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Sample records for metalloprotease family m35

  1. Identification of metalloprotease gene families in sugarcane

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    O.H.P. Ramos

    2001-12-01

    Full Text Available Metalloproteases play a key role in many physiological processes in mammals such as cell migration, tissue remodeling and processing of growth factors. They have also been identified as important factors in the patho-physiology of a number of human diseases, including cancer and hypertension. Many bacterial pathogens rely on proteases in order to infect the host. Several classes of metalloproteases have been described in humans, bacteria, snake venoms and insects. However, the presence and characterization of plant metalloproteases have rarely been described in the literature. In our research, we searched the sugarcane expressed sequence tag (SUCEST DNA library in order to identify, by homology with sequences deposited in other databases, metalloprotease gene families expressed under different conditions. Protein sequences from Arabidopsis thaliana and Glycine max were used to search the SUCEST data bank. Conserved regions corresponding to different metalloprotease domains and sequence motifs were identified in the reads to characterize each group of enzymes. At least four classes of sugarcane metalloproteases have been identified, i.e. matrix metalloproteases, zincins, inverzincins, and ATP-dependent metalloproteases. Each enzyme class was analyzed for its expression in different conditions and tissues.Metaloproteases exercem papéis importantes em muitos processos fisiológicos em mamíferos tais como migração celular, remodelamento tecidual e processamento de fatores de crescimento. Estas enzimas estão envolvidas também na pato-fisiologia de um grande número de doenças humanas como hipertensão e câncer. Muitas bactérias patogênicas dependem de proteases para infectar o hospedeiro. Diversas classes de metaloproteases foram descritas em seres humanos, bactérias, venenos de serpentes e insetos. No entanto, a presença e a caracterização de metaloproteases em plantas estão pouco descritas na literatura. Neste trabalho, foi

  2. A novel member of the thermolysin family, cloning and biochemical characterization of metalloprotease from Staphylococcus pseudintermedius

    NARCIS (Netherlands)

    Wladyka, Benedykt; Bista, Michal; Sabat, Artur J.; Bonar, Emilia; Grzeszczuk, Sabina; Hryniewicz, Waleria; Dubin, Adam

    2008-01-01

    Thermolysins constitute a family of secreted bacterial metalloproteases expressed, among others, by several pathogens. Strains of Staphylococcus pseudintermedius isolated from diseased dogs and judged as protease-positive, by skim milk agar plate culture, were investigated for protease content. No p

  3. Metalloproteases and the degradome.

    Science.gov (United States)

    Ugalde, Alejandro P; Ordóñez, Gonzalo R; Quirós, Pedro M; Puente, Xose S; López-Otín, Carlos

    2010-01-01

    Metalloproteases comprise a heterogeneous group of proteolytic enzymes whose main characteristic is the utilization of a metal ion to polarize a water molecule and perform hydrolytic reactions. These enzymes represent the most densely populated catalytic class of proteases in many organisms and play essential roles in multiple biological processes. In this chapter, we will first present a general description of the complexity of metalloproteases in the context of the degradome, which is defined as the complete set of protease genes encoded by the genome of a certain organism. We will also discuss the functional relevance of these enzymes in a large variety of biological and pathological conditions. Finally, we will analyze in more detail three families of metalloproteases: ADAMs (a disintegrin and metalloproteinase), ADAMTSs (ADAMs with thrombospondin domains), and MMPs (matrix metalloproteinases) which have a growing relevance in a number of human pathologies including cancer, arthritis, neurodegenerative disorders, and cardiovascular diseases.

  4. Astacin-like metalloproteases are a gene family of toxins present in the venom of different species of the brown spider (genus Loxosceles).

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    Trevisan-Silva, Dilza; Gremski, Luiza H; Chaim, Olga M; da Silveira, Rafael B; Meissner, Gabriel O; Mangili, Oldemir C; Barbaro, Katia C; Gremski, Waldemiro; Veiga, Silvio S; Senff-Ribeiro, Andrea

    2010-01-01

    Brown spiders have a worldwide distribution, and their venom has a complex composition containing many different molecules. Herein, we report the existence of a family of astacin-like metalloprotease toxins in Loxosceles intermedia venom, as well as in the venom of different species of Loxosceles. Using a cDNA library from the L. intermedia venom gland, we cloned two novel cDNAs encoding astacin-like metalloprotease toxins, LALP2 and LALP3. Using an anti-serum against the previously described astacin-like toxin in L. intermedia venom (LALP1), we detected the presence of immunologically-related toxins in the venoms of L. intermedia, Loxosceles laeta, and Loxosceles gaucho. Zymographic experiments showed gelatinolytic activity of crude venoms of L. intermedia, L. laeta, and L. gaucho (which could be inhibited by the divalent metal chelator 1,10-phenanthroline) at electrophoretic mobilities identical to those reported for immunological cross-reactivity. Moreover, mRNAs extracted from L. laeta and L. gaucho venom glands were screened for astacin-like metalloproteases, and cDNAs obtained using LALP1-specific primers were sequenced, and their deduced amino acid sequences confirmed they were members of the astacin family with the family signatures (HEXXHXXGXXHE and MXY), LALP4 and LALP5, respectively. Sequence comparison of deduced amino acid sequences revealed that LALP2, LALP3, LALP4, and LALP5 are related to the astacin family. This study identified the existence of gene family of astacin-like toxins in the venoms of brown spiders and raises the possibility that these molecules are involved in the deleterious effects triggered by the venom.

  5. Control of Entamoeba histolytica adherence involves metallosurface protease 1, an M8 family surface metalloprotease with homology to leishmanolysin.

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    Teixeira, Jose E; Sateriale, Adam; Bessoff, Kovi E; Huston, Christopher D

    2012-06-01

    Invasive amebiasis due to Entamoeba histolytica infection is an important cause of morbidity in developing countries. The E. histolytica genome contains two homologues to the metalloprotease leishmanolysin gene, Entamoeba histolytica MSP-1 (EhMSP-1) and EhMSP-2, while the commensal ameba Entamoeba dispar has lost EhMSP-1. In this study, we sought to characterize E. histolytica metallosurface protease 1 (EhMSP-1). Using immunoprecipitation and a model substrate, we found that EhMSP-1 was a functional metalloprotease. Confocal microscopy and flow cytometry revealed that EhMSP-1 localized to the cell surface and revealed the existence of distinct, nonclonal trophozoite populations with high and low EhMSP-1 surface abundance that became synchronized following serum starvation. Phenotypic assays were performed after silencing EhMSP-1. Adherence of EhMSP-1-deficient trophozoites to tissue culture cell monolayers was more than five times greater than that of control amebas, but surface staining of several antigens, including the galactose adherence lectin, was unchanged. EhMSP-1 silencing similarly increased adherence to both viable and apoptotic Jurkat lymphocytes. Tissue culture cell monolayer destruction was reduced by EhMSP-1 silencing, although it was blocked almost completely by inhibiting cysteine proteases. Consistent with a primary defect in regulation of amebic adherence, EhMSP-1 silencing also resulted in reduced mobility on tissue culture cell monolayers and in increased phagocytosis. In conclusion, EhMSP-1 was shown to be a surface metalloprotease involved in regulation of amebic adherence, with additional effects on cell motility, cell monolayer destruction, and phagocytosis.

  6. Physiology and pathophysiology of matrix metalloproteases

    NARCIS (Netherlands)

    Klein, T.; Bischoff, R.

    2011-01-01

    Matrix metalloproteases (MMPs) comprise a family of enzymes that cleave protein substrates based on a conserved mechanism involving activation of an active site-bound water molecule by a Zn(2+) ion. Although the catalytic domain of MMPs is structurally highly similar, there are many differences with

  7. Physiology and pathophysiology of matrix metalloproteases

    NARCIS (Netherlands)

    Klein, T; Bischoff, Rainer

    2010-01-01

    Matrix metalloproteases (MMPs) comprise a family of enzymes that cleave protein substrates based on a conserved mechanism involving activation of an active site-bound water molecule by a Zn(2+) ion. Although the catalytic domain of MMPs is structurally highly similar, there are many differences with

  8. A Disintegrin and Metalloprotease (ADAM: Historical Overview of Their Functions

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    Nives Giebeler

    2016-04-01

    Full Text Available Since the discovery of the first disintegrin protein from snake venom and the following identification of a mammalian membrane-anchored metalloprotease-disintegrin implicated in fertilization, almost three decades of studies have identified additional members of these families and several biochemical mechanisms regulating their expression and activity in the cell. Most importantly, new in vivo functions have been recognized for these proteins including cell partitioning during development, modulation of inflammatory reactions, and development of cancers. In this review, we will overview the a disintegrin and metalloprotease (ADAM family of proteases highlighting some of the major research achievements in the analysis of ADAMs’ function that have underscored the importance of these proteins in physiological and pathological processes over the years.

  9. An integrated high-performance liquid chromatography-mass spectrometry system for the activity-dependent analysis of matrix metalloproteases

    NARCIS (Netherlands)

    Freije, Robert; Klein, Theo; Ooms, Bert; Kauffman, Henk F.; Bischoff, Rainer

    2008-01-01

    Matrix metalloproteases (MMPs) comprise a family of enzymes that play important roles in mediating angiogenesis, the remodelling of tissues and in cancer metastasis. Consequently, they are attractive targets for therapeutic intervention in chronic inflammation, cancer and neurological disorders. In

  10. Electrophysiological Characterization of the Antarease Metalloprotease from Tityus serrulatus Venom

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    Zornetta, Irene; Scorzeto, Michele; Mendes Dos Reis, Pablo Victor; De Lima, Maria E.; Montecucco, Cesare; Megighian, Aram; Rossetto, Ornella

    2017-01-01

    Scorpions are among the oldest venomous living organisms and the family Buthidae is the largest and most medically relevant one. Scorpion venoms include many toxic peptides, but recently, a metalloprotease from Tityus serrulatus called antarease was reported to be capable of cleaving VAMP2, a protein involved in the neuroparalytic syndromes of tetanus and botulism. We have produced antarease and an inactive metalloprotease mutant in a recombinant form and analyzed their enzymatic activity on recombinant VAMP2 in vitro and on mammalian and insect neuromuscular junction. The purified recombinant antarease paralyzed the neuromuscular junctions of mice and of Drosophila melanogaster whilst the mutant was inactive. We were unable to demonstrate any cleavage of VAMP2 under conditions which leads to VAMP proteolysis by botulinum neurotoxin type B. Antarease caused a reduced release probability, mainly due to defects upstream of the synaptic vesicles fusion process. Paired pulse experiments indicate that antarease might proteolytically inactivate a voltage-gated calcium channel. PMID:28264432

  11. ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3

    DEFF Research Database (Denmark)

    Shi, Z; Xu, Wei; Loechel, F

    2000-01-01

    , as yet the pregnancy-specific protease, or proteases, have not been identified. We utilized a yeast two-hybrid assay and a human placental cDNA library to investigate IGFBP-3-interacting proteins. A disintegrin and metalloprotease-12 (ADAM 12), a member of a family of metalloprotease disintegrins...... that is highly expressed in placental tissue, was identified as interacting with IGFBP-3. This interaction involved the cysteine-rich domain of ADAM 12. Unlike other members of this family of disintegrin metalloproteases that are membrane proteins, ADAM 12 exists as an alternatively spliced soluble secreted...... medium on a heparin-Sepharose column also proteolyzed IGFBP-3. The degradation pattern was similar to that seen with pregnancy serum, and the presence of ADAM 12-S in serum during pregnancy was confirmed. The data suggest that ADAM 12-S has IGFBP-3 protease activity, and it may contribute to the IGFBP-3...

  12. Development of an integrated system for activity-based profiling of matrix metallo-proteases

    NARCIS (Netherlands)

    Freije, Jan Robert

    2006-01-01

    Matrix metallo-proteases constitute a family of extracellular zinc-dependent endopeptidases that are involved in degradation of extracellular matrix (ECM) components and other bioactive non-ECM molecules. A plethora of studies have implicated important roles for MMPs in many diseases (including

  13. Cell-surface metalloprotease ADAM12 is internalized by a clathrin- and Grb2-dependent mechanism

    DEFF Research Database (Denmark)

    Hansen, Dorte Stautz; Leyme, Anthony; Grandal, Michael Vibo;

    2012-01-01

    ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell-surface ...

  14. Development of an integrated system for activity-based profiling of matrix metallo-proteases

    NARCIS (Netherlands)

    Freije, Jan Robert

    2006-01-01

    Matrix metallo-proteases constitute a family of extracellular zinc-dependent endopeptidases that are involved in degradation of extracellular matrix (ECM) components and other bioactive non-ECM molecules. A plethora of studies have implicated important roles for MMPs in many diseases (including canc

  15. Helicobacter pylori and gastritis: the role of extracellular matrix metalloproteases, their inhibitors, and the disintegrins and metalloproteases--a systematic literature review.

    Science.gov (United States)

    Sampieri, Clara L

    2013-10-01

    Helicobacter pylori (H. pylori) is the etiologic agent of gastritis; it has been estimated that 50 % of the world's population could be infected by this bacteria. Gastritis may progress to chronic atrophic gastritis, a condition associated with the development of gastric cancer (GC). Several matrix metalloproteases (MMP) and tissue inhibitors of MMPs (TIMP) as well as disintegrins and metalloproteases (ADAM) have been reported as being involved in gastritis. Among other processes, these protein families participate in remodeling the extracellular matrix, cell signaling, immune response, angiogenesis, inflammation and epithelial mesenchymal transition. This systematic review analyzes the scientific evidence surrounding the relationship between members of the MMP, TIMP and ADAM families and infection by H. pylori in gastritis, considering both in vitro and in vivo studies. Given the potential clinical value of certain members of the MMP, TIMP and ADAM families as molecular markers in gastritis and the association of gastritis with GC, the need for further study is highlighted.

  16. Metalloprotease Dependent Release of Placenta Derived Fractalkine

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    Monika Siwetz

    2014-01-01

    Full Text Available The chemokine fractalkine is considered as unique since it exists both as membrane-bound adhesion molecule and as shed soluble chemoattractant. Here the hypothesis was tested whether placental fractalkine can be shed and released into the maternal circulation. Immunohistochemical staining of human first trimester and term placenta sections localized fractalkine at the apical microvillous plasma membrane of the syncytiotrophoblast. Gene expression analysis revealed abundant upregulation in placental fractalkine at term, compared to first trimester. Fractalkine expression and release were detected in the trophoblast cell line BeWo, in primary term trophoblasts and placental explants. Incubation of BeWo cells and placental explants with metalloprotease inhibitor Batimastat inhibited the release of soluble fractalkine and at the same time increased the membrane-bound form. These results demonstrate that human placenta is a source for fractalkine, which is expressed in the syncytiotrophoblast and can be released into the maternal circulation by constitutive metalloprotease dependent shedding. Increased expression and release of placental fractalkine may contribute to low grade systemic inflammatory responses in third trimester of normal pregnancy. Aberrant placental metalloprotease activity may not only affect the release of placenta derived fractalkine but may at the same time affect the abundance of the membrane-bound form of the chemokine.

  17. Metalloproteases and rotator cuff disease.

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    Del Buono, Angelo; Oliva, Francesco; Longo, Umile Giuseppe; Rodeo, Scott A; Orchard, John; Denaro, Vincenzo; Maffulli, Nicola

    2012-02-01

    The molecular changes occurring in rotator cuff tears are still unknown, but much attention has been paid to better understand the role of matrix metalloproteinases (MMP) in the development of tendinopathy. These are potent enzymes that, once activated, can completely degrade all components of the connective tissue, modify the extracellular matrix (ECM), and mediatethe development of painful tendinopathy and tendon rupture. To control the local activity of activated proteinases, the same cells produce tissue inhibitors of metalloproteinases (TIMP) that bind to the enzymes and prevent degradation. The balance between the activities of MMPs and TIMPs regulates tendon remodeling, whereas an imbalance produces a collagen dis-regulation and disturbances intendons. ADAMs (a disintegrin and metalloproteinase) are cell membrane-linked enzymes with proteolytic and cell signaling functions. ADAMTSs (ADAM with thrombospondin motifs) are secreted into the circulation, and constitute a heterogenous family of proteases with both anabolic and catabolic functions. Biologic modulation of endogenous MMP activity to basal levels may reduce pathologic tissue degradation and favorably influence healing after rotator cuff repair. Further studies are needed to better define the mechanism of action, and whether these new strategies are safe and effective in larger models. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  18. Comparison of different application strategies of divergicin M35 for inactivation of Listeria monocytogenes in cold-smoked wild salmon.

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    Tahiri, I; Desbiens, M; Kheadr, E; Lacroix, C; Fliss, I

    2009-12-01

    Cold-smoked salmon treated with divergicin M35-producing Carnobacterium divergens M35, C. divergens ATCC 35677 (a non-producer of bacteriocin), purified divergicin M35 or supernatants of C. divergens M35 culture in snow crab hepatopancreas (SCH) medium or MRS broth was challenged with Listeria monocytogenes (up to 10(3) CFU/g). Samples were stored at 4 degrees C for up to four weeks. L. monocytogenes, total bacterial and lactic acid bacterial counts were determined along with changes in total volatile base nitrogen (TVBN) and biogenic amine production as well as texture, color and odor. A 2.6 log CFU/g reduction in L. monocytogenes was obtained for up to 10 days of storage in samples treated with C. divergens M35. Purified divergicin M35 (50 microg/g), SCH supernatant or MRS supernatant brought reductions of 1 log CFU/g at the beginning of storage. However, the anti-listerial activity of the supernatants lasted for 15 days compared to 3 days for purified divergicin M35. Color and texture were affected little in samples containing C. divergens M35 compared to un-inoculated samples. TVBN and biogenic amine production, particularly tyramine, remained below the maximum acceptable level in fish appreciation. These results clearly show the potential of C. divergens M35 culture as well as divergicin M35 bio-ingredient for application to the inactivation of L. monocytogenes in ready-to-eat seafood.

  19. Modulation of the epithelial sodium channel (ENaC) by bacterial metalloproteases and protease inhibitors.

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    Butterworth, Michael B; Zhang, Liang; Liu, Xiaoning; Shanks, Robert M; Thibodeau, Patrick H

    2014-01-01

    The serralysin family of metalloproteases is associated with the virulence of multiple gram-negative human pathogens, including Pseudomonas aeruginosa and Serratia marcescens. The serralysin proteases share highly conserved catalytic domains and show evolutionary similarity to the mammalian matrix metalloproteases. Our previous studies demonstrated that alkaline protease (AP) from Pseudomonas aeruginosa is capable of activating the epithelial sodium channel (ENaC), leading to an increase in sodium absorption in airway epithelia. The serralysin proteases are often co-expressed with endogenous, intracellular or periplasmic inhibitors, which putatively protect the bacterium from unwanted or unregulated protease activities. To evaluate the potential use of these small protein inhibitors in regulating the serralysin induced activation of ENaC, proteases from Pseudomonas aeruginosa and Serratia marcescens were purified for characterization along with a high affinity inhibitor from Pseudomonas. Both proteases showed activity against in vitro substrates and could be blocked by near stoichiometric concentrations of the inhibitor. In addition, both proteases were capable of activating ENaC when added to the apical surfaces of multiple epithelial cells with similar slow activation kinetics. The high-affinity periplasmic inhibitor from Pseudomonas effectively blocked this activation. These data suggest that multiple metalloproteases are capable of activating ENaC. Further, the endogenous, periplasmic bacterial inhibitors may be useful for modulating the downstream effects of the serralysin virulence factors under physiological conditions.

  20. Modulation of the epithelial sodium channel (ENaC by bacterial metalloproteases and protease inhibitors.

    Directory of Open Access Journals (Sweden)

    Michael B Butterworth

    Full Text Available The serralysin family of metalloproteases is associated with the virulence of multiple gram-negative human pathogens, including Pseudomonas aeruginosa and Serratia marcescens. The serralysin proteases share highly conserved catalytic domains and show evolutionary similarity to the mammalian matrix metalloproteases. Our previous studies demonstrated that alkaline protease (AP from Pseudomonas aeruginosa is capable of activating the epithelial sodium channel (ENaC, leading to an increase in sodium absorption in airway epithelia. The serralysin proteases are often co-expressed with endogenous, intracellular or periplasmic inhibitors, which putatively protect the bacterium from unwanted or unregulated protease activities. To evaluate the potential use of these small protein inhibitors in regulating the serralysin induced activation of ENaC, proteases from Pseudomonas aeruginosa and Serratia marcescens were purified for characterization along with a high affinity inhibitor from Pseudomonas. Both proteases showed activity against in vitro substrates and could be blocked by near stoichiometric concentrations of the inhibitor. In addition, both proteases were capable of activating ENaC when added to the apical surfaces of multiple epithelial cells with similar slow activation kinetics. The high-affinity periplasmic inhibitor from Pseudomonas effectively blocked this activation. These data suggest that multiple metalloproteases are capable of activating ENaC. Further, the endogenous, periplasmic bacterial inhibitors may be useful for modulating the downstream effects of the serralysin virulence factors under physiological conditions.

  1. Molecular Dynamics Studies of Matrix Metalloproteases.

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    Díaz, Natalia; Suárez, Dimas

    2017-01-01

    Matrix metalloproteases are multidomain enzymes with a remarkable proteolytic activity located in the extracellular environment. Their catalytic activity and structural properties have been intensively studied during the last few decades using both experimental and theoretical approaches, but many open questions still remain. Extensive molecular dynamics simulations enable the sampling of the configurational space of a molecular system, thus contributing to the characterization of the structure, dynamics, and ligand binding properties of a particular MMP. Based on previous computational experience, we provide in this chapter technical and methodological guidelines that may be useful to and stimulate other researchers to perform molecular dynamics simulations to help address unresolved questions concerning the molecular mode of action of MMPs.

  2. Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution.

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    Henrique F Carvalho

    Full Text Available Metalloproteases have evolved in a vast number of biological systems, being one of the most diverse types of proteases and presenting a wide range of folds and catalytic metal ions. Given the increasing understanding of protein internal dynamics and its role in enzyme function, we are interested in assessing how the structural heterogeneity of metalloproteases translates into their dynamics. Therefore, the dynamical profile of the clan MA type protein thermolysin, derived from an Elastic Network Model of protein structure, was evaluated against those obtained from a set of experimental structures and molecular dynamics simulation trajectories. A close correspondence was obtained between modes derived from the coarse-grained model and the subspace of functionally-relevant motions observed experimentally, the later being shown to be encoded in the internal dynamics of the protein. This prompted the use of dynamics-based comparison methods that employ such coarse-grained models in a representative set of clan members, allowing for its quantitative description in terms of structural and dynamical variability. Although members show structural similarity, they nonetheless present distinct dynamical profiles, with no apparent correlation between structural and dynamical relatedness. However, previously unnoticed dynamical similarity was found between the relevant members Carboxypeptidase Pfu, Leishmanolysin, and Botulinum Neurotoxin Type A, despite sharing no structural similarity. Inspection of the respective alignments shows that dynamical similarity has a functional basis, namely the need for maintaining proper intermolecular interactions with the respective substrates. These results suggest that distinct selective pressure mechanisms act on metalloproteases at structural and dynamical levels through the course of their evolution. This work shows how new insights on metalloprotease function and evolution can be assessed with comparison schemes that

  3. Serine proteases and metalloproteases associated with pathogenesis but not host specificity in the Entomophthoralean fungus Zoophthora radicans.

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    Xu, J; Baldwin, D; Kindrachuk, C; Hegedus, D D

    2006-06-01

    The protease activity of a Zoophthora radicans strain that was highly infective toward Pieris brassicae (cabbage butterfly) larvae was compared with that of isogenic strains that were adapted to Plutella xylostella (diamondback moth) larvae through serial passage. All strains produced three distinct serine proteases ranging in size from 25 to 37 kDa; however, the original strain from P. brassicae also produced large amounts of an approximately 46 kDa metalloprotease. Subsequently, a cDNA encoding a 43 kDa (mature enzyme) zinc-dependent metalloprotease, ZrMEP1, was isolated from the original fungal strain and most likely corresponds to the 46 kDa protease observed with in-gel assays. ZrMEP1 possessed characteristics of both the fungalysin and thermolysin metalloprotease families found in some pulmonary and dermal pathogens. This is the first report of this type of metalloprotease from an entomo pathogenic fungus. A cDNA encoding a trypsin-like serine protease, ZrSP1, was also identified and was most similar to a serine protease from the plant pathogen Verticillium dahliae. In artificial media, ZrMEP1 and ZrSP1 were found to be differentially responsive to gelatin and catabolite repression in the fungal strains adapted to P. brassicae and P. xylostella, but their expression patterns within infected larvae were the same. It appears that while these proteases likely play a role in the infection process, they may not be major host specificity determinants.

  4. Identification, cellular distribution and potential function of the metalloprotease-disintegrin MDC9 in the kidney.

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    Mahimkar, R M; Baricos, W H; Visaya, O; Pollock, A S; Lovett, D H

    2000-04-01

    The complex interactions of glomerular and tubular epithelial cells with the basal laminae play a critical role in renal function. Disruption of these interactions has been widely implicated in glomerular diseases and acute renal failure. MDC are a large family of membrane-bound proteins containing metalloprotease, disintegrin (integrin interaction sites), and cysteine-rich domains. Little information is available concerning the presence of MDC in the kidney or their role in renal pathophysiology. Using degenerate PCR primers for the conserved metalloprotease and disintegrin domains of this protein family, cDNA templates from tubules, whole glomeruli, and glomerular epithelial cells (GEC) yielded a single, 195-bp product, which on sequence analysis corresponded to a region in the disintegrin domain of MDC9. Northern analysis of poly(A)+ RNA from tubules, whole glomeruli, and GEC revealed a 3.9-kb transcript, identical to that of mouse MDC9. Using antibodies generated against a 21-amino acid peptide present in the metalloprotease domain of MDC9, Western analysis of concanavalin A-enriched glomerular microsomal extracts demonstrated both processed (76 kD) and unprocessed (116 kD) forms of MDC9, which upon reduction changed to the corresponding 84- and 124-kD forms. Histochemical studies revealed a basolateral localization of intrinsic MDC9 protein in renal cortical tubule cells and glomerular visceral epithelial cells, which colocalized with the beta1 integrin chain. Expression of green fluorescence protein MDC9 chimeric constructs in GEC or polarized Madin-Darby canine kidney epithelial cells revealed a similar punctate basolateral surface localization. Transient overexpression of the soluble disintegrin domain-green fluorescence protein chimera in GEC led to dramatic changes in cellular morphology with rounding and detachment from cell monolayers. These studies document the presence of MDC9 in renal epithelial cells and suggest an important role for MDC9 in renal

  5. The urokinase plasminogen activator receptor-associated protein/endo180 is coexpressed with its interaction partners urokinase plasminogen activator receptor and matrix metalloprotease-13 during osteogenesis

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Netzel-Arnett, S

    2001-01-01

    The urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor family that was reported to interact with ligand-bound urokinase plasminogen activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and ...

  6. Overexpression and export of Vibrio anguillarum metalloprotease in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Zhang Fengli; Chi Zhenming; Chen Jixiang; Wu Longfei; Liang Likun

    2007-01-01

    Vibrio anguillarum metalloprotease, an extracellular zinc metalloprotease involved in the virulence mechanism of Vibrio anguillarum, is synthesized from the empA gene as a 611-residue precursor and naturally secreted via Sec secretion pathway in Vibrio anguillarum. In this study, heterologous expression of the empA gene encoding metallopmtease and export of the recombinant metalloprotease in Escherichia coliwere examined. The empA gene was subcloned into pBAD24 with arabinose promoter and sequenced. The sequence encoded a polypeptide(611 amino acids)consisting of four domains: a signal peptide, an Nterminal propeptide, a mature region and a C-terminal propeptide. The empA gene inserted in plasmid pBAD24 was overexpressed in TOP10 strain of E. Coli after arabinose induction. The 36kDa polypeptide of the recombinant metalloprotease as the mature protease was further confirmed by SDS-PAGE and immunoblotting. It was found that recombinant metalloprotease with the EmpA activity and antigenicity wasexported into the periplasm of Escherichia coli cells via Sec translocation pathway, whereas it was secreted into extracellular environments in V. Anguillarum. The results imply that the expression, export and processing mechanism of the protein in E. Coli are similar to those in V. Anguillarum.

  7. Gold Nanoparticles Inhibit Matrix Metalloproteases without Cytotoxicity.

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    Hashimoto, M; Sasaki, J I; Yamaguchi, S; Kawai, K; Kawakami, H; Iwasaki, Y; Imazato, S

    2015-08-01

    Nanoparticles (NPs) are currently the focus of considerable attention for dental applications; however, their biological effects have not been fully elucidated. The long-term, slow release of matrix metalloproteases (MMPs) digests collagen fibrils within resin-dentin bonds. Therefore, MMP inhibitors can prolong the durability of resin-dentin bonds. However, there have been few reports evaluating the combined effect of MMP inhibition and the cytotoxic effects of NPs for dentin bonding. The aim of this study was to evaluate MMP inhibition and cytotoxic responses to gold (AuNPs) and platinum nanoparticles (PtNPs) stabilized by polyvinylpyrrolidone (PVP) in cultured murine macrophages (RAW264) by using MMP inhibition assays, measuring cell viability and inflammatory responses (quantitative reverse transcription polymerase chain reaction [RT-qPCR]), and conducting a micromorphological analysis by fluorescence and transmission electron microscopy. Cultured RAW264 cells were exposed to metal NPs at various concentrations (1, 10, 100, and 400 µg/mL). AuNPs and PtNPs markedly inhibited MMP-8 and MMP-9 activity. Although PtNPs were cytotoxic at high concentrations (100 and 400 µg/mL), no cytotoxic effects were observed for AuNPs at any concentration. Transmission electron microscopy images showed a significant nonrandom intercellular distribution for AuNPs and PtNPs, which were mostly observed to be localized in lysosomes but not in the nucleus. RT-qPCR analysis demonstrated inflammatory responses were not induced in RAW264 cells by AuNPs or PtNPs. The cytotoxicity of nanoparticles might depend on the core metal composition and arise from a "Trojan horse" effect; thus, MMP inhibition could be attributed to the surface charge of PVP, which forms the outer coating of NPs. The negative charge of the surface coating of PVP binds to Zn(2+) from the active center of MMPs by chelate binding and results in MMP inhibition. In summary, AuNPs are attractive NPs that effectively

  8. Biochemical and genetic characterization of arazyme, an extracellular metalloprotease produced from Serratia proteamaculans HY-3.

    Science.gov (United States)

    Kwak, Jangyul; Lee, Kieun; Shin, Dong-Ha; Maeng, Jin-Soo; Park, Doo-Sang; Oh, Hyun Woo; Son, Kwang-Hee; Bae, Kyung-Sook; Park, Ho-Yong

    2007-05-01

    Serratia proteamaculans HY-3 isolated from the digestive tract of a spider produces an extracellular protease named arazyme, with an estimated molecular mass of 51.5 kDa. The purified enzyme was characterized as having high activities at wide pH and temperature ranges. We further characterized biochemical features of the enzymatic reactions under various reaction conditions. The protease efficiently hydrolyzed a broad range of protein substrates including albumin, keratin, and collagen. The dependence of enzymatic activities on the presence of metal ions such as calcium and zinc indicated that the enzyme is a metalloprotease, together with the previous observation that the proteolytic activity of the enzyme was not inhibited by aspartate, cysteine, or serine protease inhibitors, but strongly inhibited by 1,10-phenanthroline and EDTA. The araA gene encoding the exoprotease was isolated as a 5.6 kb BamHl fragment after PCR amplification using degenerate primers and subsequent Southern hybridization. The nucleotide sequence revealed that the deduced amino acid sequences shared extensive similarity with those of the serralysin family of metalloproteases from other enteric bacteria. A gene (inh) encoding a putative protease inhibitor was also identified immediately adjacent to the araA structural gene.

  9. Mucosal immunization with the Moraxella catarrhalis porin m35 induces enhanced bacterial clearance from the lung: a possible role for opsonophagocytosis

    Directory of Open Access Journals (Sweden)

    Donna eEaston

    2011-05-01

    Full Text Available Moraxella catarrhalis is a significant cause of respiratory tract infection against which a vaccine is sought. Several outer membrane proteins are currently under investigation as potential vaccine antigens, including the porin M35. We have previously shown that the third external loop of M35 was immunodominant over the remainder of the protein for antibody produced in mice against the refolded recombinant protein. However, as this loop is predicted to fold inside the porin channel we also predicted that it would not be accessible to these antibodies when M35 is expressed on the surface of the bacteria in its native conformation. This study investigated the functional activity of antibodies against M35 and those specific for the loop 3 region of M35 in vitro and in vivo. Antisera from mice immunized with M35 or the loop 3-deletion, M35loop3–, recombinant proteins were not bactericidal but did have enhanced opsonic activity, whereas antibodies raised against the loop 3 peptide were not opsonising indicating that the immunodominant loop 3 of M35 was not accessible to antibody as we had previously predicted. Mucosal immunization with M35, M35 that had an antigenically altered loop 3 (M35(ID78 and M35loop3– enhanced the clearance of M. catarrhalis from the lungs of mice challenged with live M. catarrhalis. The in vivo clearance of bacteria in the mice with the M35-derived protein constructs correlated significantly (p<0.001 with the opsonic activity assessed an in vitro opsonophagocytosis assay. This study has demonstrated that the immunodominat B-cell epitope to loop 3 of the M. catarrhalis outer membrane protein M35 is not associated with immune protection and that M35-specific antibodies are not bactericidal but are opsonising. The opsonising activity correlated with in vivo clearance of the bacteria suggesting that opsonising antibody may be a good correlate of immune protection.

  10. The role of serine- and metalloproteases in Nasonia vitripennis venom in cell death related processes towards a Spodoptera frugiperda Sf21 cell line.

    Science.gov (United States)

    Formesyn, Ellen M; Heyninck, Karen; de Graaf, Dirk C

    2013-08-01

    Proteases are predominant venom components of the ectoparasitoid Nasonia vitripennis. Two protease families, serine proteases and metalloproteases were examined for their possible cytotoxic functions in the Spodoptera frugiperda (Sf21) cell line using protease inhibitors that inactivate one or both protease families. Viability assays on adherent cells indicated that both protease families are among the main cytotoxic compounds of N. vitripennis venom. However, viability assays and flow cytometry performed on suspension cells 24h after envenomation revealed that inactivation of metalloproteases did not improve cell survival. These results indicate that both protease families may have tissue specific functions. Time course experiments indicate that serine proteases of N. vitripennis venom are responsible for inducing apoptosis in the Sf21 cell line. However, other venom compounds could also be involved in this process and different cell death pathways may take over when a specific type of cell death is inhibited. During parasitation of their natural hosts, both protease families may possibly function in immune related processes and tissue destruction, enabling venom distribution. Overall, this study provides important insights into the functions of serine and metalloproteases in the venom of N. vitripennis.

  11. Impact of Leishmania metalloprotease GP63 on macrophage signaling

    OpenAIRE

    Isnard, Amandine; Shio, Marina T.; Olivier, Martin

    2012-01-01

    The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly infl...

  12. Structure of the N-terminal domain of the metalloprotease PrtV from Vibrio cholerae.

    Science.gov (United States)

    Edwin, Aaron; Persson, Cecilia; Mayzel, Maxim; Wai, Sun Nyunt; Öhman, Anders; Karlsson, B Göran; Sauer-Eriksson, A Elisabeth

    2015-12-01

    The metalloprotease PrtV from Vibrio cholerae serves an important function for the ability of bacteria to invade the mammalian host cell. The protein belongs to the family of M6 proteases, with a characteristic zinc ion in the catalytic active site. PrtV constitutes a 918 amino acids (102 kDa) multidomain pre-pro-protein that undergoes several N- and C-terminal modifications to form a catalytically active protease. We report here the NMR structure of the PrtV N-terminal domain (residues 23-103) that contains two short α-helices in a coiled coil motif. The helices are held together by a cluster of hydrophobic residues. Approximately 30 residues at the C-terminal end, which were predicted to form a third helical structure, are disordered. These residues are highly conserved within the genus Vibrio, which suggests that they might be functionally important.

  13. Domain structure and function of matrix metalloprotease 23 (MMP23): role in potassium channel trafficking.

    Science.gov (United States)

    Galea, Charles A; Nguyen, Hai M; George Chandy, K; Smith, Brian J; Norton, Raymond S

    2014-04-01

    MMP23 is a member of the matrix metalloprotease family of zinc- and calcium-dependent endopeptidases, which are involved in a wide variety of cellular functions. Its catalytic domain displays a high degree of structural homology with those of other metalloproteases, but its atypical domain architecture suggests that it may possess unique functional properties. The N-terminal MMP23 pro-domain contains a type-II transmembrane domain that anchors the protein to the plasma membrane and lacks the cysteine-switch motif that is required to maintain other MMPs in a latent state during passage to the cell surface. Instead of the C-terminal hemopexin domain common to other MMPs, MMP23 contains a small toxin-like domain (TxD) and an immunoglobulin-like cell adhesion molecule (IgCAM) domain. The MMP23 pro-domain can trap Kv1.3 but not closely-related Kv1.2 channels in the endoplasmic reticulum, preventing their passage to the cell surface, while the TxD can bind to the channel pore and block the passage of potassium ions. The MMP23 C-terminal IgCAM domain displays some similarity to Ig-like C2-type domains found in IgCAMs of the immunoglobulin superfamily, which are known to mediate protein-protein and protein-lipid interactions. MMP23 and Kv1.3 are co-expressed in a variety of tissues and together are implicated in diseases including cancer and inflammatory disorders. Further studies are required to elucidate the mechanism of action of this unique member of the MMP family.

  14. Identification, cloning, expression and functional characterization of an astacin-like metalloprotease toxin from Loxosceles intermedia (brown spider) venom.

    Science.gov (United States)

    da Silveira, Rafael B; Wille, Ana C M; Chaim, Olga M; Appel, Marcia H; Silva, Dilza T; Franco, Célia R C; Toma, Leny; Mangili, Oldemir C; Gremski, Waldemiro; Dietrich, Carl P; Nader, Helena B; Veiga, Silvio S

    2007-09-01

    Injuries caused by brown spiders (Loxosceles genus) are associated with dermonecrotic lesions with gravitational spreading and systemic manifestations. The venom has a complex composition containing many different toxins, of which metalloproteases have been described in many different species of this genus. These toxins may degrade extracellular matrix constituents acting as a spreading factor. By using a cDNA library from an Loxosceles intermedia venom gland, we cloned and expressed a 900 bp cDNA, which encoded a signal peptide and a propeptide, which corresponded to a 30 kDa metalloprotease, now named LALP (Loxosceles astacin-like protease). Recombinant LALP was refolded and used to produce a polyclonal antiserum, which showed cross-reactivity with a 29 kDa native venom protein. CD analysis provided evidence that the recombinant LALP toxin was folded correctly, was still in a native conformation and had not aggregated. LALP addition to endothelial cell cultures resulted in de-adhesion of the cells, and also in the degradation of fibronectin and fibrinogen (this could be inhibited by the presence of the bivalent chelator 1,10-phenanthroline) and of gelatin in vitro. Sequence comparison (nucleotide and deduced amino acid), phylogenetic analysis and analysis of the functional recombinant toxin revealed that LALP is related in both structure and function to the astacin family of metalloproteases. This suggests that an astacin-like toxin is present in a animal venom secretion and indicates that recombinant LALP will be a useful tool for future structural and functional studies on venom and the astacin family.

  15. Modulation of CD163 expression by metalloprotease ADAM17 regulates porcine reproductive and respiratory syndrome virus entry.

    Science.gov (United States)

    Guo, Longjun; Niu, Junwei; Yu, Haidong; Gu, Weihong; Li, Ren; Luo, Xiaolei; Huang, Mingming; Tian, Zhijun; Feng, Li; Wang, Yue

    2014-09-01

    As a consequence of their effects on ectodomain shedding, members of the A disintegrin and metalloprotease (ADAM) family have been implicated in the control of various cellular processes. Although ADAM family members are also involved in cancer, inflammation, and other pathologies, it is unclear whether they affect porcine reproductive and respiratory syndrome virus (PRRSV) infection. Here, we demonstrate for the first time that inhibition of ADAM17 enhances PRRSV entry in Marc-145 and porcine alveolar macrophages (PAMs). We also demonstrate that the inhibition of ADAM17 upregulates membrane CD163 expression, a putative PRRSV receptor that is exogenously expressed in BHK-21 and endogenously expressed in Marc-145 and PAMs. Furthermore, overexpression of ADAM17 induced downregulation of CD163 expression and a reduction in PRRSV infection, whereas ablation of ADAM17 expression using specific small interfering RNA resulted in upregulation of CD163 expression with a corresponding increase in PRRSV infection. These ADAM17-mediated effects were confirmed with PRRSV nonpermissive BHK-21 cells transfected with CD163 cDNA. Overall, these findings indicate that ADAM17 downregulates CD163 expression and hinders PRRSV entry. Hence, downregulation of ADAM17 particular substrates may be an additional component of the anti-infection defenses. ADAM17 is one of the important membrane-associated metalloproteases that mediate various cellular events, as well as inflammation, cancer, and other pathologies. Here, we investigate for the first time the role of the metalloprotease ADAM17 in PRRSV infection. By using inhibitor and genetic modification methods, we demonstrate that ADAM17 negatively regulate PRRSV entry by regulating its substrate(s). More specifically, ADAM 17 mediates the downregulation of the PRRSV cellular receptor CD163. The reduction in CD163 expression represents another component of the anti-infection response initiated by ADAM17. Copyright © 2014, American Society

  16. Roles of metalloproteases in metastatic niche.

    Science.gov (United States)

    Rucci, N; Sanità, P; Angelucci, A

    2011-11-01

    Metalloproteinases (MMPs) are a cluster of at least 23 enzymes belonging to the more wide family of endopeptidases called Metzincins, whose structure is characterized by the presence of a zinc ion at the catalytic site. Although the general view of MMPs as physiologic scissors involved in extracellular matrix (ECM) degradation and tissue remodeling is still valid, additional functions have recently emerged, including the ability to cleave non ECM molecules such as growth factors, cytokines and chemokines from their membrane-anchored proforms. These functions are utilized by tumor cells and are fundamental in the determination of tumor progression and invasion. The effect of MMPs activity in cancer progression has been traditionally associated with the acquisition by tumor cells of an invasive phenotype, an indispensable requisite for the metastatic spreading of cancer cells. In addition to the traditional view, a new role for MMPs in creating a favourable microenvironment has been proposed, so that MMPs are not only involved in cell invasion, but also in signaling pathways that control cell growth, inflammation, or angiogenesis. Finally, recent evidence suggest a role of MMPs in the so called "pre-metastatic niche" that is the hypothesis of an early distant modification of the premetastatic site by primary cancer cells. This new hypothesis is changing our traditional view about MMPs and provides important insights into the effective time window for the therapeutic use of MMP inhibitors. In this review we provide the main available data about the ability of MMPs in creating a suitable microenvironment for tumor growth in metastatic sites and we indicate the implication of these data on the potential use of MMP inhibitors in the metastatic therapy.

  17. Human ADAM 12 (meltrin alpha) is an active metalloprotease

    DEFF Research Database (Denmark)

    Loechel, F; Gilpin, B J; Engvall, E

    1998-01-01

    in a latent form, probably by means of a cysteine switch. The zymogen could be activated chemically by alkylation with N-ethylmaleimide. Cleavage of the prodomain at a site for a furin-like endopeptidase resulted in an ADAM 12 protein with proteolytic activity. The protease activity was sensitive...... 12 is catalytically active. We used the trapping mechanism of alpha2-macroglobulin to assay for protease activity of wild-type and mutant ADAM 12 proteins produced in a COS cell transfection system. We found that ADAM 12 is synthesized as a zymogen, with the prodomain maintaining the metalloprotease...

  18. Detection of Vibrio anguillarum and Its Virulent Metalloprotease Using the Method of ELISA

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A method detecting pathogenic Vibrio anguillarum and its virulent metalloprotease is reported in this paper. The metalloprotease is isolated from extracellular product (ECP) of V.anguillarum by the cellophane plate technique and purified by gel filtration and ion-exchange chromatography. Anti-sera are prepared by injecting V.anguillarum cells and metalloprotease into the rabbits. Slide Agglutination Assay is used to detect V.anguillarum in the infection experiment and Enzyme Linked Immunosorbent Assay (ELISA) is carried out to detect concentration of metalloprotease. The result shows that bacterium strain M3 is able to diffuse into the viscera of infected fish through the blood circulating system 10 hours after intramuscular infection, and ELASA is a sensitive method to detect the metalloprotease with detectable amount of 7.8ng. The aim of this study is to establish a sensitive and specific method to observe the infection of V.anguillarum in the host.

  19. A functional and structural study of the major metalloprotease secreted by the pathogenic fungus Aspergillus fumigatus.

    Science.gov (United States)

    Fernández, Daniel; Russi, Silvia; Vendrell, Josep; Monod, Michel; Pallarès, Irantzu

    2013-10-01

    Fungalysins are secreted fungal peptidases with the ability to degrade the extracellular matrix proteins elastin and collagen and are thought to act as virulence factors in diseases caused by fungi. Fungalysins constitute a unique family among zinc-dependent peptidases that bears low sequence similarity to known bacterial peptidases of the thermolysin family. The crystal structure of the archetype of the fungalysin family, Aspergillus fumigatus metalloprotease (AfuMep), has been obtained for the first time. The 1.8 Å resolution structure of AfuMep corresponds to that of an autoproteolyzed proenzyme with separate polypeptide chains corresponding to the N-terminal prodomain in a binary complex with the C-terminal zinc-bound catalytic domain. The prodomain consists of a tandem of cystatin-like folds whose C-terminal end is buried into the active-site cleft of the catalytic domain. The catalytic domain harbouring the key catalytic zinc ion and its ligands, two histidines and one glutamic acid, undergoes a conspicuous rearrangement of its N-terminal end during maturation. One key positively charged amino-acid residue and the C-terminal disulfide bridge appear to contribute to its structural-functional properties. Thus, structural, biophysical and biochemical analysis were combined to provide a deeper comprehension of the underlying properties of A. fumigatus fungalysin, serving as a framework for the as yet poorly known metallopeptidases from pathogenic fungi.

  20. Reduction of the disintegrin and metalloprotease ADAM12 in preeclampsia

    DEFF Research Database (Denmark)

    Laigaard, Jennie; Sørensen, Tina; Placing, Sophie;

    2005-01-01

    OBJECTIVES: The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. METHODS: We developed a semiautomated, time-resolved, immu......OBJECTIVES: The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. METHODS: We developed a semiautomated, time......-resolved, immunofluorometric assay for the quantification of ADAM12 in serum. The assay detected ADAM12 in a range of 78-1248 microg/L. Serum samples derived from women in the first trimester of a normal pregnancy (n = 324) and from women who later developed preeclampsia during pregnancy (n = 160) were obtained from the First...... Trimester Copenhagen Study. ADAM12 levels were assayed in these serum samples. Serum levels of ADAM12 were converted to multiples of the median (MoM) after log-linear regression of concentration versus gestational age. RESULTS: Serum ADAM12 levels in women who developed preeclampsia during pregnancy had...

  1. Epidermal growth factor (EGF) ligand release by substrate-specific a disintegrin and metalloproteases (ADAMs) involves different protein kinase C (PKC) isoenzymes depending on the stimulus.

    Science.gov (United States)

    Dang, Michelle; Dubbin, Karen; D'Aiello, Antonio; Hartmann, Monika; Lodish, Harvey; Herrlich, Andreas

    2011-05-20

    The dysregulation of EGF family ligand cleavage has severe consequences for the developing as well as the adult organism. Therefore, their production is highly regulated. The limiting step is the ectodomain cleavage of membrane-bound precursors by one of several a disintegrin and metalloprotease (ADAM) metalloproteases, and understanding the regulation of cleavage is an important goal of current research. We have previously reported that in mouse lung epithelial cells, the pro-EGF ligands TGFα, neuregulin 1β (NRG), and heparin-binding EGF are differentially cleaved depending on the cleavage stimulus (Herrlich, A., Klinman, E., Fu, J., Sadegh, C., and Lodish, H. (2008) FASEB J.). In this study in mouse embryonic fibroblasts that lack different ADAMs, we show that induced cleavage of EGF ligands can involve the same substrate-specific metalloprotease but does require different stimulus-dependent signaling pathways. Cleavage was stimulated by phorbol ester (12-O-tetradecanoylphorbol-13-acetate (TPA), a mimic of diacylglycerol and PKC activator), hypertonic stress, lysophosphatidic acid (LPA)-induced G protein-coupled receptor activation, or by ionomycin-induced intracellular calcium release. Although ADAMs showed substrate preference (ADAM17, TGFα and heparin-binding EGF; and ADAM9, NRG), substrate cleavage differed substantially with the stimulus, and cleavage of the same substrate depended on the presence of different, sometimes multiple, PKC isoforms. For instance, classical PKC was required for TPA-induced but not hypertonic stress-induced cleavage of all EGF family ligands. Inhibition of PKCζ enhanced NRG release upon TPA stimulation, but it blocked NRG release in response to hypertonic stress. Our results suggest a model in which substantial regulation of ectodomain cleavage occurs not only on the metalloprotease level but also on the level of the substrate or of a third protein.

  2. Do Matrix Metalloproteases and Tissue Inhibitors of Metalloproteases in Tenocytes of the Rotator Cuff Differ with Varying Donor Characteristics?

    Directory of Open Access Journals (Sweden)

    Franka Klatte-Schulz

    2015-06-01

    Full Text Available An imbalance between matrix metalloproteases (MMPs and the tissue inhibitors of metalloproteases (TIMPs may have a negative impact on the healing of rotator cuff tears. The aim of the project was to assess a possible relationship between clinical and radiographic characteristics of patients such as the age, sex, as well as the degenerative status of the tendon and the MMPs and TIMPs in their tenocyte-like cells (TLCs. TLCs were isolated from ruptured supraspinatus tendons and quantitative Real-Time PCR and ELISA was performed to analyze the expression and secretion of MMPs and TIMPs. In the present study, MMPs, mostly gelatinases and collagenases such as MMP-2, -9 and -13 showed an increased expression and protein secretion in TLCs of donors with higher age or degenerative status of the tendon. Furthermore, the expression and secretion of TIMP-1, -2 and -3 was enhanced with age, muscle fatty infiltration and tear size. The interaction between MMPs and TIMPs is a complex process, since TIMPs are not only inhibitors, but also activators of MMPs. This study shows that MMPs and TIMPs might play an important role in degenerative tendon pathologies.

  3. Vibrio cholerae hemagglutinin(HA)/protease: an extracellular metalloprotease with multiple pathogenic activities

    Science.gov (United States)

    Benitez, Jorge A.; Silva, Anisia J.

    2016-01-01

    Vibrio cholerae of serogroup O1 and O139, the etiological agent of the diarrheal disease cholera, expresses the extracellular Zn-dependent metalloprotease hemagglutinin (HA)/protease also reported as vibriolysin. This enzyme is also produced by non-O1/O139 (non-cholera) strains that cause mild, sporadic illness (i.e. gastroenteritis, wound or ear infections). Orthologs of HA/protease are present in other members of the Vibrionaceae family pathogenic to humans and fish. HA/protease belongs to the M4 neutral peptidase family and displays significant amino acid sequence homology to Pseudomonas aeruginosa elastase (LasB) and Bacillus thermoproteolyticus thermolysin. It exhibits a broad range of potentially pathogenic activities in cell culture and animal models. These activities range from the covalent modification of other toxins, the degradation of the protective mucus barrier and disruption of intestinal tight junctions. Here we review (i) the structure and regulation of HA/protease expression, (ii) its interaction with other toxins and the intestinal mucosa and (iii) discuss the possible role(s) of HA/protease in the pathogenesis of cholera. PMID:26952544

  4. The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle ecdysis in free-living and parasitic nematodes.

    Science.gov (United States)

    Stepek, Gillian; McCormack, Gillian; Birnie, Andrew J; Page, Antony P

    2011-02-01

    Nematodes represent one of the most abundant and species-rich groups of animals on the planet, with parasitic species causing chronic, debilitating infections in both livestock and humans worldwide. The prevalence and success of the nematodes is a direct consequence of the exceptionally protective properties of their cuticle. The synthesis of this cuticle is a complex multi-step process, which is repeated 4 times from hatchling to adult and has been investigated in detail in the free-living nematode, Caenorhabditis elegans. This process is known as moulting and involves numerous enzymes in the synthesis and degradation of the collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally conserved enzymes of the astacin metalloprotease family which, when mutated, result in a phenotype associated with the late-stage moulting defects, namely the inability to remove the preceding cuticle. Extensive genome searches in the gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues. Significantly, the nas-36 gene from B. malayi could successfully complement the moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double mutants, suggesting a conserved function for NAS-36 between these diverse nematode species. This conservation between species was further indicated when the recombinant enzymes demonstrated a similar range of inhibitable metalloprotease activities.

  5. Activation of the Wnt/β-catenin pathway and tissue inhibitor of metalloprotease 1 during tertiary dentinogenesis.

    Science.gov (United States)

    Yoshioka, Seisuke; Takahashi, Yusuke; Abe, Makoto; Michikami, Ikumi; Imazato, Satoshi; Wakisaka, Satoshi; Hayashi, Mikako; Ebisu, Shigeyuki

    2013-01-01

    Tertiary dentin is deposited inside teeth after various stimuli and serves as a major defensive wall to preserve pulp cells. However, the molecular mechanisms of the activation of quiescent odontoblasts, immature pulp cells and tertiary dentin formation are still unclear. Therefore, we performed a comprehensive gene expression analysis of pulp cells after cavity preparation of 9-week-old rat molars to clarify the critical molecules in tertiary dentinogenesis. As a result, mRNA expression of various molecules was up- or down-regulated. Notably, several members of the matrix metalloprotease family and their endogenous inhibitors were up-regulated after cavity preparation. In situ hybridization showed that tissue inhibitor of metalloprotease 1 (Timp1) was widely and continuously distributed in the pulp beneath the cavity in vivo. We also observed accumulation of β-catenin in the pulp cells beneath the cavity by fluorescence immunohistochemistry. Furthermore, Timp1 transcription was repressed by a dominant-negative TCF4 in immature undifferentiated mesenchymal cells, but not altered in mature odontoblast-like cells. These results indicate that cavity preparation may activate the Wnt/β-catenin pathway and the Wnt/β-catenin pathway and Timp1 may be correlatively involved in pulp repair. Timp1 might play crucial roles in reactivation of immature pulp cells for tertiary dentinogenesis.

  6. Identification of a chitinase-modifying protein from Fusarium verticillioides: truncation of a host resistance protein by a fungalysin metalloprotease.

    Science.gov (United States)

    Naumann, Todd A; Wicklow, Donald T; Price, Neil P J

    2011-10-14

    Chitinase-modifying proteins (cmps) are proteases secreted by fungal pathogens that truncate the plant class IV chitinases ChitA and ChitB during maize ear rot. cmp activity has been characterized for Bipolaris zeicola and Stenocarpella maydis, but the identities of the proteases are not known. Here, we report that cmps are secreted by multiple species from the genus Fusarium, that cmp from Fusarium verticillioides (Fv-cmp) is a fungalysin metalloprotease, and that it cleaves within a sequence that is conserved in class IV chitinases. Protein extracts from Fusarium cultures were found to truncate ChitA and ChitB in vitro. Based on this activity, Fv-cmp was purified from F. verticillioides. N-terminal sequencing of truncated ChitA and MALDI-TOF-MS analysis of reaction products showed that Fv-cmp is an endoprotease that cleaves a peptide bond on the C-terminal side of the lectin domain. The N-terminal sequence of purified Fv-cmp was determined and compared with a set of predicted proteins, resulting in its identification as a zinc metalloprotease of the fungalysin family. Recombinant Fv-cmp also truncated ChitA, confirming its identity, but had reduced activity, suggesting that the recombinant protease did not mature efficiently from its propeptide-containing precursor. This is the first report of a fungalysin that targets a nonstructural host protein and the first to implicate this class of virulence-related proteases in plant disease.

  7. The Metalloprotease Neprilysin Degrades and Inactivates Apelin Peptides.

    Science.gov (United States)

    McKinnie, Shaun M K; Fischer, Conrad; Tran, Kelvin M H; Wang, Wang; Mosquera, Fabricio; Oudit, Gavin Y; Vederas, John C

    2016-08-17

    The apelinergic system is a mammalian peptide hormone network with key physiological roles. Apelin isoforms and analogues are believed to be promising therapeutics for cardiovascular disease. Despite extensive studies on apelin-13 degradation patterns, only one protease, angiotensin-converting enzyme 2 (ACE2), had been implicated in its physiological regulation. Through use of a peptide-based fluorescent probe, we identified the metalloprotease neprilysin (NEP, a target for Entresto used in treatment of heart failure) as an enzyme that cleaves apelin isoforms. In vitro NEP proteolysis generated fragments that lacked the ability to bind to the apelin receptor, thereby making NEP the first protease to fully inactivate apelin. The involvement of NEP in the apelinergic system contributes to the understanding of its role in cardiovascular physiology.

  8. Activation and proteolytic activity of the Treponema pallidum metalloprotease, pallilysin.

    Science.gov (United States)

    Houston, Simon; Hof, Rebecca; Honeyman, Lisa; Hassler, Julia; Cameron, Caroline E

    2012-01-01

    Treponema pallidum is a highly invasive pathogen that undergoes rapid dissemination to establish widespread infection. Previous investigations identified the T. pallidum adhesin, pallilysin, as an HEXXH-containing metalloprotease that undergoes autocatalytic cleavage and degrades laminin and fibrinogen. In the current study we characterized pallilysin's active site, activation requirements, cellular location, and fibrin clot degradation capacity through both in vitro assays and heterologous treponemal expression and degradation studies. Site-directed mutagenesis showed the pallilysin HEXXH motif comprises at least part of the active site, as introduction of three independent mutations (AEXXH [H¹⁹⁸A], HAXXH [E¹⁹⁹A], and HEXXA [H²⁰²A]) abolished pallilysin-mediated fibrinogenolysis but did not adversely affect host component binding. Attainment of full pallilysin proteolytic activity was dependent upon autocatalytic cleavage of an N-terminal pro-domain, a process which could not occur in the HEXXH mutants. Pallilysin was shown to possess a thrombin cleavage site within its N-terminal pro-domain, and in vitro studies confirmed cleavage of pallilysin with thrombin generates a truncated pallilysin fragment that has enhanced proteolytic activity, suggesting pallilysin can also exploit the host coagulation process to facilitate protease activation. Opsonophagocytosis assays performed with viable T. pallidum demonstrated pallilysin is a target of opsonic antibodies, consistent with a host component-interacting, surface-exposed cellular location. Wild-type pallilysin, but not the HEXXA mutant, degraded fibrin clots, and similarly heterologous expression of pallilysin in the non-invasive spirochete Treponema phagedenis facilitated fibrin clot degradation. Collectively these results identify pallilysin as a surface-exposed metalloprotease within T. pallidum that possesses an HEXXH active site motif and requires autocatalytic or host-mediated cleavage of a pro

  9. Differential metalloprotease content and activity of three Loxosceles spider venoms revealed using two-dimensional electrophoresis approaches.

    Science.gov (United States)

    Trevisan-Silva, Dilza; Bednaski, Aline Viana; Gremski, Luiza Helena; Chaim, Olga Meiri; Veiga, Silvio Sanches; Senff-Ribeiro, Andrea

    2013-12-15

    Loxosceles bites have been associated with characteristic dermonecrotic lesions with gravitational spreading and systemic manifestations. Venom primarily comprises peptides and protein molecules (5-40 kDa) with multiple biological activities. Although poorly studied, metalloproteases have been identified in venoms of several Loxosceles species, presenting proteolytic effects on extracellular matrix components. The characterization of an Astacin-like protease (LALP) in Loxosceles intermedia venom was the first report of an Astacin family member as a component of animal venom. Recently, these proteases were described as a gene family in L. intermedia, Loxosceles laeta and Loxosceles gaucho. Herein, the whole venom complexity of these three Loxosceles species was analyzed using two-dimensional electrophoresis (2DE). Subproteomes of LALPs were explored through 2DE immunostaining using anti-LALP1 antibodies and 2DE gelatin zymogram. Proteins presented molecular masses ranging from 24 to 29 kDa and the majority of these molecules had basic or neutral isoelectric points (6.89-9.93). Likewise, the measurement of gelatinolytic effects of Loxosceles venom using fluorescein-gelatin showed that the three venoms have distinct proteolytic activities. The metalloprotease fibrinogenolytic activities were also evaluated. All venoms showed fibrinogenolytic activity with different proteolytic effects on Aα and Bβ chains of fibrinogen. The results reported herein suggest that the LALP family is larger than indicated in previously published data and that the complex profile of the gelatinolytic activity reflects their relevance in loxoscelism. Furthermore, our investigation implicates the brown spider venom as a source of Astacin-like proteases for use in loxoscelism studies, cell biology research and biotechnological applications.

  10. Cloning, sequencing and expression of the gene encoding the extracellular metalloprotease of Aeromonas caviae.

    Science.gov (United States)

    Kawakami, K; Toma, C; Honma, Y

    2000-01-01

    A gene (apk) encoding the extracellular protease of Aeromonas caviae Ae6 has been cloned and sequenced. For cloning the gene, the DNA genomic library was screened using skim milk LB agar. One clone harboring plasmid pKK3 was selected for sequencing. Nucleotide sequencing of the 3.5 kb region of pKK3 revealed a single open reading frame (ORF) of 1,785 bp encoding 595 amino acids. The deduced polypeptide contained a putative 16-amino acid signal peptide followed by a large propeptide. The N-terminal amino acid sequence of purified recombinant protein (APK) was consistent with the DNA sequence. This result suggested a mature protein of 412 amino acids with a molecular mass of 44 kDa. However, the molecular mass of purified recombinant APK revealed 34 kDa by SDS-PAGE, suggesting that further processing at the C-terminal region took place. The 2 motifs of zinc binding sites deduced are highly conserved in the APK as well as in other zinc metalloproteases including Vibrio proteolyticus neutral protease, Emp V from Vibrio vulnificus, HA/P from Vibrio cholerae, and Pseudomonas aeruginosa elastase. Proteolytic activity was inhibited by EDTA, Zincov, 1,10-phenanthroline and tetraethylenepentamine while unaffected by the other inhibitors tested. The protease showed maximum activity at pH 7.0 and was inactivated by heating at 80 C for 15 min. These results together suggest that APK belongs to the thermolysin family of metalloendopeptidases.

  11. Purification and characterization of fibrinolytic metalloprotease from Perenniporia fraxinea mycelia.

    Science.gov (United States)

    Kim, Jae-Sung; Kim, Ji-Eun; Choi, Bong-Suk; Park, Se-Eun; Sapkota, Kumar; Kim, Seung; Lee, Hyun-Hwa; Kim, Chun-Sung; Park, Yeal; Kim, Myung-Kon; Kim, Yoon-Sik; Kim, Sung-Jun

    2008-08-01

    In this study we purified and characterized a fibrinolytic protease from the mycelia of Perenniporia fraxinea. The apparent molecular mass of the purified enzyme was estimated to be 42kDa by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), fibrin zymography and size exclusion using fast protein liquid chromatography (FPLC). The first 20 amino acid residues of the N-terminal sequence were ASYRVLPITKELLPPEFFVA, which shows a high degree of similarity with a fungalysin metallopeptidase from Coprinopsis cinerea. The optimal reaction pH value and temperature were pH 6.0 and 35-40 degrees C, respectively. Results for the fibrinolysis pattern showed that the protease rapidly hydrolyzed the fibrin alpha-chain followed by the beta-chain. The gamma-gamma chains were also hydrolyzed, but more slowly. The purified protease effectively hydrolyzed fibrinogen, preferentially digesting the Aalpha-chains of fibrinogen, followed by Bbeta- and gamma-chains. We found that protease activity was inhibited by Cu(2+), Fe(3+), and Zn(2+), but enhanced by the additions of Mn(2+), Mg(2+) and Ca(2+) metal ions. Furthermore, the protease activity was inhibited by EDTA, and it was found to exhibit a higher specificity for the chromogenic substrate S-2586 for chymotrypsin, indicating that the enzyme is a chymotrypsin-like metalloprotease. The mycelia of P. fraxinea may thus represent a source of new therapeutic agents to treat thrombosis.

  12. Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides.

    Science.gov (United States)

    Kooi, Cora; Sokol, Pamela A

    2009-09-01

    Burkholderia cenocepacia secretes two zinc-dependent metalloproteases, designated ZmpA and ZmpB. Previously, ZmpA and ZmpB have been shown to cleave several proteins important in host defence. In this study, the ability of ZmpA and ZmpB to digest and inactivate antimicrobial peptides involved in innate immunity was examined. ZmpB but not ZmpA cleaved beta-defensin-1. ZmpA but not ZmpB cleaved the cathelicidin LL-37. Both enzymes cleaved elafin and secretory leukocyte inhibitor, which are antimicrobial peptides as well as neutrophil elastase inhibitors. Both ZmpA and ZmpB cleaved protamine, a fish antimicrobial peptide, and a zmpA zmpB mutant was more sensitive to protamine killing than the parental strain. ZmpA or ZmpB cleavage of elafin inactivated its anti-protease activity. The effect of ZmpA and ZmpB on the neutrophil proteases elastase and cathepsin G was also examined but neither enzyme was active against these host proteases. These studies suggest that ZmpA and ZmpB may influence the resistance of B. cenocepacia to host antimicrobial peptides as well as alter the host protease/anti-protease balance in chronic respiratory infections.

  13. In vivo imaging of matrix metalloprotease 12 and matrix metalloprotease 13 activities in the mouse model of collagen-induced arthritis

    DEFF Research Database (Denmark)

    Lim, Ngee Han; Meinjohanns, Ernst; Bou-Gharios, George;

    2014-01-01

    from a peptide phosphinic inhibitor library. Selectivity of the probes was demonstrated in vitro using MMP-1, MMP-2, MMP-3, MMP-12, and MMP-13. In vivo activation of the probe was tested in the zymosan-induced mouse model of inflammation and probe specificity was evaluated by the metalloprotease...

  14. A function for a specific zinc metalloprotease of African trypanosomes.

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    Paul M Grandgenett

    2007-10-01

    Full Text Available The Trypanosoma brucei genome encodes three groups of zinc metalloproteases, each of which contains approximately 30% amino acid identity with the major surface protease (MSP, also called GP63 of Leishmania. One of these proteases, TbMSP-B, is encoded by four nearly identical, tandem genes transcribed in both bloodstream and procyclic trypanosomes. Earlier work showed that RNA interference against TbMSP-B prevents release of a recombinant variant surface glycoprotein (VSG from procyclic trypanosomes. Here, we used gene deletions to show that TbMSP-B and a phospholipase C (GPI-PLC act in concert to remove native VSG during differentiation of bloodstream trypanosomes to procyclic form. When the four tandem TbMSP-B genes were deleted from both chromosomal alleles, bloodstream B (-/- trypanosomes could still differentiate to procyclic form, but VSG was removed more slowly and in a non-truncated form compared to differentiation of wild-type organisms. Similarly, when both alleles of the single-copy GPI-PLC gene were deleted, bloodstream PLC (-/- cells could still differentiate. However, when all the genes for both TbMSP-B and GPI-PLC were deleted from the diploid genome, the bloodstream B (-/- PLC (-/- trypanosomes did not proliferate in the differentiation medium, and 60% of the VSG remained on the cell surface. Inhibitors of cysteine proteases did not affect this result. These findings demonstrate that removal of 60% of the VSG during differentiation from bloodstream to procyclic form is due to the synergistic activities of GPI-PLC and TbMSP-B.

  15. Metalloproteases in Trypanosoma rangeli-infected Rhodnius prolixus

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    D Feder

    1999-11-01

    Full Text Available Protease activities in the haemolymph and fat body in a bloodsucking insect, Rhodnius prolixus, infected with Trypanosoma rangeli, were investigated. After SDS-polyacrylamide gel electrophoresis containing gelatin as substrate, analysis of zymograms performed on samples of different tissues of controls and insects inoculated or orally infected with short or long epimastigotes of T. rangeli, demonstrated distinct patterns of protease activities: (i proteases were detected in the haemolymph of insects which were fed on, or inoculated with, short epimastigotes of T. rangeli (39 kDa and 33 kDa, respectively, but they were not observed in the fat body taken from these insects; (ii protease was also presented in the fat bodies derived from naive insects or controls inoculated with sterile phosphate-saline buffer (49 kDa, but it was not detected in the haemolymph of these insects; (iii no protease activity was observed in both haemolymph and fat bodies taken from insects inoculated with, or fed on, long epimastigotes of T. rangeli. Furthermore, in short epimastigotes of T. rangeli extracts, three bands of the protease activities with apparent molecular weights of 297, 198 and 95 kDa were detected while long epimastigotes preparation presented only two bands of protease activities with molecular weights of 297 and 198 kDa. The proteases from the insect infected with T. rangeli and controls belong to the class of either metalloproteases or metal-activated enzymes since they are inhibited by 1,10-phenanthroline. The significance of these proteases in the insects infected with short epimastigotes of T. rangeli is discussed in relation to the success of the establishment of infection of these parasites in its vector, R. prolixus.

  16. Calcium binding by the PKD1 domain regulates interdomain flexibility in Vibrio cholerae metalloprotease PrtV.

    Science.gov (United States)

    Edwin, Aaron; Rompikuntal, Pramod; Björn, Erik; Stier, Gunter; Wai, Sun N; Sauer-Eriksson, A Elisabeth

    2013-01-01

    Vibrio cholerae, the causative agent of cholera, releases several virulence factors including secreted proteases when it infects its host. These factors attack host cell proteins and break down tissue barriers and cellular matrix components such as collagen, laminin, fibronectin, keratin, elastin, and they induce necrotic tissue damage. The secreted protease PrtV constitutes one virulence factors of V. cholerae. It is a metalloprotease belonging to the M6 peptidase family. The protein is expressed as an inactive, multidomain, 102 kDa pre-pro-protein that undergoes several N- and C-terminal modifications after which it is secreted as an intermediate variant of 81 kDa. After secretion from the bacteria, additional proteolytic steps occur to produce the 55 kDa active M6 metalloprotease. The domain arrangement of PrtV is likely to play an important role in these maturation steps, which are known to be regulated by calcium. However, the molecular mechanism by which calcium controls proteolysis is unknown. In this study, we report the atomic resolution crystal structure of the PKD1 domain from V. cholera PrtV (residues 755-838) determined at 1.1 Å. The structure reveals a previously uncharacterized Ca(2+)-binding site located near linker regions between domains. Conformational changes in the Ca(2+)-free and Ca(2+)-bound forms suggest that Ca(2+)-binding at the PKD1 domain controls domain linker flexibility, and plays an important structural role, providing stability to the PrtV protein.

  17. Comparison of the binding specificity of two bacterial metalloproteases, LasB of Pseudomonas aeruginosa and ZapA of Proteus mirabilis, using N-alpha mercaptoamide template-based inhibitor analogues.

    Science.gov (United States)

    Carson, Louise; Cathcart, George R; Ceri, Howard; Walker, Brian; Gilmore, Brendan F

    2012-06-01

    The metalloproteases ZapA of Proteus mirabilis and LasB of Pseudomonas aeruginosa are known to be virulence factors their respective opportunistic bacterial pathogens, and are members of the structurally related serralysin and thermolysin families of bacterial metalloproteases respectively. Secreted at the site of infection, these proteases play a key role in the infection process, contributing to tissue destruction and processing of components of the host immune system. Inhibition of these virulence factors may therefore represent an antimicrobial strategy, attenuating the virulence of the infecting pathogen. Previously we have screened a library of N-alpha mercaptoamide dipeptide inhibitors against both ZapA and LasB, with the aim of mapping the S1' binding site of the enzymes, revealing both striking similarities and important differences in their binding preferences. Here we report the design, synthesis, and screening of several inhibitor analogues, based on two parent inhibitors from the original library. The results have allowed for further characterization of the ZapA and LasB active site binding pockets, and have highlighted the possibility for development of broad-spectrum bacterial protease inhibitors, effective against enzymes of the thermolysin and serralysin metalloprotease families. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition

    Science.gov (United States)

    López-Cobo, Sheila; Campos-Silva, Carmen; Valés-Gómez, Mar

    2016-01-01

    Communication within the immune system depends on the release of factors that can travel and transmit information at points distant from the cell that produced them. In general, immune cells use two key strategies that can occur either at the plasma membrane or in intracellular compartments to produce such factors, vesicle release and proteolytic cleavage. Release of soluble factors in exosomes, a subset of vesicles that originate from intracellular compartments, depends generally on biochemical and lipid environment features. This physical environment allows proteins to be recruited to membrane microdomains that will be later endocytosed and further released to the extracellular milieu. Cholesterol and sphingolipid rich domains (also known as lipid rafts or detergent-resistant membranes, DRMs) often contribute to exosomes and these membrane regions are rich in proteins modified with Glycosyl-Phosphatidyl-Inositol (GPI) and lipids. For this reason, many palmitoylated and GPI-anchored proteins are preferentially recruited to exosomes. In this review, we analyse the biochemical features involved in the release of NKG2D-ligands as an example of functionally related gene families encoding both transmembrane and GPI-anchored proteins that can be released either by proteolysis or in exosomes, and modulate the intensity of the immune response. The immune receptor NKG2D is present in all human Natural Killer and T cells and plays an important role in the first barrier of defense against tumor and infection. However, tumor cells can evade the immune system by releasing NKG2D-ligands to induce down-regulation of the receptor. Some NKG2D-ligands can be recruited to exosomes and potently modulate receptor expression and immune function, while others are more susceptible to metalloprotease cleavage and are shed as soluble molecules. Strikingly, metalloprotease inhibition is sufficient to drive the accumulation in exosomes of ligands otherwise released by metalloprotease

  19. Glycosyl-phosphatidyl-inositol (GPI-anchors and metalloproteases: their roles in the regulation of exosome composition and NKG2D-mediated immune recognition

    Directory of Open Access Journals (Sweden)

    Sheila López-Cobo

    2016-09-01

    Full Text Available Communication within the immune system depends on the release of factors that can travel and transmit information at points distant from the cell that produced them. In general, immune cells use two key strategies that can occur either at the plasma membrane or in intracellular compartments to produce such factors, vesicle release and proteolytic cleavage. Release of soluble factors in exosomes, a subset of vesicles that originate from intracellular compartments, depends generally on biochemical and lipid environment features. This physical environment allows proteins to be recruited to membrane microdomains that will be later endocytosed and further released to the extracellular milieu. Cholesterol and sphingolipid rich domains (also known as lipid rafts or detergent-resistant membranes, DRMs often contribute to exosomes and these regions are rich in proteins modified with Glycosyl-Phosphatidyl-Inositol (GPI and lipids. For this reason, many palmitoylated and GPI-anchored proteins are preferentially recruited to exosomes. In this review, we analyse the biochemical features involved in the release of NKG2D-ligands as an example of functionally related gene families encoding both transmembrane and GPI-anchored proteins that can be released either by proteolysis or in exosomes, and modulate the intensity of the immune response. The immune receptor NKG2D is present in all human Natural Killer and T cells and plays an important role in the first barrier of defence against tumor and infection. However, tumor cells can evade the immune system by releasing NKG2D-ligands to induce down-regulation of the receptor. Some NKG2D-ligands can be recruited to exosomes and potently modulate receptor expression and immune function, while other are more susceptible to metalloprotease cleavage and are shed as soluble molecules. Strikingly, metalloprotease inhibition is sufficient to drive the accumulation in exosomes of ligands otherwise released by metalloprotease

  20. Virulence of metalloproteases produced by Vibrio species on Pacific oyster Crassostrea gigas larvae.

    Science.gov (United States)

    Hasegawa, Hiroaki; Gharaibeh, Dima N; Lind, Erin J; Häse, Claudia C

    2009-06-10

    Vibrio tubiashii, a pathogen of shellfish larvae and juveniles, produces several extracellular products. Here, we document that culture supernatants of several marine Vibrio species showed toxicity to oyster larvae. Treatment of these supernatants with EDTA not only severely diminished proteolytic activities, but also dramatically reduced toxicity to the larvae. Culture supernatants of metalloprotease-deficient mutants of V. tubiashii, V. cholerae, and V. splendidus were impaired in their ability to cause larval death compared to the wild type strains. Culture supernatants of Pseudomonas aeruginosa, known to contain several secreted proteases, showed virtually no toxicity to oyster larvae. Purified V. tubiashii protease A (VtpA), but not the prototype metalloprotease, thermolysin from Bacillus thermoproteolyticus, was highly toxic to the larvae. In addition, toxicity of purified VtpA was much greater for 6-d-old oyster larvae than for 16-d-old larvae. Together, these results indicated that culture supernatants of a variety of Vibrio species are highly toxic to oyster larvae and that the production of a metalloprotease is required for this effect. We propose that there are, as yet uncharacterized, specific substrates contained in larval tissue that are degraded by VtpA as well as certain homologous metalloproteases produced by other marine Vibrio species which, in turn, may contribute to vibriosis.

  1. Expression of ADAMs ("a disintegrin and metalloprotease") in the human lung

    NARCIS (Netherlands)

    Dijkstra, Antoon; Postma, Dirkje S.; Noordhoek, Jacobien A.; Lodewijk, Monique E.; Kauffman, Henk F.; ten Hacken, Nick H. T.; Timens, Wim

    2009-01-01

    In view of the associations of "a disintegrin and metalloprotease" (ADAM) with respiratory diseases, we assessed the expression of various ADAMs in human lung tissue. Lung tissue was obtained from nine individuals who underwent surgery for lung cancer or underwent lung transplantation for emphysema.

  2. Metalloprotease Peptide Inhibitors: A Semester-Long Organic Synthetic Research Project for the Introductory Laboratory Course

    Science.gov (United States)

    Pontrello, Jason K.

    2015-01-01

    A semester-long research project to synthesize unique compounds designed after published metalloprotease peptide inhibitors is presented. The research project encompasses a set of nine organic chemistry reactions traditionally taught in the second semester lab course, and the procedures are derived from scientific literature. The two principle…

  3. Design of Peptide Hydroxamate-Based Photoreactive Activity-Based Probes of Zinc-Dependent Metalloproteases

    NARCIS (Netherlands)

    Geurink, Paul P.; Klein, Theo; Prely, Laurette; Paal, Krisztina; Leeuwenburgh, Michiel A.; van der Marel, Gijs A.; Kauffman, Henk F.; Overkleeft, Herman S.; Bischoff, Rainer

    2010-01-01

    Metalloproteases (ADAMs, MMPs) are multidomain proteins that play key roles in extracellular matrix remodelling and degradation, in cell-cell and cell-matrix interactions and in the proteolytic liberation of membrane-anchored proforms of cytokines and growth factors, the so-called ectodomain sheddin

  4. A smallest 6 kda metalloprotease, mini-matrilysin, in living world: a revolutionary conserved zinc-dependent proteolytic domain- helix-loop-helix catalytic zinc binding domain (ZBD

    Directory of Open Access Journals (Sweden)

    Yu Wei-Hsuan

    2012-05-01

    Full Text Available Abstract Background The Aim of this study is to study the minimum zinc dependent metalloprotease catalytic folding motif, helix B Met loop-helix C, with proteolytic catalytic activities in metzincin super family. The metzincin super family share a catalytic domain consisting of a twisted five-stranded β sheet and three long α helices (A, B and C. The catalytic zinc is at the bottom of the cleft and is ligated by three His residues in the consensus sequence motif, HEXXHXXGXXH, which is located in helix B and part of the adjacent Met turn region. An interesting question is - what is the minimum portion of the enzyme that still possesses catalytic and inhibitor recognition?” Methods We have expressed a 60-residue truncated form of matrilysin which retains only the helix B-Met turn-helix C region and deletes helix A and the five-stranded β sheet which form the upper portion of the active cleft. This is only 1/4 of the full catalytic domain. The E. coli derived 6 kDa MMP-7 ZBD fragments were purified and refolded. The proteolytic activities were analyzed by Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 peptide assay and CM-transferrin zymography analysis. SC44463, BB94 and Phosphoramidon were computationally docked into the 3day structure of the human MMP7 ZBD and TAD and thermolysin using the docking program GOLD. Results This minimal 6 kDa matrilysin has been refolded and shown to have proteolytic activity in the Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 peptide assay. Triton X-100 and heparin are important factors in the refolding environment for this mini-enzyme matrilysin. This minienzyme has the proteolytic activity towards peptide substrate, but the hexamer and octamer of the mini MMP-7 complex demonstrates the CM-transferrin proteolytic activities in zymographic analysis. Peptide digestion is inhibited by SC44463, specific MMP7 inhibitors, but not phosphorimadon. Interestingly, the mini MMP-7 can be processed by autolysis and producing ~ 6

  5. Isolation and characterization of metalloproteases with a novel domain structure by construction and screening of metagenomic libraries.

    Science.gov (United States)

    Waschkowitz, Tanja; Rockstroh, Stephanie; Daniel, Rolf

    2009-04-01

    Small-insert metagenomic libraries from four samples were constructed by a topoisomerase-based and a T4 DNA ligase-based approach. Direct comparison of both approaches revealed that application of the topoisomerase-based method resulted in a higher number of insert-containing clones per microg of environmental DNA used for cloning and a larger average insert size. Subsequently, the constructed libraries were partially screened for the presence of genes conferring proteolytic activity. The function-driven screen was based on the ability of the library-containing Escherichia coli clones to form halos on skim milk-containing agar plates. The screening of 80,000 E. coli clones yielded four positive clones. Two of the plasmids (pTW2 and pTW3) recovered from positive clones conferred strong proteolytic activity and were studied further. Analysis of the entire insert sequences of pTW2 (28,113 bp) and pTW3 (19,956 bp) suggested that the DNA fragments were derived from members of the genus Xanthomonas. Each of the plasmids harbored one gene (2,589 bp) encoding a metalloprotease (mprA, pTW2; mprB, pTW3). Sequence and biochemical analyses revealed that MprA and MprB are similar extracellular proteases belonging to the M4 family of metallopeptidases (thermolysin-like family). Both enzymes possessed a unique modular structure and consisted of four regions: the signal sequence, the N-terminal proregion, the protease region, and the C-terminal extension. The architecture of the latter region, which was characterized by the presence of two prepeptidase C-terminal domains and one proprotein convertase P domain, is novel for bacterial metalloproteases. Studies with derivatives of MprA and MprB revealed that the C-terminal extension is not essential for protease activity. The optimum pH and temperature of both proteases were 8.0 and 65 degrees C, respectively, when casein was used as substrate.

  6. RNA-seq-based metatranscriptomic and microscopic investigation reveals novel metalloproteases of Neobodo sp. as potential virulence factors for soft tunic syndrome in Halocynthia roretzi.

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    Ho Bin Jang

    Full Text Available Bodonids and trypanosomatids are derived from a common ancestor with the bodonids being a more primitive lineage. The Neobodonida, one of the three clades of bodonids, can be free-living, commensal or parasitic. Despite the ecological and evolutionary significance of these organisms, however, many of their biological and pathological features are currently unknown. Here, we employed metatranscriptomics using RNA-seq technology combined with field-emission microscopy to reveal the virulence factors of a recently described genus of Neobodonida that is considered to be responsible for ascidian soft tunic syndrome (AsSTS, but whose pathogenesis is unclear. Our microscopic observation of infected tunic tissues suggested putative virulence factors, enabling us to extract novel candidate transcripts; these included cysteine proteases of the families C1 and C2, serine proteases of S51 and S9 families, and metalloproteases grouped into families M1, M3, M8, M14, M16, M17, M24, M41, and M49. Protease activity/inhibition assays and the estimation of expression levels within gene clusters allowed us to identify metalloprotease-like enzymes as potential virulence attributes for AsSTS. Furthermore, a multimarker-based phylogenetic analysis using 1,184 concatenated amino acid sequences clarified the order Neobodo sp. In sum, we herein used metatranscriptomics to elucidate the in situ expression profiles of uncharacterized putative transcripts of Neobodo sp., combined these results with microscopic observation to select candidate genes relevant to pathogenesis, and used empirical screening to define important virulence factors.

  7. Rosiglitazone attenuates the metalloprotease/anti-metalloprotease imbalance in emphysema induced by cigarette smoke: involvement of extracellular signal-regulated kinase and NFκB signaling

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    Hou G

    2015-04-01

    Full Text Available Gang Hou, Yan Yin, Dan Han, Qiu-yue Wang, Jian Kang Department of Respiratory Medicine, the First Hospital of China Medical University, Shenyang, People’s Republic of China Objective: We investigated how rosiglitazone attenuated cigarette smoke (CS-induced emphysema in a rat model. In particular, we focused on its possible effects on the imbalance between metalloprotease (MMP and anti-MMP activity, mitogen-activated protein kinase (MAPK phosphorylation, and nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB signaling pathway over-activation.Methods: A total of 36 Wistar rats were divided into three groups (n=12 each: animals were exposed to CS for 12 weeks in the absence (the CS group or presence of 30 mg/kg rosiglitazone (the rosiglitazone-CS [RCS] group; a control group was treated with the rosiglitazone vehicle only, without any CS exposure. Histopathology of lung tissue in all groups was evaluated to grade severity of the disease. Expression levels of peroxisome proliferator-activated receptor γ (PPARγ, MMP2, and MMP9 in lung tissue were determined and compared using Western blotting and immunohistochemistry. Activation of MAPKs, NFκB, and the nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor, alpha (IκBα phosphorylation in lung tissue was examined by Western blotting.Results: Emphysema-related pathology, based on inter-alveolar wall distance and alveolar density, was less severe in the RCS group than in the CS group. Compared with the CS group, levels of PPARγ were higher in the RCS group, and levels of MMP2 and MMP9 proteins were lower in the RCS rats. Levels of activated MAPKs and NFκB were also lower, while the IκBαphosphorylation was increased in the lung tissue of RCS rats.Conclusion: Our findings suggest that oral administration of rosiglitazone attenuates the metalloprotease activity induced by CS, and the underlying mechanism might involve the activation of signaling pathways

  8. Inhibitors of zinc-dependent metalloproteases hinder sperm passage through the cumulus oophorus during porcine fertilization in vitro.

    Science.gov (United States)

    Beek, J; Nauwynck, H; Maes, D; Van Soom, A

    2012-12-01

    In this study, we report for the first time on a possible contribution of metalloproteases in sperm passage through the cumulus matrix in pigs. The presence of 20 μM 1,10-phenanthroline (1,10-PHEN), inhibitor of zinc-dependent metalloproteases, strongly inhibited the degree of sperm penetration in cumulus-intact (CI), but not in cumulus-free (CF), porcine oocytes during IVF. The inhibitory effect of 1,10-PHEN was due to the chelation of metal ions as a non-chelating analog (1,7-PHEN) did not affect IVF rates. Furthermore, incubation with 1,10-PHEN did not affect sperm binding to the zona pellucida nor sperm motility, membrane integrity, or acrosomal status. These findings led to the assumption that 1,10-PHEN interacts with a sperm- or cumulus-derived metalloprotease. Metalloproteases are key players in physiological processes involving degradation or remodeling of extracellular matrix. In vivo, their proteolytic activity is regulated by tissue inhibitors of metalloproteases (TIMP1-TIMP4). We tested the effect of TIMP3 on fertilization parameters after porcine IVF. Similar to 1,10-PHEN, TIMP3 inhibited total fertilization rate of CI but not CF oocytes and did not influence sperm quality parameters. Although the inhibitory effect was stronger in CI oocytes, TIMP3 also reduced the degree of sperm penetration in CF oocytes, suggesting the involvement of a metalloprotease in a subsequent step during fertilization. In conclusion, our results indicate the involvement of TIMP3-sensitive, zinc-dependent metalloprotease activity in sperm passage through the cumulus oophorus in pigs. The results should provide the basis for further biochemical research toward the localization and identification of the metalloprotease involved.

  9. Molecular detection and analysis of a novel metalloprotease gene of entomopathogenic Serratia marcescens strains in infected Galleria mellonella.

    Science.gov (United States)

    Tambong, J T; Xu, R; Sadiku, A; Chen, Q; Badiss, A; Yu, Q

    2014-04-01

    Serratia marcescens strains isolated from entomopathogenic nematodes (Rhabditis sp.) were examined for their pathogenicity and establishment in wax moth (Galleria mellonella) larvae. All the Serratia strains were potently pathogenic to G. mellonella larvae, leading to death within 48 h. The strains were shown to possess a metalloprotease gene encoding for a novel serralysin-like protein. Rapid establishment of the bacteria in infected larvae was confirmed by specific polymerase chain reaction (PCR) detection of a DNA fragment encoding for this protein. Detection of the viable Serratia strains in infected larvae was validated using the SYBR Green reverse transcriptase real-time PCR assay targeting the metalloprotease gene. Nucleotide sequences of the metalloprotease gene obtained in our study showed 72 single nucleotide polymorphisms (SNP) and 3 insertions compared with the metalloprotease gene of S. marcescens E-15. The metalloprotease gene had 60 synonymous and 8 nonsynonymous substitutions relative to the closest GenBank entry, S. marcescens E-15. A comparison of the amino acid composition of the new serralysin-like protein with that of the serralysin protein of S. marcescens E-15 revealed differences at 11 positions and a new aspartic acid residue. Analysis of the effect of protein variation suggests that a new aspartic acid residue resulting from nonsynonymous nucleotide mutations in the protein structure could have the most significant effect on its biological function. The new metalloprotease gene and (or) its product could have applications in plant agricultural biotechnology.

  10. Doxycycline, a matrix metalloprotease inhibitor, reduces vascular remodeling and damage after cerebral ischemia in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Pires, Paulo W; Rogers, Curt T; McClain, Jonathon L; Garver, Hannah S; Fink, Gregory D; Dorrance, Anne M

    2011-07-01

    Matrix metalloproteases (MMPs) are a family of zinc peptidases involved in extracellular matrix turnover. There is evidence that increased MMP activity is involved in remodeling of resistance vessels in chronic hypertension. Thus we hypothesized that inhibition of MMP activity with doxycycline (DOX) would attenuate vascular remodeling. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with DOX (50 mg·kg(-1)·day(-1) in the drinking water) for 6 wk. Untreated SHRSP were controls. Blood pressure was measured by telemetry during the last week. Middle cerebral artery (MCA) and mesenteric resistance artery (MRA) passive structures were assessed by pressure myography. MMP-2 expression in aortas was measured by Western blot. All results are means ± SE. DOX caused a small increase in mean arterial pressure (SHRSP, 154 ± 1; SHRSP + DOX, 159 ± 3 mmHg; P Damage after transient cerebral ischemia (transient MCA occlusion) was reduced in SHRSP + DOX (20.7 ± 4 vs. 45.5 ± 5% of hemisphere infarcted; P damage after cerebral ischemia.

  11. Association Of Nitric Oxide Synthase And Matrix Metalloprotease Single Nucleotide Polymorphisms With Preeclampsia And Its Complications

    OpenAIRE

    Leonardo, Daniela P.; Albuquerque, Dulcinéia M.; Carolina Lanaro; Baptista, Letícia C.; Cecatti, José G; Surita,Fernanda G; Parpinelli, Mary A; Costa, Fernando F.; Franco-Penteado, Carla F; Kleber Y Fertrin; Maria Laura Costa

    2016-01-01

    Background Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations. Objectives To investigate the association of single nucleot...

  12. A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems

    Science.gov (United States)

    Xu, Jiaxi; Mukerjee, Snigdha; Silva-Alves, Cristiane R. A.; Carvalho-Galvão, Alynne; Cruz, Josiane C.; Balarini, Camille M.; Braga, Valdir A.; Lazartigues, Eric; França-Silva, Maria S.

    2016-01-01

    ADAM17 is a metalloprotease and disintegrin that lodges in the plasmatic membrane of several cell types and is able to cleave a wide variety of cell surface proteins. It is somatically expressed in mammalian organisms and its proteolytic action influences several physiological and pathological processes. This review focuses on the structure of ADAM17, its signaling in the cardiovascular system and its participation in certain disorders involving the heart, blood vessels, and neural regulation of autonomic and cardiovascular modulation. PMID:27803674

  13. Identification and Characterization of Peptides Mimicking the Epitopes of Metalloprotease of Schistosoma Japonicum

    Institute of Scientific and Technical Information of China (English)

    Lianfei Tang; Yuxiao Chen; Linqian Wang; Shunke Zhang; Xianfang Zeng; Xinyuan Yi

    2005-01-01

    In an attempt to isolate and characterize peptides mimicking epitopes of metalloprotease and explore their immunological protection against Schistosoma japonicum (S. japonicum), polyclonal anti-metalloprotease sera was prepared to screen a 12-mer random peptide library to isolate phages binding specially to antisera IgG. Then,phage ELISA, animal immunization, DNA sequencing, Western blotting and enzymatic activity neutralizing analysis were used to characterize the selected phage clones. All of ten randomly picked clones were shown to be positive. Five peptides of different amino acid sequences deduced from DNA sequences were obtained and two of them (peptides 2 and 3) could induce significant reduction (31.0% and 31.8%, respectively) in worm burden and high reduction (52.6% and 54.9%, respectively) in liver eggs per gram (LEPG), while, unexpectedly, others (peptides 1, 4 and 5) could not elicit enough protection against infection of S. japonicum. Peptides 2 and 3 could be recognized by S. japonicum infected mouse sera (IMS) and could elicit neutralizing Abs. The results show that peptides 2 and 3 are antigenic and immunogenic. They are true mimics of epitopes of metalloprotease and useful as novel vaccine candidates against S. japonicum.

  14. Purification and characterization of a 43.5 kDa keratinolytic metalloprotease from Microsporum canis.

    Science.gov (United States)

    Brouta, F; Descamps, F; Fett, T; Losson, B; Gerday, C; Mignon, B

    2001-06-01

    A keratinolytic protease secreted by a feline clinical isolate of Microsporum canis cultivated in a broth containing feline keratin as the sole nitrogen source was purified from the culture filtrate by affinity chromatography on bacitracin-agarose and by hydrophobic chromatography on octyl-agarose. The enzyme had an apparent molecular mass of 43.5 kDa and the pI was 7.7. It had a significant activity against keratin azure, elastin-Congo red and denatured type I collagen (azocoll). Using the latter substrate, the optimum pH was around 8 and the apparent optimum temperature around 50 degrees C. The protease was strongly inhibited by 1,10-phenanthroline, phosphoramidon and EDTA. The first 13 N-terminal amino acid sequence showed a 61% homology with that of the extracellular metalloprotease of Aspergillus fumigatus and with the neutral protease I of A. oryzae, confirming that this 43.5 kDa keratinase is a metalloprotease. This keratinolytic metalloprotease could be a virulence-related factor involved in pathophysiological mechanisms of M. canis dermatophytosis.

  15. Structure-Based Design and Synthesis of a New Phenylboronic-Modified Affinity Medium for Metalloprotease Purification

    Science.gov (United States)

    Li, Shangyong; Wang, Linna; Xu, Ximing; Lin, Shengxiang; Wang, Yuejun; Hao, Jianhua; Sun, Mi

    2016-01-01

    Metalloproteases are emerging as useful agents in the treatment of many diseases including arthritis, cancer, cardiovascular diseases, and fibrosis. Studies that could shed light on the metalloprotease pharmaceutical applications require the pure enzyme. Here, we reported the structure-based design and synthesis of the affinity medium for the efficient purification of metalloprotease using the 4-aminophenylboronic acid (4-APBA) as affinity ligand, which was coupled with Sepharose 6B via cyanuric chloride as spacer. The molecular docking analysis showed that the boron atom was interacting with the hydroxyl group of Ser176 residue, whereas the hydroxyl group of the boronic moiety is oriented toward Leu175 and His177 residues. In addition to the covalent bond between the boron atom and hydroxyl group of Ser176, the spacer between boronic acid derivatives and medium beads contributes to the formation of an enzyme-medium complex. With this synthesized medium, we developed and optimized a one-step purification procedure and applied it for the affinity purification of metalloproteases from three commercial enzyme products. The native metalloproteases were purified to high homogeneity with more than 95% purity. The novel purification method developed in this work provides new opportunities for scientific, industrial and pharmaceutical projects. PMID:28036010

  16. Structure-Based Design and Synthesis of a New Phenylboronic-Modified Affinity Medium for Metalloprotease Purification

    Directory of Open Access Journals (Sweden)

    Shangyong Li

    2016-12-01

    Full Text Available Metalloproteases are emerging as useful agents in the treatment of many diseases including arthritis, cancer, cardiovascular diseases, and fibrosis. Studies that could shed light on the metalloprotease pharmaceutical applications require the pure enzyme. Here, we reported the structure-based design and synthesis of the affinity medium for the efficient purification of metalloprotease using the 4-aminophenylboronic acid (4-APBA as affinity ligand, which was coupled with Sepharose 6B via cyanuric chloride as spacer. The molecular docking analysis showed that the boron atom was interacting with the hydroxyl group of Ser176 residue, whereas the hydroxyl group of the boronic moiety is oriented toward Leu175 and His177 residues. In addition to the covalent bond between the boron atom and hydroxyl group of Ser176, the spacer between boronic acid derivatives and medium beads contributes to the formation of an enzyme-medium complex. With this synthesized medium, we developed and optimized a one-step purification procedure and applied it for the affinity purification of metalloproteases from three commercial enzyme products. The native metalloproteases were purified to high homogeneity with more than 95% purity. The novel purification method developed in this work provides new opportunities for scientific, industrial and pharmaceutical projects.

  17. Endothelin-converting enzymes and related metalloproteases in Alzheimer's disease.

    Science.gov (United States)

    Pacheco-Quinto, Javier; Herdt, Aimee; Eckman, Christopher B; Eckman, Elizabeth A

    2013-01-01

    The efficient clearance of amyloid-β (Aβ) is essential to modulate levels of the peptide in the brain and to prevent it from accumulating in senile plaques, a hallmark of Alzheimer's disease (AD) pathology.We and others have shown that failure in Aβ catabolism can produce elevations in Aβ concentration similar to those observed in familial forms of AD. Based on the available evidence, it remains plausible that in late-onset AD, disturbances in the activity of Aβ degrading enzymes could induce Aβ accumulation, and that this increase could result in AD pathology. The following review presents a historical perspective of the parallel discovery of three vasopeptidases (neprilysin and endothelin-converting enzymes-1 and -2) as important Aβ degrading enzymes. The recognition of the role of these vasopeptidases in Aβ degradation, beyond bringing to light a possible explanation of how cardiovascular risk factors may influence AD risk, highlights a possible risk of the use of inhibitors of these enzymes for other clinical indications such as hypertension. We will discuss in detail the experiments conducted to assess the impact of vasopeptidase deficiency (through pharmacological inhibition or genetic mutation) on Aβ accumulation, as well as the cooperative effect of multiple Aβ degrading enzymes to regulate the concentration of the peptide at multiple sites, both intracellular and extracellular, throughout the brain.

  18. Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites

    Science.gov (United States)

    Kini, R. Manjunatha; Koh, Cho Yeow

    2016-01-01

    Snake venom metalloproteases, in addition to their contribution to the digestion of the prey, affect various physiological functions by cleaving specific proteins. They exhibit their activities through activation of zymogens of coagulation factors, and precursors of integrins or receptors. Based on their structure–function relationships and mechanism of action, we have defined classification and nomenclature of functional sites of proteases. These metalloproteases are useful as research tools and in diagnosis and treatment of various thrombotic and hemostatic conditions. They also contribute to our understanding of molecular details in the activation of specific factors involved in coagulation, platelet aggregation and matrix biology. This review provides a ready reference for metalloproteases that interfere in blood coagulation, fibrinolysis and platelet aggregation. PMID:27690102

  19. Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites

    Directory of Open Access Journals (Sweden)

    R. Manjunatha Kini

    2016-09-01

    Full Text Available Snake venom metalloproteases, in addition to their contribution to the digestion of the prey, affect various physiological functions by cleaving specific proteins. They exhibit their activities through activation of zymogens of coagulation factors, and precursors of integrins or receptors. Based on their structure–function relationships and mechanism of action, we have defined classification and nomenclature of functional sites of proteases. These metalloproteases are useful as research tools and in diagnosis and treatment of various thrombotic and hemostatic conditions. They also contribute to our understanding of molecular details in the activation of specific factors involved in coagulation, platelet aggregation and matrix biology. This review provides a ready reference for metalloproteases that interfere in blood coagulation, fibrinolysis and platelet aggregation.

  20. A PSF-based approach to Kepler/K2 data. I. Variability within the K2 Campaign 0 star clusters M 35 and NGC 2158

    CERN Document Server

    Libralato, M; Nardiello, D; Piotto, G

    2015-01-01

    Kepler and K2 data analysis reported in the literature is mostly based on aperture photometry. Because of Kepler's large, undersampled pixels and the presence of nearby sources, aperture photometry is not always the ideal way to obtain high-precision photometry and, because of this, the data set has not been fully exploited so far. We present a new method that builds on our experience with undersampled HST images. The method involves a point-spread function (PSF) neighbour-subtraction and was specifically developed to exploit the huge potential offered by the K2 "super-stamps" covering the core of dense star clusters. Our test-bed targets were the NGC 2158 and M 35 regions observed during the K2 Campaign 0. We present our PSF modeling and demonstrate that, by using a high-angular-resolution input star list from the Asiago Schmidt telescope as the basis for PSF neighbour subtraction, we are able to reach magnitudes as faint as Kp~24 with a photometric precision of 10% over 6.5 hours, even in the densest region...

  1. Characterization of an extensin-modifying metalloprotease: N-terminal processing and substrate cleavage pattern of Pectobacterium carotovorum Prt1

    DEFF Research Database (Denmark)

    Feng, Tao; Nyffenegger, Christian; Højrup, Peter;

    2014-01-01

    Compared to other plant cell wall-degrading enzymes, proteases are less well understood. In this study, the extracellular metalloprotease Prt1 from Pectobacterium carotovorum (formerly Erwinia carotovora) was expressed in Escherichia coli and characterized with respect to N-terminal processing...

  2. Correlated structural kinetics and retarded solvent dynamics at the metalloprotease active site

    Energy Technology Data Exchange (ETDEWEB)

    Grossman, Moran; Born, Benjamin; Heyden, Matthias; Tworowski, Dmitry; Fields, Gregg B.; Sagi, Irit; Havenith, Martina

    2011-09-18

    Solvent dynamics can play a major role in enzyme activity, but obtaining an accurate, quantitative picture of solvent activity during catalysis is quite challenging. Here, we combine terahertz spectroscopy and X-ray absorption analyses to measure changes in the coupled water-protein motions during peptide hydrolysis by a zinc-dependent human metalloprotease. These changes were tightly correlated with rearrangements at the active site during the formation of productive enzyme-substrate intermediates and were different from those in an enzyme–inhibitor complex. Molecular dynamics simulations showed a steep gradient of fast-to-slow coupled protein-water motions around the protein, active site and substrate. Our results show that water retardation occurs before formation of the functional Michaelis complex. We propose that the observed gradient of coupled protein-water motions may assist enzyme-substrate interactions through water-polarizing mechanisms that are remotely mediated by the catalytic metal ion and the enzyme active site.

  3. Differential Expression of Matrix Metalloproteases in Human Fibroblasts with Different Origins

    Directory of Open Access Journals (Sweden)

    Diana Lindner

    2012-01-01

    Full Text Available Fibroblasts are widely distributed cells and are responsible for the deposition of extracellular matrix (ECM components but also secrete ECM-degrading matrix metalloproteases. A finely balanced equilibrium between deposition and degradation of ECM is essential for structural integrity of tissues. In the past, fibroblasts have typically been understood as a uniform cell population with comparable functions regardless of their origin. Here, we determined growth curves of fibroblasts derived from heart, skin, and lung and clearly show the lowest proliferation rate for cardiac fibroblasts. Furthermore, we examined basal expression levels of collagen and different MMPs in these three types of fibroblasts and compared these concerning their site of origin. Interestingly, we found major differences in basal mRNA expression especially for MMP1 and MMP3. Moreover, we treated fibroblasts with TNF-α and observed different alterations under these proinflammatory conditions. In conclusion, fibroblasts show different properties in proliferation and MMP expression regarding their originated tissue.

  4. Comprehensive inhibitor profiling of the Proteus mirabilis metalloprotease virulence factor ZapA (mirabilysin).

    Science.gov (United States)

    Carson, Louise; Cathcart, George R; Scott, Christopher J; Hollenberg, Morley D; Walker, Brian; Ceri, Howard; Gilmore, Brendan F

    2011-10-01

    In this study we report for the first time the comprehensive inhibitor profiling of the Proteus mirabilis metalloprotease virulence factor ZapA (mirabilysin) using a 160 compound focused library of N-alpha mercaptoamide dipeptides, in order to map the S(1)(') and S(2)(') binding site preferences of this important enzyme. This study has revealed a preference for the aromatic residues tyrosine and tryptophan in P(1)(') and aliphatic residues in P(2)('). From this library, six compounds were identified which exhibited sub- to low-micromolar K(i) values. The most potent inactivator, SH-CO(2)-Y-V-NH(2) was capable of preventing ZapA-mediated hydrolysis of heat-denatured IgA, indicating that these inhibitors may be capable of protecting host proteins against ZapA during colonisation and infection. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  5. The cell envelope-bound metalloprotease (camelysin) from Bacillus cereus is a possible pathogenic factor.

    Science.gov (United States)

    Fricke, B; Drössler, K; Willhardt, I; Schierhorn, A; Menge, S; Rücknagel, P

    2001-09-28

    A novel membrane proteinase of the nosocomial important bacteria species Bacillus cereus (synonyms: camelysin, CCMP) was purified up to homogeneity as was shown by mass spectrometry in its amphiphilic form. Camelysin is a neutral metalloprotease with a molecular mass of 19 kDa. Its unique N-terminus Phe-Phe-Ser-Asp-Lys-Glu-Val-Ser-Asn-Asn-Thr-Phe-Ala-Ala-Gly-Thr-Leu-Asp-Leu-Thr-Leu-Asn-Pro-Lys-Thr-Leu-Val-Asp-(Ile-Lys-Asp)- was not detected in the protein data bases during BLAST searches, but in the partially sequenced genome of Bacillus anthracis, coding for an unknown protein. Cleavage sites of the membrane proteinase for the insulin A- and B-chains were determined by mass spectrometry and N-terminal sequencing. Camelysin prefers cleavage sites in front of aliphatic and hydrophilic amino acid residues (-OH, -SO3H, amido group), avoiding bulky aromatic residues. The internally quenched fluorogenic substrates of the matrix metalloproteases 2 and 7 were cleaved with the highest efficiency at the Leu-decrease-Gly or Leu-decrease-Ala bond with the smaller residue in the P1' position. The protein specificity is broad--all various kinds of casein were cleaved as well as acid-soluble collagen, globin and ovalbumin; intact insulin was destroyed only to a low extent. Actin, collagen type I, fibrinogen, fibrin, alpha2-antiplasmin and alpha1-antitrypsin were cleaved. The protease formed SDS-stable complexes with Glu-plasminogen and antithrombin III, visible after SDS electrophoresis by gold staining and Western blot. The CCMP-plasminogen complex caused a partial activation of plasminogen to plasmin. Camelysin interacts with proteins of the blood coagulation cascade and could facilitate the penetration of fibrin clots and of the extracellular matrix during bacterial invasion.

  6. Features of Pro-σK Important for Cleavage by SpoIVFB, an Intramembrane Metalloprotease

    Science.gov (United States)

    Chen, Kangming; Xiang, Xianling; Gu, Liping

    2013-01-01

    Intramembrane proteases regulate diverse processes by cleaving substrates within a transmembrane segment or near the membrane surface. Bacillus subtilis SpoIVFB is an intramembrane metalloprotease that cleaves Pro-σK during sporulation. To elucidate features of Pro-σK important for cleavage by SpoIVFB, coexpression of the two proteins in Escherichia coli was used along with cell fractionation. In the absence of SpoIVFB, a portion of the Pro-σK was peripherally membrane associated. This portion was not observed in the presence of SpoIVFB, suggesting that it serves as the substrate. Deletion of Pro-σK residues 2 to 8, addition of residues at its N terminus, or certain single-residue substitutions near the cleavage site impaired cleavage. Certain multiresidue substitutions near the cleavage site changed the position of cleavage, revealing preferences for a small residue preceding the cleavage site N-terminally (i.e., at the P1 position) and a hydrophobic residue at the second position following the cleavage site C-terminally (i.e., P2′). These features appear to be conserved among Pro-σK orthologs. SpoIVFB did not tolerate an aromatic residue at P1 or P2′ of Pro-σK. A Lys residue at P3′ of Pro-σK could not be replaced with Ala unless a Lys was provided farther C-terminally (e.g., at P9′). α-Helix-destabilizing residues near the cleavage site were not crucial for SpoIVFB to cleave Pro-σK. The preferences and tolerances of SpoIVFB are somewhat different from those of other intramembrane metalloproteases, perhaps reflecting differences in the interaction of the substrate with the membrane and the enzyme. PMID:23585539

  7. Activation of the epidermal growth factor receptor (EGFR) by a novel metalloprotease pathway.

    LENUS (Irish Health Repository)

    Bergin, David A

    2008-11-14

    Neutrophil Elastase (NE) is a pro-inflammatory protease present at higher than normal levels in the lung during inflammatory disease. NE regulates IL-8 production from airway epithelial cells and can activate both EGFR and TLR4. TACE\\/ADAM17 has been reported to trans-activate EGFR in response to NE. Here, using 16HBE14o-human bronchial epithelial cells we demonstrate a new mechanism by which NE regulates both of these events. A high molecular weight soluble metalloprotease activity detectable only in supernatants from NE-treated cells by gelatin and casein zymography was confirmed to be meprin alpha by Western immunoblotting. In vitro studies demonstrated the ability of NE to activate meprin alpha, which in turn could release soluble TGFalpha and induce IL-8 production from 16HBE14o- cells. These effects were abrogated by actinonin, a specific meprin inhibitor. NE-induced IL-8 expression was also inhibited by meprin alpha siRNA. Immunoprecipitation studies detected EGFR\\/TLR4 complexes in NE-stimulated cells overexpressing these receptors. Confocal studies confirmed colocalization of EGFR and TLR4 in 16HBE14o- cells stimulated with meprin alpha. NFkappaB was also activated via MyD88 in these cells by meprin alpha. In bronchoalveolar lavage fluid from NE knock-out mice infected intra-tracheally with Pseudomonas aeruginosa meprin alpha was significantly decreased compared with control mice, and was significantly increased and correlated with NE activity, in bronchoalveolar lavage fluid from individuals with cystic fibrosis but not healthy controls. The data describe a previously unidentified lung metalloprotease meprin alpha, and its role in NE-induced EGFR and TLR4 activation and IL-8 production.

  8. Self-cleavage of Human CLCA1 Protein by a Novel Internal Metalloprotease Domain Controls Calcium-activated Chloride Channel Activation*♦

    Science.gov (United States)

    Yurtsever, Zeynep; Sala-Rabanal, Monica; Randolph, David T.; Scheaffer, Suzanne M.; Roswit, William T.; Alevy, Yael G.; Patel, Anand C.; Heier, Richard F.; Romero, Arthur G.; Nichols, Colin G.; Holtzman, Michael J.; Brett, Tom J.

    2012-01-01

    The chloride channel calcium-activated (CLCA) family are secreted proteins that regulate both chloride transport and mucin expression, thus controlling the production of mucus in respiratory and other systems. Accordingly, human CLCA1 is a critical mediator of hypersecretory lung diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, that manifest mucus obstruction. Despite relevance to homeostasis and disease, the mechanism of CLCA1 function remains largely undefined. We address this void by showing that CLCA proteins contain a consensus proteolytic cleavage site recognized by a novel zincin metalloprotease domain located within the N terminus of CLCA itself. CLCA1 mutations that inhibit self-cleavage prevent activation of calcium-activated chloride channel (CaCC)-mediated chloride transport. CaCC activation requires cleavage to unmask the N-terminal fragment of CLCA1, which can independently gate CaCCs. Gating of CaCCs mediated by CLCA1 does not appear to involve proteolytic cleavage of the channel because a mutant N-terminal fragment deficient in proteolytic activity is able to induce currents comparable with that of the native fragment. These data provide both a mechanistic basis for CLCA1 self-cleavage and a novel mechanism for regulation of chloride channel activity specific to the mucosal interface. PMID:23112050

  9. Self-cleavage of human CLCA1 protein by a novel internal metalloprotease domain controls calcium-activated chloride channel activation.

    Science.gov (United States)

    Yurtsever, Zeynep; Sala-Rabanal, Monica; Randolph, David T; Scheaffer, Suzanne M; Roswit, William T; Alevy, Yael G; Patel, Anand C; Heier, Richard F; Romero, Arthur G; Nichols, Colin G; Holtzman, Michael J; Brett, Tom J

    2012-12-07

    The chloride channel calcium-activated (CLCA) family are secreted proteins that regulate both chloride transport and mucin expression, thus controlling the production of mucus in respiratory and other systems. Accordingly, human CLCA1 is a critical mediator of hypersecretory lung diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, that manifest mucus obstruction. Despite relevance to homeostasis and disease, the mechanism of CLCA1 function remains largely undefined. We address this void by showing that CLCA proteins contain a consensus proteolytic cleavage site recognized by a novel zincin metalloprotease domain located within the N terminus of CLCA itself. CLCA1 mutations that inhibit self-cleavage prevent activation of calcium-activated chloride channel (CaCC)-mediated chloride transport. CaCC activation requires cleavage to unmask the N-terminal fragment of CLCA1, which can independently gate CaCCs. Gating of CaCCs mediated by CLCA1 does not appear to involve proteolytic cleavage of the channel because a mutant N-terminal fragment deficient in proteolytic activity is able to induce currents comparable with that of the native fragment. These data provide both a mechanistic basis for CLCA1 self-cleavage and a novel mechanism for regulation of chloride channel activity specific to the mucosal interface.

  10. Ikaros and its interacting partner CtBP target the metalloprotease ADAMTS10 to modulate pituitary cell function.

    Science.gov (United States)

    Shen, Zhongyi; Asa, Sylvia L; Ezzat, Shereen

    2017-01-05

    We have previously described the expression and up-regulation of the C-terminal Binding Protein (CtBP) in response to pituitary hypoxia. This co-repressor interacts with the hematopoietic factor Ikaros to target several components implicated in cellular growth and apoptotic pathways. To identify common transcriptional pituitary targets we performed promoter arrays using Ikaros and CtBP chromatin immunoprecipitated (ChIP) DNA from pituitary AtT20 cells. This approach yielded a finite list of gene targets common to both transcription factors. Of these, the metalloprotease ADAMTS10 emerged as a validated target. We show the ability of Ikaros to bind the ADAMTS10 promoter, influence its transfected activity, and induce endogenous gene expression. ADAMTS10 is expressed in primary pituitary cells and is down-regulated in Ikaros null mice. Further, knockdown of ADAMTS10 in AtT20 cells recapitulates the impact of Ikaros deficiency on POMC/ACTH hormone expression. These results uncover a novel role for the metalloprotease ADAMTS10 in the pituitary. Additionally, they position this metalloprotease as a potential functional integrator of the Ikaros-CtBP chromatin remodeling network.

  11. Mycobacterium tuberculosis Rv0198c, a putative matrix metalloprotease is involved in pathogenicity.

    Science.gov (United States)

    Muttucumaru, D G Niranjala; Smith, Debbie A; McMinn, Elizabeth J; Reese, Valerie; Coler, Rhea N; Parish, Tanya

    2011-03-01

    We are interested in the role of proteases in the biology of the global human pathogen, Mycobacterium tuberculosis. We have focused on a putative matrix metalloprotease, Rv0198c. In order to investigate its role we constructed an unmarked chromosomal deletion of the gene and analysed the phenotype of the resulting mutant. No differences in growth in axenic culture were seen and there was no measurable change in overall protease activity in cell-free extracts. Transcriptome analysis revealed a small number of changes in gene expression in aerobic growth, with Rv2488c and Rv1971 being over 40-fold up-regulated and qor (Rv1454c) being 20-fold down-regulated; in addition, changes were seen in members of the heat shock regulon. Virulence assays demonstrated that the mutant was able to replicate in human macrophage-like cells (THP-1 cell line) to a comparable degree with the wild-type. However, the mutant was hyper-virulent in the SCID and C57BL/6 mouse models. Our data suggest that Rv0198c plays a role during infection. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Association of Nitric Oxide Synthase and Matrix Metalloprotease Single Nucleotide Polymorphisms with Preeclampsia and Its Complications.

    Directory of Open Access Journals (Sweden)

    Daniela P Leonardo

    Full Text Available Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations.To investigate the association of single nucleotide polymorphisms (SNPs in NOS3 (G894T, T-786C, and a variable number of tandem repetitions VNTR in intron 4, MMP2 (C-1306T, and MMP9 (C-1562T genes with preeclampsia in patients from Southeastern Brazil.This prospective case-control study enrolled 77 women with preeclampsia and 266 control pregnant women. Clinical data were collected to assess risk factors and the presence of severe complications, such as eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets syndrome.We found a significant association between the single nucleotide polymorphism NOS3 T-786C and preeclampsia, independently from age, height, weight, or the other SNPs studied, and no association was found with the other polymorphisms. Age and history of preeclampsia were also identified as risk factors. The presence of at least one polymorphic allele for NOS3 T-786C was also associated with the occurrence of eclampsia or HELLP syndrome among preeclamptic women.Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the severity of its complications.

  13. A highly conserved metalloprotease effector enhances virulence in the maize anthracnose fungus Colletotrichum graminicola.

    Science.gov (United States)

    Sanz-Martín, José M; Pacheco-Arjona, José Ramón; Bello-Rico, Víctor; Vargas, Walter A; Monod, Michel; Díaz-Mínguez, José M; Thon, Michael R; Sukno, Serenella A

    2016-09-01

    Colletotrichum graminicola causes maize anthracnose, an agronomically important disease with a worldwide distribution. We have identified a fungalysin metalloprotease (Cgfl) with a role in virulence. Transcriptional profiling experiments and live cell imaging show that Cgfl is specifically expressed during the biotrophic stage of infection. To determine whether Cgfl has a role in virulence, we obtained null mutants lacking Cgfl and performed pathogenicity and live microscopy assays. The appressorium morphology of the null mutants is normal, but they exhibit delayed development during the infection process on maize leaves and roots, showing that Cgfl has a role in virulence. In vitro chitinase activity assays of leaves infected with wild-type and null mutant strains show that, in the absence of Cgfl, maize leaves exhibit increased chitinase activity. Phylogenetic analyses show that Cgfl is highly conserved in fungi. Similarity searches, phylogenetic analysis and transcriptional profiling show that C. graminicola encodes two LysM domain-containing homologues of Ecp6, suggesting that this fungus employs both Cgfl-mediated and LysM protein-mediated strategies to control chitin signalling. © 2015 BSPP and John Wiley & Sons Ltd.

  14. A novel matrix metalloprotease-like enzyme (karilysin) of the periodontal pathogen Tannerella forsythia ATCC 43037.

    Science.gov (United States)

    Karim, Abdulkarim Y; Kulczycka, Magdalena; Kantyka, Tomasz; Dubin, Grzegorz; Jabaiah, Abeer; Daugherty, Patrick S; Thogersen, Ida B; Enghild, Jan J; Nguyen, Ky-Anh; Potempa, Jan

    2010-01-01

    Proteases of Tannerella forsythia, a pathogen associated with periodontal disease, are implicated as virulence factors. Here, we characterized a matrix metalloprotease (MMP)-like enzyme of T. forsythia referred to as karilysin. Full-length (without a signal peptide) recombinant karilysin (49.9 kDa) processed itself into the mature 18-kDa enzyme through sequential autoproteolytic cleavage at both N- and C-terminal profragments. The first cleavage at the Asn14-Tyr15 peptide bond generated the fully active enzyme (47.9 kDa) and subsequent truncations at the C-terminus did not affect proteolytic activity. Mutation of Tyr15 to Ala generated a prokarilysin variant that processed itself into the final 18-kDa form with greatly reduced kinetics. Inactive prokarilysin with the mutated catalytic Glu residue (E136A) was processed by active karilysin at the same sites as the active enzymes. Karilysin proteolytic activity and autoprocessing were inhibited by 1,10-phenanthroline and EDTA. Calcium ions were found to be important for both the activity and thermal stability of karilysin. Using CLiPS technology, the specificity of karilysin was found to be similar to that of MMPs with preference for Leu/Tyr/Met at P1' and Pro/Ala at P3. This specificity and the ability to degrade elastin, fibrinogen and fibronectin may contribute to the pathogenicity of periodontitis.

  15. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Soares, R.P.S. [Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP (Brazil); Bydlowski, S.P.; Nascimento, N.M. [Laboratório de Investigação Médica-31, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A. [Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-04-05

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  16. Role in proinflammatory response of YghJ, a secreted metalloprotease from neonatal septicemic Escherichia coli.

    Science.gov (United States)

    Tapader, Rima; Bose, Dipro; Basu, Pallabi; Mondal, Moumita; Mondal, Ayan; Chatterjee, Nabendu Sekhar; Dutta, Pujarini; Basu, Sulagna; Bhadra, Rupak K; Pal, Amit

    2016-11-01

    Neonatal sepsis is the invasion of microbial pathogens into blood stream and is associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. The increased serum levels of cytokines were found to correlate with the severity and mortality in course of sepsis. There have been no reports on the role of microbial proteases in stimulation of proinflammatory response in neonatal sepsis. We have identified YghJ, a secreted metalloprotease from a neonatal septicemic Escherichia coli (NSEC) isolate. The protease was partially purified from culture supernatant by successive anion and gel filtration chromatography. MS/MS peptide sequencing of the protease showed homology with YghJ. YghJ was cloned, expressed and purified in pBAD TOPO expression vector. YghJ was found to be proteolytically active against Methoxysuccinyl Ala-Ala-Pro-Met-p-nitroanilide oligopeptide substrate, but not against casein and gelatin. YghJ showed optimal activity at pH 7-8 and at temperatures 37-40°C. YghJ showed clear changes in cellular morphologies of Int407, HT-29 and HEK293 cells. YghJ stimulated the secretion of cytokines IL-1α, IL-1β and TNF-α in murine macrophages (RAW 264.7) and IL-8 from human intestinal epithelial cells (HT-29). YghJ also down-regulated the production of anti-inflammatory cytokines such as IL-10. YghJ is present in both septicemic (78%) and fecal E. coli isolates (54%). However, expression and secretion of YghJ is significantly higher among the septicemic (89%) than the fecal isolates (33%). This is the first study to show the role of a microbial protease, YghJ in triggering proinflammatory response in NSEC.

  17. Invasion of the Central Nervous System by Cryptococcus neoformans Requires a Secreted Fungal Metalloprotease

    Science.gov (United States)

    Vu, Kiem; Tham, Rick; Uhrig, John P.; Thompson, George R.; Na Pombejra, Sarisa; Jamklang, Mantana; Bautos, Jennifer M.

    2014-01-01

    ABSTRACT Cryptococcus spp. cause life-threatening fungal infection of the central nervous system (CNS), predominantly in patients with a compromised immune system. Why Cryptococcus neoformans has this remarkable tropism for the CNS is not clear. Recent research on cerebral pathogenesis of C. neoformans revealed a predominantly transcellular migration of cryptococci across the brain endothelium; however, the identities of key fungal virulence factors that function specifically to invade the CNS remain unresolved. Here we found that a novel, secreted metalloprotease (Mpr1) that we identified in the extracellular proteome of C. neoformans (CnMpr1) is required for establishing fungal disease in the CNS. Mpr1 belongs to a poorly characterized M36 class of fungalysins that are expressed in only some fungal species. A strain of C. neoformans lacking the gene encoding Mpr1 (mpr1Δ) failed to breach the endothelium in an in vitro model of the human blood-brain barrier (BBB). A mammalian host infected with the mpr1Δ null strain demonstrated significant improvement in survival due to a reduced brain fungal burden and lacked the brain pathology commonly associated with cryptococcal disease. The in vivo studies further indicate that Mpr1 is not required for fungal dissemination and Mpr1 likely targets the brain endothelium specifically. Remarkably, the sole expression of CnMPR1 in Saccharomyces cerevisiae resulted in a robust migration of yeast cells across the brain endothelium, demonstrating Mpr1’s specific activity in breaching the BBB and suggesting that Mpr1 may function independently of the hyaluronic acid-CD44 pathway. This distinct role for Mpr1 may develop into innovative treatment options and facilitate a brain-specific drug delivery platform. PMID:24895304

  18. A Disintegrin and Metalloprotease 10 in neuronal maturation and gliogenesis during cortex development

    Institute of Scientific and Technical Information of China (English)

    Zhixing Ma; Qingyu Li; Zhengyu Zhang; Yufang Zheng

    2013-01-01

    The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain (NICD). A Disintegrin and Metalloprotease 10 (ADAM10) might be a physiological rate-limiting S2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is critical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAM10 mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 (E14.5) to postnatal day 1 (P1). ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin (neural stem cell marker), Tuj1 (mature neuron marker), and S100β (glia marker) showed that ADAM10 expression highly matched that of S100β and partially matched that of Tuj1 at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.

  19. Nerve Growth Factor Promotes Corneal Epithelial Migration by Enhancing Expression of Matrix Metalloprotease-9

    Science.gov (United States)

    Blanco-Mezquita, Tomas; Martinez-Garcia, Carmen; Proença, Rui; Zieske, James D.; Bonini, Stefano; Lambiase, Alessandro; Merayo-Lloves, Jesus

    2013-01-01

    Purpose. Nerve growth factor (NGF) is a neuropeptide essential for the development, survival, growth, and differentiation of corneal cells. Its effects are mediated by both TrkA and p75 receptors. Clinically relevant use of NGF was introduced to treat neurotrophic ulcerations in patients. Herein, we examine the mechanisms by which NGF enhances epithelial wound healing both in vivo and in vitro. Methods. An animal model using adult hens was implemented for the in vivo experiments. Laser ablation keratectomy was performed and animals were observed for up to 7 days. Epithelial healing was measured with fluorescein. In addition, proliferation was measured using BrdU incorporation and both TrkA and matrix metalloprotease-9 (MMP-9) expression were measured by immunohistochemistry (IHC) and Western blot (WB). In vitro experiments were carried out with telomerase-immortalized human corneal epithelial cells (HCLE). The rate of proliferation was measured using a colorimetric assay and BrdU incorporation. Real-time migration was evaluated with an inverted microscope. MMP-9 expression was evaluated by immunocytochemistry (ICC), WB, zymography, and RT-PCR. Finally, beta-4 integrin (β4) expression was assessed by ICC and WB. Results. Faster epithelial healing was observed in NGF-treated corneas compared with controls (P < 0.01). These corneas showed increased proliferation, TrkA upregulation, and enhanced MMP-9 presence (P < 0.01). In vitro, faster spreading and migration were observed in response to NGF (P < 0.01). Enhanced proliferation, as well as enhanced TrkA and MMP-9 expression, and decreased β4 levels were observed after adding NGF (P < 0.01). Conclusions. NGF plays a major role during the epithelial healing process by promoting migration, a process that is accelerated by cell spreading. This effect is mediated by both the upregulation of MMP-9 and cleavage of β4 integrin. PMID:23640040

  20. Purification and evaluation of the interference of BthMP (a metalloprotease from Bothrops moojeni in blood clotting

    Directory of Open Access Journals (Sweden)

    Manuela Andrade Santos

    2016-10-01

    Full Text Available In the present was work reported the purification of the metalloprotease BthMP, from the venom of Bothrops moojeni. For purification of the protease was used ion exchange chromatography (DEAE-Sepharose and molecular exclusion (Sephadex G-75, the product of these processes was a protein band with high purity, visualized on SDS-PAGE 14%, referred the BthMP. This protease when analyzed on MALDI-TOF revealed the molecular weight of the native form of 23.050 Da and 23.872 Da in the reduced form, and from the peptide fragments obtained by Peptide Mass Fingerprinting (PMF in MS (MALDI-TOF/TOF was observed high similarity with BmooMPα-I metalloprotease. In enzymatic terms, BthMP showed proteolytic activity on azocasein using PMSF and benzamidine, while this activity was inhibited in the presence of EDTA; 1,10-Phenanthroline and β-mercaptoethanol, it is therefore a zinc-dependent metalloprotease of the class P-I. To still with this purpose, we contemplate its enzymatic specificity of the Aα and Bβ chains of fibrinogen and also the consumption of fibrinogen in vivo. It was also found its action on the components of the coagulation cascade, due to prolongation of prothrombin time and partial thromboplastin time. Thus, the sharp fibrinogenolytic activity and the high consumption of fibrinogen in vivo are results that indicate the anticoagulant action of BthMP; furthermore, their ability to interfere with the coagulation cascade suggested that this protease is promising for future studies that might indicate a new antithrombotic agent model.

  1. Matrix Metalloprotease 3 Activity Supports Hippocampal EPSP-to-Spike Plasticity Following Patterned Neuronal Activity via the Regulation of NMDAR Function and Calcium Flux.

    Science.gov (United States)

    Brzdąk, Patrycja; Włodarczyk, Jakub; Mozrzymas, Jerzy W; Wójtowicz, Tomasz

    2017-01-01

    Matrix metalloproteases (MMPs) comprise a family of endopeptidases that are involved in remodeling the extracellular matrix and play a critical role in learning and memory. At least 24 different MMP subtypes have been identified in the human brain, but less is known about the subtype-specific actions of MMP on neuronal plasticity. The long-term potentiation (LTP) of excitatory synaptic transmission and scaling of dendritic and somatic neuronal excitability are considered substrates of memory storage. We previously found that MMP-3 and MMP-2/9 may be differentially involved in shaping the induction and expression of excitatory postsynaptic potential (EPSP)-to-spike (E-S) potentiation in hippocampal brain slices. MMP-3 and MMP-2/9 proteolysis was previously shown to affect the integrity or mobility of synaptic N-methyl-D-aspartate receptors (NMDARs) in vitro. However, the functional outcome of such MMP-NMDAR interactions remains largely unknown. The present study investigated the role of these MMP subtypes in E-S plasticity and NMDAR function in mouse hippocampal acute brain slices. The temporal requirement for MMP-3/NMDAR activity in E-S potentiation within the CA1 field largely overlapped, and MMP-3 but not MMP-2/9 activity was crucial for the gain-of-function of NMDARs following LTP induction. Functional changes in E-S plasticity following MMP-3 inhibition largely correlated with the expression of cFos protein, a marker of activity-related gene transcription. Recombinant MMP-3 promoted a gain in NMDAR-mediated field potentials and somatodendritic Ca(2+) waves. These results suggest that long-term hippocampal E-S potentiation requires transient MMP-3 activity that promotes NMDAR-mediated postsynaptic Ca(2+) entry that is vital for the activation of downstream signaling cascades and gene transcription.

  2. Probing The Lower Mass Limit for Supernova Progenitors and the High-Mass End of the Initial-Final Mass Relation from White Dwarfs in the Open Cluster M35 (NGC 2168)

    CERN Document Server

    Williams, Kurtis A; Koester, Detlev

    2008-01-01

    We present a photometric and spectroscopic study of the white dwarf population of the populous, intermediate-age open cluster M35 (NGC 2168); this study expands upon our previous study of the white dwarfs in this cluster. We spectroscopically confirm 14 white dwarfs in the field of the cluster: 12 DAs, 1 hot DQ, and 1 DB star. For each DA, we determine the white dwarf mass and cooling age, from which we derive the each star's progenitor mass. These data are then added to the empirical initial-final mass relation (IFMR), where the M35 WDs contribute significantly to the high-mass end of the relation. The resulting points are consistent with previously-published linear fits to the IFMR, modulo moderate systematics introduced by the uncertainty in the star cluster age. Based on this cluster alone, the observational lower limit on the maximum mass of white dwarf progenitors is found to be ~5.1-5.2 solar masses at the 95% confidence level; including data from other young open clusters raises this limit as high as ...

  3. Vesicle-associated membrane protein (VAMP) cleavage by a new metalloprotease from the Brazilian scorpion Tityus serrulatus.

    Science.gov (United States)

    Fletcher, Paul L; Fletcher, Maryann D; Weninger, Keith; Anderson, Trevor E; Martin, Brian M

    2010-03-01

    We present evidence that venom from the Brazilian scorpion Tityus serrulatus and a purified fraction selectively cleave essential SNARE proteins within exocrine pancreatic tissue. Western blotting for vesicle-associated membrane protein type v-SNARE proteins (or synaptobrevins) reveals characteristic alterations to venom-treated excised pancreatic lobules in vitro. Immunocytochemistry by electron microscopy confirms both the SNARE identity as VAMP2 and the proteolysis of VAMP2 as a marked decrease in secondary antibody-conjugated colloidal gold particles that are predominantly associated with mature zymogen granules. Studies with recombinant SNARE proteins were used to determine the specific cleavage site in VAMP2 and the susceptibility of VAMP8 (endobrevin). The VAMP2 cleavage site is between the transmembrane anchor and the SNARE motif that assembles into the ternary SNARE complex. Inclusion of divalent chelating agents (EDTA) with fraction nu, an otherwise active purified component from venom, eliminates SNARE proteolysis, suggesting the active protein is a metalloprotease. The unique cleavages of VAMP2 and VAMP8 may be linked to pancreatitis that develops following scorpion envenomation as both of these v-SNARE proteins are associated with zymogen granule membranes in pancreatic acinar cells. We have isolated antarease, a metalloprotease from fraction nu that cleaves VAMP2, and report its amino acid sequence.

  4. Vesicle-associated Membrane Protein (VAMP) Cleavage by a New Metalloprotease from the Brazilian Scorpion Tityus serrulatus*

    Science.gov (United States)

    Fletcher, Paul L.; Fletcher, Maryann D.; Weninger, Keith; Anderson, Trevor E.; Martin, Brian M.

    2010-01-01

    We present evidence that venom from the Brazilian scorpion Tityus serrulatus and a purified fraction selectively cleave essential SNARE proteins within exocrine pancreatic tissue. Western blotting for vesicle-associated membrane protein type v-SNARE proteins (or synaptobrevins) reveals characteristic alterations to venom-treated excised pancreatic lobules in vitro. Immunocytochemistry by electron microscopy confirms both the SNARE identity as VAMP2 and the proteolysis of VAMP2 as a marked decrease in secondary antibody-conjugated colloidal gold particles that are predominantly associated with mature zymogen granules. Studies with recombinant SNARE proteins were used to determine the specific cleavage site in VAMP2 and the susceptibility of VAMP8 (endobrevin). The VAMP2 cleavage site is between the transmembrane anchor and the SNARE motif that assembles into the ternary SNARE complex. Inclusion of divalent chelating agents (EDTA) with fraction ν, an otherwise active purified component from venom, eliminates SNARE proteolysis, suggesting the active protein is a metalloprotease. The unique cleavages of VAMP2 and VAMP8 may be linked to pancreatitis that develops following scorpion envenomation as both of these v-SNARE proteins are associated with zymogen granule membranes in pancreatic acinar cells. We have isolated antarease, a metalloprotease from fraction ν that cleaves VAMP2, and report its amino acid sequence. PMID:20026600

  5. Analysis of matrix metallo-proteases and the plasminogen system in mild cognitive impairment and Alzheimer's disease cerebrospinal fluid.

    Science.gov (United States)

    Hanzel, Cecilia E; Iulita, M Florencia; Eyjolfsdottir, Helga; Hjorth, Erik; Schultzberg, Marianne; Eriksdotter, Maria; Cuello, A Claudio

    2014-01-01

    The expression of matrix metallo-proteases (MMP-2, MMP-3, MMP-7, and MMP-9), plasminogen and their regulators (TIMP-1, tissue plasminogen activator and neuroserpin) was investigated in cerebrospinal fluid (CSF) from subjective cognitive impairment (SCI) subjects, mild cognitive impairment (MCI), and Alzheimer's disease (AD) cases. ELISA analysis revealed a significant increase in MMP-3 protein levels in CSF from AD subjects, compared to age-matched SCI and MCI cases. No significant differences in MMP-2 and MMP-9 protein levels were detected between the three groups. MMP-7 was undetectable in all three groups. MCI individuals exhibited increased levels of the metallo-protease inhibitor TIMP-1 in CSF as well as higher plasminogen and neuroserpin expression, compared to SCI subjects. Levels of tissue plasminogen activator (tPA) were significantly reduced in AD CSF. Correlation analysis revealed a significant positive association between MMP-3, p-tau, and total-tau levels. Conversely, there was a significant negative correlation between this protease and Mini-Mental State Examination (MMSE) scores. tPA positively correlated with amyloid-β levels in CSF and with MMSE scores. Our results suggest that MMP-3 and tPA, in combination with current amyloid-β and tau biomarkers, may have potential as surrogate indicators of an ongoing AD pathology.

  6. Production, purification and characterisation of thermostable metallo-protease from newly isolated Bacillus sp. KG5

    Directory of Open Access Journals (Sweden)

    Nazenin Ahmetoglu

    2015-03-01

    Full Text Available Background: Due to the importance of microbial proteases in biotechnological applications, a number of microorganisms are being explored. The production, purification and characterisation of extracellular metallo-proteases by producing Bacillus sp. KG5 was studied. Material and Methods: Bacterial strain KG5 was isolated from Kos (Bingol hot spring. The strain KG5 was identified by morphological, physiological, biochemical and 16S rRNA gene sequencing. The effects of various parameters on protease production, such as time, temperature, pH, carbon and nitrogen sources and CaCl2 were studied. The enzyme was purified by ammonium sulphate precipitation and Sephadex G-75 gel permeation chromatography. Molecular weight was calculated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE and zymographic analysis. The effects of some metal ions, chelators and inhibitors on enzyme activity were determined. Results: The optimum temperature, pH and incubation period for protease production were 40-45°C, 7.0 and 24 h, respectively. It was determined that the best nitrogen sources were yeast extract and urea, while the best carbon sources were lactose and galactose. However, glucose as a source of carbon was found to inhibit the production of the enzyme. The maximum enzyme production was increased in the presence of CaCl2. The molecular weight of purified enzyme was found to be approximately 48 kDa. It was found that the enzyme was fully stable in the presence of 2 mM CaCl2 at 50°C after 120 min. Purified protease was significantly activated by Ca2+ and Mg2+, while it was greatly inhibited by Cu2+, Zn2+, Hg2+ and SDS as well as by the metal ion chelators ethylenediaminetetraacetic (EDTA and 1,10-phenanthroline. Phenylmethylsulfonyl fluoride (PMSF had a little effect on the enzyme. Conclusions: Our findings suggest the potential of this isolate for protease production and that this enzyme may be suitable for biotechnological applications.

  7. Quantification of matrix metalloprotease-9 in bronchoalveolar lavage fluid by selected reaction monitoring with microfluidics nano-liquid-chromatography-mass spectrometry

    NARCIS (Netherlands)

    Prely, Laurette M.; Paal, Krisztina; Hermans, Jos; van der Heide, Sicco; van Oosterhout, Antoon J. M.; Bischoff, Rainer

    2012-01-01

    Quantitative protein analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the selected reaction monitoring (SRM) mode was used to quantify matrix metalloprotease-9 (MMP-9; similar to 90 kDa) in bronchoalveolar lavage fluid (BALF) from patients having undergone lung transplantatio

  8. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease.

    Science.gov (United States)

    Strongin, A Y; Collier, I; Bannikov, G; Marmer, B L; Grant, G A; Goldberg, G I

    1995-03-10

    Matrix metalloproteases are secreted by mammalian cells as zymogens and, upon activation, initiate tissue remodeling by proteolytic degradation of collagens and proteoglycans. Activation of the secreted proenzymes and interaction with their specific inhibitors determine the net enzymatic activity in the extracellular space. We have previously demonstrated that 72T4Cl can be activated by a plasma membrane-dependent mechanism specific for this enzyme. Here, we report purification of the membrane activator of 72T4Cl, which is a new metalloprotease identical to a recently cloned membrane-type matrix metalloprotease (MT-MMP). We demonstrate that activated MT-MMP acts as a cell surface tissue inhibitor of metalloprotease 2 (TIMP-2) receptor with Kd = 2.54 x 10(-9) M. The activator.TIMP-2 complex in turn acts as a receptor for 72T4Cl (Kd = 0.56 x 10(-9) M, binding to the carboxyl-end domain of the enzyme. Activation of 72T4Cl on the cell membrane provides a basic mechanism for spatially regulated extracellular proteolysis and presents a new target for prognosis and treatment of metastatic disease. The activation, purified as a tri-molecular complex of MT-MMP.TIMP2.carboxyl-end domain of 72T4Cl, is itself an activated form of MT-MMP, posing the following question: what is the mechanism of the activator's activation?

  9. A phage display delected 7-mer peptide inhibitor of the tannerella forsythia metalloprotease-like enzyme karilysin can be truncated to ser-trp-phe-pro

    DEFF Research Database (Denmark)

    Skottrup, Peter Durand; Sørensen, Grete; Ksiazek, Miroslaw

    2012-01-01

    Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a l...

  10. Temporal Gene Expression Analysis and RNA Silencing of Single and Multiple Members of Gene Family in the Lone Star Tick Amblyomma americanum

    Science.gov (United States)

    Karim, Shahid

    2016-01-01

    Saliva is an integral factor in the feeding success of veterinary and medically important ticks. Therefore, the characterization of the proteins present in tick saliva is an important area of tick research. Here, we confirmed previously generated sialotranscriptome data using quantitative real-time PCR. The information obtained in this in-depth study of gene expression was used to measure the effects of metalloprotease gene silencing on tick feeding. We analyzed the temporal expression of seven housekeeping genes and 44 differentially expressed salivary molecules selected from a previously published Amblyomma americanum sialotranscriptome. Separate reference genes were selected for the salivary glands and midgut from among the seven housekeeping genes, to normalize the transcriptional expression of differentially expressed genes. The salivary gland reference gene, ubiquitin, was used to normalize the expression of 44 salivary genes. Unsurprisingly, each gene family was expressed throughout the blood meal, but the expression of specific genes differed at each time point. To further clarify the complex nature of the many proteins found in the saliva, we disrupted the translation of several members of the metalloprotease family. Intriguingly, the nucleotide sequence similarity of the reprolysin metalloprotease gene family is so homologous that a single synthesized dsRNA sequence knocked down multiple members of the family. The use of multigene knockdown yielded a more significant picture of the role of metalloproteases in tick feeding success, and changes were observed in the female engorgement weight and larval hatching success. Interestingly, the depletion of metalloprotease transcripts also reduced the total number of bacteria present in the salivary glands. These data provide insight into the expression and functions of tick salivary proteins expressed while feeding on its host. PMID:26872360

  11. Temporal Gene Expression Analysis and RNA Silencing of Single and Multiple Members of Gene Family in the Lone Star Tick Amblyomma americanum.

    Science.gov (United States)

    Bullard, Rebekah L; Williams, Jaclyn; Karim, Shahid

    2016-01-01

    Saliva is an integral factor in the feeding success of veterinary and medically important ticks. Therefore, the characterization of the proteins present in tick saliva is an important area of tick research. Here, we confirmed previously generated sialotranscriptome data using quantitative real-time PCR. The information obtained in this in-depth study of gene expression was used to measure the effects of metalloprotease gene silencing on tick feeding. We analyzed the temporal expression of seven housekeeping genes and 44 differentially expressed salivary molecules selected from a previously published Amblyomma americanum sialotranscriptome. Separate reference genes were selected for the salivary glands and midgut from among the seven housekeeping genes, to normalize the transcriptional expression of differentially expressed genes. The salivary gland reference gene, ubiquitin, was used to normalize the expression of 44 salivary genes. Unsurprisingly, each gene family was expressed throughout the blood meal, but the expression of specific genes differed at each time point. To further clarify the complex nature of the many proteins found in the saliva, we disrupted the translation of several members of the metalloprotease family. Intriguingly, the nucleotide sequence similarity of the reprolysin metalloprotease gene family is so homologous that a single synthesized dsRNA sequence knocked down multiple members of the family. The use of multigene knockdown yielded a more significant picture of the role of metalloproteases in tick feeding success, and changes were observed in the female engorgement weight and larval hatching success. Interestingly, the depletion of metalloprotease transcripts also reduced the total number of bacteria present in the salivary glands. These data provide insight into the expression and functions of tick salivary proteins expressed while feeding on its host.

  12. Heightened cleavage of Axl receptor tyrosine kinase by ADAM metalloproteases may contribute to disease pathogenesis in SLE.

    Science.gov (United States)

    Orme, Jacob J; Du, Yong; Vanarsa, Kamala; Mayeux, Jessica; Li, Li; Mutwally, Azza; Arriens, Cristina; Min, Soyoun; Hutcheson, Jack; Davis, Laurie S; Chong, Benjamin F; Satterthwaite, Anne B; Wu, Tianfu; Mohan, Chandra

    2016-08-01

    Systemic lupus erythematosus (SLE) is characterized by antibody-mediated chronic inflammation in the kidney, lung, skin, and other organs to cause inflammation and damage. Several inflammatory pathways are dysregulated in SLE, and understanding these pathways may improve diagnosis and treatment. In one such pathway, Axl tyrosine kinase receptor responds to Gas6 ligand to block inflammation in leukocytes. A soluble form of the Axl receptor ectodomain (sAxl) is elevated in serum from patients with SLE and lupus-prone mice. We hypothesized that sAxl in SLE serum originates from the surface of leukocytes and that the loss of leukocyte Axl contributes to the disease. We determined that macrophages and B cells are a source of sAxl in SLE and in lupus-prone mice. Shedding of the Axl ectodomain from the leukocytes of lupus-prone mice is mediated by the matrix metalloproteases ADAM10 and TACE (ADAM17). Loss of Axl from lupus-prone macrophages renders them unresponsive to Gas6-induced anti-inflammatory signaling in vitro. This phenotype is rescued by combined ADAM10/TACE inhibition. Mice with Axl-deficient macrophages develop worse disease than controls when challenged with anti-glomerular basement membrane (anti-GBM) sera in an induced model of nephritis. ADAM10 and TACE also mediate human SLE PBMC Axl cleavage. Collectively, these studies indicate that increased metalloprotease-mediated cleavage of leukocyte Axl may contribute to end organ disease in lupus. They further suggest dual ADAM10/TACE inhibition as a potential therapeutic modality in SLE.

  13. IL-1β-induced matrix metalloproteinase-13 is activated by a disintegrin and metalloprotease-28-regulated proliferation of human osteoblast-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki; Kinoshita, Katsue; Hase, Naoko; Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650 (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650 (Japan); Nakamura, Hiroshi [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (Japan)

    2014-04-15

    We reported previously that matrix metalloproteinase (MMP)-13 accelerates bone remodeling in oral periradicular lesions, and indicated a potentially unique role for MMP-13 in wound healing and regeneration of alveolar bone. The ADAM (a disintegrin and metalloprotease) family is a set of multifunctional cell surface and secreted glycoproteins, of which ADAM-28 has been localized in bone and bone-like tissues. In this study, we show that interleukin (IL)-1β induces the expression of MMP-13 and ADAM-28 in homogeneous α7 integrin-positive human skeletal muscle stem cell (α7{sup +}hSMSC)-derived osteoblast-like (α7{sup +}hSMSC-OB) cells, and promotes proliferation while inhibiting apoptosis in these cells. At higher concentrations, however, IL-1β failed to induce the expression of these genes and caused an increase in apoptosis. We further employed ADAM-28 small interfering RNA (siRNA) to investigate whether IL-1β-induced MMP-13 expression is linked to this IL-1β-mediated changes in cell proliferation and apoptosis. Silencing ADAM-28 expression potently suppressed IL-1β-induced MMP-13 expression and activity, decreased cell proliferation and increased apoptosis in α7{sup +}hSMSC-OB cells. In contrast, MMP-13 siRNA had no effect on ADAM-28 expression, suggesting ADAM-28 regulates MMP-13. Exogenous MMP-13 induced α7{sup +}hSMSC-OB cell proliferation and could rescue ADAM-28 siRNA-induced apoptosis, and we found that proMMP-13 is partially cleaved into its active form by ADAM-28 in vitro. Overall, our results suggest that IL-1β-induced MMP-13 expression and changes in cell proliferation and apoptosis in α7{sup +}hSMSC-OB cells are regulated by ADAM-28. - Highlights: • IL-1β induces the MMP-13 and ADAM-28 expression in human osteoblast-like cells. • IL-1β-induced MMP-13 expression increases proliferation and decreased apoptosis. • MMP-13 expression induced by IL-1β is regulated by ADAM-28. • proMMP-13 appears to be cleaved into its active form via

  14. Vibrio Zinc-Metalloprotease Causes Photoinactivation of Coral Endosymbionts and Coral Tissue Lesions

    NARCIS (Netherlands)

    Sussman, Meir; Mieog, Jos C.; Doyle, Jason; Victor, Steven; Willis, Bette L.; Bourne, David G.

    2009-01-01

    Background: Coral diseases are emerging as a serious threat to coral reefs worldwide. Of nine coral infectious diseases, whose pathogens have been characterized, six are caused by agents from the family Vibrionacae, raising questions as to their origin and role in coral disease aetiology.

  15. Vibrio Zinc-Metalloprotease Causes Photoinactivation of Coral Endosymbionts and Coral Tissue Lesions

    NARCIS (Netherlands)

    Sussman, Meir; Mieog, Jos C.; Doyle, Jason; Victor, Steven; Willis, Bette L.; Bourne, David G.

    2009-01-01

    Background: Coral diseases are emerging as a serious threat to coral reefs worldwide. Of nine coral infectious diseases, whose pathogens have been characterized, six are caused by agents from the family Vibrionacae, raising questions as to their origin and role in coral disease aetiology. Methodolog

  16. COMPARATIVE ANALYSIS AND CLINICAL VALUE OF THE EXPRESSION OF METALLOPROTEASES AND THEIR INHIBITORS BY INTRATUMOR STROMAL MONONUCLEAR INFLAMMATORY CELLS AND THOSE AT THE INVASIVE FRONT OF BREAST CARCINOMAS

    OpenAIRE

    2010-01-01

    Abstract Aims: Matrix metalloproteases (MMPs) and their inhibitors (TIMPs) play an essential role in the degradation of stromal connective tissue and basement membrane components. The dynamic analysis of these components might help predict tumor agressiveness. Methods and Results: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, 2, 7, 9, 11, 13, 14, and TIMPs -1, 2 and 3. More than 5,000 determinations on cancer specimens ...

  17. Evidence for Cleavage of the Metalloprotease Vsm from Vibrio splendidus Strain JZ6 by an M20 Peptidase (PepT-like Protein) at Low Temperature

    OpenAIRE

    2016-01-01

    Metalloprotease Vsm is a major extracellular virulence factor of Vibrio splendidus. The toxicity of Vsm from V. splendidus strain JZ6 has been characterized, and production of this virulence factor proved to be temperature-regulated. The present study provides evidence that two forms (JZE1 and JZE2) of Vsm protein exist in extracellular products (ECPs) of strain JZ6, and a significant conversion of these two forms was detected by SDS-PAGE and immunoblotting analyses of samples obtained from c...

  18. Metalloprotease cleavage of the N terminus of the orphan G protein-coupled receptor GPR37L1 reduces its constitutive activity.

    Science.gov (United States)

    Coleman, James L J; Ngo, Tony; Schmidt, Johannes; Mrad, Nadine; Liew, Chu Kong; Jones, Nicole M; Graham, Robert M; Smith, Nicola J

    2016-04-12

    Little is known about the pharmacology or physiology of GPR37L1, a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that is abundant in the cerebellum. Mice deficient in this receptor exhibit precocious cerebellar development and hypertension. We showed that GPR37L1 coupled to the G protein Gα(s) when heterologously expressed in cultured cells in the absence of any added ligand, whereas a mutant receptor that lacked the amino terminus was inactive. Conversely, inhibition of ADAMs (a disintegrin and metalloproteases) enhanced receptor activity, indicating that the presence of the amino terminus is necessary for GPR37L1 signaling. Metalloprotease-dependent processing of GPR37L1 was evident in rodent cerebellum, where we detected predominantly the cleaved, inactive form. However, comparison of the accumulation of cAMP (adenosine 3',5'-monophosphate) in response to phosphodiesterase inhibition in cerebellar slice preparations from wild-type and GPR37L1-null mice showed that some constitutive signaling remained in the wild-type mice. In reporter assays of Gα(s) or Gα(i) signaling, the synthetic, prosaposin-derived peptide prosaptide (TX14A) did not increase GPR37L1 activity. Our data indicate that GPR37L1 may be a constitutively active receptor, or perhaps its ligand is present under the conditions that we used for analysis, and that the activity of this receptor is instead controlled by signals that regulate metalloprotease activity in the tissue.

  19. Relationship between metalloprotease expression in tumour and stromal cells and aggressive behaviour in prostate carcinoma: Simultaneous high-throughput study of multiple metalloproteases and their inhibitors using tissue array analysis of radical prostatectomy samples.

    Science.gov (United States)

    Fernandez-Gomez, Jesus; Escaf, Safwan; Gonzalez, Luis-Ovidio; Suarez, Aurelio; Gonzalez-Reyes, Salome; González, Jose; Miranda, Oscar; Vizoso, Francisco

    2011-04-01

    The aim of this study was to detect a potential association between clinicopathological factors of prostate cancer aggressiveness and the expression of matrix metalloproteases and their inhibitors in tumour and stromal cells. A tissue array technique and immunochemistry with specific antibodies against matrix metalloproteinases (MMPs)-1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors (TIMPs)-1, 2 and 3 were used to analyse the surgical specimens of 133 patients treated by radical prostatectomy. For each antibody preparation, the cellular location of immunoreactivity was determined. The expression of MMP-2 was negatively associated with high tumour grade. With regard to stromal fibroblasts, TIMP-3 expression was positively associated with histological grade. MMP-7 expression was negatively associated with pretreatment serum levels of PSA, whereas MMP-13 was positively associated with higher levels of the antigen. TIMP-2 expression by mononuclear inflammatory cells correlated significantly and negatively with tumour grade. The expression of TIMP-3 by fibroblasts was associated with a higher Gleason score. An increased expression of MMP-13 by fibroblasts was associated with a greater preoperative level of PSA. In contrast, MMP-2 expression by tumour as well as TIMP-2 expression by peritumoral inflammatory cells was associated with less aggressive prostate carcinoma characteristics.

  20. Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A Novel Contributor to Inflammation?

    Directory of Open Access Journals (Sweden)

    Marijke De Bock

    2015-01-01

    Full Text Available The coordination of tissue function is mediated by gap junctions (GJs that enable direct cell-cell transfer of metabolic and electric signals. GJs are formed by connexin (Cx proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels (HCs in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein-protein interactions and posttranslational modifications that predominantly take place in the C-terminal domain of Cx43. Matrix metalloproteases (MMPs are a major group of zinc-dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP-Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.

  1. Purification and Properties of Cold-active Metalloprotease from Curtobacterium luteum and Effect of Culture Conditions on Production

    Institute of Scientific and Technical Information of China (English)

    Mohammed Kuddus; Pramod W. Ramteke

    2008-01-01

    Curtobacterim luteum, a gram-positive psychrotrophic bacterium, secreting an extracellular protease was isolated from the soil of Gangotri glacier, Western Himalaya. The maximum enzyme production was achieved when isolate was grown in a pH-neutral medium containing skim milk at 15℃ over 120 hour. The metal ions such as Zn and Cr enhanced enzyme production. The specific activity of pudfied enzyme was 8090 u/mg after 34.1 fold purification. The 115 kD enzyme was a metalloprotease (activity inhibited by EDTA and EGTA) and showed maximum activity at 20℃ and pH 7. The enzyme was active over a broad pH range and retained 84% of its original activity between pH 6-8. There was no loss in enzyme activity when exposed for 3 hours at 4℃-20℃. However, lost 65% of activity at 30℃, and was almost inactivated at 50℃, but was resistant to repeated freezing and thawing. The enzyme activity was stimulated by manganese ions; however, it was inactivated by copper ions.

  2. Development of a quantitative real-time PCR assay for detection of Vibrio tubiashii targeting the metalloprotease gene.

    Science.gov (United States)

    Gharaibeh, Dima N; Hasegawa, Hiroaki; Häse, Claudia C

    2009-03-01

    Vibrio tubiashii has recently re-emerged as a pathogen of bivalve larvae, causing a marked increase in the mortality of these species within shellfish rearing facilities. This has resulted in substantial losses of seed production and thus created the need for specific as well as sensitive detection methods for this pathogen. In this project, quantitative PCR (qPCR) primers were developed and optimized based upon analysis of the V. tubiashii vtpA gene sequence, encoding a metalloprotease known to cause larval mortality. Standard curves were developed utilizing dilutions of known quantities of V. tubiashii cells that were compared to colony forming unit (CFU) plate counts. The assay was optimized for detection of vtpA with both lab-grown V. tubiashii samples and filter-captured environmental seawater samples seeded with V. tubiashii. In addition, the primers were confirmed to specifically detect only V. tubiashii when tested against a variety of non-target Vibrio species. Validation of the assay was completed by analyzing samples obtained from a shellfish hatchery. The development of this rapid and sensitive assay for quantitative detection of V. tubiashii will accurately determine levels of this bacterium in a variety of seawater samples, providing a useful tool for oyster hatcheries and a method to assess the presence of this bacterium in the current turbulent ocean environment.

  3. Evaluating secretion and surface attachment of SapA, an S-layer-associated metalloprotease of Caulobacter crescentus.

    Science.gov (United States)

    Gandham, Lyngrace; Nomellini, John F; Smit, John

    2012-10-01

    Caulobacter crescentus is used to display foreign peptides at high density as insertions into the surface (S)-layer protein (RsaA). Many recombinant RsaA proteins, however, are cleaved by SapA, a 71-kDa metalloprotease, suggesting a role in maintaining S-layer integrity. When overexpressed on a multicopy plasmid SapA was detected on the surface by fluorescent antibody only if RsaA and the O-side chain of LPS that mediates S-layer attachment were removed by mutation, indicating an outer membrane location beneath the S-layer. Secretion was mediated by the RsaA type 1 transporter since secretion was eliminated in transporter deficient strains or by C-terminal deletions in SapA (the presumed location of type 1 secretion signals). Secretion was required to become an active protease; mass spectrometry suggested this might be due to N-terminal processing during secretion, a feature shared with other type 1-secreted proteases. Overexpression leads to additional processing C-terminal to the protease domain, producing a 45-kDa protein. This was demonstrated to be self-processing. Deletion analysis revealed the C-terminal 100 amino acids were sufficient for anchoring and secretion. When protein G was fused to the last 238 amino acids of SapA it was secreted, surface attached and bound immunoglobulin, indicating potential for foreign protein display.

  4. Novel mode of action of plant defense peptides - hevein-like antimicrobial peptides from wheat inhibit fungal metalloproteases.

    Science.gov (United States)

    Slavokhotova, Anna A; Naumann, Todd A; Price, Neil P J; Rogozhin, Eugene A; Andreev, Yaroslav A; Vassilevski, Alexander A; Odintsova, Tatyana I

    2014-10-01

    The multilayered plant immune system relies on rapid recognition of pathogen-associated molecular patterns followed by activation of defense-related genes, resulting in the reinforcement of plant cell walls and the production of antimicrobial compounds. To suppress plant defense, fungi secrete effectors, including a recently discovered Zn-metalloproteinase from Fusarium verticillioides, named fungalysin Fv-cmp. This proteinase cleaves class IV chitinases, which are plant defense proteins that bind and degrade chitin of fungal cell walls. In this study, we investigated plant responses to such pathogen invasion, and discovered novel inhibitors of fungalysin. We produced several recombinant hevein-like antimicrobial peptides named wheat antimicrobial peptides (WAMPs) containing different amino acids (Ala, Lys, Glu, and Asn) at the nonconserved position 34. An additional Ser at the site of fungalysin proteolysis makes the peptides resistant to the protease. Moreover, an equal molar concentration of WAMP-1b or WAMP-2 to chitinase was sufficient to block the fungalysin activity, keeping the chitinase intact. Thus, WAMPs represent novel protease inhibitors that are active against fungal metalloproteases. According to in vitro antifungal assays WAMPs directly inhibited hyphal elongation, suggesting that fungalysin plays an important role in fungal development. A novel molecular mechanism of dynamic interplay between host defense molecules and fungal virulence factors is suggested.

  5. A-Disintegrin and Metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells.

    Science.gov (United States)

    Bulstrode, Harry; Jones, Louise M; Siney, Elodie J; Sampson, Jessica M; Ludwig, Andreas; Gray, William P; Willaime-Morawek, Sandrine

    2012-12-29

    It has been proposed that gliomas contain a subpopulation of 'Brain Tumor Stem Cells' (BTSCs), which demonstrate resistance to conventional therapies. A potential component of the environment governing the behavior of these BTSCs is a class of transmembrane proteins with structural and signaling functions, the A-Disintegrin And Metalloproteases (ADAMs). In this study we confirm overexpression of ADAM10 and 17 in human glioma tissue compared to human controls, and especially in tumor sphere cultures thought to enrich for BTSCs. Inhibition of ADAM10/17 function impairs the growth of tumor spheres with evidence of depletion of the sphere forming cell population. This results from a combination of reduced proliferation, cell death and a switch of sphere-forming cells away from symmetric self-renewal division towards neuronal differentiation. A developing appreciation of the role of ADAMs in BTSC promises insights into pathophysiology and potential therapeutic avenues in this intractable group of tumors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat)*

    Science.gov (United States)

    Hershko, Klilah; Simhadri, Vijaya L.; Blaisdell, Adam; Hunt, Ryan C.; Newell, Jordan; Tseng, Sandra C.; Hershko, Alon Y.; Choi, Jae Won; Sauna, Zuben E.; Wu, Andrew; Bram, Richard J.; Komar, Anton A.; Kimchi-Sarfaty, Chava

    2012-01-01

    The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients. PMID:23144461

  7. The Matrix Metalloproteases and Endothelin-1 in Infection-Associated Preterm Birth

    Directory of Open Access Journals (Sweden)

    Nicole S. Olgun

    2010-01-01

    Full Text Available Preterm birth (PTB is clinically defined as any delivery which occurs before the completion of 37 weeks of gestation, and is currently the most important problem in obstetrics. In the United States, PTB accounts for 12-13% of all live births, and, with the exception of fetuses suffering from anomalies, is the primary cause of perinatal mortality. While the risk factors for PTB are numerous, the single most common cause is intrauterine infection. As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL and delivery should be given high priority. The matrix metalloproteinases (MMPs are a family of enzymes that have been implicated in normal parturition as well as infection-triggered rupture of membranes and preterm birth. Several lines of evidence also suggest a role for endothelin-1 (ET-1 in infection-associated preterm delivery. This paper focuses on the evidence that the MMPs and ET-1 act in the same molecular pathway in preterm birth.

  8. YghJ, the secreted metalloprotease of pathogenic E. coli induces hemorrhagic fluid accumulation in mouse ileal loop.

    Science.gov (United States)

    Tapader, Rima; Bose, Dipro; Pal, Amit

    2017-04-01

    YghJ, also known as SslE (Secreted and surface associated lipoprotein) is a cell surface associated and secreted lipoprotein harbouring M60 metalloprotease domain. Though the gene is known to be conserved among both pathogenic and commensal Escherichia coli isolates, the expression and secretion of YghJ was found to be higher among diverse E. coli pathotypes. YghJ, secreted from intestinal pathogens such as enterotoxigenic E. coli (ETEC) and enteropathogenic E. coli (EPEC) has been demonstrated to possess mucinase activity and hence facilitates colonization of these enteric pathogens to intestinal epithelial cells. Importantly, YghJ is also reported to be secreted from extraintestinal pathogenic E. coli isolates. In our previous study we have shown that YghJ, purified from a neonatal septicemic E. coli isolate could trigger induction of various proinflammatory cytokines in vitro. This led us to investigate the role of YghJ in causing in vivo tissue hemorrhage. In the present study, we validate the earlier in vitro finding and have showed that YghJ can cause extensive tissue damage in mouse ileum and is also able to induce significant fluid accumulation in a dose dependent manner in a mouse ileal loop (MIL) assay. Hence, our present study not only confirms the pathogenic potential of YghJ in sepsis pathophysiology but also indicates the enterotoxic ability of YghJ which makes it an important virulence determinant of intestinal pathogenic E. coli. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Titanium dioxide nanoparticles induce matrix metalloprotease 1 in human pulmonary fibroblasts partly via an interleukin-1β-dependent mechanism.

    Science.gov (United States)

    Armand, Lucie; Dagouassat, Maylis; Belade, Esther; Simon-Deckers, Angélique; Le Gouvello, Sabine; Tharabat, Chantal; Duprez, Corinne; Andujar, Pascal; Pairon, Jean-Claude; Boczkowski, Jorge; Lanone, Sophie

    2013-03-01

    Exposure to titanium dioxide (TiO2) nanoparticles (NPs) is associated with lung remodeling, but the underlying mechanisms are unknown. Matrix metalloprotease (MMP)-1 is an important actor in matrix homeostasis and could therefore participate in TiO2 NP effects. Our aim was to evaluate the effects of TiO2 NPs on MMP-1 expression and activity in lung pulmonary fibroblasts and to understand the underlying mechanisms and assess the importance of the physicochemical characteristics of the particles in these effects. Human pulmonary fibroblasts (MRC-5 cell line and primary cells) were exposed to 10 or 100 μg/cm(2) TiO2 (two anatases, two anatase/rutile mix, one rutile NP, and one micrometric) and carbon black (CB) NPs for 6 to 48 hours. We examined cell viability, MMP-1 expression and activity, and the implication of oxidative stress, transforming growth factor (TGF)-β, extracellular MMP inducer, and IL-1β in MMP-1 expression. All TiO2 NPs induced MMP-1 (mRNA and protein expression), repression of procollagen-1, and α-actin expression, but only the two anatase/rutile mix induced MMP-1 activity. Micrometric TiO2 had smaller effects than TiO2 NPs, and CB NPs did not induce MMP-1. MMP-1 induction by TiO2 NPs was not related to TGF-β, oxidative stress, or EMPRIN expression but was related to IL-1β expression, which partly drives MMP-1 induction by two TiO2 NPs (one anatase/rutile mix and the rutile one). Taken together, our results show that TiO2 NPs are potent inducers and regulators of MMP-1 expression and activity, partly via an IL-1β-dependent mechanism. This may explain TiO2 lung remodeling effects.

  10. The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts.

    Science.gov (United States)

    Hartmann, Dieter; de Strooper, Bart; Serneels, Lutgarde; Craessaerts, Katleen; Herreman, An; Annaert, Wim; Umans, Lieve; Lübke, Torben; Lena Illert, Anna; von Figura, Kurt; Saftig, Paul

    2002-10-01

    The metalloprotease ADAM 10 is an important APP alpha-secretase candidate, but in vivo proof of this is lacking. Furthermore, invertebrate models point towards a key role of the ADAM 10 orthologues Kuzbanian and sup-17 in Notch signalling. In the mouse, this function is, however, currently attributed to ADAM 17/TACE, while the role of ADAM 10 remains unknown. We have created ADAM 10-deficient mice. They die at day 9.5 of embryogenesis with multiple defects of the developing central nervous system, somites, and cardiovascular system. In situ hybridization revealed a reduced expression of the Notch target gene hes-5 in the neural tube and an increased expression of the Notch ligand dll-1, supporting an important role for ADAM 10 in Notch signalling in the vertebrates as well. Since the early lethality precluded the establishment of primary neuronal cultures, APPs alpha generation was analyzed in embryonic fibroblasts and found to be preserved in 15 out of 17 independently generated ADAM 10-deficient fibroblast cell lines, albeit at a quantitatively more variable level than in controls, whereas a severe reduction was found in only two cases. The variability was not due to differences in genetic background or to variable expression of the alternative alpha-secretase candidates ADAM 9 and ADAM 17. These results indicate, therefore, either a regulation between ADAMs on the post-translational level or that other, not yet known, proteases are able to compensate for ADAM 10 deficiency. Thus, the observed variability, together with recent reports on tissue-specific expression patterns of ADAMs 9, 10 and 17, points to the existence of tissue-specific 'teams' of different proteases exerting alpha-secretase activity.

  11. Role of matrix metalloproteases in the kinetics of leukocyte-endothelial adhesion in post-capillary venules.

    Science.gov (United States)

    Lipowsky, Herbert H; Lescanic, Anne; Sah, Rachna

    2015-01-01

    The endothelial glycocalyx serves as a barrier to leukocyte (WBC)-endothelium (EC) adhesion. Shedding of glycans, by matrix metalloproteases (MMPs) exposes EC integrin receptors to facilitate firm adhesion. However, the effect of shedding on the strength of the adhesive bond remains to be determined. Examine the effect of MMP inhibition on the kinetics of WBC-EC adhesion under normal and inflammatory conditions to delineate differences in the duration and number of adhesive bonds. WBC adhesion in post-capillary venules was observed in rat mesentery. Adhesion duration and off-rates (KOFF) were correlated with shear stress during adhesion in response to 1 µM fMLP or 0.5 µM doxycycline (doxy, to inhibit MMP activation). Doxy increased mean adhesion time significantly from 2.5 (control) to 5.6 s, whereas fMLP increased it 8-fold to 20 s, which was not affected by pre-treatment with doxy. Estimates of the number of adhesive bonds (simplified Bell-model) revealed a significantly greater increase with fMLP compared to doxy alone, with no effect on fMLP by pretreatment with doxy. With doxy alone, KOFF was significantly 4-fold greater compared to fMLP, suggesting a much weaker bond. Although the increased number of bonds by MMP inhibition with doxy alone and fMLP were similar, the bonds due to doxy appeared weaker as evidenced by their shorter duration, and lesser reduction in KOFF relative to control. Thus doxy limits the availability of integrin binding sites during fMLP stimulated adhesion, but has a pro-adhesive effect due to increased ligands for WBC binding that arises from inhibition of normal sheddase activity on the EC.

  12. The N-Terminal Propeptide of Vibrio vulnificus Extracellular Metalloprotease Is both an Inhibitor of and a Substrate for the Enzyme▿

    OpenAIRE

    2007-01-01

    Vibrio vulnificus, a marine bacterium capable of causing wound infection and septicemia, secretes a 45-kDa metalloprotease (vEP) with many biological activities. The precursor of vEP consists of four regions: a signal peptide, an N-terminal propeptide (nPP), a C-terminal propeptide, and the mature protease. Two forms of vEP—vEP-45, which contains the mature protease plus the C-terminal propeptide, and vEP-34, which contains only the mature protease—were expressed in Escherichia coli and purif...

  13. Expression of tissue inhibitor of metalloprotease 3 is reduced in ischemic but not neuropathic ulcers from patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Menghini, R; Uccioli, L; Vainieri, E; Pecchioli, C; Casagrande, V; Stoehr, R; Cardellini, M; Porzio, O; Rizza, S; Federici, M

    2013-12-01

    Diabetic foot ulceration remains one of the most common and most serious consequences of diabetes. Persistently high levels of matrix metalloproteases (MMPs) contribute to wound chronicity. Our aim was to assess the concentrations of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in neuropathic and ischemic diabetic foot ulcers by analyzing biopsy samples. In this study, biopsies were taken from 35 diabetic foot ulcers of type 2 diabetes mellitus patients and distinguished in neuropathic (n = 14) or ischemic (n = 21). Zymography assay was utilized for the analysis of MMP-2 and MMP-9 activity. TACE activity was evaluated by a specific fluorimetric assay. mRNA levels of MMPs as well as TIMPs were detected using quantitative real-time polymerase chain reaction. The activity of MMP9 and A Disintegrin and A MetalloProtease Domain 17/TNF-Alpha Converting Enzyme (ADAM17/TACE) was significantly increased in ischemic compared to neuropathic biopsies. No differences were detected between both groups for the mRNA levels of MMPs as well as of ADAMs. However, TIMP3 mRNA expression was decreased in ischemic samples. The combination of increased activity of MMP9 and ADAM17/TACE with decreased concentrations of TIMP-3 mRNA expression in ischemic diabetic foot ulcers compared to neuropathic samples suggests that the increased proteolytic environment may represent a causative factor in the ulcer progression. New treatment strategies for healing diabetic foot ulcers could be directed toward increasing levels of TIMP3.

  14. A natural bacterial-derived product, the metalloprotease arazyme, inhibits metastatic murine melanoma by inducing MMP-8 cross-reactive antibodies.

    Directory of Open Access Journals (Sweden)

    Felipe V Pereira

    Full Text Available The increased incidence, high rates of mortality and few effective means of treatment of malignant melanoma, stimulate the search for new anti-tumor agents and therapeutic targets to control this deadly metastatic disease. In the present work the antitumor effect of arazyme, a natural bacterial-derived metalloprotease secreted by Serratia proteomaculans, was investigated. Arazyme significantly reduced the number of pulmonary metastatic nodules after intravenous inoculation of B16F10 melanoma cells in syngeneic mice. In vitro, the enzyme showed a dose-dependent cytostatic effect in human and murine tumor cells, and this effect was associated to the proteolytic activity of arazyme, reducing the CD44 expression at the cell surface, and also reducing in vitro adhesion and in vitro/in vivo invasion of these cells. Arazyme treatment or immunization induced the production of protease-specific IgG that cross-reacted with melanoma MMP-8. In vitro, this antibody was cytotoxic to tumor cells, an effect increased by complement. In vivo, arazyme-specific IgG inhibited melanoma lung metastasis. We suggest that the antitumor activity of arazyme in a preclinical model may be due to a direct cytostatic activity of the protease in combination with the elicited anti-protease antibody, which cross-reacts with MMP-8 produced by tumor cells. Our results show that the bacterial metalloprotease arazyme is a promising novel antitumor chemotherapeutic agent.

  15. Mechanism of heparin acceleration of tissue inhibitor of metalloproteases-1 (TIMP-1 degradation by the human neutrophil elastase.

    Directory of Open Access Journals (Sweden)

    Gabriel L C Nunes

    Full Text Available Heparin has been shown to regulate human neutrophil elastase (HNE activity. We have assessed the regulatory effect of heparin on Tissue Inhibitor of Metalloproteases-1 [TIMP-1] hydrolysis by HNE employing the recombinant form of TIMP-1 and correlated FRET-peptides comprising the TIMP-1 cleavage site. Heparin accelerates 2.5-fold TIMP-1 hydrolysis by HNE. The kinetic parameters of this reaction were monitored with the aid of a FRET-peptide substrate that mimics the TIMP-1 cleavage site in pre-steady-state conditionsby using a stopped-flow fluorescence system. The hydrolysis of the FRET-peptide substrate by HNE exhibits a pre-steady-state burst phase followed by a linear, steady-state pseudo-first-order reaction. The HNE acylation step (k₂ = 21±1 s⁻¹ was much higher than the HNE deacylation step (k₃ = 0.57±0.05 s⁻¹. The presence of heparin induces a dramatic effect in the pre-steady-state behavior of HNE. Heparin induces transient lag phase kinetics in HNE cleavage of the FRET-peptide substrate. The pre-steady-state analysis revealed that heparin affects all steps of the reaction through enhancing the ES complex concentration, increasing k₁ 2.4-fold and reducing k₋₁ 3.1-fold. Heparin also promotes a 7.8-fold decrease in the k₂ value, whereas the k₃ value in the presence of heparin was increased 58-fold. These results clearly show that heparin binding accelerates deacylation and slows down acylation. Heparin shifts the HNE pH activity profile to the right, allowing HNE to be active at alkaline pH. Molecular docking and kinetic analysis suggest that heparin induces conformational changes in HNE structure. Here, we are showing for the first time that heparin is able to accelerate the hydrolysis of TIMP-1 by HNE. The degradation of TIMP-1is associated to important physiopathological states involving excessive activation of MMPs.

  16. Cleavage of the Carboxyl-Terminus of LEACS2, a Tomato 1-Aminocycl opropane-1-Carboxylic Acid Synthase Isomer, by a 64-kDa Tomato Metalloprotease Produces a Truncated but Active Enzyme

    Institute of Scientific and Technical Information of China (English)

    Jian-Feng LI; Robert QI; Liang-Hu QU; Autar K Mattoo; Ning LI

    2005-01-01

    l-Aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) is the principal enzyme in phytohormone ethylene biosynthesis. Previous studies have shown that the hypervariable C-terminus of ACS is proteolytically processed in vivo. However, the protease responsible for this has not yet been identified. In the present study, we investigated the processing of the 55-kDa full-length tomato ACS (LeACS2) into 52-, 50- and 49-kDa truncated isoforms in ripening tomato (Lycopersicon esculentum Mill. cv.Cooperation 903) fruit using the sodium dodecyl sulfate-boiling method. Meanwhile, an LeACS2-processing protease was purified via multi-step column chromatography from tomato fruit. Subsequent biochemical analysis of the 64-kDa purified protease revealed that it is a metalloprotease active at multiple cleavage sites within the hypervariable C-terminus of LeACS2. N-terminal sequencing and matrix-assisted laser desorption/ionization time-of-flight analysis indicated that the LeACS2-processing metalloprotease cleaves at the C-terminal sites Lys438, Glu447, Lys448, Asn456, Ser460, Ser462, Lys463, and Leu474, but does not cleave the Nterminus of LeACS2. Four C-terminus-deleted (26-50 amino acids) LeACS2 fusion proteins were overproduced and subjected to proteolysis by this metalloprotease to identify the multiple cleavage sites located on the N-terminal side of the phosphorylation site Ser460. The results indisputably confirmed the presence of cleavage sites within the region between the α-helix domain (H14) and Ser460 for this metalloprotease.Furhermore, the resulting C-terminally truncated LeACS2 isoforms were active enzymatically. Because this protease could produce LeACS2 isoforms in vitro similar to those detected in vivo, it is proposed that this metalloprotease may be involved in the proteolysis of LeACS2 in vivo.

  17. Dissolved families

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The situation in the family preceding a family separation is studied here, to identify risk factors for family dissolution. Information registers covering prospective statistics about health aspects, demographic variables, family violence, self-destructive behaviour, unemployment, and the spousal...

  18. Dissolved families

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The situation in the family preceding a family separation is studied here, to identify risk factors for family dissolution. Information registers covering prospective statistics about health aspects, demographic variables, family violence, self-destructive behaviour, unemployment, and the spousal...

  19. Family Life

    Science.gov (United States)

    ... With Family and Friends > Family Life Request Permissions Family Life Approved by the Cancer.Net Editorial Board , ... your outlook on the future. Friends and adult family members The effects of cancer on your relationships ...

  20. Role of the virulence plasmid pR99 and the metalloprotease Vvp in resistance of Vibrio vulnificus serovar E to eel innate immunity.

    Science.gov (United States)

    Valiente, E; Lee, C T; Lamas, J; Hor, L; Amaro, C

    2008-01-01

    Vibrio vulnificus biotype 2 serovar E (VSE) is a bacterial pathogen that produces a haemorrhagic septicaemia called vibriosis in eels. Its ability to grow in blood is conferred by a recently described virulence plasmid [Lee CT, Amaro C, Wu KM, Valiente E, Chang YF, Tsai SF, et al. A common virulence plasmid in biotype 2 Vibrio vulnificus and its dissemination aided by a conjugal plasmid. Journal of Bacteriology, submitted for publication.]. In this study, we analyzed the role of this plasmid together with the role played by the metalloprotease (Vvp) in the interaction between bacteria and eel innate immunity. To this end, we compared and statistically analyzed the differences in resistance to serum and mucus factors (complement, selected antimicrobial peptides, transferrin and lysozyme) and also to phagocytosis/opsonophagocytosis between one VSE strain and its derivatives: a plasmid-cured strain and a vvp-deficient mutant. The wild-type and the metalloprotease-deficient strains were resistant to both the bactericidal action of fresh serum and the phagocytosis and opsonophagocytosis by eel phagocytes, confirming that Vvp is not involved in resistance to eel innate immunity. In contrast, the cured strain was sensitive to both the bactericidal action of eel serum activated by the alternative pathway and phagocytosis/opsonophagocytosis. Since no plasmid-encoded ORF, with homology to known genes, is related to the resistance to innate immunity [Lee CT, Amaro C, Wu KM, Valiente E, Chang YF, Tsai SF, et al. A common virulence plasmid in biotype 2 Vibrio vulnificus and its dissemination aided by a conjugal plasmid. Journal of Bacteriology, submitted for publication.], this function could be codified by one or more new genes. Further studies are underway to characterize the plasmid-encoded system responsible for V. vulnificus resistance to the innate immune system of eels.

  1. Family Therapy

    Science.gov (United States)

    ... may be credentialed by the American Association for Marriage and Family Therapy (AAMFT). Family therapy is often short term. ... challenging situations in a more effective way. References Marriage and family therapists: The friendly mental health professionals. American Association ...

  2. Familial hypertriglyceridemia

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000397.htm Familial hypertriglyceridemia To use the sharing features on this page, please enable JavaScript. Familial hypertriglyceridemia is a common disorder passed down through families. ...

  3. Family Meals

    Science.gov (United States)

    ... Teaching Kids to Be Smart About Social Media Family Meals KidsHealth > For Parents > Family Meals Print A ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  4. Family Arguments

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Arguments Page Content Article Body We seem to ...

  5. Family History

    Science.gov (United States)

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  6. Interaction between TNF and BmooMP-Alpha-I, a Zinc Metalloprotease Derived from Bothrops moojeni Snake Venom, Promotes Direct Proteolysis of This Cytokine: Molecular Modeling and Docking at a Glance

    Science.gov (United States)

    Silva, Maraisa Cristina; Lopes Silva, Tamires; Silva, Murilo Vieira; Mota, Caroline Martins; Santiago, Fernanda Maria; Fonseca, Kelly Cortes; Oliveira, Fábio; Mineo, Tiago Wilson Patriarca; Mineo, José Roberto

    2016-01-01

    Tumor necrosis factor (TNF) is a major cytokine in inflammatory processes and its deregulation plays a pivotal role in several diseases. Here, we report that a zinc metalloprotease extracted from Bothrops moojeni venom (BmooMP-alpha-I) inhibits TNF directly by promoting its degradation. This inhibition was demonstrated by both in vitro and in vivo assays, using known TLR ligands. These findings are supported by molecular docking results, which reveal interaction between BmooMP-alpha-I and TNF. The major cluster of interaction between BmooMP-alpha-I and TNF was confirmed by the structural alignment presenting Ligand Root Mean Square Deviation LRMS = 1.05 Å and Interactive Root Mean Square Deviation IRMS = 1.01 Å, this result being compatible with an accurate complex. Additionally, we demonstrated that the effect of this metalloprotease on TNF is independent of cell cytotoxicity and it does not affect other TLR-triggered cytokines, such as IL-12. Together, these results indicate that this zinc metalloprotease is a potential tool to be further investigated for the treatment of inflammatory disorders involving TNF deregulation. PMID:27447669

  7. EphrinA/EphA-induced ectodomain shedding of neural cell adhesion molecule regulates growth cone repulsion through ADAM10 metalloprotease.

    Science.gov (United States)

    Brennaman, Leann H; Moss, Marcia L; Maness, Patricia F

    2014-01-01

    EphrinA/EphA-dependent axon repulsion is crucial for synaptic targeting in developing neurons but downstream molecular mechanisms remain obscure. Here, it is shown that ephrinA5/EphA3 triggers proteolysis of the neural cell adhesion molecule (NCAM) by the metalloprotease a disintegrin and metalloprotease (ADAM)10 to promote growth cone collapse in neurons from mouse neocortex. EphrinA5 induced ADAM10 activity to promote ectodomain shedding of polysialic acid-NCAM in cortical neuron cultures, releasing a ~ 250 kDa soluble fragment consisting of most of its extracellular region. NCAM shedding was dependent on ADAM10 and EphA3 kinase activity as shown in HEK293T cells transfected with dominant negative ADAM10 and kinase-inactive EphA3 (K653R) mutants. Purified ADAM10 cleaved NCAM at a sequence within the E-F loop of the second fibronectin type III domain (Leu(671) -Lys(672) /Ser(673) -Leu(674) ) identified by mass spectrometry. Mutations of NCAM within the ADAM10 cleavage sequence prevented EphA3-induced shedding of NCAM in HEK293T cells. EphrinA5-induced growth cone collapse was dependent on ADAM10 activity, was inhibited in cortical cultures from NCAM null mice, and was rescued by WT but not ADAM10 cleavage site mutants of NCAM. Regulated proteolysis of NCAM through the ephrin5/EphA3/ADAM10 mechanism likely impacts synapse development, and may lead to excess NCAM shedding when disrupted, as implicated in neurodevelopmental disorders such as schizophrenia. PSA-NCAM and ephrinA/EphA3 coordinately regulate inhibitory synapse development. Here, we have found that ephrinA5 stimulates EphA3 kinase and ADAM10 activity to promote PSA-NCAM cleavage at a site in its second FNIII repeat, which regulates ephrinA5-induced growth cone collapse in GABAergic and non-GABAergic neurons. These findings identify a new regulatory mechanism which may contribute to inhibitory connectivity.

  8. Family Privilege

    Science.gov (United States)

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  9. Family Privilege

    Science.gov (United States)

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  10. Purification and characterization of a 630 kDa bacterial killing metalloprotease (KilC) isolated from plaice Pleuronectes platessa (L.), epidermal mucus.

    Science.gov (United States)

    Tvete, T; Haugan, K

    2008-05-01

    Antibacterial chemicals in the mucus of fish such as lysozyme, lectins, peptides and proteases provide an efficient first line of defence against pathogens. This study shows that there are at least three antibacterial proteins in plaice skin mucus in addition to lysozyme. One of these proteins is responsible for approximately 74% of the antibacterial activity and is a 630 kDa protease complex designated KilC (bacterial killing metalloprotease C). Purified KilC kills the bacteria Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa efficiently. The protease activity of KilC is dependent upon the divalent cation Mg(2+) and shows pH dual optima of 5.0 and 8.0. The enzyme has a temperature optimum of 25 degrees C and is made up of at least five different sized peptides. Studies with protease inhibitors show that the catalytic site of KilC may be cysteine- or serine protease-like. KilC may kill bacterial cells by acting directly upon the bacteria or by producing low molecular weight bioactive compounds such as peptides.

  11. Metalloprotease-mediated cleavage of PlexinD1 and its sequestration to actin rods in the motoneuron disease spinal muscular atrophy (SMA).

    Science.gov (United States)

    Rademacher, Sebastian; Verheijen, Bert M; Hensel, Niko; Peters, Miriam; Bora, Gamze; Brandes, Gudrun; Vieira de Sá, Renata; Heidrich, Natascha; Fischer, Silke; Brinkmann, Hella; van der Pol, W Ludo; Wirth, Brunhilde; Pasterkamp, R Jeroen; Claus, Peter

    2017-10-15

    Cytoskeletal rearrangement during axon growth is mediated by guidance receptors and their ligands which act either as repellent, attractant or both. Regulation of the actin cytoskeleton is disturbed in Spinal Muscular Atrophy (SMA), a devastating neurodegenerative disease affecting mainly motoneurons, but receptor-ligand interactions leading to the dysregulation causing SMA are poorly understood. In this study, we analysed the role of the guidance receptor PlexinD1 in SMA pathogenesis. We showed that PlexinD1 is cleaved by metalloproteases in SMA and that this cleavage switches its function from an attractant to repellent. Moreover, we found that the PlexinD1 cleavage product binds to actin rods, pathological aggregate-like structures which had so far been described for age-related neurodegenerative diseases. Our data suggest a novel disease mechanism for SMA involving formation of actin rods as a molecular sink for a cleaved PlexinD1 fragment leading to dysregulation of receptor signaling. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Expression of the matrix metalloproteases 2, 14, 24, and 25 and tissue inhibitor 3 as potential molecular markers in advanced human gastric cancer.

    Science.gov (United States)

    de la Peña, Sol; Sampieri, Clara Luz; Ochoa-Lara, Mariana; León-Córdoba, Kenneth; Remes-Troche, José María

    2014-01-01

    During progression of gastric cancer (GC), degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs): changes in the expression of these have been related to unfavorable prognosis in GC. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG) and GC. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle (C(T)) values, as very high (C(T) ≤ 25), high (C(T) = 26-30), moderate (C(T) = 31-35), low (C(T) = 36-39), or not detected (C(T) = 40). Strength of association was estimated between the proteins, which were detected by Western blot, and the risk of developing GC. We found a high expression of MMP1, MMP2, MMP14, TIMP1, and TIMP3; moderate one of MMP9 and MMP25, and low one of MMP13 and MMP24 in both tissues. In absolute mRNA levels, significant differences were found in expression of MMP2, MMP24, and MMP25, which are overexpressed in GC compared with SG. The presence of the proteins MMP-14 and TIMP-3 was associated with the risk of developing GC. We consider that MMP2, MMP24, and MMP25 and the proteins MMP-14 and TIMP-3 could be candidates for prognostic molecular markers in GC.

  13. The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo.

    Science.gov (United States)

    Hews, Claire L; Tran, Seav-Ly; Wegmann, Udo; Brett, Bernard; Walsham, Alistair D S; Kavanaugh, Devon; Ward, Nicole J; Juge, Nathalie; Schüller, Stephanie

    2017-01-05

    Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen and tightly adheres to human colonic epithelium by forming attaching/effacing lesions. To reach the epithelial surface, EHEC must penetrate the thick mucus layer protecting the colonic epithelium. In this study, we investigated how EHEC interacts with the intestinal mucus layer using mucin-producing LS174T colon carcinoma cells and human colonic mucosal biopsies. The level of EHEC binding and attaching/effacing lesion formation in LS174T cells was higher compared to mucin-deficient colon carcinoma cell lines, and initial adherence was independent of the presence of flagellin, Escherichia coli common pilus, or long polar fimbriae. Although EHEC infection did not affect gene expression of secreted mucins, it resulted in reduced MUC2 glycoprotein levels. This effect was dependent on the catalytic activity of the secreted metalloprotease StcE, which reduced the inner mucus layer and thereby promoted EHEC access and binding to the epithelium in vitro and ex vivo. Given the lack of efficient therapies against EHEC infection, StcE may represent a suitable target for future treatment and prevention strategies.

  14. Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumour stromal mononuclear inflammatory cells and those at the invasive front of breast carcinomas.

    Science.gov (United States)

    González, Luis O; González-Reyes, Salomé; Marín, Laura; González, Lucía; González, José M; Lamelas, Maria L; Merino, Antonio M; Rodríguez, Elena; Pidal, Iván; del Casar, José M; Andicoechea, Alejandro; Vizoso, Francisco

    2010-12-01

    Matrix metalloproteases (MMPs) and their inhibitors (TIMPs) play an essential role in the degradation of stromal connective tissue and basement membrane components. The aim of this study was to determine whether the dynamic analysis of these components can help to predict tumour aggressiveness. An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, -2, -7, -9, -11, -13 and -14 and TIMPs -1, -2 and -3. More than 5000 determinations on cancer specimens from 124 patients with invasive breast cancer were performed on the tumour centre core as well as on the invasive front. Immunostaining for MMPs/TIMPs on mononuclear inflammatory cells (MICs) was evaluated. To identify specific groups of tumours with distinct expression profiles, data obtained from both MICs populations were analysed by unsupervised hierarchical cluster analysis. When compared with MICs at the invasive front, intratumour MICs more frequently showed expression of MMP-7 and -1 and TIMP-3, but less frequently expression of MMP-9 and -11 and TIMP-2. Our data led us to consider the need of further studies in order to identify subsets of MICs and other protein elements of the microenvironment as attractive targets for new therapeutic strategies against cancer. © 2010 Blackwell Publishing Limited.

  15. A 24-kDa cloned zinc metalloprotease from Actinobacillus pleuropneumoniae is common to all serotypes and cleaves actin in vitro.

    Science.gov (United States)

    García-Cuéllar, C; Montañez, C; Tenorio, V; Reyes-Esparza, J; Durán, M J; Negrete, E; Guerrero, A; de la Garza, M

    2000-01-01

    Actinobacillus pleuropneumoniae causes pleuropneumonia in swine. This bacterium secretes proteases that degrade porcine hemoglobin and IgA in vitro. To further characterize A. pleuropneumoniae proteases, we constructed a genomic library expressed in Escherichia coli DH5alpha, and selected a clone that showed proteolytic activity. The recombinant plasmid carries an 800-base pair A. pleuropneumoniae gene sequence that.codes for a 24-kDa polypeptide. A 350-base pair PstI fragment from the sequence hybridized at high stringency with DNA from 12 serotypes of A. pleuropneumoniae, but not with DNA from Actinobacillus suis, Haemophilus parasuis, Pasteurella haemolytica, Pasteurella multocida A or D, or E. coli DH5alpha, thus showing specificity for A. pleuropneumoniae. The expressed polypeptide was recognized as an antigen by convalescent-phase pig sera. Furthermore, a polyclonal antiserum developed against the purified polypeptide recognized an A. pleuropneumoniae oligomeric protein in both crude-extract and cell-free culture media. This recombinant polypeptide cleaved azocoll, gelatin, and actin. Inhibition of the proteolytic activity by diethylpyrocarbonate suggests that this polypeptide is a zinc metalloprotease. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 6. Figure 7. PMID:10805246

  16. Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 as Potential Molecular Markers in Advanced Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Sol de la Peña

    2014-01-01

    Full Text Available Background. During progression of gastric cancer (GC, degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs and their tissue inhibitors (TIMPs: changes in the expression of these have been related to unfavorable prognosis in GC. Objective. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG and GC. Methods. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle (CT values, as very high (CT≤25, high (CT=26–30, moderate (CT=31–35, low (CT=36–39, or not detected (CT=40. Strength of association was estimated between the proteins, which were detected by Western blot, and the risk of developing GC. Results. We found a high expression of MMP1, MMP2, MMP14, TIMP1, and TIMP3; moderate one of MMP9 and MMP25, and low one of MMP13 and MMP24 in both tissues. In absolute mRNA levels, significant differences were found in expression of MMP2, MMP24, and MMP25, which are overexpressed in GC compared with SG. The presence of the proteins MMP-14 and TIMP-3 was associated with the risk of developing GC. Conclusions. We consider that MMP2, MMP24, and MMP25 and the proteins MMP-14 and TIMP-3 could be candidates for prognostic molecular markers in GC.

  17. Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 as Potential Molecular Markers in Advanced Human Gastric Cancer

    Science.gov (United States)

    de la Peña, Sol; Sampieri, Clara Luz; Ochoa-Lara, Mariana; León-Córdoba, Kenneth; Remes-Troche, José María

    2014-01-01

    Background. During progression of gastric cancer (GC), degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs): changes in the expression of these have been related to unfavorable prognosis in GC. Objective. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG) and GC. Methods. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle (CT) values, as very high (CT ≤ 25), high (CT = 26–30), moderate (CT = 31–35), low (CT = 36–39), or not detected (CT = 40). Strength of association was estimated between the proteins, which were detected by Western blot, and the risk of developing GC. Results. We found a high expression of MMP1, MMP2, MMP14, TIMP1, and TIMP3; moderate one of MMP9 and MMP25, and low one of MMP13 and MMP24 in both tissues. In absolute mRNA levels, significant differences were found in expression of MMP2, MMP24, and MMP25, which are overexpressed in GC compared with SG. The presence of the proteins MMP-14 and TIMP-3 was associated with the risk of developing GC. Conclusions. We consider that MMP2, MMP24, and MMP25 and the proteins MMP-14 and TIMP-3 could be candidates for prognostic molecular markers in GC. PMID:24669030

  18. A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.

    Directory of Open Access Journals (Sweden)

    Peter Durand Skottrup

    Full Text Available Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a likely drug target. In this study peptides were selected towards the catalytic domain from Karilysin (Kly18 by phage display. The peptides were linear with low micromolar binding affinities. The two best binders (peptide14 and peptide15, shared the consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein (MBP was produced with peptide15 fused to the N-terminus of MBP. The peptide15-MBP was expressed in E. coli and the purified fusion-protein was used to verify Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG could inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48. Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to Kly18. The WFP motif was important for inhibition and a truncation study further demonstrated that the N-terminal serine was also essential for Kly18 inhibition. The SWFP peptide had a Ki value in the low micromolar range, which was similar to the intact peptide15. In conclusion SWFP is the first reported inhibitor of Karilysin and can be used as a valuable tool in structure-function studies of Karilysin.

  19. A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.

    Science.gov (United States)

    Skottrup, Peter Durand; Sørensen, Grete; Ksiazek, Miroslaw; Potempa, Jan; Riise, Erik

    2012-01-01

    Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a likely drug target. In this study peptides were selected towards the catalytic domain from Karilysin (Kly18) by phage display. The peptides were linear with low micromolar binding affinities. The two best binders (peptide14 and peptide15), shared the consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein (MBP) was produced with peptide15 fused to the N-terminus of MBP. The peptide15-MBP was expressed in E. coli and the purified fusion-protein was used to verify Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG) could inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48). Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to Kly18. The WFP motif was important for inhibition and a truncation study further demonstrated that the N-terminal serine was also essential for Kly18 inhibition. The SWFP peptide had a Ki value in the low micromolar range, which was similar to the intact peptide15. In conclusion SWFP is the first reported inhibitor of Karilysin and can be used as a valuable tool in structure-function studies of Karilysin.

  20. Critical Role of the Disintegrin Metalloprotease ADAM-like Decysin-1 [ADAMDEC1] for Intestinal Immunity and Inflammation.

    Science.gov (United States)

    O'Shea, Nuala R; Chew, Thean S; Dunne, Jenny; Marnane, Rebecca; Nedjat-Shokouhi, Bahman; Smith, Philip J; Bloom, Stuart L; Smith, Andrew M; Segal, Anthony W

    2016-12-01

    ADAM [A Disintegrin And Metalloproteinase] is a family of peptidase proteins which have diverse roles in tissue homeostasis and immunity. Here, we study ADAM-like DECysin-1 [ADAMDEC1] a unique member of the ADAM family. ADAMDEC1 expression is restricted to the macrophage/dendritic cell populations of the gastrointestinal tract and secondary lymphoid tissue. The biological function of ADAMDEC1 is unknown but it has been hypothesised to play a role in immunity. The identification of reduced ADAMDEC1 expression in Crohn's disease patients has provided evidence of a potential role in bowel inflammation. Adamdec1(-/-) mice were exposed to dextran sodium sulphate or infected orally with Citrobacter rodentium or Salmonella typhimurium. The clinical response was monitored. The loss of Adamdec1 rendered mice more susceptible to the induction of bacterial and chemical induced colitis, as evidenced by increased neutrophil infiltration, greater IL-6 and IL-1β secretion, more weight loss and increased mortality. In the absence of Adamdec1, greater numbers of Citrobacter rodentium were found in the spleen, suggestive of a breakdown in mucosal immunity which resulted in bacteraemia. In summary, ADAMDEC1 protects the bowel from chemical and bacterial insults, failure of which may predispose to Crohn's disease. © European Crohn’s and Colitis Organisation 2016.

  1. Familial gigantism

    NARCIS (Netherlands)

    W.W. de Herder (Wouter)

    2012-01-01

    textabstractFamilial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  2. Familial gigantism

    Directory of Open Access Journals (Sweden)

    Wouter W. de Herder

    2012-01-01

    Full Text Available Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  3. Familial dermographism.

    Science.gov (United States)

    Jedele, K B; Michels, V V

    1991-05-01

    Urticaria in response to various physical stimuli has been reported in sporadic and familial patterns. The most common of these physical urticarias, dermographism, is a localized urticarial response to stroking or scratching of the skin and has not been reported previously to be familial. A four-generation family with dermographism, probably inherited as an autosomal dominant trait, is presented along with a discussion of sporadic dermographism and other types of familial physical urticarias.

  4. Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and retinal degeneration in mice.

    Science.gov (United States)

    Parry, David A; Toomes, Carmel; Bida, Lina; Danciger, Michael; Towns, Katherine V; McKibbin, Martin; Jacobson, Samuel G; Logan, Clare V; Ali, Manir; Bond, Jacquelyn; Chance, Rebecca; Swendeman, Steven; Daniele, Lauren L; Springell, Kelly; Adams, Matthew; Johnson, Colin A; Booth, Adam P; Jafri, Hussain; Rashid, Yasmin; Banin, Eyal; Strom, Tim M; Farber, Debora B; Sharon, Dror; Blobel, Carl P; Pugh, Edward N; Pierce, Eric A; Inglehearn, Chris F

    2009-05-01

    Cone-rod dystrophy (CRD) is an inherited progressive retinal dystrophy affecting the function of cone and rod photoreceptors. By autozygosity mapping, we identified null mutations in the ADAM metallopeptidase domain 9 (ADAM9) gene in four consanguineous families with recessively inherited early-onset CRD. We also found reduced photoreceptor responses in Adam9 knockout mice, previously reported to be asymptomatic. In 12-month-old knockout mice, photoreceptors appear normal, but the apical processes of the retinal pigment epithelium (RPE) cells are disorganized and contact between photoreceptor outer segments (POSs) and the RPE apical surface is compromised. In 20-month-old mice, there is clear evidence of progressive retinal degeneration with disorganized POS and thinning of the outer nuclear layer (ONL) in addition to the anomaly at the POS-RPE junction. RPE basal deposits and macrophages were also apparent in older mice. These findings therefore not only identify ADAM9 as a CRD gene but also identify a form of pathology wherein retinal disease first manifests at the POS-RPE junction.

  5. Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

    Directory of Open Access Journals (Sweden)

    Berta Temugin

    2012-03-01

    Full Text Available Abstract Background Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β. Matrix metalloprotease-9 (MMP-9 has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs and up-regulation of IL-1β in dorsal root ganglia (DRGs, and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results Subcutaneous morphine injection (10 mg/kg induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.

  6. Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

    Directory of Open Access Journals (Sweden)

    Mani Harika eVemula

    2016-03-01

    Full Text Available Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis (M.tb, the tuberculosis (TB causing bacilli in human is cleared by cell-mediated immunity (CMI with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches towards vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M.tb Zinc metalloprotease-1 (Zmp1, a secretory protein essential for intracellular survival and pathogenesis of M.tb. We observed that Zmp1 was secreted by in vitro grown M.tb under granuloma-like stress conditions (acidic, oxidative, iron deficiency and nutrient deprivation and generated Th2 cytokine microenvironment upon exogenous treatment of Peripheral Blood Mononulear Cells (PBMCs with recombinant Zmp1 (rZmp1. This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n=121 as against healthy control (n=62, household contacts (n=89 and non-specific infection controls (n=23. A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL to paucibacillary smear-negative pulmonary tuberculosis (PTB cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can be explored as antigen

  7. Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling.

    Directory of Open Access Journals (Sweden)

    Linda M Bradley

    Full Text Available The early inflammatory response to influenza virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which neutrophils gain entry to the respiratory tract and their role during pathogenesis remain unclear. Here, we report that neutrophils significantly contributed to morbidity in a pathological mouse model of influenza virus infection. Using extensive immunohistochemistry, bone marrow transfers, and depletion studies, we identified neutrophils as the predominant pulmonary cellular source of the gelatinase matrix metalloprotease (MMP 9, which is capable of digesting the extracellular matrix. Furthermore, infection of MMP9-deficient mice showed that MMP9 was functionally required for neutrophil migration and control of viral replication in the respiratory tract. Although MMP9 release was toll-like receptor (TLR signaling-dependent, MyD88-mediated signals in non-hematopoietic cells, rather than neutrophil TLRs themselves, were important for neutrophil migration. These results were extended using multiplex analyses of inflammatory mediators to show that neutrophil chemotactic factor, CCL3, and TNFα were reduced in the Myd88⁻/⁻ airways. Furthermore, TNFα induced MMP9 secretion by neutrophils and blocking TNFα in vivo reduced neutrophil recruitment after infection. Innate recognition of influenza virus therefore provides the mechanisms to induce recruitment of neutrophils through chemokines and to enable their motility within the tissue via MMP9-mediated cleavage of the basement membrane. Our results demonstrate a previously unknown contribution of MMP9 to influenza virus pathogenesis by mediating excessive neutrophil migration into the respiratory tract in response to viral replication that could be exploited for therapeutic purposes.

  8. Residues in Conserved Loops of Intramembrane Metalloprotease SpoIVFB Interact with Residues near the Cleavage Site in Pro-σK

    Science.gov (United States)

    Zhang, Yang; Luethy, Paul M.

    2013-01-01

    Intramembrane metalloproteases (IMMPs) control critical biological processes by cleaving membrane-associated proteins within a transmembrane segment or at a site near the membrane surface. Phylogenetic analysis divides IMMPs into four groups. SpoIVFB is a group III IMMP that regulates Bacillus subtilis endospore formation by cleaving Pro-σK and releasing the active sigma factor from a membrane. To elucidate the enzyme-substrate interaction, single-cysteine versions of catalytically inactive SpoIVFB and C-terminally truncated Pro-σK(1-126) (which can be cleaved by active SpoIVFB) were coexpressed in Escherichia coli, and proximity was tested by disulfide cross-linking in vivo. As expected, the results provided evidence that catalytic residue Glu-44 of SpoIVFB is near the cleavage site in the substrate. Also near the cleavage site were two residues of SpoIVFB in predicted conserved loops; Pro-135 in a short loop and Val-70 in a longer loop. Pro-135 corresponds to Pro-399 of RseP, a group I IMMP, and Pro-399 was reported previously to interact with substrate near the cleavage site, suggesting a conserved interaction across IMMP subfamilies. Val-70 follows a newly recognized conserved motif, PXGG (X is a large hydrophobic residue), which is in a hydrophobic region predicted to be a membrane reentrant loop. Following the hydrophobic region is a negatively charged region that is conserved in IMMPs of groups I and III. At least two residues with a negatively charged side chain are required in this region for activity of SpoIVFB. The region exhibits other features in IMMPs of groups II and IV. Its possible roles, as well as that of the short loop, are discussed. New insights into IMMP-substrate interaction build toward understanding how IMMPs function and may facilitate manipulation of their activity. PMID:23995631

  9. A disintegrin and metalloprotease 33 polymorphism association with COPD in long-term tobacco smokers of the ethnic Kashmiri population of India

    Directory of Open Access Journals (Sweden)

    Sonaullah Shah

    2015-01-01

    Full Text Available Background: Chronic obstructive pulmonary disease (COPD is characterized by an interaction of various environmental influences especially cigarette smoking and genetic determinants. The prevalence of this disease is ever increasing and characterization of the genetic determinants of the disease has been undertaken globally. The ′A disintegrin and metalloprotease 33′ (ADAM 33 gene is one candidate gene that has been studied. Objective: Our objective was to investigate whether single nucleotide polymorphisms in ADAM33 gene are associated with COPD in long-term tobacco smokers in the ethnic Kashmiri population of northern India. Materials and Methods: This was a randomized case-control study, which included 78 stable COPD (GOLD stage11-IV patients, who were compared with 77 age- and sex-matched long-term tobacco smokers (>20 pack years without any evidence of COPD. Polymorphic analysis for three single nucleotide polymorphisms (SNPs, (T1, T2, and Q1 of the ADAM33 gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP followed by sequencing. The data were analyzed by descriptive statistics and comparative evaluation was done by parametric/non-parametric tests. Results: The analysis of the T1, T2, and Q1 SNPs, revealed that the frequencies of the T2GG, T1GG, and the Q1AG genotypes were significantly higher in patients with COPD in comparison with the controls (P < 0.001. Similarly, the T1G and T2G allele frequency was higher in the patients than in the controls (p = 0.177 and 0.43, respectively. Conclusion: Three SNPs of the ADAM33 gene were significantly associated with COPD in the Kashmiri population of India. This study establishes the possible role of ADAM33 SNPS in the causation of COPD. Further studies across different geographical areas in the country will unravel the contribution of this gene in the causation of COPD in India.

  10. The hookworm tissue inhibitor of metalloproteases (Ac-TMP-1 modifies dendritic cell function and induces generation of CD4 and CD8 suppressor T cells.

    Directory of Open Access Journals (Sweden)

    Carmen Cuéllar

    Full Text Available Hookworm infection is a major cause of disease burden for humans. Recent studies have described hookworm-related immunosuppression in endemic populations and animal models. A Tissue Inhibitor of Metalloproteases (Ac-TMP-1 has been identified as one of the most abundant proteins released by the adult parasite. We investigated the effect of recombinant Ac-TMP-1 on dendritic cell (DC and T cell function. Splenic T cells from C57BL/6 mice injected with Ac-TMP-1 showed reduced proliferation to restimulation with anti CD3 or bystander antigens such as OVA. Incubation of bone marrow-derived DCs with Ac-TMP-1 decreased MHC Class I and, especially, Class II expression but increased CD86 and IL-10 expression. Co-incubation of splenic T cells with DCs pulsed with Ac-TMP-1 induced their differentiation into CD4+ and, particularly, CD8+ CD25+Foxp3+ T cells that expressed IL-10. These cells were able to suppress proliferation of naïve and activated CD4+ T cells by TGF-Beta-dependent (CD4+ suppressors or independent (CD8+ suppressors mechanisms. Priming of DCs with non-hookworm antigens, such as OVA, did not result in the generation of suppressor T cells. These data indicate that Ac-TMP-1 initiates the development of a regulatory response through modifications in DC function and generation of suppressor T cells. This is the first report to propose a role of suppressor CD8+ T cells in gastrointestinal helminthic infections.

  11. Evidence for cleavage of the metalloprotease Vsm from Vibrio splendidus strain JZ6 by an M20 peptidase (PepT-like protein at low temperature

    Directory of Open Access Journals (Sweden)

    Rui Liu

    2016-10-01

    Full Text Available Metalloprotease Vsm is a major extracellular virulence factor of Vibrio splendidus. The toxicity of Vsm from V. splendidus strain JZ6 has been characterized, and production of this virulence factor proved to be temperature-regulated. The present study provides evidence that two forms (JZE1 and JZE2 of Vsm protein exist in extracellular products (ECPs of strain JZ6, and a significant conversion of these two forms was detected by SDS-PAGE and immunoblotting analyses of samples obtained from cells grown at 4, 10, 16, 20, 24 and 28 ℃. Mass spectroscopy confirmed that JZE1 was composed only of the peptidase_M4 domain of Vsm, and JZE2 contained both the PepSY domain and the peptidase_M4 domain. An M20 peptidase T-like protein (PepTL was screened from the transcriptome data of strain JZ6, which was considered as a crucial molecule to produce the active Vsm (JZE1 by cleavage of the propeptide. Similar to that of Vsm, PepTL mRNA accumulation was highest at 4 ℃ (836.82-fold of that at 28 ℃, decreased with increasing of temperature and reached its lowest level at 28 ℃. Deletion of the gene encoding the PepTL resulted in a mutant strain that did not produce the JZE1 cleavage product. The peptidase activity of PepTL recombinant protein (rPepTL was confirmed by cleaving the Vsm in ECPs with an in vitro degradation reaction. These results demonstrate that PepTL participates in activating Vsm in strain JZ6 by proteolytic cleavage at low temperature.

  12. Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases.

    Science.gov (United States)

    Hagemann, Thorsten; Robinson, Stephen C; Schulz, Matthias; Trümper, Lorenz; Balkwill, Frances R; Binder, Claudia

    2004-08-01

    Apart from the neoplastic cells, malignant tumours consist of the extracellular matrix (ECM) and normal cells, in particular tumour-associated macrophages (TAM). To understand the mechanisms by which TAM can influence tumour cell invasion we co-cultured the human breast cancer cell lines MCF-7, SK-BR-3 and the benign mammary epithelial cell line hTERT-HME1 with macrophages. Co-incubation enhanced invasiveness of the tumour cells, while hTERT-HME1 remained non-invasive. Addition of the broad-spectrum matrix metalloprotease (MMP)-inhibitor FN 439, neutralizing MMP-9 or tumour necrosis factor-alpha (TNF-alpha) antibodies reduced invasiveness to basal levels. As shown by zymography, all cell lines produced low amounts of MMP-2, -3, -7 and -9 under control conditions. Basal MMP production by macrophages was significantly higher. Upon co-incubation, supernatant levels of MMPs -2, -3, -7 and -9 increased significantly, paralleled by an increase of MMP-2 activation. MMP-2 and -9 induction could be blocked by TNF-alpha antibodies. Co-culture of macrophages and hTERT-HME1 did not lead to MMP induction. In the co-cultures, mRNAs for MMPs and TNF-alpha were significantly up-regulated in macrophages, while the mRNA concentrations in the tumour cells remained unchanged. In summary, we have found that co-cultivation of tumour cells with macrophages leads to enhanced invasiveness of the malignant cells due to TNF-alpha dependent MMP induction in the macrophages.

  13. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  14. My Family

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Everyone has a family.We live in it and feel very warm.There are three persons in my family,my mother,father and I.We live together very happily and there are many interesting stories about my family. My father is a hard-working man.He works as a doctor.He always tries his best to help every,patient and make patients comfortable.But sonetimes he works so hard

  15. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  16. Family literacy

    DEFF Research Database (Denmark)

    Sehested, Caroline

    2012-01-01

    I Projekt familielæsning, der er et samarbejde mellem Nationalt Videncenter for Læsning og Hillerød Bibliotek, arbejder vi med at få kontakt til de familier, som biblioteket ellers aldrig ser som brugere og dermed også de børn, der vokser op i familier, for hvem bøger og oplæsningssituationer ikke...... er en selvfølgelig del af barndommen. Det, vi vil undersøge og ønsker at være med til at udvikle hos disse familier, er det, man kan kalde family literacy....

  17. Small Families

    Science.gov (United States)

    ... easier for both parents to combine careers with family life. The general stress level is lower because there often are fewer ... can help replace the missing ties. For many families, religious congregational ... such as youth and neighborhood activity centers also can fulfill these ...

  18. FAMILY PLATYSTOMATIDAE.

    Science.gov (United States)

    Wendt, Lisiane Dilli

    2016-06-14

    Platystomatidae (Signal Flies) are one of the largest families of Tephritoidea, with about 1200 species and four subfamilies, worldwide distributed. However, Platystomatidae are not well represented in the New World, and in the Neotropical Region only four genera and 26 species, belonging to Platystomatinae, are recorded. The family is a group understudied in Colombia and only one species is recorded to the country.

  19. The binding effectiveness of anti-r-disintegrin polyclonal antibodies against disintegrins and PII and PIII metalloproteases: An immunological survey of type A, B and A+B venoms from Mohave rattlesnakes.

    Science.gov (United States)

    Cantú, Esteban; Mallela, Sahiti; Nyguen, Matthew; Báez, Raúl; Parra, Victoria; Johnson, Rachel; Wilson, Kyle; Suntravat, Montamas; Lucena, Sara; Rodríguez-Acosta, Alexis; Sánchez, Elda E

    2017-01-01

    Snake venoms are known to have different venom compositions and toxicity, but differences can also be found within populations of the same species contributing to the complexity of treatment of envenomated victims. One of the first well-documented intraspecies venom variations comes from the Mohave rattlesnake (Crotalus scutulatus scutulatus). Initially, three types of venoms were described; type A venom is the most toxic as a result of ~45% Mojave toxin in the venom composition, type B lacks the Mojave toxin but contains over 50% of snake venom metalloproteases (SVMPs). Also, type A+B venom contains a combination of Mojave toxin and SVMP. The use of an anti-disintegrin antibody in a simple Enzyme-Linked Immunosorbent Assay (ELISA) can be used to identify the difference between the venoms of the type A, B, and A+B Mohave rattlesnakes. This study implements the use of an anti-recombinant disintegrin polyclonal antibody (ARDPA) for the detection of disintegrins and ADAMs (a disintegrin and metalloproteases) in individual crude snake venoms of Mohave rattlesnakes (Crotalus scutulatus scutulatus) of varying geographical locations. After correlation with Western blots, coagulation activity and LD50 data, it was determined that the antibody allows for a quick and cost-efficient identification of venom types. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Metalloprotease NleC suppresses host NF-κB/inflammatory responses by cleaving p65 and interfering with the p65/RPS3 interaction.

    Directory of Open Access Journals (Sweden)

    Andrea Hodgson

    2015-03-01

    Full Text Available Attaching/Effacing (A/E pathogens including enteropathogenic Escherichia coli (EPEC, enterohemorrhagic E. coli (EHEC and the rodent equivalent Citrobacter rodentium are important causative agents of foodborne diseases. Upon infection, a myriad of virulence proteins (effectors encoded by A/E pathogens are injected through their conserved type III secretion systems (T3SS into host cells where they interfere with cell signaling cascades, in particular the nuclear factor kappaB (NF-κB signaling pathway that orchestrates both innate and adaptive immune responses for host defense. Among the T3SS-secreted non-LEE-encoded (Nle effectors, NleC, a metalloprotease, has been recently elucidated to modulate host NF-κB signaling by cleaving NF-κB Rel subunits. However, it remains elusive how NleC recognizes NF-κB Rel subunits and how the NleC-mediated cleavage impacts on host immune responses in infected cells and animals. In this study, we show that NleC specifically targets p65/RelA through an interaction with a unique N-terminal sequence in p65. NleC cleaves p65 in intestinal epithelial cells, albeit a small percentage of the molecule, to generate the p65¹⁻³⁸ fragment during C. rodentium infection in cultured cells. Moreover, the NleC-mediated p65 cleavage substantially affects the expression of a subset of NF-κB target genes encoding proinflammatory cytokines/chemokines, immune cell infiltration in the colon, and tissue injury in C. rodentium-infected mice. Mechanistically, the NleC cleavage-generated p65¹⁻³⁸ fragment interferes with the interaction between p65 and ribosomal protein S3 (RPS3, a 'specifier' subunit of NF-κB that confers a subset of proinflammatory gene transcription, which amplifies the effect of cleaving only a small percentage of p65 to modulate NF-κB-mediated gene expression. Thus, our results reveal a novel mechanism for A/E pathogens to specifically block NF-κB signaling and inflammatory responses by cleaving a

  1. New approach for separating Bacillus subtilis metalloprotease and alpha-amylase by affinity chromatography and for purifying neutral protease by hydrophobic chromatography.

    Science.gov (United States)

    Lauer, I; Bonnewitz, B; Meunier, A; Beverini, M

    2000-01-14

    Proteases are commonly used in the biscuit and cracker industry as processing aids. They cause moderate hydrolysis of gluten proteins and improve dough rheology to better control product texture and crunchiness. Commercial bacterial proteases are derived from Bacillus fermentation broth. As filtration and ultrafiltration are carried out as the only recovery steps, these preparations contain also alpha-amylase and beta-glucanase as the main side activities. The aim of this study is to purify and characterize the Bacillus subtilis metalloprotease from a commercial preparation, in order to study separately the impact of the protease activity with regards to its functionality on biscuit properties. Purification was achieved by means of affinity chromatography on Cibacron Blue and HIC as a polishing step. Affinity appeared to be the most appropriate matrix for large scale purification while ion exchange chromatography was inefficient in terms of recovery yields. The crude product was first loaded on a Hi Trap Blue column (34 microm, Pharmacia Biotech); elution was carried out with a gradient of NaCl in the presence of 1 mM ZnCl2. This step was only efficient in the presence of Zn cations, because this salt promoted both protease stabilization resulting in high recovery yields and also complexation of amylase units into dimers resulting in amylase retention on the column and a better separation of the 3 activities. Beta-glucanase was mostly non retained on the column and a part was coeluted with the protease. This protease fraction was then loaded on a Resource Phe column (15 microm, Pharmacia Biotech) in a last step of polishing. Elution was carried out with a linear gradient of 100-0% ammonium sulfate 1.3 M; protease was eluted at the beginning of the gradient and well separated from amylase and glucanase trace impurities. The homogeneity of the purified protease was confirmed by SDS-PAGE, which showed that its MW was about 38. pH and temperature optima were also

  2. Androgen receptor expresion in breast cancer: Relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors

    Directory of Open Access Journals (Sweden)

    Sanchez Rosario

    2008-05-01

    Full Text Available Abstract Background In the present study we analyze, in patients with breast cancer, the tumor expression of androgen receptors (AR, its relationship with clinicopathological characteristics and with the expression of several matrix metalloproteases (MMPs and their inhibitors (TIMPs, as well as with prognosis. Methods An immunohistochemical study was performed using tissue microarrays and specific antibodies against AR, MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 2,800 determinations on tumor specimens from 111 patients with primary invasive ductal carcinoma of the breast (52 with axillary lymph node metastases and 59 without them and controls were performed. Staining results were categorized using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. Results A total of 83 cases (74.8% showed a positive immunostaining for AR, but with a wide variation in the staining score values. There were no significant associations between the total immunostaining scores for AR and any clinicopathological parameters. However, score values for MMP-1, -7 and -13, were significantly higher in AR-positive tumors than in AR-negative tumors. Likewise, when we considered the cellular type expressing each factor, we found that AR-positive tumors had a higher percentage of cases positive for MMP-1, -7, -11, and TIMP-2 in their malignant cells, as well as for MMP-1 in intratumoral fibroblasts. On the other hand, multivariate analysis demonstrated that patients with AR-positive tumors have a significant longer overall survival than those with AR-negative breast carcinomas (p = 0.03. Conclusion Our results confirm that AR are commonly expressed in breast cancer, and are correlated with the expression of some MMPs and TIMP-2. Although we found a specific value of AR expression to be a prognostic indicator in breast cancer, the functional role of AR in these

  3. Isolation, characterization and molecular three-dimensional structural predictions of metalloprotease from a phytopathogenic fungus, Alternaria solani (Ell. and Mart.) Sor.

    Science.gov (United States)

    Chandrasekaran, Murugesan; Chandrasekar, Raman; Chun, Se-Chul; Sathiyabama, Muthukrishnan

    2016-08-01

    The present study aims at isolation, identification, characterization and prediction of three-dimensional molecular architecture of a proteolytic enzyme from the early blight pathogen, Alternaria solani which are hypothesized to be a marker of phytopathogenicity. Maximum enzyme production by A. solani was observed in Czapex's Dox broth amended with 2% (w/v) casein than other inducer amendments. Results indicate that the enzyme remained highly active in a pH range of 7.0-10.0 and a temperature range of 45-50°C. The enzyme was strongly inhibited by EDTA, whereas phenylmethylsulfonyl fluoride and monovalent cations (Na(+), K(+)) had little effect. Metal ions such as MgSO4, CaCl2, KCl at 10 mM concentration showed a stimulatory effect (>85%) on protease activity. Matrix-assisted laser desorption and ionization time of flight/mass spectrometry analysis of partially purified enzyme revealed the presence of protease belonging to a keratinolytic protein (metalloprotease) of exopeptidase nature. Putative A. solani keratinolytic enzyme (AsK) is made up of 216 amino acid residues with molecular weight (MW) 24.5 kDa, having a molecular formula of C1094H1704N290O342S4. Ramachandran plot analysis of the protein residues falling into the most favored secondary structures was observed at 84.2%. The major protein structural blocks, 2-β-sheets, and 9-α-helices have a greater tendency to be conserved during the evolutionary process than do mere sequences of amino acids. Besides, AsK, model prediction showed the presence of a Zinc atom at helix regions (Helix 3, 6, 7: His(57), His(130), His(169), and Cys(123)). Thus, it can be concluded that the major proteinases of AsK are divalent cation-requiring metalloproteinases and make them potential targets of protease inhibitors designing. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. Combined expression of CTGF and tissue inhibitor of metalloprotease-1 promotes synthesis of proteoglycan and collagen type Ⅱ in rhesus monkey lumbar intervertebral disc cells in vitro

    Institute of Scientific and Technical Information of China (English)

    LIU Yong; KONG Jie; CHEN Bo-hua; HU You-gu

    2010-01-01

    Background Low back pain has emerged as a widespread disease often caused by intervertebral disc degeneration.This study aimed to establish an in vitro cell culture model of rhesus monkey lumbar intervertebral discs and to investigate the effect of combined connective tissue growth factor (CTGF) and tissue inhibitor of metalloprotease-1(TIMP-1) expression mediated by adeno-associated virus (AAV) on collagen type Ⅱ and proteoglycan levels.The purpose of these investigations was to explore potential methods for relieving the degeneration of lumbar intervertebral disc cells.Methods Rhesus monkey lumbar intervertebral disc nucleus pulposus cells (NPCs) were isolated by enzyme digestion,cultured, and transduced with rAAV2-CTGF-IRES-TIMP-1, rAAV2-CTGF, or rAAV2-TIMP-1 at a multiplicity of infection (MOl) of 106.The expression of collagen type Ⅱ and proteoglycan was measured using RT-PCR and Western blotting.The synthetic rate of proteoglycan was measured using 35S incorporation.Results Rhesus monkey lumbar intervertebral disc NPCs were transduced with rAAV2-CTGF-IRES-TIMP-1,rAAV2-CTGF, and rAAV2-TIMP-1 and the transduced genes were expressed and detected.Compared to the control,CTGF promoted the synthesis of collagen type Ⅱ and proteoglycan.TIMP-1 showed an enhancing effect on the expression of proteoglycan but no effect on collagen type Ⅱ.Expression of both genes in rhesus monkey lumbar intervertebral disc NPCs significantly enhances the synthesis of proteoglycan and collagen type Ⅱ.Conclusions Single gene transduction of CTGF or TIMP-1 can enhanced synthesis of proteoglycan.CTGF expression can also enhance collagen type Ⅱ protein synthesis.Combined transduction of both CTGF and TIMP1 can significantly promote the expression of proteoglycan and collagen type Ⅱ to levels greater than transduction of a single gene alone.Our study provides a good basis for multi-gene therapy to treat lumbar intervertebral disc degeneration.

  5. An expanded family of fungalysin extracellular metallopeptidases of Coprinopsis cinerea.

    Science.gov (United States)

    Lilly, Walt W; Stajich, Jason E; Pukkila, Patricia J; Wilke, Sarah K; Inoguchi, Noriko; Gathman, Allen C

    2008-03-01

    Proteolytic enzymes, particularly secreted proteases of fungal origin, are among the most important of industrial enzymes, yet the biochemical properties and substrate specificities of these proteins have been difficult to characterize. Genomic sequencing offers a powerful tool to identify potentially novel proteases. The genome of the model basidiomycete Coprinopsis cinereus was found to have an unusually high number of metalloproteases that closely match the M36 peptidase family known as fungalysins. The eight predicted C. cinereus fungalysins divide into two groups upon comparison with fungalysins from other fungi. One member, CcMEP1, is most similar to the single representative fungalysins from the basidiomycetes Phanerochaete chrysosporium, Cryptococcus neoformans, and Ustilago maydis, and to the fungalysin type-protein from Aspergillus fumigatus. The remaining seven C. cinereus predicted fungalysins form a group with similarity to three predicted M36 peptidases of Laccaria bicolor. All eight of the C. cinereus enzymes contain both the signature M36 Pfam domain and the FTP propeptide domain. All contain large propeptides with considerable sequence conservation near a proposed cleavage site. The predicted mature enzymes range in size from 37-46 kDa and have isoelectric points that are mildly acidic to neutral. The proximity of these genes to telomeres and/or to transposable elements may have contributed to the expansion of this gene family in C. cinereus.

  6. Family Disruptions

    Science.gov (United States)

    ... stay angry, or avoid fights altogether? Your children model themselves on you. Departures and Returns Do you or your spouse frequently travel on business? These can be disruptive times for your child and for the family ...

  7. Familial hypercholesterolemia

    Science.gov (United States)

    ... hypercholesterolemia or early heart attacks High level of LDL cholesterol in either or both parents People from families ... called fibroblasts to see how the body absorbs LDL cholesterol Genetic test for the defect associated with this ...

  8. Family matters

    DEFF Research Database (Denmark)

    Kieffer-Kristensen, Rikke; Siersma, Volkert Dirk; Teasdale, Thomas William

    2013-01-01

    OBJECTIVES: To relate illness and family factors to emotional and behavioural problems in school-age children (7–14 years old) of parents with acquired brain injury and their healthy spouses. PARTICIPANTS, MATERIALS/METHODS: Members of 35 families in which a parent had been diagnosed with acquired...... brain injury participated. Family and brain injury characteristics were reported by the ill and healthy parents. Children self-reported post-traumatic stress symptoms (PSS) using the Child Impact of Events revised (CRIES). Emotional and behavioural problems among the children were also identified...... by the parents using the Achenbach’s Child Behaviour Checklist (CBCL). RESULTS: The family stress variables relating to the healthy spouse in all six comparisons were significant (p

  9. Families in the Military

    Science.gov (United States)

    ... Contents Facts For Families Guide - View by Topic Chinese Facts for Families Guide Facts For Families Guide - Search Spanish Facts for Families Guide Facts for Families - Vietnamese Military Families No. 88; updated March 2017 Global conflict ...

  10. Análise bioquímica das metaloproteases da matriz extracelular durante atrofia experimental das glândulas salivares submandibulares em ratos Analysis of the matrix metalloproteases in duct-ligated submandibular salivary glands of rats

    Directory of Open Access Journals (Sweden)

    Ana Paula de SOUZA

    1999-04-01

    Full Text Available O presente estudo teve por objetivo analisar a expressão das metaloproteases da matriz extracelular durante a atrofia experimental das glândulas submandibulares em ratos, causada pela obstrução do ducto excretor principal. Os zimogramas realizados com extratos das porções internas e externas das glândulas salivares normais e ligadas mostraram que as principais enzimas gelatinolíticas possuíam pesos moleculares variando entre 72 kDa e 65 kDa. A atividade dessas enzimas aumentou progressivamente até o período entre 5 e 10 dias após a ligação, decrescendo nos períodos subseqüentes. Foram também detectadas bandas migrando entre 92 kDa e 72 kDa, sendo essas enzimas detectadas em quantidades significativas apenas na região da cápsula da glândula, no período de 2 dias. A confirmação de que as enzimas detectadas eram metaloproteases foi feita pelo uso de inibidores específicos. Os resultados sugerem que as metaloproteases da matriz têm um papel importante na remodelação da matriz extracelular durante a atrofia experimental da glândula submandibular.The purpose of the present study was to analyze the expression of the major metalloproteases in normal and ligated glands. The major metalloproteases detected had a molecular weight ranging from 72 to 65 kDa. The gelatinolytic activity increased progressively reaching a peak between 5 and 10 days after ligation. Bands with molecular weight ranging from 92-80 kDa were also detected in the capsule of the gland. The 92-80 kDa enzymes were only detected 2 days after ligation. The activity of these enzymes was supressed by specific inhibitors. Our results show that matrix metalloproteases play an active role in the extensive remodeling of the connective tissue that occurs during the atrophy of the submandibular gland.

  11. Family Literacy

    Directory of Open Access Journals (Sweden)

    Livija Knaflič

    1999-12-01

    Full Text Available Research in child and adult literacy demonstrates that the achievement and the level of literacy that children attain at school is connected with the social and cultural characteristics and the level of literacy of the child's family. This intergenerational transfer of the level of literacy has motivated the search for different ways of improving the level of literacy.The concept of family literacy is based on the assumption that a higher level of parent literacy means that the children may achieve the same, and it also offers better schooling prospects. Family literacy programmes help fami­lies to develop different activities, in­cluding reading and writing skills, both in their community and in everyday life.

  12. Family Structure and Family Processes in Mexican American Families

    OpenAIRE

    Zeiders, Katharine H.; Roosa, Mark W.; Tein, Jenn-Yun

    2011-01-01

    Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct,...

  13. The proteasomal Rpn11 metalloprotease suppresses tombusvirus RNA recombination and promotes viral replication via facilitating assembly of the viral replicase complex.

    Science.gov (United States)

    Prasanth, K Reddisiva; Barajas, Daniel; Nagy, Peter D

    2015-03-01

    RNA viruses co-opt a large number of cellular proteins that affect virus replication and, in some cases, viral genetic recombination. RNA recombination helps viruses in an evolutionary arms race with the host's antiviral responses and adaptation of viruses to new hosts. Tombusviruses and a yeast model host are used to identify cellular factors affecting RNA virus replication and RNA recombination. In this study, we have examined the role of the conserved Rpn11p metalloprotease subunit of the proteasome, which couples deubiquitination and degradation of proteasome substrates, in tombusvirus replication and recombination in Saccharomyces cerevisiae and plants. Depletion or mutations of Rpn11p lead to the rapid formation of viral RNA recombinants in combination with reduced levels of viral RNA replication in yeast or in vitro based on cell extracts. Rpn11p interacts with the viral replication proteins and is recruited to the viral replicase complex (VRC). Analysis of the multifunctional Rpn11p has revealed that the primary role of Rpn11p is to act as a "matchmaker" that brings the viral p92(pol) replication protein and the DDX3-like Ded1p/RH20 DEAD box helicases into VRCs. Overexpression of Ded1p can complement the defect observed in rpn11 mutant yeast by reducing TBSV recombination. This suggests that Rpn11p can suppress tombusvirus recombination via facilitating the recruitment of the cellular Ded1p helicase, which is a strong suppressor of viral recombination, into VRCs. Overall, this work demonstrates that the co-opted Rpn11p, which is involved in the assembly of the functional proteasome, also functions in the proper assembly of the tombusvirus VRCs. RNA viruses evolve rapidly due to genetic changes based on mutations and RNA recombination. Viral genetic recombination helps viruses in an evolutionary arms race with the host's antiviral responses and facilitates adaptation of viruses to new hosts. Cellular factors affect viral RNA recombination, although the role

  14. Family Circle

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Foster care is conducive to giving orphaned children a better life For most children living in orphanages, having a real home is just a pipe dream. Although they may be well looked after, receive a good education and proper nutrition, the love and care that come from being part of a real family just aren't there.

  15. My Family

    Institute of Scientific and Technical Information of China (English)

    刘才来

    2002-01-01

    There are four people in my family. They are grandma, father,mother and I. Now we all live in Wuhan. They are from different places. My grandma comes from Sichuan. She likes hot(辣4的) meat very much. She doesn't like bread or noodles at all. She likes vegetables a little. My father is from Guang Zhou.

  16. My Family

    Institute of Scientific and Technical Information of China (English)

    李梅

    2012-01-01

    There are four people in my family--my parents, my brother and I. My name is Li Mei. I'm fifteen years old. I am of medium height and build. I like English very much. It's very interesting. I can play the piano very well. It makes me feel very happy.

  17. Finding Family

    Institute of Scientific and Technical Information of China (English)

    LIU YUNYUN

    2010-01-01

    @@ It took 14 years--and just two min-utes-for an adopted Chinese girl to find her biological family. July 21 this year marked the first anniversary of Haley Butler's finding of her biological parents in Maanshan in east China's Anhui Province.

  18. FAMILY RICHARDIIDAE.

    Science.gov (United States)

    Wendt, Lisiane Dilli; Ale-Rocha, Rosaly

    2016-06-14

    Richardiidae are a family of "acalyptrate" Diptera represented by ca. 180 species distributed in the New World, mostly in the Neotropical region. The species that occur in Colombia have received little attention from taxonomists, and the great majority of them are known only from their type localities. Currently, 14 genera and 23 species are known to occur in the country.

  19. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  20. Finding Family

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Discovering her birth parents was an exciting adventure for a 15-year-old girl It took 14 years-and just two minutes-for an adopted Chinese girl to find her biological family.July 21 this year marked the first

  1. Familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Versmissen, Jorie; Vongpromek, Ranitha; Yahya, Reyhana

    2016-01-01

    cholesterol efflux capacity between male familial hypercholesterolaemia (FH) patients with and without CHD relative to their non-FH brothers, and examined HDL constituents including sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (apoM). RESULTS: Seven FH patients were asymptomatic and six had...

  2. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  3. Stromal matrix metalloprotease-13 knockout alters Collagen I structure at the tumor-host interface and increases lung metastasis of C57BL/6 syngeneic E0771 mammary tumor cells.

    Science.gov (United States)

    Perry, Seth W; Schueckler, Jill M; Burke, Kathleen; Arcuri, Giuseppe L; Brown, Edward B

    2013-09-05

    Matrix metalloproteases and collagen are key participants in breast cancer, but their precise roles in cancer etiology and progression remain unclear. MMP13 helps regulate collagen structure and has been ascribed largely harmful roles in cancer, but some studies demonstrate that MMP13 may also protect against tumor pathology. Other studies indicate that collagen's organizational patterns at the breast tumor-host interface influence metastatic potential. Therefore we investigated how MMP13 modulates collagen I, a principal collagen subtype in breast tissue, and affects tumor pathology and metastasis in a mouse model of breast cancer. Tumors were implanted into murine mammary tissues, and their growth analyzed in Wildtype and MMP13 KO mice. Following extraction, tumors were analyzed for collagen I levels and collagen I macro- and micro-structural properties at the tumor-host boundary using immunocytochemistry and two-photon and second harmonic generation microscopy. Lungs were analyzed for metastases counts, to correlate collagen I changes with a clinically significant functional parameter. Statistical analyses were performed by t-test, analysis of variance, or Wilcoxon-Mann-Whitney tests as appropriate. We found that genetic ablation of host stromal MMP13 led to: 1. Increased mammary tumor collagen I content, 2. Marked changes in collagen I spatial organization, and 3. Altered collagen I microstructure at the tumor-host boundary, as well as 4. Increased metastasis from the primary mammary tumor to lungs. These results implicate host MMP13 as a key regulator of collagen I structure and metastasis in mammary tumors, thus making it an attractive potential therapeutic target by which we might alter metastatic potential, one of the chief determinants of clinical outcome in breast cancer. In addition to identifying stromal MMP13 is an important regulator of the tumor microenvironment and metastasis, these results also suggest that stromal MMP13 may protect against breast

  4. Learning about Familial Hypercholesterolemia

    Science.gov (United States)

    ... terms used on this page Learning About Familial Hypercholesterolemia What is familial hypercholesterolemia? What are the symptoms ... Additional Resources About Familial Hypercholesterolemia What is familial hypercholesterolemia? Familial hypercholesterolemia is an inherited condition that causes ...

  5. Natural Family Planning

    Science.gov (United States)

    ... Sex and Birth Control Birth Control Natural Family Planning Natural Family Planning Birth ControlPrevention and WellnessSex and Birth Control Share Natural Family Planning Natural Family PlanningWhat is natural family planning?Natural ...

  6. Diverse functions of miR-125 family in different cell contexts

    Directory of Open Access Journals (Sweden)

    Sun Yu-Meng

    2013-01-01

    Full Text Available Abstract MicroRNAs (miRNAs are emerging as a novel class of non-coding RNA molecules that regulate gene expression at a post-transcriptional level. More than 1000 miRNAs have been identified in human cells to date, and they are reported to play important roles in normal cell homeostasis, cell metastasis and disease pathogensis and progression. MiR-125, which is a highly conserved miRNA throughout diverse species from nematode to humans, consists of three homologs hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125-2. Members of this family have been validated to be down-regulated, exhibiting its disease-suppressing properties in many different types of diseases, while they also have disease-promoting functions in certain contexts. MiR-125 targets a number of genes such as transcription factors, matrix-metalloprotease, members of Bcl-2 family and others, aberrance of which may lead to abnormal proliferation, metastasis and invasion of cells, even carcinomas. Furthermore, miR-125 plays a crucial role in immunological host defense, especially in response to bacterial or viral infections. In this review, we summarize the implication of miR-125 family in disease suppression and promotion, focusing on carcinoma and host immune responses. We also discussed the potential of this miRNA family as promising biomarkers and therapeutic targets for different diseases in future.

  7. [Family violence].

    Science.gov (United States)

    Manoudi, F; Chagh, R; Es-soussi, M; Asri, F; Tazi, I

    2013-09-01

    Family violence is a serious public health problem, the scale of which is seriously increasing in Morocco. Although it has existed for a long time, we ignore the real characteristics of this plague in our country; our work consisted in an epidemiological approach of family violence in Marrakech during 2006. After elaborating a questionnaire, which allows the study of the demographic and social profile of the families, the study of violence exercised in the family and the evaluation of the depression in the women, we led an inquiry amongst 265 women. Analysis of the results obtained has allowed us to underline the following characteristics: 16.6% of the women in our sample had been physically beaten; the young age is a risk factor; the age range most affected by violence is in women between the ages of 30 and 40 and which represent 39% of the battered women; domestic violence touches all the social, economic and cultural classes: in our study, 63% of the women having undergone violence were housewives, 25% were managers and 3% senior executives; family problems were the most important cause of violence in our study, representing 32.32%. Requests for money was the cause in 11.3% of the cases, and imposed sexual relations were found in 6.8% of the cases; alcoholism is an aggravating factor of family violence; 27.3% of the spouses who assaulted their wives were drunk; 52% of the assaulted women were victims of violence in childhood and 36% had been witness to their father's violence; in 63.6% of the cases of violence, the children were witnesses, and in 25% of the cases the children were victims of violence at the same time as their mothers; 50% of the women victims of violence did not react, while 38.6% left home, and 9.1 filed for divorce. Thirty-two percent of the assaulted woman had been traumatised by the aggression; the association of depression and violence was very high, 343% of the battered women in our study suffered from severe depression. This work

  8. My family

    Institute of Scientific and Technical Information of China (English)

    陈君怡

    2011-01-01

    I have a happy fam_ly.Lookthis is my family photo.This is mydad.He often wears a pair Ofglasses(戴着一副眼镜I_This ismy mum.She is very pretty.Sheloves me very much.The little girlin a red blouse is me.I’m smiling(微笑).I love my family.

  9. [Familial hypercholesterolemia].

    Science.gov (United States)

    Turpin, G; Bruckert, E

    1999-12-01

    Familial hypercholesterolemia is characterized by a high plasma LDL-cholesterol level. The low-density particles are the end-product of the triglyceride-rich particles, i.e. VLDL, synthetized by the liver. These triglyceride-rich particles are subsequently transformed into intermediate density lipoprotein by the lipoprotein lipase and LDL after further triglyceride hydrolysis by the hepatic lipase. The LDL particles are taken up in all cells by the mean of the LDL receptor. A large body of evidence (including experimental, clinical, epidemiological data as well as the results of large trial with lipid lowering drugs) has accumulated to establish that these particles are one of the major causative factor of atherosclerosis and its complications. Two different mechanisms may be at work in the familial hypercholesterolemia: a mutation in the LDL receptor or a single mutation in the apolipoprotein B100. Specific therapeutic intervention should be undertaken to decrease the risk to develop cardiovascular disease, mainly coronary heart disease. The therapeutic intervention includes both a diet low in saturated fatty acids and cholesterol and statins which are now the first line therapy. Fibrates are proposed to those who do not tolerate statins and LDL-apheresis is associated to statin in the rare homozygous familial hypercholesterolemia.

  10. Ancylostoma ceylanicum Excretory-Secretory Protein 2 Adopts a Netrin-Like Fold and Defines a Novel Family of Nematode Proteins

    Energy Technology Data Exchange (ETDEWEB)

    K Kucera; L Harrison; M Cappello; Y Modis

    2011-12-31

    Hookworms are human parasites that have devastating effects on global health, particularly in underdeveloped countries. Ancylostoma ceylanicum infects humans and animals, making it a useful model organism to study disease pathogenesis. A. ceylanicum excretory-secretory protein 2 (AceES-2), a highly immunoreactive molecule secreted by adult worms at the site of intestinal attachment, is partially protective when administered as a mucosal vaccine against hookworm anemia. The crystal structure of AceES-2 determined at 1.75 {angstrom} resolution shows that it adopts a netrin-like fold similar to that found in tissue inhibitors of matrix metalloproteases (TIMPs) and in complement factors C3 and C5. However, recombinant AceES-2 does not significantly inhibit the 10 most abundant human matrix metalloproteases or complement-mediated cell lysis. The presence of a highly acidic surface on AceES-2 suggests that it may function as a cytokine decoy receptor. Several small nematode proteins that have been annotated as TIMPs or netrin-domain-containing proteins display sequence homology in structurally important regions of AceES-2's netrin-likefold. Together, our results suggest that AceES-2 defines a novel family of nematode netrin-like proteins, which may function to modulate the host immune response to hookworm and other parasites.

  11. Specificity of botulinum protease for human VAMP family proteins.

    Science.gov (United States)

    Yamamoto, Hideyuki; Ida, Tomoaki; Tsutsuki, Hiroyasu; Mori, Masatoshi; Matsumoto, Tomoko; Kohda, Tomoko; Mukamoto, Masafumi; Goshima, Naoki; Kozaki, Shunji; Ihara, Hideshi

    2012-04-01

    The botulinum neurotoxin light chain (BoNT-LC) is a zinc-dependent metalloprotease that cleaves neuronal SNARE proteins such as SNAP-25, VAMP2, and Syntaxin1. This cleavage interferes with the neurotransmitter release of peripheral neurons and results in flaccid paralysis. SNAP, VAMP, and Syntaxin are representative of large families of proteins that mediate most membrane fusion reactions, as well as both neuronal and non-neuronal exocytotic events in eukaryotic cells. Neuron-specific SNARE proteins, which are target substrates of BoNT, have been well studied; however, it is unclear whether other SNARE proteins are also proteolyzed by BoNT. Herein, we define the substrate specificity of BoNT-LC/B, /D, and /F towards recombinant human VAMP family proteins. We demonstrate that LC/B, /D, and /F are able to cleave VAMP1, 2, and 3, but no other VAMP family proteins. Kinetic analysis revealed that all LC have higher affinity and catalytic activity for the non-neuronal SNARE isoform VAMP3 than for the neuronal VAMP1 and 2 isoforms. LC/D in particular exhibited extremely low catalytic activity towards VAMP1 relative to other interactions, which we determined through point mutation analysis to be a result of the Ile present at residue 48 of VAMP1. We also identified the VAMP3 cleavage sites to be at the Gln 59-Phe 60 (LC/B), Lys 42-Leu 43 (LC/D), and Gln 41-Lys 42 (LC/F) peptide bonds, which correspond to those of VAMP1 or 2. Understanding the substrate specificity and kinetic characteristics of BoNT towards human SNARE proteins may aid in the development of novel therapeutic uses for BoNT.

  12. The S8 serine, C1A cysteine and A1 aspartic protease families in Arabidopsis.

    Science.gov (United States)

    Beers, Eric P; Jones, Alan M; Dickerman, Allan W

    2004-01-01

    The Arabidopsis thaliana genome has over 550 protease sequences representing all five catalytic types: serine, cysteine, aspartic acid, metallo and threonine (MEROPS peptidase database, http://merops.sanger.ac.uk/), which probably reflect a wide variety of as yet unidentified functions performed by plant proteases. Recent indications that the 26S proteasome, a T1 family-threonine protease, is a regulator of light and hormone responsive signal transduction highlight the potential of proteases to participate in many aspects of plant growth and development. Recent discoveries that proteases are required for stomatal distribution, embryo development and disease resistance point to wider roles for four additional multigene families that include some of the most frequently studied (yet poorly understood) plant proteases: the subtilisin-like, serine proteases (family S8), the papain-like, cysteine proteases (family C1A), the pepsin-like, aspartic proteases (family A1) and the plant matrixin, metalloproteases (family M10A). In this report, 54 subtilisin-like, 30 papain-like and 59 pepsin-like proteases from Arabidopsis, are compared with S8, C1A and A1 proteases known from other plant species at the functional, phylogenetic and gene structure levels. Examples of structural conservation between S8, C1A and A1 genes from rice, barley, tomato and soybean and those from Arabidopsis are noted, indicating that some common, essential plant protease roles were established before the divergence of monocots and eudicots. Numerous examples of tandem duplications of protease genes and evidence for a variety of restricted expression patterns suggest that a high degree of specialization exists among proteases within each family. We propose that comprehensive analysis of the functions of these genes in Arabidopsis will firmly establish serine, cysteine and aspartic proteases as regulators and effectors of a wide range of plant processes.

  13. Roles within the Family

    Science.gov (United States)

    ... Life Listen Español Text Size Email Print Share Roles Within the Family Page Content Article Body Families ... family unit, and which rights, privileges, obligations, and roles are assigned to each family member. In most ...

  14. Integrating Family Resilience and Family Stress Theory.

    Science.gov (United States)

    Patterson, Joan M.

    2002-01-01

    The construct, family resilience, is defined differently by practitioners and researchers. This study tries to clarify the concept of family resilience. The foundation is family stress and coping theory, particularly the stress models that emphasize adaptation processes in families exposed to major adversities. (JDM)

  15. Family Matters

    Directory of Open Access Journals (Sweden)

    Isabel de Riquer

    2011-04-01

    Full Text Available The scene is at the court of James I of Aragon in the mid-13th c., the place is the royal palace of Barcelona or any of the crown's other possessions, and the dramatis personae include the heir to the throne, prince Peire (future king Peire the Great, and the court's most famous troubadour, Cerverí de Girona (fl. 1259-85. Author of the largest corpus of any Occitan troubadour (114 poems, Cerverì distinguishes himself by the surprises and challenges he presents to his audience: an alba (the most openly erotic genre to the Virgin Mary, the Cobla in sis lengatges (Cobla in Six Languages, the apparently nonsensical Vers estrayn. Cerverì borrows equally from the folk-inspired Galician-Portuguese poetry and from the French tradition, including the chanson de malmariée, where a young woman bemoans being sold off by her family to an old man (gilos, "Jealous" and separated from her youthful doulz amis, some even praying for the death of their husband. Both within that tradition and among Cerverì's three chansons de malmariée, the Gelosesca stands out as "especially determined" to lose her husband, using every "solution" (prayer, black magic, potion or experimenta.

  16. Synergistic Action of a Metalloprotease and a Serine Protease from Fusarium oxysporum f. sp. lycopersici Cleaves Chitin-Binding Tomato Chitinases, Reduces Their Antifungal Activity, and Enhances Fungal Virulence.

    Science.gov (United States)

    Jashni, Mansoor Karimi; Dols, Ivo H M; Iida, Yuichiro; Boeren, Sjef; Beenen, Henriek G; Mehrabi, Rahim; Collemare, Jérôme; de Wit, Pierre J G M

    2015-09-01

    As part of their defense strategy against fungal pathogens, plants secrete chitinases that degrade chitin, the major structural component of fungal cell walls. Some fungi are not sensitive to plant chitinases because they secrete chitin-binding effector proteins that protect their cell wall against these enzymes. However, it is not known how fungal pathogens that lack chitin-binding effectors overcome this plant defense barrier. Here, we investigated the ability of fungal tomato pathogens to cleave chitin-binding domain (CBD)-containing chitinases and its effect on fungal virulence. Four tomato CBD chitinases were produced in Pichia pastoris and were incubated with secreted proteins isolated from seven fungal tomato pathogens. Of these, Fusarium oxysporum f. sp. lycopersici, Verticillium dahliae, and Botrytis cinerea were able to cleave the extracellular tomato chitinases SlChi1 and SlChi13. Cleavage by F. oxysporum removed the CBD from the N-terminus, shown by mass spectrometry, and significantly reduced the chitinase and antifungal activity of both chitinases. Both secreted metalloprotease FoMep1 and serine protease FoSep1 were responsible for this cleavage. Double deletion mutants of FoMep1 and FoSep1 of F. oxysporum lacked chitinase cleavage activity on SlChi1 and SlChi13 and showed reduced virulence on tomato. These results demonstrate the importance of plant chitinase cleavage in fungal virulence.

  17. Family and family therapy in Russia.

    Science.gov (United States)

    Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

    2012-04-01

    This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized.

  18. Bequeathing Family Continuity.

    Science.gov (United States)

    Spanier, Graham B.

    1989-01-01

    Notes that many children who experience abuse, family disruption, or poverty reach adulthood with a strong commitment to family life. Questions whether changes in American families are indicators of pathology, deterioration, and instability; and asks how dysfunctional families transmit commitment to the concept of family to succeeding generations.…

  19. Family Reading Night

    Science.gov (United States)

    Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

    2007-01-01

    This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

  20. Family Factors in Small Family Business Growth

    National Research Council Canada - National Science Library

    Jim Cater; Marilyn Young

    2016-01-01

    .... We suggest that while all three patterns of small family business growth may lead to individual company success and sustainability, businesses with units in multiple trade areas may be most adept at managing the six family factors.

  1. Consuming Family Dinner Time

    National Research Council Canada - National Science Library

    Kelli Gutierrez; Linda Price; Eric Arnould

    2008-01-01

      Our study examines whether and how family dinners are embedded in the centrifugal and centripetal dynamics of everyday family life, the diversity of meanings they have for families and the intentions...

  2. Family Adjustment to Aphasia

    Science.gov (United States)

    ... Public / Speech, Language and Swallowing / Disorders and Diseases Family Adjustment to Aphasia Richard S. was a senior manager ... It also presents a great challenge to the family. There may be tension among family members and ...

  3. Improving Family Communications

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Listen Español Text Size Email Print Share Improving Family Communications Page Content Article Body How can I ...

  4. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  5. Family Activities for Fitness

    Science.gov (United States)

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  6. Branding a family business

    OpenAIRE

    Pohjola, Matti

    2016-01-01

    This master’s thesis main object was to understand better the very little researched topic: branding a family business. The main aim was to seek the values used behind family business that are the family values used in the brand and how the branding has been implemented in a family company. A qualitative method was chosen for this research for an interpretative analysis of the subject. Five family companies were chosen for the interviews. All these family companies are known Fi...

  7. Family Health History and Diabetes

    Science.gov (United States)

    ... Diabetes Diabetes Risk Test Family Health History Quiz Family Health History Quiz Family health history is an ... health problems. Four Questions You Should Ask Your Family About Diabetes & Family Health History Knowing your family ...

  8. Families and family therapy in Hong Kong.

    Science.gov (United States)

    Tse, Samson; Ng, Roger M K; Tonsing, Kareen N; Ran, Maosheng

    2012-04-01

    Family therapy views humans not as separate entities, but as embedded in a network of relationships, highlighting the reciprocal influences of one's behaviours on one another. This article gives an overview of family demographics and the implementation of family therapy in Hong Kong. We start with a review of the family demographics in Hong Kong and brief notes on families in mainland China. Demographics show that the landscape has changed markedly in the past decade, with more cross-border marriages, an increased divorce rate, and an ageing overall population - all of which could mean that there is increasing demand for professional family therapy interventions. However, only a limited number of professionals are practising the systems-based approach in Hong Kong. Some possible reasons as to why family therapy is not well disseminated and practised are discussed. These reasons include a lack of mental health policy to support family therapy, a lack of systematic family therapy training, and a shortage of skilled professionals. Furthermore, challenges in applying the western model in Chinese culture are also outlined. We conclude that more future research is warranted to investigate how family therapy can be adapted for Chinese families.

  9. Family psychology and family therapy in Japan.

    Science.gov (United States)

    Kameguchi, K; Murphy-Shigematsu, S

    2001-01-01

    The development of family psychology and family therapy in Japan has occurred mostly since the 1980s. This development was originally activated by the major social issue in contemporary Japan of school refusal, in which more than 127,000 children either overtly refuse to or claim that they cannot go to school. From a family perspective, this problem is analyzed as it relates to the confusion that children experience from unbalanced and unclear boundaries in family relations or "membranes." An approach to family therapy that adapts systems theory and integrates a clay sculpting medium has been developed to work with Japanese families confronting this problem. The design and implementation of preventative family psychology programs applied at the community level are also an important part of the future development in these fields.

  10. Structural basis for the inhibition of M1 family aminopeptidases by the natural product actinonin: Crystal structure in complex with E. coli aminopeptidase N.

    Science.gov (United States)

    Ganji, Roopa Jones; Reddi, Ravikumar; Gumpena, Rajesh; Marapaka, Anil Kumar; Arya, Tarun; Sankoju, Priyanka; Bhukya, Supriya; Addlagatta, Anthony

    2015-05-01

    Actinonin is a pseudotripeptide that displays a high affinity towards metalloproteases including peptide deformylases (PDFs) and M1 family aminopeptidases. PDF and M1 family aminopeptidases belong to thermolysin-metzincin superfamily. One of the major differences in terms of substrate binding pockets between these families is presence (in M1 aminopeptidases) or absence (in PDFs) of an S1 substrate pocket. The binding mode of actinonin to PDFs has been established previously; however, it is not clear how the actinonin, without a P1 residue, would bind to the M1 aminopeptidases. Here we describe the crystal structure of Escherichia coli aminopeptidase N (ePepN), a model protein of the M1 family aminopeptidases in complex with actinonin. For comparison we have also determined the structure of ePepN in complex with a well-known tetrapeptide inhibitor, amastatin. From the comparison of the actinonin and amastatin ePepN complexes, it is clear that the P1 residue is not critical as long as strong metal chelating head groups, like hydroxamic acid or α-hydroxy ketone, are present. Results from this study will be useful for the design of selective and efficient hydroxamate inhibitors against M1 family aminopeptidases.

  11. Family doctors' involvement with families in Estonia

    Directory of Open Access Journals (Sweden)

    Lember Margus

    2004-10-01

    Full Text Available Abstract Background Family doctors should care for individuals in the context of their family. Family has a powerful influence on health and illness and family interventions have been shown to improve health outcomes for a variety of health problems. The aim of the study was to investigate the Estonian family doctors' (FD attitudes to the patients' family-related issues in their work: to explore the degree of FDs involvement in family matters, their preparedness for management of family-related issues and their self-assessment of the ability to manage different family-related problems. Methods A random sample (n = 236 of all FDs in Estonia was investigated using a postal questionnaire. Altogether 151 FDs responded to the questionnaire (response rate 64%, while five of them were excluded as they did not actually work as FDs. Results Of the respondents, 90% thought that in managing the health problems of patients FDs should communicate and cooperate with family members. Although most of the family doctors agreed that modifying of the health damaging risk factors (smoking, alcohol and drug abuse of their patients and families is their task, one third of them felt that dealing with these problems is ineffective, or perceived themselves as poorly prepared or having too little time for such activities. Of the respondents, 58% (n = 83 were of the opinion that they could modify also relationship problems. Conclusions Estonian family doctors are favourably disposed to involvement in family-related problems, however, they need some additional training, especially in the field of relationship management.

  12. Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome.

    Science.gov (United States)

    Oller, Jorge; Méndez-Barbero, Nerea; Ruiz, E Josue; Villahoz, Silvia; Renard, Marjolijn; Canelas, Lizet I; Briones, Ana M; Alberca, Rut; Lozano-Vidal, Noelia; Hurlé, María A; Milewicz, Dianna; Evangelista, Arturo; Salaices, Mercedes; Nistal, J Francisco; Jiménez-Borreguero, Luis Jesús; De Backer, Julie; Campanero, Miguel R; Redondo, Juan Miguel

    2017-02-01

    Heritable thoracic aortic aneurysms and dissections (TAAD), including Marfan syndrome (MFS), currently lack a cure, and causative mutations have been identified for only a fraction of affected families. Here we identify the metalloproteinase ADAMTS1 and inducible nitric oxide synthase (NOS2) as therapeutic targets in individuals with TAAD. We show that Adamts1 is a major mediator of vascular homeostasis, given that genetic haploinsufficiency of Adamts1 in mice causes TAAD similar to MFS. Aortic nitric oxide and Nos2 levels were higher in Adamts1-deficient mice and in a mouse model of MFS (hereafter referred to as MFS mice), and Nos2 inactivation protected both types of mice from aortic pathology. Pharmacological inhibition of Nos2 rapidly reversed aortic dilation and medial degeneration in young Adamts1-deficient mice and in young or old MFS mice. Patients with MFS showed elevated NOS2 and decreased ADAMTS1 protein levels in the aorta. These findings uncover a possible causative role for the ADAMTS1-NOS2 axis in human TAAD and warrant evaluation of NOS2 inhibitors for therapy.

  13. Competitiveness of Family Businesses

    NARCIS (Netherlands)

    M.A.A.M. Leenders (Mark); E. Waarts (Eric)

    2001-01-01

    textabstractThe purpose of this study is to systematically examine the advantages and disadvantages of different types of family businesses. We distinguish four different types of family businesses based on their family and business orientation: (1) House of Business, (2) Family Money Machine, (3) F

  14. Families in Transition .

    Science.gov (United States)

    Bundy, Michael L., Ed.; Gumaer, James, Ed.

    1984-01-01

    Focuses on disrupted families and the role of the school counselor in helping children adjust. Describes characteristics of healthy families, and discusses the transition to the blended family, effects of divorce groups on children's classroom behavior, counseling children in stepfamilies, single-parent families, and parenting strengths of single…

  15. Competitiveness of Family Businesses

    NARCIS (Netherlands)

    M.A.A.M. Leenders (Mark); E. Waarts (Eric)

    2001-01-01

    textabstractThe purpose of this study is to systematically examine the advantages and disadvantages of different types of family businesses. We distinguish four different types of family businesses based on their family and business orientation: (1) House of Business, (2) Family Money Machine, (3) F

  16. Family Therapy for the "Truncated" Nuclear Family.

    Science.gov (United States)

    Zuk, Gerald H.

    1980-01-01

    The truncated nuclear family consists of a two-generation group in which conflict has produced a polarization of values. The single-parent family is at special risk. Go-between process enables the therapist to depolarize sharply conflicted values and reduce pathogenic relating. (Author)

  17. Strengthening Family Practices for Latino Families

    Science.gov (United States)

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    This study examined the effectiveness of a culturally adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9- to 12-year-old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted…

  18. Putting the "family" back into family therapy.

    Science.gov (United States)

    Breunlin, Douglas C; Jacobsen, Elizabeth

    2014-09-01

    In this article, we examine the field of family therapy by drawing a distinction between two forms of practice: Whole Family Therapy (WFT), defined as treating the whole family, and Relational Family Therapy (RFT), defined as working with a subsystem of the family or an individual while retaining a systemic lens. Our thesis is that the practice of WFT has been in decline for some time and steps must be taken to keep it from becoming a defunct practice. We consider the trajectory of WFT and RFT throughout the development of family therapy through reference to the people, the literature, training, and practice patterns associated with family therapy. We remind the reader of the many benefits of WFT and suggest that today WFT is likely to be practiced in conjunction with RFT and individual therapy. Since training of family therapists today is largely located in degree-granting programs, we identify constraints to including WFT in such programs. We conclude by offering suggestions that can enhance a program's ability to train students in WFT. © 2014 FPI, Inc.

  19. Strengthening Family Practices for Latino Families

    Science.gov (United States)

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    This study examined the effectiveness of a culturally adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9- to 12-year-old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted…

  20. Vasoinhibins: a family of N-terminal prolactin fragments that inhibit angiogenesis and vascular function.

    Science.gov (United States)

    Clapp, Carmen; González, Carmen; Macotela, Yazmín; Aranda, Jorge; Rivera, José C; García, Celina; Guzmán, Jessica; Zamorano, Miriam; Vega, Claudia; Martín, Cecilia; Jeziorski, Michael C; de la Escalera, Gonzalo Martínez

    2006-01-01

    Antiangiogenic molecules derived from prolactin (PRL) are not a single entity, but rather a family of peptides with different molecular masses, all containing the N-terminal region of PRL. Cleavage of PRL by cathepsin-D or by matrix metalloproteases generates N-terminal fragments that act on endothelial cells to suppress vasodilation and angiogenesis and promote vascular regression. N-terminal PRL fragments have been identified in cartilage and retina, where angiogenesis is highly restricted. In vivo experiments demonstrate that these PRL fragments exert a tonic and essential suppression of retinal blood vessel growth and dilation. Similar PRL fragments have been detected in the pituitary gland, a highly vascularized organ where the control of vascular growth may differ from that in tissues where angiogenesis is highly restricted. We have previously proposed the name vasoinhibins to describe the collection of N-terminal PRL fragments having blood vessel-blocking activity, and here we discuss their promise as factors to control vascular function in health and disease.

  1. Regulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways.

    Science.gov (United States)

    Dang, Michelle; Armbruster, Nicole; Miller, Miles A; Cermeno, Efrain; Hartmann, Monika; Bell, George W; Root, David E; Lauffenburger, Douglas A; Lodish, Harvey F; Herrlich, Andreas

    2013-06-11

    Ectodomain cleavage of cell-surface proteins by A disintegrin and metalloproteinases (ADAMs) is highly regulated, and its dysregulation has been linked to many diseases. ADAM10 and ADAM17 cleave most disease-relevant substrates. Broad-spectrum metalloprotease inhibitors have failed clinically, and targeting the cleavage of a specific substrate has remained impossible. It is therefore necessary to identify signaling intermediates that determine substrate specificity of cleavage. We show here that phorbol ester or angiotensin II-induced proteolytic release of EGF family members may not require a significant increase in ADAM17 protease activity. Rather, inducers activate a signaling pathway using PKC-α and the PKC-regulated protein phosphatase 1 inhibitor 14D that is required for ADAM17 cleavage of TGF-α, heparin-binding EGF, and amphiregulin. A second pathway involving PKC-δ is required for neuregulin (NRG) cleavage, and, indeed, PKC-δ phosphorylation of serine 286 in the NRG cytosolic domain is essential for induced NRG cleavage. Thus, signaling-mediated substrate selection is clearly distinct from regulation of enzyme activity, an important mechanism that offers itself for application in disease.

  2. Choosing a Family Doctor

    Science.gov (United States)

    ... nav nav, .header-9#header-section #main-nav, #overlay-menu nav, #mobile-menu, #one-page-nav li . ... editorial staff Home Your Health Resources Doctor Visit Preparation Choosing a Family Doctor Choosing a Family Doctor ...

  3. Loosely coupled class families

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    are expressed using virtual classes seem to be very tightly coupled internally. While clients have achieved the freedom to dynamically use one or the other family, it seems that any given family contains a xed set of classes and we will need to create an entire family of its own just in order to replace one......Families of mutually dependent classes that may be accessed polymor- phically provide an advanced tool for separation of concerns, in that it enables client code to use a group of instances of related classes safely without depending on the exact classes involved. However, class families which...... of the members with another class. This paper shows how to express class families in such a manner that the classes in these families can be used in many dierent combinations, still enabling family polymorphism and ensuring type safety....

  4. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000408.htm Familial lipoprotein lipase deficiency To use the sharing features on this page, please enable JavaScript. Familial lipoprotein lipase deficiency is a group of rare genetic ...

  5. Familial Mediterranean fever

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000363.htm Familial Mediterranean fever To use the sharing features on this page, please enable JavaScript. Familial Mediterranean fever (FMF) is a rare disorder passed down through ...

  6. Importance of Family Routines

    Science.gov (United States)

    ... Structure Your Child's Nighttime Routine . Weekends: Weekends are good times for family togetherness. You might go grocery shopping as a family, visit museums and zoos, do chores​ that everyone participates in, go on ...

  7. Assessing postpartum family functioning.

    Science.gov (United States)

    Midmer, D; Talbot, Y

    1988-09-01

    The birth of a child requires adaptation and reorganization within the family system in order to accommodate the new family member and to allow the family to continue in its psychosocial development. Knowledge of the normative and transitional changes required at this stage of family life will enhance family practitioners' understanding of some of the common concerns and complaints related to them by various family members during the postpartum period. The Family FIRO model represents a helpful conceptual framework to increase the family physician's understanding of the issues of inclusion, control, and intimacy that are highlighted during the transition to parenthood. The authors briefly present this model and discuss its application to postpartum adjustment and its implications for health-care professionals.

  8. Family Practice Consultation.

    African Journals Online (AJOL)

    gauge the patients' opin:on on the family doctors' role regardirg prayer ... family practice consultation arc presented. ... patients' expectation of prayer and ..... New developments and frequently asked questions covering - high and low BMI, ...

  9. MSUD Family Support Group

    Science.gov (United States)

    ... Group The MSUD Family Support Group is a non-profit 501 (c)(3) organization for those with MSUD ... Family Support Group is a 501(c)(3) non-profit organization with no paid staff. Funds are needed ...

  10. National Military Family Association

    Science.gov (United States)

    ... 931.6632 info@MilitaryFamily.org © 2016 - National Military Family Association Twitter Facebook Pinterest Instagram Charity Navigator Four Star Charity GuideStar Exchange Better Business Bureau Charity Watch Independent Charity of America nonprofit ...

  11. Familial Episodic Amaurosis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-08-01

    Full Text Available A family with a stereotyped unilateral or bilateral transient visual loss, that recurred many times daily and was associated with childhood epilepsy and familial hemiplegic migraine, is reported from University Hospitals, Geneva, Switzerland.

  12. IGSF9 Family Proteins

    DEFF Research Database (Denmark)

    Hansen, Maria; Walmod, Peter Schledermann

    2013-01-01

    The Drosophila protein Turtle and the vertebrate proteins immunoglobulin superfamily (IgSF), member 9 (IGSF9/Dasm1) and IGSF9B are members of an evolutionarily ancient protein family. A bioinformatics analysis of the protein family revealed that invertebrates contain only a single IGSF9 family gene......, the longest isoforms of the proteins have the same general organization as the neural cell adhesion molecule family of cell adhesion molecule proteins, and like this family of proteins, IGSF9 family members are expressed in the nervous system. A review of the literature revealed that Drosophila Turtle...... facilitates homophilic cell adhesion. Moreover, IGSF9 family proteins have been implicated in the outgrowth and branching of neurites, axon guidance, synapse maturation, self-avoidance, and tiling. However, despite the few published studies on IGSF9 family proteins, reports on the functions of both Turtle...

  13. Family Caregiver Alliance

    Science.gov (United States)

    ... on your schedule. Look for our launch soon! FAMILY CARE NAVIGATOR ─ Click on Your State AL AK ... County Smart Patients Caregivers Community In partnership with Family Caregiver Alliance Learn more Caregiver Research Veterans suffer ...

  14. Family and Enterprise

    OpenAIRE

    Fletcher, Denise Elaine

    2006-01-01

    This chapter provides a review of the different approaches that have been utilised to examine the link between family and enterprise. Definitional issues are addressed, as are rationalist and ‘systems’ ways of evaluating the relationship between family and enterprise. Criticism is made of the effects of rationalist thinking on studies of family businesses which have tended to create duality and polarity in our understanding of the family-enterprise relationship. It is argued that a developm...

  15. Family Obligations in Denmark

    DEFF Research Database (Denmark)

    Koch-Nielsen, Inger

    How is the balance in obligations between the Family and the Danish Welfare State? Can we observe a trend to shift the responsibility back to the family? This booklet intends to sketch the legal framework around the division of responsibilities between the Family and the state and to analyse...... to what extent and where the unit of rights and obliagations is the individual and where it is the family or household....

  16. Family Obligations in Denmark

    DEFF Research Database (Denmark)

    Koch-Nielsen, Inger

    How is the balance in obligations between the Family and the Danish Welfare State? Can we observe a trend to shift the responsibility back to the family? This booklet intends to sketch the legal framework around the division of responsibilities between the Family and the state and to analyse...... to what extent and where the unit of rights and obliagations is the individual and where it is the family or household....

  17. Strengths of Remarried Families.

    Science.gov (United States)

    Knaub, Patricia Kain; And Others

    1984-01-01

    Focuses on remarried families' (N=80) perceptions of family strengths, marital satisfaction, and adjustment to the remarried situation. Results indicated that although most would like to make some changes, scores on the measurements used were high. A supportive environment was the most important predictor of family strength and success. (JAC)

  18. Family systems and fertility

    NARCIS (Netherlands)

    Moenkediek, Bastian

    2016-01-01

    This thesis studies the role of regional family organization principles, so called family systems, for explaining fertility behaviours in different parts of Europe. Studying family systems and its impact on fertility is important, because many aspects of societal life, such as the organization of we

  19. Families in Transition.

    Science.gov (United States)

    Britton, Patti O., Ed.; McGee, Michael, Ed.

    1987-01-01

    This issue of "Emphasis" deals with families in transition, providing some model programs for the new family and some historical perspectives on how families have developed over time. Articles include: (1) "Nostalgia on the Right" (Nancy Theriot); (2) "Heart to Heart" (Nancy Harrington-MacLennan); (3) "The Media Get the Message" (Janet Alyn); (4)…

  20. Books in the Family.

    Science.gov (United States)

    Swinger, Alice K.

    1989-01-01

    Opportunities for parents to encourage reading in the family are noted and ways to enhance the reading experience are discussed, including writing letters to book characters, singing combined with reading aloud, supplementing school subjects with enjoyable reading, sharing books at family gatherings, and using family experiences for book…

  1. Single Mothers "Do" Family

    Science.gov (United States)

    Nelson, Margaret K.

    2006-01-01

    This paper explores how single mothers both incorporate others into family life (e.g., when they ask others to care for their children) and simultaneously "do families" in a manner that holds out a vision of a "traditional" family structure. Drawing on research with White, rural single mothers, the author explores the manner in which these women…

  2. A型肉毒毒素轻链多步纯化及其金属蛋白酶活性研究%Multi-step purifications of botulinum neurotoxin A light chain and identification of its metalloproteases activity

    Institute of Scientific and Technical Information of China (English)

    卢晓雪; 赵缓; 黄彦杰; 李涛; 王慧

    2016-01-01

    目的:利用基因工程方法原核表达N-His标签的A型肉毒毒素轻链( BoNT-ALC)蛋白,多步纯化获得高纯度蛋白,并对其金属蛋白酶活性进行鉴定。方法以A型肉毒毒素为模板,构建重组表达载体pET22b-ALC,转化BL21(DE3),诱导蛋白表达,采用镍柱亲和纯化、阴离子交换以及分子筛纯化获取高纯度目的蛋白;通过体外切割特异性底物SNAP-25实验进行酶活性研究。结果与结论获得高纯度的BoNT-ALC蛋白,对金属蛋白酶活性进行了验证。该纯化方法获得的蛋白纯度高、均一性好,且具有很好的酶活性,为后续研究奠定了基础。%Objective To obtain highly purified botulinum neurotoxin A light chain(BoNT-ALC) protein in E.coli by genetic engineering and multi-step purifications, and identify its metalloproteases activity.Methods The full-length of BoNT-ALC was cloned from BoNT A by PCR and inserted into plasmid pET-22b.Then pET-22b-ALC was transformed into E.coli BL21( DE3) strains and induced by IPTG.The protein was purified by Ni-NTA sepharose,anion exchange column and gel filtration.The enzymatic activity of the protein was identified by SNAP-25.Results and Conclusion A highly purified and homogeneous protein is obtained, which shows good enzymatic activity.

  3. Family traditions and generations.

    Science.gov (United States)

    Schneiderman, Gerald; Barrera, Maru

    2009-01-01

    Currently, traditional family values that have been passed down through generations appear to be at risk. This has significant implications for the stability and health of individuals, families, and communities. This article explores selected issues related to intergenerational transmission of family values and cultural beliefs, with particular reference to Western culture and values that are rooted in Jewish and Christian traditions. It also examines family values and parenting styles as they influence the developing perspective of children and the family's adaptation to a changing world.

  4. Asteroid family ages

    CERN Document Server

    Spoto, Federica; Knezevic, Zoran

    2015-01-01

    A new family classification, based on a catalog of proper elements with $\\sim 384,000$ numbered asteroids and on new methods is available. For the $45$ dynamical families with $>250$ members identified in this classification, we present an attempt to obtain statistically significant ages: we succeeded in computing ages for $37$ collisional families. We used a rigorous method, including a least squares fit of the two sides of a V-shape plot in the proper semimajor axis, inverse diameter plane to determine the corresponding slopes, an advanced error model for the uncertainties of asteroid diameters, an iterative outlier rejection scheme and quality control. The best available Yarkovsky measurement was used to estimate a calibration of the Yarkovsky effect for each family. The results are presented separately for the families originated in fragmentation or cratering events, for the young, compact families and for the truncated, one-sided families. For all the computed ages the corresponding uncertainties are pro...

  5. Inside the Family Firm

    DEFF Research Database (Denmark)

    Bennedsen, Morten; Nielsen, Kasper; Pérez-González, Francisco

    2005-01-01

    This paper uses a unique dataset from Denmark to investigate (1) the role of family characteristics in corporate decision making, and (2) the consequences of these decisions on firm performance. We focus on the decision to appoint either a family or an external chief executive officer (CEO). We...... show that a departing CEO's family characteristics have a strong predictive power in explaining CEO succession decisions: family CEOs are more frequently selected the larger the size of the family, the higher the ratio of male children and when the departing CEOs had only had one spouse. We...... then analyze the impact of family successions on performance. We overcome endogeneity and omitted variables problems of previous papers in the literature by using the gender of a departing CEO's first-born child as an instrumental variable (IV) for family successions. This is a plausible IV as male first...

  6. Inside the Family Firm

    DEFF Research Database (Denmark)

    Bennedsen, Morten; Nielsen, Kasper; Pérez-González, Francisco

    2005-01-01

    This paper uses a unique dataset from Denmark to investigate (1) the role of family characteristics in corporate decision making, and (2) the consequences of these decisions on firm performance. We focus on the decision to appoint either a family or an external chief executive officer (CEO). We...... show that a departing CEO's family characteristics have a strong predictive power in explaining CEO succession decisions: family CEOs are more frequently selected the larger the size of the family, the higher the ratio of male children and when the departing CEOs had only had one spouse. We...... then analyze the impact of family successions on performance. We overcome endogeneity and omitted variables problems of previous papers in the literature by using the gender of a departing CEO's first-born child as an instrumental variable (IV) for family successions. This is a plausible IV as male first...

  7. Family governance practices and teambuilding : Paradox of the enterprising family

    NARCIS (Netherlands)

    Berent-Braun, M.M.; Uhlaner, L.M.

    2012-01-01

    This paper explores the relationship between family governance practices and financial performance of the business and family assets of business-owning families. A business-owning family that shares a focus on preserving and growing wealth as a family is defined as the enterprising family. Results o

  8. 24 CFR 982.515 - Family share: Family responsibility.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner is...

  9. Opening Doors: Understanding School and Family Influences on Family Involvement

    Science.gov (United States)

    Carlisle, Erin; Stanley, Lindsey; Kemple, Kristen Mary

    2005-01-01

    Family involvement in schooling can benefit young children, teachers, and families. Family involvement in schools can be influenced by both school-related and family-related factors. School-related factors include teachers' attitudes toward families, and school and teacher expectations. Family-related factors include ethnicity, prior school…

  10. Family governance practices and teambuilding : Paradox of the enterprising family

    NARCIS (Netherlands)

    Berent-Braun, M.M.; Uhlaner, L.M.

    2012-01-01

    This paper explores the relationship between family governance practices and financial performance of the business and family assets of business-owning families. A business-owning family that shares a focus on preserving and growing wealth as a family is defined as the enterprising family. Results o

  11. Family governance practices and teambuilding : Paradox of the enterprising family

    NARCIS (Netherlands)

    Berent-Braun, M.M.; Uhlaner, L.M.

    2012-01-01

    This paper explores the relationship between family governance practices and financial performance of the business and family assets of business-owning families. A business-owning family that shares a focus on preserving and growing wealth as a family is defined as the enterprising family. Results

  12. Family dynamics and family psychotherapy of psychosomatic.

    Science.gov (United States)

    Wirsching, M; Stierlin, H

    1979-01-01

    Family therapy of psychosomatic disorders is oftern difficult and comparable to the therapy of psychotic patients. Nonetheless, the results published today by authors such as Minuchin and Selvini and our own experiences are promising indeed. We have found that what seemed to be a deep-rooted psychic structure changed rapidly and enduringly if the relationship field changed. Amelioration of symptoms is in many cases easily attained if they are understood in their function within a relational system. Also, we regard the system or family approach as a chance for medical practice. The general practioner who usually deals with family systems has, in our view, an ideal position to bring about change if he uses his authority and trust properly. He has to obtain a positive, not pathology-oriented view and should use family and social resources in spite of engaging in an often fruitless and endless contact with the designated patient, which only serves to maintain and even to increase the homeostatic lock of the family system.

  13. Familial pituitary tumor syndromes.

    Science.gov (United States)

    Elston, Marianne S; McDonald, Kerrie L; Clifton-Bligh, Roderick J; Robinson, Bruce G

    2009-08-01

    The vast majority of pituitary tumors are benign and occur sporadically; however, they can still result in significant morbidity and even premature mortality through mass effects and hormone dysfunction. The etiology of sporadic tumors is still poorly understood; by contrast, advances have been made in our understanding of familial pituitary adenoma syndromes in the past decade. Currently, four genes are known to be associated with familial pituitary tumor syndromes: MEN1, CDKN1B, PRKAR1A and AIP. The first three genes are associated with a variety of extrapituitary pathologies, for example, primary hyperparathyroidism with multiple endocrine neoplasia type 1, which might aid identification of these syndromes. By contrast, AIP mutations seem to occur in the setting of isolated familial pituitary adenomas, particularly of the growth-hormone-secreting subtype. Awareness and identification of familial pituitary tumor syndromes is important because of potential associated pathologies and important implications for family members. Here, we review the current knowledge of familial pituitary tumor syndromes.

  14. Advancing family psychology.

    Science.gov (United States)

    Fiese, Barbara H

    2016-02-01

    To realize the broad and complex nature of the field of family psychology, I have slightly revised the mission statement of the Journal of Family Psychology (JFP) to capture contemporary scholarship in family psychology and to advance systems perspectives in this top-tier scientific journal. Over the next 6 years, I hope that authors will consider JFP as an outlet for their best work in the following areas: (1) JFP addresses societal challenges faced by families today; (2) JFP publishes important studies on what makes couple and family relationships work; (3) JFP is a leader in publishing reports that use cutting-edge sophisticated approaches to research design and data analysis; and (4) JFP imparts knowledge about effective therapy and prevention programs relevant to couples and families. The journal is also expanding its publication rate to eight issues per year.

  15. Metalloprotease Dependent Release of Placenta Derived Fractalkine

    OpenAIRE

    Monika Siwetz; Astrid Blaschitz; Julia Kremshofer; Jelena Bilic; Gernot Desoye; Berthold Huppertz; Martin Gauster

    2014-01-01

    The chemokine fractalkine is considered as unique since it exists both as membrane-bound adhesion molecule and as shed soluble chemoattractant. Here the hypothesis was tested whether placental fractalkine can be shed and released into the maternal circulation. Immunohistochemical staining of human first trimester and term placenta sections localized fractalkine at the apical microvillous plasma membrane of the syncytiotrophoblast. Gene expression analysis revealed abundant upregulation in pla...

  16. Peptidomimetics and metalloprotease inhibitors as anticancer drugs

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the de-velopment of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeu-tic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity.

  17. Therapeutic applications of collagenase (metalloproteases: A review

    Directory of Open Access Journals (Sweden)

    Hamzeh Alipour

    2016-11-01

    Full Text Available Non-invasive therapeutic methods have recently been used in medical sciences. Enzymes have shown high activity at very low concentrations in laboratories and pharmaceutical, enabling them to play crucial roles in different biological phenomena related to living organism, especially human medicine. Recently, using the therapeutic methods based on non-invasive approaches has been emphasized in medical society. Researchers have focused on producing medicines and tools reducing invasive procedures in medical. Collagenases are proteins which catalyze chemical processes and break the peptide bonds in collagen. Collagen may be generated more than the required amount or produced in unsuitable sites or may not degrade after a certain time. In such cases, using an injectable collagenase or its ointment can be helpful in collagen degradation. In both in vitro and in vivo tests, it has been revealed that collagenases have several therapeutic properties in wound healing, burns, nipple pain and some diseases including intervertebral disc herniation, keloid, cellulite, lipoma among others. This review describes the therapeutic application of collagenase in medical sciences and the process for its production using novel methods, paving the way for more effective and safe applications of collagenases.

  18. KSF of family business

    OpenAIRE

    Boroš, Petr

    2014-01-01

    Family business is a business in which family members have a large stake in ownership and also a deciding vote on business operation. This thesis deals with what makes the family businesses thriving. The research is conducted using the Good to Great framework by Jim Collins. Based mainly on quantitative and qualitative survey of 8 Czech companies of various fields and sizes, it was discovered that there are some links between the companies' success. These findings yield a set of recommendatio...

  19. Family in contemporary society

    OpenAIRE

    Rabije Murati

    2016-01-01

    The family is part of social change and, as such changes and transform into steps with modern trends of society. Family function in a given society is structured according to the overall changes that occur in all areas of social life, not neglecting family life. The contemporary conditions impose requirements that must be met to move forward with the times that follow. In particular, should highlight the social changes that are related to the growth and advancement of the educational and prof...

  20. The Hoffmeister asteroid family

    Science.gov (United States)

    Carruba, V.; Novaković, B.; Aljbaae, S.

    2017-03-01

    The Hoffmeister family is a C-type group located in the central main belt. Dynamically, it is important because of its interaction with the ν1C nodal secular resonance with Ceres, which significantly increases the dispersion in inclination of family members at a lower semimajor axis. As an effect, the distribution of inclination values of the Hoffmeister family at a semimajor axis lower than its centre is significantly leptokurtic, and this can be used to set constraints on the terminal ejection velocity field of the family at the time it was produced. By performing an analysis of the time behaviour of the kurtosis of the vW component of the ejection velocity field [γ2(vW)], as obtained from Gauss' equations, for different fictitious Hoffmeister families with different values of the ejection velocity field, we were able to exclude that the Hoffmeister family should be older than 335 Myr. Constraints from the currently observed inclination distribution of the Hoffmeister family suggest that its terminal ejection velocity parameter VEJ should be lower than 25 m s-1. Results of a Yarko-YORP Monte Carlo method to family dating, combined with other constraints from inclinations and γ2(vW), indicate that the Hoffmeister family should be 220^{+60}_{-40} Myr old, with an ejection parameter VEJ = 20 ± 5 m s-1.

  1. Family in contemporary society

    Directory of Open Access Journals (Sweden)

    Rabije Murati

    2016-01-01

    Full Text Available The family is part of social change and, as such changes and transform into steps with modern trends of society. Family function in a given society is structured according to the overall changes that occur in all areas of social life, not neglecting family life. The contemporary conditions impose requirements that must be met to move forward with the times that follow. In particular, should highlight the social changes that are related to the growth and advancement of the educational and professional standards, which will increase the overall impact on the family and its function. If you're looking for full responsibility of parents in the upbringing of children then it is necessary to see the conditions in which the family lives. For normal education and the rights of children with special meaning the number of members in the (quantity family. The tendency to a higher standard of economic life, a small number of children in the family and it is more than obvious that fewer family members or less have greater opportunity for parents to pay more attention to their children. One of the main roles of family, no matter where they are located in the city, village, developed or developing countries, by all means participate, intermediates and transfers the moral, social and other values in modern life.

  2. Saturating Sperner families

    CERN Document Server

    Gerbner, Dániel; Lemons, Nathan; Pálvölgyi, Dömötör; Palmer, Cory; Patkós, Balázs

    2011-01-01

    A family $\\cF \\subseteq 2^{[n]}$ saturates the monotone decreasing property $\\cP$ if $\\cF$ satisfies $\\cP$ and one cannot add any set to $\\cF$ such that property $\\cP$ is still satisfied by the resulting family. We address the problem of finding the minimum size of a family saturating the $k$-Sperner property and the minimum size of a family that saturates the Sperner property and that consists only of $l$-sets and $(l+1)$-sets.

  3. The DLGAP family

    DEFF Research Database (Denmark)

    Rasmussen, Andreas H; Rasmussen, Hanne B; Silahtaroglu, Asli

    2017-01-01

    downstream signalling in the neuron. The postsynaptic density, a highly specialized matrix, which is attached to the postsynaptic membrane, controls this downstream signalling. The postsynaptic density also resets the synapse after each synaptic firing. It is composed of numerous proteins including a family...... in the postsynapse, the DLGAP family seems to play a vital role in synaptic scaling by regulating the turnover of both ionotropic and metabotropic glutamate receptors in response to synaptic activity. DLGAP family has been directly linked to a variety of psychological and neurological disorders. In this review we...... focus on the direct and indirect role of DLGAP family on schizophrenia as well as other brain diseases....

  4. Communication in family businesses : Relationships between family and non-family managers

    OpenAIRE

    Grytsaieva, Tetiana; Strandberg, Johan

    2016-01-01

    Problem: Family firms often comprise of a complex web of relationships between family and non-family managers that are active within the business. Family enterprises are also known for their closed communication and decision-making practices. It often occurs that families do not include non-family managers into important business-related discussions and do not consult their decisions with managers from outside of the family. At the same time, research in the area of family business defines th...

  5. The Rafita asteroid family

    Science.gov (United States)

    Aljbaae, S.; Carruba, V.; Masiero, J. R.; Domingos, R. C.; Huaman, M.

    2017-01-01

    The Rafita asteroid family is an S-type group located in the middle main belt, on the right side of the 3J:-1A mean-motion resonance. The proximity of this resonance to the family left side in semi-major axis caused many former family members to be lost. As a consequence, the family shape in the (a, 1/D) domain is quite asymmetrical, with a preponderance of objects on the right side of the distribution. The Rafita family is also characterized by a leptokurtic distribution in inclination, which allows the use of methods of family age estimation recently introduced for other leptokurtic families such as Astrid, Hansa, Gallia, and Barcelona. In this work we propose a new method based on the behavior of an asymmetry coefficient function of the distribution in the (a, 1/D) plane to date incomplete asteroid families such as Rafita. By monitoring the time behavior of this coefficient for asteroids simulating the initial conditions at the time of the family formation, we were able to estimate that the Rafita family should have an age of 490 ± 200 Myr, in good agreement with results from independent methods such as Monte Carlo simulations of Yarkovsky and Yorp dynamical induced evolution and the time behaviour of the kurtosis of the sin (i) distribution. Asteroids from the Rafita family can reach orbits similar to 8% of the currently known near Earth objects. ≃1% of the simulated objects are present in NEO-space during the final 10 Myr of the simulation, and thus would be comparable to objects in the present-day NEO population.

  6. Diagnostic value of a distintegrin and metalloproteases-8 in non-small cell lung cancer%解整合素-金属蛋白酶8对非小细胞肺癌的诊断价值

    Institute of Scientific and Technical Information of China (English)

    陈飞鹏; 黄金桔; 邬勇坚; 阳隽

    2009-01-01

    目的 探讨解整合素-金属蛋白酶8(ADAM8)对非小细胞肺癌患者(NSCLC)的诊断价值.方法 应用ELISA方法 检测62例NSCLC患者、27例良性肺病患者和32例健康体检者血清中的ADAM8蛋白表达水平.结果 NSCLC组血清ADAM8水平[(456.88±143.87)ng/L]高于良性肺病组[(271.63±74.20)ng/L]和正常对照组[(253.09±72.15)ng/L],差异均有统计学意义(P均<0.01),良性肺病组AD-AM8表达水平比正常对照组略高,但差异无统计学意义(P0.05);ADAM8在腺癌患者中表达水平与鳞癌相比差异无统计学意义[(462.54±161.387)ng/L与(449.04±118.03)ng/L,P0.05],Ⅲ、Ⅳ期NSCLC患者血清中ADAM8的水平[(498.80±151.80)ng/L]高于Ⅰ、Ⅱ期患者[(385.80±95.85)ng/L],差异有统计学意义(P<0.01);检测ADAM8对NSCLC的诊断敏感性为77.4%,特异性为90.6%.结论 ADAM8在NSCLC患者血清中过度表达,表明其与肺癌的发生和转移有着密切的关系,检测ADAM8对NSCLC的诊断有一定的辅助价值.%Objective To study the diagnostic values of a distintegrin and metalloproteases-8 (ADAMS) in non-small cell lung cancer(NSCLC).Methods The serum protein level of ADAM8 was assayed by ELISA in 62 NSCLC patients,27 lung benign lesions and 32 healthy people.Results The serum levels of ADAM8 of NSCLC [(456.88±143.87)ng/L] were higher than those with lung benign lesions[ (271.63±74.20) ng/L] and normal controls(253.09±72.15 ng/L) (P<0.01), but there was no significant difference between lung benign lesions and normal controls (P0.05).No significant difference was found between adenocarcinoma and squamous cell carcinoma in serum ADAM8 level,the serum levels of ADAM8 in NSCLC with stages Ⅲ-Ⅳ [ (498.80 ± 151.80) ng/L] were higher than those with stages Ⅰ -Ⅱ[(385.80±95.85) ng/L] (P <0.01 ).The diagnostic sensitivity of detection of ADAM8 for NSCLC was 77.4% and the specificity was 90.6%.Conclusion The overexpression of ADAM8 in serum of NSCLC patients indicates that ADAM8 is related

  7. 梅毒螺旋体金属蛋白酶水解纤维蛋白原的活性研究%The Fibrinolytic Potential of Treponema Pallidum Metalloprotease

    Institute of Scientific and Technical Information of China (English)

    刘双全

    2015-01-01

    Objective To investigate the fibrinolytic potential of Treponema pallidum metalloprotease Tp0751,provi-ding the experimental basis for further research on syphilis pathogenic mechanism. Methods Constructed the H198A mutant Tp0751 and H202A mutant Tp0751 with two-point technology. Wide-type and Mutant Tp0751 recombinant protein were expressed in E. coli BL21. And detected their degradation activity to fibrinogen. Results Three fusion protein with molecular weight about 26KDa were attained after expression and purification,The wild type Tp0751 can degradate plas-minogen-free human fibrinogen,fibrinogen was absolutely degradated 24h post-incubation,The H198A mutant Tp0751 can also degradate plasminogen-free human fibrinogen,but which was partly degradated 24h post-incubation;The H202A mutant Tp0751 can not degradate plasminogen-free human fibrinogen,fibrinogen was scarcely degradated 24h post-incubation. Conclusion The wild type Tp0751 can degradate plasminogen-free human fibrinogen,The HEXXH motif may have a im-portant role on Tp0751 to the degradation of plasminogen-free human fibrinogen,residue H202,but not H198,from the palli-lysin HEXXH motif is required for fibrinogen degradation.%目的:研究梅毒螺旋体金属蛋白酶Tp0751对细胞外基质纤维蛋白原的水解能力,为深入研究TP的致病机制提供实验依据。方法采用两点法构建H198A突变型及H202A突变型Tp0751基因,分别构建野生型和突变型Tp0751原核载体进行诱导表达;体外实验检测Tp0751野生型Tp0751蛋白、H198A Tp0751突变型蛋白、H202ATp0751突变型蛋白对纤维蛋白原的降解活性。结果成功表达并纯化了野生型Tp0751蛋白、H198A Tp0751突变体蛋白、H202A Tp0751突变体蛋白,各蛋白相对分子量大小约为26kD;纤维蛋白原在与野生型Tp0751蛋白作用约24h后被完全水解;与 H198A Tp0751突变体蛋白作用约24 h 后部分水解,尚有部分未被降解;与H202A Tp0751

  8. Closure Issues with Families.

    Science.gov (United States)

    Craig, Steven E.; Bischof, Gary H.

    Closure of the counseling relationship constitutes both an ending and a beginning. Although closure signifies the ending of the present counseling relationship, many family counselors conceptualize closure as the start of a working relationship between counselor and family that may be summoned in future times of crisis or during a difficult life…

  9. Selecting Family Interventions.

    Science.gov (United States)

    Watts, Richard E.

    Just as counseling approaches designed for individuals have their theory-specific techniques, family counseling approaches also have theory-specific interventions and strategies. Whatever presenting problem the family brings to counseling, one or more of four essential components (communication, problem solving, roles and boundaries) is typically…

  10. Assessment of Troubled Families.

    Science.gov (United States)

    Combs-Orme, Terri; Thomas, Katherine H.

    1997-01-01

    Tests the utility of four standardized instruments used in assessing 105 families that sought services in a juvenile corrections setting for their teenage children. Results demonstrate that parents and adolescents can complete standardized assessment instruments and that the information provided can help in understanding distressed families. (RJM)

  11. Family Reunion Health Guide

    Science.gov (United States)

    ... be a sign of kidney disease. Encourage your family to keep their blood pressure at or below the number set by their ... Share NKDEP brochures about diabetes and high blood pressure. Encourage family members to take the information with them when ...

  12. Privacy in the family

    NARCIS (Netherlands)

    Newell, Bryce; Metoyer, Cheryl A.; Moore, Adam D.

    2015-01-01

    Popular access to increasingly sophisticated forms of electronic surveillance technologies has altered the dynamics of family relationships. Monitoring, mediated and facilitated by practices of both covert and overt electronic surveillance, has changed the nature of privacy within the family. In thi

  13. Narrative Family Therapy.

    Science.gov (United States)

    Walsh, William M.; Keenan, Robert

    1997-01-01

    States that narrative family therapy is informed by social constructionism and postmodern worldviews, and is a relatively significant departure from mainstream psychotherapy. Discusses the use of narrative family therapy. Uses the story of Adam and Eve in the Garden of Eden as an example. (MKA)

  14. Marriage or Family Therapy.

    Science.gov (United States)

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  15. Family Report 2011

    NARCIS (Netherlands)

    Freek Bucx

    2011-01-01

    Original title: Gezinsrapport 2011. Between 2007 and 2010 the Netherlands had its first ever Minister for Youth and Family. The position of the family in modern society is a subject of considerable debate, not just at political and policy level, but also in society itself. Voices are frequently hea

  16. Familie og arv

    DEFF Research Database (Denmark)

    Nielsen, Linda

    1995-01-01

    Familie og arv, familie, arv, børn, ægteskab, ægtefælle, skilsmisse, formuefællesskab, forældremyndighed, fælleseje, særråden, særeje, død, uskiftet bo, underholdspligt, samliv, tvangsarv, deling...

  17. Golden Matrix Families

    Science.gov (United States)

    Fontaine, Anne; Hurley, Susan

    2011-01-01

    This student research project explores the properties of a family of matrices of zeros and ones that arises from the study of the diagonal lengths in a regular polygon. There is one family for each n greater than 2. A series of exercises guides the student to discover the eigenvalues and eigenvectors of the matrices, which leads in turn to…

  18. Internationalization of Family Businesses

    DEFF Research Database (Denmark)

    Boyd, Britta; Hollensen, Svend; Goto, Toshio

    2010-01-01

    -depth qualitative interviews reveal the driving forces on both sides and show how the psychic distance can be reduced between the different parent firms including the joint venture (JV) child. The purpose of this study is to compare equal split or equity joint ventures of non-family and family firms regarding...

  19. America's Family Time Famine.

    Science.gov (United States)

    Mattox, Jr., William R.

    1990-01-01

    Parents spend increasingly less time with their children because of the pressures of dual careers and single parenthood. Economic pressures and social values have affected sharing of family time. Studies show both parents and children consider spending time together the most important element in improving family life. (BC)

  20. Marriage or Family Therapy.

    Science.gov (United States)

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  1. The Family Victivallaceae

    NARCIS (Netherlands)

    Plugge, C.M.; Zoetendal, E.G.

    2014-01-01

    The family Victivallaceae is a member of the order Victivallales and holds only two cultured representatives: Victivallis vadensis strain CelloT and the uncharacterized strain NML 080035. They are Gram-negative, nonmotile, and anaerobic. Within the family as well as the order, cloned 16S rRNA gene s

  2. The family Cyclobacteriaceae

    Digital Repository Service at National Institute of Oceanography (India)

    AnilKumar, P.; Srinivas, T.N.R.

    , Rhodonellum, and Shivajiella Phylogenetic analysis based on 16S rRNA gene sequences clearly clustered all the genera into the family Cyclobacteriaceae Members of the family are known to have a wide range of morphological properties like cell shape, size...

  3. Why the Family?

    NARCIS (Netherlands)

    Ferracioli, L.

    2015-01-01

    Among the most pressing philosophical questions occupying those interested in the ethics of the family is why should parents, as opposed to charity workers or state officials, raise children? In their recent Family Values, Brighouse and Swift have further articulated and strengthen their own

  4. Changing Families, Changing Workplaces

    Science.gov (United States)

    Bianchi, Suzanne M.

    2011-01-01

    American families and workplaces have both changed dramatically over the past half-century. Paid work by women has increased sharply, as has family instability. Education-related inequality in work hours and income has grown. These changes, says Suzanne Bianchi, pose differing work-life issues for parents at different points along the income…

  5. Familial malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kopf, A.W.; Hellman, L.J.; Rogers, G.S.; Gross, D.F.; Rigel, D.S.; Friedman, R.J.; Levenstein, M.; Brown, J.; Golomb, F.M.; Roses, D.F.; Gumport, S.L.

    1986-10-10

    Characteristics associated with familial compared with nonfamilial malignant melanoma were assessed. These data were obtained from consecutive prospectively completed questionnaires on 1169 cases of cutaneous malignant melanoma. Of these, 69 patients indicated a positive family history for this cancer. Among the various clinical and histological variables compared, those that significantly correlated with the familial occurrence of malignant melanoma include younger age at first diagnosis, smaller diameter of the lesion, lower Clark level, decreased frequency of nonmelanoma skin cancer, and reduced prevalence of noncutaneous cancer. Increased awareness of malignant melanoma among family members could account for some of these observations. Identification of the familial variety of malignant melanoma has practical implications concerning early detection and prompt intervention.

  6. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L

    2015-01-01

    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however......, with the advent of next-generation sequencing, a small number of new high-penetrance genes have recently been uncovered. This approach has identified the lineage-specific oncogene MITF as a susceptibility gene both in melanoma families and in the general population, as well as the discovery of telomere...... maintenance as a key pathway underlying melanoma predisposition. Given these rapid recent advances, this approach seems likely to continue to pay dividends. Here, we review the currently known familial melanoma genes, providing evidence that most additionally confer risk to other cancers, indicating...

  7. Maintenance of family networks

    DEFF Research Database (Denmark)

    marsico, giuseppina; Chaudhary, N; Valsiner, Jaan

    2015-01-01

    Families are social units that expand in time (across generations) and space (as a geographically distributed sub-structures of wider kinship networks). Understanding of intergenerational family relations thus requires conceptualization of communication processes that take place within a small...... collective of persons linked with one another by a flexible social network. Within such networks, Peripheral Communication Patterns set the stage for direct everyday life activities within the family context. Peripheral Communication Patterns are conditions where one family network member (A) communicates...... manifestly with another member (B) with the aim of bringing the communicative message to the third member (C) who is present but is not explicitly designated as the manifest addressee of the intended message. Inclusion of physically non-present members of the family network (elders living elsewhere, deceased...

  8. Negotiating Family Tracking

    DEFF Research Database (Denmark)

    Sonne Damkjær, Maja; Albrechtslund, Anders; Bøge, Ask Risom

    This presentation explores the question: What motivates the use of tracking technologies in families, and how does the use transform the relations between parent and child? The purpose is to investigate why tracking technologies are used in families and how these technologies potentially change...... the relation between parents and children. The use of tracking technologies in families implicate negotiations about the boundaries of trust and intimacy in parent-child relations which can lead to strategies of resistance or modification (Fotel and Thomsen, 2004; Rooney, 2010; Steeves and Jones, 2010......). In the presentation, we report from a qualitative study that focuses on intergenerational relations. The study draws on empirical data from workshops with Danish families as well as individual and group interviews. We aim to gain insights about the sharing habits and negotiations in intimate family relations...

  9. Fighting for the family

    DEFF Research Database (Denmark)

    Heiselberg, Maj Hedegaard

    2016-01-01

    The article explores how military deployment affects the everyday lives of Danish soldiers’ families. By approaching the challenges faced by soldiers and their partners from an anthropological perspective of the family, the article provides new insights into the social consequences of military...... deployment and the processes of militarization at home. Drawing on ethnographic examples from recent fieldwork among women, children, and soldiers at different stages of deployment, the article demonstrates how soldiers and their families attempt to live up to ideals about parenthood and family by creating...... ‘relational spaces’ that allow them to preserve intimate relationships despite geographical distances. Besides dealing with the practical responsibilities of everyday life, soldiers’ partners also fight to maintain the sense of closeness associated with normative ideals about family relations and a ‘good...

  10. Family Reconstruction: The Family within-a Group Experience.

    Science.gov (United States)

    Satir, Virginia; And Others

    1988-01-01

    Presents Virginia Satir's Family Reconstruction, a group therapy experience that blends and extends her 1982 process therapy and 1983 conjoint family therapy approaches. Describes the family reconstruction process, the review of family reconstruction data in the pregroup interview, the family reconstruction process in the counseling group, and the…

  11. Family Reconstruction: The Family within-a Group Experience.

    Science.gov (United States)

    Satir, Virginia; And Others

    1988-01-01

    Presents Virginia Satir's Family Reconstruction, a group therapy experience that blends and extends her 1982 process therapy and 1983 conjoint family therapy approaches. Describes the family reconstruction process, the review of family reconstruction data in the pregroup interview, the family reconstruction process in the counseling group, and the…

  12. 75 FR 17946 - Family Report, MTW Family Report

    Science.gov (United States)

    2010-04-08

    ... URBAN DEVELOPMENT Family Report, MTW Family Report AGENCY: Office of the Chief Information Officer, HUD... understand demographic, family profile, income, and housing information for participants in the Public... Following Information Title of Proposal: Family Report, MTW Family Report. OMB Approval Number: 2577-0083...

  13. [Family oriented nursing care].

    Science.gov (United States)

    Lima-Rodríguez, Joaquin Salvador; Lima-Serrano, Marta; Sáez-Bueno, Africa

    2009-01-01

    Nursing has experienced an important methodological development, in which it gives priority to the individual, although at a socioeconomic level a marked interest is seen in the health care of the family unit and the NANDA (North American Nursing Diagnosis Association), NIC (Nursing Interventions Classification) and NOC (Nursing Outcomes Classification) nursing guidelines, using diagnoses, criteria of results and interventions orientated towards this aim. We consider to the family as an opened system consisted of human elements, with a common history, which they form a functional unit been ruled by own procedure. In this paper we look at those aspects that must be taken into account in nursing assessment of families from a systemic perspective, including some tools for data collection and analysis of information. In addition, we identify specific areas of intervention. We believe that the family must be studied from a nursing care point of view with its own characteristics as opposed to those possessed individually by each of its members. We also believe that, when assessment is centred on the Henderson unaided activities study or the Gordon functional health patterns, they are not useful in assessing the family unit. This work offers an assessment method centred on the family unit, which helps to identify the nursing diagnoses applicable to it. Our proposal, which has been successfully used by nursing students over the last few years, hopes to contribute to quality clinical practice with a tool orientated towards the family.

  14. Gender and family stability

    Directory of Open Access Journals (Sweden)

    2001-02-01

    Full Text Available The increasing trend of partnership disruption among families with children in recent decades has been accompanied by substantial changes in traditional gender roles in industrialized countries. Yet, relatively little is known about the effects of changing gender relations on family stability in the European context. In this paper, we study such gender influences at the familial and societal level in Sweden and Hungary between the mid-1960s and the early 1990s. We focus on the disruption of the first parental union (i.e. the union in which a couple's first child was born. Our analysis is based on data extracted from the Swedish and Hungarian Fertility and Family Surveys of 1992/93. We use the method of hazard regression. The results suggest (i that the establishment of the dual-earner family model influences family stability only if it is accompanied by some changes in traditional gender relations within the family, and (ii that women's and men's labor-market behavior have different effects in spite of the relatively long history of women's (also mothers' labor-force participation in both Sweden and Hungary.

  15. Ethnic family structure.

    Science.gov (United States)

    Mcdonald, P

    1989-04-01

    Using information from large-scale statistical collections and elaborations from ethnographic studies, this paper examines the underlying social processes and structures of migrant families in Australia. Migrants in Australia are often confronted by family values and behavior which run counter to their own. For some migrants, particularly those from the United Kingdom and Western European countries, there is little conflict as Australian family values and behavior approximate their own; the feminine conception of the family is not foreign to them. On the other hand, migrants from Mediterranean countries and from Asia are likely to face a clash between the masculine conception of the family and the dominant feminine conception they find in Australia. Economic structure also often forces an accommodation to the feminine conception of the family. For example, migrant women in Australia are heavily involved in the work force outside the family circle, and, in the main, have relatively low fertility. Age at marriage is increasing and many single women of migrant origin are being educated at the tertiary level and are working before marriage. These changes necessarily expose women and youths to the dominant social values and increase their economic independence, thus disrupting the conventional male family authority. There is evidence of a degree of accommodation to Australian patterns of behavior in migrant groups more inclined to a masculine conception of the family. In other areas, however, which are less directly related to economic pressure, migrant values have been far less accommodating. There is still a high level of endogamy, the 1st birth occurs soon after marriage, divorce rates are low, and the aged are very likely to live with their children. Large migrant groups have been able to maintain these patterns of behavior through the formation of ethnic substructures that form their principal social environment. In the longer term, however, their children are

  16. Family Structure and Social Influence.

    Science.gov (United States)

    Olson, Dawn R.

    Regardless of family form, there is a universal belief that one's family is the most powerful agent of socialization. A sample of 38 junior high school students from single parent and nuclear families completed a questionnaire in order to examine the relative effects of peer influence and family influence in single parent and nuclear families.…

  17. Family Systems and Fertility Intentions

    NARCIS (Netherlands)

    Mönkediek, Bastian; Bras, Hilde

    2017-01-01

    Family systems, as normative frameworks in which family processes unfold, are believed to exert a major influence on fertility. While a number of studies have addressed family system effects on family size and the timing of births, the question of how family systems influence fertility intentions

  18. The contribution of familiness to the performance of family businesses

    Directory of Open Access Journals (Sweden)

    W. P. Venter

    2004-12-01

    Full Text Available While family businesses are known to consistently outperform non-family businesses in financial terms over the long run, family businesses have received comparatively little attention from researchers. In this article an explanation is offered for this superior performance in the form of the concept of "familiness" - the unique contribution that family involvement brings to any business (which is divided into founder capital and family capital. It is explained that family businesses possess no general competitive advantage over non-family businesses. The unique strength of successful family businesses does not lie in their espoused advantages, but in their ability to sustain and adapt, through family capital, the culture created by the founder. An evolutionary conceptual model of the creation and transmission of familiness is provided to explain how this unique strength influences family business performance over the long run.

  19. Family Background and Entrepreneurship

    DEFF Research Database (Denmark)

    Lindquist, Matthew J.; Sol, Joeri; Van Praag, Mirjam

    Vast amounts of money are currently being spent on policies aimed at promoting entrepreneurship. The success of such policies, however, rests in part on the assumption that individuals are not ‘born entrepreneurs’. In this paper, we assess the importance of family background and neighborhood...... treatment within families by gender and birth order does little to further increase our estimates of the importance of family-wide factors. We then go on to show that neighborhood effects, sibling peer effects, and parental income and education explain very little of these correlations. Parental...

  20. The Family Saprospiraceae

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Nielsen, Per Halkjær

    2014-01-01

    The Saprospiraceae, a family within the order Sphingobacteriales and the phylum Bacteroidetes, embrace the genera Saprospira, Lewinella, Haliscomenobacter, Aureispira, ‘‘Rubidimonas,’’ and ‘‘Portibacter.’’ The composition of the family, and delineation of genera and species, is largely defined...... associated with predation of other bacteria and algae. Family members are likely important in the breakdown of complex organic compounds in the environment. Such a role is at least demonstrated in situ for activated sludge wastewater treatment systems where these organisms are frequently observed...

  1. Family Background and Entrepreneurship

    DEFF Research Database (Denmark)

    Lindquist, Matthew J.; Sol, Joeri; Van Praag, Mirjam

    Vast amounts of money are currently being spent on policies aimed at promoting entrepreneurship. The success of such policies, however, rests in part on the assumption that individuals are not ‘born entrepreneurs’. In this paper, we assess the importance of family background and neighborhood...... treatment within families by gender and birth order does little to further increase our estimates of the importance of family-wide factors. We then go on to show that neighborhood effects, sibling peer effects, and parental income and education explain very little of these correlations. Parental...

  2. Cloning and Expression of Metalloprotease Gene from Schistosoma japoncum and its Immunoprotective Efficiency%日本血吸虫金属蛋白酶基因的克隆和表达及其对小鼠的免疫保护性研究

    Institute of Scientific and Technical Information of China (English)

    徐斌; 鞠川; 卢艳; 莫筱谨; 冯正; 许学年; 胡薇

    2011-01-01

    Objective To clone and express a metalloprotease gene of Schistosoma japonicum, purify the expressed protein, and investigate the induced immune response in mice and its localization in the parasite. Methods Specific primers were designed according to the EST sequence and used for amplification of the encoding sequence from the S.japonicum cDNA clone containing S.japonicum metalloprotease. The gene was subcloned into pET-28a plasmid and expressed, and the recombinant protein was purified with HisoTag affinity chromatography. Western blotting was used to analyze the immunogenicity. Eighteen C57BC/6 mice were divided into two groups. Mice in group A were immunized each with 25 μg purified recombinant SjB04 at every 2 weeks for 3 times. Mice in group B received only adjuvant as control. Each mouse was challenged by (40±2) cercariae at the third week after the last immunization. Fecal samples were collected for 6 days from 37th days after challenge. Eggs per gram feces and rate of egg reduction were calculated. S.japonicum adult worms were collected from infected mice, and used for preparing frozen sections and indirect immunofluorescence staining with specific polyclone antibody to S. japonicum metalloprotease. Results The metalloprotease gene SjB04 was cloned, sequenced and expressed. The immuno-fluorescence localization showed that SjB04 protein distributed mainly in the intestinal epithelium of the adult worm. The recombinant protein was specifically recognized by the S. japonicum-infected rabbit sera, showing that the expressed product possessed antigenicity. Mice immunized with the recombinant protein revealed a reduction in numher of adult worms, eggs in feces by 27.1% and 57.8%,respectively. Conclusion The recombinant protein of' S.japonicum metalloprotease has been obtained with Mr 36500.The protein locates in the intestinal epithelium of adult worm. Immunization with the SjB04 protein induces significant reduction of fecal eggs.%目的 克隆和表达

  3. Family and non-family business differences in Estonia

    Directory of Open Access Journals (Sweden)

    Maret Kirsipuu

    2014-01-01

    Full Text Available This paper seeks to identify differences between family enterprises and non-family enterprises. The concepts of entrepreneurship, entrepreneur and enterprise/business are clarified. The paper contains the results of research conducted by the author among family entrepreneurs in 2007–2012 that can be compared to the research results reached by Wahl (2011. This research demonstrates that there are differences between family entrepreneurs and non-family entrepreneurs, which are primarily caused by that family entrepreneurs value first of all their family members, family traditions and only then profit earning.

  4. Everyday Family Life

    DEFF Research Database (Denmark)

    Westerling, Allan

    2010-01-01

    project takes a social psychological approach, combining quantitative and qualitative methods in a longitudinal study of family life. The knowledge interest of the project is the constitution of communality and individuality in everyday family life. This article presents the theoretical framework...... and the conceptualization of everyday family life of the social psychological research agenda in this field. The main line of argument is that ongoing modernization is synonymous with accelerated processes of detraditionalization and individualization. This calls for a re-conceptualisation of ‘the family’ which enables...... researchers to grasp both continuity and change. The article refers to everyday life studies and social psychology and argues that the term ‘family life’ my serve as one stepping stone for transgressing the dichotomy. Furthermore the article unfolds the implications of this framework for the research design...

  5. The Family Startup Program

    DEFF Research Database (Denmark)

    Trillingsgaard, Tea; Maimburg, Rikke Damkjær; Simonsen, Marianne

    2015-01-01

    Background: Inadequate parenting is an important public health problem with possible severe and long-term consequences related to child development. We have solid theoretical and political arguments in favor of efforts enhancing the quality of the early family environment in the population at large....../design: Participants will be approximately 2500 pregnant women and partners. Inclusion criteria are parental age above 18 and the mother expecting first child. Families are recruited when attending routine pregnancy scans provided as a part of the publicly available prenatal care program at Aarhus University Hospital...... and community resources. The program consists of twelve group sessions, with nine families in each group, continuing from pregnancy until the child is 15 months old. TAU is the publicly available pre- and postnatal care available to families in both conditions. Analyses will employ survey data, administrative...

  6. Familial Mediterranean Fever

    Science.gov (United States)

    ... don't use genetic tests as the sole method of diagnosing familial Mediterranean fever. There's no cure ... may be options, though these treatments are considered experimental. Other medications include rilonacept (Arcalyst) and anakinra (Kineret). ...

  7. Familial Adenomatous Polyposis

    Science.gov (United States)

    ... have a de novo (new) mutation in the APC gene. Most colorectal cancer is sporadic, meaning it occurs by chance, and ... a mutation in the APC gene. If an APC gene mutation is found, other family members may be ... tumor ...

  8. Familial Periodic Paralyses

    Science.gov (United States)

    ... and less severe than the hypokalemic form. Muscle spasms are common. × Definition Familial periodic paralyses are a ... and less severe than the hypokalemic form. Muscle spasms are common. View Full Definition Treatment Treatment of ...

  9. Children and Families: 1984?

    Science.gov (United States)

    Bronfenbrenner, Urie

    1981-01-01

    In order to develop normally, children need emotional involvement and shared activities with one or more adult(s). Public policy in the United States, unlike that of most industrialized societies, is not supportive of family life. (Author/GC)

  10. Unique Family Living Situations

    Science.gov (United States)

    ... be treated with medicine?ResourcesAmerican Academy of Child & Adolescent Psychiatry, Divorce and Children Last Updated: January 2017 This article was contributed by: familydoctor.org editorial staff Tags: Adolescent, child, Psychiatric and Psychologic Emotional Well-Being, Family ...

  11. Familial Pompe Disease

    National Research Council Canada - National Science Library

    Tecellioglu, Mehmet; Kamisli, Ozden

    2015-01-01

    .... We present a family with Pompe disease consisting of the asymptomatic mother and two siblings who presented with muscle weakness and respiratory failure and who had been followed-up with a diagnosis...

  12. Benign Familial Infantile Seizures

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-03-01

    Full Text Available The history, classification, clinical and EEG features, genetics, differential diagnosis, and outcome of “benign familial infantile seizures” (BFIS are reviewed from the Neurology Department, Bambino Gesu Children Hospital, Rome, Italy.

  13. Families talen en algebra

    NARCIS (Netherlands)

    Asveld, P.R.J.

    1976-01-01

    Operaties op formele talen geven aanleiding tot bijbehorende operatoren op families talen. Bepaalde onderwerpen uit de algebra (universele algebra, tralies, partieel geordende monoiden) kunnen behulpzaam zijn in de studie van verzamelingen van dergelijke operatoren.

  14. Homozygous familial hypercholesterolaemia

    Directory of Open Access Journals (Sweden)

    Dogra A

    1993-01-01

    Full Text Available A boy with multiple xanthomatosis with deranged lipid profile consistent with homozygous familial hypercholesterolaemia is reported for its rarity and exotic presentation and biochemical abnormalities of lipids in parents.

  15. Everyday Family Life

    DEFF Research Database (Denmark)

    Westerling, Allan

    2010-01-01

    What are the implications of ongoing processes of modernization and individualization for social relations in everyday life? This overall research question is the pivotal point in empirical studies at the Centre of Childhood-, Youth- and Family Life Research at Roskilde University. One research...... project takes a social psychological approach, combining quantitative and qualitative methods in a longitudinal study of family life. The knowledge interest of the project is the constitution of communality and individuality in everyday family life. This article presents the theoretical framework...... and the conceptualization of everyday family life of the social psychological research agenda in this field. The main line of argument is that ongoing modernization is synonymous with accelerated processes of detraditionalization and individualization. This calls for a re-conceptualisation of ‘the family’ which enables...

  16. Family Weight School treatment

    DEFF Research Database (Denmark)

    Nowicka, Paulina; Höglund, Peter; Pietrobelli, Angelo

    2008-01-01

    OBJECTIVE: The aim was to evaluate the efficacy of a Family Weight School treatment based on family therapy in group meetings with adolescents with a high degree of obesity. METHODS: Seventy-two obese adolescents aged 12-19 years old were referred to a childhood obesity center by pediatricians...... and school nurses and offered a Family Weight School therapy program in group meetings given by a multidisciplinary team. Intervention was compared with an untreated waiting list control group. Body mass index (BMI) and BMI z-scores were calculated before and after intervention. RESULTS: Ninety percent...... group with initial BMI z-score 3.5. CONCLUSIONS: Family Weight School treatment model might be suitable for adolescents with BMI z...

  17. Asbestos: Protect Your Family

    Science.gov (United States)

    ... Related Topics: Asbestos Contact Us Share Protect Your Family How to Identify Materials That May Contain Asbestos ... Improper removal may actually increase your and your family’s exposure to asbestos fibers. Top of Page Asbestos ...

  18. 5. Natural Family Planning

    African Journals Online (AJOL)

    Sitwala

    influencing utilization of Natural Family Planning .... Because of the potential benefits of FP, it is important to any community ... Data was collected over a period of 4 months after approval ..... The DHMT to educate parents on the importance of.

  19. Family Demands, Social Support and Family Functioning in Taiwanese Families Rearing Children with Down Syndrome

    Science.gov (United States)

    Hsiao, C-Y.

    2014-01-01

    Background: Down syndrome (DS) affects not only children but also their families. Much remains to be learned about factors that influence how families of children with DS function, especially families in non-Western populations. The purpose of this cross-sectional, correlational study was to examine how family demographics, family demands and…

  20. Family Demands, Social Support and Family Functioning in Taiwanese Families Rearing Children with Down Syndrome

    Science.gov (United States)

    Hsiao, C-Y.

    2014-01-01

    Background: Down syndrome (DS) affects not only children but also their families. Much remains to be learned about factors that influence how families of children with DS function, especially families in non-Western populations. The purpose of this cross-sectional, correlational study was to examine how family demographics, family demands and…

  1. Familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen

    1989-01-01

    of frequent occurrence of premalignant duodenal adenomas. The prognosis is good after prophylactic colectomy in patients without carcinoma. All first degree relatives of affected family members should be examined regularly with proctosigmoidoscopy from the age of ten, and prophylaxis should be organised using...... a national or regional polyposis register. The recent detection of a specific gene for familial adenomatous polyposis is a long step forward, and several problems may be solved by increasing international cooperation....

  2. WOMEN IN FAMILY BUSINESS

    OpenAIRE

    Anshu,

    2012-01-01

    The role of women in family businesses is explored in the paper. Although recognized as generally very important players, the role of women is often defined as invisible in business decision-making, supportive in men’s traditional business domains and only rarelyadequately recognized and rewarded. The paper explores possible differences in the views of men and women who manage small family firms. Their attitudes opposing the traditional business roles ofwomen, different views on managerial, o...

  3. Fixpoints vs Moore Families

    DEFF Research Database (Denmark)

    Zhang, Fuyuan; Nielson, Flemming; Nielson, Hanne Riis

    2012-01-01

    of a CTL formula can be described as the least element in a Moore family of acceptable sets of states for the static analysis. Turning the attention to the μ-calculus we are able to generalise this result to the alternation-free fragment whereas even for the fragment of alternation depth 2 we show...... that the fixed point characterisation cannot be recast as a Moore family property....

  4. Familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen

    1989-01-01

    Familial adenomatous polyposis is an autosomal dominant disease that includes early development of up to thousands of colorectal adenomas and several extracolonic manifestations. All untreated patients will develop colorectal adenocarcinoma. The treatment of choice is colectomy and ileorectal ana...... a national or regional polyposis register. The recent detection of a specific gene for familial adenomatous polyposis is a long step forward, and several problems may be solved by increasing international cooperation....

  5. Myth of the Perfect Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share The "Perfect" Family Page Content Article Body Is there such a ...

  6. Familial gastric cancer

    Directory of Open Access Journals (Sweden)

    Bresciani Cláudio

    2003-01-01

    Full Text Available BACKGROUND: Familial aggregation of gastric cancer has pointed out to a possible hereditary and genetic factor involved in the carcinogenesis of this disease. The diffuse type gastric cancer patients are frequently younger and the tumor has locally infiltrative growth pattern early in its development. Observation of families with frequent early onset gastric cancer has led to the identification of a novel gene implicated in gastric cancer susceptibility: CDH1/E-cadherin. Diffuse familiar gastric cancer is defined as any family presenting: two first-degree relatives with diffuse gastric cancer, one of them with age under 50 years or at least 3 first-degree relatives irrespective age of onset. CASE REPORT: The family reported by us does not fit in any of the classification proposed. The precise identification of these families by clinical and molecular tools is of great importance. The case reported is an example of a family that probably is a form of hereditary gastric cancer not yet fully understood. CONCLUSION: Soon there will be new criteria, possibly including genetic and molecular characteristics.

  7. [Family, Suicide and Mourning].

    Science.gov (United States)

    Garciandía Imaz, José Antonio

    2013-01-01

    Death is an event that always breaks into family life in a surprising way. Of all the deaths, suicide is the one which more strongly questions the functionality of a family and increases the risk of difficulties in the mourning process. Families in which a suicide has occurred are exposed to a greater possibility of disintegration, disorganization and pathological expressions in their members. To present a reduced and circumscribed narrative revision, restricted to examine the relationship between suicide and the mourning process in the family. The suicide of a loved one is an event that may contribute to pathological grief and mental dysfunctions in surviving relatives. Death in the family is a natural phenomenon. However, death by suicide is one of the phenomena that can generate more alterations in the structure and organization of the family, due to the difficulty related to the mourning process. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  8. Familial Fahr disease in a Turkish family.

    Science.gov (United States)

    Kotan, Dilcan; Aygul, Recep

    2009-01-01

    Fahr syndrome refers to a rare syndrome characterized by symmetrical and bilateral intracranial calcification. We present a 42-year-old woman with Fahr disease, but lacking extrapyramidal symptoms or a metabolic disorder. Her neurological examination was normal. Computed tomographic scans demonstrated symmetrical calcification over the basal ganglia, thalamus and cerebellum. No underlying cause for the bilateral calcification was found. When screening other family members, we detected Fahr syndrome in her two daughters and three brothers, revealing that the disease was an autosomal dominant trait. Fahr disease may be clinically asymptomatic, but have pronounced positive brain imaging findings. Computed tomographic scanning remains the most effective screening tool for adult relatives.

  9. The intersubjectivity of family consumption

    DEFF Research Database (Denmark)

    Linnet, Jeppe Trolle

    This study of everyday consumption is based on an ethnographic fieldwork conducted among four Danish middle-class families in Copenhagen, from which an illustrative example of family car purchase is drawn. By introducing two new concepts to the study of family consumption; intra-family consumer...... identity and family scape, I analyze how family members negotiate purchase decisions, and relate to each other’s preferences and desires, as well as those of other families. I consider how family members' interrelations as consumers and long-term negotiations over symbolic meanings of consumption...

  10. Changing families, changing workplaces.

    Science.gov (United States)

    Bianchi, Suzanne M

    2011-01-01

    American families and workplaces have both changed dramatically over the past half-century. Paid work by women has increased sharply, as has family instability. Education-related inequality in work hours and income has grown. These changes, says Suzanne Bianchi, pose differing work-life issues for parents at different points along the income distribution. Between 1975 and 2009, the labor force rate of mothers with children under age eighteen increased from 47.4 percent to 71.6 percent. Mothers today also return to work much sooner after the birth of a child than did mothers half a century ago. High divorce rates and a sharp rise in the share of births to unmarried mothers mean that more children are being raised by a single parent, usually their mother. Workplaces too have changed, observes Bianchi. Today's employees increasingly work nonstandard hours. The well-being of highly skilled workers and less-skilled workers has been diverging. For the former, work hours may be long, but income has soared. For lower-skill workers, the lack of "good jobs" disconnects fathers from family obligations. Men who cannot find work or have low earnings potential are much less likely to marry. For low-income women, many of whom are single parents, the work-family dilemma is how to care adequately for children and work enough hours to support them financially. Jobs for working-class and lower middle-class workers are relatively stable, except in economic downturns, but pay is low, and both parents must work full time to make ends meet. Family income is too high to qualify for government subsidized child care, but too low to afford high-quality care in the private market. These families struggle to have a reasonable family life and provide for their family's economic well-being. Bianchi concludes that the "work and family" problem has no one solution because it is not one problem. Some workers need more work and more money. Some need to take time off around the birth of a child

  11. Family planning Indonesia.

    Science.gov (United States)

    Singarimbun, M

    1968-06-01

    The growth of family planning activities in Indonesia in the Postwar period is traced; and future prospects for family planning are assessed. Transmigration projects initiated by the Dutch and supported by President Sukarno after Indonesian independence as a means of decreasing population pressure on the island of Java, are identified as the only official response to the population problem until 1965. In the face of the government's opposition to the idea of birth control as a population control measure, the activities of the Indonesian Planned Parenthood Association (IPPA) after its founding in 1957 were limited to advising mothers on spacing of their children for health reasons. Statements made in support of a national family planning program by government officials at a 1967 IPPA Congress and on other occasions are noted. The major components of an approved national family planning program to start in 1969 are described. However, the government's policy as of late 1967 and early 1968 is characterized as one of mainly benevolent encouragement and help to voluntary organizations. The chief impediment to family planning in Indonesia is said to be a lack of motivation and the force of traditional values that favor large families. On the positive side are: 1) Studies showing considerable interest in birth control by the rural population; 2) A long history of traditional birth control practices; 3) The absence of outright opposition by religious groups to the principle of family planning. However, financial costs, the need for the training of personnel, and a general unawareness of the magnitude of the task lying ahead constitute other formidable obstacles.

  12. Cardiomyopathy, familial dilated

    Directory of Open Access Journals (Sweden)

    Mestroni Luisa

    2006-07-01

    Full Text Available Abstract Dilated cardiomyopathy (DCM is a heart muscle disease characterized by ventricular dilatation and impaired systolic function. Patients with DCM suffer from heart failure, arrhythmia, and are at risk of premature death. DCM has a prevalence of one case out of 2500 individuals with an incidence of 7/100,000/year (but may be under diagnosed. In many cases the disease is inherited and is termed familial DCM (FDC. FDC may account for 20–48% of DCM. FDC is principally caused by genetic mutations in FDC genes that encode for cytoskeletal and sarcomeric proteins in the cardiac myocyte. Family history analysis is an important tool for identifying families affected by FDC. Standard criteria for evaluating FDC families have been published and the use of such criteria is increasing. Clinical genetic testing has been developed for some FDC genes and will be increasingly utilized for evaluating FDC families. Through the use of family screening by pedigree analysis and/or genetic testing, it is possible to identify patients at earlier, or even presymptomatic stages of their disease. This presents an opportunity to invoke lifestyle changes and to provide pharmacological therapy earlier in the course of disease. Genetic counseling is used to identify additional asymptomatic family members who are at risk of developing symptoms, allowing for regular screening of these individuals. The management of FDC focuses on limiting the progression of heart failure and controlling arrhythmia, and is based on currently accepted treatment guidelines for DCM. It includes general measures (salt and fluid restriction, treatment of hypertension, limitation of alcohol intake, control of body weight, moderate exercise and pharmacotherapy. Cardiac resynchronization, implantable cardioverter defibrillators and left ventricular assist devices have progressively expanding usage. Patients with severe heart failure, severe reduction of the functional capacity and depressed

  13. Familial pancreatic cancer.

    Science.gov (United States)

    Klein, A P; Hruban, R H; Brune, K A; Petersen, G M; Goggins, M

    2001-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.

  14. 85例孕早期妇女解整合素-金属蛋白酶12分析%Analysis on disintegrin- metalloprotease 12 in 85 women during the first trimester of pregnancy

    Institute of Scientific and Technical Information of China (English)

    许飞; 郭彩琴; 许婷殊; 王峻峰; 陈道桢

    2011-01-01

    目的:探讨解整合素-金属蛋白酶12(ADAM12)在孕早期妇女中不同孕周的正常参考值范围,为孕早期产前筛查胎儿唐氏综合征提供实验室依据.方法:收集2008年6月~2009年6月在无锡市妇幼保健院自愿参加孕早期产前筛查的孕妇静脉血血清样本共85份,-70℃保存,孕周为5~10周,常规三联产前筛查采用Wallac产筛软件,ADAM12水平检测采用时间分辨荧光免疫法,用SPSS11.5统计软件、Microsoft Excel软件对结果进行分析.结果:孕早期妇女ADAM12检测结果因孕周而异,本研究孕5周共10例,ADAM12平均值为5.68 ng/ml;孕6周共19例,ADAM12平均值为7.29 ng/ml;孕7周共26例,ADAM12平均值为70.64ng/ml;孕8周共16例,ADAM12平均值为89.40ng/ml;孕9周共10例,ADAM12平均值为111.91 ng/ml;孕10周共9例,ADAM12平均值为139.76 ng/ml.ADAM12水平随孕周增加而升高,并因孕周不同呈相关性,P<0.05,但孕早期ADAM12水平整体偏低.结论:ADAM12在孕早期是一种有效的筛查指标,可为提前诊断唐氏综合征提供实验室依据,但目前因标本量不够大,尚不具备条件建立孕早期ADAM12的正常参考值范围.%Objective: To explore the normal reference range of disintegrin - metalloprotease 12 (ADAM12) in pregnant women during the first trimester of pregnancy of different gestational weeks, provide laboratory evidence for prenatal screening of fetal Down's syndrome during the first trimester of pregnancy.Methods: 85 serum samples from venous blood of pregnant women who received prenatal screening voluntarily during the first trimester of pregnancy in the hospital from June 2008 to June 2009 were collected and reserved in - 70℃, the gestational weeks of the pregnant women were from 5 to 10 gestational weeks, routine trigeminal prenatal screening was conducted by Wallae software, time - resolved fluorescence immunoassay was used to detect the level of ADAM12; SPSS11.5 software and Microsoft Excel software were used for

  15. Opportunity NYC--Family Rewards: Qualitative Study of Family Communication

    Science.gov (United States)

    Fraker, Carolyn A.; Greenberg, David

    2011-01-01

    Aimed at low-income families in six of New York City's highest-poverty communities, the Family Rewards program ties cash rewards to a pre-specified set of activities. This paper presents the qualitative findings from interviews with 77 families. It examines how families incorporated the program into their households, and specifically the…

  16. Engaging Families in In-Home Family Intervention

    Science.gov (United States)

    Thompson, Ronald W.; Koley, Sarah

    2014-01-01

    Boys Town has created a program called In-Home Family Services to deliver help to families in stress. In-home family intervention programs have become widely used to help more families who are at risk and experiencing difficulties with a wide range of problems including domestic violence, child behavior problems, parent-child and family…

  17. Acculturation gaps in Vietnamese immigrant families: Impact on family relationships

    OpenAIRE

    Ho, Joyce; Birman, Dina

    2010-01-01

    Vietnamese immigrants in the United States face acculturation challenges involving the individual, family, and community. Experts suggest that immigrant family members acculturate at different rates resulting in an acculturation gap, which negatively influences family adjustment. In this study we examined the degree and patterns of acculturation differences between 104 first generation immigrant Vietnamese adolescents and their parents, and whether acculturation gap affected family relationsh...

  18. Family environment patterns in families with bipolar children.

    Science.gov (United States)

    Belardinelli, Cecilia; Hatch, John P; Olvera, Rene L; Fonseca, Manoela; Caetano, Sheila C; Nicoletti, Mark; Pliszka, Steven; Soares, Jair C

    2008-04-01

    We studied the characteristics of family functioning in bipolar children and healthy comparison children. We hypothesized that the family environment of bipolar children would show greater levels of dysfunction as measured by the Family Environment Scale (FES). We compared the family functioning of 36 families that included a child with DSM-IV bipolar disorder versus 29 comparison families that included only healthy children. All subjects and their parents were assessed with the K-SADS-PL interview. The parents completed the FES to assess their current family functioning. Multivariate analysis of variance was used to compare the family environment of families with and without offspring with bipolar disorder. Parents of bipolar children reported lower levels of family cohesion (pparents with no bipolar children. Secondary analyses within the bipolar group revealed lower levels of organization (p=0.031) and cohesion (p=0.014) in families where a parent had a history of mood disorders compared to families where parents had no history of mood disorders. Length of illness in the affected child was inversely associated with family cohesion (r=-0.47, p=0.004). Due to the case-control design of the study, we cannot comment on the development of these family problems or attribute their cause specifically to child bipolar disorder. Families with bipolar children show dysfunctional patterns related to interpersonal interactions and personal growth. A distressed family environment should be addressed when treating children with bipolar disorder.

  19. Engaging Families in In-Home Family Intervention

    Science.gov (United States)

    Thompson, Ronald W.; Koley, Sarah

    2014-01-01

    Boys Town has created a program called In-Home Family Services to deliver help to families in stress. In-home family intervention programs have become widely used to help more families who are at risk and experiencing difficulties with a wide range of problems including domestic violence, child behavior problems, parent-child and family…

  20. Acculturation gaps in Vietnamese immigrant families: Impact on family relationships

    OpenAIRE

    Ho, Joyce; Birman, Dina

    2010-01-01

    Vietnamese immigrants in the United States face acculturation challenges involving the individual, family, and community. Experts suggest that immigrant family members acculturate at different rates resulting in an acculturation gap, which negatively influences family adjustment. In this study we examined the degree and patterns of acculturation differences between 104 first generation immigrant Vietnamese adolescents and their parents, and whether acculturation gap affected family relationsh...

  1. Use of family management styles in family intervention research.

    Science.gov (United States)

    Alderfer, Melissa A

    2006-01-01

    Family management styles (FMSs) explain some of the complexities embedded in a family with a child who has chronic illness. The FMS typologies provide descriptions of family adjustment and management of care. These 5 distinct patterns may be valuable in tailoring and evaluating family interventions in research.

  2. 75 FR 9247 - Single Family Mortgage Insurance Premium, Single Family

    Science.gov (United States)

    2010-03-01

    ... URBAN DEVELOPMENT Single Family Mortgage Insurance Premium, Single Family AGENCY: Office of the Chief... the Single Family Premium Collection Subsystem-Upfront (SFPCS-U) to remit the upfront premium to... manage and process upfront single family mortgage insurance premium collections and corrections to submit...

  3. Education, Parenting and Family: The Social Geographies of Family Learning

    Science.gov (United States)

    Wainwright, Emma; Marandet, Elodie

    2017-01-01

    This paper explores the relationship between education, parenting and family through the prism and particularities of family learning. Family learning is an example of an educational initiative, primarily aimed at parents and linked to wider policy concerns, which can be explored through a mapping of its social geographies; family learning is…

  4. Sustainability of Rural Family Enterprises

    Directory of Open Access Journals (Sweden)

    Maret Kirsipuu

    2012-12-01

    Full Text Available Family enterprises have been researched in traditional, stable market economies, to a lesser extent also in former socialist economies. A special focus has been on family enterprises’ sustainability and it has been discovered that one of the main pain spots is the change of generation related problems. Family enterprises can be sustainable only when they are prepared for a generation change. Family business culture and family traditions in Estonia have been broken. After Estonia regained independence in 1991, entrepreneurs started to restore previous farms and wished to continue family traditions of their ancestors; entrepreneurship started to develop and many people, especially in rural areas, started a family business. In 2012, these family entrepreneurs have a choice to make how to ensure that their family business will stay sustainable, how to pass family business over to their descendants so that the family business traditions won’t cease. This paper seeks to analyse factors that inhibit sustainability of family enterprises. The data sources are special scientific literature and the questionnaire surveys and interviews with family entrepreneurs conducted by the author over 2007−2011. It is possible to ensure that a family enterprise is sustainable only when the family entrepreneurs are prepared for the generation change. The present and future family entrepreneurs in Estonia can get information from this paper about the problems that may arise in connection with the generation change and knowledge to ensure sustainability of their family business.

  5. WOMEN IN FAMILY BUSINESS

    Directory of Open Access Journals (Sweden)

    Mr Anshu

    2012-04-01

    Full Text Available The role of women in family businesses is explored in the paper. Although recognized as generally very important players, the role of women is often defined as invisible in business decision-making, supportive in men’s traditional business domains and only rarelyadequately recognized and rewarded. The paper explores possible differences in the views of men and women who manage small family firms. Their attitudes opposing the traditional business roles ofwomen, different views on managerial, ownership and transition issues and possible gender discrimination are examined. The findings support the paradigm of a different, more feminine style of management, while signs of discrimination are not clearly revealed. This paper is based on a research intended to provide acomparative analysis of the status of women entrepreneurs and men entrepreneurs in Family Business in India. It first draws demographic & psychographic profiles of women and men entrepreneurs in family business, identifies & addresses operational problems faced by women and men entrepreneurs in family business, draws theirinclination for future plans for growth and expansion and also for the furtherance of research on women entrepreneurs in India.

  6. Familial pituitary adenomas.

    Science.gov (United States)

    Vandeva, S; Vasilev, V; Vroonen, L; Naves, L; Jaffrain-Rea, M-L; Daly, A F; Zacharieva, S; Beckers, A

    2010-12-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas.

  7. [The LDL receptor family].

    Science.gov (United States)

    Meilinger, Melinda

    2002-12-29

    The members of the LDL receptor family are structurally related endocytic receptors. Our view on these receptors has considerably changed in recent years. Not only have new members of the family been identified, but also several interesting observations have been published concerning the biological function of these molecules. The LDL receptor family members are able to bind and internalize a plethora of ligands; as a consequence, they play important roles in diverse physiological processes. These receptors are key players in the lipoprotein metabolism, vitamin homeostasis, Ca2+ homeostasis, cell migration, and embryonic development. Until recently, LDL receptor family members were thought to be classic endocytic receptors that provide cells with metabolites on one hand, while regulating the concentration of their ligands in the extracellular fluids on the other hand. However, recent findings indicate that in addition to their cargo transport function, LDL receptor family members can act as signal transducers, playing important roles in the development of the central nervous system or the skeleton. Better understanding of physiological and pathophysiological functions of these molecules may open new avenues for the treatment or prevention of many disorders.

  8. Family focused nursing education

    Directory of Open Access Journals (Sweden)

    R. A. E. Thompson

    1993-05-01

    Full Text Available At the present time the majority of nurse education programmes are firmly tied to the perspectives of curative medicine within hospitals - they are disease and hospital oriented. This model, which indicates a 'sickness’ concept of nursing is entirely inappropriate if contemporary and future health care needs are to be met. The shift in education should be towards a health, family and whole person centered approach. The family is the most fundamental and dynamic unit in society with a profound influence upon its members. Besides performing a variety of other functions, the family has a central role in promoting and maintaining the health of its members. Because the family unit is the microcosm of society and accurately reflects the needs of society at large it is appropriate that this should be a key area of experience. Family attachments during training provide opportunities for close and committed contact with people in their everyday world and for learning what is really important to them.

  9. Understanding Family Interaction Patterns in Families With Alzheimer's Disease.

    Science.gov (United States)

    Schaber, Patricia; Blair, Kate; Jost, Ellen; Schaffer, Molly; Thurner, Emily

    2016-01-01

    This qualitative study explores the dynamic changes that occur in family interaction patterns when Alzheimer's disease is present. Semi-structured interviews were conducted with 15 participants who have a family member with the disease. Using modified analytic induction, guided by the dimensions of the Family Fundamental Interpersonal Relations Orientation (FIRO) Model, participants shared how Alzheimer's disease affected family structure, control dynamics, and intimacy among family members. Findings demonstrate that (a) families reorganize and restructure based on geographic proximity and shifting roles, act out of filial responsibility, and strive to preserve shared meanings and rituals; (b) decision making increases around care of the person with Alzheimer's disease and shifts to the primary caregiver or other family members based on their abilities; and (c) expressions of intimacy intensify while personality is preserved in the person with the disease. The Family FIRO model can inform practitioners using family-centered care with families with Alzheimer's disease.

  10. Understanding family member suicide narratives by investigating family history.

    Science.gov (United States)

    Ratnarajah, Dorothy; Maple, Myfanwy; Minichiello, Victor

    2014-01-01

    The complex family environments in which a suicide death had previously occurred were explored in a qualitative study of narratives of suicide-bereaved participants. The participants searched for reasons why the suicide occurred in their family. Family patterning stories and the context of the environment in which the suicide death occurred provided an additional depth of meaning into the relational aspects of the family. Fractured families emerged as an important theme. Shared in the narratives were stories of conditions within the family that may have contributed to vulnerability towards persistent negative feelings about their lives, their family, and their future. The study also identifies the strengths of family culture that led to resilience in the suicide bereaved. These stories highlight the importance of support for those bereaved by the suicide of a close family member and the issues that places people in vulnerable situations that perhaps may explain the increased risk of suicide for those bereaved family members.

  11. Fostering families' and children's rights to family connections.

    Science.gov (United States)

    Landsman, Miriam J; Boel-Studt, Sharma

    2011-01-01

    Recent federal legislation strengthens children's and families' rights to family-centered practice by increasing the responsibility of child welfare agencies to identify and engage extended family members in providing care and support to children placed out of the home. Preliminary results from an experimental study of a federally funded family finding project found greater involvement of family, kin, and informal supports and a higher likelihood of reunification or relative placement compared with standard child welfare services.

  12. Dignifying families at risk

    DEFF Research Database (Denmark)

    Villumsen, Anne Marie Anker

    2017-01-01

    Workshop på konference: Through the voices of families at risk, the aim of the presentation is to display how a change in caseworker approach and municipal organization can dignify families at risk and create change in the families’ experiences of collaboration, agency and of self. Qualitative...... adult who handles the financials and one (or more) from child protection. Most likely, the several different caseworkers from different departments are combined with different professionals related to the different initiatives launched by the different departments. Therefore, it is not unrealistic...... measures the idea is to enable these families away from being at risk. Grad af anerkendelse: International Links: http://ifsweurope2017.yourhost.is/workshops/...

  13. Families from Supergroups

    CERN Document Server

    Barr, S M

    2016-01-01

    As was shown in 1984 by Caneschi, Farrar, and Schwimmer, decomposing representations of the supergroup SU(M|N), can give interesting anomaly-free sets of fermion representations of SU(M) x SU(N) x U(1). It is shown here that such groups can be used to construct realistic grand unified models with non-abelian gauged family symmetries. A particularly simple three-family example based on SU(5) x SU(2) x U(1) is studied. The forms of the mass matrices, including that of the right-handed neutrinos, are determined in terms of SU(2) Clebsch coefficients. Models of this type would have a rich phenomenology if part of the family symmetry is broken near the electroweak scale.

  14. Familial gigantiform cementoma

    Energy Technology Data Exchange (ETDEWEB)

    Han, Won Jeong; Kim, Eun Kyung [Dankook Univ. School of Dentistry, Seoul (Korea, Republic of)

    2006-09-15

    Familial gigantiform cementoma is a rate fibro-cemento-osseous disease of the jaws which appears to be transmitted as an autosomal dominant trait with variable expressivity of the phenotype. A 7-year-old girl visited DKUDH complaining of the painless facial deformity. Clinically, significant facie-lingual expansion was observed at the left maxilla, left mandibular body and symphysis portion. Malposition of lower anterior teeth was found. Panoramic radiograph and CT scan showed the extensive expandile mixed lesion at maxilla and mandible. Bone scan revealed hot spot at the maxilla and left side of mandible. Histologic examination revealed moderately dense fibrous connective tissue with scattered masses resembling cementum. The patient's mother had a history of the mandibular resection due to benign tumor. Her younger brother had buccal expansion of right mandible. We report our finding of a family that has exhibited clinical, radiographic and histologic findings consistent with the familial gigantiform dementoma.

  15. Innovation in Family Firms

    DEFF Research Database (Denmark)

    Filser, Matthias; Brem, Alexander; Gast, Johanna

    2016-01-01

    Over the past decade, research on innovation in family firms has received growing attention by scholars and practitioners around the globe with a wide range of aspects explored within the current body of literature. Despite the constantly growing number of scientific publications, research lacks...... a comprehensive and critical review of past and present research achievements. First, conducting a bibliometric analysis with a focus on innovation in family firms, we identify five topical clusters that help to understand the foundations of recent findings: namely ownership and governance, structural settings......, organizational culture and behaviour, resources, and innovation and strategy. Second, based on a thorough literature review the major research avenues are reflected. The comparison of the results of both analyses showed the following areas for future research on family firm innovation: members‘ individual human...

  16. Family ties and residential locations

    NARCIS (Netherlands)

    Mulder, C.H.; Cooke, T.J.

    2009-01-01

    In this paper, and in the Special Issue it introduces, the focus is on the role of family ties in residential location choice and, conversely, the role of residential locations in maintaining family ties. Not only do events in the nuclear family trigger residential relocations, but nearby family mem

  17. Gendered Discourse about Family Business

    Science.gov (United States)

    Danes, Sharon M.; Haberman, Heather R.; McTavish, Donald

    2005-01-01

    Language patterns of family business owners were explored by identifying discourse styles and emphasized ideas in four presenting contexts: business, family, intersection of family and business, and business success. The content analysis supports the existence of a general discourse style within family businesses and of similarities and…

  18. 75 FR 63753 - Family Offices

    Science.gov (United States)

    2010-10-18

    ... family, provides advice to a broader group of clients and much more resembles the business model common... investment advisory business, and not a family managing its own wealth. 2. Ownership and Control We propose... feature helped distinguish these family offices from the family-run investment advisory businesses...

  19. The intersubjectivity of family consumption

    DEFF Research Database (Denmark)

    Linnet, Jeppe Trolle

    This study of everyday consumption is based on an ethnographic fieldwork conducted among four Danish middle-class families in Copenhagen, from which an illustrative example of family car purchase is drawn. By introducing two new concepts to the study of family consumption; intra-family consumer...

  20. APPROACH TO SMALL FAMILY NORM

    Directory of Open Access Journals (Sweden)

    Nonibala

    2014-09-01

    Full Text Available The Idea of approach to maintain small family norm in the family and so to the society is the hope for almost all of the couples as the saying -"Small family is a happy family". And every couple always thinks and plan for a safer and better future.

  1. APPROACH TO SMALL FAMILY NORM

    OpenAIRE

    Nonibala

    2014-01-01

    The Idea of approach to maintain small family norm in the family and so to the society is the hope for almost all of the couples as the saying -"Small family is a happy family". And every couple always thinks and plan for a safer and better future.

  2. FAMily-Oriented Support (FAMOS)

    DEFF Research Database (Denmark)

    Salem, Hanin; Johansen, Christoffer; Schmiegelow, Kjeld

    2017-01-01

    by tracking procedures and parents’ evaluations. Results: A total of 68 families (68 mothers, 60 fathers, 68 children with cancer and 73 siblings) were enrolled, with a participation rate of 62% of families. Fathers were highly represented (88% of families); also families with single parents (12%) and parents...

  3. The Economy, Families and Schools

    Science.gov (United States)

    Williamson, Ronald

    2010-01-01

    The recession has impacted American families and the schools their children attend like nothing in recent memory. Many families continue to struggle with the impact of joblessness. The number of homeless children and youth is staggering. Families struggle with access to health care, growing hunger and greater instability in the family unit.…

  4. 解密"family"

    Institute of Scientific and Technical Information of China (English)

    王松海

    2009-01-01

    @@ 小朋友们,你一定熟悉"family"这个单词吧,它的意思是"家,家庭".提起它,你是否会想到自己的爸爸和妈妈呢?为什么?因为"family"这个单词本身就包含了爸爸和妈妈,而且还表达了对他们的爱呢!下面就听我细细地为你解读吧!

  5. My Family s Looks

    Institute of Scientific and Technical Information of China (English)

    侯耀南

    2006-01-01

    I have a happy family.There are three people in my family: My mother, my father and I. Let me tell you about my family’s looks: My father has short straight hair and bright black eyes. He is medium build and he is very tall. He is such a good teacher that all of us love and respect him. He likes telling jokes. He never stops talking. I love my hand- some father just because he loves me. My mother is a kind and gentle woman. She has long curly fair hair. She is tall and slim. I think she is beautiful. But no...

  6. FAMILY DISORGANISATION AND CHILDREN

    OpenAIRE

    Dr. V.N. Sreekumar

    2017-01-01

    Abstract                           The family is based on and supports primary relations. It provides Very serious especially if the parents don't get along, Insecurity, instability, problems in school, at home, etc. Counseling is always helpful, someone non-biased so the child feels they can trust someone. Children that come from broken families will most likely have a difficult time in life, struggle and turn to drug abuse or other negative behavior. Some kids get made fun of and have ...

  7. Familial hemicrania continua.

    Science.gov (United States)

    Weatherall, Mark W; Bahra, Anish

    2011-01-01

    There are now three known causative genes for familial hemiplegic migraine and increasing evidence to support a genetic predisposition to the more common types of migraine with and without aura, and for cluster headache. We present the first reported case of familial hemicrania continua. A mother and daughter developed hemicrania continua at the same time of life. Both showed an absolute response to indometacin and at similar doses. Both also suffered from migraine with aura. We discuss the increasing support for a genetic predisposition to dysfunction of the pain system within the brain manifesting as primary headache.

  8. Contemporary family life

    DEFF Research Database (Denmark)

    Viala, Eva Silberschmidt

    2011-01-01

    Based on a longitudinal interview-study of ten heterosexual couples and first-time parents, in Denmark the author argues that addressing contemporary everyday family life as a joint venture with contradictions contribute new insights into the complexities, contradictions, and ambiguities linked...... of complementary gender roles as well as in new understandings of gender equality based on ideals of mutual trust, respect and support. As a result, it is important to investigate how parenthood, family life and parental roles are constantly reflected upon and reproduced, negotiated and transformed through...

  9. OCULAR COLOBAMATA IN A FAMILY

    Directory of Open Access Journals (Sweden)

    Sheetal

    2015-04-01

    Full Text Available AIM: To identify the proportion of cases affected in a family with ocular colobamata . MATERIAL: Ocular colobomata present in a family METHOD: Visual acuity, Slit lamp examination, Ophthalmoscopy, Fundus Photography, B - Scan, Family members were examined. RESULTS: Family showed poor visual acuity, Iris and Choridal Coloboma without optic disc involvement and normal corneal diameter. CONCLUSION: Ocular coloboma occurring in patients of my study is family and genetically determined.

  10. Another way to teach family: family nursing game

    Directory of Open Access Journals (Sweden)

    Carla Sílvia Neves da Nova Fernandes

    2014-10-01

    Full Text Available Current paper describes the application of an innovative strategy to teach family, within a hospital context, by sensitizing nurses on the family subject through the use of a game. Given the hospitalization of a relative, the family faces changes in its dynamics caused by the crisis it is exposed to. It is the relevance for including the family within the care process. Since nurses are expected to assume a key role for which they need specific competence to intervene in families when experiencing an eventual crisis. The in-service education becomes a strategy of generating new skills and enhances human capital to improve the quality of nursing care. Considering the importance of including family in the care context, a playful tool called Family Nursing Game has been invented for teaching the family, especially by passing a model of family intervention. The strategy is based on the belief of the existence of relationship between game and learning.

  11. Crowding and Family Relations

    Science.gov (United States)

    Booth, Alan; Edwards, John N.

    1976-01-01

    The effect of household and neighborhood crowding on the relations between spouses, those between parents and children, and the relations among children are examined; a sample of urban families residing in conditions ranging from open to highly compressed provided the data for the investigation and multiple regression was used to analyze the…

  12. Serving Migrant Families, 1975.

    Science.gov (United States)

    Oliver, Barbara, Ed.

    The directory describes services provided to migratory agricultural workers and their families, through the governmental and nongovernmental agencies interested in and responsible for their well-being. Agencies are grouped into: (1) United States government agencies, (2) North Carolina State government agencies, and (3) private organizations.…

  13. Family Sequencing and Cooperation

    NARCIS (Netherlands)

    Grundel, S.; Ciftci, B.B.; Borm, P.E.M.; Hamers, H.J.M.

    2012-01-01

    To analyze the allocation problem of the maximal cost savings of the whole group of jobs, we define and analyze a so-called corresponding cooperative family sequencing game which explicitly takes into account the maximal cost savings for any coalition of jobs. Using nonstandard techniques we prove t

  14. Families of Parabolas.

    Science.gov (United States)

    Owens, John E.

    1992-01-01

    Explores families of parabolas that result from the graphs of quadratic functions. Computer software allows students to quickly depict a series of graphs and make conjectures about emerging patterns. Discusses cases in different parameters in the quadratic are varied to produce different effects in which the parabolas. (MDH)

  15. It Takes a Family

    Centers for Disease Control (CDC) Podcasts

    2007-11-01

    This podcast follows an African American man with diabetes and his family as they discuss living healthfully with diabetes.  Created: 11/1/2007 by National Diabetes Education Program (NDEP), a joint program of the Centers for Disease Control and Prevention and the National Institutes of Health.   Date Released: 11/12/2007.

  16. Family Feathers. [Videotape Series].

    Science.gov (United States)

    1999

    Family Feathers is a set of 18 videotapes for parents of preschool children, created by the Alaska Native Home Base Video Project of the Tlingit and Haida Head Start Program. This series offers culturally relevant solutions to the challenges of parenting, drawing on practical advice from Tlingit and Haida parents, wisdom from elders, and some of…

  17. A Family of Mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ 一、故事内容 There is a family of mice in my house. They are father mouse, mother mouse and baby mouse. Baby mouse likes dancing. He is very cute. Father mouse likes watching TV. He likes the sports on TV best. These three mice are clever.

  18. The Pycnogonid family Austrodecidae

    NARCIS (Netherlands)

    Stock, J.H.

    1957-01-01

    DE PYCNOGONIDEN- FAMILIE AUSTRODECIDAE Toen mij, in 1954, uit Oslo een verzameling Pycnogonida van de „Norwegian Scientific Expedition to Tristan da Cunda 1937—1938“ ter bewerking werd opgezonden, kon ik niet vermoeden dat deze kleine collectie aanleiding zou geven tot een uitgebreide revisie van ee

  19. Family Play Therapy.

    Science.gov (United States)

    Ariel, Shlomo

    This paper examines a case study of family play therapy in Israel. The unique contributions of play therapy are evaluated including the therapy's accessibility to young children, its richness and flexibility, its exposure of covert patterns, its wealth of therapeutic means, and its therapeutic economy. The systematization of the therapy attempts…

  20. Families and Communities (Bookalogues).

    Science.gov (United States)

    Martinez, Miriam; Nash, Marcia F.

    1993-01-01

    Presents brief reviews of 26 picture books, chapter books, and informational books that deal with families and/or communities. Notes that the picture books and chapter books cover a wide variety of genres including poetry, realistic fiction, and fantasy and that the informational books have a variety of formats, with the "photo essay" dominating.…

  1. Aging and the Family.

    Science.gov (United States)

    Clark, C. Roberta

    1984-01-01

    Discusses emotional, social, medical, and nutritional needs of older people, and stresses the need for education of the families of the elderly and the need for a coordinated approach to service delivery to this population. In this way, maximum independence of the aged can be achieved. (NRJ)

  2. Not Your Family Farm

    Science.gov (United States)

    Tenopir, Carol; Baker, Gayle; Grogg, Jill E.

    2007-01-01

    The information industry continues to consolidate, just as agribusiness has consolidated and now dominates farming. Both the family farm and the small information company still exist but are becoming rarer in an age of mergers, acquisitions, and increased economies of scale. Small companies distinguish themselves by high quality, special themes,…

  3. Family Constellations in Europe

    NARCIS (Netherlands)

    A. Puur; L. Sakkeus; N. Schenk (Niels); A. Põldma

    2010-01-01

    textabstractThe importance of one’s family in times of need is unquestionable. Young children rely on their parents for proper living conditions, who in turn receive help from their aging parents in raising and caring for their children. There also comes a time when elderly parents themselves requir

  4. Family, Friends and Fertility

    NARCIS (Netherlands)

    Balbo, Nicoletta Franca Germana

    2012-01-01

    In deze dissertatie wordt een belangrijke nieuwe verklaring van vruchtbaarheidsgedrag ontwikkeld. De nadruk in deze nieuwe benadering ligt op het meso-niveau, dus op factoren die relatie hebben met het netwerk van de informele relaties die iemand deelt met familie en vrienden (d.w.z. het sociale

  5. Familial Crouzon syndrome

    Directory of Open Access Journals (Sweden)

    Y Samatha

    2010-01-01

    Full Text Available Crouzon syndrome is an autosomal dominant condition of the craniosynostotic syndromes without syndactyly and with various dentofacial anomalies. Craniosynostosis, maxillary hypoplasia, shallow orbits, ocular proptosis and hypertelorism are the characteristic features of Crouzon syndrome. This report describes the variable clinical features in affected individuals over two generations of a family with dentofacial deformities and review of literature.

  6. Familial Brain Arteriovenous Malformations

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-11-01

    Full Text Available Researchers at University Medical Centre Utrecht, the Netherlands, reviewed the literature on patients with familial brain arteriovenous malformations (BAVMs, and their age, sex, and clinical presentation were compared with those in population-based patients with sporadic BAVMs.

  7. The family Planococcaceae

    Digital Repository Service at National Institute of Oceanography (India)

    Shivaji, S.; Srinivas, T.N.R.; Reddy, G.S.N.

    , Ureibacillus, and Viridibacillus Members of the family are Gram-variable, spore forming or nonspore forming, and motile or nonmotile; morphology varies from trichomes in case of Caryophanon, filamentous in case of Filibacter to rods or rod-cocci, or spherical...

  8. The colpitts oscillator family

    DEFF Research Database (Denmark)

    Lindberg, Erik; Murali, K.; Tamasevicius, A.

    A tutorial study of the Colpitts oscillator family defined as all oscillators based on a nonlinear amplifier and a three- terminal linear resonance circuit with one coil and two capacitors. The original patents are investigated. The eigenvalues of the linearized Jacobian for oscillators based...

  9. Predicting the Proteins of Angomonas deanei, Strigomonas culicis and Their Respective Endosymbionts Reveals New Aspects of the Trypanosomatidae Family

    Science.gov (United States)

    Motta, Maria Cristina Machado; Martins, Allan Cezar de Azevedo; de Souza, Silvana Sant’Anna; Catta-Preta, Carolina Moura Costa; Silva, Rosane; Klein, Cecilia Coimbra; de Almeida, Luiz Gonzaga Paula; de Lima Cunha, Oberdan; Ciapina, Luciane Prioli; Brocchi, Marcelo; Colabardini, Ana Cristina; de Araujo Lima, Bruna; Machado, Carlos Renato; de Almeida Soares, Célia Maria; Probst, Christian Macagnan; de Menezes, Claudia Beatriz Afonso; Thompson, Claudia Elizabeth; Bartholomeu, Daniella Castanheira; Gradia, Daniela Fiori; Pavoni, Daniela Parada; Grisard, Edmundo C.; Fantinatti-Garboggini, Fabiana; Marchini, Fabricio Klerynton; Rodrigues-Luiz, Gabriela Flávia; Wagner, Glauber; Goldman, Gustavo Henrique; Fietto, Juliana Lopes Rangel; Elias, Maria Carolina; Goldman, Maria Helena S.; Sagot, Marie-France; Pereira, Maristela; Stoco, Patrícia H.; de Mendonça-Neto, Rondon Pessoa; Teixeira, Santuza Maria Ribeiro; Maciel, Talles Eduardo Ferreira; de Oliveira Mendes, Tiago Antônio; Ürményi, Turán P.; de Souza, Wanderley; Schenkman, Sergio; de Vasconcelos, Ana Tereza Ribeiro

    2013-01-01

    Endosymbiont-bearing trypanosomatids have been considered excellent models for the study of cell evolution because the host protozoan co-evolves with an intracellular bacterium in a mutualistic relationship. Such protozoa inhabit a single invertebrate host during their entire life cycle and exhibit special characteristics that group them in a particular phylogenetic cluster of the Trypanosomatidae family, thus classified as monoxenics. In an effort to better understand such symbiotic association, we used DNA pyrosequencing and a reference-guided assembly to generate reads that predicted 16,960 and 12,162 open reading frames (ORFs) in two symbiont-bearing trypanosomatids, Angomonas deanei (previously named as Crithidia deanei) and Strigomonas culicis (first known as Blastocrithidia culicis), respectively. Identification of each ORF was based primarily on TriTrypDB using tblastn, and each ORF was confirmed by employing getorf from EMBOSS and Newbler 2.6 when necessary. The monoxenic organisms revealed conserved housekeeping functions when compared to other trypanosomatids, especially compared with Leishmania major. However, major differences were found in ORFs corresponding to the cytoskeleton, the kinetoplast, and the paraflagellar structure. The monoxenic organisms also contain a large number of genes for cytosolic calpain-like and surface gp63 metalloproteases and a reduced number of compartmentalized cysteine proteases in comparison to other TriTryp organisms, reflecting adaptations to the presence of the symbiont. The assembled bacterial endosymbiont sequences exhibit a high A+T content with a total of 787 and 769 ORFs for the Angomonas deanei and Strigomonas culicis endosymbionts, respectively, and indicate that these organisms hold a common ancestor related to the Alcaligenaceae family. Importantly, both symbionts contain enzymes that complement essential host cell biosynthetic pathways, such as those for amino acid, lipid and purine/pyrimidine metabolism

  10. Predicting the proteins of Angomonas deanei, Strigomonas culicis and their respective endosymbionts reveals new aspects of the trypanosomatidae family.

    Directory of Open Access Journals (Sweden)

    Maria Cristina Machado Motta

    Full Text Available Endosymbiont-bearing trypanosomatids have been considered excellent models for the study of cell evolution because the host protozoan co-evolves with an intracellular bacterium in a mutualistic relationship. Such protozoa inhabit a single invertebrate host during their entire life cycle and exhibit special characteristics that group them in a particular phylogenetic cluster of the Trypanosomatidae family, thus classified as monoxenics. In an effort to better understand such symbiotic association, we used DNA pyrosequencing and a reference-guided assembly to generate reads that predicted 16,960 and 12,162 open reading frames (ORFs in two symbiont-bearing trypanosomatids, Angomonas deanei (previously named as Crithidia deanei and Strigomonas culicis (first known as Blastocrithidia culicis, respectively. Identification of each ORF was based primarily on TriTrypDB using tblastn, and each ORF was confirmed by employing getorf from EMBOSS and Newbler 2.6 when necessary. The monoxenic organisms revealed conserved housekeeping functions when compared to other trypanosomatids, especially compared with Leishmania major. However, major differences were found in ORFs corresponding to the cytoskeleton, the kinetoplast, and the paraflagellar structure. The monoxenic organisms also contain a large number of genes for cytosolic calpain-like and surface gp63 metalloproteases and a reduced number of compartmentalized cysteine proteases in comparison to other TriTryp organisms, reflecting adaptations to the presence of the symbiont. The assembled bacterial endosymbiont sequences exhibit a high A+T content with a total of 787 and 769 ORFs for the Angomonas deanei and Strigomonas culicis endosymbionts, respectively, and indicate that these organisms hold a common ancestor related to the Alcaligenaceae family. Importantly, both symbionts contain enzymes that complement essential host cell biosynthetic pathways, such as those for amino acid, lipid and purine

  11. [Return to the family].

    Science.gov (United States)

    Ouaidou, N G

    1993-08-01

    Sahelian countries occupy an inglorious place in the global list of human development. The human development index is superior to the gross national product (GNP) at measuring the progress of a country in terms of development, because it includes income, longevity, and educational level. The highest ranked Sahelian country holds the 114th position out of a 173 countries. The low human development index scores for the Sahel reflects the socioeconomic crisis which has overcome these countries. In 1991, only 3 of 9 Sahelian countries had a mean GP equal or superior to US$500. Just 2 countries had a life expectancy greater than 50 years. In fact, the Sahel had a lower life expectancy than all of Africa (50 years) and much lower than Asia (64 years) and Latin America (67 years). The economic crisis is worse than the cold statistics show. It destabilizes the most disadvantaged populations. The pressure it exerts often leads public authorities to adopt unpopular measures. It depreciates some sociocultural values and disintegrates traditional social structures. It is accentuated by the effects of war and drought. Internal and external migration increases even as urban hope is uncertain. For most people, the family (the traditional framework of individual development) is ready to break apart, leaving only a disincarnate nuclear entity to subsist. Yet, African history is built around the extended family: the place of reproduction, production, distribution, formation, management, perpetuation of demographic behavior, and social control. Senegal and Mali have created ministries which invest in families. The Third African Conference on Population, in 1992, chose its theme to be the relationship between family, population, and sustainable development. It is important to return to the natural or primordial framework--family--as a refuge against the economic crisis.

  12. Transfers of Family Businesses to Non-Family Buyers - The Selling Business Family Perspective

    OpenAIRE

    Sten, Jan

    2006-01-01

    This study focuses on business families and how they handle transitions such as business transfers. It also tries to shift the balance of research away from successions and towards business transfers as a key topic for family business researchers. In addition, it contributes to the family business research field by further highlighting the importance of the various different contributions in the family business from business family members other than the entrepreneurial founder. Based on ...

  13. Changes in modern family life and the transformation of the family and family life in Serbia

    OpenAIRE

    Milivojević, Snežana M.

    2014-01-01

    The theoretical framework of this topic can be built on an analysis of the following issues: developmental changes in the family; the transformation of the function of a modern family; changes in the structure of families and relationships among its members; the transition model of marriage and parenting; the impact of social, economic, and demographic factors on the transformation of the family. Review of the prospects for the future development of the family points out the changes in marria...

  14. Family size effects: a review.

    Science.gov (United States)

    Wagner, M E; Schubert, H J; Schubert, D S

    1985-03-01

    Larger families are more frequent with early marriage and rapid birth of the first child. In larger families, child rearing becomes more rule ridden, less individualized, with corporal punishment and less investment of resources. Smaller families tend to result in higher IQ, academic achievement, and occupational performance. Large families produce more delinquents and alcoholics. Perinatal morbidity and mortality rates are higher in large families as birth weights decrease. Mothers of large families are at higher risk of several physical diseases. Common methodological errors are indicated and exemplary studies are described.

  15. Children's Views on Family Communications in Families with their ...

    African Journals Online (AJOL)

    Mrs Afam

    Children in many families have witnessed or experienced family violence, disunity, conflicts, extreme deprivation, and malnutrition. The extent children view ... in order to find out the relative opinion, belief, attitude and status of that population.

  16. Study of a family that overcomes poverty issues: family resilience?

    Directory of Open Access Journals (Sweden)

    María Ángela Mattar Yunes

    2015-09-01

    Full Text Available Generally, researches with families focus the difficulties and the negative aspects of family life by bringing up their maladjustments and failures. The interest in family resilience contributes to change this logic by demonstrating the healthy aspects of the family world. Nevertheless, the term resilience presents ideological controversies which are more severe when the discussion is about families and poverty. In order to diminish these contradictions this study adopted a systemic concept of resilience which refers to “those processes that make possible to overcome adversities”. A case study was realized with a low income family who lived in a “very poor” neighborhood in the deep south of Brazil. The methodological strategies to the formal investigation of the family were: life history of the family using the principles of reflexive interview, genograms and data analyses through the approach of the grounded theory. The results showed that the family lived a number of risk experiences such as adoption, privation of basic needs, migration and diseases. Among the indicators of their abilities of “overcoming adversities”, emerged the belief system as the core of the discourses. The family showed that they value the interpersonal relationships through intra and extra familiar interactions based in the patterns of help, learning, affection and solidarity. During the crisis the family gives meaning to the difficulties in order to maintaining the situation controlled through cohesion, open communication, mutual respect and getting support of the extended family/ social network. The pos-adversity period is perceived as benefic and transforming as the family feels stronger and with feelings of solidarity, which is a mark of this family. Their attitude in relation to the neighborhood is active in the sense of promoting the welfare of other families who live in the same social address. Would those above identified processes be adequate to

  17. Enhancing family resilience through family narrative co-construction.

    Science.gov (United States)

    Saltzman, William R; Pynoos, Robert S; Lester, Patricia; Layne, Christopher M; Beardslee, William R

    2013-09-01

    We draw upon family resilience and narrative theory to describe an evidence-based method for intervening with military families who are impacted by multiple wartime deployments and psychological, stress-related, or physical parental injuries. Conceptual models of familial resilience provide a guide for understanding the mechanics of how families respond and recover from exposure to extreme events, and underscore the role of specific family processes and interaction patterns in promoting resilient capabilities. Leading family theorists propose that the family's ability to make meaning of stressful and traumatic events and nurture protective beliefs are critical aspects of resilient adaptation. We first review general theoretical and empirical research contributions to understanding family resilience, giving special attention to the circumstances, challenges, needs, and strengths of American military families. Therapeutic narrative studies illustrate the processes through which family members acquire meaning-making capacities, and point to the essential role of parents' in facilitating discussions of stressful experiences and co-constructing coherent and meaningful narratives. This helps children to make sense of these experiences and develop capacities for emotion regulation and coping. Family-based narrative approaches provide a structured opportunity to elicit parents' and children's individual narratives, assemble divergent storylines into a shared family narrative, and thereby enhance members' capacity to make meaning of stressful experiences and adopt beliefs that support adaptation and growth. We discuss how family narratives can help to bridge intra-familial estrangements and re-engage communication and support processes that have been undermined by stress, trauma, or loss. We conclude by describing a family-based narrative intervention currently in use with thousands of military children and families across the USA.

  18. Family and Cultural Capital. The perspective of familiness

    OpenAIRE

    Ortíz García, Pilar; Olaz Capitán, Ángel José; Monreal Martínez, Juan

    2014-01-01

    The influence of the family on a business, its commitment to the company and the values it conveys form a capital capable of influencing the global development of a business. This research analyzes family capital and in particular its cultural components as a resource influencing the direction of the company. Corporate culture as a guiding philosophy for family business strategy is a key factor in its success. In short, the cultural capital of a family business is a capac...

  19. FRANCHISE FROM FAMILY BUSINESS?

    Directory of Open Access Journals (Sweden)

    Adrián NAGY

    2016-06-01

    Full Text Available The purpose of this study was to examine the franchise as a form of enterprise in perspective to existing family businesses and how can they operate this way. Why is this form better for them, what advantages it has? In this case an ice cream shop’s economic inidicators were examined ,one which is owned by a hungarian family in Jász-Nagykun-Szolnok county who runs several shops like this. That is why this study was made, to find out if it is possible to run it sucsessfully and what costs does the newcomers in the franchise business network have to pay and how much is the time on the return of investments.

  20. Marriage and Family Therapy

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    About the author: Chen Yiyun graduated from the Russian Language and Literature Departraent at Beijing University in 1964. She then enrolled at the Sociology Institute of the China Academy of Social Sciences in 1978. Upon graduation, she remained at the Institute as a research fellow. She later became editor-in-chief of the magazine Sociology Abroad. She translated and edited dozens of sociology books. In 1988, after she returned from the United States, she devoted herself to the research of sociology and marriage consultation. In 1993, Chen set up the Jinglun Family Science Center, a non-governmental organization which is a combination of scientific research and social practice. She organized scholars, social workers and volunteers from sectors of public health, education and legislation to conduct useful activities to promote democracy in the family, equality, health and civilization.

  1. Familial hypophosphatemic rickets

    Directory of Open Access Journals (Sweden)

    Sattur A

    2010-01-01

    Full Text Available Rickets is the failure of mineralization of osteoid and newly formed bones in a child skeleton. It is commonly associated with vitamin D deficiency; however, it can be because of a decrease in the serum phosphate levels leading to inadequate mineralization of cartilage and bone, consequent skeletal deformities, and growth retardation. The hypophosphatemic conditions that interfere in bone mineralization comprise many hereditary or acquired diseases. One of the hereditary types of hypophosphatemic rickets is the familial hypophosphatemic rickets. This rare variety was diagnosed in a 9-year-old patient who had come with a chief complaint of a missing tooth. In the present case, radiographic aspects of oral and systemic manifestations of familial hypophosphatemic rickets are highlighted.

  2. Familial neurohypophyseal diabetes insipidus

    DEFF Research Database (Denmark)

    Kvistgaard, Helene

    2011-01-01

    Familial neurohypophyseal diabetes insipidus (FNDI) is characterized by severe low-solute polyuria and polydipisa. The disease is caused by a deficient neurosecretion of the antidiuretic hormone arginine vasopressin (AVP). The hormone is normally synthesized by the magnocellular neurons in the pa......Familial neurohypophyseal diabetes insipidus (FNDI) is characterized by severe low-solute polyuria and polydipisa. The disease is caused by a deficient neurosecretion of the antidiuretic hormone arginine vasopressin (AVP). The hormone is normally synthesized by the magnocellular neurons...... as one sporadic case of early-onset diabetes insipidus. Genetic testing of the sporadic case of diabetes insipidus revealed a highly unusual mosaicism for a variation in the gene encoding the AVP receptor (AVPR2). This mosaicism had resulted in a partial phenotype and initial diagnostic difficulties...

  3. Familial reactive perforating collagenosis

    Directory of Open Access Journals (Sweden)

    Bhat Yasmeen

    2009-01-01

    Full Text Available Background: Reactive perforating collagenosis (RPC is one of the rare forms of transepidermal elimination in which genetically altered collagen is extruded from the epidermis. This disease usually starts in early childhood as asymptomatic umbilicated papules on extremities, and the lesions become more conspicuous with age. Aims: The objective of our study was to determine the clinico-pathological features of RPC and the response to various treatment modalities. Methods: Ten patients of RPC, belonging to five different families, were studied clinically. Various laboratory investigations were carried out and diagnosis was made by histopathology of the lesions. Patients were given various topical and oral treatments. Results: RPC is familial in most cases without any definite inheritance pattern. It begins in childhood and the lesions are usually recurrent and become profuse and large with age. Systemic diseases have no role in the onset of lesions. Conclusion: Oral and topical retinoids in combination with emollients is the best treatment option.

  4. Designing Product Families

    DEFF Research Database (Denmark)

    Pedersen, Per Erik Elgård; Miller, Thomas Dedenroth

    1998-01-01

    Manufacturing companies that operate with products aimed at different market segments and applications are experiencing an increasing demand from customers who expect products to be tailored to their exact needs rather than accepting general products based on average customer needs. This trend ha...... led to a new business paradigm, "mass customization", where companies strive to provide highly customized products while still maintaining the efficiency of the classical mass production enterprise. One of the key factors in mass customization has been efficient use of product platforms...... as a foundation for the customization process, whereby the customized products become variants of a product family with a high degree of reuse and utilization of kinship between the individual variants.With this paper, we will discuss the development of platform based product families from three points of view...

  5. Intermediate Family Therapy Skills

    OpenAIRE

    2001-01-01

    The field of marriage and family therapy (MFT) has prospered since its beginnings nearly 50 years ago. In order to keep the field current and competitive with other related professions, empirical research is necessary. Although there has been an upsurge of research on the effectiveness and specialty areas of MFT, one area has been overlooked: skills. THe empirical research that has been performed has focused its attention on beginning therapists. The current research took the next step in...

  6. Family planning: where now?

    Science.gov (United States)

    Saunders, L

    1977-01-01

    The focus is in terms of family planning as an exercise in induced social change; the objective is to alter the reproductive patterns of societies sufficiently to bring about a significant reduction in fertility. The year 1974 emerges as the year in which family planning as a social movement achieved maturity and was confirmed as a legitimate area for national policy and programming, a year of determined and varied efforts to reduce population growth. In affirming the rights and responsibilities of people and the obligations of governments in population concerns, the Bucharest Conference conferred its seal of approval on a movement that had made considerable progress since it began early in the 19th century. The evolution of birth control as a social movement which began with Francis Place's printing and distributing contraceptive bills in 1820 was encouraged by other writings in England and the U.S. over the next 50 years. Several overlapping phases can be distinguished in the global response to a new sense of urgence regarding population concerns following World War 2. Moving from a global perspective to consideration of family planning as it exists in the programs of individual countries, the achievement is not so great and the prospects are less hopeful. Although it has had success as a social movement and is now accepted as a government responsibility, family planning programs still have a long way to go before they develop the scope, vigor, and versatility that is required for there to be widespread demographic change. 1 change that is needed is for a stronger and more visible political commitment and commitment on the basis of demographic rather than health or welfare reasons.

  7. The chicken SLAM family.

    Science.gov (United States)

    Straub, Christian; Viertlboeck, Birgit C; Göbel, Thomas W

    2013-01-01

    The signaling lymphocytic activation molecule (SLAM) family of receptors is critically involved in the immune regulation of lymphocytes but has only been detected in mammals, with one member being present in Xenopus. Here, we describe the identification, cloning, and analysis of the chicken homologues to the mammalian SLAMF1 (CD150), SLAMF2 (CD48), and SLAMF4 (CD244, 2B4). Two additional chicken SLAM genes were identified and designated SLAMF3like and SLAM5like in order to stress that those two receptors have no clear mammalian counterpart but share some features with mammalian SLAMF3 and SLAMF5, respectively. Three of the chicken SLAM genes are located on chromosome 25, whereas two are currently not yet assigned. The mammalian and chicken receptors share a common structure with a V-like domain that lacks conserved cysteine residues and a C2-type Ig domain with four cysteines forming two disulfide bonds. Chicken SLAMF2, like its mammalian counterpart, lacks a transmembrane and cytoplasmic domain and thus represents a glycosyl-phosphatidyl-inositol-anchored protein. The cytoplasmic tails of SLAMF1 and SLAMF4 display two and four conserved immunoreceptor tyrosine-based switch motifs (ITSMs), respectively, whereas both chicken SLAMF3like and SLAMF5like have only a single ITSM. We have also identified the chicken homologues of the SLAM-associated protein family of adaptors (SAP), SAP and EAT-2. Chicken SAP shares about 70 % identity with mammalian SAP, and chicken EAT-2 is homologous to mouse EAT-2, whereas human EAT-2 is much shorter. The characterization of the chicken SLAM family of receptors and the SAP adaptors demonstrates the phylogenetic conservation of this family, in particular, its signaling capacities.

  8. Origin of family symmetries

    Energy Technology Data Exchange (ETDEWEB)

    Nilles, Hans Peter [Bonn Univ. (Germany). Bethe Center for Theoretical Physics; Bonn Univ. (Germany). Physikalisches Inst.; Ratz, Michael [Technische Univ. Muenchen, Garching (Germany). Physik-Department; Vaudrevange, Patrick K.S. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2012-04-15

    Discrete (family) symmetries might play an important role in models of elementary particle physics. We discuss the origin of such symmetries in the framework of consistent ultraviolet completions of the standard model in field and string theory. The symmetries can arise due to special geometrical properties of extra compact dimensions and the localization of fields in this geometrical landscape. We also comment on anomaly constraints for discrete symmetries.

  9. What determines family structure?

    OpenAIRE

    Blau, David M.; van der Klaauw, Wilbert

    2010-01-01

    We estimate the effects of policy and labor market variables on the fertility, union formation and dissolution, type of union (cohabiting versus married), and partner choices of the NLSY79 cohort of women. These demographic behaviors interact to determine the family structure experienced by the children of these women: living with the biological mother and the married or cohabiting biological father, a married or cohabiting step father, or no man. We find that the average wage rates available...

  10. Tom’s family

    Institute of Scientific and Technical Information of China (English)

    周昕睿

    2015-01-01

    Tom’s family lives at Eighty-sixth King Street.Tom’s mother is a housewife and his father is a policeman.In the morning,Tom’s father goes to work and Tom goes to school.His father takes him to school every day.Tom’s mother stays at home and does the housework every day.She always eats lunch at noon.

  11. Hadamard partitioned difference families

    OpenAIRE

    Buratti, Marco

    2017-01-01

    We prove that every Hadamard difference set of order $u^2$ leads to a partitioned difference family of any order $v\\equiv4u^2$ (mod $8u^2$) and blocks of sizes $4u^2-2u$, $4u^2$ and $4u^2+2u$ provided that the maximal prime power divisors of $v\\over4u^2$ are all greater than $4u^2+2u$.

  12. Family Planning Services

    Institute of Scientific and Technical Information of China (English)

    米国庆

    1994-01-01

    According to the China national programme of economic and social development, by 2000 the standard of living of Chinese people will have been fairly welloff. In order to accomplish the goal, the government has comprised the population development in the national social economic development programme. Family planning (FP) work will contribute to the general goal of social economy and development. Reform and open policy and establishment of socialist market economy sys

  13. Family Planning in China

    Institute of Scientific and Technical Information of China (English)

    朱耀华

    1994-01-01

    China is a developing country with vast territory, numerous population and relatively poor economic foundation. The basic features of China's population are of great quantity and considerable annual increase of population as well as its uneven distribution in different regions. For improvement of living standard of the people,Chinese Government began to advocate family planning throughout this country in the beginning of the 1970s while a strenuous effort was made to develop economy.

  14. Family Counseling Interventions: Understanding Family Systems and the Referral Process.

    Science.gov (United States)

    McWhirter, Ellen Hawley; And Others

    1993-01-01

    This article describes concepts underlying the idea of the "family as a system"; compares and contrasts four approaches to family therapy (those of Virginia Satir, Jay Haley, Murray Bowen, and Salvador Minuchin); and offers suggestions to teachers referring parents for family counseling. (DB)

  15. Family Structure, Family Processes, and Adolescent Smoking and Drinking

    Science.gov (United States)

    Brown, Susan L.; Rinelli, Lauren N.

    2010-01-01

    This study examined whether family structure was associated with adolescent risk behaviors, including smoking and drinking. Family living arrangements have become increasingly diverse, yet research on adolescent risk behaviors has typically relied on measures of family structure that do not adequately capture this diversity. Data from the…

  16. Using Our Understanding of Families to Strengthen Family Involvement

    Science.gov (United States)

    Knopf, Herman T.; Swick, Kevin J.

    2008-01-01

    The purpose of this article is to help teachers become more responsive to the changing needs and contexts of families in their efforts to establish relationships and encourage family participation. Through this article, the authors describe the changing landscape of parenting and the stressors experienced by contemporary families. The authors then…

  17. A Family Affair : Explaining Co-Working By Family Members

    NARCIS (Netherlands)

    Ruijter, Esther de; Lippe, Tanja van der; Raub, Werner; Weessie, Jeroen

    2008-01-01

    This study focuses on co-working by intimate partners and other family members in entrepreneurs’ businesses. We hypothesize that co-working by family is beneficial because it reduces trust problems associated with employment relations. On the other hand, co-working is risky because co-working family

  18. Changing Families, Changing Responsibilities: Family Obligations Following Divorce and Remarriage.

    Science.gov (United States)

    Ganong, Lawrence H.; Coleman, Marilyn

    The high incidence of divorce and remarriage means that the structure of American families is changing. Drawing on 13 studies that explore intergenerational obligations, this book discusses the responsibilities of family members to one another after divorce and remarriage. Chapter 1, "Who Is Responsible for Dependent Family Members?," presents an…

  19. Family Counseling Interventions: Understanding Family Systems and the Referral Process.

    Science.gov (United States)

    McWhirter, Ellen Hawley; And Others

    1993-01-01

    This article describes concepts underlying the idea of the "family as a system"; compares and contrasts four approaches to family therapy (those of Virginia Satir, Jay Haley, Murray Bowen, and Salvador Minuchin); and offers suggestions to teachers referring parents for family counseling. (DB)

  20. A Family Affair : Explaining Co-Working By Family Members

    NARCIS (Netherlands)

    Ruijter, Esther de; Lippe, Tanja van der; Raub, Werner; Weessie, Jeroen

    2008-01-01

    This study focuses on co-working by intimate partners and other family members in entrepreneurs’ businesses. We hypothesize that co-working by family is beneficial because it reduces trust problems associated with employment relations. On the other hand, co-working is risky because co-working family

  1. Changing Families, Changing Responsibilities: Family Obligations Following Divorce and Remarriage.

    Science.gov (United States)

    Ganong, Lawrence H.; Coleman, Marilyn

    The high incidence of divorce and remarriage means that the structure of American families is changing. Drawing on 13 studies that explore intergenerational obligations, this book discusses the responsibilities of family members to one another after divorce and remarriage. Chapter 1, "Who Is Responsible for Dependent Family Members?," presents an…

  2. Fostering Families' and Children's Rights to Family Connections

    Science.gov (United States)

    Landsman, Miriam J.; Boel-Studt, Shamra

    2011-01-01

    Recent federal legislation strengthens children's and families' rights to family-centered practice by increasing the responsibility of child welfare agencies to identify and engage extended family members in providing care and support to children placed out of the home. Preliminary results from an experimental study of a federally funded family…

  3. Psychoanalysis: a dysfunctional family?

    Science.gov (United States)

    Grosskurth, P

    1998-01-01

    The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve.

  4. Cybernetics of Brief Family Therapy.

    Science.gov (United States)

    Keeney, Bradford P.; Ross, Jeffrey M.

    1983-01-01

    Presents a cybernetic view of brief family therapy. Includes a historical discussion of the key ideas underlying brief family therapy, a cybernetic model of therapeutic change, and a clinical case for exemplification. (Author/JAC)

  5. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations Rotavirus One family's struggles with rotavirus We provide ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...

  6. One Family's Struggle with Chickenpox

    Medline Plus

    Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations Chickenpox (Varicella) One family's struggles with chickenpox We ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...

  7. National Survey of Family Growth

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Survey of Family Growth (NSFG) gathers information on family life, marriage and divorce, pregnancy, infertility, use of contraception, and men's and...

  8. Families classification including multiopposition asteroids

    Science.gov (United States)

    Milani, Andrea; Spoto, Federica; Knežević, Zoran; Novaković, Bojan; Tsirvoulis, Georgios

    2016-01-01

    In this paper we present the results of our new classification of asteroid families, upgraded by using catalog with > 500,000 asteroids. We discuss the outcome of the most recent update of the family list and of their membership. We found enough evidence to perform 9 mergers of the previously independent families. By introducing an improved method of estimation of the expected family growth in the less populous regions (e.g. at high inclination) we were able to reliably decide on rejection of one tiny group as a probable statistical fluke. Thus we reduced our current list to 115 families. We also present newly determined ages for 6 families, including complex 135 and 221, improving also our understanding of the dynamical vs. collisional families relationship. We conclude with some recommendations for the future work and for the family name problem.

  9. One Family's Struggle with Chickenpox

    Medline Plus

    Full Text Available ... Tos Ferina AAP CME ask your doctor brochure family stories faq meet dr. gary freed meet keri ... media video/audio pneumonia tb overview links & resources families advocacy about civil rights kids' rights sample school ...

  10. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... Tos Ferina AAP CME ask your doctor brochure family stories faq meet dr. gary freed meet keri ... media video/audio pneumonia tb overview links & resources families advocacy about civil rights kids' rights sample school ...

  11. Genetics Home Reference: familial porencephaly

    Science.gov (United States)

    ... Stroke Johns Hopkins Medicine Department of Neurology and Neurosurgery: Intracerebral Hemorrhage Johns Hopkins Medicine Department of Neurology and Neurosurgery: Stroke MalaCards: familial porencephaly Orphanet: Familial porencephaly Patient ...

  12. A Family Finds Its Way

    Science.gov (United States)

    ... Past Issues Cover Story: Traumatic Brain Injury A Family Finds Its Way Past Issues / Fall 2008 Table ... are living with serious health conditions as a family. Photo courtesy of Stefan Radtke, www.stefanradtke.com ...

  13. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... Tos Ferina AAP CME ask your doctor brochure family stories faq meet dr. gary freed meet keri ... media video/audio pneumonia tb overview links & resources families advocacy about civil rights kids' rights sample school ...

  14. Energize Yourself and Your Family

    Science.gov (United States)

    ... Direction Keeping Active & Healthy Eating for the Whole Family Did you know? Eating healthy foods and staying ... charge up your body for work, play, and family feel better about yourself and manage stress better ...

  15. One Family's Struggle with Chickenpox

    Medline Plus

    Full Text Available ... Tos Ferina AAP CME ask your doctor brochure family stories faq meet dr. gary freed meet keri ... media video/audio pneumonia tb overview links & resources families advocacy about civil rights kids' rights sample school ...

  16. Family Reintegration Following Guard Deployment

    Science.gov (United States)

    2010-09-20

    expectations is a key process that has to occur for successful reintegration of the veteran back into the family. Both parties have to work out their...describe veterans and families perceptions of: Aim 1. Their experience with family reintegration and the challenges reintegration presents; Aim 2...deployment, and post deployment shape the degree of challenges with reintegration that a veteran and their family will encounter. Pre-deployment, the

  17. Pars planitis in a family.

    Science.gov (United States)

    Tejada, P; Sanz, A; Criado, D

    1994-01-01

    The familial occurrence of pars planitis is rare. We have found ten cases reported previously. We describe a new case of pars planitis in a family. The affected members included a mother and two of her four children. The family was tested for HLA antigens in order to establish a comparison with others HLA types by different authors. We have not identified any cause for the familial occurrence of this disease. We discuss the role of genetic and ambiental factors.

  18. Canada's family violence initiative: partnerships

    OpenAIRE

    Scott Elaine

    1994-01-01

    Under Canada's four-year, $136 million Family Violence Initiative, the federal government is calling upon all Canadians to work in partnerships towards the elimination of family violence - child abuse, violence against women, and elder (senior) abuse. Family violence is a complex problem and requires the efforts of all Canadians to resolve it. One of the key themes of the Initiative - a multidisciplinary approach to the problem of family violence - is reflected in the selection and developmen...

  19. Contribution on family business definition

    OpenAIRE

    Vallone, C

    2013-01-01

    Despite numerous researches and an ample literature, there is not a unanimously and approved family business definition which identify family businesses from nonfamily businesses. Which are the aspects to describe exactly a family business? Which are the aspects that help to recognise family business from nonfamily business? Answering to these questions means to circumscribe the field of investigation, and obtain a comparable sample for international researches; to individualize the presence ...

  20. Family conditions and children abuse

    OpenAIRE

    Platone, Maria Luisa

    2010-01-01

    This article deals with family conditions (structure and family system interactive patterns) which are considered as risk factors for children abuse. Method. Descriptive research multimethod (cuantitative and cualitative), data were obtained from a retrospective study (1970-2000) of public and private elementary schools, from pre-school to sixth grade. The instruments used were: 1) the family test drawing, 2) a questionnaire to the child. 3) a questionnaire to the teachers about family condit...

  1. 76 FR 37983 - Family Offices

    Science.gov (United States)

    2011-06-29

    ... or entities with no family relations to nevertheless receive investment advice from the family office... throughout this Release and rule 202(a)(11)(G)-1 has the same meaning as in section 202(a)(5) of the Advisers... is an individual or couple.\\18\\ They noted that in many cases, however, family offices are...

  2. Theme Section: Focus on Families.

    Science.gov (United States)

    Ungar, Manya; And Others

    1988-01-01

    A collection of 14 brief articles considers the effects of family environment and lifestyle on children and provides suggestions for healthier family relations. The articles cover such topics as: family stress; preschool academic programs; stepfamilies; corporate child care; fathers; divorce; only children; single and working parents; and death.…

  3. Family members' experiences of autopsy

    NARCIS (Netherlands)

    Oppewal, F; Meyboom-de Jong, B

    2001-01-01

    Background. The experiences of family members will teach us how to handle an autopsy, the ultimate quality assessment tool. Objective. The aim of this study was to determine surviving family members' experience of autopsy. Method. Seven GPs were asked to approach surviving family members of autopsie

  4. Children's Impressions of Television Families.

    Science.gov (United States)

    Wartella, Ellen

    This research study examines the types of social behaviors portrayed by families in various television series and explores children's impressions of the TV family members. Content analysis of nine family-oriented TV series was employed to describe the ranges of behaviors of fathers, mothers and children on television. Eleven shows from each series…

  5. Does Addiction Run in Families?

    Science.gov (United States)

    ... Addiction? » Does Addiction Run in Families? Does Addiction Run in Families? Listen PDF: EasyToRead_WhatIsAddiction_Final_ ... English Español "Heart disease runs in some families. Addiction runs in ours." ©istock.com/ Antonio_Diaz Matt's ...

  6. Family Textbooks Twelve Years Later

    Science.gov (United States)

    Glenn, Norval D.

    2009-01-01

    In 1996 the author conducted an intensive study of twenty current family textbooks published in the United States, the results of which appeared in an academic journal article and a nonacademic report in 1997. The study included practical "functionalist" marriage and family textbooks and more academic sociology of the family books; these…

  7. NASA Science Served Family Style

    Science.gov (United States)

    Noel-Storr, Jacob; Mitchell, S.; Drobnes, E.

    2010-01-01

    Family oriented innovative programs extend the reach of many traditional out-of-school venues to involve the entire family in learning in comfortable and fun environments. Research shows that parental involvement is key to increasing student achievement outcomes, and family-oriented programs have a direct impact on student performance. Because families have the greatest influence on children's attitudes towards education and career choices, we have developed a Family Science program that provides families a venue where they can explore the importance of science and technology in our daily lives by engaging in learning activities that change their perception and understanding of science. NASA Family Science Night strives to change the way that students and their families participate in science, within the program and beyond. After three years of pilot implementation and assessment, our evaluation data shows that Family Science Night participants have positive change in their attitudes and involvement in science.  Even after a single session, families are more likely to engage in external science-related activities and are increasingly excited about science in their everyday lives.  As we enter our dissemination phase, NASA Family Science Night will be compiling and releasing initial evaluation results, and providing facilitator training and online support resources. Support for NASA Family Science Nights is provided in part through NASA ROSES grant NNH06ZDA001N.

  8. Family Dinners. For Parents Particularly.

    Science.gov (United States)

    Klein, Helen Altman

    2001-01-01

    Asserts that family dinners deserve attention as a positive contributor to children's well-being. Maintains that family dinners give stability to a potentially confusing day, present a place for children to express themselves, and provide children's first community. Includes ideas for helping families identify their own dinner patterns and…

  9. Family members' experiences of autopsy

    NARCIS (Netherlands)

    Oppewal, F; Meyboom-de Jong, B

    Background. The experiences of family members will teach us how to handle an autopsy, the ultimate quality assessment tool. Objective. The aim of this study was to determine surviving family members' experience of autopsy. Method. Seven GPs were asked to approach surviving family members of

  10. The growing VAO flavoprotein family

    NARCIS (Netherlands)

    Leferink, Nicole G. H.; Heuts, Dominic P. H. M.; Fraaije, Marco W.; van Berkel, Willem J. H.

    2008-01-01

    The VAO flavoprotein family is a rapidly growing family of oxidoreductases that favor the covalent binding of the FAD cofactor. In this review we report on the catalytic properties of some newly discovered VAO family members and their mode of flavin binding. Covalent binding of the flavin is a self-

  11. Family control and financing decisions

    NARCIS (Netherlands)

    Croci, Ettore; Doukas, John A.; Gonenc, Halit

    2011-01-01

    This study uses a comprehensive European dataset to investigate the role of family control in corporate financing decisions during the period 1998-2008. We find that family firms have a preference for debt financing, a non-control-diluting security, and are more reluctant than non-family firms to ra

  12. Ecological Correlates of Family Functioning.

    Science.gov (United States)

    Meyers, Steven A.; Varkey, Soji; Aguirre, Angela M.

    2002-01-01

    Explores how parents' psychological functioning, social relationships, and demographic characteristics relate to family functioning with a sample of 197 participants. Significant associations between predictor variables and family functioning were found as rated by mothers, caseworkers, and coders of family interaction tasks. (JDM)

  13. Administration for Children and Families

    Science.gov (United States)

    ... Releases RSS Feeds Speeches Videos What is the Administration for Children & Families? The Administration for Children and Families (ACF) is a division ... Center Blog Press Releases RSS Feeds Speeches Videos Administration for Children & Families U.S. Department of Health & Human ...

  14. Family identity: black-white interracial family health experience.

    Science.gov (United States)

    Byrd, Marcia Marie; Garwick, Ann Williams

    2006-02-01

    The purpose of this interpretive descriptive study was to describe how eight Black-White couples with school-aged children constructed their interracial family identity through developmental transitions and interpreted race to their children. Within and across-case data analytic strategies were used to identify commonalities and variations in how Black men and White women in couple relationships formed their family identities over time. Coming together was the core theme described by the Black-White couples as they negotiated the process of forming a family identity. Four major tasks in the construction of interracial family identity emerged: (a) understanding and resolving family of origin chaos and turmoil, (b) transcending Black-White racial history, (c) articulating the interracial family's racial standpoint, and (d) explaining race to biracial children across the developmental stages. The findings guide family nurses in promoting family identity formation as a component of family health within the nurse-family partnership with Black-White mixed-race families.

  15. Family burden, family health and personal mental health.

    Science.gov (United States)

    Ennis, Edel; Bunting, Brendan P

    2013-03-21

    The economic and moral implications of family burden are well recognised. What is less understood is whether or how family health and family burden relate to personal mental health. This study examines family health and perceived family burden as predictors of personal mental health, taking personal and sociodemographic factors into consideration. Data used was from the National Comorbidity Study Replication (NCS-R), namely the random 30% of participants (N = 3192) to whom the family burden interview was administered. Measures of family burden and mental health were considered for analysis. Binary logistic regressions were used as means of analyses. Perception of family burden was associated with an increased vulnerability to personal mental health problems, as was the presence of mental health difficulties within the family health profile. Which member of the family (kinship) was ill bore no relation to prediction of personal mental health. Personal and socio-demographic factors of sex, age, marital status, education and household income were all predictive of increased vulnerability to mental health problems over the last 12 months. Certain elements of family health profile and its perceived burden on the individuals themselves appears related to risk of personal incidence of mental health problems within the individuals themselves. For moral and economic reasons, further research to understand the dynamics of these relationships is essential to aid developing initiatives to protect and support the mental health and wellbeing of relatives of ill individuals.

  16. Family dynamics and infant temperament in Danish families

    DEFF Research Database (Denmark)

    Wilson, M.E.; Hall, Elisabeth O.C.; White, M.A.

    1994-01-01

    Transition to parenthood involves the fine balance of family dynamics which both affect, and are affected by, the infant's temperament. The purpose of this study was to investigate changes in family dynamics over the transition to parenthood and the relationship of family dynamics to infant...... temperament. A sample of 99 families in Odense, Denmark, completed the Family Dynamics Measure in the third trimester of pregnancy and again when the infant was 8-9 months old. At this second time, the mothers also completed the Revised Infant Temperament Questionnaire. Overall we found small changes......, although always in a negative direction, in family dynamics over this transition. The largest change was an increase in perceived role conflict reported by both mothers and fathers. Mothers reported more role conflict than fathers. Positive family dynamics were related to infant rhythmicity....

  17. Dual-career family as an exampleof egalitarian family

    Directory of Open Access Journals (Sweden)

    Joanna Ostrouch-Kamińska

    2011-11-01

    Full Text Available The economic, cultural, and social transformation, growth of women's economic strength as well as the level of their education, and development of ideas of equal rights of women and men on the labour market and in social life cause changes in gender relation in the family. Poles more and more often declare and support egalitarian family, and a new model of a family appears among existing ones – dual-career family.The main aim of the article is to consider the sources of its rise, description of gender positions in marital relation, the division of tasks and responsibilities, possible dilemmas and conflicts, but also emotional, intellectual and social advantages. The analysis were put into context of changes in defining and describing family, and also in context of different family discourses. One of them was underlined the most – egalitarian one as the most approximate to the way of defining and understanding dual-career family model.

  18. How Family Leisure Influences Family Functionality in Single-Parent Families

    National Research Council Canada - National Science Library

    Debra Pakstis; Pei-Chun Hsieh

    2015-01-01

      [...]since communication has been identified as a key component in the core and balance model and also plays a vital role in impacting family adaptability and family cohesion, recreation therapists working...

  19. [Family warmth cures].

    Science.gov (United States)

    Inthamun, P

    1996-04-01

    Women in Thailand are increasingly finding themselves responsible for caring for the physical and mental health of HIV-infected men. The author gained such experience caring for her husband, while her suffering since youth of a series of chronic illnesses helped her to understand that life is full of surprises. Moreover, meditation also helps her to squarely confront problems as they arise, such as when she learned that she contracted HIV from her husband 5 years ago. The author then learned about AIDS and attended, together with her husband, conferences on HIV/AIDS to learn how to care for them both. She also enrolled in a Red Cross program on in-home care. In 1994, the husband returned home from the hospital in poor health, with little time left to live. However, surrounded by the warmth and affection of home, friends, and family, the man¿s health status improved to the extent that his opportunistic diseases disappeared. Since that experience, the author visits other households where people are living with AIDS in an attempt to bring them moral support, to teach about in-home care, and to coordinate hospital care when needed. The author now knows that HIV-seropositive people can contribute considerably to help the lives of both others living with AIDS and the general community. She is determined to show that families working together can reduce the level of suffering experienced by HIV-infected individuals and that such people will survive longer through families¿ efforts.

  20. The cullin protein family.

    Science.gov (United States)

    Sarikas, Antonio; Hartmann, Thomas; Pan, Zhen-Qiang

    2011-01-01

    Cullin proteins are molecular scaffolds that have crucial roles in the post-translational modification of cellular proteins involving ubiquitin. The mammalian cullin protein family comprises eight members (CUL1 to CUL7 and PARC), which are characterized by a cullin homology domain. CUL1 to CUL7 assemble multi-subunit Cullin-RING E3 ubiquitin ligase (CRL) complexes, the largest family of E3 ligases with more than 200 members. Although CUL7 and PARC are present only in chordates, other members of the cullin protein family are found in Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana and yeast. A cullin protein tethers both a substrate-targeting unit, often through an adaptor protein, and the RING finger component in a CRL. The cullin-organized CRL thus positions a substrate close to the RING-bound E2 ubiquitin-conjugating enzyme, which catalyzes the transfer of ubiquitin to the substrate. In addition, conjugation of cullins with the ubiquitin-like molecule Nedd8 modulates activation of the corresponding CRL complex, probably through conformational regulation of the interactions between cullin's carboxy-terminal tail and CRL's RING subunit. Genetic studies in several model organisms have helped to unravel a multitude of physiological functions associated with cullin proteins and their respective CRLs. CRLs target numerous substrates and thus have an impact on a range of biological processes, including cell growth, development, signal transduction, transcriptional control, genomic integrity and tumor suppression. Moreover, mutations in CUL7 and CUL4B genes have been linked to hereditary human diseases.

  1. Familial Mediterranean Fever (FMF

    Directory of Open Access Journals (Sweden)

    Onur Albayrak

    2009-08-01

    Full Text Available Familial Mediterranean Fever (FMF is an autosomal recessive genetic disease that affects males and females. FMF gene is on the short arm of chromosome 16. It is most often found in Jews, Arabs, Turks, and Armenians. Amyloidosis is charecterized by the deposition of a particular protein between the cells in the tissue. It is a potentially serious complication of FMF. The kidney is a prime target for the amyloid. [Archives Medical Review Journal 2009; 18(4.000: 260-267

  2. Balancing family and work

    Science.gov (United States)

    Showstack, Randy

    2011-08-01

    More than 45% of women scientists at top universities in the United States have indicated that their careers have kept them from having as many children as they want, according to an 8 August study, “Scientists want more children,” which appears in the journal PLoS ONE. The study, by sociologists Elaine Howard Ecklund of Rice University and Anne Lincoln of Southern Methodist University, indicates that 24.5% of male scientists surveyed indicated the same concerns. The study also found that among junior scientists, 29% of women indicated concern that a science career would prevent them from having a family; 7% of men indicated the same concern.

  3. QUAD FAMILY CENTERING.

    Energy Technology Data Exchange (ETDEWEB)

    PINAYEV, I.

    2005-11-01

    It is well known that beam position monitors (BPM) utilizing signals from pickup electrodes (PUE) provide good resolution and relative accuracy. The absolute accuracy (i.e. position of the orbit in the vacuum chamber) is not very good due to the various reasons. To overcome the limitation it was suggested to use magnetic centers of quadrupoles for the calibration of the BPM [1]. The proposed method provides accuracy better then 200 microns for centering of the beam position monitors using modulation of the whole quadrupole family.

  4. Congenital familial hypertonia.

    Science.gov (United States)

    DeLuca, Carl F; Cashore, William J

    2002-09-01

    1. This complex of symptoms appears to be congenital, familial, and hereditary. It is apparently transmitted by a dominant gene, probably on chromosome 5. 2. Hypertonicity with rigidity of all voluntary muscles usually presents at birth. 3. Feeding problems are due to dysphagia or laryngospasm associated with aspiration and dyspnea. 4. Respiratory problems are characterized by apneic episodes due to muscle spasm. 5. Prolonged episodes of muscular rigidity secondary to sudden stimuli result in frequent falls, characteristically en bloc, like a statue. 6. Continuous electromyographic activity even at rest (with absence of fasciculations) improves after intravenous diazepam.

  5. Familial vesicoureteral reflux

    OpenAIRE

    朴, 勺; 新井, 豊; 友吉, 唯夫; 吉田, 修

    1983-01-01

    Primary vesicoureteral reflux was seen in 2 siblings in a family of 5 (1 daughter and 2 sons). Voiding cystogram of elder sister, who complained of fever and backache, showed bilateral reflux at the age of 6. Left reflux disappeared soon but right reflux persisted. Right antireflux operation was performed at the age of 9, but right renal function deteriorated gradually. Right nephrectomy was done at the age of 12 because of persistent pyuria and renal stones. The second case was her younger b...

  6. Familial hyperamylasemia Hiperamilasemia familiar

    Directory of Open Access Journals (Sweden)

    Yu Kar Ling Koda

    2002-01-01

    Full Text Available A 7-year-old white boy was referred to us with a history of 3 attacks of hypogastric pain over the previous 2 years and persistently elevated serum amylase concentrations. At physical examination, he was well with no evidence of clinical abnormalities. His weight and height were normal. Laboratory diagnostic investigations were all normal except for the presence of Ascaris lumbricoides in the feces and persistently elevated serum amylase levels. Serum amylase determinations in the family members were normal in his father and maternal grandmother but elevated in his mother, sister, maternal aunt, and uncle, all of whom asymptomatic. Macroamylasemia was excluded in the child and in the mother. The finding of persistently elevated amylasemia in the child and in the other family members spanning 3 generations, and the exclusion of diseases that lead to hyperamilasemia are consistent with the diagnosis of familial hyperamylasemia. Until now, only 1 similar case has been reported. Familial hyperamylasemia must be considered in the differential diagnosis of hyperamylasemias in childhood.Paciente branco, masculino, sete anos, encaminhado com história de três episódios de dor abdominal no baixo ventre nos últimos dois anos e níveis elevados de amilase sérica. Ao exame físico encontrava-se em bom estado geral, com desenvolvimento pondo-estatural normal e sem sinais ou sintomas de quaisquer anormalidades clínicas. Os exames complementares para investigação diagnóstica revelaram-se todos normais com exceção do exame parasitológico de fezes que revelou Ascaris lumbricoides e dos níveis séricos de amilase que se encontravam persistentemente elevados. Amilasemias realizadas nos familiares, todos assintomáticos, mostraram níveis normais no pai e na avó materna e elevados na mãe, na irmã , na tia e no tio maternos. Macroamilasemia foi excluída na criança e na mãe. O encontro de níveis séricos de amilase persistentemente elevados na

  7. Celibacy and Family Disruption

    Directory of Open Access Journals (Sweden)

    Emaletdinov B. M.

    2013-01-01

    Full Text Available Causes for celibacy, divorces and successful marriage are discussed in the article. Absence of true love and inability to build and keep it are the main reasons for family disruption. Amorousness, immature love and various forms of false or flawed love substitute the true feeling. It is caused by increased women’s independence, loss of mutual understanding and trust (due to infidelity or jealousy, incompatibility of characters or values. Celibacy is often conditioned by physical disability, revaluation of freedom and independence, huge requirements to partners, consumer attitude to life, infertility, alcohol and drug abuse, abnormalities in personality and sexuality.

  8. The laminin family.

    Science.gov (United States)

    Aumailley, Monique

    2013-01-01

    Laminins are large molecular weight glycoproteins constituted by the assembly of three disulfide-linked polypeptides, the α, β and γ chains. The human genome encodes 11 genetically distinct laminin chains. Structurally, laminin chains differ by the number, size and organization of a few constitutive domains, endowing the various members of the laminin family with common and unique important functions. In particular, laminins are indispensable building blocks for cellular networks physically bridging the intracellular and extracellular compartments and relaying signals critical for cellular behavior, and for extracellular polymers determining the architecture and the physiology of basement membranes.

  9. Family Ties and Civic Virtues

    DEFF Research Database (Denmark)

    Ljunge, Jan Martin

    I establish a positive relationship between family ties and civic virtues, as captured by disapproval of tax and benefit cheating, corruption, and a range of other dimensions of exploiting others for personal gain. I find that family ties are a complement to social capital, using within country...... evidence from 83 nations and data on second generation immigrants in 29 countries with ancestry in 85 nations. Strong families cultivate universalist values and produce more civic and altruistic individuals. The results provide a constructive role for families in promoting family values that support...

  10. Familial risk factors in autism.

    Science.gov (United States)

    Brimacombe, Michael; Xue Ming; Parikh, Amisha

    2007-05-01

    Familial history risk factors in relation to autism were examined in a cohort of 164 autistic children referred to The Autism Center at New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, over a 2-year period (2001-2003). Information related to familial history was obtained from each family and reviewed by a clinician. It is shown that these families carry a higher overall burden of psychiatric and developmental illnesses compared to reported national levels. These families also carry a relatively high incidence of medical disorders, independently of developmental and psychiatric disorders. This work supports the underlying presence of genetic factors in the etiology of autism.

  11. Juvenile Delinquency and Family Structure

    Directory of Open Access Journals (Sweden)

    Miguel Alberto Ramírez Villaseñor

    2001-07-01

    Full Text Available The present study is an analysis of twelve family structure variables in a sample of 250 under-age offenders' families. All families had been remitted to the Parents Group at the Behavioral Control Clinic between February and September, 1988, charged with theft and/or drug abuse. There are certain factors in those families ( such as immigration, the attributed value of the identified patient, his adolescent stage, the presence of extensive family members and a dead brother that seem to decide the symptomatology even more than other frequently mentioned variables (i.e., parents civil status, separations, divorces, new marriages, mother's occupation. The detected family structure seems to show a very close link between mother and identified patient that displaces the father to the system's periphery. We consider that this form of family structure leads to situations such as single mothers or promiscuous daughters who show similar symptoms to those shown in the identified patient.

  12. Family dynamics and postnatal depression.

    Science.gov (United States)

    Tammentie, T; Tarkka, M-T; Astedt-Kurki, P; Paavilainen, E; Laippala, P

    2004-04-01

    Research has shown that postnatal depression (PND) affects 10-15% of mothers in Western societies. PND is not easily identified and therefore it often remains undetected. Untreated depression has a detrimental effect on the mother and child and the entire family. The purpose of this study was to ascertain the state of family dynamics after delivery and whether the mother's PND was associated with family dynamics. The study used a survey covering the catchment area of one Finnish university hospital. Both primi- and multiparas took part and data were collected using the Edinburgh Postnatal Depression Scale (EPDS) for mothers and the Family Dynamics Measure II (FDM II) for both mothers and fathers. The data were analysed using SPSS statistical programme and frequency and percentage distributions, means and standard deviations were examined. Correlations were analysed using Spearman's correlation coefficients. The significance of any differences between mothers' and fathers' scores was determined with a paired t-test. Of the families participating in the study (373 mothers and 314 partners), 13% of the mothers suffered from PND symptoms (EPDS score of 13 or more). As a whole, family dynamics in the families participating in the study were reported to be rather good. However, mothers having depressive symptoms reported more negative family dynamics compared with other families. With the exception of individuation, mothers having depressive symptoms reported more negative family dynamics than their partners. With the exception of role reciprocity, non-depressed mothers reported more positive family dynamics than their partners. Knowledge of the association of mothers' PND with family dynamics could help to develop nursing care at maternity and child welfare clinics and maternity hospitals. Depressed mothers and their families need support to be able to make family dynamics as good as possible.

  13. FAMILIAL MEDITERRANEAN FEVER AND HYPERCOAGULABILITY

    Directory of Open Access Journals (Sweden)

    Oshrat E. Tayer-Shifman

    2011-01-01

    Full Text Available family: ">Familial Mediterranean fever (FMF is an autosomal recessive hereditary disease which is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease. As such, FMF is a prototype of autoinflammatory diseases where genetic changes lead to acute inflammatory episodesfamily: ">.family: "> Systemic inflammation – in general - may increase procoagulant factors, and decrease natural anticoagulants and fibrinolytic activityfamily: ">.family: "> Therefore, it is anticipated to see more thrombotic events among FMF patients compared with healthy subjectsfamily: ">.family: "> However, reviewing the current available literature and based upon our personal experience, thrombotic events related purely to FMF are very rarefamily: ">.family: "> Possible explanation for this discrepancy is that along with the procoagulant activity during FMF acute attacks, anticoagulant and fibrinolytic changes are also taking placefamily: ">.family: "> Furthermore, it may well be that during the acute attack of FMF the procoagulant factors are consumed or used for the purpose of inflammation so that nothing is left for their role in the coagulation pathwayfamily: ">. family: ">Colchicine may also play a role in reducing inflammation thereby decreasing hypercoagulabilty

  14. Schaefer's "family cap".

    Science.gov (United States)

    1994-02-14

    Criticism was directed to Maryland Governor William Donald Shaefer's proposal to put family caps on welfare payments to recipients. The idea was to stop automatic increases in welfare payments if a recipient has an additional child. The objection was that 77%, or the bulk of welfare recipients, have only one or two children, and there is little, if any, evidence that welfare caps influence childbearing. The consequences of such reform would be the penalization of children. The political reality is that symbolism has become more important than facts. Putting a cap on welfare may make people feel better about welfare, and may show fairness to working people who don't get raises when their family size increases, but there are other implications. The messages to welfare recipients to stop having children, but not providing the means to do so, is hypocritical. Medicaid abortions were restricted in 1978 by politicians, but provision for better access to contraceptives was never promoted or achieved. Circumstances limit opportunities. The quality of care in public health clinics is abysmal: long lines and overcrowding, and inadequate proximity to welfare recipients' housing. Transportation, particularly in rural areas, is an impediment to access. It is estimated that only 60% of women eligible for government-funded contraception have access. A sign of serious welfare reform will be budget appropriations for day care, job training, and other reform programs.

  15. Family medicine in Cuba

    Directory of Open Access Journals (Sweden)

    Eduardo Alemañy Pérez

    2013-04-01

    Full Text Available Over the past 50 years, the Cuban health system has been developing a roster of programs to ensure its social mission: to achieve a health status of the population consistent with the priority established by the highest authorities of the country. In response to the call of the Commander in Chief, Fidel Castro Ruz, to create a different doctor and a new specialist that would take into account the needs of the Cuban population; the family doctor model was implemented. Thus, in the decade of the eighties, the “Family Doctor and Nurse Working Program” was established, together with the corresponding polyclinic and hospital. At the same time, comprehensive general medicine as a medical specialty was created to serve the primary health care services. Both actions constituted a vital component in the development of Cuban public health services in recent decades. This article presents an account of the unique characteristics of these processes, while highlighting their impact on health indicators, as well as the participation of this specialty in the training of human resources for the health system.

  16. FAMILIAL ADENOMATOUS POLYPOSIS

    Institute of Scientific and Technical Information of China (English)

    XU Ning; DING Yan-qing; XU Li

    1999-01-01

    @@ Clinical History A 41-year-old female was admitted into Nan Fang Hospital for severe abdominal pain with bloody-mucoid stool for a month. The symptoms started a year ago without obvious causes and she did not have any systemic treatment.The patient felt fatigue and loss of weight for the last three months and increased frequency of bloody-mucoid discharge from 2-4 times/day to 10 times/day for the last month. Two weeks ago the patient had a proctoscope with biopsy in Pan Yu people's Hospital. The pathological diagnosis was rectal villous adenoma with focal malignant changes. Rectal examination in this hospital found a rectal mass, 4 cm from the anus, longitudinal growing and occupying a quarter of the circumference. Further colonofiberscope diagnosis was familial polyposis of colon.Family history showed that her father died of lung cancer,her mother died of colonic cancer and her brother and sister were healthy. A total colo-rectectomy with ileostomy was performed.

  17. A compact SADM family

    Science.gov (United States)

    Barbet, Vincent; Le Quintrec, Cyrille; Jeandot, Xavier; Chaix, Alain; Grain, Eric; Roux, Jerome

    2005-07-01

    Alcatel Space has developed a new SADM family driven by cost, modularity, mass and performances. The modularity concept is based on separating the rotation drive function from the electrical transfer function. The drive actuator has been designed for various applications where pointing and reliability is needed. It can be associated with high dissipative rotary devices (SA collectors, RF joints..). The design goal was to minimize the number of parts in order to reach the most simple and compact mechanism. Mass reduction was achieved by reducing as much as possible the load path between the Solar Array interface and the spacecraft interface. Following these guidelines, the drive actuator was developed and qualified on ATV SADM (part od Alcatel Space Solar Array Drive Sub System for ATV). Further more a high power integrated collector was qualified inside the SADM for Geo-stationary telecom satellite (SPACEBUS platforms). Fine thermal and mechanical modeling was necessary to predict SADM behaviors for the numerous thermal environments over the missions (steady and transient cases). These modeling were well correlated through mechanical and thermal balances qualification tests. The challenging approach of thermal dissipation in a compact design leads to a family of 3 SADM capabilities form 2kW up to 15kW per SADM weighing less than 4.5 kg each.

  18. Familial Gastric Cancers

    Science.gov (United States)

    Setia, Namrata; Clark, Jeffrey W.; Duda, Dan G.; Hong, Theodore S.; Kwak, Eunice L.; Mullen, John T.

    2015-01-01

    Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%–3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Implications for Practice: Although the majority of gastric adenocarcinomas are sporadic with many of those related to chronic Helicobacter pylori infection, approximately 10% of the cases show familial aggregation, and a specific hereditary cause is determined in 1%–3% cases. This review describes the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Ultimately, a better understanding of the biology of these conditions should allow early identification and intervention as part of a multidisciplinary approach involving oncologists, surgeons, genetic counselors, and pathologists. PMID:26424758

  19. Familial hypercholesterolemia: A review

    Directory of Open Access Journals (Sweden)

    Mithun J Varghese

    2014-01-01

    Full Text Available Familial hypercholesterolemia (FH is a genetic disorder of lipoprotein metabolism resulting in elevated serum low-density lipoprotein (LDL cholesterol levels leading to increased risk for premature cardiovascular diseases (CVDs. The diagnosis of this condition is based on clinical features, family history, and elevated LDL-cholesterol levels aided more recently by genetic testing. As the atherosclerotic burden is dependent on the degree and duration of exposure to raised LDL-cholesterol levels, early diagnosis and initiation of treatment is paramount. Statins are presently the mainstay in the management of these patients, although newer drugs, LDL apheresis, and other investigational therapies may play a role in certain subsets of FH, which are challenging to treat. Together these novel treatments have notably improved the prognosis of FH, especially that of the heterozygous patients. Despite these achievements, a majority of children fail to attain targeted lipid goals owing to persistent shortcomings in diagnosis, monitoring, and treatment. This review aims to highlight the screening, diagnosis, goals of therapy, and management options in patients with FH.

  20. Familial adenomatous polyposis

    Directory of Open Access Journals (Sweden)

    Rozen Paul

    2009-10-01

    Full Text Available Abstract Familial adenomatous polyposis (FAP is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE, desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system. A less aggressive variant of FAP, attenuated FAP (AFAP, is characterized by fewer colorectal adenomatous polyps (usually 10 to 100, later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC gene. Most patients (~70% have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP, which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a