS-2 in these processes. Altogether, the findings suggest that IRS-1 is involved in the early stages of breast cancer establishment and that IRS-2 is required for its maintenance and progression to malignancy. (6 figures, 20 refs.)

  3. Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Pujuguet, Philippe; Simian, Marina; Liaw, Jane; Timpl, Rupert; Werb, Zena; Bissell, Mina J..

    2000-02-01

    Nidogen-1 (entactin) acts as a bridge between the extracellular matrix molecules laminin-1 and type IV collagen, and thus participates in the assembly of basement membranes. To investigate the role of nidogen-1 in regulating cell-type-specific gene expression in mammary epithelium, we designed a culture microecosystem in which each component, including epithelial cells, mesenchymal cells, lactogenic hormones and extracellular matrix, could be controlled. We found that primary and established mesenchymal and myoepithelial cells synthesized and secreted nidogen-1, whereas expression was absent in primary and established epithelial cells. In an epithelial cell line containing mesenchymal cells, nidogen-1 was produced by the mesenchymal cells but deposited between the epithelial cells. In this mixed culture, mammary epithelial cells express b-casein in the presence of lactogenic hormones. Addition of either laminin-1 plus nidogen-1, or laminin-1 alone to mammary epithelial cells induced b- casein production. We asked whether recombinant nidogen-1 alone could signal directly for b-casein. Nidogen-1 did not induce b-casein synthesis in epithelial cells, but it augmented the inductive capacity of laminin-1. These data suggest that nidogen-1 can cooperate with laminin-1 to regulate b-casein expression. Addition of full length nidogen-1 to the mixed cultures had no effect on b-casein gene expression; however, a nidogen-1 fragment containing the laminin-1 binding domain, but lacking the type IV collagen-binding domain, had a dominant negative effect on b-casein expression. These data point to a physiological role for nidogen-1 in the basement membrane-induced gene expression by epithelial cells.

  4. Convergence of bone morphogenetic protein and laminin-1 signaling pathways promotes proliferation and colony formation by fetal mouse pancreatic cells

    International Nuclear Information System (INIS)

    Jiang Fangxu; Harrison, Leonard C.

    2005-01-01

    We previously reported that bone morphogenetic proteins (BMPs), members of the transforming growth factor superfamily, together with the basement membrane glycoprotein laminin-1 (Ln-1), promote proliferation of fetal pancreatic cells and formation of colonies containing peripheral insulin-positive cells. Here, we further investigate the cross-talk between BMP and Ln-1 signals. By RT-PCR, receptors for BMP (BMPR) (excepting BMPR-1B) and Ln-1 were expressed in the fetal pancreas between E13.5 and E17.5. Specific blocking antibodies to BMP-4 and -6 and selective BMP antagonists partially inhibited colony formation by fetal pancreas cells. Colony formation induced by BMP-6 and Ln-1 was completely abolished in a dose-dependent manner by blocking Ln-1 binding to its α 6 integrin and α-dystroglycan receptors or by blocking the Ln-1 signaling molecules, phosphatidyl-inositol-3-kinase (P13K) and MAP kinase kinase-1. These results demonstrate a convergence of BMP and Ln-1 signaling through P13K and MAP kinase pathways to induce proliferation and colony formation in E15.5 fetal mouse pancreatic cells

  5. Increased mRNA expression of a laminin-binding protein in human colon carcinoma: Complete sequence of a full-length cDNA encoding the protein

    International Nuclear Information System (INIS)

    Yow, Hsiukang; Wong, Jau Min; Chen, Hai Shiene; Lee, C.; Steele, G.D. Jr.; Chen, Lanbo

    1988-01-01

    Reliable markers to distinguish human colon carcinoma from normal colonic epithelium are needed particularly for poorly differentiated tumors where no useful marker is currently available. To search for markers the authors constructed cDNA libraries from human colon carcinoma cell lines and screened for clones that hybridize to a greater degree with mRNAs of colon carcinomas than with their normal counterparts. Here they report one such cDNA clone that hybridizes with a 1.2-kilobase (kb) mRNA, the level of which is ∼9-fold greater in colon carcinoma than in adjacent normal colonic epithelium. Blot hybridization of total RNA from a variety of human colon carcinoma cell lines shows that the level of this 1.2-kb mRNA in poorly differentiated colon carcinomas is as high as or higher than that in well-differentiated carcinomas. Molecular cloning and complete sequencing of cDNA corresponding to the full-length open reading frame of this 1.2-kb mRNA unexpectedly show it to contain all the partial cDNA sequence encoding 135 amino acid residues previously reported for a human laminin receptor. The deduced amino acid sequence suggests that this putative laminin-binding protein from human colon carcinomas consists of 295 amino acid residues with interesting features. There is an unusual C-terminal 70-amino acid segment, which is trypsin-resistant and highly negatively charged

  6. Divergent mechanisms underlie Smad4-mediated positive regulation of the three genes encoding the basement membrane component laminin-332 (laminin-5)

    International Nuclear Information System (INIS)

    Zboralski, Dirk; Böckmann, Miriam; Zapatka, Marc; Hoppe, Sabine; Schöneck, Anna; Hahn, Stephan A; Schmiegel, Wolff; Schwarte-Waldhoff, Irmgard

    2008-01-01

    Functional inactivation of the tumor suppressor Smad4 in colorectal and pancreatic carcinogenesis occurs coincident with the transition to invasive growth. Breaking the basement membrane (BM) barrier, a prerequisite for invasive growth, can be due to tumor induced proteolytic tissue remodeling or to reduced synthesis of BM molecules by incipient tumor cells. Laminin-332 (laminin-5), a heterotrimeric BM component composed of α3-, β3- and γ2-chains, has recently been identified as a target structure of Smad4 and represents the first example for expression control of an essential BM component by a tumor and invasion suppressor. Biochemically Smad4 is a transmitter of signals of the TGFβ superfamily of cytokines. We have reported previously, that Smad4 functions as a positive transcriptional regulator of constitutive and of TGFβ-induced transcription of all three genes encoding Laminin-332, LAMA3, LAMB3 and LAMC2. Promoter-reporter constructs harboring 4 kb upstream regions, each of the three genes encoding Laminin-322 as well as deletion and mutations constructs were established. Promoter activities and TGFβ induction were assayed through transient transfections in Smad4-negative human cancer cells and their stable Smad4-positive derivatives. Functionally relevant binding sites were subsequently confirmed through chromatin immunoprecipitation. Herein, we report that Smad4 mediates transcriptional regulation through three different mechanisms, namely through Smad4 binding to a functional SBE site exclusively in the LAMA3 promoter, Smad4 binding to AP1 (and Sp1) sites presumably via interaction with AP1 family components and lastly a Smad4 impact on transcription of AP1 factors. Whereas Smad4 is essential for positive regulation of all three genes, the molecular mechanisms are significantly divergent between the LAMA3 promoter as compared to the LAMB3 and LAMC2 promoters. We hypothesize that this divergence in modular regulation of the three promoters may lay the

  7. Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction

    KAUST Repository

    Patel, Trushar R.

    2015-07-26

    Laminins are key basement membrane molecules that influence several biological activities and are linked to a number of diseases. They are secreted as heterotrimeric proteins consisting of one α, one β, and one γ chain, followed by their assembly into a polymer-like sheet at the basement membrane. Using sedimentation velocity, dynamic light scattering, and surface plasmon resonance experiments, we studied self-association of three laminin (LM) N-terminal fragments α-1 (hLM α-1 N), α-5 (hLM α-5 N) and β-3 (hLM β-3 N) originating from the short arms of the human laminin αβγ heterotrimer. Corresponding studies of the hLM α-1 N C49S mutant, equivalent to the larval lethal C56S mutant in zebrafish, have shown that this mutation causes enhanced self-association behavior, an observation that provides a plausible explanation for the inability of laminin bearing this mutation to fulfill functional roles in vivo, and hence for the deleterious pathological consequences of the mutation on lens function.

  8. Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction

    KAUST Repository

    Patel, Trushar R.; Nikodemus, Denise; Besong, Tabot M.D.; Reuten, Raphael; Meier, Markus; Harding, Stephen E.; Winzor, Donald J.; Koch, Manuel; Stetefeld, Jö rg

    2015-01-01

    Laminins are key basement membrane molecules that influence several biological activities and are linked to a number of diseases. They are secreted as heterotrimeric proteins consisting of one α, one β, and one γ chain, followed by their assembly into a polymer-like sheet at the basement membrane. Using sedimentation velocity, dynamic light scattering, and surface plasmon resonance experiments, we studied self-association of three laminin (LM) N-terminal fragments α-1 (hLM α-1 N), α-5 (hLM α-5 N) and β-3 (hLM β-3 N) originating from the short arms of the human laminin αβγ heterotrimer. Corresponding studies of the hLM α-1 N C49S mutant, equivalent to the larval lethal C56S mutant in zebrafish, have shown that this mutation causes enhanced self-association behavior, an observation that provides a plausible explanation for the inability of laminin bearing this mutation to fulfill functional roles in vivo, and hence for the deleterious pathological consequences of the mutation on lens function.

  9. Hypertonic saline impedes tumor cell-endothelial cell interaction by reducing adhesion molecule and laminin expression.

    LENUS (Irish Health Repository)

    Shields, Conor J

    2012-02-03

    BACKGROUND: Hypertonic saline infusion dampens inflammatory responses and suppresses neutrophil-endothelial interaction by reducing adhesion molecule expression. This study tested the hypothesis that hypertonic saline attenuates tumor cell adhesion to the endothelium through a similar mechanism. METHODS: Human colon cancer cells (LS174T) were transfected with green fluorescent protein and exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 under hypertonic and isotonic conditions for 1 and 4 hours. Confluent human umbilical vein endothelial cells were similarly exposed. Cellular apoptosis and expression of adhesion molecules and laminin were measured by flow cytometry. Tumor cell adhesion to endothelium and laminin was assessed with fluorescence microscopy. Data are represented as mean +\\/- standard error of mean, and an ANOVA test was performed to gauge statistical significance, with P <.05 considered significant. RESULTS: Hypertonic exposure significantly reduced tumor cell adhesion despite the presence of the perioperative cell stressors (42 +\\/- 2.9 vs 172.5 +\\/- 12.4, P <.05), attenuated tumor cell beta-1 integrin (14.43 vs 23.84, P <.05), and endothelial cell laminin expression (22.78 +\\/- 2.2 vs 33.74 +\\/- 2.4, P <.05), but did not significantly alter cell viability. CONCLUSION: Hypertonic saline significantly attenuates tumor cell adhesion to endothelium by inhibiting adhesion molecule and laminin expression. This may halt the metastatic behavior of tumor cells shed at surgery.

  10. Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.

    Science.gov (United States)

    Körner, Zandra; Fontes-Oliveira, Cibely C; Holmberg, Johan; Carmignac, Virginie; Durbeej, Madeleine

    2014-05-01

    Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Stromal laminin chain distribution in normal, hyperplastic and malignant oral mucosa: relation to myofibroblast occurrence and vessel formation.

    Science.gov (United States)

    Franz, Marcus; Wolheim, Anke; Richter, Petra; Umbreit, Claudia; Dahse, Regine; Driemel, Oliver; Hyckel, Peter; Virtanen, Ismo; Kosmehl, Hartwig; Berndt, Alexander

    2010-04-01

    The contribution of stromal laminin chain expression to malignant potential, tumour stroma reorganization and vessel formation in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the expression of the laminin chains alpha2, alpha3, alpha4, alpha5 and gamma2 in the stromal compartment/vascular structures in OSCC was analysed. Frozen tissue of OSCC (9x G1, 24x G2, 8x G3) and normal (2x)/hyperplastic (11x) oral mucosa was subjected to laminin chain and alpha-smooth muscle actin (ASMA) immunohistochemistry. Results were correlated to tumour grade. The relation of laminin chain positive vessels to total vessel number was assessed by immunofluorescence double labelling with CD31. Stromal laminin alpha2 chain significantly decreases and alpha3, alpha4, alpha5 and gamma2 chains and also ASMA significantly increase with rising grade. The amount of stromal alpha3, alpha4 and gamma2 chains significantly increased with rising ASMA positivity. There is a significant decrease in alpha3 chain positive vessels with neoplastic transformation. Mediated by myofibroblasts, OSCC development is associated with a stromal up-regulation of laminin isoforms possibly contributing to a migration promoting microenvironment. A vascular basement membrane reorganization concerning alpha3 and gamma2 chain laminins during tumour angioneogenesis is suggested.

  12. Mesenchymal Stromal Cells for Sphincter Regeneration: Role of Laminin Isoforms upon Myogenic Differentiation

    Science.gov (United States)

    Seeger, Tanja; Hart, Melanie; Patarroyo, Manuel; Rolauffs, Bernd; Aicher, Wilhelm K.; Klein, Gerd

    2015-01-01

    Multipotent mesenchymal stromal cells (MSCs) are well known for their tri-lineage potential and ability to differentiate in vitro into osteogenic, chondrogenic or adipogenic lineages. By selecting appropriate conditions MSCs can also be differentiated in vitro into the myogenic lineage and are therefore a promising option for cell-based regeneration of muscle tissue such as an aged or damaged sphincter muscle. For the differentiation into the myogenic lineage there is still a need to evaluate the effects of extracellular matrix proteins such as laminins (LM) which are crucial for different stem cell types and for normal muscle function. The laminin family consists of 16 functionally different isoforms with LM-211 being the most abundant isoform of adult muscle tissues. In the sphincter tissue a strong expression of the isoforms LM-211/221, LM-411/421 and LM-511/521 can be detected in the different cell layers. Bone marrow-derived MSCs in culture, however, mainly express the isoforms LM-411 and LM-511, but not LM-211. Even after myogenic differentiation, LM-211 can hardly be detected. All laminin isoforms tested (LM-211, LM-411, LM-511 and LM-521) showed a significant inhibition of the proliferation of undifferentiated MSCs but, with the exception of LM-521, they had no influence on the proliferation of MSCs cultivated in myogenic medium. The strongest cellular adhesion of MSCs was to LM-511 and LM-521, whereas LM-211 was only a weakly-adhesive substrate for MSCs. Myogenic differentiation of MSCs even reduced the interaction with LM-211, but it did not affect the interaction with LM-511 and LM-521. Since during normal myogenesis the latter two isoforms are the major laminins surrounding developing myogenic progenitors, α5 chain-containing laminins are recommended for further improvements of myogenic differentiation protocols of MSCs into smooth muscle cells. PMID:26406476

  13. Mesenchymal Stromal Cells for Sphincter Regeneration: Role of Laminin Isoforms upon Myogenic Differentiation.

    Directory of Open Access Journals (Sweden)

    Tanja Seeger

    Full Text Available Multipotent mesenchymal stromal cells (MSCs are well known for their tri-lineage potential and ability to differentiate in vitro into osteogenic, chondrogenic or adipogenic lineages. By selecting appropriate conditions MSCs can also be differentiated in vitro into the myogenic lineage and are therefore a promising option for cell-based regeneration of muscle tissue such as an aged or damaged sphincter muscle. For the differentiation into the myogenic lineage there is still a need to evaluate the effects of extracellular matrix proteins such as laminins (LM which are crucial for different stem cell types and for normal muscle function. The laminin family consists of 16 functionally different isoforms with LM-211 being the most abundant isoform of adult muscle tissues. In the sphincter tissue a strong expression of the isoforms LM-211/221, LM-411/421 and LM-511/521 can be detected in the different cell layers. Bone marrow-derived MSCs in culture, however, mainly express the isoforms LM-411 and LM-511, but not LM-211. Even after myogenic differentiation, LM-211 can hardly be detected. All laminin isoforms tested (LM-211, LM-411, LM-511 and LM-521 showed a significant inhibition of the proliferation of undifferentiated MSCs but, with the exception of LM-521, they had no influence on the proliferation of MSCs cultivated in myogenic medium. The strongest cellular adhesion of MSCs was to LM-511 and LM-521, whereas LM-211 was only a weakly-adhesive substrate for MSCs. Myogenic differentiation of MSCs even reduced the interaction with LM-211, but it did not affect the interaction with LM-511 and LM-521. Since during normal myogenesis the latter two isoforms are the major laminins surrounding developing myogenic progenitors, α5 chain-containing laminins are recommended for further improvements of myogenic differentiation protocols of MSCs into smooth muscle cells.

  14. Adhesion of Trypanosoma cruzi trypomastigotes to fibronectin or laminin modifies tubulin and paraflagellar rod protein phosphorylation.

    Directory of Open Access Journals (Sweden)

    Eliciane C Mattos

    Full Text Available BACKGROUND: The unicellular parasite Trypanosoma cruzi is the causative agent of Chagaś disease in humans. Adherence of the infective stage to elements of the extracellular matrix (ECM, as laminin and fibronectin, is an essential step in host cell invasion. Although members of the gp85/TS, as Tc85, were identified as laminin and fibronectin ligands, the signaling events triggered on the parasite upon binding to these molecules are largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Viable infective parasites were incubated with laminin, fibronectin or bovine serum albumin for different periods of time and the proteins were separated by bidimensional gels. The phosphoproteins were envisaged by specific staining and the spots showing phosphorylation levels significantly different from the control were excised and identified by MS/MS. The results of interest were confirmed by immunoblotting or immunoprecipitation and the localization of proteins in the parasite was determined by immunofluorescence. Using a host cell-free system, our data indicate that the phosphorylation contents of T. cruzi proteins encompassing different cellular functions are modified upon incubation of the parasite with fibronectin or laminin. CONCLUSIONS/SIGNIFICANCE: Herein it is shown, for the first time, that paraflagellar rod proteins and α-tubulin, major structural elements of the parasite cytoskeleton, are predominantly dephosphorylated during the process, probably involving the ERK1/2 pathway. It is well established that T. cruzi binds to ECM elements during the cell infection process. The fact that laminin and fibronectin induce predominantly dephosphorylation of the main cytoskeletal proteins of the parasite suggests a possible correlation between cytoskeletal modifications and the ability of the parasite to internalize into host cells.

  15. NC1 domain of type VII collagen binds to the beta3 chain of laminin 5 via a unique subdomain within the fibronectin-like repeats.

    Science.gov (United States)

    Chen, M; Marinkovich, M P; Jones, J C; O'Toole, E A; Li, Y Y; Woodley, D T

    1999-02-01

    Type VII collagen, the major component of anchoring fibrils, consists of a central collagenous triple-helical domain flanked by two noncollagenous, globular domains, NC1 and NC2. Approximately 50% of the molecular mass of the molecule is consumed by the NC1 domain. We previously demonstrated that NC1 binds to various extracellular matrix components including a complex of laminin 5 and laminin 6 (Chen et al, 1997a). In this study, we examined the interaction of NC1 with laminin 5 (a component of anchoring filaments). Both authentic and purified recombinant NC1 bound to human and rat laminin 5 as measured by enzyme-linked immunosorbant assay and by binding of 125I-radiolabeled NC1 to laminin 5-coated wells, but not to laminin 1 or albumin. NC1 bound predominantly to the beta3 chain of laminin 5, but also to the gamma2 chain when examined by a protein overlay assay. The binding of 125I-NC1 to laminin 5 was inhibited by a 50-fold excess of unlabeled NC1 or de-glycosylated NC1, as well as a polyclonal antibody to laminin 5 or a monoclonal antibody to the beta3 chain. In contrast, the NC1-laminin 5 interaction was not affected by a monoclonal antibody to the alpha3 chain. Using NC1 deletion mutant recombinant proteins, a 285 AA (residues 760-1045) subdomain of NC1 was identified as the binding site for laminin 5. IgG from an epidermolysis bullosa acquisita serum containing autoantibodies to epitopes within NC1 that colocalized with the laminin 5 binding site inhibited the binding of NC1 to laminin 5. Thus, perturbation of the NC1-laminin 5 interaction may contribute to the pathogenesis of epidermolysis bullosa acquisita.

  16. Hyaluronic acid-laminin hydrogels increase neural stem cell transplant retention and migratory response to SDF-1α.

    Science.gov (United States)

    Addington, C P; Dharmawaj, S; Heffernan, J M; Sirianni, R W; Stabenfeldt, S E

    2017-07-01

    The chemokine SDF-1α plays a critical role in mediating stem cell response to injury and disease and has specifically been shown to mobilize neural progenitor/stem cells (NPSCs) towards sites of neural injury. Current neural transplant paradigms within the brain suffer from low rates of retention and engraftment after injury. Therefore, increasing transplant sensitivity to injury-induced SDF-1α represents a method for increasing neural transplant efficacy. Previously, we have reported on a hyaluronic acid-laminin based hydrogel (HA-Lm gel) that increases NPSC expression of SDF-1α receptor, CXCR4, and subsequently, NPSC chemotactic migration towards a source of SDF-1α in vitro. The study presented here investigates the capacity of the HA-Lm gel to promote NPSC response to exogenous SDF-1α in vivo. We observed the HA-Lm gel to significantly increase NPSC transplant retention and migration in response to SDF-1α in a manner critically dependent on signaling via the SDF-1α-CXCR4 axis. This work lays the foundation for development of a more effective cell therapy for neural injury, but also has broader implications in the fields of tissue engineering and regenerative medicine given the essential roles of SDF-1α across injury and disease states. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Assays of dioxins and dioxin-like compounds in actually contaminated soils using transgenic tobacco plants carrying a recombinant mouse aryl hydrocarbon receptor-mediated β-glucuronidase reporter gene expression system.

    Science.gov (United States)

    Inui, Hideyuki; Gion, Keiko; Utani, Yasushi; Wakai, Taketo; Kodama, Susumu; Eun, Heesoo; Kim, Yun-Seok; Ohkawa, Hideo

    2012-01-01

    The transgenic tobacco plant XD4V-26 carrying the recombinant mouse aryl hydrocarbon receptor XD4V-mediated β-glucuronidase (GUS) reporter gene expression system was used for assay of dioxins and dioxin-like compounds consisting of polychlorinated dibenzeno-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls (Co-PCBs) in actually contaminated soils. The transgenic tobacco plant XD4V-26 showed a significant dose-dependent induced GUS activity when cultured on MS medium containing PCB126 [toxic equivalency factor (TEF) = 0.1]. In contrast, PCB169 and PCB180, which have 0.03 of TEF and unassigned TEF values, respectively, did not significantly induce GUS activity under the same conditions as with PCB126. When the tobacco plants were cultivated for up to 5 weeks on actually contaminated soils with dioxins and dioxin-like compounds collected from the periphery of an incinerator used for disposal of residential and industrial wastes, GUS activity in the leaves was dose-dependently increased. The plants clearly detected 360 pg-TEQ g(-1) of dioxins and dioxin-like compounds in this assay. There was a positive correlation between GUS activity and TEQ value of dioxins and dioxin-like compounds in the plants. This assay does not require any extraction and purification processes for the actually contaminated soil samples.

  18. Whole-Genome Sequencing of Invasion-Resistant Cells Identifies Laminin α2 as a Host Factor for Bacterial Invasion

    DEFF Research Database (Denmark)

    van Wijk, Xander M.; Döhrmann, Simon; Hallstrom, Bjorn

    2017-01-01

    cells. Whole-genome sequencing and transcriptome sequencing (RNA-Seq) uncovered a deletion in the gene encoding the laminin subunit α2 (Lama2) that eliminated much of domain L4a. Silencing of the long Lama2 isoform in wild-type cells strongly reduced bacterial invasion, whereas transfection with human...... LAMA2 cDNA significantly enhanced invasion in pgsA745 cells. The addition of exogenous laminin-α2β1γ1/laminin-α2β2γ1 strongly increased bacterial invasion in CHO cells, as well as in human alveolar basal epithelial and human brain microvascular endothelial cells. Thus, the L4a domain in laminin α2...

  19. Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy.

    Science.gov (United States)

    Rooney, Jachinta E; Knapp, Jolie R; Hodges, Bradley L; Wuebbles, Ryan D; Burkin, Dean J

    2012-04-01

    Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a lethal muscle-wasting disease that is caused by mutations in the LAMA2 gene, resulting in the loss of laminin-α2 protein. MDC1A patients exhibit severe muscle weakness from birth, are confined to a wheelchair, require ventilator assistance, and have reduced life expectancy. There are currently no effective treatments or cures for MDC1A. Laminin-α2 is required for the formation of heterotrimeric laminin-211 (ie, α2, β1, and γ1) and laminin-221 (ie, α2, β2, and γ1), which are major constituents of skeletal muscle basal lamina. Laminin-111 (ie, α1, β1, and γ1) is the predominant laminin isoform in embryonic skeletal muscle and supports normal skeletal muscle development in laminin-α2-deficient muscle but is absent from adult skeletal muscle. In this study, we determined whether treatment with Engelbreth-Holm-Swarm-derived mouse laminin-111 protein could rescue MDC1A in the dy(W-/-) mouse model. We demonstrate that laminin-111 protein systemically delivered to the muscles of laminin-α2-deficient mice prevents muscle pathology, improves muscle strength, and dramatically increases life expectancy. Laminin-111 also prevented apoptosis in laminin-α2-deficient mouse muscle and primary human MDC1A myogenic cells, which indicates a conserved mechanism of action and cross-reactivity between species. Our results demonstrate that laminin-111 can serve as an effective protein substitution therapy for the treatment of muscular dystrophy in the dy(W-/-) mouse model and establish the potential for its use in the treatment of MDC1A. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. The heterotrimeric laminin coiled-coil domain exerts anti-adhesive effects and induces a pro-invasive phenotype.

    Directory of Open Access Journals (Sweden)

    Patricia Santos-Valle

    Full Text Available Laminins are large heterotrimeric cross-shaped extracellular matrix glycoproteins with terminal globular domains and a coiled-coil region through which the three chains are assembled and covalently linked. Laminins are key components of basement membranes, and they serve as attachment sites for cell adhesion, migration and proliferation. In this work, we produced a recombinant fragment comprising the entire laminin coiled-coil of the α1-, β1-, and γ1-chains that assemble into a stable heterotrimeric coiled-coil structure independently of the rest of the molecule. This domain was biologically active and not only failed to serve as a substrate for cell attachment, spreading and focal adhesion formation but also inhibited cell adhesion to laminin when added to cells in a soluble form at the time of seeding. Furthermore, gene array expression profiling in cells cultured in the presence of the laminin coiled-coil domain revealed up-regulation of genes involved in cell motility and invasion. These findings were confirmed by real-time quantitative PCR and zymography assays. In conclusion, this study shows for the first time that the laminin coiled-coil domain displays anti-adhesive functions and has potential implications for cell migration during matrix remodeling.

  1. INHERITED PATHOLOGY OF β2-LAMININ (PIERSON SYNDROME: CLINICAL AND GENETIC ASPECTS

    Directory of Open Access Journals (Sweden)

    M.Yu. Kagan

    2010-01-01

    Full Text Available For the last decade a great successes were attained in the study of molecular bases of glomerular diseases. It was certain that the most frequent reasons of congenital and infantile nephrotic syndrome are mutations in the genes of NPHS1, NPHS2, and WT1. Nevertheless, until now, a number of patients, having combination of early nephrotic syndrome with inherent pathology of other organs, which etiology remains un known. These cases continue to be intensively probed. One of the most important recent achievements in understanding of molecular mechanisms of early nephrotic syndrome is the discovery of mutations of gene of LAMB2, encoding β2 laminin, as the cause of Pearson syndrome (OMIM#609049. In this article the author presents the basic genetic and clinical descriptions of this recently identified pathology. Key words: Pearson syndrome, congenital nephrotic syndrome, β2 laminin, malformation of organ of vision. (Pediatric Pharmacology. – 2010; 7(3:114-117

  2. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis.

    Directory of Open Access Journals (Sweden)

    Duane Delimont

    Full Text Available It has been known for some time that laminins containing α1 and α2 chains, which are normally restricted to the mesangial matrix, accumulate in the glomerular basement membranes (GBM of Alport mice, dogs, and humans. We show that laminins containing the α2 chain, but not those containing the α1 chain activates focal adhesion kinase (FAK on glomerular podocytes in vitro and in vivo. CD151-null mice, which have weakened podocyte adhesion to the GBM rendering these mice more susceptible to biomechanical strain in the glomerulus, also show progressive accumulation of α2 laminins in the GBM, and podocyte FAK activation. Analysis of glomerular mRNA from both models demonstrates significant induction of MMP-9, MMP-10, MMP-12, MMPs linked to GBM destruction in Alport disease models, as well as the pro-inflammatory cytokine IL-6. SiRNA knockdown of FAK in cultured podocytes significantly reduced expression of MMP-9, MMP-10 and IL-6, but not MMP-12. Treatment of Alport mice with TAE226, a small molecule inhibitor of FAK activation, ameliorated fibrosis and glomerulosclerosis, significantly reduced proteinuria and blood urea nitrogen levels, and partially restored GBM ultrastructure. Glomerular expression of MMP-9, MMP-10 and MMP-12 mRNAs was significantly reduced in TAE226 treated animals. Collectively, this work identifies laminin α2-mediated FAK activation in podocytes as an important early event in Alport glomerular pathogenesis and suggests that FAK inhibitors, if safe formulations can be developed, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages.

  3. Vimentin and laminin are altered on cheek pouch microvessels of streptozotocin-induced diabetic hamsters

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    Jemima Fuentes R Silva

    2011-01-01

    Full Text Available OBJECTIVE: Normal endothelial cells respond to shear stress by elongating and aligning in the direction of fluid flow. Hyperglycemia impairs this response and contributes to microvascular complications, which result in deleterious effects to the endothelium. This work aimed to evaluate cheek pouch microvessel morphological characteristics, reactivity, permeability, and expression of cytoskeleton and extracellular matrix components in hamsters after the induction of diabetes with streptozotocin. METHODS: Syrian golden hamsters (90-130 g were injected with streptozotocin (50 mg/kg, i.p. or vehicle either 6 (the diabetes mellitus 6 group or 15 (the diabetes mellitus 15 group days before the experiment. Vascular dimensions and density per area of vessels were determined by morphometric and stereological measurements. Changes in blood flow were measured in response to acetylcholine, and plasma extravasation was measured by the number of leakage sites. Actin, talin, α-smooth muscle actin, vimentin, type IV collagen, and laminin were detected by immunohistochemistry and assessed through a semiquantitative scoring system. RESULTS: There were no major alterations in the lumen, wall diameters, or densities of the examined vessels. Likewise, vascular reactivity and permeability were not altered by diabetes. The arterioles demonstrated increased immunoreactivity to vimentin and laminin in the diabetes mellitus 6 and diabetes mellitus 15 groups. DISCUSSION: Antibodies against laminin and vimentin inhibit branching morphogenesis in vitro. Therefore, laminin and vimentin participating in the structure of the focal adhesion may play a role in angiogenesis. CONCLUSIONS: Our results indicated the existence of changes related to cell-matrix interactions, which may contribute to the pathological remodeling that was already underway one week after induction of experimental diabetes.

  4. The role of alpha3beta1 integrin in determining the supramolecular organization of laminin-5 in the extracellular matrix of keratinocytes.

    Science.gov (United States)

    deHart, Gregory W; Healy, Kevin E; Jones, Jonathan C R

    2003-02-01

    Analyses of mice with targeted deletions in the genes for alpha3 and beta1 integrin suggest that the alpha3beta1 integrin heterodimer likely determines the organization of the extracellular matrix within the basement membrane of skin. Here we tested this hypothesis using keratinocytes derived from alpha3 integrin-null mice. We have compared the organizational state of laminin-5, a ligand of alpha3beta1 integrin, in the matrix of wild-type keratinocytes with that of laminin-5 in the matrix of alpha3 integrin-null cells. Laminin-5 distributes diffusely in arc structures in the matrix of wild-type mouse keratinocytes, whereas laminin-5 is organized into linear, spike-like arrays by the alpha3 integrin-null cells. The fact that alpha3 integrin-null cells are deficient in their ability to assemble a proper laminin-5 matrix is also shown by their failure to remodel laminin-5 when plated onto surfaces coated with purified laminin-5 protein. In sharp contrast, wild-type keratinocytes organize exogenously added laminin-5 into discrete ring-like organizations. These findings led us next to assess whether differences in laminin-5 organization in the matrix of the wild-type and alpha3 integrin-null cells impact cell behavior. Our results indicate that alpha3 integrin-null cells are more motile than their wild-type counterparts and leave extensive trails of laminin-5 over the surface on which they move. Moreover, HEK 293 cells migrate significantly more on the laminin-5-rich matrix derived from the alpha3 integrin-null cells than on the wild-type keratinocyte laminin-5 matrix. In addition, alpha3 integrin-null cells show low strength of adhesion to surfaces coated with purified laminin-5 compared to wild-type cells although both the wild type and the alpha3 integrin-null keratinocytes adhere equally strongly to laminin-5 that has been organized into arrays by other epithelial cells. These data suggest: (1) that alpha3beta1 integrin plays an important role in determining the

  5. The extracellular matrix component laminin promotes gap junction formation in the rat anterior pituitary gland.

    Science.gov (United States)

    Horiguchi, Kotaro; Kouki, Tom; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

    2011-03-01

    Folliculo-stellate (FS) cells in the anterior pituitary gland are believed to have multifunctional properties. FS cells connect to each other not only by mechanical means, but also by gap junctional cell-to-cell communication. Using transgenic rats that express green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary gland (S100b-GFP rats), we recently revealed that FS cells in primary culture markedly change their shape, and form numerous interconnections with neighboring FS cells in the presence of laminin, an extracellular matrix (ECM) component of the basement membrane. Morphological and functional changes in cells are believed to be partly modified by matricrine signaling, by which ECM components function as cellular signals. In the present study, we examined whether gap junction formation between FS cells is affected by matricrine cues. A cell sorter was used to isolate FS cells from male S100b-GFP rat anterior pituitary for primary culture. We observed that mRNA and protein levels of connexin 43 in gap junction channels were clearly higher in the presence of laminin. In addition, we confirmed the formation of gap junctions between FS cells in primary culture by electron microscopy. Interestingly, we also observed that FS cells in the presence of laminin displayed well-developed rough endoplasmic reticulum and Golgi apparatus. Our findings suggest that, in anterior pituitary gland, FS cells may facilitate functional roles such as gap junctional cell-to-cell communication by matricrine signaling.

  6. Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

    Energy Technology Data Exchange (ETDEWEB)

    Alcaraz, Jordi; Xu, Ren; Mori, Hidetoshi; Nelson, Celeste M.; Mroue, Rana; Spencer, Virginia A.; Brownfield, Doug; Radisky, Derek C.; Bustamante, Carlos; Bissell, Mina J.

    2008-10-20

    In the mammary gland, epithelial cells are embedded in a 'soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for {beta}-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of {beta}-casein expression required both laminin signalling and a 'soft' extracellular matrix, as is the case in normal tissues in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of {beta}-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis.

  7. Laminin active peptide/agarose matrices as multifunctional biomaterials for tissue engineering.

    Science.gov (United States)

    Yamada, Yuji; Hozumi, Kentaro; Aso, Akihiro; Hotta, Atsushi; Toma, Kazunori; Katagiri, Fumihiko; Kikkawa, Yamato; Nomizu, Motoyoshi

    2012-06-01

    Cell adhesive peptides derived from extracellular matrix components are potential candidates to afford bio-adhesiveness to cell culture scaffolds for tissue engineering. Previously, we covalently conjugated bioactive laminin peptides to polysaccharides, such as chitosan and alginate, and demonstrated their advantages as biomaterials. Here, we prepared functional polysaccharide matrices by mixing laminin active peptides and agarose gel. Several laminin peptide/agarose matrices showed cell attachment activity. In particular, peptide AG73 (RKRLQVQLSIRT)/agarose matrices promoted strong cell attachment and the cell behavior depended on the stiffness of agarose matrices. Fibroblasts formed spheroid structures on the soft AG73/agarose matrices while the cells formed a monolayer with elongated morphologies on the stiff matrices. On the stiff AG73/agarose matrices, neuronal cells extended neuritic processes and endothelial cells formed capillary-like networks. In addition, salivary gland cells formed acini-like structures on the soft matrices. These results suggest that the peptide/agarose matrices are useful for both two- and three-dimensional cell culture systems as a multifunctional biomaterial for tissue engineering. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  9. Optical Carry Adder.

    Science.gov (United States)

    1987-03-01

    AOM’s) with the deflected beam as the modulator "on" state. These AOM’s ( TeO2 crystals, manufactured by Newport E.O. Systems) have high deflection...caused by the slow acoustic propagation (4.2 - 105 cm/s for TeO2 ), but this delay can be minimized by placing the laser beam close to the acoustic...dependent jitter in the optical carry to below 1 ns, the total carry path must be less than 30 cm long (or 20 cm in glass , 14 cm in LiNbO 3). Thus, a 32

  10. Structural organization of the human and mouse laminin beta2 chain genes, and alternative splicing at the 5' end of the human transcript

    DEFF Research Database (Denmark)

    Durkin, M E; Gautam, M; Loechel, F

    1996-01-01

    We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon-intron organ......We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon...

  11. Basement Membrane Type IV Collagen and Laminin: An Overview of Their Biology and Value as Fibrosis Biomarkers of Liver Disease.

    Science.gov (United States)

    Mak, Ki M; Mei, Rena

    2017-08-01

    Basement membranes provide structural support to epithelium, endothelium, muscles, fat cells, Schwann cells, and axons. Basement membranes are multifunctional: they modulate cellular behavior, regulate organogenesis, promote tissue repair, form a barrier to filtration and tumor metastasis, bind growth factors, and mediate angiogenesis. All basement membranes contain type IV collagen (Col IV), laminin, nidogen, and perlecan. Col IV and laminin self-assemble into two independent supramolecular networks that are linked to nidogen and perlecan to form a morphological discernable basement membrane/basal lamina. The triple helical region, 7S domain and NCI domain of Col IV, laminin and laminin fragment P1 have been evaluated as noninvasive fibrosis biomarkers of alcoholic liver disease, viral hepatitis, and nonalcoholic fatty liver disease. Elevated serum Col IV and laminin are related to degrees of fibrosis and severity of hepatitis, and may reflect hepatic basement membrane metabolism. But the serum assays have not been linked to disclosing the anatomical sites and lobular distribution of perisinusoidal basement membrane formation in the liver. Hepatic sinusoids normally lack a basement membrane, although Col IV is a normal matrix component of the space of Disse. In liver disease, laminin deposits in the space of Disse and codistributes with Col IV, forming a perisinusoidal basement membrane. Concomitantly, the sinusoidal endothelium loses its fenestrae and is transformed into vascular type endothelium. These changes lead to capillarization of hepatic sinusoids, a significant pathology that impairs hepatic function. Accordingly, codistribution of Col IV and laminin serves as histochemical marker of perisinusoidal basement membrane formation in liver disease. Anat Rec, 300:1371-1390, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis

    Science.gov (United States)

    Bryan, Chase D.; Chien, Chi-Bin; Kwan, Kristen M.

    2016-01-01

    The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1UW1) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1UW1 mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis. PMID:27339294

  13. In vitro Evaluation of Calcium Phosphate Precipitation on Possibly Bioactive Titanium Surfaces in the Presence of Laminin

    Directory of Open Access Journals (Sweden)

    Kostas Bougas

    2011-07-01

    Full Text Available Objectives: The aim of the present study was to evaluate calcium phosphate precipitation and the amount of precipitated protein on three potentially bioactive surfaces when adding laminin in simulated body fluid.Material and Methods: Blasted titanium discs were prepared by three different techniques claimed to provide bioactivity: alkali and heat treatment (AH, anodic oxidation (AO or hydroxyapatite coating (HA. A blasted surface incubated in laminin-containing simulated body fuid served as a positive control (B while a blasted surface incubated in non laminin-containing simulated body fuid served as a negative control (B-. The immersion time was 1 hour, 24 hours, 72 hours and 1 week. Surface topography was investigated by interferometry and morphology by Scanning Electron Microscopy (SEM. Analysis of the precipitated calcium and phosphorous was performed by Energy Dispersive X-ray Spectroscopy (EDX and the adsorbed laminin was quantified by iodine (125I labeling.Results: SEM demonstrated that all specimens except for the negative control were totally covered with calcium phosphate (CaP after 1 week. EDX revealed that B- demonstrated lower sum of Ca and P levels compared to the other groups after 1 week. Iodine labeling demonstrated that laminin precipitated in a similar manner on the possibly bioactive surfaces as on the positive control surface.Conclusions: Our results indicate that laminin precipitates equally on all tested titanium surfaces and may function as a nucleation center thus locally elevating the calcium concentration. Nevertheless further studies are required to clarify the role of laminin in the interaction of biomaterials with the host bone tissue.

  14. One-Step Purification of Human Skeletal Muscle Myoblasts and Subsequent Expansion Using Laminin-Coated Surface.

    Science.gov (United States)

    Chowdhury, Shiplu Roy; binti Ismail, Annis; Chee, Sia Chye; bin Laupa, Mohd Suffian; binti Jaffri, Fadhlun; Saberi, Salfarina Ezrina Mohmad; Idrus, Ruszymah Bt Hj

    2015-11-01

    Skeletal myoblasts have been extensively used to study muscle growth and differentiation, and were recently tested for their application as cell therapy and as a gene delivery system to treat muscle and nonmuscle diseases. However, contamination of fibroblasts in isolated cells from skeletal muscle is one of the long-standing problems for routine expansion. This study aimed to establish a simple one-step process to purify myoblasts and maintain their purity during expansion. Mixed cells were preplated serially on laminin- and collagen type I-coated surfaces in a different array for 5, 10, and 15 min. Immunocytochemical staining with antibodies specific to myoblasts was performed to evaluate myoblast attachment efficiency, purity, and yield. It was found that laminin-coated surface favors the attachment of myoblasts. Highest myoblast purity of 78.9% ± 6.8% was achieved by 5 min of preplating only on the laminin-coated surface with a yield of 56.9% ± 3.3%. Primary cells, isolated from skeletal muscle (n = 4), confirm the enhancement of purity through preplating on laminin-coated surface for 5 min. Subsequent expansion after preplating enhanced myoblast purity due to an increase in myoblast growth than fibroblasts. Myoblast purity of ∼ 98% was achieved when another preplating was performed during passaging. In conclusion, myoblasts can be purified and efficiently expanded in one step by preplating on laminin-coated surface, which is a simple and robust technique.

  15. Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro

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    Marvin Paulo Lins

    Full Text Available BACKGROUND: Several evidences indicate that hormones and neuropeptides function as immunomodulators. Among these, growth hormone (GH is known to act on the thymic microenvironment, supporting its role in thymocyte differentiation. The aim of this study was to evaluate the effect of GH on human thymocytes and thymic epithelial cells (TEC in the presence of laminin. RESULTS: GH increased thymocyte adhesion on BSA-coated and further on laminin-coated surfaces. The number of migrating cells in laminin-coated membrane was higher in GH-treated thymocyte group. In both results, VLA-6 expression on thymocytes was constant. Also, treatment with GH enhanced laminin production by TEC after 24 h in culture. However, VLA-6 integrin expression on TEC remained unchanged. Finally, TEC/thymocyte co-culture model demonstrated that GH elevated absolute number of double-negative (CD4-CD8- and single-positive CD4+ and CD8+ thymocytes. A decrease in cell number was noted in double-positive (CD4+CD8+ thymocytes. CONCLUSIONS: The results of this study demonstrate that GH is capable of enhancing the migratory capacity of human thymocytes in the presence of laminin and promotes modulation of thymocyte subsets after co-culture with TEC.

  16. Growth Factor and Laminin Effect with Muscular Fiber Sheath on Repairing of the Sciatica Nerve

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    S Torabi

    2014-01-01

    Background & aim: Peripheral nerve injuries which can lead to a physical disability. If the defect is very low, direct suture without tension on both ends of the cut nerve regeneration is considered as a standard procedure. Otherwise, to reconstruct the axons, the gap must be filled by graft material in order to the guidance. Due to the similarity of the matrix tubular skeletal muscle and nerve muscles graft was used to repair in this study. Methods: In the present experimental study, 42 female Wistar rats were divided into three groups and underwent surgery. In the first group a narrow strip of muscle was prepared by freezing – thawing, and later sutured between the distal and proximal sciatic nerve. In the second group, the gap caused by muscle graft was regenerated and the nerve growth factor and laminin was injected into the graft. In the control group, the two ends of the cut nerve were hidden beneath the adjacent muscles. Next, a group of rats with sciatic functional index was investigated for the behavioral. On the other group were examined for histological studies after two months. Results: Sciatic functional index and Mean counts of myelinated fibers in two graft groups compared with the control group was significant p<0.05. Statistical analysis was performed using ANOVA test. Conclusion: co-axially aligned muscle grafts were an appropriate alternative substitute for repairing. It seems that the nerve growth factor and laminin have a positive role in axonal regeneration and functional recovery acceleration. Key words: Sciatic Functional Index, muscle graft, NGF, Laminin

  17. ADAM12 overexpression does not improve outcome in mice with laminin alpha2-deficient muscular dystrophy

    DEFF Research Database (Denmark)

    Guo, Ling T; Shelton, G Diane; Wewer, Ulla M

    2005-01-01

    We have recently shown that overexpression of ADAM12 results in increased muscle regeneration and significantly reduced pathology in mdx, dystrophin deficient mice. In the present study, we tested the effect of overexpressing ADAM12 in dy(W) laminin-deficient mice. dy mice have a very severe...... clinical phenotype and would be expected to benefit greatly from enhanced regeneration. We found that dy(W) mice overexpressing ADAM12 indeed have increased muscle regeneration, as evidenced by increased numbers of muscle fibers expressing fetal myosin. However, overexpression of ADAM12 had no significant...

  18. Double immunohistochemical staining with laminin 5 (γ2 chain) and collagen IV in colorectal neoplasms

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Bzorek, Michael; Warnecke, Mads

    2016-01-01

    divided according to the primary histopathological diagnoses of tubular adenoma, tubulovillous adenoma, adenoma with pseudoinvasion and glandular adenocarcinoma stages pT1, pT2 or pT3, were included in the study. In normal colonic mucosa, no expression of laminin 5 staining was observed. BM was always...... as a supplement for the diagnosis of pT1 CRC. In adenomas, the double staining highlights the areas for the pathologist to pay extra attention. By itself, the double staining cannot determine whether or not there is invasion. Morphology remains the single most important factor in differentiating adenoma...

  19. Linkage of genes for laminin B1 and B2 subunits on chromosome 1 in mouse.

    Science.gov (United States)

    Elliott, R W; Barlow, D; Hogan, B L

    1985-08-01

    We have used cDNA clones for the B1 and B2 subunits of laminin to find restriction fragment length DNA polymorphisms for the genes encoding these polypeptides in the mouse. Three alleles were found for LamB2 and two for LamB1 among the inbred mouse strains. The segregation of these polymorphisms among recombinant inbred strains showed that these genes are tightly linked in the central region of mouse Chromosome 1 between Sas-1 and Ly-m22, 7.4 +/- 3.2 cM distal to the Pep-3 locus. There is no evidence in the mouse for pseudogenes for these proteins.

  20. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

    International Nuclear Information System (INIS)

    Cação-Benedini, L.O.; Ribeiro, P.G.; Prado, C.M.; Chesca, D.L.; Mattiello-Sverzut, A.C.

    2014-01-01

    Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres

  1. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Cação-Benedini, L.O.; Ribeiro, P.G. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Prado, C.M.; Chesca, D.L. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattiello-Sverzut, A.C. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

  2. Perspectives on the Trypanosoma cruzi–host cell receptor interactions

    Science.gov (United States)

    Villalta, Fernando; Scharfstein, Julio; Ashton, Anthony W.; Tyler, Kevin M.; Guan, Fangxia; Mukherjee, Shankar; Lima, Maria F.; Alvarez, Sandra; Weiss, Louis M.; Huang, Huan; Machado, Fabiana S.

    2009-01-01

    Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets. PMID:19283409

  3. Mycobacterial laminin-binding histone-like protein mediates collagen-dependent cytoadherence

    Directory of Open Access Journals (Sweden)

    André Alves Dias

    2012-12-01

    Full Text Available When grown in the presence of exogenous collagen I, Mycobacterium bovis BCG was shown to form clumps. Scanning electron microscopy examination of these clumps revealed the presence of collagen fibres cross-linking the bacilli. Since collagen is a major constituent of the eukaryotic extracellular matrices, we assayed BCG cytoadherence in the presence of exogenous collagen I. Collagen increased the interaction of the bacilli with A549 type II pneumocytes or U937 macrophages, suggesting that BCG is able to recruit collagen to facilitate its attachment to host cells. Using an affinity chromatography approach, we have isolated a BCG collagen-binding protein corresponding to the previously described mycobacterial laminin-binding histone-like protein (LBP/Hlp, a highly conserved protein associated with the mycobacterial cell wall. Moreover, Mycobacterium leprae LBP/Hlp, a well-characterized adhesin, was also able to bind collagen I. Finally, using recombinant fragments of M. leprae LBP/Hlp, we mapped the collagen-binding activity within the C-terminal domain of the adhesin. Since this protein was already shown to be involved in the recognition of laminin and heparan sulphate-containing proteoglycans, the present observations reinforce the adhesive activities of LBP/Hlp, which can be therefore considered as a multifaceted mycobacterial adhesin, playing an important role in both leprosy and tuberculosis pathogenesis.

  4. Recombinant human laminin isoforms can support the undifferentiated growth of human embryonic stem cells

    International Nuclear Information System (INIS)

    Miyazaki, Takamichi; Futaki, Sugiko; Hasegawa, Kouichi; Kawasaki, Miwa; Sanzen, Noriko; Hayashi, Maria; Kawase, Eihachiro; Sekiguchi, Kiyotoshi; Nakatsuji, Norio; Suemori, Hirofumi

    2008-01-01

    Human embryonic stem cells (hESCs) are thought to be a promising cell source for cell transplantation therapy. For such a clinical application, the hESCs should be manipulated using appropriate and qualified materials. In this study, we examined the efficacy of recombinant human laminin (rhLM) isoforms on the undifferentiated growth of hESCs. We first determined the major integrins expressed on the hESCs to reveal the preference of the hESCs for rhLMs, and found that the hESCs mainly expressed integrin α6β1, which binds predominantly to laminin-111, -332 and -511/-521. When the hESCs were seeded onto rhLMs, the cells indeed adhered markedly to rhLM-332, and to rhLM-511 and rhLM-111 to a lesser extent. The hESCs proliferated on these three rhLMs for several passages while preserving their pluripotency. These results show that rhLM-111, -332, and -511 are good substrates to expand undifferentiated hESCs due to their high affinity to integrin α6β1 expressed on hESCs

  5. Expression of periglandular tenascin-C and basement membrane laminin in normal prostate, benign prostatic hyperplasia and prostate carcinoma

    NARCIS (Netherlands)

    Xue, Y.; Li, J.; Latijnhouwers, M. A.; Smedts, F.; Umbas, R.; Aalders, T. W.; Debruyne, F. M.; de la Rosette, J. J.; Schalken, J. A.

    1998-01-01

    To evaluate the structural relationship of the distribution between tenascin (tenascin-C, an extra-cellular matrix glycoprotein involved in stromal-epithelial interactions in both normal and pathological conditions) and laminin, an important component of the basement membrane, in normal and

  6. Laminin and collagen modulate expression of the small leucine-rich proteoglycan fibromodulin in rat anterior pituitary gland.

    Science.gov (United States)

    Syaidah, Rahimi; Horiguchi, Kotaro; Fujiwara, Ken; Tsukada, Takehiro; Kikuchi, Motoshi; Yashiro, Takashi

    2013-11-01

    The anterior pituitary is a complex organ consisting of five types of hormone-producing cells, non–hormone-producing cells such as folliculostellate (FS) cells and vascular cells (endothelial cells and pericytes). We have previously shown that FS cells and pericytes produce fibromodulin, a small leucine-rich proteoglycan (SLRP). SLRPs are major proteoglycans of the extracellular matrix (ECM) and are important in regulating cell signaling pathways and ECM assembly. However, the mechanism regulating fibromodulin expression in the anterior pituitary has not been elucidated. Here, we investigate whether fibromodulin expression is modulated by major anterior pituitary ECM components such as laminin and type I collagen. Using transgenic rats expressing green fluorescent protein (GFP) specifically in FS cells, we examine fibromodulin expression in GFP-positive (FS cells) and GFP-negative cells (e.g., pericytes, endocrine cells and endothelial cells). Immunostaining and Western blot analysis were used to assess protein expression in the presence and absence of laminin or type I collagen. We confirmed fibromodulin expression in the pituitary and observed the up-regulation of fibromodulin in FS cells in the presence of ECM components. However, neither laminin nor type I collagen affected expression in GFP-negative cells. This suggests that laminin and type I collagen support the function of FS cells by increasing fibromodulin protein expression in the anterior pituitary.

  7. Laminin α2 chain-deficiency is associated with microRNA deregulation in skeletal muscle and plasma

    Directory of Open Access Journals (Sweden)

    Johan eHolmberg

    2014-07-01

    Full Text Available MicroRNAs (miRNAs are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A. MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs are markedly elevated in laminin α2 chain-deficient mice and partially normalized in response to proteasome inhibition therapy. Altogether, our data suggest important roles for miRNAs in MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as promising biomarkers for the progression of MDC1A.

  8. Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications

    Directory of Open Access Journals (Sweden)

    John Ong

    2018-03-01

    Full Text Available Summary: Use of hepatocytes derived from induced pluripotent stem cells (i-Heps is limited by their functional differences in comparison with primary cells. Extracellular niche factors likely play a critical role in bridging this gap. Using image-based characterization (high content analysis; HCA of freshly isolated hepatocytes from 17 human donors, we devised and validated an algorithm (Hepatocyte Likeness Index; HLI for comparing the hepatic properties of cells against a physiological gold standard. The HLI was then applied in a targeted screen of extracellular niche factors to identify substrates driving i-Heps closer to the standard. Laminin 411, the top hit, was validated in two additional induced pluripotent stem cell (iPSC lines, primary tissue, and an in vitro model of α1-antitrypsin deficiency. Cumulatively, these data provide a reference method to control and screen for i-Hep differentiation, identify Laminin 411 as a key niche protein, and underscore the importance of combining substrates, soluble factors, and HCA when developing iPSC applications. : Rashid and colleagues demonstrate the utility of a high-throughput imaging platform for identification of physiologically relevant extracellular niche factors to advance i-Heps closer to their primary tissue counterparts. The extracellular matrix (ECM protein screen identified Laminin 411 as an important niche factor facilitating i-Hep-based disease modeling in vitro. Keywords: iPS hepatocytes, extracellular niche, image-based screening, disease modeling, laminin

  9. A novel cell binding site in the coiled‐coil domain of laminin involved in capillary morphogenesis

    DEFF Research Database (Denmark)

    Sanz, Laura; García-Bermejo, Laura; Blanco, Francisco J

    2003-01-01

    Recently, we reported the isolation and characterization of an anti‐laminin antibody that modulates the extracellular matrix‐dependent morphogenesis of endothelial cells. Here we use this antibody to precisely map the binding site responsible for mediating this biologically important interaction....

  10. A splice site mutation in laminin-α2 results in a severe muscular dystrophy and growth abnormalities in zebrafish.

    Directory of Open Access Journals (Sweden)

    Vandana A Gupta

    Full Text Available Congenital muscular dystrophy (CMD is a clinically and genetically heterogeneous group of inherited muscle disorders. In patients, muscle weakness is usually present at or shortly after birth and is progressive in nature. Merosin deficient congenital muscular dystrophy (MDC1A is a form of CMD caused by a defect in the laminin-α2 gene (LAMA2. Laminin-α2 is an extracellular matrix protein that interacts with the dystrophin-dystroglycan (DGC complex in membranes providing stability to muscle fibers. In an N-ethyl-N-nitrosourea mutagenesis screen to develop zebrafish models of neuromuscular diseases, we identified a mutant fish that exhibits severe muscular dystrophy early in development. Genetic mapping identified a splice site mutation in the lama2 gene. This splice site is highly conserved in humans and this mutation results in mis-splicing of RNA and a loss of protein function. Homozygous lama2 mutant zebrafish, designated lama2(cl501/cl501, exhibited reduced motor function and progressive degeneration of skeletal muscles and died at 8-15 days post fertilization. The skeletal muscles exhibited damaged myosepta and detachment of myofibers in the affected fish. Laminin-α2 deficiency also resulted in growth defects in the brain and eye of the mutant fish. This laminin-α2 deficient mutant fish represents a novel disease model to develop therapies for modulating splicing defects in congenital muscular dystrophies and to restore the muscle function in human patients with CMD.

  11. Punch grafting of chronic ulcers in patients with laminin-332-deficient, non-Herlitz junctional epidermolysis bullosa

    NARCIS (Netherlands)

    Yuen, Wing Yan; Huizinga, Janneke; Jonkman, Marcel F.

    Background: Epidermolysis bullosa (EB) is a genetic, heterogeneous, trauma-induced blistering disease. Patients with laminin-332-deficient non-Herlitz junctional EB (JEB-nH) can have impaired wound healing witnessed by persistent, small, deep ulcers on the hands and feet that adversely affect the

  12. Immunohistochemical Analysis of Collagen IV and Laminin Expression in Spontaneous Melanoma Regression in the Melanoma-Bearing Libechov Minipig

    Czech Academy of Sciences Publication Activity Database

    Plánská, Daniela; Burocziová, Monika; Strnádel, Ján; Horák, Vratislav

    2015-01-01

    Roč. 48, č. 1 (2015), s. 15-26 ISSN 0044-5991 R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 ; RVO:61388971 Keywords : collagen IV * laminin * MeLiM * porcine melanoma * spontaneous regression Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.912, year: 2015

  13. Clinical significance of serum laminin in the patients with diabetic nephropathy

    International Nuclear Information System (INIS)

    Wang Lu; Qian Caifeng; Lu Aibin

    2002-01-01

    The concentration of serum LN is determined by radioimmunoassay in 78 diabetic patients and 30 normal subjects as control. The mean concentration of LN in total 78 diabetic patients [(132.54 +- 31.05) μg/L] is higher than that of control [(97.63 +- 19.31) μg/L, P<0.01], especially in group B [(134.25 +- 29.12)μg/L] and group C [(158.51 +- 37.82)μg/L] are remarkably higher as comparable with control (P<0.01). There is significantly positive correlation between serum LN and diabetic duration, UAE, FBG. The results show that abnormal laminin metabolism exists in diabetic patients. The increased serum LN level in diabetic patients related to the severity of diabetic renal lesion and could be an early and sensitive marker of DN

  14. The relationship of serum and urinary laminin and glomerular filtration rate in diabetes mellitus

    International Nuclear Information System (INIS)

    Li Jianlin

    2002-01-01

    Objective: To observe the relationship of serum and urinary laminin and glomerular filtration rate (GFR) in diabetes mellitus. Methods: The level of serum and urinary laminin was measured by radioimmunoassay, GFR acquired by 99m Tc diethylenetriamine pentaacetic acid ( 99m Tc-DTPA), renal dynamic imaging in 75 diabetes mellitus and 42 normal subjects. Results: (1) The level of serum LN (136.30 ± 11.20 ng/ml) and urinary LN (31.76 ± 5.77 ng/ml) in diabetic nephropathy was significantly higher than that in diabetes without nephrosis group (P<0.05) and control group (P<0.01), the level of serum LN (126.54 ± 6.98 ng/ml) and urinary LN (26.27 ± 3.81 ng/ml) in diabetes without nephrosis group was significantly higher than that in control group (P<0.05); the GFR of diabetic nephropathy (78.84 ± 10.79 ng/ml) was significantly lower than that in diabetes without nephrosis group (P<0.05) and control group (P<0.01); the level of serum (131.49 ± 10.74 ng/ml) and urinary LN (29.05 ± 5.60 ng/ml) in diabetes mellitus was significantly higher than that in control group (P<0.05), but GFR was significantly lower than that in control group (P<0.05). (2) The value of GFR in diabetes mellitus lasted less than 1 year was higher than that of control group (P<0.05), but inverse in diabetes mellitus more than 10 years (P<0.05). (3) The level of serum and urinary LN had significantly negative correlation with GFR (P<0.01). Conclusion: LN may accelerates the alteration of GFR and causes microangiopathy of diabetic nephropathy. It may be an important indicator in the diagnosis of the early diabetic nephropathy

  15. Magnetic Resonance Imaging Is Sensitive to Pathological Amelioration in a Model for Laminin-Deficient Congenital Muscular Dystrophy (MDC1A.

    Directory of Open Access Journals (Sweden)

    Ravneet Vohra

    Full Text Available To elucidate the reliability of MRI as a non-invasive tool for assessing in vivo muscle health and pathological amelioration in response to Losartan (Angiotensin II Type 1 receptor blocker in DyW mice (mouse model for Laminin-deficient Congenital Muscular Dystrophy Type 1A.Multiparametric MR quantifications along with histological/biochemical analyses were utilized to measure muscle volume and composition in untreated and Losartan-treated 7-week old DyW mice.MRI shows that DyW mice have significantly less hind limb muscle volume and areas of hyperintensity that are absent in WT muscle. DyW mice also have significantly elevated muscle levels (suggestive of inflammation and edema. Muscle T2 returned to WT levels in response to Losartan treatment. When considering only muscle pixels without T2 elevation, DyW T2 levels are significantly lower than WT (suggestive of fibrosis whereas Losartan-treated animals do not demonstrate this decrease in muscle T2. MRI measurements suggestive of elevated inflammation and fibrosis corroborate with increased Mac-1 positive cells as well as increased Picrosirius red staining/COL1a gene expression that is returned to WT levels in response to Losartan.MRI is sensitive to and tightly corresponds with pathological changes in DyW mice and thus is a viable and effective non-invasive tool for assessing pathological changes.

  16. CD90-positive cells, an additional cell population, produce laminin α2 upon transplantation to dy3k/dy3k mice

    International Nuclear Information System (INIS)

    Fukada, So-ichiro; Yamamoto, Yukiko; Segawa, Masashi; Sakamoto, Kenta; Nakajima, Mari; Sato, Masaki; Morikawa, Daisuke; Uezumi, Akiyoshi; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Tsujikawa, Kazutake; Yamamoto, Hiroshi

    2008-01-01

    Laminin α2 is a component of skeletal and cardiac muscle basal lamina. A defect of the laminin α2 chain leads to severe congenital muscular dystrophy (MDC1A) in humans and dy/dy mice. Myogenic cells including myoblasts, myotubes, and myofibers in skeletal muscle are a possible source of the laminin α2 chain, and myogenic cells are thus proposed as a cell source for congenital muscular dystrophy therapy. However, we observed production of laminin α2 in non-myogenic cells of normal mice, and we could enrich these laminin α2-producing cells in CD90 + cell fractions. Intriguingly, the number of CD90 + cells increased dramatically during skeletal muscle regeneration in mice. This fraction did not include myogenic cells but exhibited a fibroblast-like phenotype. Moreover, these cells were resident in skeletal muscle, not derived from bone marrow. Finally, the production of laminin α2 in CD90 + cells was not dependent on fusion with myogenic cells. Thus, CD90 + cells are a newly identified additional cell fraction that increased during skeletal muscle regeneration in vivo and could be another cell source for therapy for lama2-deficient muscular dystrophy

  17. Laminin Peptide-Immobilized Hydrogels Modulate Valve Endothelial Cell Hemostatic Regulation.

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    Liezl Rae Balaoing

    Full Text Available Valve endothelial cells (VEC have unique phenotypic responses relative to other types of vascular endothelial cells and have highly sensitive hemostatic functions affected by changes in valve tissues. Furthermore, effects of environmental factors on VEC hemostatic function has not been characterized. This work used a poly(ethylene glycol diacrylate (PEGDA hydrogel platform to evaluate the effects of substrate stiffness and cell adhesive ligands on VEC phenotype and expression of hemostatic genes. Hydrogels of molecular weights (MWs 3.4, 8, and 20 kDa were polymerized into platforms of different rigidities and thiol-modified cell adhesive peptides were covalently bound to acrylate groups on the hydrogel surfaces. The peptide RKRLQVQLSIRT (RKR is a syndecan-1 binding ligand derived from laminin, a trimeric protein and a basement membrane matrix component. Conversely, RGDS is an integrin binding peptide found in many extracellular matrix (ECM proteins including fibronectin, fibrinogen, and von Willebrand factor (VWF. VECs adhered to and formed a stable monolayer on all RKR-coated hydrogel-MW combinations. RGDS-coated platforms supported VEC adhesion and growth on RGDS-3.4 kDa and RGDS-8 kDa hydrogels. VECs cultured on the softer RKR-8 kDa and RKR-20 kDa hydrogel platforms had significantly higher gene expression for all anti-thrombotic (ADAMTS-13, tissue factor pathway inhibitor, and tissue plasminogen activator and thrombotic (VWF, tissue factor, and P-selectin proteins than VECs cultured on RGDS-coated hydrogels and tissue culture polystyrene controls. Stimulated VECs promoted greater platelet adhesion than non-stimulated VECs on their respective culture condition; yet stimulated VECs on RGDS-3.4 kDa gels were not as responsive to stimulation relative to the RKR-gel groups. Thus, the syndecan binding, laminin-derived peptide promoted stable VEC adhesion on the softer hydrogels and maintained VEC phenotype and natural hemostatic function. In

  18. Laminin-521 Promotes Rat Bone Marrow Mesenchymal Stem Cell Sheet Formation on Light-Induced Cell Sheet Technology

    Directory of Open Access Journals (Sweden)

    Zhiwei Jiang

    2017-01-01

    Full Text Available Rat bone marrow mesenchymal stem cell sheets (rBMSC sheets are attractive for cell-based tissue engineering. However, methods of culturing rBMSC sheets are critically limited. In order to obtain intact rBMSC sheets, a light-induced cell sheet method was used in this study. TiO2 nanodot films were coated with (TL or without (TN laminin-521. We investigated the effects of laminin-521 on rBMSCs during cell sheet culturing. The fabricated rBMSC sheets were subsequently assessed to study cell sheet viability, reattachment ability, cell sheet thickness, collagen type I deposition, and multilineage potential. The results showed that laminin-521 could promote the formation of rBMSC sheets with good viability under hyperconfluent conditions. Cell sheet thickness increased from an initial 26.7 ± 1.5 μm (day 5 up to 47.7 ± 3.0 μm (day 10. Moreover, rBMSC sheets maintained their potential of osteogenic, adipogenic, and chondrogenic differentiation. This study provides a new strategy to obtain rBMSC sheets using light-induced cell sheet technology.

  19. Immunohistochemical Analysis of Collagen IV and Laminin Expression in Spontaneous Melanoma Regression in the Melanoma-Bearing Libechov Minipig

    International Nuclear Information System (INIS)

    Planska, Daniela; Burocziova, Monika; Strnadel, Jan; Horak, Vratislav

    2015-01-01

    Spontaneous regression (SR) of human melanoma is a rare, well-documented phenomenon that is not still fully understood. Its detailed study cannot be performed in patients due to ethical reasons. Using the Melanoma-bearing Libechov Minipig (MeLiM) animals of various ages (from 3 weeks to 8 months) we implemented a long-term monitoring of melanoma growth and SR. We focused on immunohistochemical detection of two important extracellular matrix proteins, collagen IV and laminin, which are associated with cancer. We showed that SR of melanoma is a highly dynamic process. The expression of collagen IV and laminin correlated with changes in population of melanoma cells. Tumours of 3-week-old animals consisted primarily of melanoma cells with a granular expression of collagen IV and laminin around them. Thereafter, melanoma cells were gradually destroyed and tumour tissue was rebuilt into the connective tissue. Collagen IV expression slightly increased in tumours of 10-week-old pigs showing extracellular fibrous appearance. In tumours of older animals, areas lacking melanoma cells demonstrated a low expression and areas still containing melanoma cells a high expression of both proteins. We considered the age of 10 weeks as a turning point in the transition between tumour growth and SR of the MeLiM melanoma

  20. Human beta 2 chain of laminin (formerly S chain): cDNA cloning, chromosomal localization, and expression in carcinomas

    DEFF Research Database (Denmark)

    Wewer, U M; Gerecke, D R; Durkin, M E

    1994-01-01

    or other known laminin genes. Immunostaining showed that the beta 2 chain is localized to the smooth muscle basement membranes of the arteries, while the homologous beta 1 chain is confined to the subendothelial basement membranes. The beta 2 chain was found in the basement membranes of ovarian carcinomas......Overlapping cDNA clones that encode the full-length human laminin beta 2 chain, formerly called the S chain, were isolated. The cDNA of 5680 nt contains a 5391-nt open reading frame encoding 1797 amino acids. At the amino terminus is a 32-amino-acid signal peptide that is followed by the mature...... beta 2 chain polypeptide of 1765 amino acids with a calculated molecular mass of 192,389 Da. The human beta 2 chain is predicted to have all of the seven structural domains typical of the beta chains of laminin, including the short cysteine-rich alpha region. The amino acid sequence of human beta 2...

  1. Senescence-Induced Alterations of Laminin Chain Expression Modulate Tumorigenicity of Prostate Cancer Cells1

    Science.gov (United States)

    Sprenger, Cynthia C T; Drivdahl, Rolf H; Woodke, Lillie B; Eyman, Daniel; Reed, May J; Carter, William G; Plymate, Stephen R

    2008-01-01

    Prostate cancer is an age-associated epithelial cancer, and as such, it contributes significantly to the mortality of the elderly. Senescence is one possible mechanism by which the body defends itself against various epithelial cancers. Senescent cells alter the microenvironment, in part, through changes to the extracellular matrix. Laminins (LMs) are extracellular proteins important to both the structure and function of the microenvironment. Overexpression of the senescence-associated gene mac25 in human prostate cancer cells resulted in increased mRNA levels of the LM α4 and β2 chains compared to empty vector control cells. The purpose of this study was to examine the effects of these senescence-induced LM chains on tumorigenicity of prostate cancer cells. We created stable M12 human prostate cancer lines overexpressing either the LM α4 or β2 chain or both chains. Increased expression of either the LM α4 or β2 chain resulted in increased in vitro migration and in vivo tumorigenicity of those cells, whereas high expression of both chains led to decreased in vitro proliferation and in vivo tumorigenicity compared to M12 control cells. This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer. PMID:19048114

  2. Senescence-Induced Alterations of Laminin Chain Expression Modulate Tumorigenicity of Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Cynthia C.T. Sprenger

    2008-12-01

    Full Text Available Prostate cancer is an age-associated epithelial cancer, and as such, it contributes significantly to the mortality of the elderly. Senescence is one possible mechanism by which the body defends itself against various epithelial cancers. Senescent cells alter the microenvironment, in part, through changes to the extracellular matrix. Laminins (LMs are extracellular proteins important to both the structure and function of the microenvironment. Overexpression of the senescence-associated gene mac25 in human prostate cancer cells resulted in increased mRNA levels of the LM α4 and β2 chains compared to empty vector control cells. The purpose of this study was to examine the effects of these senescence-induced LM chains on tumorigenicity of prostate cancer cells. We created stable M12 human prostate cancer lines overexpressing either the LM α4 or β2 chain or both chains. Increased expression of either the LM α4 or β2 chain resulted in increased in vitro migration and in vivo tumorigenicity of those cells, whereas high expression of both chains led to decreased in vitro proliferation and in vivo tumorigenicity compared to M12 control cells. This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer.

  3. A newly identified protein of Leptospira interrogans mediates binding to laminin.

    Science.gov (United States)

    Longhi, Mariana T; Oliveira, Tatiane R; Romero, Eliete C; Gonçales, Amane P; de Morais, Zenaide M; Vasconcellos, Silvio A; Nascimento, Ana L T O

    2009-10-01

    Pathogenic Leptospira is the aetiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. The search for novel antigens that could be relevant in host-pathogen interactions is being pursued. These antigens have the potential to elicit several activities, including adhesion. This study focused on a hypothetical predicted lipoprotein of Leptospira, encoded by the gene LIC12895, thought to mediate attachment to extracellular matrix (ECM) components. The gene was cloned and expressed in Escherichia coli BL21 Star (DE3)pLys by using the expression vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and characterized by circular dichroism spectroscopy. The capacity of the protein to mediate attachment to ECM components was evaluated by binding assays. The leptospiral protein encoded by LIC12895, named Lsa27 (leptospiral surface adhesin, 27 kDa), bound strongly to laminin in a dose-dependent and saturable fashion. Moreover, Lsa27 was recognized by antibodies from serum samples of confirmed leptospirosis specimens in both the initial and the convalescent phases of the disease. Lsa27 is most likely a surface protein of Leptospira as revealed in liquid-phase immunofluorescence assays with living organisms. Taken together, these data indicate that this newly identified membrane protein is expressed during natural infection and may play a role in mediating adhesion of L. interrogans to its host.

  4. Novel Leptospira interrogans protein Lsa32 is expressed during infection and binds laminin and plasminogen.

    Science.gov (United States)

    Domingos, Renan F; Fernandes, Luis G; Romero, Eliete C; de Morais, Zenaide M; Vasconcellos, Silvio A; Nascimento, Ana L T O

    2015-04-01

    Pathogenic Leptospira is the aetiological agent of leptospirosis, a life-threatening disease of human and veterinary concern. The quest for novel antigens that could mediate host-pathogen interactions is being pursued. Owing to their location, these antigens have the potential to elicit numerous activities, including immune response and adhesion. This study focuses on a hypothetical protein of Leptospira, encoded by the gene LIC11089, and its three derived fragments: the N-terminal, intermediate and C terminus regions. The gene coding for the full-length protein and fragments was cloned and expressed in Escherichia coli BL21(SI) strain by using the expression vector pAE. The recombinant protein and fragments tagged with hexahistidine at the N terminus were purified by metal affinity chromatography. The leptospiral full-length protein, named Lsa32 (leptospiral surface adhesin, 32 kDa), adheres to laminin, with the C terminus region being responsible for this interaction. Lsa32 binds to plasminogen in a dose-dependent fashion, generating plasmin when an activator is provided. Moreover, antibodies present in leptospirosis serum samples were able to recognize Lsa32. Lsa32 is most likely a new surface protein of Leptospira, as revealed by proteinase K susceptibility. Altogether, our data suggest that this multifaceted protein is expressed during infection and may play a role in host-L. interrogans interactions. © 2015 The Authors.

  5. Recapitulation of Extracellular LAMININ Environment Maintains Stemness of Satellite Cells In Vitro.

    Science.gov (United States)

    Ishii, Kana; Sakurai, Hidetoshi; Suzuki, Nobuharu; Mabuchi, Yo; Sekiya, Ichiro; Sekiguchi, Kiyotoshi; Akazawa, Chihiro

    2018-02-13

    Satellite cells function as precursor cells in mature skeletal muscle homeostasis and regeneration. In healthy tissue, these cells are maintained in a state of quiescence by a microenvironment formed by myofibers and basement membrane in which LAMININs (LMs) form a major component. In the present study, we evaluated the satellite cell microenvironment in vivo and found that these cells are encapsulated by LMα2-5. We sought to recapitulate this satellite cell niche in vitro by culturing satellite cells in the presence of recombinant LM-E8 fragments. We show that treatment with LM-E8 promotes proliferation of satellite cells in an undifferentiated state, through reduced phosphorylation of JNK and p38. On transplantation into injured muscle tissue, satellite cells cultured with LM-E8 promoted the regeneration of skeletal muscle. These findings represent an efficient method of culturing satellite cells for use in transplantation through the recapitulation of the satellite cell niche using recombinant LM-E8 fragments. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins.

    Science.gov (United States)

    Halper, Jaroslava; Kjaer, Michael

    2014-01-01

    Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds. Fibronectin with its muldomain structure plays a role of "master organizer" in matrix assembly as it forms a bridge between cell surface receptors, e.g., integrins, and compounds such collagen, proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of fibrillin-1 into a structured network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin by thrombin, it also binds to a variety of compounds, particularly to various growth factors, and as such fibrinogen is a player in cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer of the monomeric soluble precursor tropoelastin, is the main component of elastic fibers in matrix tissue where it provides elastic recoil and resilience to a variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate activity of TGFβs through their association with fibrillin microfibrils. Elastin also plays a role in cell adhesion, cell migration, and has the ability to participate in cell signaling. Mutations in the elastin gene lead to cutis laxa. Fibrillins represent the predominant core of the microfibrils in elastic as well as non

  7. Lsa63, a newly identified surface protein of Leptospira interrogans binds laminin and collagen IV.

    Science.gov (United States)

    Vieira, Monica L; de Morais, Zenaide M; Gonçales, Amane P; Romero, Eliete C; Vasconcellos, Silvio A; Nascimento, Ana L T O

    2010-01-01

    Leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease that affects populations worldwide. We have identified in proteomic studies a protein that is encoded by the gene LIC10314 and expressed in virulent strain of L. interrogans serovar Pomona. This protein was predicted to be surface exposed by PSORT program and contains a p83/100 domain identified by BLAST analysis that is conserved in protein antigens of several strains of Borrelia and Treponema spp. The proteins containing this domain have been claimed antigen candidates for serodiagnosis of Lyme borreliosis. Thus, we have cloned the LIC10314 and expressed the protein in Escherichia coli BL21-SI strain by using the expression vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and characterized by circular dichroism spectroscopy. This protein is conserved among several species of pathogenic Leptospira and absent in the saprophytic strain L. biflexa. We confirm by liquid-phase immunofluorescence assays with living organisms that this protein is most likely a new surface leptospiral protein. The ability of the protein to mediate attachment to ECM components was evaluated by binding assays. The leptospiral protein encoded by LIC10314, named Lsa63 (Leptospiral surface adhesin of 63kDa), binds strongly to laminin and collagen IV in a dose-dependent and saturable fashion. In addition, Lsa63 is probably expressed during infection since it was recognized by antibodies of serum samples of confirmed-leptospirosis patients in convalescent phase of the disease. Altogether, the data suggests that this novel identified surface protein may be involved in leptospiral pathogenesis. 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

  8. Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans

    Directory of Open Access Journals (Sweden)

    Hunter Gary R

    2008-08-01

    Full Text Available Abstract Background The objective of the present study was to map candidate loci influencing naturally occurring variation in triacylglycerol (TAG storage using quantitative complementation procedures in Drosophila melanogaster. Based on our results from Drosophila, we performed a human population-based association study to investigate the effect of natural variation in LAMA5 gene on body composition in humans. Results We identified four candidate genes that contributed to differences in TAG storage between two strains of D. melanogaster, including Laminin A (LanA, which is a member of the α subfamily of laminin chains. We confirmed the effects of this gene using a viable LanA mutant and showed that female flies homozygous for the mutation had significantly lower TAG storage, body weight, and total protein content than control flies. Drosophila LanA is closely related to human LAMA5 gene, which maps to the well-replicated obesity-linkage region on chromosome 20q13.2-q13.3. We tested for association between three common single nucleotide polymorphisms (SNPs in the human LAMA5 gene and variation in body composition and lipid profile traits in a cohort of unrelated women of European American (EA and African American (AA descent. In both ethnic groups, we found that SNP rs659822 was associated with weight (EA: P = 0.008; AA: P = 0.05 and lean mass (EA: P= 0.003; AA: P = 0.03. We also found this SNP to be associated with height (P = 0.01, total fat mass (P = 0.01, and HDL-cholesterol (P = 0.003 but only in EA women. Finally, significant associations of SNP rs944895 with serum TAG levels (P = 0.02 and HDL-cholesterol (P = 0.03 were observed in AA women. Conclusion Our results suggest an evolutionarily conserved role of a member of the laminin gene family in contributing to variation in weight and body composition.

  9. Diseased muscles that lack dystrophin or laminin-α2 have altered compositions and proliferation of mononuclear cell populations

    Directory of Open Access Journals (Sweden)

    Miller Jeffrey

    2005-04-01

    Full Text Available Abstract Background Multiple types of mononucleate cells reside among the multinucleate myofibers in skeletal muscles and these mononucleate cells function in muscle maintenance and repair. How neuromuscular disease might affect different types of muscle mononucleate cells had not been determined. In this study, therefore, we examined how two neuromuscular diseases, dystrophin-deficiency and laminin-α2-deficiency, altered the proliferation and composition of different subsets of muscle-derived mononucleate cells. Methods We used fluorescence-activated cell sorting combined with bromodeoxyuridine labeling to examine proliferation rates and compositions of mononuclear cells in diseased and healthy mouse skeletal muscle. We prepared mononucleate cells from muscles of mdx (dystrophin-deficient or Lama2-/- (laminin-α2-deficient mice and compared them to cells from healthy control muscles. We enumerated subsets of resident muscle cells based on Sca-1 and CD45 expression patterns and determined the proliferation of each cell subset in vivo by BrdU incorporation. Results We found that the proliferation and composition of the mononucleate cells in dystrophin-deficient and laminin-α2-deficient diseased muscles are different than in healthy muscle. The mdx and Lama2-/- muscles showed similar significant increases in CD45+ cells compared to healthy muscle. Changes in proliferation, however, differed between the two diseases with proliferation increased in mdx and decreased in Lama2-/- muscles compared to healthy muscles. In particular, the most abundant Sca-1-/CD45- subset, which contains muscle precursor cells, had increased proliferation in mdx muscle but decreased proliferation in Lama2-/- muscles. Conclusion The similar increases in CD45+ cells, but opposite changes in proliferation of muscle precursor cells, may underlie aspects of the distinct pathologies in the two diseases.

  10. Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Simian, Marina; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Shyamala, Gopalan

    2009-05-11

    Expression of the A and B forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional A form of PR as a transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics. We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levels of latency-associated peptide and transforming growth factor beta 1 (TGF{beta}1) between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography. The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E + P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/estrogen receptor alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGF{beta}1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and collagen IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady-state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild-type mice, but is achieved only by treatment with P in PR-A mice. These data

  11. A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations.

    Science.gov (United States)

    Calì, Tito; Lopreiato, Raffaele; Shimony, Joshua; Vineyard, Marisa; Frizzarin, Martina; Zanni, Ginevra; Zanotti, Giuseppe; Brini, Marisa; Shinawi, Marwan; Carafoli, Ernesto

    2015-06-26

    The particular importance of Ca(2+) signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca(2+) ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca(2+). A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with global developmental delay, generalized hypotonia and cerebellar ataxia. The mutation (a R482H replacement) impairs the Ca(2+) ejection function of the pump. It reduces the ability of the pump expressed in model cells to control Ca(2+) transients generated by cell stimulation and impairs its Ca(2+) extrusion function under conditions of low resting cytosolic Ca(2+) as well. In silico analysis of the structural effect of the mutation suggests a reduced stabilization of the portion of the pump surrounding the mutated residue in the Ca(2+)-bound state. The patient also carries two missense mutations in LAMA1, encoding laminin subunit 1α. On the basis of the family pedigree of the patient, the presence of both PMCA3 and laminin subunit 1α mutations appears to be necessary for the development of the disease. Considering the observed defect in cellular Ca(2+) homeostasis and the previous finding that PMCAs act as digenic modulators in Ca(2+)-linked pathologies, the PMCA3 dysfunction along with LAMA1 mutations could act synergistically to cause the neurological phenotype. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations*

    Science.gov (United States)

    Calì, Tito; Lopreiato, Raffaele; Shimony, Joshua; Vineyard, Marisa; Frizzarin, Martina; Zanni, Ginevra; Zanotti, Giuseppe; Brini, Marisa; Shinawi, Marwan; Carafoli, Ernesto

    2015-01-01

    The particular importance of Ca2+ signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca2+ ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca2+. A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with global developmental delay, generalized hypotonia and cerebellar ataxia. The mutation (a R482H replacement) impairs the Ca2+ ejection function of the pump. It reduces the ability of the pump expressed in model cells to control Ca2+ transients generated by cell stimulation and impairs its Ca2+ extrusion function under conditions of low resting cytosolic Ca2+ as well. In silico analysis of the structural effect of the mutation suggests a reduced stabilization of the portion of the pump surrounding the mutated residue in the Ca2+-bound state. The patient also carries two missense mutations in LAMA1, encoding laminin subunit 1α. On the basis of the family pedigree of the patient, the presence of both PMCA3 and laminin subunit 1α mutations appears to be necessary for the development of the disease. Considering the observed defect in cellular Ca2+ homeostasis and the previous finding that PMCAs act as digenic modulators in Ca2+-linked pathologies, the PMCA3 dysfunction along with LAMA1 mutations could act synergistically to cause the neurological phenotype. PMID:25953895

  13. Matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in paediatric burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors.

    Science.gov (United States)

    Weremijewicz, Artur; Matuszczak, Ewa; Sankiewicz, Anna; Tylicka, Marzena; Komarowska, Marta; Tokarzewicz, Anna; Debek, Wojciech; Gorodkiewicz, Ewa; Hermanowicz, Adam

    2018-01-30

    The purpose of this study was the determination of matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in the blood plasma of burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors. 31 children scalded by hot water who were managed at the Department of Paediatric Surgery between 2014-2015, after primarily presenting with burns in 4-20% TBSA were included into the study (age 9 months up to 14 years, mean age 2,5+1 years). There were 10 girls and 21 boys. Venous blood samples were drawn 2-6h, and 12-16h after the thermal injury, and on the subsequent days 3, 5 and 7. The matrix metalloproteinase-2, collagen type IV and laminin-5 concentrations were assessed using Surface Plasmon Resonance Imaging by the investigators blinded to the other data. The MMP-2, laminin-5 and collagen type IV concentrations in the blood plasma of patients with burns, were highest 12-16h after thermal injury, the difference was statistically significant. The MMP-2, laminin-5 and collagen type IV concentrations measured 3 days, 5 days and 7 days after the thermal injury, slowly decreased over time, and on the 7th day reached the normal range, when compared with the concentration measured in controls. Current work is the first follow-up study regarding MMP-2 in burns. MMP-2, laminin-5 and collagen type IV levels were elevated early after burn injury in the plasma of studied patients, and were highest 12-16h after the injury. MMP-2, laminin-5 and collagen type IV levels were not proportional to the severity of the burn. We believe in the possibility that the gradual decrease of MMP-2, collagen type IV and laminin-5 concentrations could be connected with the process of healing, but to prove it, more investigation is needed in this area. The SPR imaging biosensor is a good diagnostic tool for determination of MMP-2, laminin-5 and collagen type IV in blood plasma of patients with burns. Copyright © 2017 Elsevier Ltd

  14. Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tao, E-mail: 11140021@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Hu, Youdong [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China); Tan, Jianying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Liu, Shihui [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Chen, Junying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Guo, Xin; Pan, Changjiang [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Li, Xia, E-mail: xial_li@qq.com [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China)

    2017-02-01

    Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

  15. Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

    International Nuclear Information System (INIS)

    Liu, Tao; Hu, Youdong; Tan, Jianying; Liu, Shihui; Chen, Junying; Guo, Xin; Pan, Changjiang; Li, Xia

    2017-01-01

    Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

  16. How honey bees carry pollen

    Science.gov (United States)

    Matherne, Marguerite E.; Anyanwu, Gabriel; Leavey, Jennifer K.; Hu, David L.

    2017-11-01

    Honey bees are the tanker of the skies, carrying thirty percent of their weight in pollen per foraging trip using specialized orifices on their body. How do they manage to hang onto those pesky pollen grains? In this experimental study, we investigate the adhesion force of pollen to the honeybee. To affix pollen to themselves, honey bees form a suspension of pollen in nectar, creating a putty-like pollen basket that is skewered by leg hairs. We use tensile tests to show that the viscous force of the pollen basket is more than ten times the honeybee's flight force. This work may provide inspiration for the design of robotic flying pollinators.

  17. The laminin beta 1-competing peptide YIGSR induces a hypercontractile, hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Bos, I. Sophie T.; Halayko, Andrew J.; Zaagsma, Johan; Meurs, Herman

    2010-01-01

    Background: Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hyper)contractile phenotype is dependent on laminin, which can

  18. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

    Science.gov (United States)

    Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

    1999-01-01

    We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

  19. Can alterations in integrin and laminin-5 expression be used as markers of malignancy?

    DEFF Research Database (Denmark)

    Thorup, A K; Reibel, J; Schiødt, M

    1998-01-01

    Development of squamous cell carcinomas (SCCs) involves alterations in the adhesive interactions in the epithelium and invasion through the basement membrane. Therefore, changes in the expression of receptors and ligands involved in cell-cell and cell-matrix adhesion may be essential for the tran...

  20. Tissue-engineered cartilaginous constructs for the treatment of caprine cartilage defects, including distribution of laminin and type IV collagen.

    Science.gov (United States)

    Jeng, Lily; Hsu, Hu-Ping; Spector, Myron

    2013-10-01

    The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

  1. Laminin-332 alters connexin profile, dye coupling and intercellular Ca2+ waves in ciliated tracheal epithelial cells

    Directory of Open Access Journals (Sweden)

    Olsen Colin E

    2006-08-01

    Full Text Available Abstract Background Tracheal epithelial cells are anchored to a dynamic basement membrane that contains a variety of extracellular matrix proteins including collagens and laminins. During development, wound repair and disease of the airway epithelium, significant changes in extracellular matrix proteins may directly affect cell migration, differentiation and events mediated by intercellular communication. We hypothesized that alterations in cell matrix, specifically type I collagen and laminin α3β3γ2 (LM-332 proteins within the matrix, directly affect intercellular communication in ciliated rabbit tracheal epithelial cells (RTEC. Methods Functional coupling of RTEC was monitored by microinjection of the negatively charged fluorescent dyes, Lucifer Yellow and Alexa 350, into ciliated RTEC grown on either a LM-332/collagen or collagen matrix. Coupling of physiologically significant molecules was evaluated by the mechanism and extent of propagated intercellular Ca2+ waves. Expression of connexin (Cx mRNA and proteins were assayed by reverse transcriptase – polymerase chain reaction and immunocytochemistry, respectively. Results When compared to RTEC grown on collagen alone, RTEC grown on LM-332/collagen displayed a significant increase in dye transfer. Although mechanical stimulation of RTEC grown on either LM-332/collagen or collagen alone resulted in intercellular Ca2+ waves, the mechanism of transfer was dependent on matrix: RTEC grown on LM-332/collagen propagated Ca2+waves via extracellular purinergic signaling whereas RTEC grown on collagen used gap junctions. Comparison of RTEC grown on collagen or LM-332/collagen matrices revealed a reorganization of Cx26, Cx43 and Cx46 proteins. Conclusion Alterations in airway basement membrane proteins such as LM-332 can induce connexin reorganizations and result in altered cellular communication mechanisms that could contribute to airway tissue function.

  2. Augmentation de l'expression de la chaine α1 de la laminine 111, un potentiel traitement pour la Dystrophie musculaire de Duchenne

    OpenAIRE

    Perrin, Arnaud

    2016-01-01

    La protéine hétérotrimérique laminine-111 permet le lien entre la matrice-extracellulaire et l’intégrine α7β1 du sarcolemme, remplaçant ainsi dans les muscles dystrophiques, des liens normalement assurés par le complexe de la dystrophine. L’injection de laminine-111 dans des souris mdx a permis, entre autre, l’augmentation de l'expression de l'intégrine α7β1, d’empêcher les bris du sarcolemme lors de la contraction musculaire, de restaurer un niveau normal de la créatine kinase sérique, ainsi...

  3. Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Soendergaard, Christoffer; Jørgensen, Steffen

    2017-01-01

    and to assess the influence of inflammation. Transcriptional regulation of LAMC2 was examined by reporter gene assays, overexpression, and shRNA-mediated knock-down of CDX2. CDX2-DNA interactions were assessed by chromatin immunoprecipitation on Caco-2 cells without or with TNF-α, as well as in purified colonic......The expression of Caudal-related homeobox transcription factor 2 (CDX2) is impaired by tumor necrosis factor-α (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) in ulcerative colitis (UC). Laminin subunit γ2 (LAMC2) is an epithelial basement membrane protein implicated in cell migration......, proliferation, differentiation, as well as tumor invasion and intestinal inflammation, and its expression is enhanced by TNF-α in a NF-κB-dependent regulation of the recently identified LAMC2 enhancer. The aim was to determine whether CDX2 is involved in the basal regulation of LAMC2 in epithelial cells...

  4. Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Agneta Månsson-Broberg

    2016-04-01

    Full Text Available The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.

  5. Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK

    Directory of Open Access Journals (Sweden)

    Chiou Shih-Hwa

    2010-07-01

    Full Text Available Abstract Background Islet transplantation provides a promising cure for Type 1 diabetes; however it is limited by a shortage of pancreas donors. Bone marrow-derived multipotent mesenchymal stem cells (MSCs offer renewable cells for generating insulin-producing cells (IPCs. Methods We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation. Results Here, we report adding extracellular matrix proteins (ECM such as fibronectin (FN or laminin (LAM enhances pancreatic differentiation with increases in insulin and Glut2 gene expressions, proinsulin and insulin protein levels, and insulin release in response to elevated glucose concentration. Adding FN or LAM induced activation of Akt and ERK. Blocking Akt or ERK by adding LY294002 (PI3K specific inhibitor, PD98059 (MEK specific inhibitor or knocking down Akt or ERK failed to abrogate FN or LAM-induced enhancement of IPC differentiation. Only blocking both of Akt and ERK or knocking down Akt and ERK inhibited the enhancement of IPC differentiation by adding ECM. Conclusions These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through activation of Akt and ERK pathways.

  6. Clinical value of the joint measurement of serum concentrations of type IV collagen and laminin in patients with diabetic nephropathy

    International Nuclear Information System (INIS)

    Wang Lu; Wang Ping; Li Yongpei

    2004-01-01

    Objective: To study clinical value of the joint measurement of serum concentrations of type IV collagen (IV C) and laminin (LN) in patients with diabetic nephropathy (DN) by radioimmunoassay (RIA). Methods: Serum concentrations of IV C, LN were measured by RIA in 35 diabetic patients with normalbuminuria (group A), 28 cases of microalbuminuria (group B), 15 cases of macroalbuminuria (group C) and 30 normal subjects as control . Results: The serum concentrations of IV C, LN in total 78 diabetic patients [(97.6 ± 19.2), (132.4 ± 31.5) μg/L] were higher than that of the controls [(77.4 ± 8.2), (101.5 ± 17.6) μg/L, P<0.05], especially in group B and C, it was remarkably higher compared with the controls (P<0.05, P<0.01). There was significant positive correlation of serum IV C, LN to diabetic duration and the levels of blood urea nitrogen (BUN), creatinine (Cr), urinary albumin excretion rate (UAER). Conclusions: The results suggest that the joint measurement of serum levels of IV C, LN and UAER in DN patients might better evaluate the development process of DN, and be of help for early diagnosis and treatment of DN. Serum levels of IV C, LN and UAER in DN patients may become the reliable clinical markers for assessing the severity and predicting the prognosis of DN

  7. Immobilization of Dystrophin and Laminin α2-Chain Deficient Zebrafish Larvae In Vivo Prevents the Development of Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Mei Li

    Full Text Available Muscular dystrophies are often caused by genetic alterations in the dystrophin-dystroglycan complex or its extracellular ligands. These structures are associated with the cell membrane and provide mechanical links between the cytoskeleton and the matrix. Mechanical stress is considered a pathological mechanism and muscle immobilization has been shown to be beneficial in some mouse models of muscular dystrophy. The zebrafish enables novel and less complex models to examine the effects of extended immobilization or muscle relaxation in vivo in different dystrophy models. We have examined effects of immobilization in larvae from two zebrafish strains with muscular dystrophy, the Sapje dystrophin-deficient and the Candyfloss laminin α2-chain-deficient strains. Larvae (4 days post fertilization, dpf of both mutants have significantly lower active force in vitro, alterations in the muscle structure with gaps between muscle fibers and altered birefringence patterns compared to their normal siblings. Complete immobilization (18 hrs to 4 dpf was achieved using a small molecular inhibitor of actin-myosin interaction (BTS, 50 μM. This treatment resulted in a significantly weaker active contraction at 4 dpf in both mutated larvae and normal siblings, most likely reflecting a general effect of immobilization on myofibrillogenesis. The immobilization also significantly reduced the structural damage in the mutated strains, showing that muscle activity is an important pathological mechanism. Following one-day washout of BTS, muscle tension partly recovered in the Candyfloss siblings and caused structural damage in these mutants, indicating activity-induced muscle recovery and damage, respectively.

  8. Consumerism and the Sister Carrie's American Dream%Consumerism and the Sister Carrie''s American Dream

    Institute of Scientific and Technical Information of China (English)

    卢亚丽

    2017-01-01

    From the aspect of consumerism to this text analyze Sister Carrie's"American dream"destruction. The author wholly and deeply analyzes the embodiment of consumerism in Dreiser's Sister Carrie and Dreiser's outlook and values under the effect of consumerism. To prove that the reason for destruction of Carrie's American dream is consumerism.

  9. Energetics of load carrying in Nepalese porters.

    Science.gov (United States)

    Bastien, Guillaume J; Schepens, Bénédicte; Willems, Patrick A; Heglund, Norman C

    2005-06-17

    Nepalese porters routinely carry head-supported loads equal to 100 to 200% of their body weight (Mb) for many days up and down steep mountain footpaths at high altitudes. Previous studies have shown that African women carry head-supported loads of up to 60% of their Mb far more economically than army recruits carrying equivalent loads in backpacks. Here we show that Nepalese porters carry heavier loads even more economically than African women. Female Nepalese porters, for example, carry on average loads that are 10% of their Mb heavier than the maximum loads carried by the African women, yet do so at a 25% smaller metabolic cost.

  10. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  11. Consumerism and the Sister Carrie's American Dream

    Institute of Scientific and Technical Information of China (English)

    卢亚丽

    2017-01-01

    From the aspect of consumerism to this text analyze Sister Carrie's"American dream"destruction. The author wholly and deeply analyzes the embodiment of consumerism in Dreiser's Sister Carrie and Dreiser's outlook and values under the effect of consumerism. To prove that the reason for destruction of Carrie's American dream is consumerism.

  12. Local Dynamic Stability Associated with Load Carrying

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2013-03-01

    Conclusion: Current study confirmed the sensitivity of local dynamic stability measure in load carrying situation. It was concluded that load carrying tasks were associated with declined local dynamic stability, which may result in increased risk of fall accident. This finding has implications in preventing fall accidents associated with occupational load carrying.

  13. Host factors that modify Plasmodium falciparum adhesion to endothelial receptors.

    Science.gov (United States)

    Mahamar, Almahamoudou; Attaher, Oumar; Swihart, Bruce; Barry, Amadou; Diarra, Bacary S; Kanoute, Moussa B; Cisse, Kadidia B; Dembele, Adama B; Keita, Sekouba; Gamain, Benoît; Gaoussou, Santara; Issiaka, Djibrilla; Dicko, Alassane; Duffy, Patrick E; Fried, Michal

    2017-10-24

    P. falciparum virulence is related to adhesion and sequestration of infected erythrocytes (IE) in deep vascular beds, but the endothelial receptors involved in severe malaria remain unclear. In the largest ever study of clinical isolates, we surveyed adhesion of freshly collected IE from children under 5 years of age in Mali to identify novel vascular receptors, and examined the effects of host age, hemoglobin type, blood group and severe malaria on levels of IE adhesion to a panel of endothelial receptors. Several novel molecules, including integrin α3β1, VE-cadherin, ICAM-2, junctional adhesion molecule-B (JAM-B), laminin, and cellular fibronectin, supported binding of IE from children. Severe malaria was not significantly associated with levels of IE adhesion to any of the 19 receptors. Hemoglobin AC, which reduces severe malaria risk, reduced IE binding to the receptors CD36 and integrin α5β1, while hemoglobin AS did not modify IE adhesion to any receptors. Blood groups A, AB and B significantly reduced IE binding to ICAM-1. Severe malaria risk varies with age, but age significantly impacted the level of IE binding to only a few receptors: IE binding to JAM-B decreased with age, while binding to CD36 and integrin α5β1 significantly increased with age.

  14. Characterization of the human laminin beta2 chain locus (LAMB2): linkage to a gene containing a nonprocessed, transcribed LAMB2-like pseudogene (LAMB2L) and to the gene encoding glutaminyl tRNA synthetase (QARS)

    DEFF Research Database (Denmark)

    Durkin, M E; Jäger, A C; Khurana, T S

    1999-01-01

    The laminin beta2 chain is an important constituent of certain kidney and muscle basement membranes. We have generated a detailed physical map of a 110-kb genomic DNA segment surrounding the human laminin beta2 chain gene (LAMB2) on chromosome 3p21.3-->p21.2, a region paralogous with the chromosome...... 7q22-->q31 region that contains the laminin beta1 chain gene locus (LAMB1). Several CpG islands and a novel polymorphic microsatellite marker (D3S4594) were identified. The 3' end of LAMB2 lies 16 kb from the 5' end of the glutaminyl tRNA synthetase gene (QARS). About 20 kb upstream of LAMB2 we...... found a gene encoding a transcribed, non-processed LAMB2-like pseudogene (LAMB2L). The sequence of 1.75 kb of genomic DNA at the 3' end of LAMB2L was similar to exons 8-12 of the laminin beta2 chain gene. The LAMB2L-LAMB2-QARS cluster lies telomeric to the gene encoding the laminin-binding protein...

  15. Measuring Social carrying Capacity: An Exploratory Study

    OpenAIRE

    López-Bonilla, Jesús Manuel; López-Bonilla, Luis Miguel

    2007-01-01

    The tourist carrying capacity commands a growing interest given that it is closely linked with sustainable tourist development. The justification of the utility of this concept is given by means of a simple and efficient methodological proposal, by analysing the social carrying capacity. To this end, an empirical application is carried out in the Western Andalusia. In some of the cases analysed, the satisfaction of the tourist is found to decline when the levels of the tourist use are higher ...

  16. The Concept of Carrying Capacity in Tourism

    Directory of Open Access Journals (Sweden)

    Josef Zelenka

    2014-05-01

    Full Text Available Carrying capacity is often pragmatically, theoretically as well as purely intuitively considered as a concept in the context of tourism sustainability. The carrying capacity application has the greatest potential in protected areas, in frequently visited cultural and natural attractions, and in relation to sustaining of the lifestyle of the local community and tourism destination potential in general. Despite its importance, partial applications, determination of basic theoretical principles, and specifying connection to the other theoretical concepts in tourism (particularly destination life cycle, LAC concept, visitors management, there still is a rightful opinion of some authors suggesting that there is no consistent theory of tourism carrying capacity. This theory would be the base for sophisticated practical carrying capacity applications. This paper is therefore focused on introduction of the theoretical concept of carrying capacity, which can be discussed and possibly further elaborated.

  17. Inhibition on Apoptosis Induced by Elevated Hydrostatic Pressure in Retinal Ganglion Cell-5 via Laminin Upregulating β1-integrin/Focal Adhesion Kinase/Protein Kinase B Signaling Pathway.

    Science.gov (United States)

    Li, Yi; Chen, Yan-Ming; Sun, Ming-Ming; Guo, Xiao-Dan; Wang, Ya-Chen; Zhang, Zhong-Zhi

    2016-04-20

    Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells (RGCs). High intraocular pressure (HIOP), the main risk factor, causes the optic nerve damage. However, the precise mechanism of HIOP-induced RGC death is not yet completely understood. This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures, explore whether laminin is associated with apoptosis under pressure, whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival. RGC-5 cells were exposed to 0, 20, 40, and 60 mmHg in a pressurized incubator for 6, 12, and 24 h, respectively. The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blotting of cleaved caspase-3 protein. Location and expression of laminin were detected by immunofluorescence. The expression of β1-integrin, phosphorylation of focal adhesion kinase (FAK) and protein kinase B (PKB, or AKT) were investigated with real-time polymerase chain reaction and Western blotting analysis. Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells. Pressure with 40 mmHg for 24 h induced a maximum apoptosis. Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h. After pretreating with laminin, RGC-5 cells survived from elevated pressure. Furthermore, β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group. The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure. Laminin can protect RGC-5 cells against high pressure via β1-integrin/FAK/AKT signaling pathway. These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure, and laminin or activating β1-integrin

  18. Parallelization of Reversible Ripple-carry Adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock

    2009-01-01

    The design of fast arithmetic logic circuits is an important research topic for reversible and quantum computing. A special challenge in this setting is the computation of standard arithmetical functions without the generation of \\emph{garbage}. Here, we present a novel parallelization scheme...... wherein $m$ parallel $k$-bit reversible ripple-carry adders are combined to form a reversible $mk$-bit \\emph{ripple-block carry adder} with logic depth $\\mathcal{O}(m+k)$ for a \\emph{minimal} logic depth $\\mathcal{O}(\\sqrt{mk})$, thus improving on the $mk$-bit ripple-carry adder logic depth $\\mathcal...

  19. Gun Carrying by High School Students in Boston, MA: Does Overestimation of Peer Gun Carrying Matter?

    Science.gov (United States)

    Hemenway, David; Vriniotis, Mary; Johnson, Renee M.; Miller, Matthew; Azrael, Deborah

    2011-01-01

    This paper investigates: (1) whether high school students overestimate gun carrying by their peers, and (2) whether those students who overestimate peer gun carrying are more likely to carry firearms. Data come from a randomly sampled survey conducted in 2008 of over 1700 high school students in Boston, MA. Over 5% of students reported carrying a…

  20. Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid

    Directory of Open Access Journals (Sweden)

    Sachiro eKakinoki

    2014-07-01

    Full Text Available We developed a microfibrous poly(L-lactic acid (PLLA nerve conduit with a three-layered structure to simultaneously enhance nerve regeneration and prevent adhesion of surrounding tissue. The inner layer was composed of PLLA microfiber containing 25% elastin-laminin mimetic protein (AG73-(VPGIG30 that promotes neurite outgrowth. The thickest middle layer was constructed of pure PLLA microfibers that impart the large mechanical stremgth to the conduit. A 10% poly(ethylene glycol was added to the outer layer to prevent the adhesion with the surrounding tissue. The AG73-(VPGIG30 composisting of an elastin-like repetitive sequence (VPGIG30 and a laminin-derived sequence (RKRLQVQLSIRT: AG73 was biosynthesized using Escherichia coli. The PLLA microfibrous conduits were fabricated using an electrospinning procedure. AG73-(VPGIG30 was successfully mixed in the PLLA microfibers, and the PLLA/AG73-(VPGIG30 microfibers were stable under physiological conditions. The PLLA/AG73-(VPGIG30 microfibers enhanced adhesion and neurite outgrowth of PC12 cells. The electrospun microfibrous conduit with a three-layered structure was implanted for bridging a 2.0-cm gap in the tibial nerve of a rabbit. Two months after implantation, no adhesion of surrounding tissue was observed, and the action potential was slightly improved in the nerve conduit with the PLLA/AG73-(VPGIG30 inner layer.

  1. Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid)

    Science.gov (United States)

    Kakinoki, Sachiro; Nakayama, Midori; Moritan, Toshiyuki; Yamaoka, Tetsuji

    2014-07-01

    We developed a microfibrous poly(L-lactic acid) (PLLA) nerve conduit with a three-layered structure to simultaneously enhance nerve regeneration and prevent adhesion of surrounding tissue. The inner layer was composed of PLLA microfiber containing 25% elastin-laminin mimetic protein (AG73-(VPGIG)30) that promotes neurite outgrowth. The thickest middle layer was constructed of pure PLLA microfibers that impart the large mechanical stremgth to the conduit. A 10% poly(ethylene glycol) was added to the outer layer to prevent the adhesion with the surrounding tissue. The AG73-(VPGIG)30 composisting of an elastin-like repetitive sequence (VPGIG)30 and a laminin-derived sequence (RKRLQVQLSIRT: AG73) was biosynthesized using Escherichia coli. The PLLA microfibrous conduits were fabricated using an electrospinning procedure. AG73-(VPGIG)30 was successfully mixed in the PLLA microfibers, and the PLLA/AG73-(VPGIG)30 microfibers were stable under physiological conditions. The PLLA/AG73-(VPGIG)30 microfibers enhanced adhesion and neurite outgrowth of PC12 cells. The electrospun microfibrous conduit with a three-layered structure was implanted for bridging a 2.0-cm gap in the tibial nerve of a rabbit. Two months after implantation, no adhesion of surrounding tissue was observed, and the action potential was slightly improved in the nerve conduit with the PLLA/AG73-(VPGIG)30 inner layer.

  2. Levels of α7 integrin and laminin-α2 are increased following prednisone treatment in the mdx mouse and GRMD dog models of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Ryan D. Wuebbles

    2013-09-01

    Duchenne muscular dystrophy (DMD is a fatal neuromuscular disease for which there is no cure and limited treatment options. Prednisone is currently the first line treatment option for DMD and studies have demonstrated that it improves muscle strength. Although prednisone has been used for the treatment of DMD for decades, the mechanism of action of this drug remains unclear. Recent studies have shown that the α7β1 integrin is a major modifier of disease progression in mouse models of DMD and is therefore a target for drug-based therapies. In this study we examined whether prednisone increased α7β1 integrin levels in mdx mouse and GRMD dog models and myogenic cells from humans with DMD. Our results show that prednisone promotes an increase in α7 integrin protein in cultured myogenic cells and in the muscle of mdx and GRMD animal models of DMD. The prednisone-mediated increase in α7 integrin was associated with increased laminin-α2 in prednisone-treated dystrophin-deficient muscle. Together, our results suggest that prednisone acts in part through increased merosin in the muscle basal lamina and through sarcolemmal stabilization of α7β1 integrin in dystrophin-deficient muscle. These results indicate that therapies that target an increase in muscle α7β1 integrin, its signaling pathways and/or laminin could be therapeutic in DMD.

  3. Entamoeba histolytica: a beta 1 integrin-like fibronectin receptor assembles a signaling complex similar to those of mammalian cells.

    Science.gov (United States)

    Flores-Robles, Donaciano; Rosales, Carlos; Rosales-Encina, José Luis; Talamás-Rohana, Patricia

    2003-01-01

    During tissue invasion, Entamoeba histolytica trophozoites interact with endothelial cells and extracellular matrix (ECM) proteins such as fibronectin (FN), collagen, and laminin. It has been demonstrated that trophozoites interact with FN through a beta1 integrin-like FN receptor (beta 1EhFNR), activating tyrosine kinases. In order to characterize the signaling process triggered by the amoebic receptor, activation, and association of tyrosine kinases and structural proteins were determined. As a result of FN binding by the beta 1EhFNR, the receptor itself, FAK, and paxillin were phosphorylated in tyrosine. Co-immunoprecipitation experiments showed that a multimolecular signaling complex was formed by the amoebic FN receptor, FAK, paxillin, and vinculin. These results strongly suggest that a signaling pathway, similar to the one used in mammalian cells, is activated when E. histolytica trophozoites adhere to FN.

  4. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  5. Abstraction carrying code and resource-awareness

    OpenAIRE

    Hermenegildo, Manuel V.; Albert Albiol, Elvira; López García, Pedro; Puebla Sánchez, Alvaro Germán

    2005-01-01

    Proof-Carrying Code (PCC) is a general approach to mobile code safety in which the code supplier augments the program with a certifícate (or proof). The intended benefit is that the program consumer can locally validate the certifícate w.r.t. the "untrusted" program by means of a certifícate checker—a process which should be much simpler, eíñcient, and automatic than generating the original proof. Abstraction Carrying Code (ACC) is an enabling technology for PCC in which an abstract mod...

  6. Transgenic cassava lines carrying heterologous alternative oxidase ...

    African Journals Online (AJOL)

    Afuape

    2013-07-03

    Jul 3, 2013 ... production of flowers, apomixis (Nassar et al., 2000; ... In order to increase the stress tolerance capacity of ... stress-related procedure due to the activities of auxin ... the evaluation of the transgenic lines for rate of OES .... Some transgenic lines carrying the 35S-AOX fragment amplified using 35S303F1 and.

  7. Infections That Pets Carry (For Parents)

    Science.gov (United States)

    ... how to protect your family from infections. How Pets Spread Infections Like people, all animals carry germs . Illnesses common among housepets — ... get an infection that can be passed to people. Safely Caring for Your Pet Here are some tips to help your family ...

  8. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene (PEP-cDNA) in prokaryotic and mammalian expression vectors in ... pGEX6p2-PEP and pUcD3-FLAG-PEP constructed vectors were transformed into the one shot TOP10 and JM105 bacterial competent cells, respectively.

  9. Magnetoacoustic waves in current-carrying plasmas

    International Nuclear Information System (INIS)

    Brennan, M.H.

    1980-04-01

    The results of theoretical and experimental investigations of the characteristics of magnetoacoustic waves in non-uniform, current-carrying plasmas are reviewed. Dissipative MHD and collisionless theories are considered. Also discussed is the use of magnetoacoustic waves in plasma diagnostics and plasma heating

  10. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    Nov 16, 2009 ... The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene. (PEP-cDNA) in prokaryotic and mammalian expression vectors in chimeric cDNA types, encompassing. GST and FLAG with PEP-cDNA. PEP-cDNA was sub-cloned in pGEX6p2 prokaryotic expression ...

  11. Transgenic cassava lines carrying heterologous alternative oxidase ...

    African Journals Online (AJOL)

    Afuape

    2013-07-03

    Jul 3, 2013 ... Organized embryogenic callus development: In our experiment, somatic embryos were developed from leaf lobes collected from transgenic cassava lines carrying the AtAOX1a gene. Immature leaf lobes measuring about 1 to 6 mm obtained from about six weeks old in vitro derived plants were used.

  12. Tissue-specific expression of the human laminin alpha5-chain, and mapping of the gene to human chromosome 20q13.2-13.3 and to distal mouse chromosome 2 near the locus for the ragged (Ra) mutation

    DEFF Research Database (Denmark)

    Durkin, M E; Loechel, F; Mattei, M G

    1997-01-01

    , heart, lung, skeletal muscle, kidney, and pancreas. The human laminin alpha5-chain gene (LAMA5) was assigned to chromosome 20q13.2-q13.3 by in situ hybridization, and the mouse gene (Lama5) was mapped by linkage analysis to a syntonic region of distal chromosome 2, close to the locus for the ragged (Ra...

  13. Research on Water Resources Design Carrying Capacity

    Directory of Open Access Journals (Sweden)

    Guanghua Qin

    2016-04-01

    Full Text Available Water resources carrying capacity (WRCC is a recently proposed management concept, which aims to support sustainable socio-economic development in a region or basin. However, the calculation of future WRCC is not well considered in most studies, because water resources and the socio-economic development mode for one area or city in the future are quite uncertain. This paper focused on the limits of traditional methods of WRCC and proposed a new concept, water resources design carrying capacity (WRDCC, which incorporated the concept of design. In WRDCC, the population size that the local water resources can support is calculated based on the balance of water supply and water consumption, under the design water supply and design socio-economic development mode. The WRDCC of Chengdu city in China is calculated. Results show that the WRDCC (population size of Chengdu city in development modeI (II, III will be 997 ×104 (770 × 104, 504 × 104 in 2020, and 934 × 104 (759 × 104, 462 × 104 in 2030. Comparing the actual population to the carrying population (WRDCC in 2020 and 2030, a bigger gap will appear, which means there will be more and more pressure on the society-economic sustainable development.

  14. Distribution of a 69-kD laminin-binding protein in aortic and microvascular endothelial cells: modulation during cell attachment, spreading, and migration

    DEFF Research Database (Denmark)

    Yannariello-Brown, J; Wewer, U; Liotta, L

    1988-01-01

    cells identified this protein in BAEC lysates. In frozen sections, these polyclonal antibodies and monoclonal antibodies raised against human tumor 69-kD stained the endothelium of bovine aorta and the medial smooth muscle cells, but not surrounding connective tissue or elastin fibers. When...... nonpermeabilized BAEC were stained in an in vitro migration assay, there appeared to be apical patches of 69 kD staining in stationary cells. However, when released from contact inhibition, 69 kD was localized to ruffling membranes on cells at the migrating front. Permeabilized BAEC stained for 69 kD diffusely...... in permeabilized cultured microvascular endothelial cells in a continuous staining pattern at 6 h postplating which redistributed to punctate patches along the length of the filaments at confluence (96 h). In addition, 69 kD co-distribution with laminin could also be demonstrated in cultured subconfluent cells...

  15. Knockdown of Laminin gamma-3 (Lamc3 impairs motoneuron guidance in the zebrafish embryo [version 1; referees: 2 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Alexander M. J. Eve

    2017-11-01

    Full Text Available Background: Previous work in the zebrafish embryo has shown that laminin γ-3 (lamc3 is enriched in endothelial cells marked by expression of fli1a, but the role of Lamc3 has been unknown. Methods: We use antisense morpholino oligonucleotides, and CRISPR/Cas9 mutagenesis of F0 embryos, to create zebrafish embryos in which lamc3 expression is compromised. Transgenic imaging, immunofluorescence, and in situ hybridisation reveal that Lamc3 loss-of-function affects the development of muscle pioneers, endothelial cells, and motoneurons. Results: Lamc3 is enriched in endothelial cells during zebrafish development, but it is also expressed by other tissues. Depletion of Lamc3 by use of antisense morpholino oligonucleotides perturbs formation of the parachordal chain and subsequently the thoracic duct, but Lamc3 is not required for sprouting of the cardinal vein. F0 embryos in which lamc3 expression is perturbed by a CRISPR/Cas9 approach also fail to form a parachordal chain, but we were unable to establish a stable lamc3 null line. Lamc3 is dispensable for muscle pioneer specification and for the expression of netrin-1a in these cells. Lamc3 knockdown causes netrin-1a up-regulation in the neural tube and there is increased Netrin-1 protein throughout the trunk of the embryo. Axonal guidance of rostral primary motoneurons is defective in Lamc3 knockdown embryos. Conclusions: We suggest that knockdown of Lamc3 perturbs migration of rostral primary motoneurons at the level of the horizontal myoseptum, indicating that laminin γ3 plays a role in motoneuron guidance.

  16. Disruption of fibronectin matrix affects type IV collagen, fibrillin and laminin deposition into extracellular matrix of human trabecular meshwork (HTM) cells.

    Science.gov (United States)

    Filla, Mark S; Dimeo, Kaylee D; Tong, Tiegang; Peters, Donna M

    2017-12-01

    Fibronectin fibrils are a major component of the extracellular matrix (ECM) of the trabecular meshwork (TM). They are a key mediator of the formation of the ECM which controls aqueous humor outflow and contributes to the pathogenesis of glaucoma. The purpose of this work was to determine if a fibronectin-binding peptide called FUD, derived from the Streptococcus pyogenes Functional Upstream Domain of the F1 adhesin protein, could be used to control fibronectin fibrillogenesis and hence ECM formation under conditions where its expression was induced by treatment with the glucocorticoid dexamethasone. FUD was very effective at preventing fibronectin fibrillogenesis in the presence or absence of steroid treatment as well as the removal of existing fibronectin fibrils. Disruption of fibronectin fibrillogenesis by FUD also disrupted the incorporation of type IV collagen, laminin and fibrillin into the ECM. The effect of FUD on these other protein matrices, however, was found to be dependent upon the maturity of the ECM when FUD was added. FUD effectively disrupted the incorporation of these other proteins into matrices when added to newly confluent cells that were forming a nascent ECM. In contrast, FUD had no effect on these other protein matrices if the cell cultures already possessed a pre-formed, mature ECM. Our studies indicate that FUD can be used to control fibronectin fibrillogenesis and that these fibrils play a role in regulating the assembly of other ECM protein into matrices involving type IV collagen, laminin, and fibrillin within the TM. This suggests that under in vivo conditions, FUD would selectively disrupt fibronectin fibrils and de novo assembly of other proteins into the ECM. Finally, our studies suggest that targeting fibronectin fibril assembly may be a viable treatment for POAG as well as other glaucomas involving excessive or abnormal matrix deposition of the ECM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Wound healing effects of collagen-laminin dermal matrix impregnated with resveratrol loaded hyaluronic acid-DPPC microparticles in diabetic rats.

    Science.gov (United States)

    Gokce, Evren H; Tuncay Tanrıverdi, Sakine; Eroglu, Ipek; Tsapis, Nicolas; Gokce, Goksel; Tekmen, Isıl; Fattal, Elias; Ozer, Ozgen

    2017-10-01

    An alternative formulation for the treatment of diabetic foot wounds that heal slowly is a requirement in pharmaceutical field. The aim of this study was to develop a dermal matrix consisting of skin proteins and lipids with an antioxidant that will enhance healing and balance the oxidative stress in the diabetic wound area due to the high levels of glucose. Thus a novel three dimensional collagen-laminin porous dermal matrix was developed by lyophilization. Resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine microparticles were combined with this dermal matrix. Characterization, in vitro release, microbiological and in vivo studies were performed. Spherical microparticles were obtained with a high RSV encapsulation efficacy. The microparticles were well dispersed in the dermal matrix from the surface to deeper layers. Collagenase degraded dermal matrix, however the addition of RSV loaded microparticles delayed the degradation time. The release of RSV was sustained and reached 70% after 6h. Histological changes and antioxidant parameters in different treatment groups were investigated in full-thickness excision diabetic rat model. Collagen fibers were intense and improved by the presence of formulation without any signs of inflammation. The highest healing score was obtained with the dermal matrix impregnated with RSV-microparticles with an increased antioxidant activity. Collagen-laminin dermal matrix with RSV microparticles was synergistically effective due to presence of skin components in the formulation and controlled release achieved. This combination is a safe and promising option for the treatment of diabetic wounds requiring long recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Placarding of road vehicles carrying radioactive materials

    International Nuclear Information System (INIS)

    1977-09-01

    The purpose of this Code is to give guidance on the placarding requirements for vehicles carrying radioactive materials by road in Great Britain and on the continent of Europe. Additional placards may be required regarding dangerous properties other than radioactivity. The labelling of packages for transport is dealt with in AECP 1030. This Code deals with two aspects of road vehicle placarding:-(a) placarding on the outside of road vehicles in Great Britain and on the continent of Europe, (b) a fireproof placard fixed in the driver's cab. Responsibility for placarding the vehicle rests with the carrier, but in practice the consignor may need to provide the placards. (U.K.)

  19. Killing cancer cells by targeted drug-carrying phage nanomedicines

    Directory of Open Access Journals (Sweden)

    Yacoby Iftach

    2008-04-01

    Full Text Available Abstract Background Systemic administration of chemotherapeutic agents, in addition to its anti-tumor benefits, results in indiscriminate drug distribution and severe toxicity. This shortcoming may be overcome by targeted drug-carrying platforms that ferry the drug to the tumor site while limiting exposure to non-target tissues and organs. Results We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated filamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1000 over the corresponding free drugs. Conclusion The results of the proof-of concept study presented here reveal important features regarding the potential of filamentous phages to serve as drug-delivery platform, on the affect of drug solubility or hydrophobicity on the target specificity of the platform and on the effect of drug release mechanism on the potency of the platform. These results define targeted drug-carrying filamentous phage nanoparticles as a unique type of antibody-drug conjugates.

  20. Killing cancer cells by targeted drug-carrying phage nanomedicines

    Science.gov (United States)

    Bar, Hagit; Yacoby, Iftach; Benhar, Itai

    2008-01-01

    Background Systemic administration of chemotherapeutic agents, in addition to its anti-tumor benefits, results in indiscriminate drug distribution and severe toxicity. This shortcoming may be overcome by targeted drug-carrying platforms that ferry the drug to the tumor site while limiting exposure to non-target tissues and organs. Results We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated filamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1000 over the corresponding free drugs. Conclusion The results of the proof-of concept study presented here reveal important features regarding the potential of filamentous phages to serve as drug-delivery platform, on the affect of drug solubility or hydrophobicity on the target specificity of the platform and on the effect of drug release mechanism on the potency of the platform. These results define targeted drug-carrying filamentous phage nanoparticles as a unique type of antibody-drug conjugates. PMID:18387177

  1. Cryptococcus neoformans carried by Odontomachus bauri ants

    Directory of Open Access Journals (Sweden)

    Mariana Santos de Jesus

    2012-06-01

    Full Text Available Cryptococcus neoformans is the most common causative agent of cryptococcosis worldwide. Although this fungus has been isolated from a variety of organic substrates, several studies suggest that hollow trees constitute an important natural niche for C. neoformans. A previously surveyed hollow of a living pink shower tree (Cassia grandis positive for C. neoformans in the city of Rio de Janeiro, Brazil, was chosen for further investigation. Odontomachus bauri ants (trap-jaw ants found inside the hollow were collected for evaluation as possible carriers of Cryptococcus spp. Two out of 10 ants were found to carry phenoloxidase-positive colonies identified as C. neoformans molecular types VNI and VNII. The ants may have acted as a mechanical vector of C. neoformans and possibly contributed to the dispersal of the fungi from one substrate to another. To the best of our knowledge, this is the first report on the association of C. neoformans with ants of the genus Odontomachus.

  2. Voltage-carrying states in superconducting microstrips

    International Nuclear Information System (INIS)

    Stuivinga, M.E.C.

    1983-01-01

    When the critical current is exceeded in a superconducting microstrip, voltage-carrying states with a resistance significantly below the normal state resistance can occur. Phase-slip centers (PSC) appear at about the critical temperature. These are successive local voltage units which manifest themselves as strip-like increments in voltage in the I-V characteristic. For temperatures off the critical temperature the PSC regime degenerates into a region of normal material, a so-called hot spot. These two phenomena, PSC and hot spots, form the subject of this thesis. To gain a better understanding of the phase-slip center process, an experiment was designed to measure local values of the quasi-particle and pair potential. The results of local potential and gap measurements at a PSC in aluminium are presented and discussed. Special attention is paid to pair-breaking interactions which can shorten the relaxation time. A non-linear differential equation is derived which describes the development of a PSC into a normal hot spot under the influence of Joule heating. It incorporates the temperature rise due to the dissipative processes occurring in the charge imbalance tails. Numerical solutions are presented for a set of parameters, including those for aluminium and tin. Subsequently, they are compared with experiments. (Auth.)

  3. Detecting Vessels Carrying Migrants Using Machine Learning

    Science.gov (United States)

    Sfyridis, A.; Cheng, T.; Vespe, M.

    2017-10-01

    Political instability, conflicts and inequalities result into significant flows of people worldwide, moving to different countries in search of a better life, safety or to be reunited with their families. Irregular crossings into Europe via sea routes, despite not being new, have recently increased together with the loss of lives of people in the attempt to reach EU shores. This highlights the need to find ways to improve the understanding of what is happening at sea. This paper, intends to expand the knowledge available on practices among smugglers and contribute to early warning and maritime situational awareness. By identifying smuggling techniques and based on anomaly detection methods, behaviours of interest are modelled and one class support vector machines are used to classify unlabelled data and detect potential smuggling vessels. Nine vessels are identified as potentially carrying irregular migrants and refugees. Though, further inspection of the results highlights possible misclassifications caused by data gaps and limited knowledge on smuggling tactics. Accepted classifications are considered subject to further investigation by the authorities.

  4. Retinal oscillations carry visual information to cortex

    Directory of Open Access Journals (Sweden)

    Kilian Koepsell

    2009-04-01

    Full Text Available Thalamic relay cells fire action potentials that transmit information from retina to cortex. The amount of information that spike trains encode is usually estimated from the precision of spike timing with respect to the stimulus. Sensory input, however, is only one factor that influences neural activity. For example, intrinsic dynamics, such as oscillations of networks of neurons, also modulate firing pattern. Here, we asked if retinal oscillations might help to convey information to neurons downstream. Specifically, we made whole-cell recordings from relay cells to reveal retinal inputs (EPSPs and thalamic outputs (spikes and then analyzed these events with information theory. Our results show that thalamic spike trains operate as two multiplexed channels. One channel, which occupies a low frequency band (<30 Hz, is encoded by average firing rate with respect to the stimulus and carries information about local changes in the visual field over time. The other operates in the gamma frequency band (40-80 Hz and is encoded by spike timing relative to retinal oscillations. At times, the second channel conveyed even more information than the first. Because retinal oscillations involve extensive networks of ganglion cells, it is likely that the second channel transmits information about global features of the visual scene.

  5. DETECTING VESSELS CARRYING MIGRANTS USING MACHINE LEARNING

    Directory of Open Access Journals (Sweden)

    A. Sfyridis

    2017-10-01

    Full Text Available Political instability, conflicts and inequalities result into significant flows of people worldwide, moving to different countries in search of a better life, safety or to be reunited with their families. Irregular crossings into Europe via sea routes, despite not being new, have recently increased together with the loss of lives of people in the attempt to reach EU shores. This highlights the need to find ways to improve the understanding of what is happening at sea. This paper, intends to expand the knowledge available on practices among smugglers and contribute to early warning and maritime situational awareness. By identifying smuggling techniques and based on anomaly detection methods, behaviours of interest are modelled and one class support vector machines are used to classify unlabelled data and detect potential smuggling vessels. Nine vessels are identified as potentially carrying irregular migrants and refugees. Though, further inspection of the results highlights possible misclassifications caused by data gaps and limited knowledge on smuggling tactics. Accepted classifications are considered subject to further investigation by the authorities.

  6. Scavenger receptors in homeostasis and immunity.

    Science.gov (United States)

    Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

    2013-09-01

    Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

  7. Can `loss and damage' carry the load?

    Science.gov (United States)

    Verchick, Robert R. M.

    2018-05-01

    Even assuming a heroic rush towards carbon reduction and adaptation, some regions of the world will be hammered hard by climate impacts. Thus, a global consensus now sees the need for a supplemental plan to deal with the kind of harms that cannot be avoided-what Parties call `loss and damage'. For a loss-and-damage plan to work, it must be capable of carrying the load, the load being whatever minimal standards that morality and political consensus require. But if residual risk climbs too high, it will fall short of even the most basic expectations. The Paris Agreement calls for holding the rise in global average temperature to `well below 2°C above pre-industrial levels', while working to limit the increase to 1.5°C. How much difference is in that half-degree? From the point of view of residual risk, quite a lot. According to a 2016 study published by the European Geosciences Union, a jump from 1.5°C to 2°C could produce outsize impacts, particularly in tropical latitudes. That difference could mark the line between a plan that is politically and morally defensible and one that is not. At the very least, the difference is enough to inform the design and expectations of any future plan. This article is part of the theme issue `The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

  8. BLOOD SUBSTITUTES: EVOLUTION FROM NON-CARRYING TO OXYGEN AND GAS CARRYING FLUIDS

    Science.gov (United States)

    Cabrales, Pedro; Intaglietta, Marcos

    2013-01-01

    The development of oxygen (O2) carrying blood substitutes has evolved from the goal of replicating blood O2 transports properties to that of preserving microvascular and organ function, reducing the inherent or potential toxicity of the material used to carry O2, and treating pathologies initiated by anemia and hypoxia. Furthermore, the emphasis has shifted from blood replacement fluid to “O2 therapeutics” that restore tissue oxygenation to specific tissues regions. This review covers the different alternatives, potential and limitations of hemoglobin based O2 carriers (HBOCs) and perfluorocarbon based O2 carriers (PFCOCs), with emphasis on the physiological conditions disturbed in the situation that they will be used. It describes how concepts learned from plasma expanders without O2 carrying capacity can be applied to maintain O2 delivery and summarizes the microvascular responses due to HBOCs and PFCOCs. This review also presents alternative applications of HBOCs and PFCOCs namely: 1) How HBOC O2 affinity can be engineered to target O2 delivery to hypoxic tissues; and 2) How the high gas solubility of PFCOCs provides new opportunities for carrying, dissolving and delivering gases with biological activity. It is concluded that current blood substitutes development has amplified their applications horizon by devising therapeutic functions for oxygen carriers requiring limited O2 delivery capacity restoration. Conversely, full, blood-like O2 carrying capacity re-establishment awaits control of O2 carrier toxicity. PMID:23820271

  9. Receptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-05-01

    This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

  10. Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

    Science.gov (United States)

    Pachathundikandi, Suneesh Kumar; Tegtmeyer, Nicole; Backert, Steffen

    2013-01-01

    Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori targets more than 40 known host protein receptors on epithelial or immune cells. A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the integrin α5β1 receptor. Other targeted membrane-based receptors include the integrins αvβ3, αvβ5, and β2 (CD18), RPTP-α/β, GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor, Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met. In addition, H. pylori is able to activate the intracellular receptors NOD1, NOD2, and NLRP3 with important roles in innate immunity. Here we review the interplay of various bacterial factors with host protein receptors. The contribution of these interactions to signal transduction and pathogenesis is discussed. PMID:24280762

  11. Molecularly imprinted nanoparticles with recognition properties towards a laminin H-Tyr-Ile-Gly-Ser-Arg-OH sequence for tissue engineering applications

    International Nuclear Information System (INIS)

    Rosellini, Elisabetta; Barbani, Niccoletta; Giusti, Paolo; Ciardelli, Gianluca; Cristallini, Caterina

    2010-01-01

    Nanotechnology is an emerging field that promises to revolutionize medicine and is increasingly used in tissue engineering applications. Our research group proposed for the first time molecular imprinting as a new nanotechnology for the creation of advanced synthetic support structures for cell adhesion and proliferation. The aim of this work was the synthesis and characterization of molecularly imprinted polymers with recognition properties towards a laminin peptide sequence and their application as functionalization structures in the development of bioactive materials. Nanoparticles with an average diameter of 200 nm were synthesized by precipitation polymerization of methacrylic acid in the presence of the template molecule and trimethylpropane trimethacrylate as the cross-linking agent. The imprinted nanoparticles showed good performance in terms of recognition capacity and selectivity. The cytotoxicity tests showed normal vitality of C2C12 myoblasts cultured in the medium that was put in contact with the imprinted polymers. After the deposition on the polymeric film surface, the imprinted particles maintained their specific recognition and rebinding behaviour, showing an even higher quantitative binding than free nanoparticles. Preliminary in vitro cell culture tests demonstrated the ability of functionalized materials to promote cell adhesion, proliferation and differentiation, suggesting that molecular imprinting can be used as an innovative functionalization technique.

  12. Monolayer culturing and cloning of human pluripotent stem cells on laminin-521-based matrices under xeno-free and chemically defined conditions.

    Science.gov (United States)

    Rodin, Sergey; Antonsson, Liselotte; Hovatta, Outi; Tryggvason, Karl

    2014-10-01

    A robust method for culturing human pluripotent stem (hPS) cells under chemically defined and xeno-free conditions is an important tool for stem cell research and for the development of regenerative medicine. Here, we describe a protocol for monolayer culturing of Oct-4-positive hPS cells on a specific laminin-521 (LN-521) isoform, under xeno-free and chemically defined conditions. The cells are dispersed into single-cell suspension and then plated on LN-521 isoform at densities higher than 5,000 cells per cm², where they attach, migrate and survive by forming small monolayer cell groups. The cells avidly divide and expand horizontally until the entire dish is covered by a confluent monolayer. LN-521, in combination with E-cadherin, allows cloning of individual hPS cells in separate wells of 96-well plates without the presence of rho-associated protein kinase (ROCK) inhibitors or any other inhibitors of anoikis. Characterization of cells maintained for several months in culture reveals pluripotency with a minimal degree of genetic abnormalities.

  13. Bioconjugation of laminin peptide YIGSR with poly(styrene co-maleic acid) increases its antimetastatic effect on lung metastasis of B16-BL6 melanoma cells.

    Science.gov (United States)

    Mu, Y; Kamada, H; Kaneda, Y; Yamamoto, Y; Kodaira, H; Tsunoda, S; Tsutsumi, Y; Maeda, M; Kawasaki, K; Nomizu, M; Yamada, Y; Mayumi, T

    1999-02-05

    A comb-shaped polymeric modifier, SMA [poly(styrene comaleic anhydride)], which binds to plasma albumin in blood was used to modify the synthetic cell-adhesive laminin peptide YIGSR, and its inhibitory effect on experimental lung metastasis of B16-BL6 melanoma cells was examined. YIGSR was chemically conjugated with SMA via formation of an amide bond between the N-terminal amino group of YIGSR and the carboxyl anhydride of SMA. The antimetastatic effect of SMA-conjugated YIGSR was approximately 50-fold greater than that of native YIGSR. When injected intravenously, SMA-YIGSR showed a 10-fold longer plasma half-life than native YIGSR in vivo. In addition, SMA-YIGSR had the same binding affinity to plasma albumin as SMA, while native YIGSR did not bind to albumin. These findings suggested that the enhanced antimetastatic effect of SMA-YIGSR may be due to its prolonged plasma half-life by binding to plasma albumin, and that bioconjugation of in vivo unstable peptides with SMA may facilitate their therapeutic use. Copyright 1999 Academic Press.

  14. Co-delivery of a laminin-111 supplemented hyaluronic acid based hydrogel with minced muscle graft in the treatment of volumetric muscle loss injury.

    Directory of Open Access Journals (Sweden)

    Stephen M Goldman

    Full Text Available Minced muscle autografting mediates de novo myofiber regeneration and promotes partial recovery of neuromuscular strength after volumetric muscle loss injury (VML. A major limitation of this approach is the availability of sufficient donor tissue for the treatment of relatively large VMLs without inducing donor site morbidity. This study evaluated a laminin-111 supplemented hyaluronic acid based hydrogel (HA+LMN as a putative myoconductive scaffolding to be co-delivered with minced muscle grafts. In a rat tibialis anterior muscle VML model, delivery of a reduced dose of minced muscle graft (50% of VML defect within HA+LMN resulted in a 42% improvement of peak tetanic torque production over unrepaired VML affected limbs. However, the improvement in strength was not improved compared to a 50% minced graft-only control group. Moreover, histological analysis revealed that the improvement in in vivo functional capacity mediated by minced grafts in HA+LMN was not accompanied by a particularly robust graft mediated regenerative response as determined through donor cell tracking of the GFP+ grafting material. Characterization of the spatial distribution and density of macrophage and satellite cell populations indicated that the combination therapy damps the heightened macrophage response while re-establishing satellite content 14 days after VML to a level consistent with an endogenously healing ischemia-reperfusion induced muscle injury. Moreover, regional analysis revealed that the combination therapy increased satellite cell density mostly in the remaining musculature, as opposed to the defect area. Based on the results, the following salient conclusions were drawn: 1 functional recovery mediated by the combination therapy is likely due to a superposition of de novo muscle fiber regeneration and augmented repair of muscle fibers within the remaining musculature, and 2 The capacity for VML therapies to augment regeneration and repair within the

  15. The Glycolytic Enzyme Triosephosphate Isomerase of Trichomonas vaginalis Is a Surface-Associated Protein Induced by Glucose That Functions as a Laminin- and Fibronectin-Binding Protein.

    Science.gov (United States)

    Miranda-Ozuna, Jesús F T; Hernández-García, Mar S; Brieba, Luis G; Benítez-Cardoza, Claudia G; Ortega-López, Jaime; González-Robles, Arturo; Arroyo, Rossana

    2016-10-01

    Triosephosphate isomerase of Trichomonas vaginalis (TvTIM) is a 27-kDa cytoplasmic protein encoded by two genes, tvtim1 and tvtim2, that participates in glucose metabolism. TvTIM is also localized to the parasite surface. Thus, the goal of this study was to identify the novel functions of the surface-associated TvTIM in T. vaginalis and to assess the effect of glucose as an environmental factor that regulates its expression and localization. Reverse transcription-PCR (RT-PCR) showed that the tvtim genes were differentially expressed in response to glucose concentration. tvtim1 was overexpressed under glucose-restricted (GR) conditions, whereas tvtim2 was overexpressed under glucose-rich, or high-glucose (HG), conditions. Western blot and indirect immunofluorescence assays also showed that glucose positively affected the amount and surface localization of TvTIM in T. vaginalis Affinity ligand assays demonstrated that the recombinant TvTIM1 and TvTIM2 proteins bound to laminin (Lm) and fibronectin (Fn) but not to plasminogen. Moreover, higher levels of adherence to Lm and Fn were detected in parasites grown under HG conditions than in those grown under GR conditions. Furthermore, pretreatment of trichomonads with an anti-TvTIMr polyclonal antibody or pretreatment of Lm- or Fn-coated wells with both recombinant proteins (TvTIM1r and TvTIM2r) specifically reduced the binding of live parasites to Lm and Fn in a concentration-dependent manner. Moreover, T. vaginalis was exposed to different glucose concentrations during vaginal infection of women with trichomoniasis. Our data indicate that TvTIM is a surface-associated protein under HG conditions that mediates specific binding to Lm and Fn as a novel virulence factor of T. vaginalis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. Inhibition of vimentin or B1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xueping; Fournier, Marcia V; Ware, Joy L; Bissell, Mina J; Yacoub, Adly; Zehner, Zendra E

    2008-06-12

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin, or {alpha}6 and {beta}1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of {alpha}6 and {beta}1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and {beta}1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499-508].

  17. Extracellular matrix organization in developing muscle: correlation with acetylcholine receptor aggregates.

    Science.gov (United States)

    Bayne, E K; Anderson, M J; Fambrough, D M

    1984-10-01

    Monoclonal antibodies recognizing laminin, heparan sulfate proteoglycan, fibronectin, and two apparently novel connective tissue components have been used to examine the organization of extracellular matrix of skeletal muscle in vivo and in vitro. Four of the five monoclonal antibodies are described for the first time here. Immunocytochemical experiments with frozen-sectioned muscle demonstrated that both the heparan sulfate proteoglycan and laminin exhibited staining patterns identical to that expected for components of the basal lamina. In contrast, the remaining matrix constituents were detected in all regions of muscle connective tissue: the endomysium, perimysium, and epimysium. Embryonic muscle cells developing in culture elaborated an extracellular matrix, each antigen exhibiting a unique distribution. Of particular interest was the organization of extracellular matrix on myotubes: the build-up of matrix components was most apparent in plaques overlying clusters of an integral membrane protein, the acetylcholine receptor (AChR). The heparan sulfate proteoglycan was concentrated at virtually all AChR clusters and showed a remarkable level of congruence with receptor organization; laminin was detected at 70-95% of AChR clusters but often was not completely co-distributed with AChR within the cluster; fibronectin and the two other extracellular matrix antigens occurred at approximately 20, 8, and 2% of the AChR clusters, respectively, and showed little or no congruence with AChR. From observations on the distribution of extracellular matrix components in tissue cultured fibroblasts and myogenic cells, several ideas about the organization of extracellular matrix are suggested. (a) Congruence between AChR clusters and heparan sulfate proteoglycan suggests the existence of some linkage between the two molecules, possibly important for regulation of AChR distribution within the muscle membrane. (b) The qualitatively different patterns of extracellular matrix

  18. 30 CFR 56.16014 - Operator-carrying overhead cranes.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Operator-carrying overhead cranes. 56.16014 Section 56.16014 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Storage and Handling § 56.16014 Operator-carrying overhead cranes. Operator-carrying overhead cranes shall...

  19. 30 CFR 57.16014 - Operator-carrying overhead cranes.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Operator-carrying overhead cranes. 57.16014 Section 57.16014 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Storage and Handling § 57.16014 Operator-carrying overhead cranes. Operator-carrying overhead cranes shall...

  20. 46 CFR 111.105-35 - Vessels carrying coal.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Vessels carrying coal. 111.105-35 Section 111.105-35...-GENERAL REQUIREMENTS Hazardous Locations § 111.105-35 Vessels carrying coal. (a) The following are Class II, Division 1, (Zone 10 or Z) locations on a vessel that carries coal: (1) The interior of each coal...

  1. Covalent co-immobilization of heparin/laminin complex that with different concentration ratio on titanium surface for selectively direction of platelets and vascular cells behavior

    International Nuclear Information System (INIS)

    Wang, Jian; Chen, Yuan; Liu, Tao; Wang, Xue; Liu, Yang; Wang, Yuan; Chen, Junying; Huang, Nan

    2014-01-01

    Highlights: • Extracellular matrix inspired surface modification with fibronectin, heparin and VEGF to construct a favorable microenvironment for selectively anticoagulant and promote endothelialization. • Take the advantage of specific intermolecular interaction, the bioactivity of above biomolecules was more efficiently maintained in compared with the common used covalent immobilization method. • Poly-l-lysine was used as a novel interlayer for surface amination, and in comparison, PLL coating was more feasible and the degradation product had no harm to human body. - Abstract: Surface biofunctional modification of coronary artery stent to improve the hemocompatibility and selectively accelerate endothelium regeneration but prevent restenosis have been become a new hotspot. For this, a novel method was developed in this work by co-immobilization of Ln and heparin complex on poly-L-lysine modified Ti surface. Take the advantage of the specific interaction between Ln and heparin, Ln and heparin complexes with different concentration ratios were set up for creating different exposure density of these two types of biomolecules. According to biocompatibility evaluation results, the Hep/Ln complexes modified surface displayed less platelet adhesion and activation. Especially, on L(150)H and L(200)H surface, the AT III binding quantity, APTT value and anti-coagulation property of modified surface were significantly promoted. Furthermore, the adherent density and proliferation activity of ECs and EPCs were positively correlated with Ln concentration. Notably, the proliferation of both ECs and EPCs on L(100)H, L(150)H and L(200)H surface were greatly promoted. Another hand, the proliferation activity of SMCs was significantly inhibited on Hep/Ln modified surfaces, which was considered mainly due to the inhibitory effect of heparin to SMCs. According to the existing results, this study demonstrated that in a certain range of heparin and laminin concentration ratio

  2. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier integrity through a mechanism involving P2X7 receptors.

    Science.gov (United States)

    Rubio-Araiz, Ana; Perez-Hernandez, Mercedes; Urrutia, Andrés; Porcu, Francesca; Borcel, Erika; Gutierrez-Lopez, Maria Dolores; O'Shea, Esther; Colado, Maria Isabel

    2014-08-01

    The recreational drug 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') produces a neuro-inflammatory response in rats characterized by an increase in microglial activation and IL-1β levels. The integrity of the blood-brain barrier (BBB) is important in preserving the homeostasis of the brain and has been shown to be affected by neuro-inflammatory processes. We aimed to study the effect of a single dose of MDMA on the activity of metalloproteinases (MMPs), expression of extracellular matrix proteins, BBB leakage and the role of the ionotropic purinergic receptor P2X7 (P2X7R) in the changes induced by the drug. Adult male Dark Agouti rats were treated with MDMA (10 mg/kg, i.p.) and killed at several time-points in order to evaluate MMP-9 and MMP-3 activity in the hippocampus and laminin and collagen-IV expression and IgG extravasation in the dentate gyrus. Microglial activation, P2X7R expression and localization were also determined in the dentate gyrus. Separate groups were treated with MDMA and the P2X7R antagonists Brilliant Blue G (BBG; 50 mg/kg, i.p.) or A-438079 (30 mg/kg, i.p.). MDMA increased MMP-3 and MMP-9 activity, reduced laminin and collagen-IV expression and increased IgG immunoreactivity. In addition, MDMA increased microglial activation and P2X7R immunoreactivity in these cells. BBG suppressed the increase in MMP-9 and MMP-3 activity, prevented basal lamina degradation and IgG extravasation into the brain parenchyma. A-438079 also prevented the MDMA-induced reduction in laminin and collagen-IV immunoreactivity. These results indicate that MDMA alters BBB permeability through an early P2X7R-mediated event, which in turn leads to enhancement of MMP-9 and MMP-3 activity and degradation of extracellular matrix.

  3. Structural and Molecular Modeling Features of P2X Receptors

    Directory of Open Access Journals (Sweden)

    Luiz Anastacio Alves

    2014-03-01

    Full Text Available Currently, adenosine 5'-triphosphate (ATP is recognized as the extracellular messenger that acts through P2 receptors. P2 receptors are divided into two subtypes: P2Y metabotropic receptors and P2X ionotropic receptors, both of which are found in virtually all mammalian cell types studied. Due to the difficulty in studying membrane protein structures by X-ray crystallography or NMR techniques, there is little information about these structures available in the literature. Two structures of the P2X4 receptor in truncated form have been solved by crystallography. Molecular modeling has proven to be an excellent tool for studying ionotropic receptors. Recently, modeling studies carried out on P2X receptors have advanced our knowledge of the P2X receptor structure-function relationships. This review presents a brief history of ion channel structural studies and shows how modeling approaches can be used to address relevant questions about P2X receptors.

  4. Training to Increase Safe Tray Carrying Among Cocktail Servers

    OpenAIRE

    Scherrer, Megan D; Wilder, David A

    2008-01-01

    We evaluated the effects of training on proper carrying techniques among 3 cocktail servers to increase safe tray carrying on the job and reduce participants' risk of developing musculoskeletal disorders. As participants delivered drinks to their tables, their finger, arm, and neck positions were observed and recorded. Each participant received individual safety training that focused on proper carrying positions and techniques after baseline data were collected. A multiple baseline design acr...

  5. Organization and carrying out the triathlon competitions in Ukraine

    Directory of Open Access Journals (Sweden)

    Volodymyr Vodlozerov

    2016-02-01

    Full Text Available Purpose: the aim is analyzing of system of organization and carrying out the triathlon competitions in Ukraine in accordance with rules of triathlon international federation. Material & Methods: comparative analysis of process of organization and carrying out the triathlon competitions in the world and Ukraine was carried out on basis of specialist literature studying, normative base of sports organizations (triathlon federation. Results: inconsistencies were identified in competitions carried out in cold season, particularity of triathlon that intends overcoming the combined distance without time durations between stages. Conclusions: recommendation in eliminate inconsistencies that affect to performance of triathlon competitions in Ukraine was suggested.

  6. The Population Growth and Carrying Capacity in Semarang City

    Science.gov (United States)

    Hariyanto; Hadi, Sudharto P.; Buchori, Imam

    2018-02-01

    Population growth and development of city activities take some lands to carry them. As a result, land use competition happens among persons, society or sector. Land necessity for settlement, industry, or sector has taken over farm land, therefore farm land has been converted intensively and massively. Chronologically, population growth will cause land necessity increase. Unproductive land, especially farm land will be converted. Furthermore, farm land conversion will cause carrying capacity change. Carrying capacity has certain bio capacity. With the population growth, it will increase resource consumption; on the other side, farm land conversion will decrease carrying capacity. The objective of the study is to know about the influence of population growth towards carrying capacity (bio capacity) in Semarang city. Land consumption per capita is indeed influenced by city population, the higher the population is, the lower the land consumption per capita. With the population growth, it will influence carrying capacity. Carrying capacity here is the ratio of area to population. Analytical descriptive method is applied in the study with all sub-districts in Semarang city as the analysis unit. Population here is sub-district area and population per sub-district in Semarang city. Population growth data period is from 2000 until 2015. Main variables of the study are area per sub-district, population, population growth, carrying capacity. Result of the study shows significant influence of carrying capacity decrease, especially some outskirts in Semarang city. This condition happens because the outskirts in Semarang city tend to have dense population growth. Range of carrying capacity in Semarang city is from 0,007 to 0,117 of 0 to 1. Almost all sub-districts in Semarang city show miserable condition, except Mijen and Tugu. The conclusion of the study is that population will decrease carrying capacity. Therefore, the government should control population growth by paying

  7. 46 CFR 111.105-45 - Vessels carrying agricultural products.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Vessels carrying agricultural products. 111.105-45... ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-45 Vessels carrying agricultural products. (a) The following areas are Class II, Division 1, (Zone 10 or Z) locations on vessels...

  8. 25 CFR 23.51 - Grant carry-over authority.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Grant carry-over authority. 23.51 Section 23.51 Indians... Uniform Grant Administration Provisions and Requirements § 23.51 Grant carry-over authority. Unless... two years beyond the initial grant funding period and must be utilized only for the intent, purpose...

  9. 14 CFR 121.589 - Carry-on baggage.

    Science.gov (United States)

    2010-01-01

    ... (c) and (d). (c) No certificate holder may allow an airplane to take off or land unless each article... holder may allow the boarding of carry-on baggage on an airplane unless each passenger's baggage has been... program in its operations specifications. In addition, no passenger may board an airplane if his/her carry...

  10. Evaluating total carrying capacity of tourism using impact indicators

    Directory of Open Access Journals (Sweden)

    R. Sharma

    2016-03-01

    Full Text Available The carrying capacity is well identified tool to manage problems due to uncontrolled tourism for any destination. This report highlights the carrying capacity estimation of Kerwa tourism area, Bhopal, India. The methodology used in this report is a new two-tier mechanism of impact analysis using index numbers derived from a survey of 123 stakeholders. From this the individual component impact analysis and the total carrying capacity of the area is computed in order to state the insight of the total carrying capacity left for the tourism activities in Kerwa tourism area. It is calculated from, the results so obtained, that the Kerwa catchment area falls in “very low impact category” and hence in a healthy state of the artwork in terms of total carrying capacity. The study conveys the current need in the destination management and tourism development as a road map for the destination managers for implementing sustainable tourism.

  11. The flexible application of carrying capacity in ecology

    Directory of Open Access Journals (Sweden)

    Eric J. Chapman

    2018-01-01

    Full Text Available Carrying capacity encompasses a broad collection of approaches used to better understand biotic interactions in ecosystems and is often applied with no explicit regard to its historical origin. In this paper, we reviewed the primary literature to examine how carrying capacity is applied in ecology. We focused our review on ecosystem studies—studies that frame their results at the ecosystem level—published after the 1950s and highlight emerging trends of this concept. We found that while carrying capacity offers some underlying commonalities, a wide range of definitions and approaches hinders a unified framework to better understand biotic ecosystem interactions. Not surprisingly, these studies most often use K—the number of individuals that the environment “can support” in a given area—to define carrying capacity, despite considerable ambiguity and uncertainty in this approach. Furthermore, the studies that we reviewed spanned several levels of ecological organization: molecules to communities and up to landscapes. To add further complexity, it is not clear whether carrying capacity was intended as a dynamic concept subject to temporal variability as it was often applied in the reviewed studies. We found that carrying capacity is most often applied to studies in conservation biology, rangeland and wildlife management, aquaculture, and fisheries biology. We explore ecosystem level responses to implications of “carrying capacity” overshoot and discuss proposed mechanisms that govern ecosystem carrying capacity. We discuss the usefulness of the concept and end with suggestions to improve carrying capacity's general application in ecosystem studies. Keywords: Carrying capacity, Conservation biology, Ecosystems, Ecosystem management, Natural resources

  12. US Public Opinion on Carrying Firearms in Public Places.

    Science.gov (United States)

    Wolfson, Julia A; Teret, Stephen P; Azrael, Deborah; Miller, Matthew

    2017-06-01

    To estimate US public opinion, overall and by gun ownership status, about the public places where legal gun owners should be allowed to carry firearms. We fielded an online survey among 3949 adults, including an oversample of gun owners and veterans, in April 2015. We used cross-tabulations with survey weights to generate nationally representative estimates. Fewer than 1 in 3 US adults supported gun carrying in any of the specified venues. Support for carrying in public was consistently higher among gun owners than among non-gun owners. Overall, support for carrying in public was lowest for schools (19%; 95% confidence interval [CI] = 16.7, 21.1), bars (18%; 95% CI = 15.9, 20.6), and sports stadiums (17%; 95% CI = 15.0, 19.5). Most Americans, including most gun owners, support restricting public places legal gun owners can carry firearms. These views contrast sharply with the current trend in state legislatures of expanding where, how, and by whom guns can be carried in public. Recent state laws and proposed federal legislation that would force states to honor out-of-state concealed carry permits are out of step with American public opinion.

  13. Research on Psychological Carrying Capacity of Tourism Destination

    Institute of Scientific and Technical Information of China (English)

    Fan Zhiyong; Zhong Sheng

    2009-01-01

    As a part of the carrying capacity system of tourism destination,tourism psychological carrying capacity and its makeup are very important indexes which reflect the harmonious development of tourism destination develops harmoniously,but the academy has not paid enough attention to them.Based on the concept and connotation of psychological carrying capacity,this paper explains the influencing factors which affect the psychological capacity of the tourist and the resident after the acknowledged concept,and then designs a harmonious development model of tourism destination.Finally,it offers some countermeasures against the overloading psychological capacity.

  14. Foreign exchange predictability and the carry trade: a decomposition approach

    Czech Academy of Sciences Publication Activity Database

    Anatolyev, Stanislav; Gospodinov, N.; Jamali, I.; Liu, X.

    2017-01-01

    Roč. 42, June (2017), s. 199-211 ISSN 0927-5398 Institutional support: RVO:67985998 Keywords : exchange rate forecasting * carry trade * return decomposition Subject RIV: AH - Economics OBOR OECD: Finance Impact factor: 0.979, year: 2016

  15. Study on Tourist Carrying Capacity Based on Matter Element Analysis

    Institute of Scientific and Technical Information of China (English)

    LiuYunguo; FanTing; LiXin; ZhouMing; WangXianhai

    2005-01-01

    This paper proposes that it is necessary to implement the concept of tourist carrying capacity to facilitate the tourism planning, and presents a method to evaluate the carrying capacity. The method called matter element analysis can solve the uncertain and incompatible problem of the evaluated factors in assessing carrying capacity.The current state of a destination's carrying capacity can be determined by establishing the standard indexes and the matter element model. Through the evaluating of the travel industry zones of the Autonomous Prefecture of Western Hunan, the method is proved to be simple and feasible, and it is improved to be significant for the tourism planning and determination as well as the sustainable development of the regional tourism.

  16. Estimating the recreational carrying capacity of a lowland river section.

    Science.gov (United States)

    Lorenz, Stefan; Pusch, Martin T

    2012-01-01

    Recreational boating represents a major human use of inland waters in many regions. However, boating tourism may affect the ecological integrity of surface waters in multiple ways. In particular, surface waves produced by boating may disturb freshwater invertebrates, such as interrupting the filtration activity of benthic mussels. As mussels may significantly contribute to self-purification, disturbance may have crucial impacts on water quality, and thus on water tourism. In this paper we calculate the carrying capacity of a river section for sustainable boating tourism based on the preservation of water quality. This approach is complemented by spatial and social approaches for carrying capacity estimates. The ecological carrying capacity significantly decreases with lower water levels during summer. Hence, the analysis of variables that influence the river's carrying capacity allows the formation of recommendations for management measures that integrate social, touristic and ecological aspects.

  17. Assessment of feeding value of vegetable-carried pineapple fruit ...

    African Journals Online (AJOL)

    This study compared the sun-drying characteristics of five blends each (w/w; 1:1, 1:1.5, 1:2, 1:2.5, 1:3) of wheat offal-carried pineapple waste (WO:PW) and brewers' dried grains-carried pineapple waste (BDG:PW), assessed the blends for their nutrient contents and the feeding value of the optimum blends with Red Sokoto ...

  18. Carrying capacity: the tradition and policy implications of limits

    Directory of Open Access Journals (Sweden)

    Virginia Deane Abernethy

    2001-01-01

    Full Text Available ABSTRACT: Within just the last few centuries, science and technology have enlarged human capabilities and population size until humans now take, for their own use, nearly half of the Earth's net terrestrial primary production. An ethical perspective suggests that potentials to alter, or further increase, humanity's use of global resources should be scrutinized through the lenses of self-interested foresightedness and respect for non-human life. Without overtly invoking ethics, studies of the carrying capacity achieve just this objective. Carrying capacity is an ecological concept that expresses the relationship between a population and the natural environment on which it depends for ongoing sustenance. Carrying capacity assumes limits on the number of individuals that can be supported at a given level of consumption without degrading the environment and, therefore, reducing future carrying capacity. That is, carrying capacity addresses long-term sustainability. Worldviews differ in the importance accorded to the carrying capacity concept. This paper addresses three worldviews - ecological, romantic, and entrepreneurial - and explores the ethics and the policy implications of their contrasting perspectives.

  19. The LDL receptor.

    Science.gov (United States)

    Goldstein, Joseph L; Brown, Michael S

    2009-04-01

    In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

  20. Method for rendering harmless sulfur dioxide-carrying gases and sulfur-carrying waste water from pyrolysis of oil shale

    Energy Technology Data Exchange (ETDEWEB)

    Aspegren, O E.A.; Eklund, A J

    1951-03-15

    A method is described for rendering harmless sulfur dioxide-carrying gases, which are formed in processes for the manufacture of solid, liquid, or gaseous products by pyrolysis of oil shale, and thereby to extract valuable products, characterized in that the sulfur dioxide-carrying gases are washed with a solution or sludge obtained by leaching wholly or partly burned-out residues from the pyrolysis.

  1. [Ecological carrying capacity and Chongming Island's ecological construction].

    Science.gov (United States)

    Wang, Kaiyun; Zou, Chunjing; Kong, Zhenghong; Wang, Tianhou; Chen, Xiaoyong

    2005-12-01

    This paper overviewed the goals of Chongming Island's ecological construction and its background, analyzed the current eco-economic status and constraints of the Island, and put forward some scientific issues on its ecological construction. It was suggested that for the resources-saving and sustainable development of the Island, the researches on its ecological construction should be based on its ecological carrying capacity, fully take the regional characteristics into consideration, and refer the successful development modes at home and abroad. The carrying capacity study should ground on systemic and dynamic views, give a thorough evaluation of the Island's present carrying capacity, simulate its possible changes, and forecast its demands and risks. Operable countermeasures to promote the Island's carrying capacity should be worked out, new industry structure, population scale, and optimized distribution projects conforming to regional carrying capacity should be formulated, and effective ecological security alarming and control system should be built, with the aim of providing suggestions and strategic evidences for the decision-making of economic development and sustainable environmental resources use of the region.

  2. Carrying capacity of water resources in Bandung Basin

    Science.gov (United States)

    Marganingrum, D.

    2018-02-01

    The concept of carrying capacity is widely used in various sectors as a management tool for sustainable development processes. This idea has also been applied in watershed or basin scale. Bandung Basin is the upstream of Citarum watershed known as one of the national strategic areas. This area has developed into a metropolitan area loaded with various environmental problems. Therefore, research that is related to environmental carrying capacity in this area becomes a strategic issue. However, research on environmental carrying capacity that has been done in this area is still partial either in water balance terminology, land suitability, ecological footprint, or balance of supply and demand of resources. This paper describes the application of the concept of integrated environmental carrying capacity in order to overcome the increasing complexity and dynamic environmental problems. The sector that becomes the focus of attention is the issue of water resources. The approach method to be carried out is to combine the concept of maximum balance and system dynamics. The dynamics of the proposed system is the ecological dynamics and population that cannot be separated from one another as a unity of the Bandung Basin ecosystem.

  3. Concepts for reducing nuclear utility inventory carrying costs

    International Nuclear Information System (INIS)

    Graybill, R.E.; DiCola, F.E.; Solanas, C.H.

    1985-01-01

    Nuclear utilities are under pressure to reduce their operating and maintenance expenses such that the total cost of generating electricity through nuclear power remains an economically attractive option. One area in which expenses may be reduced is total inventory carrying cost. The total inventory carrying cost consists of financing an inventory, managing the inventory, assuring quality, engineering of acceptable parts specifications, and procuring initial and replenishment stock. Concepts and methodology must be developed to reduce the remaining expenses of a utility's total inventory carrying cost. Currently, two concepts exist: pooled inventory management system (PIMS), originally established by General Electric Company and a group of boiling water reactor owners, and Nuclear Parts Associates' (NUPA) shared inventory management program (SIMP). Both concepts share or pool parts and components among utilities. The SIMP program objectives and technical activities are summarized

  4. Delay model and performance testing for FPGA carry chain TDC

    International Nuclear Information System (INIS)

    Kang Xiaowen; Liu Yaqiang; Cui Junjian Yang Zhangcan; Jin Yongjie

    2011-01-01

    Time-of-flight (TOF) information would improve the performance of PET (position emission tomography). TDC design is a key technique. It proposed Carry Chain TDC Delay model. Through changing the significant delay parameter of model, paper compared the difference of TDC performance, and finally realized Time-to-Digital Convertor (TDC) based on Carry Chain Method using FPGA EP2C20Q240C8N with 69 ps LSB, max error below 2 LSB. Such result could meet the TOF demand. It also proposed a Coaxial Cable Measuring method for TDC testing, without High-precision test equipment. (authors)

  5. Evaluation of carrying capacity and territorial environmental sustainability

    Directory of Open Access Journals (Sweden)

    Giuseppe Ruggiero

    2012-09-01

    Full Text Available Land use has a great impact on environmental quality, use of resources, state of ecosystems and socio-economic development. Land use can be considered sustainable if the environmental pressures of human activities do not exceed the ecological carrying capacity. A scientific knowledge of the capability of ecosystems to provide resources and absorb waste is a useful and innovative means of supporting territorial planning. This study examines the area of the Province of Bari to estimate the ecosystems’ carrying capacity, and compare it with the current environmental pressures exerted by human activities. The adapted methodology identified the environmentally sustainable level for one province.

  6. Carry trade as a speculative investment strategy in Serbia

    Directory of Open Access Journals (Sweden)

    Bungin Sanja

    2012-12-01

    Full Text Available This paper is analyses causes and the consequences of a speculative investment carry trade strategy in the exchange market in Serbia. The presence of such type of investor is related to high yields of risk free securities denominated in dinars, as well as the perception of future movements of dinar exchange rate related to currency that serves as source of investment. The consequences of carry trade may significantly influence exchange rate movements when monetary policy has limited facilities to combat negative and sudden shocks.

  7. General relativistic galvano-gravitomagnetic effect in current carrying conductors

    International Nuclear Information System (INIS)

    Ahmedov, B.J.

    1998-11-01

    The analogy between general relativity and electromagnetism suggests that there is a galvano-gravitomagnetic effect, which is the gravitational analogue of the Hall effect. This new effect takes place when a current carrying conductor is placed in a gravitomagnetic field and the conduction electrons moving inside the conductor are deflected transversally with respect to the current flow. In connection with this galvano-gravitomagnetic effect, we explore the possibility of using current carrying conductors for detecting the gravitomagnetic field of the Earth. (author)

  8. The First Fifteen Years of Steroid Receptor Research in Zebrafish; Characterization and Functional Analysis of the Receptors

    Directory of Open Access Journals (Sweden)

    Marcel J. M. Schaaf

    2017-07-01

    Full Text Available Steroid hormones regulate a wide range of processes in our body, and their effects are mediated by steroid receptors. In addition to their physiological role, these receptors mediate the effects of endocrine disrupting chemicals (EDCs and are widely used targets for dugs involved in the treatment of numerous diseases, ranging from cancer to inflammatory disorders. Over the last fifteen years, the zebrafish has increasingly been used as an animal model in steroid receptor research. Orthologues of all human steroid receptor genes appear to be present in zebrafish. All zebrafish steroid receptors have been characterized in detail, and their expression patterns have been analyzed. Functional studies have been performed using morpholino knockdown of receptor expression and zebrafish lines carrying mutations in one of their steroid receptor genes. To investigate the activity of the receptors in vivo, specific zebrafish reporter lines have been developed, and transcriptomic studies have been carried out to identify biomarkers for steroid receptor action. In this review, an overview of research on steroid receptors in zebrafish is presented, and it is concluded that further exploitation of the possibilities of the zebrafish model system will contribute significantly to the advancement of steroid receptor research in the next decade.

  9. Foreign exchange predictability and the carry trade: a decomposition approach

    Czech Academy of Sciences Publication Activity Database

    Anatolyev, Stanislav; Gospodinov, N.; Jamali, I.; Liu, X.

    2017-01-01

    Roč. 42, June (2017), s. 199-211 ISSN 0927-5398 Institutional support: Progres-Q24 Keywords : exchange rate forecasting * carry trade * return decomposition Subject RIV: AH - Economics OBOR OECD: Finance Impact factor: 0.979, year: 2016

  10. Debris-carrying camouflage among diverse lineages of Cretaceous insects.

    Science.gov (United States)

    Wang, Bo; Xia, Fangyuan; Engel, Michael S; Perrichot, Vincent; Shi, Gongle; Zhang, Haichun; Chen, Jun; Jarzembowski, Edmund A; Wappler, Torsten; Rust, Jes

    2016-06-01

    Insects have evolved diverse methods of camouflage that have played an important role in their evolutionary success. Debris-carrying, a behavior of actively harvesting and carrying exogenous materials, is among the most fascinating and complex behaviors because it requires not only an ability to recognize, collect, and carry materials but also evolutionary adaptations in related morphological characteristics. However, the fossil record of such behavior is extremely scarce, and only a single Mesozoic example from Spanish amber has been recorded; therefore, little is known about the early evolution of this complicated behavior and its underlying anatomy. We report a diverse insect assemblage of exceptionally preserved debris carriers from Cretaceous Burmese, French, and Lebanese ambers, including the earliest known chrysopoid larvae (green lacewings), myrmeleontoid larvae (split-footed lacewings and owlflies), and reduviids (assassin bugs). These ancient insects used a variety of debris material, including insect exoskeletons, sand grains, soil dust, leaf trichomes of gleicheniacean ferns, wood fibers, and other vegetal debris. They convergently evolved their debris-carrying behavior through multiple pathways, which expressed a high degree of evolutionary plasticity. We demonstrate that the behavioral repertoire, which is associated with considerable morphological adaptations, was already widespread among insects by at least the Mid-Cretaceous. Together with the previously known Spanish specimen, these fossils are the oldest direct evidence of camouflaging behavior in the fossil record. Our findings provide a novel insight into early evolution of camouflage in insects and ancient ecological associations among plants and insects.

  11. MRSA carrying mecC in captive mara

    DEFF Research Database (Denmark)

    Gongora, Carmen Espinosa; Harrison, Ewan M; Moodley, Arshnee

    2015-01-01

    C-carrying MRSA ST130 clone is widespread in a variety of unrelated hosts in Denmark. Since the mara at Copenhagen Zoo have limited contact with humans and other animal species, it remains unclear whether mara are natural hosts of ST130 or acquired this lineage from unknown sources. The broad host range of MRSA...

  12. Development of heavy load carrying vehicle for nuclear power station

    International Nuclear Information System (INIS)

    Terabayashi, Yasuharu; Oono, Hiroo; Aizu, Takao; Kawaguchi, Kaname; Yamanaka, Masayuki; Hirobe, Tamio; Inagaki, Yoshiaki.

    1985-01-01

    In nuclear power stations, in order to carry out sound and stable operation, the routine inspection and regular inspection of machinery and equipment are performed, therefore, the transportation of heavy things is frequently carried out. Especially, the transportation of heavy things over the steps of passages and stairs requires much labor. Therefore, Chubu Electric Power Co., Inc. and Chubu Plant Service Co., Ltd. carried out the research on the development of a vehicle for transporting heavy components of nuclear power plants. In this research, it was aimed at developing a vehicle which can carry heavy components and get over a step, climb and descend stairs, and run through a narrow passage having many curves as well as running on flat ground. For this purpose, the actual state of the transportation of heavy things was investigated during the regular inspection of a nuclear power station, and on the basis of this results, a prototype vehicle was made and tested. Thereafter, a transporting vehicle of actual scale was made and tested. The investigation of actual state and the examination of the fundamental concept, the design, trial manufacture and verifying test are reported. (Kako, I.)

  13. Stress Carry-Over and College Student Health Outcomes

    Science.gov (United States)

    Pedersen, Daphne E.

    2012-01-01

    Objective: Using a stress carry-over perspective, this study examines the relationship between stress stemming from school and family domains and physical and mental health outcomes. Methods: The study sample included 268 undergraduate men and women from a Midwestern university. Participants completed an anonymous online questionnaire. OLS…

  14. Carrying capacity of a heterogeneous lake for migrating swans

    NARCIS (Netherlands)

    Gyimesi, A.

    2010-01-01

    One way to express the value of a natural habitat is its capacity to harbour a particular target species. In the case of migratory birds, the cumulative number of birds that can be accommodated at a site for a given period of time (‘bird-days’) became an accepted currency for this carrying capacity.

  15. Plasma generator utilizing dielectric member for carrying microwave energy

    International Nuclear Information System (INIS)

    Aklufi, M.E.; Brock, D.W.

    1991-01-01

    This patent describes a system in which electromagnetic energy is used to generate a plasma from a gas. It comprises a reaction chamber which is evacuated to less than ambient pressure and into which the gas is introduced; and a nonconductive member for carrying the electromagnetic energy and for emitting the electromagnetic energy so that a plasma is formed from the gas

  16. "The Bell Curve" and Carrie Buck: Eugenics Revisited.

    Science.gov (United States)

    Smith, J. David

    1995-01-01

    The 1994 publication of "The Bell Curve" by R. Herrnstein and C. Murray is compared to other examples of eugenic principles, including the sterilization of "feebleminded" Carrie Buck, family degeneracy studies focusing on lower class Caucasian families, and other works that view the poorest and least educated members of society…

  17. Carrying capacity of Chaetoceros gracilis in Homa Lagoon and the ...

    African Journals Online (AJOL)

    The possibility for nutrient limitation to affect C. gracilis was assessed from two different ecosystems (Izmir Bay and Homa Lagoon). Our goal was to determine the growth rate of all nutrients and the maximum levels of the C. gracilis phytoplankton biomass (the maximum biomass carrying capacity) on the extent of its full ...

  18. Hotspot relaxation dynamics in a current-carrying superconductor

    Science.gov (United States)

    Marsili, F.; Stevens, M. J.; Kozorezov, A.; Verma, V. B.; Lambert, Colin; Stern, J. A.; Horansky, R. D.; Dyer, S.; Duff, S.; Pappas, D. P.; Lita, A. E.; Shaw, M. D.; Mirin, R. P.; Nam, S. W.

    2016-03-01

    We experimentally studied the dynamics of optically excited hotspots in current-carrying WSi superconducting nanowires as a function of bias current, bath temperature, and excitation wavelength. We observed that the hotspot relaxation time depends on bias current, temperature, and wavelength. We explained this effect with a model based on quasiparticle recombination, which provides insight into the quasiparticle dynamics of superconductors.

  19. The logistic model-generated carrying capacities for wild herbivores ...

    African Journals Online (AJOL)

    Jesse

    Under this formulation, both carrying capacity and exchange ratios are endogenously determined (Kinyua and Njoka, 2001), making it possible to empirically estimate the population growth models for Grant's gazelle, Thompson's gazelle and Zebra. (1) for i = 1,…,n-1 j = 1,…,2 and i ≠ j. Here Hit+1, measured in animal units, ...

  20. Cognitive Load in Voice Therapy Carry-Over Exercises

    Science.gov (United States)

    Iwarsson, Jenny; Morris, David Jackson; Balling, Laura Winther

    2017-01-01

    Purpose: The cognitive load generated by online speech production may vary with the nature of the speech task. This article examines 3 speech tasks used in voice therapy carry-over exercises, in which a patient is required to adopt and automatize new voice behaviors, ultimately in daily spontaneous communication. Method: Twelve subjects produced…

  1. The KB WOT Fisheries Programme carried out in 2015

    NARCIS (Netherlands)

    Damme, van C.J.G.; Verver, S.W.

    2017-01-01

    The KB WOT Fisheries programme is established to maintain and develop the expertise needed to carry out the statutory obligations of the Netherlands in fisheries monitoring and advice. It is also a flexible program which responds to changes over time in WOT requirements, fisheries management and

  2. Trials carried out on corrosive (fluorinated) atmosphere vacuum gauges

    International Nuclear Information System (INIS)

    Constant, M.; Houyvet, A.; Noe, P.

    1966-01-01

    Study of the stability of readings given by a modified Pirani type measurement probe with a view to long term operation in the presence of corrosive gases. Results of measurements carried out before and after use under these conditions. (author) [fr

  3. Random noise characterization on the carrying capacities of a ...

    African Journals Online (AJOL)

    The process of the survival of species dependent on a limited resource in a polluted environment which isnot a new idea can be described by the technique of a mathematical modelling. We have utilised the technique of a numerical simulation to study the impact of environmental random noise on the carrying capacities of ...

  4. Application of Load Carrying Sandwich Elements in Wind Turbine Blades

    DEFF Research Database (Denmark)

    Jensen, Jacob Fisker; Schultz, Jacob Pagh; Berggreen, Carl Christian

    2005-01-01

    The present work investigates the possibilities and drawbacks when applying sandwich as opposed to single skin composites in the flanges of the load carrying spar in a future 180 m wind turbine rotor. FEA is applied to investigate two basic designs with single skin and sandwich flanges respectively...

  5. Must-carry regulation: a must or a burden?

    NARCIS (Netherlands)

    van Eijk, N.; van der Sloot, B.; Nikoltchev, S.

    2012-01-01

    The first must-carry rules date back to 1990, the time when space on analogue broadcasting networks was limited and when supply grew quickly due to the introduction of private broadcasters. To ensure that channels of general interest would still be transmitted, countries introduced rules to regulate

  6. El naturalismo americano: Theodore Dreiser y Sister Carrie

    Directory of Open Access Journals (Sweden)

    Dolores G. ALONSO MULAS

    2009-08-01

    Full Text Available Para situar a un escritor, como Theodore Dreiser, y especialmente su novela Sister Carrie dentro de un movimiento literario y de una etapa determinada de la historia americana, es necesario dar un breve repaso al naturalismo, llegado a América a través de Stephen Crane

  7. Violence and weapon carrying in music videos. A content analysis.

    Science.gov (United States)

    DuRant, R H; Rich, M; Emans, S J; Rome, E S; Allred, E; Woods, E R

    1997-05-01

    The positive portrayal of violence and weapon carrying in televised music videos is thought to have a considerable influence on the normative expectations of adolescents about these behaviors. To perform a content analysis of the depictions of violence and weapon carrying in music videos, including 5 genres of music (rock, rap, adult contemporary, rhythm and blues, and country), from 4 television networks and to analyze the degree of sexuality or eroticism portrayed in each video and its association with violence and weapon carrying, as an indicator of the desirability of violent behaviors. Five hundred eighteen videos were recorded during randomly selected days and times of the day from the Music Television, Video Hits One, Black Entertainment Television, and Country Music Television networks. Four female and 4 male observers aged 17 to 24 years were trained to use a standardized content analysis instrument. Interobserver reliability testing resulted in a mean (+/- SD) percentage agreement of 89.25% +/- 7.10% and a mean (+/- SD) kappa of 0.73 +/- 0.20. All videos were observed by rotating 2-person, male-female teams that were required to reach agreement on each behavior that was scored. Music genre and network differences in behaviors were analyzed with chi 2 tests. A higher percentage (22.4%) of Music Television videos portrayed overt violence than Video Hits One (11.8%), Country Music Television (11.8%), and Black Entertainment Television (11.5%) videos (P = .02). Rap (20.4%) had the highest portrayal of violence, followed by rock (19.8%), country (10.8%), adult contemporary (9.7%), and rhythm and blues (5.9%) (P = .006). Weapon carrying was higher on Music Television (25.0%) than on Black Entertainment Television (11.5%), Video Hits One (8.4%), and Country Music Television (6.9%) (P violence (P violence and weapon carrying, which is glamorized by music artists, actors, and actresses.

  8. Clearance kinetics and matrix binding partners of the receptor for advanced glycation end products.

    Directory of Open Access Journals (Sweden)

    Pavle S Milutinovic

    Full Text Available Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE. Previous studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin. Soluble RAGE administered intratracheally, intravenously, or intraperitoneally, does not distribute in a specific fashion to any healthy mouse tissue, suggesting against the existence of accessible sRAGE sinks and receptors in the healthy mouse. Intratracheal administration is the only effective means of delivering exogenous sRAGE to the lung, the organ in which RAGE is most highly expressed; clearance of sRAGE from lung does not differ appreciably from that of albumin.

  9. A METHOD OF SECURITY SCANNING OF CARRY-ON ITEMS, AND A CARRY-ON ITEMS SECURITY SCANNING SYSTEM

    DEFF Research Database (Denmark)

    2017-01-01

    A security scanning system (1) comprises a first stage module (3) having at least one X-ray source (6) and at least three first detectors (7) that are line-shaped and arranged in mutually different orientations and have at least dual energy resolution. A group of carry-on items (4) on a carrier...

  10. Carrying capacity in a heterogeneous environment with habitat connectivity.

    Science.gov (United States)

    Zhang, Bo; Kula, Alex; Mack, Keenan M L; Zhai, Lu; Ryce, Arrix L; Ni, Wei-Ming; DeAngelis, Donald L; Van Dyken, J David

    2017-09-01

    A large body of theory predicts that populations diffusing in heterogeneous environments reach higher total size than if non-diffusing, and, paradoxically, higher size than in a corresponding homogeneous environment. However, this theory and its assumptions have not been rigorously tested. Here, we extended previous theory to include exploitable resources, proving qualitatively novel results, which we tested experimentally using spatially diffusing laboratory populations of yeast. Consistent with previous theory, we predicted and experimentally observed that spatial diffusion increased total equilibrium population abundance in heterogeneous environments, with the effect size depending on the relationship between r and K. Refuting previous theory, however, we discovered that homogeneously distributed resources support higher total carrying capacity than heterogeneously distributed resources, even with species diffusion. Our results provide rigorous experimental tests of new and old theory, demonstrating how the traditional notion of carrying capacity is ambiguous for populations diffusing in spatially heterogeneous environments. © 2017 John Wiley & Sons Ltd/CNRS.

  11. Experiments on criticality carried out from 1975 till 1980

    International Nuclear Information System (INIS)

    Heinicke, W.; Tischer, A.; Weber, W.J.

    1981-11-01

    The report on hand includes the experiments on criticality published from 1975 till 1980. About 90 experiments with the most important related data are listed. They are capable of being called up, with the data base system KRITEXP, by 14 different descriptors or printed in any arrangement or order. This is the basis for a global or purposeful verification of the calculating method for criticality safety. The proof of reliability of the calculations for the criticality analysis are immediately relevant for the licencing procedure under atomic law for all plants of the nuclear fuel cycle where nuclear fuels are handled. Since no criticality experiments are being carried out in the Federal Republic of Germany, the data collection on hand will help to fill this gap with regard to the assessment of experiments carried out in other countries. (orig.) [de

  12. Apparatus for carrying out ultrasonic inspection of pressure vessels

    International Nuclear Information System (INIS)

    Dent, K.H.; Challender, R.S.

    1975-01-01

    Apparatus is described for use in carrying out ultrasonic inspection of coolant nozzles of nuclear reactor pressure vessels. It comprises a manipulator for supporting an ultrasonic scanning transducer within the coolant nozzle. The manipulator is carried by a support located within the pressure vessel and comprises a pair of legs pivotable in caliper manner to span the base of the nozzle. Means are provided for pivoting the legs together to enable free entry of the manipulator and scanning transducer into the nozzle, and for pivoting the legs apart to bring the transducer into an operating position adjacent to the wall of the nozzle. The manipulator is rotatable within the nozzle to enable scanning of its interior surface. (U.K.)

  13. Behavioral Indicators of Legal and Illegal Gun Carrying

    Science.gov (United States)

    2015-05-01

    foundation to develop training for law enforcement and security personnel to utilize behavioral indicators in a safe, legal, and effective manner...hope to develop more efficient and effective means of assisting the police to identify and safely interdict persons carrying illegal firearms. This...by Velcro hook and loop fastener tape. Attached to the elastic wrap is a pocket with a security strap that holds the gun in place. When fastened to

  14. A portable virtual machine target for proof-carrying code

    DEFF Research Database (Denmark)

    Franz, Michael; Chandra, Deepak; Gal, Andreas

    2005-01-01

    Virtual Machines (VMs) and Proof-Carrying Code (PCC) are two techniques that have been used independently to provide safety for (mobile) code. Existing virtual machines, such as the Java VM, have several drawbacks: First, the effort required for safety verification is considerable. Second and mor...... simultaneously providing efficient justin-time compilation and target-machine independence. In particular, our approach reduces the complexity of the required proofs, resulting in fewer proof obligations that need to be discharged at the target machine....

  15. Cognitive Load in Voice Therapy Carry-Over Exercises

    DEFF Research Database (Denmark)

    Iwarsson, Jenny; Morris, David Jackson; Balling, Laura Winther

    2017-01-01

    Purpose The cognitive load generated by online speech production may vary with the nature of the speech task. This article examines 3 speech tasks used in voice therapy carry-over exercises, in which a patient is required to adopt and automatize new voice behaviors, ultimately in daily spontaneous...... to automation of revised speech behavior and that self-reports may be a reliable index of cognitive load....

  16. Digitization Projects Carried out by the Mathematical Institute Belgrade

    OpenAIRE

    Ognjanovič, Zoran; Mijajlovič, Žarco

    2004-01-01

    In this paper some current digitization projects carried out by the Mathematical Institute of Serbian Academy of Science and Arts Belgrade and the Faculty of Mathematics Belgrade are described. The projects concern developing of a virtual library of retro-digitized books and an Internet data base and presentation of electronic editions of some leading Serbian journals in science and arts, and the work on the South-Eastern European Digitization Initiative (SEEDI).

  17. Effect of multipurpose solutions against Acinetobacter carrying QAC genes.

    Science.gov (United States)

    Boost, Maureen V; Chan, Jessica; Shi, Guang-sen; Cho, Pauline

    2014-03-01

    Acinetobacter has low virulence but causes infections in subjects with reduced immunity. It has been reported in ocular infections including those of patients using contact lenses. Treatment is difficult because Acinetobacter is frequently multidrug resistant. Antibiotic-resistant strains frequently also harbor genes for antiseptic resistance (quaternary ammonium compound [QAC]) genes. Because Acinetobacter is part of the normal flora, it may contaminate contact lens and accessories. This study aims to investigate carriage rates of QAC genes in household and clinical isolates of Acinetobacter and to determine the effectiveness of two multipurpose solutions (MPSs) for soft lenses against organisms carrying QAC genes. DNA was extracted from 11 bathroom isolates and 15 clinical isolates and amplified by polymerase chain reaction to determine the presence of qacEΔ1. Gene-positive and gene-negative control strains were used to challenge the two MPSs, and minimum inhibitory concentrations (MICs) of these organisms to benzalkonium chloride and chlorhexidine gluconate were determined. More than 90% of isolates carried qacEΔ1. The MICs of clinical isolates were higher than those of isolates of bathrooms. Both MPSs were able to produce a 3-log reduction in the numbers of all isolates. Although most isolates carried qacEΔ1 and elevated MICs to benzalkonium chloride and chlorhexidine gluconate were observed, all were susceptible to both MPSs tested. However, if there were to be poor compliance with care procedures, it is probable that such organisms could survive in the presence of diluted or expired solutions.

  18. Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines▿

    Science.gov (United States)

    Yacoby, Iftach; Bar, Hagit; Benhar, Itai

    2007-01-01

    While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of ∼20,000 compared to the free drug. PMID:17404004

  19. Urban development control based on transportation carrying capacity

    Science.gov (United States)

    Miharja, M.; Sjafruddin, A. H.

    2017-06-01

    Severe transportation problems in Indonesian urban areas are stimulated by one fundamental factor, namely lack of awareness on transportation carrying capacity in these areas development control. Urban land use development towards more physical coverage is typically not related with the capability of transportation system to accommodate additional trips volume. Lack of clear connection between development permit with its implication on the transportation side has led to a phenomenon of exceeding transport demand over supply capacity. This paper discusses the concept of urban land use development control which will be related with transport carrying capacity. The discussion would cover both supply and demand sides of transportation. From supply side, the analysis regarding the capacity of transport system would take both existing as well as potential road network capacity could be developed. From demand side, the analysis would be through the control of a maximum floor area and public transport provision. Allowed maximum floor area for development would be at the level of generating traffic at reasonable volume. Ultimately, the objective of this paper is to introduce model to incorporate transport carrying capacity in Indonesian urban land use development control.

  20. Complete Spinal Accessory Nerve Palsy From Carrying Climbing Gear.

    Science.gov (United States)

    Coulter, Jess M; Warme, Winston J

    2015-09-01

    We report an unusual case of spinal accessory nerve palsy sustained while transporting climbing gear. Spinal accessory nerve injury is commonly a result of iatrogenic surgical trauma during lymph node excision. This particular nerve is less frequently injured by blunt trauma. The case reported here results from compression of the spinal accessory nerve for a sustained period-that is, carrying a load over the shoulder using a single nylon rope for 2.5 hours. This highlights the importance of using proper load-carrying equipment to distribute weight over a greater surface area to avoid nerve compression in the posterior triangle of the neck. The signs and symptoms of spinal accessory nerve palsy and its etiology are discussed. This report is particularly relevant to individuals involved in mountaineering and rock climbing but can be extended to anyone carrying a load with a strap over one shoulder and across the body. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  1. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

    Science.gov (United States)

    Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

    2008-08-01

    Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

  2. Detector for the liquid carried over in a gas

    International Nuclear Information System (INIS)

    Delisle, J.P.; Eperonnat, P.; Lions, N.

    1965-01-01

    This report describes an optical detector for the detection of a liquid carried over by a gas. The device is sensitive to a cumulated quantity of liquid equal to a few cubic millimetres and is capable of operating an alarm from a distance. The prototype was constructed and tested as detector for the oil leaking in the argon compressed by a diaphragm compressor. A patent for this apparatus under the number: P.V.954.703, has been deposited on 22.11.1963. (authors) [fr

  3. Shielding calculations for ships carrying irradiated nuclear fuel

    International Nuclear Information System (INIS)

    Burstall, R.F.; Dean, M.H.

    1983-01-01

    A number of ships have been constructed to carry irradiated fuel from Japan to the UK and France, for reprocessing. About twenty transport flasks may be carried on each voyage. Permanent shielding must be provided on the ships to ensure that no member of the crew receives an annual dose rate greater than a specified limit. As the fuel is of varying type and radiation history, and as flasks of differing designs are used, many calculations are needed. There are a number of difficulties in making shielding calculations for the ships. The geometry is complex, dimensions are large, and considerable air spaces are involved. The paper considers possible methods of calculation. The line-of-sight method is chosen for most of the calculations, for both gamma radiation and neutrons. The basic data which is used in the calculations is described. As the methods of calculation are somewhat approximate, it is necessary to provide confirmation that they are sufficiently accurate. Validation has been provided in two ways. First, measurements have been made on board the ships, and these have been checked against calculation. Second, a simplified model of the flasks and ship has been set up, and calculations checked against more sophisticated methods. Results of the validation checks are presented, and it is shown that adequate accuracy is achieved. (author)

  4. Shielding calculations for ships carrying irradiated nuclear fuel

    International Nuclear Information System (INIS)

    Dean, M.H.

    1985-01-01

    A number of ships have been constructed to carry irradiated fuel from Japan to the U.K. and France, for reprocessing. About 20 transport flasks may be carried on each voyage. Permanent shielding must be provided on the ships to ensure that no member of the crew receives an annual dose greater than a specified limit. As the fuel is of varying type and radiation history, and as flasks of differing designs are used, many shielding calculations are needed. There are a number of difficulties in making shielding calculations for the ships. The geometry is complex, dimensions are large and considerable air spaces are involved. The paper considers possible methods of calculation. The line-of-sight method is chosen for most of the calculations, for both γ-radiation and neutrons. The basic data which is used in the calculations is described. As the methods of calculation are somewhat approximate, it is necessary to provide confirmation that they are sufficiently accurate. Validation has been provided in two ways. First, measurements have been made on board one of the ships, Pacific Crane, and these have been checked against calculation. Second, a simplified model of the flasks and ship has been set up, and calculations checked against more sophisticated methods. Results of the validation checks are presented, and it is shown that adequate accuracy is achieved. (author)

  5. Extinguishing experiments of sodium fires carried out by TNO

    International Nuclear Information System (INIS)

    Meijer, G.J.A.M.; Rulkens, W.H.

    1979-01-01

    For the collection of burning sodium from the components and pipes of the secondary circuit of SNR 300, spill-trays are foreseen which are connected to dump tanks. These spill-trays are covered with a sieve in order to reduce the flow of air to the sodium in the spill-tray and hence to reduce the burning rate. In order to further minimize the consequences of a large sodium fire for the components, the licensing authority required as a back-up the installation of a remotely operated distribution system by means of which an extinguishing powder can be sprayed upon the spill-trays. Experiments were carried out in which the effectiveness of different extinguishing powders in combination with the sieve covered spill-trays were tested in a comparative manner. Attention was paid to the question whether such a spray system would have also additional benefits in the case of smaller sodium leaks. To this purpose three commercially available extinguishing powders were tested, one on a sodium chloride, two on a carbonate base. Also the effectiveness of the sieves proper with respect to reducing the burning rate was tested without applying any extinguishing powders. Finally for a reference some tests were done on open spill-trays, i.e. spill-trays not covered with a sieve.The investigations which were carried out in 1976-1977 were limited to fire experiments, aspects of transport of the powder in the distribution system were not investigated

  6. Langkawi Island, Social Aspect and the Carrying Capacity

    Directory of Open Access Journals (Sweden)

    Mohamad Diana

    2014-01-01

    Full Text Available The aptitude to convince a range of preferences has facilitated the island tourism attractions to achieve international recognition and at present KILIM Geopark is enjoyed by a prominent percentage of individuals wide-reaching. Conventional knowledge has that the island attractions are operating on the limited immobile resources, of which, have raised the scholars’ concerns over the carrying capacity issue. When analyzing carrying capacity, scholars have traditionally focused on the environmental part, hence, this working paper is motivated to convey onto the table issues relating to the social characteristics. This particular paper employed the self-administered questionnaire survey instrument which was structured to answer the two-fold objective specifically the tourists’ satisfaction level with their tourism experience and knowledge gap in relation to improving the island tourism. Targeting the tourists with minimum age of 18, this working paper collects information on the tourists’ perception towards hospitality, facilities and safety issues. In addition, this working paper comes to scrutinize different results of demographic factors as compared to what have been documented by earlier studies. Besides, it is learned that ‘safety issue’ variable plays an important role when it comes to the following factors: tourist arrival, access to facilities and tourism experience.

  7. Exosomes carrying immunoinhibitory proteins and their role in cancer.

    Science.gov (United States)

    Whiteside, T L

    2017-09-01

    Recent emergence of exosomes as information carriers between cells has introduced us to a new previously unknown biological communication system. Multi-directional cross-talk mediated by exosomes carrying proteins, lipids and nucleic acids between normal cells, cells harbouring a pathogen or cancer and immune cells has been instrumental in determining outcomes of physiological as well as pathological conditions. Exosomes play a key role in the broad spectrum of human diseases. In cancer, tumour-derived exosomes carry multiple immunoinhibitory signals, disable anti-tumour immune effector cells and promote tumour escape from immune control. Exosomes delivering negative signals to immune cells in cancer, viral infections, autoimmune or other diseases may interfere with therapy and influence outcome. Exosomes can activate tissue cells to produce inhibitory factors and thus can suppress the host immune responses indirectly. Exosomes also promise to be non-invasive disease biomarkers with a dual capability to provide insights into immune dysfunction as well as disease progression and outcome. © 2017 British Society for Immunology.

  8. Necking down of sausages in current-carrying plasma pinches

    International Nuclear Information System (INIS)

    Trubnikov, B.A.; Zhdanov, S.K.

    1986-01-01

    The evolution of long-wave perturbations is shown to be equivalent, for various unstable media, to the dynamics of a gas with a negative adiabatic index γ. This evolution is described (for various values at N) by the quasi-Chaplygin system of equations Several examples of such media are considered, including a ''Chaplygin gas'' (N = 3), drops on a ceiling or ''solitons which have broken'' (N = 0), necks in a current-carrying plasma pinch with a skin effect, for both incompressible and compressible models (N = 2), and the breakup of liquid jets into drops (N = 3/2). A principle for selecting evolutionary solutions corresponding to the absence of perturbations in the limit t → -∞ is formulated. In the cases N = 0 and N = 2, a hodograph transformation reduces system (1) to a magnetostatic equation (ΔA)/sub phi/ = -(4π/c)j/sub phi/ and all the instability modes are equivalent to multipoles of circular currents which are localized on a circle. Exact solutions are given for periodic and isolated (localized) perturbations. The breakup of a medium into distinct blobs, in particular, the rupture of necks in a current-carrying plasma pinch, is demonstrated

  9. Oxygen carrying perfluorochemical emulsion as an adjuvant to radiation therapy

    International Nuclear Information System (INIS)

    Teicher, B.A.; Rose, C.M.

    1984-01-01

    The potential of a perfluorochemical emulsion which as an excellent carrying capacity for oxygen to enhance the ability of radiation therapy to delay the growth of Lewis lung tumor was examined. There was a highly significant effect produced by the addition of perfluorochemical emulsion and carbogen breathing in combination with irradiation. With single dose x-ray treatment the dose of perfluorochemical emulsion was varied from 0.05-0.6 ml addition to the blood volume of the animals. The dose response effect was very broad peaking at 0.3-0.4 ml which gave a dose modifying effect of 2.8 +- 0.6 with 1000 rad of x-rays. The addition of 0.3 ml of perfluorochemical free annex solution with carbogen breathing produced a small enhancement in tumor growth delay addition of the same volume of the complete emulsion increased the tumor growth delay time about 3-fold compared to the annex solution. When the perfluorochemical emulsion was added to a fractionated course of radiation therapy a dose modifying effect of 1.8 +- 0.3 was obtained. Oxygen carrying perfluorochemical emulsions may provide a nontoxic clinically useful means of increasing the effectiveness of radiation therapy and of certain chemotherapeutic agents

  10. STS-99 workers carry new Master Events Controller to Endeavour

    Science.gov (United States)

    2000-01-01

    Workers carry the replacement Enhanced Main Events Controller (E- MEC) to Shuttle Endeavour at Launch Pad 39A for installation in the aft compartment of the payload bay. The original E-MEC became suspect during the Jan. 31 launch countdown and mission STS-99 was delayed when NASA managers decided to replace it. Each Shuttle carries two enhanced master events controllers (E-MECs), which provide relays for onboard flight computers to send signals to arm and fire pyrotechnics that separate the solid rockets and external tank during assent. Both E-MECs are needed for the Shuttle to be cleared for flight. Currently Endeavour and Columbia are the only two orbiters with the E-MECs. Built by Rockwell's Satellite Space Electronics Division, Anaheim, Calif., each unit weighs 65 pounds and is approximately 20 inches long, 13 inches wide and 8 inches tall. Previously, three Shuttle flights have been scrubbed or delayed due to faulty MECs: STS-73, STS-49 and STS-41-D. The next scheduled date for launch of STS-99 is Feb. 11 at 12:30 p.m. EST.

  11. Acetylcholine receptor antibody

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

  12. Cooperative ethylene receptor signaling

    OpenAIRE

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

  13. Modelling of carry-over in recovery furnaces

    Energy Technology Data Exchange (ETDEWEB)

    Fakhrai, Reza [Royal Inst. of Tech., Stockholm (Sweden). Dept. of Metallurgy

    2000-04-01

    Development of mathematical modelling of the combustion process in the furnace of recovery boilers is the subject of this work. This work as a continuation of many years of modelling efforts carried out at KTH/Vaerme- och Ugnsteknik focussed particularly on: char bed modelling; droplets-wall interaction modelling; and carry-over modelling. The char bed model has been studied. Droplets/parcels were considered as a single reactor working independently of the other droplets. The mass of the droplets was not distributed uniformly but induced in the landing place. The droplets hitting the char bed will stick to it and they are alive and part of the calculation. In this way the distribution of the mass on the char bed is only dependent on the parameters which effect flight history such as droplet/parcel diameter, boilers flow field, etc. The droplet- wall interaction model has been studied and found to be very important for obtaining the correct temperature distribution in the recovery furnace. The new approach is based on removal of droplets which hits the wall in the upper part of the recovery boiler from carryover calculation. This model has been proposed and implemented into the GRFM (General Recovery Furnace Model). The carryover modelling effort was based on mass balance in which the number and physical statistics of the droplets/parcel were estimated and the amount of unburned mass was calculated. All of the above listed models were tested together with all other models of heat and mass transfer processes in recovery furnaces using a GRFM. Three-dimensional numerical simulations of the industrial recovery boiler (63 kg/s, 82 bar, 480 deg C) were performed. The number of grid was 232,000 and the number of air ports in this simulation was 178. The air entering the furnace by these ports has different flow rates. Flow and temperature fields as well as species distributions were calculated. The results show good agreement with previously published data and modelling

  14. Central alpha2 adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

    International Nuclear Information System (INIS)

    Adler, C.H.

    1986-01-01

    The alpha 2 adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha 2 adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha 2 adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha 2 agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha 2 adrenergic autoreceptors, which inhibit stimulation-evoked release of 3 H-norepinephrine ( 3 H-NE) and alpha 2 adrenergic heteroreceptors which inhibit stimulation-evoked release of 3 H-serotonin ( 3 H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha 2 adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha 2 adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha 2 adrenergic receptor; and (2) alterations in the number of alpha 2 receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve

  15. Time dependent variation of carrying capacity of prestressed precast beam

    Science.gov (United States)

    Le, Tuan D.; Konečný, Petr; Matečková, Pavlína

    2018-04-01

    The article deals with the evaluation of the precast concrete element time dependent carrying capacity. The variation of the resistance is inherited property of laboratory as well as in-situ members. Thus the specification of highest, yet possible, laboratory sample resistance is important with respect to evaluation of laboratory experiments based on the test machine loading capabilities. The ultimate capacity is evaluated through the bending moment resistance of a simply supported prestressed concrete beam. The probabilistic assessment is applied. Scatter of random variables of compressive strength of concrete and effective height of the cross section is considered. Monte Carlo simulation technique is used to investigate the performance of the cross section of the beam with changes of tendons’ positions and compressive strength of concrete.

  16. Tax shields, financial expenses and losses carried forward

    Directory of Open Access Journals (Sweden)

    Ignacio Vélez-Pareja

    2016-09-01

    Full Text Available This article deals with the proper procedure for calculating Tax Shields (TS. The calculation includes cases where Losses Carried Forward are allowed and there is financial Other Income (OI. The procedure takes into account the magnitude of Adjusted Earnings before Interest and Taxes (EBITAdj –that is, EBIT + OI – OE excluding Financial- compared with Financial Expenses (FE. This comparison defines three intervals and results for TS. If EBITAdj. 0 and less than FE, TSis T × EBITAdj.; finally if EBITAdj. > FE, TSis T × FE. When firm possesses OI, TS are not equivalent to the difference in taxes and an adjustment is needed. Proper calculation of TS is important because their value might represent a substantial part of firm value.

  17. Stabilization of magnetohydrodynamic instabilities in a current-carrying stellarator

    International Nuclear Information System (INIS)

    Matsuoka, K.; Miyamoto, K.

    1979-02-01

    Stable profiles against MHD instabilities are given in a cylindrical current-carrying stellarator. The comparison theorem, i.e., guiding principle for stabilization, is obtained in the same way as in a tokamak. As the external rotational transform due to an l = 2 helical field increases, MHD properties in a stellarator are improved than in a tokamak and the minimum value of q(a) which provides simultaneous stabilization of MHD modes can be lowered less than 2 even without a conducting shell. In an l = 3 stellarator, however, as shown from the Euler equation, the configuration becomes more unstable than in a tokamak and strong tailoring of the current profile is necessary in order to stabilize MHD modes. (author)

  18. Process for carrying out analyses based on concurrent reactions

    Energy Technology Data Exchange (ETDEWEB)

    Glover, J S; Shepherd, B P

    1980-01-03

    The invention refers to a process for carrying out analyses based on concurrent reactions. A part of a compound to be analysed is subjected with a standard quantity of this compound in a labelled form to a common reaction with a standard quantity of a reagent, which must be less than the sum of the two parts of the reacting compound. The parts of the marked reaction compound and the labelled final compound resulting from the concurrence are separated in a tube (e.g. by centrifuging) after forced phase change (precipitation, absorption etc.) and the radio-activity of both phases in contact is measured separately. The shielded measuring device developed for this and suitable for centrifuge tubes of known dimensions is also included in the patent claims. The insulin concentration of a defined serum is measured as an example of the applications of the method (Radioimmunoassay).

  19. Localization of extracellular matrix laminin and fibronectin in male rats infected by candida albicans, with the property expected as facilitator molecules and treated by pomegranate extract and nystatin as antifungal substance

    Energy Technology Data Exchange (ETDEWEB)

    Kumolosasi, E.S.; Barlian, A.; Sukandar, E.Y.

    1998-12-16

    Candida albicans is one of the parasitic fungi that often infects the tissue's surface in human. Nystatin has been long known as the most potent antifungal drug. One of natural products, Punica granatum, was shown to have antifungal effect as the result of ten years' investigation. In this research, male rats that were infected by C. albicans orally for 24 hours were cured by P. granatum extract with a dose of 50 mg/200 g body weight and by Nystatin 9.10{sup 3} IU/200 g body weight. Fifteen hours later, the rats were sacrificed and the small intestines were prepared for histology with semithin sectioning method. Microscopic observations showed that the inflammation occurred in the small intestines of the infected rats without any medication. However, for the rats that were treated with P. granatum extract, the small intestine area was almost in the similar condition with nin-infected rats. The small intestine of the rats treated by Nystatin showed minor inflammation. The immunocytochemistry procedure in this research still need modification to be able to detect Laminin and Fibronectin and clarify their roles in the invasion of C. albicans. (author)

  20. IRSN safety research carried out for reviewing safety cases

    International Nuclear Information System (INIS)

    Serres, Ch.

    2010-01-01

    Christophe Serres from IRSN (France) described the independent role of the IRSN regarding research related to nuclear safety in the context of the French Planning Act of 28 June 2006 foreseeing a licence application to be submitted in 2015 for the creation of a deep geological repository. IRSN research programme is organised along research activities devoted to addressing independently-identified k ey safety issues . These 'key issues' should also be of prime concern for the implementer since they relate to the demonstration of the overall safety of the repository, and the level of funding that the implementer should afford to research activities of concern for safety. He explained that the quality and independency of the research programme carried out by IRSN allow building and improving a set of scientific knowledge and technical skills that serves the public mission of delivering technical appraisal and advice, e.g., on behalf of the national safety authority. In particular they contribute to improving the decisional process by making possible scientific dialogue with stakeholders independently from regulator or implementer. The current IRSN R and D programme is developed along the following lines: - Test the adequacy of experimental methods for which feedback is not sufficient. - Develop basic scientific knowledge in the fields where there is a need for better understanding of complex phenomena and interactions. - Develop and use numerical modelling tools to support studies on complex phenomena and interactions. - Perform specific experimental tests aiming at assessing the key parameters that may warrant the performances of the different components of the repository. These studies are carried out by means of experiments performed either at IRSN surface laboratories, or in the Tournemire Experimental Station (TES), an underground facility operated by IRSN in the south-east of France. Targeted actions on research related to operational safety and reversibility

  1. Characterization of LH induced current carrying fast electrons in JET

    Energy Technology Data Exchange (ETDEWEB)

    Ramponi, G.; Airoldi, A. [Consiglio Nazionale delle Ricerche, Milan (Italy). Lab. di Fisica del Plasma; Bartlett, D.; Brusati, M.; Froissard, P.; Gormezano, C.; Rimini, F.; Silva, R.P. da; Tanzi, C.P. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking

    1992-12-31

    Lower Hybrid Current Drive (LHCD) experiments have recently been made at JET by coupling up to 2.4 MW of RF power at 3.7 GHz, with a power spectrum centered at n{sub ||} = 1.8 {+-} 0.2 corresponding to a resonating electron energy of about 100 keV via Electron Landau Damping. The Current Drive (CD) efficiency has been observed to increase when LH and ICRH power are applied simultaneously to the plasma, suggesting that a part of the fast magnetosonic wave is absorbed on the LH-generated fast electrons. An important problem of CD experiments in tokamaks is the determination of the radial distribution of the driven current and the characterization in the momentum space of the current carrying fast electrons by using appropriate diagnostic tools. For this purpose, a combined analysis of the Electron Cyclotron Emission (ECE) and of the Fast Electron Bremsstrahlung (FEB) measurements has been made, allowing the relevant parameters of the suprathermal electrons to be estimated. (author) 5 refs., 5 figs., 2 tabs.

  2. Characterization of LH induced current carrying fast electrons in JET

    International Nuclear Information System (INIS)

    Ramponi, G.; Airoldi, A.; Bartlett, D.; Brusati, M.; Froissard, P.; Gormezano, C.; Rimini, F.; Silva, R.P. da; Tanzi, C.P.

    1992-01-01

    Lower Hybrid Current Drive (LHCD) experiments have recently been made at JET by coupling up to 2.4 MW of RF power at 3.7 GHz, with a power spectrum centered at n || = 1.8 ± 0.2 corresponding to a resonating electron energy of about 100 keV via Electron Landau Damping. The Current Drive (CD) efficiency has been observed to increase when LH and ICRH power are applied simultaneously to the plasma, suggesting that a part of the fast magnetosonic wave is absorbed on the LH-generated fast electrons. An important problem of CD experiments in tokamaks is the determination of the radial distribution of the driven current and the characterization in the momentum space of the current carrying fast electrons by using appropriate diagnostic tools. For this purpose, a combined analysis of the Electron Cyclotron Emission (ECE) and of the Fast Electron Bremsstrahlung (FEB) measurements has been made, allowing the relevant parameters of the suprathermal electrons to be estimated. (author) 5 refs., 5 figs., 2 tabs

  3. Mutagenic effects on indica rice carried by satellite

    International Nuclear Information System (INIS)

    Wu Dezhi; Liu Yongzhu; Guo Tao; Zhang Jianguo; Chen Zhiqiang; Wang Hui

    2010-01-01

    Dried seeds of four indica rice varieties were carried into space by satellite Shijia No.8, the mutagenic effects of space condition on the seeds vigor and agronomic traits in the SP 1 generation, and on the agronomic traits, amylose conent and bacterial resistance in the SP 2 generation were studied. The results showed that the space condition slightly damaged rice seeds, with the physiological damage rate of germination rate, bud length, plant height and seed-setting rate in the SP 1 ranged from 0 to 26.9%. Different varieties responded differently to the space conditions, and the order from strong to weak was Gui 99, Hanghui 7, R998, Jinhang 138. Compared with the control, no trait showed segregation in the SP 1 generation. Some traits appeared larger segregation in the SP 2 generation, and the mutants of plant height, number of tillers, weight of grain, amylose content and bacterial blight resistance were isolated in the SP 2 generation, and these mutation traits could be inherited the SP 3 generation. Space conditions not only produced mutants of rice agronomic traits, but also produced mutants of rice quality and disease resistance. (authors)

  4. Carrying photosynthesis genes increases ecological fitness of cyanophage in silico.

    Science.gov (United States)

    Hellweger, Ferdi L

    2009-06-01

    Several viruses infecting marine cyanobacteria carry photosynthesis genes (e.g. psbA, hli) that are expressed, yield proteins (D1, HLIP) and help maintain the cell's photosynthesis apparatus during the latent period. This increases energy and speeds up virus production, allowing for a reduced latent period (a fitness benefit), but it also increases the DNA size, which slows down new virus production and reduces burst size (a fitness cost). How do these genes affect the net ecological fitness of the virus? Here, this question is explored using a combined systems biology and systems ecology ('systems bioecology') approach. A novel agent-based model simulates individual cyanobacteria cells and virus particles, each with their own genes, transcripts, proteins and other properties. The effect of D1 and HLIP proteins is explicitly considered using a mechanistic photosynthesis component. The model is calibrated to the available database for Prochlorococcus ecotype MED4 and podovirus P-SSP7. Laboratory- and field-scale in silico survival, competition and evolution (gene packaging error) experiments with wild type and genetically engineered viruses are performed to develop vertical survival and fitness profiles, and to determine the optimal gene content. The results suggest that photosynthesis genes are nonessential, increase fitness in a manner correlated with irradiance, and that the wild type has an optimal gene content.

  5. Interchain interactions in charged diacetylenic oligomers carrying bulk substituents revisited

    International Nuclear Information System (INIS)

    Ottonelli, M.; Izzo, G.M.M.; Comoretto, D.; Musso, G.F.; Dellepiane, G.

    2006-01-01

    We are studying how the electronic properties of an aggregate, built with conjugated oligomers carrying bulk substituents, are affected by intermolecular interactions. In this paper we apply the CEO (Collective Electronic Oscillator) method, on the basis of the semiempirical INDO/S Hamiltonian, to compute the electronic density matrix modifications following the photon absorption in a doubly charged cluster of two units of a fully carbazolyl-substituted oligodiacetylene tetramer, taken as a model system. The picture that had emerged from our previous calculations based on the less sophisticated CIS (Configuration Interaction including Singles) approach is seen to be confirmed. Despite the large separation between the backbones, a through-space charge transfer occurs between the two oligomers due to the fact that the excess charge, contrary to what is generally believed, is not localized on the conjugated backbone, but is spread out over the carbazolyl moieties of the charged molecule. Consideration of this kind of interaction improves the theoretical results obtained for the isolated charged oligomer chain, and aids in better explaining some features of the experimental photoinduced spectra of the corresponding polymer

  6. Single-electron states near a current-carrying core

    International Nuclear Information System (INIS)

    Masale, M.

    2004-01-01

    The energy spectrum of an electron confined near a current-carrying core is obtained as a function of the azimuthal applied magnetic field within the effective-mass approximation. The double degeneracy of the non-zero electron's axial wave number (k z ) states is lifted by the current-induced magnetic field while that of the non-zero azimuthal quantum number (m) states is preserved. A further analysis is the evaluations of the oscillator strengths for optical transitions involving the lowest-order pair of the electron's energy subbands within the dipole approximation. The radiation field is taken as that of elliptically polarized light incident along the core axis. In this polarization and within the dipole approximation, the allowed transitions are only those governed by the following specific selection rules. The azimuthal quantum numbers of the initial and final states must differ by unity while the electron's axial wave number is conserved. The azimuthal magnetic field is also found to lift the multiple degeneracies of the k z ≠0 interaction integrals as well as those of the oscillator strengths for optical transitions

  7. Roadmap and performance carried out during Ciemat site decommissioning

    International Nuclear Information System (INIS)

    Quinones, Javier; Diaz Diaz, Jose Luis

    2005-01-01

    Ciemat (Research Centre for Energy, Environment and Technology) located in the heart of the Ciudad Universitaria of Madrid, occupies a property of 20 Ha. Since its creation in 1951 as JEN, and in 1986 renowned as Ciemat, it has involved on R and D projects in the field of Energy and Environment, i.e., Nuclear Fission, Nuclear Fusion, Fossils Fuels, Renewable Energy. As a consequence of the R and D projects developed between 1951 - 1986 on Nuclear Fission field (fuel design, fabrication, characterization on irradiated fuels, safety studies, etc) and to the diversification of the goals as well, it is necessary to Decommissioning and Dismantling (D and D) from nuclear facilities (nuclear reactor, Hot Cells, Irradiation facility), buildings and soils. Preparations for D and D included a staged shutdown of operations, planning documentation and licensing for decommissioning. As a prerequisite to Ciemat application for a decommissioning license and nuclear environmental assessment was carried out according to Spanish Nuclear Council (CSN) and approval of the site decommissioning project was obtained in 2000 and valid until December 31, 2006. Since 2001 - 2003 is underway and focussed on the radiological characterization of the site (divided in pieces of ground), when each piece of ground is characterized a planning for D and D is presented to CSN in order to obtain a license for actuation. Nowadays several pieces of ground are decontaminated and modifications have been done in order to achieve a safe state of storage-with-surveillance. Later phases have planned waste management improvements for selected wastes already on temporally storage, eventually followed by final decommissioning of facilities and buildings and cleaning of contaminants from soils and removal of waste from the site. This paper describes the planning, nuclear and environment assessment and descriptions of decommissioning activities currently underway at Ciemat. (Author)

  8. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  9. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  10. Glucocorticoid receptor modulators.

    Science.gov (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

    2018-06-01

    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  12. T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids.

    Science.gov (United States)

    Wun, Kwok S; Reijneveld, Josephine F; Cheng, Tan-Yun; Ladell, Kristin; Uldrich, Adam P; Le Nours, Jérôme; Miners, Kelly L; McLaren, James E; Grant, Emma J; Haigh, Oscar L; Watkins, Thomas S; Suliman, Sara; Iwany, Sarah; Jimenez, Judith; Calderon, Roger; Tamara, Kattya L; Leon, Segundo R; Murray, Megan B; Mayfield, Jacob A; Altman, John D; Purcell, Anthony W; Miles, John J; Godfrey, Dale I; Gras, Stephanie; Price, David A; Van Rhijn, Ildiko; Moody, D Branch; Rossjohn, Jamie

    2018-04-01

    The hallmark function of αβ T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses.

  13. Assessing the air pollution carrying capacity of the northern Puget Sound region: an application of TAPAS

    Energy Technology Data Exchange (ETDEWEB)

    Wood, M.C.; Childs J.E.; Marlatt, W.E.

    1980-09-01

    The technique discussed, the Topographic Air Pollution Analysis System (TAPAS), was developed to provide valid information on the dispersion capability of the lower atmosphere in areas characterized by complex terrain features. A study was undertaken to assess the air quality (SO/sub 2/) impacts associated with energy development in the region and to determine the constraints on energy development due to regulated limitations on the amount of air quality degradation allowable in the area. The emission constraint analysis for the northern Puget Sound region indicated that total SO/sub 2/ emissions in the core area (on an annual basis) are less than half of the amount that could be tolerated in the entire core region while maintaining ambient concentrations within state and federal annual average limitations. However, comparison of source characteristics with source location and grid cell emission restrictions indicated that localized areas adjacent to the major point sources are already far in excess of the SO/sub 2/ carrying capacity. This conclusion is supported by air quality monitoring data that indicate state standard violations at several receptor locations within the study area. The annual maps of wind patterns and PI-Matrix values show areas of both good and poor dispersion characteristics under the most prevalent flow conditions.

  14. Tensorial spacetime geometries carrying predictive, interpretable and quantizable matter dynamics

    International Nuclear Information System (INIS)

    Rivera Hernandez, Sergio

    2012-01-01

    Which tensor fields G on a smooth manifold M can serve as a spacetime structure? In the first part of this thesis, it is found that only a severely restricted class of tensor fields can provide classical spacetime geometries, namely those that can carry predictive, interpretable and quantizable matter dynamics. The obvious dependence of this characterization of admissible tensorial spacetime geometries on specific matter is not a weakness, but rather presents an insight: it was Maxwell theory that justified Einstein to promote Lorentzian manifolds to the status of a spacetime geometry. Any matter that does not mimick the structure of Maxwell theory, will force us to choose another geometry on which the matter dynamics of interest are predictive, interpretable and quantizable. These three physical conditions on matter impose three corresponding algebraic conditions on the totally symmetric contravariant coefficient tensor field P that determines the principal symbol of the matter field equations in terms of the geometric tensor G: the tensor field P must be hyperbolic, time-orientable and energy-distinguishing. Remarkably, these physically necessary conditions on the geometry are mathematically already sufficient to realize all kinematical constructions familiar from Lorentzian geometry, for precisely the same structural reasons. This we were able to show employing a subtle interplay of convex analysis, the theory of partial differential equations and real algebraic geometry. In the second part of this thesis, we then explore general properties of any hyperbolic, time-orientable and energy-distinguishing tensorial geometry. Physically most important are the construction of freely falling non-rotating laboratories, the appearance of admissible modified dispersion relations to particular observers, and the identification of a mechanism that explains why massive particles that are faster than some massless particles can radiate off energy until they are slower than all

  15. Tensorial spacetime geometries carrying predictive, interpretable and quantizable matter dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Rivera Hernandez, Sergio

    2012-02-15

    Which tensor fields G on a smooth manifold M can serve as a spacetime structure? In the first part of this thesis, it is found that only a severely restricted class of tensor fields can provide classical spacetime geometries, namely those that can carry predictive, interpretable and quantizable matter dynamics. The obvious dependence of this characterization of admissible tensorial spacetime geometries on specific matter is not a weakness, but rather presents an insight: it was Maxwell theory that justified Einstein to promote Lorentzian manifolds to the status of a spacetime geometry. Any matter that does not mimick the structure of Maxwell theory, will force us to choose another geometry on which the matter dynamics of interest are predictive, interpretable and quantizable. These three physical conditions on matter impose three corresponding algebraic conditions on the totally symmetric contravariant coefficient tensor field P that determines the principal symbol of the matter field equations in terms of the geometric tensor G: the tensor field P must be hyperbolic, time-orientable and energy-distinguishing. Remarkably, these physically necessary conditions on the geometry are mathematically already sufficient to realize all kinematical constructions familiar from Lorentzian geometry, for precisely the same structural reasons. This we were able to show employing a subtle interplay of convex analysis, the theory of partial differential equations and real algebraic geometry. In the second part of this thesis, we then explore general properties of any hyperbolic, time-orientable and energy-distinguishing tensorial geometry. Physically most important are the construction of freely falling non-rotating laboratories, the appearance of admissible modified dispersion relations to particular observers, and the identification of a mechanism that explains why massive particles that are faster than some massless particles can radiate off energy until they are slower than all

  16. The importance of the adenosine A(2A) receptor-dopamine D(2) receptor interaction in drug addiction.

    Science.gov (United States)

    Filip, M; Zaniewska, M; Frankowska, M; Wydra, K; Fuxe, K

    2012-01-01

    Drug addiction is a serious brain disorder with somatic, psychological, psychiatric, socio-economic and legal implications in the developed world. Illegal (e.g., psychostimulants, opioids, cannabinoids) and legal (alcohol, nicotine) drugs of abuse create a complex behavioral pattern composed of drug intake, withdrawal, seeking and relapse. One of the hallmarks of drugs that are abused by humans is that they have different mechanisms of action to increase dopamine (DA) neurotransmission within the mesolimbic circuitry of the brain and indirectly activate DA receptors. Among the DA receptors, D(2) receptors are linked to drug abuse and addiction because their function has been proven to be correlated with drug reinforcement and relapses. The recognition that D(2) receptors exist not only as homomers but also can form heteromers, such as with the adenosine (A)(2A) receptor, that are pharmacologically and functionally distinct from their constituent receptors, has significantly expanded the range of potential drug targets and provided new avenues for drug design in the search for novel drug addiction therapies. The aim of this review is to bring current focus on A(2A) receptors, their physiology and pharmacology in the central nervous system, and to discuss the therapeutic relevance of these receptors to drug addiction. We concentrate on the contribution of A(2A) receptors to the effects of different classes of drugs of abuse examined in preclinical behavioral experiments carried out with pharmacological and genetic tools. The consequences of chronic drug treatment on A(2A) receptor-assigned functions in preclinical studies are also presented. Finally, the neurochemical mechanism of the interaction between A(2A) receptors and drugs of abuse in the context of the heteromeric A(2A)-D(2) receptor complex is discussed. Taken together, a significant amount of experimental analyses provide evidence that targeting A(2A) receptors may offer innovative translational strategies

  17. Angiotensin type 2 receptors

    DEFF Research Database (Denmark)

    Sumners, Colin; de Kloet, Annette D; Krause, Eric G

    2015-01-01

    In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

  18. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  19. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  20. Internalisation of gonadotrophin-receptor complex in ovarian luteal cells

    International Nuclear Information System (INIS)

    Conn, P.M.; Conti, M.; Harwood, J.P.; Dufau, M.L.; Catt, K.J.

    1978-01-01

    Following evidence that certain protein hormones can enter target cells the present investigation was undertaken which shows that gonadotrophin-induced receptor loss may occur by a process of internalisation of the hormone-receptor complex following the initial interaction of gonadotrophin with the cell surface. Localisation studies were carried out in 33-d old female rats previously treated with pregnant mare serum gonadotrophin and human chorionic gonadotrophin (hCG) to induce ovarian luteinisation. Animals were injected with 125 I-hCG to label the ovarian receptors for luteinising hormone in vivo. Microscope autoradiographs demonstrating distribution of 125 I-hCG in ovaries at various times following injection are shown. The combined results from the autoradiographs and from solubilisation experiments were used to determine the location and nature of the hCG-receptor complex following occupancy and loss of receptors from the plasma membrane of luteinised ovarian cells. (U.K.)

  1. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    IAS Admin

    Director of ... function of the Lp is to deliver lipids throughout the insect body for metabolism ... Lipid is used as a major energy source for development as well as other metabolic .... LpR4 receptor variant was expressed exclusively in the brain and.

  2. Expanded cellular clones carrying replication-competent HIV-1 persist, wax, and wane.

    Science.gov (United States)

    Wang, Zheng; Gurule, Evelyn E; Brennan, Timothy P; Gerold, Jeffrey M; Kwon, Kyungyoon J; Hosmane, Nina N; Kumar, Mithra R; Beg, Subul A; Capoferri, Adam A; Ray, Stuart C; Ho, Ya-Chi; Hill, Alison L; Siliciano, Janet D; Siliciano, Robert F

    2018-03-13

    The latent reservoir for HIV-1 in resting CD4 + T cells is a major barrier to cure. Several lines of evidence suggest that the latent reservoir is maintained through cellular proliferation. Analysis of this proliferative process is complicated by the fact that most infected cells carry defective proviruses. Additional complications are that stimuli that drive T cell proliferation can also induce virus production from latently infected cells and productively infected cells have a short in vivo half-life. In this ex vivo study, we show that latently infected cells containing replication-competent HIV-1 can proliferate in response to T cell receptor agonists or cytokines that are known to induce homeostatic proliferation and that this can occur without virus production. Some cells that have proliferated in response to these stimuli can survive for 7 d while retaining the ability to produce virus. This finding supports the hypothesis that both antigen-driven and cytokine-induced proliferation may contribute to the stability of the latent reservoir. Sequencing of replication-competent proviruses isolated from patients at different time points confirmed the presence of expanded clones and demonstrated that while some clones harboring replication-competent virus persist longitudinally on a scale of years, others wax and wane. A similar pattern is observed in longitudinal sampling of residual viremia in patients. The observed patterns are not consistent with a continuous, cell-autonomous, proliferative process related to the HIV-1 integration site. The fact that the latent reservoir can be maintained, in part, by cellular proliferation without viral reactivation poses challenges to cure.

  3. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  4. Do Weapons Facilitate Adolescent Delinquency? An Examination of Weapon Carrying and Delinquency Among Adolescents.

    Science.gov (United States)

    Emmert, Amanda D; Hall, Gina Penly; Lizotte, Alan J

    2018-03-01

    This article examines whether weapon carrying influences the frequency and variety of violent, property, and drug delinquency adolescents commit through fixed-effects analyses of data from the Rochester Youth Development Study (RYDS). We conclude that weapon carrying contributes to violent, substance, and property delinquency, and delinquent behaviors learned during weapon carrying continue to affect substance and property delinquency long after carrying has ceased.

  5. A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion properties of human colon cancer cells.

    Science.gov (United States)

    Pelissier-Rota, M; Chartier, N T; Bonaz, B; Jacquier-Sarlin, M R

    2017-07-01

    Patients with inflammatory bowel disease often suffer from chronic and relapsing intestinal inflammation that favor the development of colitis associated cancer. An alteration of the epithelial intestinal barrier function observed in IBD is supposed to be a consequence of stress. It has been proposed that corticotrophin-releasing factor receptor (CRF2), one of the two receptors of CRF, the principal neuromediator of stress, acts on cholinergic nerves to induce stress-mediated epithelial barrier dysfunction. Non-neuronal acetylcholine (Ach) and muscarinic receptors (mAchR) also contribute to alterations of epithelial cell functions. In this study, we investigated the mechanisms through which stress and Ach modulate epithelial cell adhesive properties. We show that Ach-induced activation of mAchR in HT-29 cells results in cell dissociation together with changes in cell-matrix contacts, which correlates with the acquisition of invasive potential consistent with a matrix metalloproteinase (MMP) mode of invasion. These processes result from mAchR subsequent stimulation of the cascade of src/Erk and FAK activation. Ach-induced secretion of laminin 332 leads to α3β1 integrin activation and RhoA-dependent reorganization of the actin cytoskeleton. We show that Ach-mediated effects on cell adhesion are blocked by astressin 2b, a CRF2 antagonist, suggesting that Ach action depends partly on CRF2 signaling. This is reinforced by the fact that Ach-mediated activation of mAchR stimulates both the synthesis and the release of CRF2 ligands in HT-29 cells (effects blocked by atropine). In summary, our data provides evidence for a novel intracellular circuit involving mAchR acting on CRF2-signaling that could mediate colonic mucosal barrier dysfunction and exacerbate mucosal inflammation. Copyright © 2017. Published by Elsevier B.V.

  6. Exclusion of candidate genes from the chromosome 1q juvenile glaucoma region and mapping of the peripheral cannabis receptor gene (CNR2) to chromosome 1

    Energy Technology Data Exchange (ETDEWEB)

    Sunden, S.L.F.; Nichols, B.E.; Alward, W.L.M. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1994-09-01

    Juvenile onset primary open angle glaucoma has been mapped by linkage to 1q21-q31. Several candidate genes were evaluated in the same family used to identify the primary linkage. Atrionatriuretic peptide receptor A (NPR1) and laminin C1 (LAMC1) have been previously mapped to this region and could putatively play a role in the pathogenesis of glaucoma. A third gene, the peripheral cannabis receptor (CNR2) was not initially mapped in humans but was a candidate because of the relief that cannabis affords some patients with primary open angle glaucoma. Microsatellites associated with NPR1 and LAMC1 revealed multiple recombinations in affected members of this pedigree. CNR2 was shown to be on chromosome 1 by PCR amplification of a 150 bp fragment of the 3{prime} untranslated region in monochromosomal somatic cell hybrids (NIGMS panel No. 2). These primers also revealed a two allele single strand conformation polymorphism which showed multiple recombinants with juvenile onset primary open angle glaucoma in large pedigrees, segregating this disorder. The marker was then mapped to 1p34-p36 by linkage, with the most likely location between liver alkaline phosphatase (ALPL) and alpha-L-1 fucosidase (FUCA1).

  7. Effects of ionizing irradiation on the estradiol and progesterone receptors in rat mammary tumors

    International Nuclear Information System (INIS)

    Janssens, J.P.; Wittevrongel, C.; Van Dam, J.; Goddeeris, P.; Lauwerijns, J.M.; De Loecker, W.

    1981-01-01

    The determination of estradiol and progesterone receptor concentrations in mammary tumors is useful in predicting the hormone responsiveness. As this assay is carried out on tumor tissue which may have been subjected to radiotherapy, the possibility of an ionizing irradiation affecting the steroid receptor levels in neoplastic tissue should be taken into account. The steroid receptor concentrations are examined in dimethylbenz(a)anthracene-induced tumors os Sprague-Dawley rats. The estradiol and the progesterone receptor titers become reduced significantly after treatment with 20 Gray while an application with 7 Gray does not affect the titer values. After treatment of the tumor with 20 Gray, the steroid receptor concentrations decrease progressively, reaching a maximal reduction 20 to 30 days after exposure. As radiation treatment affects the receptor concentrations, this should be kept in mind when interpreting the steroid receptor concentrations

  8. [Ecotourism carrying capacity of Hangzhou Xixi National Wetland Park in China].

    Science.gov (United States)

    Li, Rui; Rong, Liang

    2007-10-01

    In this paper, an integrated estimation on the ecotourism carrying capacity of Hangzhou Xixi National Wetland Park in China was made from the aspects of ecological carrying capacity, spatial carrying capacity, facility carrying capacity, management carrying capacity, and psychological carrying capacity. The results indicated that the tourism carrying capacity of the Park was 4 145 - 6 450 persons per day. The rational distance between man and bird was first adopted to determine the ecotourism carrying capacity of wetland, which provided an effective solution both to fully ensure bird safety and to appropriately develop wetland tourism. The estimation of psychological carrying capacity based on tourist satisfaction degree reflected more objectively the extent the tourist demands satisfied at the planning, construction and management of tour places. Such an integrated estimation method based on the distance between man and bird and the tourist satisfaction degree could be of practical and instructive significances in the planning and management of wetland parks.

  9. Pentoxifylline regulates the cellular adhesion and its allied receptors to extracellular matrix components in breast cancer cells.

    Science.gov (United States)

    Goel, Peeyush N; Gude, Rajiv P

    2014-02-01

    Pentoxifylline (PTX) is a methylxanthine derivative that improves blood flow by decreasing its viscosity. Being an inhibitor of platelet aggregation, it can thus reduce the adhesiveness of cancer cells prolonging their circulation time. This delay in forming secondary tumours makes them more prone to immunological surveillance. Recently, we have evaluated its anti-metastatic efficacy against breast cancer, using MDA-MB-231 model system. In view of this, we had ascertained the effect of PTX on adhesion of MDA-MB-231 cells to extracellular matrix components (ECM) and its allied receptors such as the integrins. PTX affected adhesion of breast cancer cells to matrigel, collagen type IV, fibronectin and laminin in a dose dependent manner. Further, PTX showed a differential effect on integrin expression profile. The experimental metastasis model using NOD-SCID mice showed lesser tumour island formation when treated with PTX compared to the control. These findings further substantiate the anti-adhesive potential of PTX in breast cancer and warrant further insights into the functional regulation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  11. Maintenance of prolactin receptors in human breast cancer

    International Nuclear Information System (INIS)

    Ben-David, M.; Dror, Y.; Biran, S.

    1981-01-01

    Breast tissue specimens of 110 women with various stages of breast cancer were tested in vitro to determine their specific binding sites for human prolactin. In contrast to the case of steroid receptors, binding sites for prolactin were found in the vast majority of breast cancer tissue. Distribution profiles giving amount of prolactin receptor and their affinity coefficients were found to be similar in the tissues of women whose ages, hormonal status, or stage of breast cancer varied. These findings show that in contrast to steroid receptors, human breast cancer tissue maintains binding sites for prolactin. The findings also indicate that there may be a higher dependency of breast cancer on prolactin than on steroids. Clinical trials must be carried out to determine the role of ''positive'' prolactin receptors in prognosis and prediction of response to future hormone therapy. (author)

  12. Weapon carrying and psychopathic-like features in a population-based sample of Finnish adolescents.

    Science.gov (United States)

    Saukkonen, Suvi; Laajasalo, Taina; Jokela, Markus; Kivivuori, Janne; Salmi, Venla; Aronen, Eeva T

    2016-02-01

    We investigated the prevalence of juvenile weapon carrying and psychosocial and personality-related risk factors for carrying different types of weapons in a nationally representative, population-based sample of Finnish adolescents. Specifically, we aimed to investigate psychopathic-like personality features as a risk factor for weapon carrying. The participants were 15-16-year-old adolescents from the Finnish self-report delinquency study (n = 4855). Four different groups were formed based on self-reported weapon carrying: no weapon carrying, carrying knife, gun or other weapon. The associations between psychosocial factors, psychopathic-like features and weapon carrying were examined with multinomial logistic regression analysis. 9% of the participants had carried a weapon in the past 12 months. Adolescents with a history of delinquency, victimization and antisocial friends were more likely to carry weapons in general; however, delinquency and victimization were most strongly related to gun carrying, while perceived peer delinquency (antisocial friends) was most strongly related to carrying a knife. Better academic performance was associated with a reduced likelihood of carrying a gun and knife, while feeling secure correlated with a reduced likelihood of gun carrying only. Psychopathic-like features were related to a higher likelihood of weapon carrying, even after adjusting for other risk factors. The findings of the study suggest that adolescents carrying a weapon have a large cluster of problems in their lives, which may vary based on the type of weapon carried. Furthermore, psychopathic-like features strongly relate to a higher risk of carrying a weapon.

  13. Assays for calcitonin receptors

    International Nuclear Information System (INIS)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is 125 I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed

  14. Sdelki carry trade ne roskosh, a sredstvo nakoplenija / Darius Gecevicius, Dmitri Fokin

    Index Scriptorium Estoniae

    Gecevicius, Darius

    2007-01-01

    Strateegia carry trade kasutamisest valuutaturgudel. Carry trade on tehing, mis enamasti toimub valuutaturul, kus investor laenab raha sisse valuutas, mille intressid on madalamad ning paigutab selle valuutas, kus intressid on kõrgemad. Diagramm

  15. Human Factors Evaluation of the Modular Lightweight Load-Carrying Equipment (MOLLE) System

    National Research Council Canada - National Science Library

    Sampson, James

    2001-01-01

    .... The FEA was used in drafting a new user requirements document and initiating the development of a modular load-carrying system which ultimately became known as the Modular Lightweight Load-carrying Equipment (MOLLE...

  16. Biomechanical, Physiological, and Agility Performance of Soldiers Carrying Loads: A Comparison of the Modular Lightweight Load Carrying Equipment and a Lightning Packs, LLC, Prototype

    Science.gov (United States)

    2016-12-27

    angle, hip angle, and sagittal plane hip moments. In terms of energy harvesting and production during walking, the current weight penalty of carrying...MODULAR LIGHTWEIGHT LOAD CARRYING EQUIPMENT) HUMAN FACTORS ENGINEERING U.S. Army Natick Soldier Research, Development and Engineering Center ATTN...pack type and walking speed at a 0% grade. .......................................................35  vii Table 20: Means (SE) of the mean and

  17. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striki...

  18. 46 CFR 25.45-2 - Cooking systems on vessels carrying passengers for hire.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Cooking systems on vessels carrying passengers for hire... REQUIREMENTS Cooking, Heating, and Lighting Systems § 25.45-2 Cooking systems on vessels carrying passengers for hire. (a) No fuel may be used in any cooking system on any vessel carrying passengers for hire...

  19. 36 CFR 1005.4 - Commercial passenger-carrying motor vehicles.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Commercial passenger-carrying motor vehicles. 1005.4 Section 1005.4 Parks, Forests, and Public Property PRESIDIO TRUST COMMERCIAL AND PRIVATE OPERATIONS § 1005.4 Commercial passenger-carrying motor vehicles. Passenger-carrying motor...

  20. Integrin-mediated targeting of protein polymer nanoparticles carrying a cytostatic macrolide

    Science.gov (United States)

    Shi, Pu

    nanoparticulate drug delivery. To explore this approach, genetically engineered diblock copolymers were constructed from elastin-like polypeptides (ELPs) that assemble small nanoparticles. ELPs are protein polymers of the sequence (Val-Pro-Gly-Xaa-Gly)n, where the identity of Xaa and n determine their assembly properties. Initially, a screening assay for model drug encapsulation in ELP nanoparticles was developed, which showed that Rose Bengal and Rapa have high non-specific encapsulation in the core of ELP nanoparticles with a sequence where Xaa = Ile or Phe. While excellent at entrapping these drugs, their release was relatively fast compared to their intended mean residence time in the human body. Having determined that Rapa can be non-specifically entrapped in the core of ELP nanoparticles, FK506 binding protein 12 (FKBP), which is the cognate protein target of Rapa, was genetically fused to the surface of these nanoparticles (FSI) to enhance their avidity towards Rapa. The fusion of FKBP to these nanoparticles slowed the terminal half-life of drug release to 57.8 h. To determine if this class of drug carriers has potential applications in vivo, FSI/Rapa was administered to mice carrying a human breast cancer model (MDA-MB-468). Compared to free drug, FSI encapsulation significantly decreased gross toxicity and enhanced the anti-cancer activity. In conclusion, protein polymer nanoparticles decorated with the cognate receptor of a high potency, low solubility drug (Rapa) efficiently improved drug loading capacity and its release. This approach has applications to the delivery of Rapa and its analogs; furthermore, this strategy has broader applications in the encapsulation, targeting, and release of other potent small molecules. Elastin-like polypeptides (ELPs) are genetically encoded protein polymers that reversibly phase separate in response to stimuli. They respond sharply to small shifts in temperature and form dense microdomains in the living eukaryotic cytosol. This

  1. TLX: An elusive receptor.

    Science.gov (United States)

    Benod, Cindy; Villagomez, Rosa; Webb, Paul

    2016-03-01

    TLX (tailless receptor) is a member of the nuclear receptor superfamily and belongs to a class of nuclear receptors for which no endogenous or synthetic ligands have yet been identified. TLX is a promising therapeutic target in neurological disorders and brain tumors. Thus, regulatory ligands for TLX need to be identified to complete the validation of TLX as a useful target and would serve as chemical probes to pursue the study of this receptor in disease models. It has recently been proved that TLX is druggable. However, to identify potent and specific TLX ligands with desirable biological activity, a deeper understanding of where ligands bind, how they alter TLX conformation and of the mechanism by which TLX mediates the transcription of its target genes is needed. While TLX is in the process of escaping from orphanhood, future ligand design needs to progress in parallel with improved understanding of (i) the binding cavity or surfaces to target with small molecules on the TLX ligand binding domain and (ii) the nature of the TLX coregulators in particular cell and disease contexts. Both of these topics are discussed in this review. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  3. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown ...

  4. adrenergic receptor with preeclampsia

    African Journals Online (AJOL)

    User

    2011-05-09

    May 9, 2011 ... due to a post- receptor defect (Karadas et al., 2007). Several polymorphisms have ... the detection of the Arg16Gly polymorphism, overnight digestion at. 37°C with 10 U ..... DW, Wood AJ, Stein CM (2004). Beta2-adrenoceptor ...

  5. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  6. Introducing carrying capacity-based normalisation in LCA: framework and development of references at midpoint level

    DEFF Research Database (Denmark)

    Bjørn, Anders; Hauschild, Michael Zwicky

    2015-01-01

    carrying capacity-based normalisation references. The purpose of this article is to present a framework for normalisation against carrying capacity-based references and to develop average normalisation references (NR) for Europe and the world for all those midpoint impact categories commonly included....... A literature review was carried out to identify scientifically sound thresholds for each impact category. Carrying capacities were then calculated from these thresholds and expressed in metrics identical to midpoint indicators giving priority to those recommended by ILCD. NR was expressed as the carrying...... ozone formation and soil quality were found to exceed carrying capacities several times.The developed carrying capacity-based normalisation references offer relevant supplementary reference information to the currently applied references based on society’s background interventions by supporting...

  7. Olfactory Receptor Database: a sensory chemoreceptor resource

    OpenAIRE

    Skoufos, Emmanouil; Marenco, Luis; Nadkarni, Prakash M.; Miller, Perry L.; Shepherd, Gordon M.

    2000-01-01

    The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has bee...

  8. A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres.

    Science.gov (United States)

    Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

    2013-10-15

    Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nM and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres.

  9. Localization of P2X receptor subtypes 2, 3 and 7 in human urinary bladder.

    Science.gov (United States)

    Svennersten, Karl; Hallén-Grufman, Katarina; de Verdier, Petra J; Wiklund, N Peter; Poljakovic, Mirjana

    2015-08-08

    Voiding dysfunctions are a common problem that has a severe negative impact on the quality of life. Today there is a need for new drug targets for these conditions. The role of ATP receptors in bladder physiology has been studied for some time, primarily in animal models. The aim of this work is to investigate the localization of the ATP receptors P2X2, P2X3 and P2X7 and their colocalization with vimentin and actin in the human urinary bladder. Immunohistochemical analysis was conducted on full-thickness bladder tissues from fundus and trigonum collected from 15 patients undergoing open radical cystectomy due to chronic cystitis, bladder cancer or locally advanced prostate cancer. Colocalization analyses were performed between the three different P2X subtypes and the structural proteins vimentin and actin. Specimens were examined using epifluorescence microscopy and correlation coefficients were calculated for each costaining as well as the mean distance from the laminin positive basal side of the urothelium to the vimentin positive cells located in the suburothelium. P2X2 was expressed in vimentin positive cells located in the suburothelium. Less distinct labelling of P2X2 was also observed in actin positive smooth muscle cells and in the urothelium. P2X3 was expressed in vimentin positive cells surrounding the smooth muscle, and in vimentin positive cells located in the suburothelium. Weaker P2X3 labelling was seen in the urothelium. P2X7 was expressed in the smooth muscle cells and the urothelium. In the suburothelium, cells double positive for P2X2 and vimentin where located closer to the urothelium while cells double positive for P2X3 and vimentin where located further from the urothelium. The results from this study demonstrate that there is a significant difference in the expression of the purinergic P2X2, P2X3 and P2X7 receptors in the different histological layers of the human urinary bladder.

  10. The role of P2X receptors in bone biology.

    Science.gov (United States)

    Jørgensen, N R; Syberg, S; Ellegaard, M

    2015-01-01

    Bone is a highly dynamic organ, being constantly modeled and remodeled in order to adapt to the changing need throughout life. Bone turnover involves the coordinated actions of bone formation and bone degradation. Over the past decade great effort has been put into the examination of how P2X receptors regulate bone metabolism and especially for the P2X7 receptor an impressive amount of evidence has now documented its expression in osteoblasts, osteoclasts, and osteocytes as well as important functional roles in proliferation, differentiation, and function of the cells of bone. Key evidence has come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very recently a report from a genetic study in multiple myeloma demonstrated that decreased P2X7 receptor function was associated with increased risk of developing multiple myeloma. In contrast, the risk of developing myeloma bone disease and subsequent vertebral fractures was increased in subjects carrying P2X7 receptor gain-of-function alleles as compared to subjects only carrying loss-of-function or normal functioning alleles. It is evident that P2X receptors are important in regulating bone turnover and maintaining bone mass, and thereby holding great potential as novel drug targets for treatment of bone diseases. However, further research is needed before we fully understand the roles and effects of P2X receptors in bone.

  11. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  12. Systemic vascular phenotypes of Loeys-Dietz syndrome in a child carrying a de novo R381P mutation in TGFBR2: a case report

    OpenAIRE

    Uike, Kiyoshi; Matsushita, Yuki; Sakai, Yasunari; Togao, Osamu; Nagao, Michinobu; Ishizaki, Yoshito; Nagata, Hazumu; Yamamura, Kenichiro; Torisu, Hiroyuki; Hara, Toshiro

    2013-01-01

    Background Loeys?Dietz syndrome, also known as Marfan syndrome type II, is a rare connective tissue disorder caused by dominant mutations in transforming growth factor-beta receptors (TGFBR1 and 2). Case presentation We report a 7-year-old Japanese boy with Loeys?Dietz syndrome who carried a novel, de novo missense mutation in TGFBR2 (c.1142g?>?c, R381P). He showed dysmorphic faces and skeletal malformations that were typical in previous cases with Loeys-Dietz syndrome. The cardiac studies di...

  13. Structural Insights into Selective Ligand-Receptor Interactions Leading to Receptor Inactivation Utilizing Selective Melanocortin 3 Receptor Antagonists.

    Science.gov (United States)

    Cai, Minying; Marelli, Udaya Kiran; Mertz, Blake; Beck, Johannes G; Opperer, Florian; Rechenmacher, Florian; Kessler, Horst; Hruby, Victor J

    2017-08-15

    Systematic N-methylated derivatives of the melanocortin receptor ligand, SHU9119, lead to multiple binding and functional selectivity toward melanocortin receptors. However, the relationship between N-methylation-induced conformational changes in the peptide backbone and side chains and melanocortin receptor selectivity is still unknown. We conducted comprehensive conformational studies in solution of two selective antagonists of the third isoform of the melanocortin receptor (hMC3R), namely, Ac-Nle-c[Asp-NMe-His 6 -d-Nal(2') 7 -NMe-Arg 8 -Trp 9 -Lys]-NH 2 (15) and Ac-Nle-c[Asp-His 6 -d-Nal(2') 7 -NMe-Arg 8 -NMe-Trp 9 -NMe-Lys]-NH 2 (17). It is known that the pharmacophore (His 6 -DNal 7 -Arg 8 -Trp 9 ) of the SHU-9119 peptides occupies a β II-turn-like region with the turn centered about DNal 7 -Arg 8 . The analogues with hMC3R selectivity showed distinct differences in the spatial arrangement of the Trp 9 side chains. In addition to our NMR studies, we also carried out molecular-level interaction studies of these two peptides at the homology model of hMC3R. Earlier chimeric human melanocortin 3 receptor studies revealed insights regarding the binding and functional sites of hMC3R selectivity. Upon docking of peptides 15 and 17 to the binding pocket of hMC3R, it was revealed that Arg 8 and Trp 9 side chains are involved in a majority of the interactions with the receptor. While Arg 8 forms polar contacts with D154 and D158 of hMC3R, Trp 9 utilizes π-π stacking interactions with F295 and F298, located on the transmembrane domain of hMC3R. It is hypothesized that as the frequency of Trp 9 -hMC3R interactions decrease, antagonistic activity increases. The absence of any interactions of the N-methyl groups with hMC3R suggests that their primary function is to modulate backbone conformations of the ligands.

  14. Kinetic characteristics of the gait of a musician carrying or not his instrument

    Directory of Open Access Journals (Sweden)

    Carlos Bolli Mota

    2009-01-01

    Full Text Available The integrity of the locomotor system can be compromised by the transport of certain objects, especially when done in an inadequate manner. Due to their weight and size, the transport of musical instruments can contribute to body dysfunctions in musicians who frequently have to carry their instruments, influencing balance andbody posture. Thus, the soil reaction force was investigated during the gait of a musician carrying or not his instrument. Two AMTI (Advanced Mechanical Technologies, Inc. platforms were used for kinetic data acquisition. A total of 40 measurements were obtainedfor gait and balance: 20 without carrying the instrument and 20 while carrying the instrument. The t test showed significant differences between the two situations for all variables analyzed. The results suggest that the locomotor system suffers alterationswhen carrying any kind of load, as was the case here in which the subject carried 7.75% of his own weight.

  15. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  16. Rural Settlement Development and Environment Carrying Capacity Changes in Progo River Basin

    OpenAIRE

    Su Ritohardoyo; P Priyono

    2016-01-01

    Generally the broader rural settlement the heavier population pressure on agricultural land. It indicates that carrying capacity of the rural environment threatened lower. The spatial distribution of the threat in a river basin is quite important as one of the river basin management inputs. Therefore, this article aims at exposing result of research about influence rural population growth and rural settlement land changes to environment carrying capacity. This research was carried out in the ...

  17. Infant carrying methods: Correlates and associated musculoskeletal disorders among nursing mothers in Nigeria.

    Science.gov (United States)

    Ojukwu, Chidiebele Petronilla; Anyanwu, Godson Emeka; Anekwu, Emelie Morris; Chukwu, Sylvester Caesar; Fab-Agbo, Chukwubuikem

    2017-10-01

    Infant carrying is an integral part of the mothering occupation. Paucity of data exists on its correlates and associated musculoskeletal injuries. In this study, factors and musculoskeletal injuries associated with infant carrying were investigated in 227 nursing mothers, using a structured questionnaire. 77.1% utilised the back infant carrying methods (ICM). Maternal comfort was the major factor influencing participants' (37.4%) choices of ICMs. Infant's age (p = .000) and transportation means (p = .045) were significantly associated with ICMs. Low back pain (82.8%) and upper back pain (74.9%) were the most reported musculoskeletal discomforts associated with ICMs, especially among women who utilised back ICM. Back ICM is predominantly used by nursing mothers. Impact statement Infant carrying has been associated with increased energy cost and biomechanical changes. Currently, there is a paucity of data on infant carrying-related musculoskeletal injuries. In this study, investigating factors and musculoskeletal injuries associated with infant carrying, the results showed that back infant carrying method is predominantly used by nursing mothers. Age of the infant and mothers' means of transportation were determinant factors of infant carrying methods. Among the several reported infant carrying-related musculoskeletal disorders, low back and upper back pain were the most prevalent, especially among women who utilised the back infant carrying method. There is need for women's health specialists to introduce appropriate ergonomic training and interventions on infant carrying tasks in order to improve maternal musculoskeletal health during the childbearing years and beyond. Further experimental studies on the effects of various infant carrying methods on the musculoskeletal system are recommended.

  18. 46 CFR 35.25-15 - Carrying of excess steam-TB/ALL.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Carrying of excess steam-TB/ALL. 35.25-15 Section 35.25... § 35.25-15 Carrying of excess steam—TB/ALL. It shall be the duty of the chief engineer of any tank vessel to see that a steam pressure is not carried in excess of that allowed by the certificate of...

  19. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...... the world covering a wide spectrum from fundamental mechanistic studies to metabolism, clinical studies, and drug development. In this report, we summarize the recent and exciting findings presented by the speakers at the meeting....

  20. Neurotransmitter receptor imaging

    International Nuclear Information System (INIS)

    Cordes, M.; Hierholzer, J.; Nikolai-Beyer, K.

    1993-01-01

    The importance of neuroreceptor imaging in vivo using single photon emission tomography (SPECT) and positron emission tomography (PET) has increased enormously. The principal neurotransmitters, such as dopamine, GABA/benzodiazepine, acetylcholine, and serotonin, are presented with reference to anatomical, biochemical, and physiological features. The main radioligands for SPECT and PET are introduced, and methodological characteristics of both PET and SPECT presented. Finally, the results of neurotransmitter receptor imaging obtained so far will be discussed. (orig.) [de

  1. Thyroid Stimulating Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Murat Tuncel

    2017-02-01

    Full Text Available Thyroid stimulating hormone receptor (TSHR plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  2. Hepatic macrophage complement receptor clearance function following injury.

    Science.gov (United States)

    Cuddy, B G; Loegering, D J; Blumenstock, F A; Shah, D M

    1986-03-01

    Previous work has demonstrated that in vivo hepatic macrophage complement receptor clearance function is depressed following thermal injury. The present study was carried out to determine if complement receptor function depression is associated with other states of depressed host defense. Hepatic complement receptor clearance function was determined from the hepatic uptake of rat erythrocytes coated with antierythrocyte IgM (EIgM) in rats. Receptor function was determined following cannulation of a carotid artery, laparotomy plus enterotomy, hemorrhagic shock, trauma, thermal injury, acute bacteremia, acute endotoxemia, and injection of erythrocyte stroma, gelatinized lipid emulsion, or colloidal carbon. Hepatic uptake of EIgM was depressed following each of these experimental interventions except arterial cannulation. This effect was shown not to be due to a decrease in hepatic blood flow or depletion of complement and was therefore due to a depression in hepatic macrophage complement receptor clearance function. Thus, impairment of hepatic macrophage complement receptor function is associated with several states of depressed host defense.

  3. Specifying the Role of Exposure to Violence and Violent Behavior on Initiation of Gun Carrying: A Longitudinal Test of Three Models of Youth Gun Carrying

    Science.gov (United States)

    Spano, Richard; Pridemore, William Alex; Bolland, John

    2012-01-01

    Two waves of longitudinal data from 1,049 African American youth living in extreme poverty are used to examine the impact of exposure to violence (Time 1) and violent behavior (Time 1) on first time gun carrying (Time 2). Multivariate logistic regression results indicate that (a) violent behavior (Time 1) increased the likelihood of initiation of…

  4. Preliminary research on quantitative methods of water resources carrying capacity based on water resources balance sheet

    Science.gov (United States)

    Wang, Yanqiu; Huang, Xiaorong; Gao, Linyun; Guo, Biying; Ma, Kai

    2018-06-01

    Water resources are not only basic natural resources, but also strategic economic resources and ecological control factors. Water resources carrying capacity constrains the sustainable development of regional economy and society. Studies of water resources carrying capacity can provide helpful information about how the socioeconomic system is both supported and restrained by the water resources system. Based on the research of different scholars, major problems in the study of water resources carrying capacity were summarized as follows: the definition of water resources carrying capacity is not yet unified; the methods of carrying capacity quantification based on the definition of inconsistency are poor in operability; the current quantitative research methods of water resources carrying capacity did not fully reflect the principles of sustainable development; it is difficult to quantify the relationship among the water resources, economic society and ecological environment. Therefore, it is necessary to develop a better quantitative evaluation method to determine the regional water resources carrying capacity. This paper proposes a new approach to quantifying water resources carrying capacity (that is, through the compilation of the water resources balance sheet) to get a grasp of the regional water resources depletion and water environmental degradation (as well as regional water resources stock assets and liabilities), figure out the squeeze of socioeconomic activities on the environment, and discuss the quantitative calculation methods and technical route of water resources carrying capacity which are able to embody the substance of sustainable development.

  5. Review on the Evaluation System of Public Safety Carrying Capacity about Small Town Community

    Institute of Scientific and Technical Information of China (English)

    Ming; SUN; Tianyu; ZHU

    2014-01-01

    Recently,small town community public safety problem has been increasingly highlighted,but its research is short on public safety carrying capacity. Through the investigation and study of community public safety carrying capacity,this paper analyzes the problem of community public safety in our country,to construct index evaluation system of public safety carrying capacity in small town community. DEA method is used to evaluate public safety carrying capacity in small town community,to provide scientific basis for the design of support and standardization theory about small town community in public safety planning.

  6. New insights in the role of working memory in carry and borrow operations

    Directory of Open Access Journals (Sweden)

    Ineke Imbo

    2005-06-01

    Full Text Available The present paper provides a state-of-the-art overview concerning the role of working memory in carry and borrow operations in mental arithmetic. The role of the executive working-memory component is discussed, alongside the contribution of the phonological and visuo-spatial working-memory components. Moreover, a broad view on various carry characteristics (such as the number of carry/borrow operations and the value of the carry and various operations (addition, subtraction, and multiplication is provided. Finally, some ideas for further research are offered.

  7. Concept and Connotation of Water Resources Carrying Capacity in Water Ecological Civilization Construction

    Science.gov (United States)

    Chao, Zhilong; Song, Xiaoyu; Feng, Xianghua

    2018-01-01

    Water ecological civilization construction is based on the water resources carrying capacity, guided by the sustainable development concept, adhered to the human-water harmony thoughts. This paper has comprehensive analyzed the concept and characteristics of the carrying capacity of water resources in the water ecological civilization construction, and discussed the research methods and evaluation index system of water carrying capacity in the water ecological civilization construction, finally pointed out that the problems and solutions of water carrying capacity in the water ecological civilization construction and put forward the future research prospect.

  8. Characterization of the interleukin 3 receptor

    International Nuclear Information System (INIS)

    Murthy, S.C.; Mui, A.L.; Krystal, G.

    1990-01-01

    A variety of homobifunctional crosslinking agents have been used to gain insight into the nature of the murine interleukin 3 (mIL-3) receptor. When [125I]mIL-3 was cross-linked to receptor sites on the surfaces of intact B6SUtA1 cells with disuccinimidyl suberate (DSS), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed the existence of two radiolabeled species with molecular weights of 140 (p140) and 70 (p70) kd (after subtraction of [125I]mIL-3). The relative intensities of the two bands did not change when the [125I]mIL-3 concentration was varied, confirming Scatchard results which suggested only one affinity class. However, when [125I]mIL-3 was crosslinked to intact cells and then incubated at 37 degrees C, the intensity of p140 decreased relative to p70, suggesting a conversion of p140 to p70. This conversion could be inhibited by sodium azide, methylamine, and bacitracin and could also be prevented by first boiling for 1 min in 2% SDS and 5% 2-mercaptoethanol. The putative protease that carried out this apparent conversion appeared to be associated both with plasma membranes prepared from these cells and also with solubilized receptors. Moreover, when p140, crosslinked with both dithiobis succinimidylpropionate and glutaraldehyde, was purified and reelectrophoresed under reducing conditions, p70 could be generated. N-glycanase digestion of p140 and p70 revealed a similar level of N-linked carbohydrate, which upon closer study appeared to consist of two chains, a 3-kd and an 8-kd moiety. Consistent with this data, we propose that the receptor is a 140-kd glycoprotein that is cleaved to a 70-kd surface protein upon mIL-3 binding and chemical crosslinking

  9. Characterisation of the Redox Sensitive NMDA Receptor

    KAUST Repository

    Alzahrani, Ohood

    2016-05-01

    mutated NMDA NR1/NR2A C320A C87A receptor response that showed altered activity upon mutation up to the control level. Future experiments need to be carried out on different redox-sensitive residues of various NMDA receptor subunits to reveal the exact molecular mechanisms of L-lactate.

  10. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  11. Expression of extracellular matrix components and their receptors in the central nervous system during experimental Toxoplasma gondii and Trypanosoma cruzi infection

    Directory of Open Access Journals (Sweden)

    Silva A.A.

    1999-01-01

    Full Text Available Alterations in extracellular matrix (ECM expression in the central nervous system (CNS usually associated with inflammatory lesions have been described in several pathological situations including neuroblastoma and demyelinating diseases. The participation of fibronectin (FN and its receptor, the VLA-4 molecule, in the migration of inflammatory cells into the CNS has been proposed. In Trypanosoma cruzi infection encephalitis occurs during the acute phase, whereas in Toxoplasma infection encephalitis is a chronic persisting process. In immunocompromised individuals such as AIDS patients, T. cruzi or T. gondii infection can lead to severe CNS damage. At the moment, there are no data available regarding the molecules involved in the entrance of inflammatory cells into the CNS during parasitic encephalitis. Herein, we characterized the expression of the ECM components FN and laminin (LN and their receptors in the CNS of T. gondii- and T. cruzi-infected mice. An increased expression of FN and LN was detected in the meninges, leptomeninges, choroid plexus and basal lamina of blood vessels. A fine FN network was observed involving T. gondii-free and T. gondii-containing inflammatory infiltrates. Moreover, perivascular spaces presenting a FN-containing filamentous network filled with a4+ and a5+ cells were observed. Although an increased expression of LN was detected in the basal lamina of blood vessels, the CNS inflammatory cells were a6-negative. Taken together, our results suggest that FN and its receptors VLA-4 and VLA-5 might be involved in the entrance, migration and retention of inflammatory cells into the CNS during parasitic infections.

  12. 42 CFR 71.56 - African rodents and other animals that may carry the monkeypox virus.

    Science.gov (United States)

    2010-10-01

    ... the monkeypox virus. 71.56 Section 71.56 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND... and other animals that may carry the monkeypox virus. (a) What actions are prohibited? What animals... transmitting or carrying the monkeypox virus. Such products include, but are not limited to, fully taxidermied...

  13. Free vibrations of a multi-span Timoshenko beam carrying multiple ...

    Indian Academy of Sciences (India)

    natural frequency values and mode shapes for a beam carrying any number of spring masses. Naguleswaran (2002, 2003) obtained the natural frequency values of the beams on up to five resilient supports including ends and carrying several particles by using EBT and obtained a fourth-order determinant equated to zero.

  14. Form and Function of Carrying Tools in Traditional and Contemporary Culture

    Directory of Open Access Journals (Sweden)

    Hendriana Werdhaningsih

    2009-07-01

    Full Text Available The Javanese Traditional Carrying Tools are categorized into two kinds based used of materials: anyaman made of woven bamboo or rattan and the other was made of cloth. The Traditional Javanese Carrying Tools that were made of bamboo/ rattan is actually a kind of container with different shapes. The types of goods that were brought was related to the shapes of the containers, demonstrate the type of interactions between the carrier and the goods. The Traditional Carrying Tools made of cloth have the flexibility in terms of being the containers of the carried goods. Selendang is used to carry goods, including the bamboo/ rattan containers and to carry babies. It can be used rumpled and straightened depends on the technical needs of carrying tools preferred by the user. In contemporary culture, the form and design of carrying tools more less construct by fashion and trends besides those practical used. Some product are being 'classic', some other are being 'fad'. Both products, traditional and contemporary have their own style, uniqueness, and own context. Analyzing both in design point of view is important as evaluation process, to finding new problems that will be starting point to create new products. Indonesia is well known for its abundant richness in traditions, which include the culture, the art, and the traditional products. Such treasure of traditions can inspire the development and invention of various kinds of artwork and current products.

  15. 33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

    Science.gov (United States)

    2010-07-01

    ... Inspection endorsed to allow the NLS to be carried in that cargo tank, and if the ship engages in a foreign... unless the ship has a Certificate of Inspection endorsed to allow the NLS to be carried in that cargo... Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  16. Gun Cultures or Honor Cultures? Explaining Regional and Race Differences in Weapon Carrying

    Science.gov (United States)

    Felson, Richard B.; Pare, Paul-Philippe

    2010-01-01

    We use the National Violence against Women (and Men) Survey to examine the effects of region and race on the tendency to carry weapons for protection. We find that Southern and Western whites are much more likely than Northern whites to carry guns for self-protection, controlling for their risk of victimization. The difference between Southern and…

  17. Effect of Gun Carrying on Perceptions of Risk Among Adolescent Offenders.

    Science.gov (United States)

    Loughran, Thomas A; Reid, Joan A; Collins, Megan Eileen; Mulvey, Edward P

    2016-02-01

    We observed how perceptions of risks, costs, crime rewards, and violence exposure change as individual gun-carrying behavior changes among high-risk adolescents. We analyzed a longitudinal study (2000-2010) of serious juvenile offenders in Maricopa County, Arizona, or Philadelphia County, Pennsylvania, assessing within-person changes in risk and reward perceptions, and violence exposure as individuals initiated or ceased gun carrying. Despite being associated with heightened exposure to violence, gun carrying was linked to lower perceptions of risks and costs and higher perceived rewards of offending. Gun carrying was not time-stable, as certain individuals both started and stopped carrying during the study. Within-person changes in carrying guns were associated with shifting perceptions of risks, costs, and rewards of crime, and changes in exposure to violence in expected directions. Gun carrying reduces perceptions of risks associated with offending while increasing actual risk of violence exposure. This suggests that there is an important disconnect between perceptions and objective levels of safety among high-risk youths. Gun-carrying decisions may not only be influenced by factors of protection and self-defense, but also by perceptions of risks and reward associated with engaging in crime more generally.

  18. Carry A. Nation: "The Famous and Original Bar Room Smasher" Curriculum Packet.

    Science.gov (United States)

    Kansas State Historical Society, Topeka.

    Carry Nation's personality, religious beliefs, and marriages to Charles Gloyd and, after his death, to David Nation all formed her into the reformer for which she became known. Carry Nation was involved in a variety of reform causes including prohibition, anti-smoking, women's health, and suffrage. Her prohibition reform efforts took place after…

  19. Prediction of bird-day carrying capacity on a staging site: a test of depletion models

    NARCIS (Netherlands)

    Nolet, B.A.; Gyimesi, A.; Klaassen, R.H.G.

    2006-01-01

    1. The carrying capacity of a site for migratory water birds, expressed in bird-days, can be of particular conservation value. Several attempts have been made to model this carrying capacity using ideal free distribution models such as, for instance, depletion models, in which the distribution is

  20. Youths Carrying a Weapon or Using a Weapon in a Fight: What Makes the Difference?

    Science.gov (United States)

    Thurnherr, Judit; Michaud, Pierre-Andre; Berchtold, Andre; Akre, Christina; Suris, Joan-Carles

    2009-01-01

    The objective of this study was to characterize weapon-carrying adolescents and to assess whether weapon carriers differ from weapon users. Data were drawn from a cross-sectional school-based survey of 7548 adolescents aged 16-20 years in Switzerland. Youths carrying a weapon were compared with those who do not. Subsequently, weapon carriers were…

  1. Revisiting the carry-over effects of advertising in franchise industries

    OpenAIRE

    Park, Kwangmin; Jang, SooCheong (Shawn)

    2016-01-01

    Despite prior studies, little has been done to understand the advertising carry-over effect. The purpose of this study is to investigate the heterogeneous attributes of the carry-over effect by focusing on the differences between the franchise and the non-franchise firms. pp.785-800

  2. Adolescents Carrying Handguns and Taking Them to School: Psychosocial Correlates among Public School Students in Illinois.

    Science.gov (United States)

    Williams, Sunyna S.; Mulhall, Peter F.; Reis, Janet S.; DeVille, John O.

    2002-01-01

    Examines psychosocial correlates of adolescents carrying a handgun and taking a handgun to school. Survey participants were approximately 22,000 6th, 8th, and 10th grade public school students from Illinois. Results showed that the strongest correlates of handgun carrying behaviors were variables directly associated with handguns and violence,…

  3. 46 CFR 98.25-5 - How anhydrous ammonia may be carried.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false How anhydrous ammonia may be carried. 98.25-5 Section 98... Anhydrous Ammonia in Bulk § 98.25-5 How anhydrous ammonia may be carried. (a) Anhydrous ammonia shall be..., except as otherwise provided in paragraph (b) of this section. (b) When anhydrous ammonia is to be...

  4. Examining Adolescent Suicidal Behaviors in Relation to Gun Carrying and Bullying

    Science.gov (United States)

    Romero, Andrea; Bauman, Sheri; Ritter, Marissa; Anand, Payal

    2017-01-01

    Guided by the interpersonal theory of suicide, this study examines the associations between gun carrying, bullying, and suicidal behaviors among high school students. Arizona Youth Risk Behavior Surveys were completed by 2,677 students in 2011; 9.0% reported suicide attempt in the past year, 5.5% carried a gun in the past 30 days, 8.5% were…

  5. The qualification requirements for personnel carry out the testing for the pressure equipment materials

    International Nuclear Information System (INIS)

    Wojas, M.; Walczak, M.

    2006-01-01

    The article contains information about qualification requirements for personnel carry out the destructive and non-destructive testing for the pressure equipment materials based on the Directive 97/23/CE(PED). Competence laboratory carry out the testing. The responsibility lies with producer / employer. The producer / employer could elaborate the written practice procedure for qualification and certification testing personnel. (authors)

  6. 36 CFR 702.8 - Use and carrying of food and beverages in Library buildings.

    Science.gov (United States)

    2010-07-01

    ... CONDUCT ON LIBRARY PREMISES § 702.8 Use and carrying of food and beverages in Library buildings. Consumption of food and beverages in Library buildings is prohibited except at point of purchase or other authorized eating places. Under no circumstances may food or beverages be carried to the bookstacks or other...

  7. Isometric arm strength and subjective rating of upper limb fatigue in two-handed carrying tasks.

    Science.gov (United States)

    Li, Kai Way; Chiu, Wen-Sheng

    2015-01-01

    Sustained carrying could result in muscular fatigue of the upper limb. Ten male and ten female subjects were recruited for measurements of isometric arm strength before and during carrying a load for a period of 4 minutes. Two levels of load of carrying were tested for each of the male and female subjects. Exponential function based predictive equations for the isometric arm strength were established. The mean absolute deviations of these models in predicting the isometric arm strength were in the range of 3.24 to 17.34 N. Regression analyses between the subjective ratings of upper limb fatigue and force change index (FCI) for the carrying were also performed. The results indicated that the subjective rating of muscular fatigue may be estimated by multiplying the FCI with a constant. The FCI may, therefore, be adopted as an index to assess muscular fatigue for two-handed carrying tasks.

  8. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin

    2013-12-01

    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  9. Adenosine Receptors and Wound Healing

    Directory of Open Access Journals (Sweden)

    Bruce N. Cronstein

    2004-01-01

    Full Text Available Recent studies have demonstrated that application of topical adenosine A2A receptor agonists promotes more rapid wound closure and clinical studies are currently underway to determine the utility of topical A2A adenosine receptor agonists in the therapy of diabetic foot ulcers. The effects of adenosine A2A receptors on the cells and tissues of healing wounds have only recently been explored. We review here the known effects of adenosine A2A receptor occupancy on the cells involved in wound healing.

  10. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

    2001-01-01

    expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets.......A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...

  11. Adenosine receptor desensitization and trafficking.

    Science.gov (United States)

    Mundell, Stuart; Kelly, Eamonn

    2011-05-01

    As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Environmental sustainability control by water resources carrying capacity concept: application significance in Indonesia

    Science.gov (United States)

    Djuwansyah, M. R.

    2018-02-01

    This paper reviews the use of Water Resources carrying capacity concept to control environmental sustainability with the particular note for the case in Indonesia. Carrying capacity is a capability measure of an environment or an area to support human and the other lives as well as their activities in a sustainable manner. Recurrently water-related hazards and environmental problems indicate that the environments are exploited over its carrying capacity. Environmental carrying capacity (ECC) assessment includes Land and Water Carrying Capacity analysis of an area, suggested to always refer to the dimension of the related watershed as an incorporated hydrologic unit on the basis of resources availability estimation. Many countries use this measure to forecast the future sustainability of regional development based on water availability. Direct water Resource Carrying Capacity (WRCC) assessment involves population number determination together with their activities could be supported by available water, whereas indirect WRCC assessment comprises the analysis of supply-demand balance status of water. Water resource limits primarily environmental carrying capacity rather than the land resource since land capability constraints are easier. WRCC is a crucial factor known to control land and water resource utilization, particularly in a growing densely populated area. Even though capability of water resources is relatively perpetual, the utilization pattern of these resources may change by socio-economic and cultural technology level of the users, because of which WRCC should be evaluated periodically to maintain usage sustainability of water resource and environment.

  13. State Gun Law Environment and Youth Gun Carrying in the United States.

    Science.gov (United States)

    Xuan, Ziming; Hemenway, David

    2015-11-01

    Gun violence and injuries pose a substantial threat to children and youth in the United States. Existing evidence points to the need for interventions and policies for keeping guns out of the hands of children and youth. (1) To examine the association between state gun law environment and youth gun carrying in the United States, and (2) to determine whether adult gun ownership mediates this association. This was a repeated cross-sectional observational study design with 3 years of data on youth gun carrying from US states. The Youth Risk Behavior Survey comprises data of representative samples of students in grades 9 to 12 from biennial years of 2007, 2009, and 2011. We hypothesized that states with more restrictive gun laws have lower rates of youth gun carrying, and this association is mediated by adult gun ownership. State gun law environment as measured by state gun law score. Youth gun carrying was defined as having carried a gun on at least 1 day during the 30 days before the survey. In the fully adjusted model, a 10-point increase in the state gun law score, which represented a more restrictive gun law environment, was associated with a 9% decrease in the odds of youth gun carrying (adjusted odds ratio [AOR], 0.91 [95% CI, 0.86-0.96]). Adult gun ownership mediated the association between state gun law score and youth gun carrying (AOR, 0.94 [ 95% CI, 0.86-1.01], with 29% attenuation of the regression coefficient from -0.09 to -0.07 based on bootstrap resampling). More restrictive overall gun control policies are associated with a reduced likelihood of youth gun carrying. These findings are relevant to gun policy debates about the critical importance of strengthening overall gun law environment to prevent youth gun carrying.

  14. Physical and emotional health problems experienced by youth engaged in physical fighting and weapon carrying.

    Directory of Open Access Journals (Sweden)

    Sophie D Walsh

    Full Text Available Then aims of the current study were 1 to provide cross-national estimates of the prevalence of physical fighting and weapon carrying among adolescents aged 11-15 years; (2 To examine the possible effects of physical fighting and weapon carrying on the occurrence of physical (medically treated injuries and emotional health outcomes (multiple health complaints among adolescents within the theoretical framework of Problem Behaviour Theory. 20,125 adolescents aged 11-15 in five countries (Belgium, Israel, USA, Canada, FYR Macedonia were surveyed via the 2006 Health Behaviour in School Aged Children survey. Prevalence was calculated for physical fighting and weapon carrying along with physical and emotional measures that potentially result from violence. Regression analyses were used to quantify associations between violence/weapon carrying and the potential health consequences within each country. Large variations in fighting and weapon carrying were observed across countries. Boys reported more frequent episodes of fighting/weapon carrying and medically attended injuries in every country, while girls reported more emotional symptoms. Although there were some notable variations in findings between different participating countries, increased weapon carrying and physical fighting were both independently and consistently associated with more frequent reports of the potential health outcomes. Adolescents engaging in fighting and weapon carrying are also at risk for physical and emotional health outcomes. Involvement in fighting and weapon carrying can be seen as part of a constellation of risk behaviours with obvious health implications. Our findings also highlight the importance of the cultural context when examining the nature of violent behaviour for adolescents.

  15. Glove powder's carrying capacity for latex protein: analysis using the ASTM ELISA test.

    Science.gov (United States)

    Beezhold, D; Horton, K; Hickey, V; Daddona, J; Kostyal, D

    2003-01-01

    Glove donning powders carry latex proteins and disperse them into the workplace environment. We have used the ASTM D6499 ELISA to quantify the amount of latex antigen bound to and carried by glove powders. We could differentiate between a small amount of protein actually bound to the powders and a larger amount carried by the powder. Enhanced binding of a major allergen, Hev b 5, to the starch powders was demonstrated by Western blot. The D6499 ELISA is able to measure total latex antigen, soluble and powder bound, simultaneously without the need to centrifuge the samples.

  16. On-line measurements of liquid carry-over from scrubbers using radioactive tracers

    Energy Technology Data Exchange (ETDEWEB)

    Haugan, A; Hassfjell, S [Institute for Energy Technology, Kjeller (Norway); Finborud, A [Mator, Porsgrunn (Norway)

    2004-07-01

    A method to measure liquid carry-over from scrubbers using gamma-emitting tracers is described and results from field tests at two onshore installations are presented. One water/1,2-ethanediol (MEG) and two hydrocarbon liquid (condensate) tracers have been used in the tests. One of the condensate tracers deposited to some extent inside the process pipe, while the other had a too high vapor pressure. The water/MEG tracer showed no MEG carry-over while the carry-over of MEG was documented to be considerable. (author)

  17. On-line measurements of liquid carry-over from scrubbers using radioactive tracers

    International Nuclear Information System (INIS)

    Haugan, A.; Hassfjell, S.; Finborud, A.

    2004-01-01

    A method to measure liquid carry-over from scrubbers using gamma-emitting tracers is described and results from field tests at two onshore installations are presented. One water/1,2-ethanediol (MEG) and two hydrocarbon liquid (condensate) tracers have been used in the tests. One of the condensate tracers deposited to some extent inside the process pipe, while the other had a too high vapor pressure. The water/MEG tracer showed no MEG carry-over while the carry-over of MEG was documented to be considerable. (author)

  18. Impact of Flexibility Options on Grid Economic Carrying Capacity of Solar and Wind: Three Case Studies

    Energy Technology Data Exchange (ETDEWEB)

    Denholm, Paul [National Renewable Energy Lab. (NREL), Golden, CO (United States); Novacheck, Joshua [National Renewable Energy Lab. (NREL), Golden, CO (United States); Jorgenson, Jennie [National Renewable Energy Lab. (NREL), Golden, CO (United States); O' Connell, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-12-01

    In this study, we attempt to quantify the benefits of various options of grid flexibility by measuring their impact on two measures: economic carrying capacity and system costs. Flexibility can increase economic carrying capacity and reduce overall system costs. In some cases, options that provide a limited increase in economic carrying capacity can provide significant operational savings, thus demonstrating the need to evaluate flexibility options using multiple metrics. The value of flexibility options varies regionally due to different generation mixes and types of renewables. The more rapid decline in PV value compared to wind makes PV more dependent on adding flexibility options, including transmission and energy storage.

  19. Quantifying spatially derived carrying capacity occupation: Framework for characterisation modelling and application to terrestrial acidification

    DEFF Research Database (Denmark)

    Bjørn, Anders; Margni, M.; Bulle, C.

    *year. This metric resembles that of the ecological footprint method and may be compared to the availability of land or water. The framework was applied to the terrestrial acidification impact category. The geochemical steady-state model PROFILE was used to quantify carrying capacities as deposition levels......The popularity of the ecological footprint method and the planetary boundaries concept shows an increasing interest among decision makers in comparing environmental impacts to carrying capacities of natural systems. Recently carrying capacity-based normalisation references were developed for impact...

  20. Axonal GABAA receptors.

    Science.gov (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M

    2008-09-01

    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

  1. Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

    Directory of Open Access Journals (Sweden)

    Luigi F. Agnati

    2007-01-01

    Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

  2. Receptor studies in biological psychiatry

    International Nuclear Information System (INIS)

    Fujiwara, Yutaka

    1992-01-01

    Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

  3. Correlates of Weapon Carrying in School among Adolescents in Three Countries

    Czech Academy of Sciences Publication Activity Database

    Stickley, A.; Koyanagi, A.; Koposov, R.; Blatný, Marek; Hrdlička, M.; Schwab-Stone, M.; Ruchkin, V.

    2015-01-01

    Roč. 39, č. 1 (2015), s. 99-108 ISSN 1945-7359 Institutional support: RVO:68081740 Keywords : adolescent * Czech Republic * Russia * United States * weapon carrying Subject RIV: AN - Psychology Impact factor: 1.270, year: 2015

  4. Information technologies in carrying out monitoring comparisons of pedagogical higher education institutions

    Directory of Open Access Journals (Sweden)

    Вадим Валерьевич Гриншкун

    2014-12-01

    Full Text Available In article various approaches to use of information technologies when carrying out monitoring researches of higher educational institutions are described. Results of researches are considered on the example of indicators of pedagogical university.

  5. 46 CFR 167.60-15 - Manning and persons allowed to be carried.

    Science.gov (United States)

    2010-10-01

    ... PUBLIC NAUTICAL SCHOOL SHIPS Certificates of Inspection § 167.60-15 Manning and persons allowed to be carried. The Officer in Charge, Marine Inspection, shall specify in the Certificate of Inspection the...

  6. Temperature dependences of growth rates and carrying capacities of marine bacteria depart from metabolic theoretical predictions

    KAUST Repository

    Huete-Stauffer, Tamara Megan; Arandia-Gorostidi, Nestor; Dí az-Pé rez, Laura; Moran, Xose Anxelu G.

    2015-01-01

    Using the metabolic theory of ecology (MTE) framework, we evaluated over a whole annual cycle the monthly responses to temperature of the growth rates (μ) and carrying capacities (K) of heterotrophic bacterioplankton at a temperate coastal site. We

  7. Geometry of carrying simplices of 3-species competitive Lotka–Volterra systems

    International Nuclear Information System (INIS)

    Baigent, Stephen

    2013-01-01

    We investigate the existence, uniqueness and Gaussian curvature of the invariant carrying simplices of 3 species autonomous totally competitive Lotka–Volterra systems. Explicit examples are given where the carrying simplex is convex or concave, but also where the curvature is not single-signed. Our method monitors the curvature of an evolving surface that converges uniformly to the carrying simplex, and generally relies on establishing that the Gaussian image of the evolving surface is confined to an invariant cone. We also discuss the relationship between the curvature of the carrying simplex near an interior fixed point and its Split Lyapunov stability. Finally we comment on extensions to general Lotka–Volterra systems that are not competitive. (paper)

  8. Carrying capacities for nature parks as engines for sustainable regional development

    DEFF Research Database (Denmark)

    Brandt, Jesper; Holmes, Esbern

    as a departure for the comparison of the protectional conditions for the parks. Many other aspects of the nature and social carrying capacities however also constitute important conditions for the park management. Increasing emphasis on visitor experience is not only a challenge for the nature protection......Growth in the number of visitors is an upcoming problem in nature parks. Nature parks are at the same time facing increasing demand, falling public appropriations and receding focus on their conservation functions. To ensure a balancing of nature protection and economic utilization the concept...... of carrying capacity has received increasing attention among park-authorities all over the world. A comparative analysis of conditions and initiatives related to visitor/nature carrying capacities in 8 nature parks in the Baltic region has been carried out. All the parks are candidates for recognition...

  9. Carrying Capacity Model Applied to Coastal Ecotourism of Baluran National Park, Indonesia

    Science.gov (United States)

    Armono, H. D.; Rosyid, D. M.; Nuzula, N. I.

    2017-07-01

    The resources of Baluran National Park have been used for marine and coastal ecotourism. The increasing number of visitors has led to the increasing of tourists and its related activities. This condition will cause the degradation of resources and the welfare of local communities. This research aims to determine the sustainability of coastal ecotourism management by calculating the effective number of tourists who can be accepted. The study uses the concept of tourism carrying capacity, consists the ecological environment, economic, social and physical carrying capacity. The results of the combined carrying capacity analysis in Baluran National Park ecotourism shows that the number of 3.288 people per day (151.248 tourists per year) is the maximum number of accepted tourists. The current number of tourist arrivals is only 241 people per day (87.990 tourists per year) which is far below the carrying capacity.

  10. Modifications carried out in Heavy Water Plant, Tuticorin for maximising productivity (Paper No. 1.6)

    International Nuclear Information System (INIS)

    Periakaruppan, M.; Sunderesan, S.; Chellapandi, D.

    1992-01-01

    Many modifications have been carried out in Heavy Water Plant, Tuticorin, after commissioning of the plant in July 1978. During the initial 4/5 years many teething problems were faced and they have been tackled effectively with suitable modifications which resulted in sustained production from the year 1984 onwards. In this paper some modifications carried out and changes in operational procedures adopted which resulted in achieving sustained production year after year since 1984 are described. (author)

  11. Review of the Main Activities Carried out by the CSN in the Last Five Years

    International Nuclear Information System (INIS)

    2006-01-01

    Nearing the time to finalise a new phase for the Consejo de Seguridad Nuclear, it is time to make a brief account of the main activities carried out over the past five years. During this period, one in which the CSN celebrated its 25th Anniversary, the organisation has served a social demand in a modernisation and adjustment process, followed by the continuous improvement process which throughout its history the former management, teams have carried out with great stamina and dedication. (Author)

  12. Carry-Over Effects on the Annual Cycle of a Migratory Seabird: an Experimental Study

    OpenAIRE

    Fayet, Annette; Freeman, R; Shoji, A; Kirk, HL; Padget, O; Perrins, CM; Guilford, T

    2016-01-01

    1. Long-lived migratory animals must balance the cost of current reproduction with their own condition ahead of a challenging migration and future reproduction. In these species, carry-over effects, which occur when events in one season affect the outcome of the subsequent season, may be particularly exacerbated. However, how carry-over effects influence future breeding outcomes and whether (and how) they also affect behaviour during migration and wintering is unclear. 2. Here we inve...

  13. Works carried out in the south of Cerro Largo district. Uranium prospection programme. Preliminary report

    International Nuclear Information System (INIS)

    Goso, H.

    1978-01-01

    During the carried out work of radimetric preliminary Investigation in the northeast of the uraniferous country were detected radimetric anonalias which are associated to the formation San Gregorio and Tres Islas. Later the works of prospection ratified those anomalies to which they defined in the environs other anomalies. The studies of revision of these conducted anomalies they took to conclude the necessity to carry out a detailed study of the area to that district was denominated Cerro Largo Sur

  14. Reproductive and life cycle strategies in egg-carrying cyclopoid and free-spawning calanoid copepods

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Sabatini, Marian

    1994-01-01

    Egg-carrying cyclopoid copepods have lower fecundity and feeding rates, and longer egg hatching times, than free-spawning calanoid copepods. Simple demographic considerations suggest that the lower feeding and fecundity of egg-carrying cyclopoids are adaptations to the potentially elevated...... mortality of ovigerous females, while the shorter egg hatching time and higher feeding and fecundity rates found in free-spawning calanoid copepods represent adaptations to the very high mortality rates experienced by suspended eggs....

  15. Carrying capacity of Peucang Island for ecotourism management in Ujung Kulon National Park

    Science.gov (United States)

    Wiyono, K. H.; Muntasib, E. K. S. H.; Yulianda, F.

    2018-05-01

    Peucang Island is one of island in Ujung Kulon National Park (UKNP), appointed as priority area and welcome area for tourism. This research aimed to calculate the carrying capacity of Peucang Island for ecotourism development (Study sites of this research are Karang Copong jungle trail and 8 sites of Peucangs beach). This research used observation method (wildlife exploration, measure the lenght of jungle track, and measure 10 parameters of beach), literature study and and interview method to collect data. The data of jungle track analyzed use Cifuentes’s formula. The result showed that Karang Copong jungle trekking had 20,000 visitors/day for Physical Carrying Capacity (PCC), 4 838 visitors/day for Real Carrying Capacity (RCC), and 6 visitors/day for Efective Carrying Capacity (ECC). Observation of biological aspect showed that there were some damages of vegetation along the track, and the changes in animal behavior. The data of beach carrying capacity analyzed use Yulianda’s formula that measured with the suitability map approach. Based on the suitability map, two beaches were classified in suitable category, while six beaches) were classified in highly suitable category for tourism activities. All of the beaches had different number of carrying capacity, specifically there are 70 visitors/day in highly suitable beach and 27 visitors/day in suitable beach. The number of visitor nowadays still not exceed from carrying capacity number of PCC, RCC of jungle trails and carrying capacity of the beach area, but the number has exceeded from the ECC numbers.

  16. An apparatus for separating and continuously recovering a particulate material carried by a gas stream

    International Nuclear Information System (INIS)

    Becker, W.R.; Dada, A.G.; Dehollander, W.R.; Sloat, R.J.

    1974-01-01

    Description is given of an apparatus adapted to separate and recover a particulate material carried by hot corrosive gases. The apparatus comprises a flow-channel connected to a gas stream source carrying a particulate material, a first and second tubes connected to said flow-channel, filtrating devices, recovery containers and flow-restricting valves. This can be applied to the recovery of uranium oxides generated by flame reactions [fr

  17. Quadruped robots for nuclear facilities. Development of cooperative carrying and unloading functions

    International Nuclear Information System (INIS)

    2016-01-01

    As the Fukushima Daiichi Nuclear Power Station (hereafter refers to as 1F) became the high dose environment by the Great East Japan Earthquake, remotely operated robots were required in order to reduce workers' radiation exposure. We developed a quadruped robot to walk the stairs and narrow passages with carrying burdens such as investigation tools. This robot investigated water leakage from vent pipes at underground of 1F unit 2. There are various works towards the decommissioning such as measuring doses of radiation, cutting pipes, connecting wires and more. It is desirable to carry various work tools and to unload them at destinations with remotely operated robots. To this end, we have developed carrying and unloading functions of the robot. In addition, we have developed cooperative carrying functions that two quadruped robots carry and unload a burden which is too long or heavy for individual robot. As a result, it was realized that two robots carried the pipe of 48 kg while getting over a step of 100 mm and unloading it at a destination. (author)

  18. Sensitivity of the speed evaluation tests of carrying the ball in youth soccer players

    Directory of Open Access Journals (Sweden)

    Rakojević Bojan

    2016-01-01

    Full Text Available This research is aimed at examining sensitivity of the speed evaluation tests while carrying the ball. The research included 76 male examinees, aged 17 years (+/- 6 months, who were divided into two qualitatively different subgroups. For determining the speed while carrying the ball, the tests of M type of carrying the ball between cones and slalom ball carrying with a pass were performed. The obtained results proved that the examinees from the group of more successful soccer players (Group 1 scored better on the applied tests when compared to the results of the group consisting of the soccer players from lower ranked clubs and who are not national team members (Group 2. High values of the result homogeneity in the two groups (for the Groups 1 and 2 it was 75% and 68.75% respectively lead to the conclusion that this ability is essential characteristics of young soccer players. The coefficient of discrimination of 0.269 for the results of M type test and 0.197 for the results of the test of carrying the ball with a pass indicate that the results of the two tests provide possibility to qualitatively distinguish youth players. Therefore, it can be concluded that as a technical element, carrying the ball significantly affects the quality of players' performance.

  19. [Knowledge, attitudes, and practices about Carrión's disease in rural Ancash, Peru].

    Science.gov (United States)

    Llerena Luna, Carolina; Schweig Groisman, Maggie; Ugarte-Gil, César Augusto

    2013-05-01

    To assess knowledge, attitudes, and practices about Carrión's disease (bartonellosis) in rural communities with a history of epidemic outbreaks. A cross-sectional survey study was conducted in the communities of Huaripampa, Orcosh, and Opayaco (Ancash, Peru) in July 2010, to assess knowledge, attitudes, and practices about Carrión's disease. Interviewees were aged >18 years and had resided in the community for at least one year. A total of 276 residents were surveyed; 36.6% were men, and 72.5% had not heard of Carrión's disease. Of those familiar with it, most (38.7%) said that it spreads through bites, and 26% did not know how it spreads. Regarding actions to take if Carrión's disease develops, 69.3% of respondents said they would go to a health center and over half reported having recommended preventive practices to relatives or acquaintances in the past. Even though these three communities have a history of Carrión's disease, their inhabitants did not demonstrate adequate knowledge, attitudes, or practices for preventing it. In view of this, and given that this illness has cyclical outbreaks, it is imperative to design and implement a program to educate residents of these communities-focusing on the role of habits and customs-about how to prevent Carrión's disease, as well as the region's other main endemic diseases.

  20. Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

    Directory of Open Access Journals (Sweden)

    A. Beaudet

    1998-11-01

    Full Text Available This paper reviews the use of confocal microscopy as it pertains to the identification of G-protein coupled receptors and the study of their dynamic properties in cell cultures and in mammalian brain following their tagging with specific fluorescent ligands. Principles that should guide the choice of suitable ligands and fluorophores are discussed. Examples are provided from the work carried out in the authors' laboratory using custom synthetized fluoresceinylated or BODIPY-tagged bioactive peptides. The results show that confocal microscopic detection of specifically bound fluorescent ligands permits high resolution appraisal of neuropeptide receptor distribution both in cell culture and in brain sections. Within the framework of time course experiments, it also allows for a dynamic assessment of the internalization and subsequent intracellular trafficking of bound fluorescent molecules. Thus, it was found that neurotensin, somatostatin and mu- and delta-selective opioid peptides are internalized in a receptor-dependent fashion and according to receptor-specific patterns into their target cells. In the case of neurotensin, this internalization process was found to be clathrin-mediated, to proceed through classical endosomal pathways and, in neurons, to result in a mobilization of newly formed endosomes from neural processes to nerve cell bodies and from the periphery of cell bodies towards the perinuclear zone. These mechanisms are likely to play an important role for ligand inactivation, receptor regulation and perhaps also transmembrane signaling.

  1. Quantitative analysis of receptor imaging

    International Nuclear Information System (INIS)

    Fu Zhanli; Wang Rongfu

    2004-01-01

    Model-based methods for quantitative analysis of receptor imaging, including kinetic, graphical and equilibrium methods, are introduced in detail. Some technical problem facing quantitative analysis of receptor imaging, such as the correction for in vivo metabolism of the tracer and the radioactivity contribution from blood volume within ROI, and the estimation of the nondisplaceable ligand concentration, is also reviewed briefly

  2. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.

    2015-01-01

    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  3. Neurobeachin regulates neurotransmitter receptor trafficking to synapses

    NARCIS (Netherlands)

    Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

    2013-01-01

    The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

  4. A Novel Mechanism of Androgen Receptor Action

    National Research Council Canada - National Science Library

    Roberts, Jr, Charles T

    2006-01-01

    .... Specifically, the authors had determined that the androgen receptor controls the expression of the cell-surface receptor for the hormone IGF-1 at the level of translation of the IGF-1 receptor mRNA...

  5. Quantitative densitometry of neurotransmitter receptors

    International Nuclear Information System (INIS)

    Rainbow, T.C.; Bleisch, W.V.; Biegon, A.; McEwen, B.S.

    1982-01-01

    An autoradiographic procedure is described that allows the quantitative measurement of neurotransmitter receptors by optical density readings. Frozen brain sections are labeled in vitro with [ 3 H]ligands under conditions that maximize specific binding to neurotransmitter receptors. The labeled sections are then placed against the 3 H-sensitive LKB Ultrofilm to produce the autoradiograms. These autoradiograms resemble those produced by [ 14 C]deoxyglucose autoradiography and are suitable for quantitative analysis with a densitometer. Muscarinic cholinergic receptors in rat and zebra finch brain and 5-HT receptors in rat brain were visualized by this method. When the proper combination of ligand concentration and exposure time are used, the method provides quantitative information about the amount and affinity of neurotransmitter receptors in brain sections. This was established by comparisons of densitometric readings with parallel measurements made by scintillation counting of sections. (Auth.)

  6. Dopamine Receptors and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS. In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.

  7. Inhibition of cAMP-Dependent PKA Activates β2-Adrenergic Receptor Stimulation of Cytosolic Phospholipase A2 via Raf-1/MEK/ERK and IP3-Dependent Ca2+ Signaling in Atrial Myocytes.

    Science.gov (United States)

    Pabbidi, M R; Ji, X; Maxwell, J T; Mignery, G A; Samarel, A M; Lipsius, S L

    2016-01-01

    We previously reported in atrial myocytes that inhibition of cAMP-dependent protein kinase (PKA) by laminin (LMN)-integrin signaling activates β2-adrenergic receptor (β2-AR) stimulation of cytosolic phospholipase A2 (cPLA2). The present study sought to determine the signaling mechanisms by which inhibition of PKA activates β2-AR stimulation of cPLA2. We therefore determined the effects of zinterol (0.1 μM; zint-β2-AR) to stimulate ICa,L in atrial myocytes in the absence (+PKA) and presence (-PKA) of the PKA inhibitor (1 μM) KT5720 and compared these results with atrial myocytes attached to laminin (+LMN). Inhibition of Raf-1 (10 μM GW5074), phospholipase C (PLC; 0.5 μM edelfosine), PKC (4 μM chelerythrine) or IP3 receptor (IP3R) signaling (2 μM 2-APB) significantly inhibited zint-β2-AR stimulation of ICa,L in-PKA but not +PKA myocytes. Western blots showed that zint-β2-AR stimulation increased ERK1/2 phosphorylation in-PKA compared to +PKA myocytes. Adenoviral (Adv) expression of dominant negative (dn) -PKCα, dn-Raf-1 or an IP3 affinity trap, each inhibited zint-β2-AR stimulation of ICa,L in + LMN myocytes compared to control +LMN myocytes infected with Adv-βgal. In +LMN myocytes, zint-β2-AR stimulation of ICa,L was enhanced by adenoviral overexpression of wild-type cPLA2 and inhibited by double dn-cPLA2S505A/S515A mutant compared to control +LMN myocytes infected with Adv-βgal. In-PKA myocytes depletion of intracellular Ca2+ stores by 5 μM thapsigargin failed to inhibit zint-β2-AR stimulation of ICa,L via cPLA2. However, disruption of caveolae formation by 10 mM methyl-β-cyclodextrin inhibited zint-β2-AR stimulation of ICa,L in-PKA myocytes significantly more than in +PKA myocytes. We conclude that inhibition of PKA removes inhibition of Raf-1 and thereby allows β2-AR stimulation to act via PKCα/Raf-1/MEK/ERK1/2 and IP3-mediated Ca2+ signaling to stimulate cPLA2 signaling within caveolae. These findings may be relevant to the remodeling of

  8. Ghrelin receptor mutations--too little height and too much hunger

    DEFF Research Database (Denmark)

    Holst, Birgitte; Schwartz, Thue W

    2006-01-01

    The ghrelin receptor is known from in vitro studies to signal in the absence of the hormone ghrelin at almost 50% of its maximal capacity. But, as for many other 7-transmembrane receptors, the in vivo importance of this ligand-independent signaling has remained unclear. In this issue of the JCI......, Pantel et al. find that a natural mutation in the ghrelin receptor, Ala204Glu, which is associated with a selective loss of constitutive activity without affecting ghrelin affinity, potency, or efficacy, segregates in 2 families with the development of short stature (see the related article beginning...... on page 760). By combination of the observations from this study with those related to the phenotype of subjects carrying another natural ghrelin receptor mutation, Phe279Leu, having identical molecular-pharmacological properties, it is proposed that selective lack of ghrelin receptor constitutive...

  9. Estimation of carrying angle based on CT images in preoperative surgical planning for cubitus deformities

    International Nuclear Information System (INIS)

    Park, Shinsuk; Kim, Eugene

    2009-01-01

    Conventionally, the carrying angle of the elbow is measured using simple two-dimensional radiography or goniometry, which has questionable reliability. This study proposes a novel method for estimating carrying angles using computed tomography that can enhance the reliability of the angle measurement. Data of CT scans from 25 elbow joints were processed to build segmented three-dimensional models. The cross-sectional centerlines of the ulna and the humerus were traced from the 3D models, and the angle between 2 vectors formed from the centerlines of the humerus and the ulna was defined as the 'three-dimensional carrying angle.' These angles were compared with those measured by simple radiograph. Two cases of angular deformity were underwent surgery based on this preoperative surgical planning, and the postoperative 3D carrying angles were evaluated using the proposed method. The mean value of the calculated three-dimensional carrying angle was 20.7deg±3.61, while it was 16.3deg±3.21 based on simple radiography without statistical difference. Based on the 3D carrying angle estimations, 2 surgical cases of cubitus deformities were planned by comparison with the normal contra-lateral elbow. Postoperative angle estimations confirmed that the corrected angles were nearly identical to the planned angles for both cases. The results of this study showed that the carrying angle can be accurately estimated using three-dimensional CT and that the proposed method is useful in evaluating deformities of the elbow with high reliability. (author)

  10. Molecular characterization of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, A.D.

    1986-01-01

    The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

  11. Introductory statement: Of receptors and analogs in renin-angiotensin-aldosterone and adrenergic systems

    International Nuclear Information System (INIS)

    Eliahou, H.E.; Iaina, A.

    1980-01-01

    This article reports on the role of the octapeptides angiotensin II (A II)-effector and its receptor on hypertensive patients and in animal experiments. By applying the A-II-receptor blockers, vasodilates drugs, β-receptor blockers and by sodium depletion, the behaviour of the blood pressure, the plasmareninactivity, and of the aldosteron were investigated; a comparative investigation between the A II and A III effectors was also carried out. The iodo-hippurate uptake was reduced with an artificially produced renal arterial ischemia. In general, this investigation provided new viewpoints in the understanding of the possible pathogenetic mechanism of essential hypertonism. (APR) [de

  12. Occurrence of Enterobacter hormaechei carrying blaNDM-1 and blaKPC-2 in China.

    Science.gov (United States)

    Yang, Biwei; Feng, Yu; McNally, Alan; Zong, Zhiyong

    2018-02-01

    Three carbapenem-resistant clinical isolates of the Enterobacter cloacae complex (ECC) were recovered from different patients in a hospital. All 3 isolates carried 2 carbapenemase genes bla KPC-2 and bla NDM-1 . A study was performed to characterize their relatedness and to investigate possible links among the patients. Whole genome sequencing revealed that the isolates were Enterobacter hormaechei and belonged to ST177 of the ECC. There were 19-142 single nucleotide polymorphisms (SNPs) between the isolates, suggesting that the isolates were likely from a central reservoir, which might have existed for some time. bla KPC-2 and bla NDM-1 were carried on 2 different IncF-type plasmids in the isolates. The 3 bla NDM-1 -carrying plasmids were almost identical and were self-transmissible, while the bla KPC-2 -carrying plasmids were only transmissible in the presence of the bla NDM-1 -carrying plasmid. The source of and direct links among them were not identified, suggesting a hospital transmission of a common multidrug resistant strain. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Analysis of Environmental Carrying Capacity with Emergy Perspective of Jeju Island

    Directory of Open Access Journals (Sweden)

    Chanhoon Jung

    2018-05-01

    Full Text Available Jeju Island experienced an approximately 42% increase in energy consumption from 2006 to 2015 and the demand for energy consumption is expected to continue to increase. Thus, Jeju Island is planning a project entitled “Carbon Free Island by 2030” to promote sustainable development and is required to estimate the environmental carrying capacity for future energy demand changes. The purpose of this study was to calculate the emergy inherent in Jeju Island’s energy, materials, and information in 2015 using the emergy analysis method and local characteristics. In addition, this study aimed to estimate the emergy indices to evaluate the environmental carrying capacity for sustainable development in 2005, 2015, and 2030 considering the future energy demand. This study’s outputs provide the environmental carrying capacity with emergy indices, such as the percent renewable (%Renew, emergy yield ratio (EYR, environmental loading ratio (ELR, sustainability index (SI, and carrying capacity of the population (CCP for social and economic activities on Jeju Island, which are expected to be saturated. These findings show regions with heavy tourism require development strategies, including the concept of environmental carrying capacity.

  14. Firearm carrying and concurrent substance use behaviours in a community-based sample of emerging adults.

    Science.gov (United States)

    Buschmann, Robert N; Prochaska, John D; Baillargeon, Jacques G; Temple, Jeff R

    2017-12-01

    This paper examines associations between high-risk gun carrying and substance use in emerging adults (ages 18-22). The coexistence of these high-risk behaviours in a general population of emerging adults can have disastrous consequences. Dating it Safe is an ongoing longitudinal (2010-2016) survey of emerging adults recruited from seven high schools in five south-east Texas-area school districts (current sample n=684). Multiple logistic regression modelling was used to examine the association between past-year use of legal and illegal substances and past-year firearm carrying for a reason other than sport or hunting. 6% of emerging adults carried firearms in the past year, with most (68%) carrying for protection. Use of cocaine, hallucinogens, methamphetamine, ecstasy and prescription medications in the past year, as well as episodic heavy drinking in the past month, was associated with increased risk of carrying a firearm (ppast-year substance use behaviours. These findings extend previous research and suggest directions for further exploration of the clustering of high-risk behaviours in emerging adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Modelling of carrying capacity in National Park - Fruška Gora (Serbia case study

    Directory of Open Access Journals (Sweden)

    Vujko Aleksandra

    2017-03-01

    Full Text Available Negative effects of tourism development in a destination are usually the consequence of the high concentration of tourists, accommodation facilities and the activities that are practiced in a relatively restricted area. One of the most important measures to protect the areas is to calculate the maximum number of tourists that can simultaneously reside in a region, i.e. the determination of the carrying capacity. This paper outlines a method for determining carrying capacity based on zoning of environmental resources and zoning within a region. The paper argues for a return to the idea of identifying maximum appropriate number of users. The main hypothesis of the paper is based on the statement that the development of tourism in Fruška Gora (Mountain National Park in Northern Serbia must be in accordance with the basic principles of sustainability, including the determination of carrying capacity. The main research goal was to show the opinion of local residents about the uncontrolled development of tourism, and to determine the carrying capacity in four sports and recreational zones of the mountain. The carrying capacity of the area is calculated by Lavery and Stanev formulas.

  16. Why do three-wheelers carrying schoolchildren suffer very low fatal crashes?

    Directory of Open Access Journals (Sweden)

    Gaurav Pandey

    2015-03-01

    Full Text Available This paper investigates the possible causes of low fatalities in three-wheelers (autorickshaw carrying schoolchildren in India. The data was collected in the form of First Information Report (FIR from local police stations from 2007 to 2012 and video-graphic surveys were done on four arterial roads running through Ludhiana, Punjab, India. Surveys were also done on one subarterial road near school zone which was used by three-wheelers carrying schoolchildren. The objective of the study was to investigate the hypothesis that drivers behave differently while following or overtaking three-wheelers carrying children. Many researchers have investigated the effect of passengers on the driver of the same vehicle, but there was no evidence of any study which investigated the effect of child passengers on nearby vehicles. It was found that heavy vehicles maintain more gaps while following or overtaking three-wheelers carrying children as compared to those not carrying children. It was also found that this effect is more prominent at speeds higher than 40 km/h. On the other hand lighter vehicles keep the highest lateral and longitudinal gaps to heavy vehicles and three-wheelers without children respectively.

  17. Carrying capacity of U.S. agricultural land: Ten diet scenarios

    Directory of Open Access Journals (Sweden)

    Christian J. Peters

    2016-07-01

    Full Text Available Abstract Strategies for environmental sustainability and global food security must account for dietary change. Using a biophysical simulation model we calculated human carrying capacity under ten diet scenarios. The scenarios included two reference diets based on actual consumption and eight “Healthy Diet” scenarios that complied with nutritional recommendations but varied in the level of meat content. We considered the U.S. agricultural land base and accounted for losses, processing conversions, livestock feed needs, suitability of land for crops or grazing, and land productivity. Annual per capita land requirements ranged from 0.13 to 1.08 ha person-1 year-1 across the ten diet scenarios. Carrying capacity varied from 402 to 807 million persons; 1.3 to 2.6 times the 2010 U.S. population. Carrying capacity was generally higher for scenarios with less meat and highest for the lacto-vegetarian diet. However, the carrying capacity of the vegan diet was lower than two of the healthy omnivore diet scenarios. Sensitivity analysis showed that carrying capacity estimates were highly influenced by starting assumptions about the proportion of cropland available for cultivated cropping. Population level dietary change can contribute substantially to meeting future food needs, though ongoing agricultural research and sustainable management practices are still needed to assure sufficient production levels.

  18. Modification Of Carry-Blair Transport Media For Storage Salmonella typhi

    Directory of Open Access Journals (Sweden)

    Yati Supriatin

    2016-09-01

    Full Text Available The aim of this study was to determine transport media modification as alternative media to replace Carry Blair. One type of transport media that often use to carry faeces specimens suspected to contain Salmonella typhi is Carry-Blair media. Studies have been conducted experimentally by storing Salmonella typhi on alternative transport media with Peptone composition, disodium Phosphate, Sodium chloride, Calcium chloride, which is made using a semi-solid and Carry-Blair as a control. Three variety of storage was done (0 hour,6 hours,9 hours at a temperature 4⁰-8⁰C and then Salmonella typhi was inoculated in Salmonella Shigella Agar using spread plate technique incubated during 24 hours at 37⁰C, counted the number of colonies by the plate count method using the colony counter. The results of ANOVA could be concluded that modification media could be use as alternative media replace Carry-Blair at 6 hours. Based on regression correlation test was assumed that the Salmonella typhi bacteria still life at less than 11 hours 54 minutes.

  19. Categorical and continuous - disentangling the neural correlates of the carry effect in multi-digit addition

    Directory of Open Access Journals (Sweden)

    Dressel Katharina

    2010-11-01

    Full Text Available Abstract Background Recently it was suggested that the carry effect observed in addition involves both categorical and continuous processing characteristics. Methods In the present study, we aimed at identifying the specific neural correlates associated with processing either categorical or continuous aspects of the carry effect in an fMRI study on multi-digit addition. Results In line with our expectations, we observed two distinct parts of the fronto-parietal network subserving numerical cognition to be associated with either one of these two characteristics. On the one hand, the categorical aspect of the carry effect was associated with left-hemispheric language areas and the basal ganglia probably reflecting increased demands on procedural and problem solving processes. Complementarily, the continuous aspect of the carry effect was associated with increased intraparietal activation indicating increasing demands on magnitude processing as well as place-value integration with increasing unit sum. Conclusions In summary, the findings suggest representations and processes underlying the carry effect in multi-digit addition to be more complex and interactive than assumed previously.

  20. Profile of women who carried out smoking cessation treatment: a systematic review.

    Science.gov (United States)

    Pereira, Caroline Figueira; de Vargas, Divane

    2015-01-01

    OBJECTIVE Analyze the profile of women, in health services, who carry out treatment for smoking cessation. METHODS Systematic review that used the following sources of information: Cummulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Biblioteca Virtual em Saúde (BVS), Scopus and Web of Science. We included quantitative studies that addressed the characterization of women, in health services, who carried out treatment for smoking cessation, resulting in 12 articles for analysis. The assessment of the methodological quality of the studies was performed using the instrument MAStARI from Joanna Briggs Institute. RESULTS The predominant profile of women who carried out treatment for smoking cessation in health services was composed of white, married, employed, and highly level educated women. Women who carried out the treatment for smoking cessation in specialized services had a more advanced age, were white, were married and had a diagnosis of depression. The quality level of most studies was moderate. CONCLUSIONS The profile of women who carry out treatment for smoking cessation, either in general or specialized health services, is composed of white, married, and highly level educated women. Publications about smoking women are scarce and the lack of Brazilian studies characterizing the profile of women who start treatment for smoking cessation shows the need for studies that explore this subject.

  1. Profile of women who carried out smoking cessation treatment: a systematic review

    Directory of Open Access Journals (Sweden)

    Caroline Figueira Pereira

    2015-01-01

    Full Text Available OBJECTIVE Analyze the profile of women, in health services, who carry out treatment for smoking cessation. METHODS Systematic review that used the following sources of information: Cummulative Index to Nursing and Allied Health Literature (CINAHL, PubMed, Biblioteca Virtual em Saúde (BVS, Scopus and Web of Science. We included quantitative studies that addressed the characterization of women, in health services, who carried out treatment for smoking cessation, resulting in 12 articles for analysis. The assessment of the methodological quality of the studies was performed using the instrument MAStARI from Joanna Briggs Institute. RESULTS The predominant profile of women who carried out treatment for smoking cessation in health services was composed of white, married, employed, and highly level educated women. Women who carried out the treatment for smoking cessation in specialized services had a more advanced age, were white, were married and had a diagnosis of depression. The quality level of most studies was moderate. CONCLUSIONS The profile of women who carry out treatment for smoking cessation, either in general or specialized health services, is composed of white, married, and highly level educated women. Publications about smoking women are scarce and the lack of Brazilian studies characterizing the profile of women who start treatment for smoking cessation shows the need for studies that explore this subject.

  2. Axisymmetrical separator for separating particulate matter from a fluid carrying medium

    Science.gov (United States)

    Linhardt, Hans D.

    1984-09-04

    A separator for separating particles carried in a fluid carrying medium is disclosed. The separator includes an elongated duct and associated openings incorporated in a solid body. The duct is axisymmetrical relative to its longitudinal axis, and includes a curved wall portion having a curved cross-section taken along the longitudinal axis. An axisymmetrical opening located downstream of the curved wall portion leads from the duct into an axisymmetrical channel which is substantially radially disposed relative to the longitudinal axis. Continuation of the duct downstream of the opening is a discharge portion which is substantially colinear with the longitudinal axis. In operation, a substantial majority of the fluid carrying medium leaves the duct radially through the opening and channel in a state substantially free of particles. A remaining small portion of the fluid carrying medium and a substantial majority of the particles are channelled into the discharge portion by centrifugal forces arising due to travel of the particles along the curved walls. For industrial scale separation of particles from a fluid carrying medium, such as for the clean-up of stack gases, an array of several hundred to several thousand of the separators is provided.

  3. Evaluation of Resources Carrying Capacity in China Based on Remote Sensing and GIS

    Science.gov (United States)

    Liu, K.; Gan, Y. H.; Zhang, T.; Luo, Z. Y.; Wang, J. J.; Lin, F. N.

    2018-04-01

    This paper accurately extracted the information of arable land, grassland (wetland), forest land, water area and construction land, based on 1 : 250000 basic geographic information data. It made model modification of comprehensive CCRR to achieve carrying capacity calculation taking resource quality into consideration. Ultimately it achieved a comprehensive assessment of CCRR status in China. The top ten cities where the status of carrying capacity of resources was overloaded were Wenzhou, Shanghai, Chengdu, Baoding, Shantou, Jieyang, Dongguan, Fuyang, Zhoukou and Handan. The cities were basically distributed in the central and southern areas with convenient transportation and more economically developed areas. Among the cities in surplus status, resources carrying capacity in Hulun Buir was the most abundant, followed by Heihe, Bayingolin Mongol Autonomous Prefecture, Qiqihar, Chifeng and Jiamusi, all of which were located in northeastern China with a small population and plentiful cultivated land.

  4. Generalizability of carry-over effects in the emotional Stroop task.

    Science.gov (United States)

    Waters, Andrew J; Sayette, Michael A; Franken, Ingmar H A; Schwartz, Joseph E

    2005-06-01

    The emotional Stroop task has been the most widely used task to examine attentional bias to emotionally salient stimuli. In one format of this task, words are presented to participants in a mixed randomized or quasi-randomized sequence. Using a mixed smoking Stroop task, we have previously demonstrated that smokers are slower to respond to words which follow smoking-related words than words which follow neutral words. Here we show that this carry-over effect is present in heroin addicts-but not control subjects-in a heroin Stroop task, and in normal subjects in a stress Stroop task. Thus, the effect generalizes to other populations. In addition, an examination of the studies that have collected data from both mixed and blocked formats provides converging evidence for the presence of carry-over effects. We discuss the implications of the carry-over effect for research using the emotional Stroop task.

  5. Carrying an anti-nuclear-power badge in the teaching profession

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The carrying of an anti-nuclear-power badge by a teacher during school hours violates the order to practice reticence in political activities. At the beginning of 1977 some teachers, the plaintiff as well, carried anti-nuclear-power badges, i.e. a round badge with a stylized red sun on a yellow background with the inscription 'Nuclear power - No, thank you'. Following a general direction by the educational authorities, the headmistress forbade plaintiff on 4.11.77 to visibly carry this badge during lessons. This protest having been without success, action was brought with partial success at the Administrative and Higher Administrative Court. The Federal Administrative Court dismissed the case. (orig./HSCH) [de

  6. First Identification of a Patient Colonized With Klebsiella pneumoniae Carrying blaNDM-1 in Taiwan

    Directory of Open Access Journals (Sweden)

    Hua-Shin Wu

    2010-11-01

    Full Text Available New Delhi metallo-β-lactamase 1 (NDM-1 is a novel type of metallo-β-lactamase (MBL. Enterobacteriaceae carrying this NDM-1 encoding gene, blaNDM-1, have been identified worldwide. Bacteria carrying blaNDM-1 are not only resistant to carbapenem, but also highly resistant to many classes of antibiotics, which indicate the importance of prompt identification of these bacteria and implementation of strict infection control measures to prevent their transmission. Here, we report the first identification and management of a patient colonized with Klebsiella pneumoniae carrying blaNDM-1 in Taiwan, who returned from New Delhi where he had been hospitalized for a gun-shot injury.

  7. Trivial dynamics in discrete-time systems: carrying simplex and translation arcs

    Science.gov (United States)

    Niu, Lei; Ruiz-Herrera, Alfonso

    2018-06-01

    In this paper we show that the dynamical behavior in (first octant) of the classical Kolmogorov systems of competitive type admitting a carrying simplex can be sometimes determined completely by the number of fixed points on the boundary and the local behavior around them. Roughly speaking, T has trivial dynamics (i.e. the omega limit set of any orbit is a connected set contained in the set of fixed points) provided T has exactly four hyperbolic nontrivial fixed points in with local attractors on the carrying simplex and local repellers on the carrying simplex; and there exists a unique hyperbolic fixed point in Int. Our results are applied to some classical models including the Leslie–Gower models, Atkinson-Allen systems and Ricker maps.

  8. The effect of the spaceship carrying on the biological characters and sod activity of eggplant

    International Nuclear Information System (INIS)

    Wang Shiheng; Zhang Ya; Zhu Shuijin; Wang Yanfan

    2004-01-01

    The effects of the space shuttle carrying on the growth and biological characters of eggplant SP 1 population were studied. The results showed that the effect of space shuttle carrying on the growth and development of eggplant SP 1 were very significant on the characters such as the plant height, reproductive development, leaf size, fruit length, fruit quality and fruiting rate etc, especially on the plant development and the fruit size, and it is hopeful to select some good eggplant germplasm or cultivars from the population. The SOD activity showed that the SOD level in the mutant-1 plant was one time more than that in control plant, indicating that the space shuttle carrying may increase the expression of some genes and lead to the great change in morphological characters

  9. Performance of women with fibromyalgia in walking up stairs while carrying a load

    Directory of Open Access Journals (Sweden)

    Daniel Collado-Mateo

    2016-02-01

    Full Text Available Background. Fibromyalgia is a chronic disease characterized by widespread pain and other associated symptoms. It has a relevant impact on physical fitness and the ability to perform daily living tasks. The objective of the study was to analyze the step-by-step-performance and the trunk tilt of women with fibromyalgia in the 10-step stair climbing test compared with healthy controls. Methods. A cross-sectional study was carried out. Twelve women suffering from fibromyalgia and eight healthy controls were recruited from a local association. Participants were asked to climb 10 stairs without carrying a load and 10 stairs carrying a load of 5 kg in each hand. Mediolateral trunk tilt was assessed using the “Functional Assessment of Biomechanics (FAB” wireless motion capture device, and the time between steps was assessed via weight-bearing insoles. Results. Trunk tilt in the stair-climbing task carrying a load was significantly higher in women with fibromyalgia when compared to the healthy controls (2.31 (0.63 vs. 1.69 (0.51 respectively. The effect of carrying a load was significantly higher for women with fibromyalgia compared with healthy controls at the intermediate and final part of the task. Discussion. Trunk tilt during stair climbing while carrying a load was higher in women with FM, which could increase the risk of falling. Additionally, women with FM experienced a higher pace slowdown as a consequence of the load, which supports the need of including specific strength and resistance training to physical therapies for this population.

  10. Botanical Composition, Grass Production, and Carrying Capacity of Pasture in Timor Tengah Selatan District

    Directory of Open Access Journals (Sweden)

    V. E. Se’u

    2015-12-01

    Full Text Available This study was conducted to analyze the botanical composition, grass production, carrying capacity, and potential production of nutrients in pasture located in Timor Tengah Selatan Regency. The experiment was conducted from February to July 2013, using field survey method. The botanical composition, grass production and carrying capacity on real condition were analyzed descriptively, while the grass production and carrying capacity based of cutting arrangement were analyzed by using randomized block factorial design with 3 altitude locations (Sub District of Mollo Utara with altitude of 1007 m above sea level; Sub District of Noebeba, 500 m ASL, and Sub District of Amanuban Selatan, 65 m ASL x 2 cutting intervals (1 and 2 month and 5 replications. The results showed that the grass type dominated the pasture in the Sub District of Mollo Utara, while legum type was more dominant in the pasture in the Sub Districts of Noebeba and Amanuban Selatan. The potential production of dry matter grass in Timor Tengah Selatan Regency based on real condition was 150 to 390 kg/ha/yr, this could accommodate 0.24 to 0.63 AU/ha/yr. The arrangement of cutting interval by 1 month in Mollo Utara and 2 months in Noebeba and Amanuban Selatan could increase (P<0.05 grass production and carrying capacity. The potential productions of grass nutrients were higher in Sub District of Mollo Utara, while potential production of grass dry matter was higher in Sub Districts of Noebeba and Amanuban Selatan. It was concluded that grass dry matter potential production and carrying capacity in Timor Tengah Selatan Regency were low. The arrangement of cutting interval could increase grass dry matter potential production, carrying capacity, nutrition production, and quality of nutrition.

  11. Performance of women with fibromyalgia in walking up stairs while carrying a load.

    Science.gov (United States)

    Collado-Mateo, Daniel; Adsuar, José C; Olivares, Pedro R; Dominguez-Muñoz, Francisco J; Maestre-Cascales, Cristina; Gusi, Narcis

    2016-01-01

    Background. Fibromyalgia is a chronic disease characterized by widespread pain and other associated symptoms. It has a relevant impact on physical fitness and the ability to perform daily living tasks. The objective of the study was to analyze the step-by-step-performance and the trunk tilt of women with fibromyalgia in the 10-step stair climbing test compared with healthy controls. Methods. A cross-sectional study was carried out. Twelve women suffering from fibromyalgia and eight healthy controls were recruited from a local association. Participants were asked to climb 10 stairs without carrying a load and 10 stairs carrying a load of 5 kg in each hand. Mediolateral trunk tilt was assessed using the "Functional Assessment of Biomechanics (FAB)" wireless motion capture device, and the time between steps was assessed via weight-bearing insoles. Results. Trunk tilt in the stair-climbing task carrying a load was significantly higher in women with fibromyalgia when compared to the healthy controls (2.31 (0.63) vs. 1.69 (0.51) respectively). The effect of carrying a load was significantly higher for women with fibromyalgia compared with healthy controls at the intermediate and final part of the task. Discussion. Trunk tilt during stair climbing while carrying a load was higher in women with FM, which could increase the risk of falling. Additionally, women with FM experienced a higher pace slowdown as a consequence of the load, which supports the need of including specific strength and resistance training to physical therapies for this population.

  12. Stargazin Modulation of AMPA Receptors

    Directory of Open Access Journals (Sweden)

    Sana A. Shaikh

    2016-10-01

    Full Text Available Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA-type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with auxiliary proteins, such as stargazin, which can markedly alter receptor trafficking and gating. Here, we used luminescence resonance energy transfer measurements to map distances between the full-length, functional AMPA receptor and stargazin expressed in HEK293 cells and to determine the ensemble structural changes in the receptor due to stargazin. In addition, we used single-molecule fluorescence resonance energy transfer to study the structural and conformational distribution of the receptor and how this distribution is affected by stargazin. Our nanopositioning data place stargazin below the AMPA receptor ligand-binding domain, where it is well poised to act as a scaffold to facilitate the long-range conformational selection observations seen in single-molecule experiments. These data support a model of stargazin acting to stabilize or select conformational states that favor activation.

  13. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  14. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  15. Carry-chain propagation delay impacts on resolution of FPGA-based TDC

    International Nuclear Information System (INIS)

    Dong Lei; Yang Junfeng; Song Kezhu

    2014-01-01

    The architecture of carry chains in Field-Programmable Gate Array (FPGA) is introduced in this paper. The propagation delay time of the rising and falling edges in the carry chains are calculated according to the architecture and they are predicted not equal in most cases. Tests show that the measuring results of the propagation delay time in EP3C120F484C8N series FPGA of Altera are in line with the inference. The difference of propagation delay time results in different accuracies of Time-to-Digital Converter (TDC). This phenomenon shall be considered in the design of TDC implemented in FPGA. It can ensure better accuracy. (authors)

  16. Risk-premia, Carry-trade Dynamics, and Economic Value of Currency Speculation

    DEFF Research Database (Denmark)

    Wagner, Christian

    2012-01-01

    In this paper, we derive the dynamics and assess the economic value of currency speculation by formalizing the concept of a trader inaction range. We show that exchange rate returns comprise a time-varying risk-premium and that uncovered interest parity (UIP) holds in a speculative sense. The often......-cited ‘forward bias puzzle’ originates from the omission of the risk-premium in standard UIP tests. Consistent with its popularity among market professionals, the carry-trade strategy can be rationalized as it systematically collects risk-premia, however, the economic value generated by bilateral carry-trades...

  17. EVALUATION OF SHEAR STRENGTH FOR UPPER SLABS OF CAISSON FOUNDATION BASED ON LOAD CARRYING MECHANISM

    Science.gov (United States)

    Hattori, Hisamichi; Tadokoro, Toshiya; Tanimura, Yukihiro; Nishioka, Hidetoshi; Watanabe, Tadatomo; Maruyama, Osamu

    In upper slabs of caisson foundation, a seismic desi gn is difficult with an incr ease in earthquake load. So we carried out loading tests and FEM analysis for upper slabs of caisson foundation. As a result, we proposed a new design method which takes into co nsideration the effective width on the pull out side based on crack pattern of test specimens, which is not considered in the existing design method. Moreover, we proposed a rational design method based on load carrying mechanism for upper slabs of caisson foundation.

  18. Investigation of diversity of plasmids carrying the blaTEM-52 gene

    DEFF Research Database (Denmark)

    Bielak, Eliza Maria; Bergenholtz, Rikke D.; Jørgensen, Mikael Skaanning

    2011-01-01

    OBJECTIVES: To investigate the diversity of plasmids that carry blaTEM-52 genes among Escherichia coli and Salmonella enterica originating from animals, meat products and humans. METHODS: A collection of 22 blaTEM-52-encoding plasmids was characterized by restriction fragment length polymorphism...... of self-transfer to a plasmid-free E. coli recipient. CONCLUSIONS: The blaTEM-52 gene found in humans could have been transmitted on transferable plasmids originating from animal sources. Some of the blaTEM-52 plasmids carry replicons that differ from the classical ones. Two novel replicons were detected...

  19. A Case Study in Carry Trade and Cross Pair Allegiance Switching, Pre and Post 2008

    OpenAIRE

    Brian Twomey

    2015-01-01

    EUR/USD, USD/JPY and the position of EUR/JPY was investigated in this paper using regression analysis with the overarching question where EUR/JPY sits in relation to both pairs and its position in terms of a carry trade. What was determined was EUR/JPY switches allegiance period to period. The carry trade premise is to borrow a low interest rate currency and lend in a high interest rate currency. The low interest rate currency becomes the fund currency while the high interest rate currency be...

  20. Cuttings-carried theory and erosion rule in gas drilling horizontal well

    Directory of Open Access Journals (Sweden)

    Wei Na

    2014-01-01

    Full Text Available In gas horizontal drilling, the gas with cuttings will go through the annulus at high speed which will lead strong erosion to the drill tools. This paper proposes a cuttings-carried theory and modified the critical cuttings-carried model for the gas-solid flow. Meanwhile, the erosive energy is obtained through simulating the gas-solid mixture in different conditions. The study result has positive significance on the determination of reasonable injection volume by optimizing construction parameters of horizontal well in gas drilling.