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Sample records for matrix metalloproteinase-3 role

  1. Spontaneous metastasis in matrix metalloproteinase 3-deficient mice

    DEFF Research Database (Denmark)

    Juncker-Jensen, Anna; Rømer, John; Pennington, Caroline J

    2009-01-01

    Matrix metalloproteinases (MMPs) have been linked to the metastatic potential of tumor cells due to their ability to degrade the extracellular matrix. MMP-3 (stromelysin-1) is upregulated in a wide variety of human tumors. We used the MMTV-PyMT breast cancer model to determine if MMP-3 is involved...

  2. Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression

    NARCIS (Netherlands)

    Posthumus, MD; Limburg, PC; Westra, J; van Leeuwen, MA; van Rijswijk, MH

    2000-01-01

    Objective. To analyze the clinical significance of serial measurements of serum matrix metalloproteinase 3 (MMP-3) levels in relation to markers of disease activity and radiological progression in early rheumatoid arthritis (RA). Methods. In a 3 year prospective study of 33 patients with early RA (s

  3. Structure of matrix metalloproteinase-3 with a platinum-based inhibitor.

    Science.gov (United States)

    Belviso, Benny Danilo; Caliandro, Rocco; Siliqi, Dritan; Calderone, Vito; Arnesano, Fabio; Natile, Giovanni

    2013-06-18

    An X-ray investigation has been performed with the aim of characterizing the binding sites of a platinum-based inhibitor (K[PtCl3(DMSO)]) of matrix metalloproteinase-3 (stromelysin-1). The platinum complex targets His224 in the S1' specificity loop, representing the first step in the selective inhibition process (PDB ID code 4JA1).

  4. Elevated expression of matrix metalloproteinase-3 in human osteosarcoma and its association with tumor metastasis.

    Science.gov (United States)

    Huang, Jie-Feng; Du, Wen-Xi; Chen, Jun-Jie

    2016-01-01

    Matrix metalloproteinase-3 (MMP-3) is one of the several MMPs that is associated with malignant tumors of breast, colon, cervix and lung, where its expression has been correlated with tumor invasion and metastasis. However, the role of MMP-3 in metastasis of osteosarcoma has not yet been explored. MMP-3 expression in 15 primary and metastatic osteosarcomas with case-matched adjacent non-tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. Further, MMP-3 mRNA and protein levels were also determined in osteoblast and osteosarcoma cell lines. Additionally, migration and invasion assays were performed in MMP-3 knockdown cells. MMP-3 was expressed in 86.6% (13/15) of the osteosarcoma patients and its expression was significantly higher in metastatic tumors as compared to the primary osteosarcoma tumor tissues. Furthermore, osteosarcoma cell lines showed higher MMP-3 expression as compared to osteoblast cell lines. siRNA-mediated MMP-3 knockdown in osteosarcoma cell lines significantly inhibited their migration and invasion properties. Our results demonstrated that MMP-3 expression is deregulated in osteosarcomas and this potentially contributes to metastasis and might be a promising marker for the prognosis and therapy of metastatic osteosarcoma.

  5. Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet's disease. Does interleukin-1beta play a major role in Behçet's synovitis?

    Science.gov (United States)

    Pay, Salih; Erdem, Hakan; Pekel, Aysel; Simsek, Ismail; Musabak, Ugur; Sengul, Ali; Dinc, Ayhan

    2006-05-01

    The objective of this study has been the well established fact that proinflammatory cytokines and metalloproteinases play a crucial role in the pathogenesis of chronic arthritis as well as the development of pannus, with the eventual erosive changes. Among the proinflammatory cytokines, interleukin-18 (IL-18) has been shown to contribute to the pathogenesis of chronic synovitis by increasing the secretion of interleukin-1beta (IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) and also stimulating angiogenesis. The aim of this study is to investigate the synovial IL-18, IL-1beta, TNF-alpha and matrix metalloproteinase-3 (MMP-3) levels in patients with Behçet's disease (BD), and compare them with the levels of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). 30 patients with BD, 20 with RA, and 20 with OA were included in the study. The synovial levels of IL-18, IL-1beta, TNF-alpha and MMP-3 were detected using the two-step sandwich ELISA method. The synovial IL-18, TNF-alpha and MMP-3 levels were significantly higher in RA patients than patients with BD (P=0.004, 0.019, 0.025, respectively) and with OA (P=0.004, 0.045, 0.032, respectively). There were no differences, with respect to the cytokine levels, when patients with BD were compared with those with OA. Patients with RA and BD had higher IL-1beta levels than patients with OA (P=0.017, 0.013, respectively). However, no such difference was found for IL-1beta between BD and RA patients. Among patients with RA, positive correlations were found between TNF-alpha and MMP-3 (r=0.683, P=0.001). Our results showed that MMP-3 and proinflammatory cytokines, except IL-1beta, were expressed in relatively small quantities in Behçet's synovitis. Detection of the lower levels of these cytokines and metalloproteinases might explain the non-erosive character of Behçet's arthritis. We suggest that IL-1beta may be involved in the pathogenesis of Behçet's synovitis.

  6. Role of matrix metalloproteinase 3 in supraspinal ligament degeneration due to ankylosing spondylitis%MMP-3在强直性脊柱炎棘上韧带退变中的作用

    Institute of Scientific and Technical Information of China (English)

    许红飞; 初同伟; 张超; 张莹; 黄晨; 刘栓得

    2012-01-01

    Objective To study the expression of matrix metalloproteinase 3 (MMP-3) and its effect on supraspinal ligament degeneration due to ankylosing spondylitis ( AS ) . Methods Expression of MMP-3 and type I collagen in ligaments was detected by immunohistochemistry. Proteoglycan level in ligaments was measured by ELISA. Supraspinal ligament morphology was observed under scanning electron microscope and transmission electron microscope, respectively. Collagen fibril distribution density and positively-stained collagen area were analyzed by Image-Pro Plus(IPP). Results MMP-3 was highly expressed in vascular smooth muscle cells and endothelial cells in AS group but not in control group. The proteoglycan level was significantly higher in control group than in AS group (19. 462 ±2. 174 vs 7. 477 ± 2. 512 μg/mg). The collagen fibrils were regularly arranged in control group and apparently exposed with massive degradation of matrix in AS group. The distribution density of collagen fibrils was 218. 02 ± 10. 39/|xm2 and 122. 47 ±22. 42μm2 in control group and AS group, respectively. The proportion of positively-stained collagen area was significantly higher in control group than in AS group [ (60. 23 ±3.41) % vs (43. 37 ±5. 96)% , P <0. 05]. Conclusion MMP-3 is highly expressed in supraspinal ligament blood vessels of active AS patients by promoting the growth of blood vessels, activating the degradation of proteoglycan, and destroying the normal ultra-structure of ligaments, and is thus involved in the degenerative ossification process of ligaments.%目的 探讨基质金属蛋白酶3(matrix metalloproteinase3,MMP-3)在强直性脊柱炎(ankylosing spondylitis,AS)棘上韧带中的表达及在韧带退变中的作用.方法 免疫组化检测MMP-3、Ⅰ型胶原在韧带中的表达,酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测韧带中蛋白聚糖(proteoglycan)的含量,扫描电镜及透射电镜对棘上韧

  7. Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells.

    Science.gov (United States)

    Deb, Gauri; Thakur, Vijay S; Limaye, Anil M; Gupta, Sanjay

    2015-06-01

    Aberrant epigenetic silencing of the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) gene that negatively regulates matrix metalloproteinases (MMPs) activity has been implicated in the pathogenesis and metastasis of breast cancer. In the present study, we demonstrate that green tea polyphenols (GTP) and its major constituent, epigallocatechin-3-gallate (EGCG) mediate epigenetic induction of TIMP-3 levels and play a key role in suppressing invasiveness and gelatinolytic activity of MMP-2 and MMP-9 in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 breast cancer cells with 20 µM EGCG and 10 µg/mL GTP for 72 h significantly induces TIMP-3 mRNA and protein levels. Interestingly, investigations into the molecular mechanism revealed that TIMP-3 repression in breast cancer cells is mediated by epigenetic silencing mechanism(s) involving increased activity of the enhancer of zeste homolog 2 (EZH2) and class I histone deacetylases (HDACs), independent of promoter DNA hypermethylation. Treatment of breast cancer cells with GTP and EGCG significantly reduced EZH2 and class I HDAC protein levels. Furthermore, transcriptional activation of TIMP-3 was found to be associated with decreased EZH2 localization and H3K27 trimethylation enrichment at the TIMP-3 promoter with a concomitant increase in histone H3K9/18 acetylation. Our findings highlight TIMP-3 induction as a key epigenetic event modulated by GTPs in restoring the MMP:TIMP balance to delay breast cancer progression and invasion.

  8. The anti-inflammatory effects of matrix metalloproteinase-3 on irreversible pulpitis of mature erupted teeth.

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    Hisanori Eba

    Full Text Available Matrix metalloproteinases (MMPs are involved in extracellular matrix degradation and the modulation of cell behavior. These proteinases have also been implicated in tissue repair and regeneration. Our previous studies have demonstrated that MMP-3 elicits stimulatory effects on the proliferation and the migration of endothelial cells as well as anti-apoptotic effects on these cells in vitro. In addition, we found that MMP-3 enhanced the regeneration of lost pulp tissue in a rat incisor pulp injury model. However, continuously erupting rodent incisors exhibit significantly different pulp organization compared with mature erupted teeth. Therefore, we have further extended these studies using a canine irreversible pulpitis model to investigate the effects of MMP-3. In this study, the crowns of the canine mature premolars were removed and the pulp tissues were amputated. The amputated pulp tissues remained exposed for 24 or 72 hours to induce mild or severe irreversible pulpitis, respectively, followed by sealing of the cavities. In both models, the whole pulp tissues became necrotic by day 14. In this mild pulpitis model, the regeneration of pulp tissue with vasculature and nerves was observed until 14 days after sealing with MMP-3, followed by extracellular matrix formation in the regenerated pulp tissues until day 28. The treatment with MMP-3 resulted in a decrease in the number of macrophage and antigen-presenting cells and a significant inhibition of IL-6 expression on day 3. The inhibition of MMP-3 activity abolished these anti-inflammatory effects. Immunofluorescence staining demonstrated that MMP-3 was involved in the modification of serum-derived hyaluronan-associated proteins and hyaluronan (SHAP-HA complexes possibly through the degradation of versican. These results demonstrate that MMP-3 can act as an anti-inflammatory agent and suggest that MMP-3 might represent a useful therapy for the treatment of mild irreversible pulpitis.

  9. Serum Matrix Metalloproteinase-3 as a Noninvasive Biomarker of Histological Synovitis for Diagnosis of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Jian-Da Ma

    2014-01-01

    Full Text Available Objective. To explore the correlation between matrix metalloproteinase- (MMP- 3 and histological synovitis in rheumatoid arthritis (RA. Methods. Serum MMP-3 of 62 patients with active RA was detected by ELISA. Serial synovial tissue sections from all RA patients, 13 osteoarthritis, and 10 orthopedic arthropathies patients were stained with hematoxylin and eosin and immunohistochemically for MMP-3, CD3, CD20, CD38, CD68, and CD15. Results. The percentage of lining MMP3+ cells was significantly higher in RA patients especially with high grade synovitis and it was significantly correlated with Krenn’s synovitis score r=0.574, P<0.001 and sublining inflammatory cells. Multivariate stepwise linear regression analysis revealed that the association of the percentage of lining MMP3+ cells with activation of synovial stroma, sublining CD68+ macrophages, and CD15+ neutrophils was stronger than other histological indicators. The percentage of lining MMP3+ cells was significantly correlated with serum MMP-3 in RA r=0.656, P<0.001. Serum MMP-3 was higher in RA patients with high grade synovitis than that of low grade synovitis and significantly correlated with synovitis score and activation of synovial stroma subscore (all P<0.05. Conclusion. Serum MMP-3 may be an alternative noninvasive biomarker of histological synovitis and RA diagnosis.

  10. Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression

    Science.gov (United States)

    Su, Chun-Wen; Su, Bo-Feng; Chiang, Whei-Ling; Yang, Shun-Fa; Chen, Mu-Kuan; Lin, Chiao-Wen

    2017-01-01

    Oral cancer is the most common malignancy with poor prognosis and is the fourth most common cancer in men in Taiwan. The tissue inhibitor of metalloproteinase-3 (TIMP3) acts as a tumor suppressor gene by inhibiting the growth, angiogenesis, migration, and invasion of cancer cells. However, few studies have examined the association of plasma TIMP3 levels with oral squamous cell carcinoma (OSCC), and the role of plasma TIMP3 levels in OSCC progression is still unclear. We measured the plasma TIMP3 levels of 450 OSCC patients and 64 healthy controls by using a commercial enzyme-linked immunosorbent assay. We also analyzed TIMP3 mRNA levels of 328 OSCC patients and 32 normal tissues from The Cancer Genome Atlas (TCGA) dataset. Our results revealed that plasma TIMP3 levels were significantly lower in patients with OSCC than in healthy controls (p < 0.001). Moreover, plasma TIMP3 levels in patients with OSCC were significantly associated with the tumor stage and tumor status but not with the lymph node status, metastasis, and cell differentiation. To verify our findings, we also examined TCGA bioinformatics database and discovered similar results for the association with the pathological stage of OSCC. In conclusion, our results suggest that plasma TIMP3 is a potential biomarker for predicting the tumor stage and T status in patients with OSCC. PMID:28138307

  11. Comparison of matrix metalloproteinase-3 and tissue inhibitor of matrix metalloproteinase-1 levels in gingival crevicular fluid in periodontal health, disease and after treatment: A clinico biochemical study

    Directory of Open Access Journals (Sweden)

    P Mohan Kumar

    2013-01-01

    Full Text Available Background: Considering the role of matrix metalloproteinase-3 (MMP-3 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 in the pathogenesis of periodontitis, the present study is to estimate the levels of MMP-3 and TIMP-1 in gingival crevicular fluid (GCF in periodontal health, disease and to evaluate the effect of periodontal therapy on MMP-3 and TIMP-1 concentrations in GCF. Materials and Methods: A periodontal examination and collection of GCF by extra-crevicular method was performed in 30 subjects selected randomly and categorized into 3 groups. Group I consists of 10 subjects Group II consists of 20 patients and Group III consists of 20 patients of Group II. Non surgical periodontal therapy was performed, and GCF was collected after 8 weeks from the same site of 20 chronic periodontitis patients who are considered as Group III. MMP- 3 and TIMP-1 levels were estimated in GCF-samples by using enzyme-linked immunosorbent assay. The findings were analyzed using the software and descriptive statistical methods such as Mann- Whitney U-test and Kruskal-Wallis test. P value < 0.001 was considered significant. Results: MMP-3 and TIMP-1 was detected in all samples. Highest mean MMP-3 concentrations in GCF were obtained for Group II (7.490 ng/ml while the lowest concentrations were seen in Group I (0.344 ng/ml and Group III (2.129 ng/ml. This suggests that MMP-3 levels in GCF increases proportionally with the progression of periodontal disease and decreases after treatment. Lowest mean TIMP-1 concentrations in GCF were obtained for Group-II (1.592 ng/ml, while the highest concentrations were seen in Group-I (8.78 ng/ml and Group-III (6.40 ng/ml. This suggests that TIMP-1 levels in GCF decreases proportionally with progression of periodontal disease and increases after treatment. Conclusion: There is a substantial increase in the concentrations of MMP-3 and decrease in TIMP-1 as periodontal disease progress. Since MMP-3 and TIMP-1 levels

  12. Vitamin D Receptor Gene, Matrix Metalloproteinase 3 Polymorphisms and the Risk of Intervertebral Disc Degeneration Susceptibility: Meta-Analysis

    Science.gov (United States)

    Huang, Yongjing; Zhao, Shujie; Xu, Nanwei

    2016-01-01

    Several studies have evaluated the association between vitamin D receptor, matrix metalloproteinase 3 (MMP-3) polymorphisms and the risk of intervertebral disc degeneration susceptibility. The findings were inconsistent. This meta-analysis aimed to systematically assess the association between vitamin D receptor, MMP-3 polymorphisms and the risk of intervertebral disc degeneration susceptibility. A search of various databases was done covering all papers published until December 31th, 2014. Eight, 4, 3 studies were finally included that addressed the risk of intervertebral disc degeneration susceptibility and vitamin D receptor FokI (rs2228570), ApaI (rs7975232), and MMP-3 (rs731236) polymorphisms, respectively. FokI (f vs. F: summary odds ratio [OR], 1.13; 95% confidence interval [CI], 0.76–1.69; ff vs. FF: OR, 1.02; 95% CI, 0.59–1.77; ff vs. Ff/FF: OR, 1.05; 95% CI, 0.70–1.58), ApaI (a vs. A: OR, 0.73; 95% CI, 0.45–1.19; aa vs. AA: OR, 0.53; 95% CI, 0.22–1.25 p=0.14; aa vs. AA/Aa: OR, 0.69; 95% CI, 0.53–0.89) in the vitamin D receptor gene and MMP3 polymorphisms (5A vs. 6A: OR, 1.92; 95% CI, 0.77–4.80; 5A5A vs. 6A6A: OR, 2.17; 95% CI, 0.75–6.24; 5A5A vs. 5A6A/6A6A: OR, 1.58; 95% CI, 0.72–3.44) were not obviously associated with risk of intervertebral disc degeneration susceptibility. FokI, ApaI polymorphisms in the vitamin D receptor gene and MMP-3 polymorphism are not obvious risk factors for intervertebral disc degeneration susceptibility.

  13. The presence of promatrix metalloproteinase-3 and its relation with different categories of coal workers' pneumoconiosis

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    Remzi Altin

    2004-01-01

    Full Text Available Extracellular matrix formation (ECM and remodeling are critical events related to the pathogenesis of pulmonary fibrosis. Matrix metalloproteinases play an essential role in degrading and remodeling the ECM. In this study, we tried to show the presence and correlation of promatrix metalloproteinase-3 (proMMP-3 (the inactive form of metalloproteinase-3 levels in coal workers' pneumoconiosis (CWP with different categories.

  14. Molecular Characterization and Expression Analysis of Matrix Metalloproteinase 3 in the Asian Yellow Pond Turtle Mauremys mutica

    Institute of Scientific and Technical Information of China (English)

    Mi ZHAO; Yan SHI; Jian ZHAO; Xinping ZHU; Kunci CHEN; Debo PAN; Chengqing WEI

    2014-01-01

    Matrix metallopeptidase 3 is a zinc-containing proteinase that participates in tissue remodeling and immune responses. In this study, a cDNA encoding matrix metallopeptidase 3 was isolated and characterized from the Asian yellow pond turtle Mauremys mutica (designated as MaMMP3). The MaMMP3 cDNA is 1805 bp and consists of a 5'-untranslated region (UTR) of 56 bp, a 3'-UTR of 243 bp, and an open reading frame (ORF) of 1506 bp encoding 481 amino acids. Homology analysis of MaMMP3 revealed that the MaMMP3 shared 25%-63%similarity to other known MMP3 sequences. The genomic sequence covers 6007 bp. Comparative analysis of the cDNA sequence revealed that the Asian yellow pond turtle MMP3 has eight exons and seven introns. The phylogenetic tree showed that the MaMMP3 is closely related to Gallus gallus MMP3 and Taeniopygia guttata MMP3. The mRNA expression of the MaMMP3 in normal group without any bacterial challenge could be detected in all studied tissues including kidney, heart, live and spleen, with the highest level in the spleen. The results of immune challenge showed that the expression level of MaMMP3 was up-regulated in the spleen and liver. These results provided an important information for studying the roles of Asian yellow pond turtle MMP3 in immunity further.

  15. The Ras guanine nucleotide exchange factor RasGRF1 promotes matrix metalloproteinase-3 production in rheumatoid arthritis synovial tissue

    NARCIS (Netherlands)

    de Abreu, J.R.F.; de Launay, D.; Sanders, M.E.; Grabiec, A.M.; van de Sande, M.G.; Tak, P.P.; Reedquist, K.A.

    2009-01-01

    Introduction Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis ( RA) patients share many similarities with transformed cancer cells, including spontaneous production of matrix metalloproteinases ( MMPs). Altered or chronic activation of proto-oncogenic Ras family GTPases is thought to

  16. The Diagnostic Utility of Anti-cyclic Citrullinated Peptide Antibodies, Matrix Metalloproteinase-3, Rheumatoid Factor, Erythrocyte Sedimentation Rate, and C-reactive Protein in Patients with Erosive and Non-erosive Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    O. Shovman

    2005-01-01

    Full Text Available Objective: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3, anti-cyclic citrullinated peptide (CCP antibodies, rheumatoid factor (RF, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP in patients with erosive and non-erosive rheumatoid arthritis (RA.

  17. Matrix metalloproteinase-3 in articular cartilage is upregulated by joint immobilization and suppressed by passive joint motion.

    Science.gov (United States)

    Leong, Daniel J; Gu, Xiang I; Li, Yonghui; Lee, Jonathan Y; Laudier, Damien M; Majeska, Robert J; Schaffler, Mitchell B; Cardoso, Luis; Sun, Hui B

    2010-06-01

    Both underloading and overloading of joints can lead to articular cartilage degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here we examine the effects of reduced loading of rat hindlimbs on articular cartilage expression of MMP-3, which not only digests matrix components but also activates other proteolytic enzymes. We show that hindlimb immobilization resulted in elevated MMP-3 mRNA expression at 6h that was sustained throughout the 21day immobilization period. MMP-3 upregulation was higher in the medial condyle than the lateral, and was greatest in the superficial cartilage zone, followed by middle and deep zones. These areas also showed decreases in safranin O staining, consistent with reduced cartilage proteoglycan content, as early as 7days after immobilization. One hour of daily moderate mechanical loading, applied as passive joint motion, reduced the MMP-3 and ADAMTS-5 increases that resulted from immobilization, and also prevented changes in safranin O staining. Intra-articular injections of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), dampened the catabolic effects of a 7day immobilization period, indicating a likely requirement for MMP-3 in the regulation of proteoglycan levels through ADAMTS-5. These results suggest that biomechanical forces have the potential to combat cartilage destruction and can be critical in developing effective therapeutic strategies.

  18. Polyphosphate induces matrix metalloproteinase-3-mediated proliferation of odontoblast-like cells derived from induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Hase, Naoko; Yamaguchi, Hideyuki; Hiyama, Taiki; Kawai, Rie [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 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (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 464-8650 (Japan)

    2015-05-01

    Inorganic polyphosphate [Poly(P)] may represent a physiological source of phosphate and has the ability to induce bone differentiation in osteoblasts. We previously reported that cytokine-induced matrix metalloproteinase (MMP)-3 accelerates the proliferation of purified odontoblast-like cells. In this study, MMP-3 small interfering RNA (siRNA) was transfected into odontoblast-like cells derived from induced pluripotent stem cells to investigate whether MMP-3 activity is induced by Poly(P) and/or is associated with cell proliferation and differentiation into odontoblast-like cells. Treatment with Poly(P) led to an increase in both cell proliferation and additional odontoblastic differentiation. Poly(P)-treated cells showed a small but significant increase in dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) mRNA expression, which are markers of mature odontoblasts. The cells also acquired additional odontoblast-specific properties including adoption of an odontoblastic phenotype typified by high alkaline phosphatase (ALP) activity and a calcification capacity. In addition, Poly(P) induced expression of MMP-3 mRNA and protein, and increased MMP-3 activity. MMP-3 siRNA-mediated disruption of the expression of these effectors potently suppressed the expression of odontoblastic biomarkers ALP, DSPP, and DMP-1, and blocked calcification. Interestingly, upon siRNA-mediated silencing of MMP-3, we noted a potent and significant decrease in cell proliferation. Using specific siRNAs, we revealed that a unique signaling cascade, Poly(P)→MMP-3→DSPP and/or DMP-1, was intimately involved in the proliferation of odontoblast-like cells. - Highlights: • Polyphosphate increases proliferation of iPS cell-derived odontoblast-like cells. • Polyphosphate-induced MMP-3 results in an increase of cell proliferation. • Induced cell proliferation involves MMP-3, DSPP, and/or DMP-1 sequentially. • Induced MMP-3 also results in an increase of odontoblastic

  19. Red ginseng saponin extract attenuates murine collagen-induced arthritis by reducing pro-inflammatory responses and matrix metalloproteinase-3 expression.

    Science.gov (United States)

    Kim, Ki Rim; Chung, Tae Yong; Shin, Heungsop; Son, Sung Ho; Park, Kwang-Kyun; Choi, Jong-Hoon; Chung, Won-Yoon

    2010-01-01

    Ginseng, the root of Panax ginseng C. A. MEYER, has been used as a food product and medicinal ingredient. In this study, we assessed the anti-arthritic effects of red ginseng saponin extract (RGSE), including ginsenosides Rg3, Rk1 and Rg5 as major components, on a murine type II collagen (CII)-induced arthritis (CIA), which is a valid animal model of human arthritis. Oral administration of RGSE at 10 mg/kg reduced the clinical arthritis score and paw swelling in the CIA mice, and inhibited joint space narrowing and histological arthritis, illustrating the severity of synovial hyperplasia, inflammatory cell infiltration, pannus formation, and erosion of cartilage. RGSE inhibited the expression of matrix metalloproteinase-3 and nitrotyrosine formation, and recovered the expression of superoxide dismutase in the joints of the CIA mice. Orally administered RGSE also reduced the levels of serum tumor necrosis factor-alpha and interleukin-1beta in the CIA mice. CII- or lipopolysaccharide-stimulated cytokine production, in addition to CII-specific proliferation, was reduced in the spleen cells of the RGSE-treated CIA mice, as compared with those from vehicle-treated CIA mice. Furthermore, RGSE administration protected against CIA-induced oxidative tissue damage by restoring the increased malondialdehyde levels and the decreased glutathione levels and catalase activities almost to control levels. Therefore, RGSE may be a beneficial supplement which can improve human arthritis.

  20. Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Hase, Naoko; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (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 464-8650 (Japan)

    2015-02-01

    A pro-inflammatory cytokine mixture (CM: interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ) and IL-1β-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells. - Highlights: • Pro-inflammatory cytokines induce MMP-3 activity in human odontoblast-like cells. • Increased MMP-3 activity can promote cell proliferation in odontoblasts. • Specific loss of MMP-3 increases apoptosis in odontoblasts. • MMP-3 has potential as a promising new target for pupal repair and regeneration.

  1. Curcumin alleviates matrix metalloproteinase-3 and -9 activities during eradication of Helicobacter pylori infection in cultured cells and mice.

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    Kundu, Parag; De, Ronita; Pal, Ipsita; Mukhopadhyay, Asish K; Saha, Dhira Rani; Swarnakar, Snehasikta

    2011-01-21

    Current therapy-regimens against Helicobacter pylori (Hp) infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS) cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag)(+ve) and cag(-ve) Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT) alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin's action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities.

  2. Curcumin alleviates matrix metalloproteinase-3 and -9 activities during eradication of Helicobacter pylori infection in cultured cells and mice.

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    Parag Kundu

    Full Text Available Current therapy-regimens against Helicobacter pylori (Hp infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag(+ve and cag(-ve Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin's action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities.

  3. Expression of tumor necrosis factor-alpha converting enzyme and matrix metalloproteinase-3 in proliferated synovium in a patient with synovitis-acne-pustulosis-hyperostosis-osteitis syndrome: a case report

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    Komiya Koichiro

    2009-09-01

    Full Text Available Abstract Introduction Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO syndrome is a rare disorder. The etiology remains unknown and the treatment is still empirical. Synovitis is one of the major manifestations, but information on histopathological features is still lacking. In this case, we investigated the histopathological features of SAPHO syndrome synovitis. Case presentation We present the case of a 53-year-old Japanese woman with SAPHO syndrome accompanied by marked knee synovitis and palmoplantar pustulosis. We found abundant sterile joint fluid in the right knee, and a blood test showed abnormally high values of C-reactive protein (17.26 mg/dl and matrix metalloproteinase-3 (800 ng/ml. Arthroscopic surgery revealed marked proliferation of villous synovial tissues similar to rheumatoid arthritis and standard microscopic findings were also similar to rheumatoid arthritis. Furthermore, for the first time, we demonstrated by immunohistochemistry the expression of tumor necrosis factor-alpha (TNF-α converting enzyme, TNF-α and matrix metalloproteinase-3 in the proliferated synovial lining cells. After arthroscopic synovectomy, her knee symptoms immediately diminished and laboratory data (matrix metalloproteinase-3 and C-reactive protein normalized within 2 weeks of surgery. Conclusion We demonstrate the expression of TNF-α converting enzyme, TNF-α and matrix metalloproteinase-3 in SAPHO syndrome synovitis for the first time and also show, both macro- and microscopically, the similarity between SAPHO syndrome and rheumatoid arthritis synovitis. These new findings support the recently reported successful treatment of SAPHO syndrome with antirheumatic drugs, especially with anti-TNF-α agents.

  4. α2 Integrin, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-3 act sequentially to induce differentiation of mouse embryonic stem cells into odontoblast-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Kawai, Rie; Hase, Naoko; Hiyama, Taiki; Yamaguchi, Hideyuki [Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651 (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan)

    2015-02-01

    We previously reported that interleukin 1β acts via matrix metalloproteinase (MMP)-3 to regulate cell proliferation and suppress apoptosis in α2 integrin-positive odontoblast-like cells differentiated from mouse embryonic stem (ES) cells. Here we characterize the signal cascade underpinning odontoblastic differentiation in mouse ES cells. The expression of α2 integrin, extracellular matrix metalloproteinase inducer (Emmprin), and MMP-3 mRNA and protein were all potently increased during odontoblastic differentiation. Small interfering RNA (siRNA) disruption of the expression of these effectors potently suppressed the expression of the odontoblastic biomarkers dentin sialophosphoprotein, dentin matrix protein-1 and alkaline phosphatase, and blocked odontoblast calcification. Our siRNA, western blot and blocking antibody analyses revealed a unique sequential cascade involving α2 integrin, Emmprin and MMP-3 that drives ES cell differentiation into odontoblasts. This cascade requires the interaction between α2 integrin and Emmprin and is potentiated by exogenous MMP-3. Finally, although odontoblast-like cells potently express α2, α6, αV, β1, and β3, integrins, we confirmed that β1 integrin acts as the trigger for ES cell differentiation, apparently in complex with α2 integrin. These results demonstrate a unique and unanticipated role for an α2 integrin-, Emmprin-, and MMP-3-mediated signaling cascade in driving mouse ES cell differentiation into odontoblast-like cells. - Highlights: • Odontoblast differentiation requires activation of α2 integrin, Emmprin and MMP-3. • α2 integrin, Emmprin and MMP-3 form a sequential signaling cascade. • β1 integrin acts a specific trigger for odontoblast differentiation. • The role of these effectors is highly novel and unanticipated.

  5. Interleukin-4 inhibition of interleukin-1-induced expression of matrix metalloproteinase-3 (MMP-3 is independent of lipoxygenase and PPARγ activation in human gingival fibroblasts

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    Gorski Grzegorz

    2007-02-01

    Full Text Available Abstract Background Interleukin 4 (IL-4 has been shown to suppress interleukin-1 (IL-1 induced expression of matrix metalloproteinase-3 (MMP-3 in human synovial and gingival fibroblasts, but the mechanism of suppression has not been determined. Activators of peroxisome proliferator-activated receptor-γ (PPARγ have been shown to inhibit cytokine induced expression of MMPs in other cell types, and IL-4 has been shown to activate PPARγ by stimulating production of ligands through the lipoxygenase pathway. It has been suggested that PPARγ may inhibit expression of MMPs by competing with transcription factor AP-1 for binding to a putative composite binding element in the promoters. The objective of this study was to determine whether the suppressive effects of IL-4 on the IL-1 induced expression of MMP-3 involve activation of lipoxygenase and/or PPARγ. Results Western blotting revealed the presence of PPARγ in nuclear extract of HGF. IL-1 induced binding of nuclear extract to the putative composite PPRE/AP-1 site was diminished in the presence of pioglitazone, but there was no evidence of any change in the composition of the retarded complexes, and no evidence of PPARγ binding to this site. Nordihydroguaiaretic acid (NDGA, a non-selective lipoxygenase inhibitor, and MK886, a specific inhibitor of 5-lipoxygenase, induced MMP-3 expression synergistically with IL-1. However IL-4 was still able to inhibit MMP-3 expression in the presence of NDGA or MK886 and IL-1. Activation of PPARγ with pioglitazone not only failed to inhibit IL-1 induced expression of MMP-3 mRNA, but rather super-induced MMP-3 in the presence of IL-1. PPARγ antagonist GW9662 failed to abolish the suppressive effects of IL-4. Another PPARγ activator, 15-deoxy-Delta12,14prostaglandin J2 (15dPGJ2, also super-induced MMP-3 mRNA, and this was due at least in part to increased transcription. Conclusion IL-4 suppression of IL-1-induced MMP-3 expression in HGF is independent of

  6. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF alpha inhibitors

    DEFF Research Database (Denmark)

    Pedersen, S.J.; Hetland, M.L.; Sørensen, Inge Juul;

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated...... with tumor necrosis factor-alpha (TNF alpha) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n = 32, and psoriatic arthritis, n = 17) initiating TNF alpha inhibitor therapy (infliximab, n = 38......Euro parts per thousand 0.001), whereas total aggrecan was lower (662 mu g/l (223-2,219) vs. 816 (399-2,190),p a parts per thousand currency signaEuro parts per thousand 0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p a parts per thousand currency signa...

  7. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. In this work we confirm that placental leukocytes from human term

  8. Matrix Metalloproteinase-3 (MMP-3 Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Directory of Open Access Journals (Sweden)

    Arturo Flores-Pliego

    Full Text Available The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9 it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation.Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence.Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05, when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05 and up to 72 h (P≤0.001, when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005 when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells.In this work we confirm that placental leukocytes from

  9. 退变腰椎Modic改变及分型与肿瘤坏死因子α、基质金属蛋白酶3的表达%Modic changing and typing of degenerative lumbar and the expression of tumor necrosis factor alpha and matrix metalloproteinase 3

    Institute of Scientific and Technical Information of China (English)

    姜世峰; 申才良; 董福龙; 张建湘; 李勇

    2012-01-01

    BACKGROUND: In recent years, a large number of reports have shown that in lumbar degenerative diseases, inflammatory cytokines play an important role, and the signals of the degenerative lumbar endplate and regional vertebral endplate are changed on MRI.OBJECTIVE: To investigate the effect of tumor necrosis factor alpha and matrix metalloproteinase 3 expression on Modic changes of lumbar endplate and the bone under endplate on MRI.METHODS: In the experimental group, 20 lumbar endplates were obtained during surgery from the patients with lumbar degeneration treated by lumbar interbody fusion. Both Modic type Ⅰ and Modic type Ⅱ contained 10 cases. As the control group, 10 lumbar endplates were also got during surgery from patients with trauma of vertebra treated with lumbar interbody fusion. The expression of tumor necrosis factor alpha and matrix metalloproteinase 3 in lumbar endplate was tested by immunohistochemical staining.RESULTS AND CONCLUSION: The positive ratio of tumor necrosis factor alpha and matrix metalloproteinase 3 in the experimental group was significantly higher than that in the control group (P < 0.05); the expressions of tumor necrosis factor alpha and matrix metalloproteinase 3 in Modic type Ⅰ were significantly higher than those in Modic type Ⅱ (P < 0.05); in the experimental group, the expression of matrix metalloproteinase 3 showed no correlation with the expression of tumor necrosis factor alpha. The expression of tumor necrosis factor alpha and matrix metalloproteinase 3 may promote vertebral endplates degeneration; there was significant difference of the tumor necrosis factor alpha and matrix metalloproteinase 3 expression between different Modic types.%背景:大量文献报道了炎性细胞因子在腰椎退变性疾病中发挥着重要的作用,并发现这些退变的腰椎终板及终板下区域椎体在MRI上出现信号的改变.目的:探讨肿瘤坏死因子α、基质金属蛋白酶3与腰椎终板及终板下骨质

  10. Synergistic effect of stromelysin-1 (matrix metalloproteinase-3 promoter (-1171 5A->6A polymorphism in oral submucous fibrosis and head and neck lesions

    Directory of Open Access Journals (Sweden)

    Shukla Shirish

    2010-07-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are enzymes that degrade all the components of extra cellular matrix and collagen. Various types of MMPs are known to be expressed and activated in patients with oral submucous fibrosis (OSMF as well as head and neck squamous cell carcinoma (HNSCC. The purpose of this study was to asses the association of the single nucleotide polymorphism (SNP adenosine insertion/deletion polymorphism (-1171 5A->6A in the MMP-3 promoter region in these lesions. Methods MMP-3 SNP was genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP analysis in a case control study consisting of 362 participants; 101 cases of OSMF, 135 of HNSCC and 126 controls, compared for age, sex and habits. ROC distribution was plotted to assess the contributions of genetic variation in MMP-3 genotypes with relation to age. Results Analysis of MMP 3 (-1171 5A->6A polymorphism revealed the frequency of 5A allele in OSMF, HNSCC and controls to be 0.15, 0.13 and 0.07, respectively. A significant difference was found in 5A genotype frequency between OSMF (5A genotype frequency = 0.15, p = 0.01, OR = 2.26, 95% CI = 1.22-4.20 and in controls (5A genotype frequency 0.07 as well as HNSCC (5A genotype frequency 0.13, p = 0.03,95%CI = 1.06-3.51 and controls (5A genotype frequency = 0.07 In this study, 5A genotype had greater than two fold risk for developing OSMF (OR = 2.26 and nearly the same in case of HNSCC (OR = 1.94 as compared to controls. In patients with OSMF as well as HNSCC, the ROC analysis between the MMP-3 genotype and age, 6A/6A allele was found to be significant in patients both over and under 45 years of age; while the 5A/5A carrier alleles showed an association only in patients less than 45 years of age. Conclusions This study concluded that the expression of MMP-3 genotype associated with the 5A alleles, it may have an important role in the susceptibility of the patients to develop OSMF and HNSCC.

  11. IL-1β-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Hase, Naoko; Hiyama, Taiki; Yamaguchi, Hideyuki; Kawai, Rie [Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651 (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan)

    2014-10-15

    We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into α2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis in these cells, suggesting that MMP-3 plays a potentially unique physiological role in the regeneration of odontoblast-like cells. Here, we examined whether up-regulation of MMP-3 activity by IL-1β was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1β increased mRNA and protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and Wnt5b were found to increase MMP-3 mRNA, protein and activity, and interestingly the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a, Wnt5b and Lrp5 suppressed the IL-1β-induced increase in MMP-3 expression and suppressed cell proliferation, an effect rescued by application of exogenous Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP-3 in effecting IL-1β-induced proliferation of ES cell-derived odontoblast-like cells. - Highlights: • IL-1β induces Wnt5, Lrp5/Fzd9 and MMP-3 in ES cell-derived odontoblast-like cells. • IL-1β-induced Wnt5 expression results in increased cell proliferation. • Exogenous Wnt5 increases MMP-3 activity and cell proliferation. • Exogenous Wnt5 rescues IL-1β-driven proliferation with anti-Wnt5 siRNA suppression. • IL-1β-induced cell proliferation involves Wnt5, Lrp5, and MMP-3 sequentially.

  12. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF alpha inhibitors

    DEFF Research Database (Denmark)

    Pedersen, S.J.; Hetland, M.L.; Sørensen, Inge Juul

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......; etanercept, n = 8; and adalimumab, n = 3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n = 4), missing baseline samples (n = 3), and adverse events (n = 5) were...... excluded. Patients with SpA had compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 mu g/l (14-572) vs. 43 (20-184)), and MMP-3 (43 mu g/l (9.1-401) vs. 16 (2.5-47), p a parts per thousand currency signa...

  13. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Ostergaard, Mikkel; Nielsen, Hans Jørgen

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......; and adalimumab, n=3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n=4), missing baseline samples (n=3), and adverse events (n=5) were excluded. Patients with SpA had...... compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 µg/l (14-572) vs. 43 (20-184)), and MMP-3 (43 µg/l (9.1-401) vs. 16 (2.5-47), p=0.001), whereas total aggrecan was lower (662 µg/l (223-2,219) vs. 816 (399...

  14. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Hetland, Merete Lund; Sørensen, Inge Juul

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......; and adalimumab, n=3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n=4), missing baseline samples (n=3), and adverse events (n=5) were excluded. Patients with SpA had...... compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 μg/l (14-572) vs. 43 (20-184)), and MMP-3 (43 μg/l (9.1-401) vs. 16 (2.5-47), p≤0.001), whereas total aggrecan was lower (662 μg/l (223-2,219) vs. 816 (399...

  15. Matrix metalloproteinase-3 promoter polymorphisms but not dupA-H. pylori correlate to duodenal ulcers in H. pylori-infected females

    Directory of Open Access Journals (Sweden)

    Yeh Yi-Chun

    2010-08-01

    Full Text Available Abstract Background This study investigated if the H. pylori dupA genotype and certain host single nucleotide polymorphisms (SNPs of matrix metalloproteinases (MMPs and their inhibitors (TIMPs, including MMP-3, MMP-7, MMP-9, TIMP-1 and TIMP-2, might correlate with ulcer risk of H. pylori-infected Taiwanese patients. Results Of the 549 H. pylori-infected patients enrolled, 470 patients (265 with gastritis, 118 with duodenal ulcer, and 87 with gastric ulcer received SNPs analysis of MMP-3-1612 6A > 5A, MMP-7-181 A > G, MMP-9exon 6 A > G, TIMP-1372 T > C and TIMP-2-418 G > C by PCR-RFLP. The 181 collected H. pylori isolates were detected for the dupA genotype by PCR. The rates of dupA-positive H. pylori infection were similar among patients with duodenal ulcer (22.8%, gastric ulcer (20.0%, and gastritis (25.5% (p > 0.05. Males had higher rates of duodenal ulcer and gastric ulcer than females (p H. pylori-infected patients, the MMP-3 6A6A genotype were more common in patients with duodenal ulcers than in those with gastritis (87.7% vs. 74.9%, p p H. pylori-infected females. Conclusions The MMP-3 promoter polymorphism, but not the dupA-status, may correlate with susceptibility to duodenal ulcer after H. pylori infection in Taiwanese females.

  16. The diagnostic utility of anti-cyclic citrullinated peptide antibodies, matrix metalloproteinase-3, rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein in patients with erosive and non-erosive rheumatoid arthritis.

    Science.gov (United States)

    Shovman, O; Gilburd, B; Zandman-Goddard, G; Sherer, Y; Orbach, H; Gerli, R; Shoenfeld, Y

    2005-09-01

    To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA). We assembled a training set, consisting of 60 patients with RA, all fulfilling the revised criteria of the American College of Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF were detected by latex-enhanced immunonephelometric assay. CRP was measured by latex turbidimetric immunoassay. The levels of anti-CCP antibody titers and ESR were significantly higher in patients with erosive disease than those in non-erosive RA patients (p elevated titers of anti-CCP antibodies was found in RA patients with erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively). The ROC curves of anti-CCP passed closer to the upper left corner than those other markers and area under the curve (AUC) of anti-CCP was significantly larger than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP, 0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher for anti-CCP antibodies in comparison to other markers. We did not find significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as ESR or CRP. However, we confirmed the correlation of elevated titers of anti-CCP antibodies and RF in both groups of patients whereas the degree of correlation was more significant in non-erosive patients. The results of our study suggest that the presence of elevated anti-CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and ESR in patients with erosive RA.

  17. Expression of matrix metalloproteinases-3 gene in lens epithelial cell and its significance%基质金属蛋白酶3在晶状体上皮细胞中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    杨晶晶; 何湘珍; 向浩天; 周晓敏; 王云; 蔡素萍

    2012-01-01

    Background Posterior capsular opacification(PCO) is common complication after extrecapsular extract of cataract.Matrix metalloproteinases-3 (MMP-3) can degrade all the extracellular matrix except polyose.The gene therapy of PCO upon MMP-3 is the researching hot topic.Fibronectin ( FN ) is a degrade gelatin,so its expression can reflect the effect of MMP-3 on LECs indirectly. Objective The aim of this study was to construct MMP-3 eukaryotic recombination plasmid and transfect to lens epithelium cells(LECs) for the observation of MMP3 expression,and to explore the feasibility of gene therapy for after cataract. Methods Six fresh lenses were obtained from pigs.LECs were cultured using explant method.The eukaryotic expression vector pEGFP-N1-MMP-3 was reconstructed with MMP-3 and pEGFP-N1 plasmids.The accuracy of MMP-3 gene fragment was confirmed by double enzyme digestion and DNA sequencing analysis.After transfecting pEGFP-N1-MMP-3 into LECs of pig,the expression of MMP-3 protein in the cells was indirectly observed by green fluorescent protein.The expression of FN in LECs was detected using Western blot. Results The result of double enzyme digestion was consistent with the base number of pEGFP-N1 plasmids and target fragment.By enlacing the result of DNA sequencing analysis with software,the resemblance of the DNA sequence of MMP-3 from recombination plasmid pEGFP-N1-MMP-3 and that of homo MMP-3 was 99.6%,indicating that the target fragment was inserted to pEGFP-N1 plasmids successfully.Green fluorescence for GFP was seen in the LECs in pEGFP-N1-MMP-3 transfected group,but absent response for GFP was in empty vector group.Western blot revealed that the relative expression level of FN in LECs was 0.666±0.008 in pEGFP-N1-MMP-3 trasfected group and 0.326 ±0.071 in empty vector group,with a significant difference between these two groups(P=0.000). Conclusions Eukaryotic recombination plasmid pEGFP-N1-MMP-3 is successfully constructed,and MMP-3 can be expressed in

  18. Minimally invasive colorectal resection is associated with significantly elevated levels of plasma matrix metalloproteinase 3 (MMP-3) during the first month after surgery which may promote the growth of residual metastases.

    Science.gov (United States)

    Shantha Kumara, H M C; Gaita, David J; Miyagaki, Hiromichi; Yan, Xiaohong; Herath, Sonali A C; Cekic, Vesna; Whelan, Richard L

    2014-12-01

    MMP-3, a member of the matrix metalloproteinase (MMP) family, is involved in the breakdown of the extracellular matrix in tissue remodeling and may also play a role in cancer progression and metastasis. Minimally invasive colorectal resection (MICR) may increase plasma MMP-3 levels directly via surgical trauma or indirectly due to surgery-associated elevations in TNF-α and IL1 which are regulators of MMP-3. This study's purpose was to evaluate plasma MMP-3 levels during the first month after MICR for colorectal cancer. Patients enrolled in an IRB approved data/plasma bank who underwent elective MICR for CRC. Blood plasma samples had been collected preoperatively, on postoperative day (POD) 1, 3 and at varying postoperative time points and were stored at -80 °C. The late samples (POD 7-41) were bundled into 7 day time blocks and considered as single time points. MMP-3 levels were analyzed in duplicate via ELISA and the results reported as mean ± SD. The paired t test was used for analysis (significance, p MICR met the inclusion criteria. The mean PreOp MMP-3 level was 14.9 ± 7.8 ng/ml (n = 73). Significantly elevated mean plasma levels were noted on POD 1 (21.4 ± 14.7 ng/ml, n = 73, p MICR for CRC. The early postoperative increase in MMP-3 levels may be due to the surgery-related acute inflammatory response; the elevation noted during weeks 2-3 may be related to wound healing. Increased MMP-3 levels may promote metastases or the growth of residual cancer.

  19. Expression and clinical significance of matrix metalloproteinase-3 and osteopontin in cervical carcinoma%基质金属蛋白酶-3和骨桥蛋白在子宫颈癌组织中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    刘伟; 郑曙民

    2010-01-01

    Objective To study the expressions of matrix metalloproteinase-3 (MMP-3) and osteopontin (OPN) in cervical carcinoma and their relationship with invasion and metastasis. Methods The expression of MMP-3 and OPN were detected in 54 cases of cervical cancer tissues by immunohistochemical SP method. Compared with 15 cases of normal cervical tissues, the relationship was analyzed between both protein expressions and clinical pathology. Results The expression positive rates of MMP-3 and OPN in cervical cancer tissues (70.37 % and 66.7 %, respectively) were significantly higher than those of normal cervical tissues (20 % and 0, respectively), were significantly higher with infiltration depth >1/2 and lymph node metastasis than those with depth≤1/2 and without metastasis , respectively(P 1/2的阳性表达率显著高于间质浸润深度≤1/2者(P<0.05);子宫颈癌有淋巴结转移者MMP-3和OPN的阳性表达率显著高于无转移者(P<0.05),其表达与浸润深度、淋巴结转移相关.MMP-3与OPN的表达呈显著正相关(r=0.401,P<0.05).结论 MMP-3和OPN与子宫颈癌的浸润转移有关.

  20. Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage [v2; ref status: indexed, http://f1000r.es/1ks

    Directory of Open Access Journals (Sweden)

    Abigail L Clutterbuck

    2013-08-01

    Full Text Available Objective: Curcumin (diferuloylmethane is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA. The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β-stimulated inflammation and catabolism in an explant model of cartilage inflammation. Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2 and matrix metalloproteinase (MMP-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days. Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001 after 24 hours. After 48 hours and five days, curcumin (≥25μM significantly increased cell death (p<0.001 both time points. In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM significantly reduced IL-1β-stimulated PG (p<0.05 and PGE2 release (p<0.001 from explants, whilst curcumin (≥12μM significantly reduced MMP-3 release (p<0.01. Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

  1. Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage [v1; ref status: indexed, http://f1000r.es/1cl

    Directory of Open Access Journals (Sweden)

    Abigail L Clutterbuck

    2013-07-01

    Full Text Available Objective: Curcumin (diferuloylmethane is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA. The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β-stimulated inflammation and catabolism in an explant model of cartilage inflammation. Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2 and matrix metalloproteinase (MMP-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days. Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001 after 24 hours. After 48 hours and five days, curcumin (≥25μM significantly increased cell death (p<0.001 both time points. In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM significantly reduced IL-1β-stimulated PG (p<0.05 and PGE2 release (p<0.001 from explants, whilst curcumin (≥12μM significantly reduced MMP-3 release (p<0.01. Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

  2. The significance of determination of Matrix Metalloproteinase-3(MMP-3)content in lumbar disc herniation.%腰椎间盘突出症血清MMP-3测定的意义

    Institute of Scientific and Technical Information of China (English)

    郑昱新; 石印玉

    2001-01-01

    Objective To investigate the relationship between sero-matrix mefalloproteinase-3(MMP-3) content and lumbar disc herniation.Method The sero-MMP-3 content in 32 patients with lumbar disc herniation and 10 normal human were determined with enzyme-immunoassay method.Result The mean sero-MMP-3 content in lumbar disc herniation was 35.57ng/ml,while normal human27.56ng/ml,the deference was siginificant (P<0.01).However the sero-MMP-3 content in lumbar disc prolapsus was siginificantly higher than that in nonprolapsus(P<0.05).Conclusion The determination of sero-MMP-3 content can be used as assistant diagnosis of the lumbar disc herniation,furthermore confirm the relationship between sero-MMP-3 content and degree of lumbar disc degeneration.%目的 进一步研究血清MMP-3的含量与腰椎间盘突出症发病的关系。方法 32例腰椎间盘突出症患者和10例正常人,用酶免疫法测定他们血清MMP-3的含量。结果 腰椎间盘突出症患者血清MMP-3含量的平均值为:35.57ng/ml,而正常人平均值为:27.56ng/ml,两者的差异有显著性意义(P<0.01)。其中脱出型腰椎间盘突出症患者的血清MMP-3含量明显高于非脱出型患者(P<0.05)。结论 血清MMP-3的测定可作为对腰椎间盘突出症的辅助诊断,并且证实血清MMP-3的含量与腰椎间盘的退变程度相关。

  3. 系统性红斑狼疮患者外周血中基质金属蛋白酶-3及其金属蛋白酶组织抑制剂-1的表达及其临床意义%Matrix metalloproteinases-3 and tissue inhibitor of metalloproteinases-1 in the serum of patients with systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    刘博; 赵铖; 米存东; 陈战瑞; 雷玲

    2011-01-01

    Objective To investigate the serum concentration of matrix metalloproteinases -3 and its its inhibitor tissue inhibitor of metalloproteinases -1 in the patients with systemic lupus erythematosus ( SLE )and correlate them with clinic and pathologic parameters . Methods Serum levels of MMP-3 and TIMP-1 in a group of 60 patients with SLE and 30 healthy controls were assessed by ELISA . Results The MMP-3 and TIMP-1 serum levels were lower in SLE group than in the control group ,hut the MMP-3/TIMP-1 ratio was higher in SLE group than in the control group (P < 0. 001 ) ;The MMP-3 and TIMP-1 serum levels were lower in the lupus nephritis ( LN) group than in the SLE patients without LN ( P < 0. 001 ) ;The MMP-3 and TIMP1 serum levels were lower in active SLE patients than in inactive ones ( P < 0. 001 ) ; There had no difference with MMP-3 and TIMP-1 serum levels and MMP-3/TIMP-1 ratio among the WHO class Ⅱ,Ⅲ,Ⅳ,Ⅴ LN groups (P > 0. 05 ) ; The serum levels of MMP-3 and TIMP-1 were negatively correlated to proteinuria,systemic lupus erythematosus disease activity index ( SLEDAI) and anti-dsDNA ( rs-MMP-3 = - 0. 507 ,- 0. 817 , - 0. 457 ,P < 0. 001 ; rs-TIMP-1 = - 0. 416 , - 0. 720 , - 0. 506 ,P < 0. 001 ) , and were positively correlated to C3 , C4 ( rs-MMP-3 = 0. 346 ,0. 377 ,P < 0. 01 ; rs-TIMP-1 = 0. 418 , 0. 361 ,P< 0. 01 ) ; There was no correlation between serum levels of MMP -3 and TIMP-1 and erythrocyte sedimentation rate ( ESR) , C reactive protein ( CRP) , blood urea nitrogen ( BUN) , serum creatinine ( Scr) . Conclusions Serum levels of MMP-3 and TIMP-1 were degraded in patients with SLE and they can reflect the activity of the disease . The imbalance between these two factors may play an important role in SLE pathogenesis .%目的 研究系统性红斑狼疮(SLE)患者血清中基质金属蛋白酶-3(MMP-3)及金属蛋白酶组织抑制剂-1(TIMP-1)的表达,分析MMP-3、TIMP-1 与各临床指标及不同肾脏病

  4. Constructing and identifying a lentiviral vector of RNA interference targeting matrix metalloproteinases-3 gene in human degenerative nucleus pulposus cells%人基质金属蛋白酶3基因RNA慢病毒载体构建及在人退变髓核细胞中的鉴定

    Institute of Scientific and Technical Information of China (English)

    曹进; 傅培荣; 房晶; 杨建坤; 位华卫; 李思源; 高峰; 西永明

    2016-01-01

    BACKGROUND: Inhibiting the degradation of extracellular matrix in the intervertebral disc can delay the degenerative process of intervertebral disc. Matrix metalloproteinases-3 (MMP3) is considered as a key enzyme for degradation of extracelular matrix components such as type II collagen and aggrecan. OBJECTIVE:To construct the short hairpin RNA lentiviral vector targeting human MMP3 gene and to detect its efficiency of gene silence by infecting human degenerative nucleus pulposus cells. METHODS:According to the human MMP3 mRNA (NM_002422.4) sequence, four groups of the short hairpin RNA gene sequences targeting MMP3 were designed, synthesized and annealed to form double stranded DNA fragments, which were connected with the LV3 vectors digested by BamHI andEcoRI enzymes, and then transfected into the competent cels. The positive clones were identified by PCR, and analyzed by sequencing. The packaging and titer of lentivirus were determined after transfecting 293T cells. Human degenerative nucleus pulposus cels were infected with lentivirus vector, and the transfection efficiency of each group was observed under inverted fluorescence microscope. The interfering efficiency was detected by real time-PCR and western blot at 72 and 96 hours. RESULTS AND CONCLUSION:The ds-oligo DNA was successfully inserted into the lentiviral vector as confirmed by electrophoresis and sequence analysis. The recombinant lentivirus was harvested from 293T cels with a viral titer of 1-5 ×108 TU/mL. RNA interference targeting the GCC AGG CTT TCC CAA GCA AAT sequences with the highest interfering efficiency in MMP3 gene at 72 and 96 hours resulted in suppression of MMP3 mRNA expression by 98% and 72%, respectively; and at 96 hours, the interfering efficiency of protein expression was 57.2%. The recombinant lentivirus vector containing RNA interference targeting MMP3 gene is successfuly constructed, which lays a foundation for further studies on the MMP3 function and gene therapy.%背景:

  5. The application of matrix metalloproteinase-3 and 7 joints ultrasonic score in assessment of disease activity in patients with rheumatoid arthritis%血清基质金属蛋白酶-3和7个关节超声评分在类风湿关节炎病情活动性评估中的应用

    Institute of Scientific and Technical Information of China (English)

    周凌; 宋婧; 陈凌; 徐沪济

    2016-01-01

    目的 探讨血清基质金属蛋白酶-3(MMP-3)和7个关节超声评分(US7评分)在类风湿关节炎(RA)患者病情活动性评估中的应用.方法 选2014年12月-2015年6月第二军医大学附属长征医院风湿免疫科确诊的RA患者133例,根据28个关节疾病活动指数(DAS28)分为稳定期(DAS28<2.6)、轻度活动期(DAS 28≥2.6 ~ <3.2)、中度活动期(DAS 28≥3.2~ <5.1)、重度活动期(DAS28 ≥5.1).另选同期健康体检者53例.免疫比浊法测所有受试者血清MMP-3水平.彩色多普勒超声观察RA患者7个关节,并进行US7评分.采用ROC曲线评判MMP-3、US7评分及MMP-3联合US7评分对RA疾病活动评估的效能.结果 中度活动期RA患者血清MMP-3水平为105.1(61.70,172.70) μg/L,重度活动期RA患者血清MMP-3水平为363.1(161.50,475.90) μg/L,高于健康体检者[35.20(25.90,48.90) μg/L;P<0.001]和稳定期RA患者[33.40(22.60,678.40)μg/L;P <0.001].重度活动期RA患者US7评分高于稳定期RA患者[7.0(2.5,11.0)比0(0,2.0);P<0.001].RA患者MMP-3水平与US7评分呈正相关(r=0.566,P<0.001).对RA病情活动评估,MMP-3联合US7评分(AUC为0.863 2)与MMP-3(AUC为0.854 3)比,差异无统计学意义(P>0.05);与US7评分(AUC为0.764 3)比,差异有统计学意义(P<0.01).结论 MMP-3和US7评分可以作为RA活动性的评价指标,特别是对中重度活动性RA患者.MMP-3与US7评分密切相关,但MMP-3和US7评分联合使用并未提高RA活动性的评价效能.%Objective To evaluate the significance of serum matrix metalloproteinase-3 (MMP-3) and joint ultrasonography in assessing the activity of rheumatoid arthritis (RA) by comparing MMP-3 level and the ultrasonic 7 joints (US7) score in RA patients.Methods Serum MMP-3 level and US7 score were measured in 133 RA patients by immune turbidity and Doppler ultrasound.Synchronous 53 healthy subjects were recruited as controls.Clinical data were collected.Erythrocyte sedimentation rate (ESR),serum level of

  6. Complex role of matrix metalloproteinases in angiogenesis

    Institute of Scientific and Technical Information of China (English)

    SANGQINGXIANGAMY

    1998-01-01

    Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a significant role in regulating angiogenesis,the process of new blood vessel formation.Interstitial collagenase (MMP-1),72kDa gelatinase A/type IV collagenase (MMP-2),and 92 kDA gelatinase B/type IV collagenase (MMP-9) dissolve extracellular matrix (ECM) and may initiate and promote angiogenesis.TIMP-1,TIMP-2,TIMP-3,and possibly,TIMP-4 inhibit neovascularization.A new paradign is emerging that matrilysin (MMP-7),MMP-9,and metalloelastase (MMP-12) may block angiogenesis by converting plasminogen to angiostatin,which is one of the most potent angiogenesis antagonists.MMPs and TIMPs play a complex role in regulating angiogenesis.An understanding of the biochemical and cellular pathways and mechanisms of angiogenesis will provide important information to allow the control of angiogenesis,e.g.the stimulation of angiogenesis for coronary collateral circulation formation;while the inhibition for treating arthritis and cancer.

  7. Tissue inhibitor of metalloproteinase-3 (TIMP3) promotes endothelial apoptosis via a caspase-independent mechanism.

    Science.gov (United States)

    Qi, Jian Hua; Anand-Apte, Bela

    2015-04-01

    Tissue inhibitor of metalloproteinases-3 (TIMP3) is a tumor suppressor and a potent inhibitor of angiogenesis. TIMP3 exerts its anti-angiogenic effect via a direct interaction with vascular endothelial growth factor (VEGF) receptor-2 (KDR) and inhibition of proliferation, migration and tube formation of endothelial cells (ECs). TIMP3 has also been shown to induce apoptosis in some cancer cells and vascular smooth muscle cells via MMP inhibition and caspase-dependent mechanisms. In this study, we examined the molecular mechanisms of TIMP3-mediated apoptosis in endothelial cells. We have previously demonstrated that mice developed smaller tumors with decreased vascularity when injected with breast carcinoma cells overexpressing TIMP3, than with control breast carcinoma cells. TIMP3 overexpression resulted in increased apoptosis in human breast carcinoma (MDA-MB435) in vivo but not in vitro. However, TIMP3 could induce apoptosis in ECs in vitro. The apoptotic activity of TIMP3 in ECs appears to be independent of MMP inhibitory activity. Furthermore, the equivalent expression of functional TIMP3 promoted apoptosis and caspase activation in ECs expressing KDR (PAE/KDR), but not in ECs expressing PDGF beta-receptor (PAE/β-R). Surprisingly, the apoptotic activity of TIMP3 appears to be independent of caspases. TIMP3 inhibited matrix-induced focal adhesion kinase (FAK) tyrosine phosphorylation and association with paxillin and disrupted the incorporation of β3 integrin, FAK and paxillin into focal adhesion contacts on the matrix, which were not affected by caspase inhibitors. Thus, TIMP3 may induce apoptosis in ECs by triggering a caspase-independent cell death pathway and targeting a FAK-dependent survival pathway.

  8. 膝关节软骨中基质金属蛋白酶13及其组织抑制剂1的表达%Expression of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase 1 in knee articular cartilage

    Institute of Scientific and Technical Information of China (English)

    杨立群; 张国彬; 习瑾昆; 田发明

    2015-01-01

    BACKGROUND:Tissue inhibitor of matrix metaloproteinase 1 (TIMP-1) is the corresponding antagonist of matrix metaloproteinase 13 (MMP-13), and their balance between expression and functional activity exerts an important role in the metabolic state of the extracelular matrix. During the development of osteoarthritis, however, TIMP-1 and MMP-13 expressions and their expression ratio show unclear changes in DH guinea pigs. OBJECTIVE:To explore the expression levels of MMP-13 and TIMP-1 in DH guinea pigs with different ages, and to analyze the relationship between the ratio of MMP-13 to TIMP-1 and the age-dependent degenerative changes in the articular cartilage. METHODS:Twenty-four female Dunkin Hartley guinea pigs were sacrificed at age of 2, 4, 8, 12 months separately, with six animals at each time point. The knee joints were colected and gross visual appearance of the articular cartilage was observed, then were decalcified and prepared for paraffin sections. VG staining and Mankin score were used to analyze the histological changes. Immunohistochemistry was conducted to assess the expression levels of MMP-13 and TIMP-1 in the cartilage. Integrated absorbance values were used as the quantitive analysis calculated by Image pro-Plus 6.0. Linear regression analysis was done to analysis the relationship between Mankin score and the ratio of MMP-13/TIMP-1. RESULTS AND CONCLUSION:Normal appearance in the articular cartilage was observed in 2-month-old DH guinea pigs, while degenerative changes in the articular cartilage were shown in 4-month-old animals, which became severer with age. Significant difference was found in Mankin score between any two groups (P   目的:探讨不同月龄DH豚鼠关节软骨中基质金属蛋白酶13、基质金属蛋白酶组织抑制剂1表达比值的变化及其与DH豚鼠增龄性原发骨性关节炎发病过程中软骨退变程度的关系。  方法:选取2,4,8,12月龄雌性DH各6只,取膝关节观察关节

  9. Tissue inhibitor of metalloproteinases-3 peptides inhibit angiogenesis and choroidal neovascularization in mice.

    Directory of Open Access Journals (Sweden)

    Jian Hua Qi

    Full Text Available Tissue inhibitors of metalloproteinases (TIMPs while originally characterized as inhibitors of matrix metalloproteinases (MMPs have recently been shown to have a wide range of functions that are independent of their MMP inhibitory properties. Tissue inhibitor of metalloproteinases-3 (TIMP-3 is a potent inhibitor of VEGF-mediated angiogenesis and neovascularization through its ability to block the binding of VEGF to its receptor VEGFR-2. To identify and characterize the anti-angiogenic domain of TIMP-3, structure function analyses and synthetic peptide studies were performed using VEGF-mediated receptor binding, signaling, migration and proliferation. In addition, the ability of TIMP-3 peptides to inhibit CNV in a mouse model was evaluated. We demonstrate that the anti-angiogenic property resides in the COOH-terminal domain of TIMP-3 protein which can block the binding of VEGF specifically to its receptor VEGFR-2, but not to VEGFR-1 similar to the full-length wild-type protein. Synthetic peptides corresponding to putative loop 6 and tail region of TIMP-3 have anti-angiogenic properties as determined by inhibition of VEGF binding to VEGFR-2, VEGF-induced phosphorylation of VEGFR-2 and downstream signaling pathways as well as endothelial cell proliferation and migration in response to VEGF. In addition, we show that intravitreal administration of TIMP-3 peptide could inhibit the size of laser-induced choroidal neovascularization lesions in mice. Thus, we have identified TIMP-3 peptides to be efficient inhibitors of angiogenesis and have a potential to be used therapeutically in diseases with increased neovascularization.

  10. Expression of interleukin-6 and matrix metalloproteinase-3 in the synovial fluid of osteoarthritis patients%骨性关节炎关节液中白细胞介素6和基质金属蛋白酶3的表达

    Institute of Scientific and Technical Information of China (English)

    艾倩; 杨会明

    2015-01-01

    背景:已有实验证实膝骨关节炎的发病与炎症细胞因子有密切的关系。目的:研究骨性关节炎患者关节液中白细胞介素6和基质金属蛋白酶3水平及其相关性,以及两者与骨性关节炎严重程度之间的相关性。方法:收集关节穿刺治疗的骨性关节炎患者关节液标本78份,应用ELISA法检测标本中白细胞介素6和基质金属蛋白酶3质量浓度,并对患者骨性关节炎严重程度进行HSS评分,采用Pearson相关分析探讨白细胞介素6、基质金属蛋白酶3和美国纽约特种外科医院(HSS)评分两两之间的相关性。结果与结论:骨性关节炎患者膝关节液中白细胞介素6为(13.1±5.7)μg/L,基质金属蛋白酶3为(989.3±429.5)μg/L, HSS为(56.4±12.0)分。Pearson相关分析显示白细胞介素6、基质金属蛋白酶3的表达水平呈显著性正相关关系(r=0.70,P <0.001);白细胞介素6和基质金属蛋白酶3均与关节美国纽约特种外科医院(HSS)评分均呈负相关关系(r=-0.70,r=-0.75,P<0.001)。结果显性关节液中白细胞介素6和基质金属蛋白酶3水平之间,以及两者与骨性关节炎严重程度之间均呈正相关,提示测定骨性关节炎患者关节液中白细胞介素6和基质金属蛋白酶3水平对早期诊断和治疗具有重要意义。%BACKGROUND:It is confirmed that the onset of osteoarthritis is closely related to inflammatory cytokines. OBJECTIVE: To investigate the levels of interleukin-6 and matrix metaloproteinase-3 in the synovial fluid of patients with osteoarthritis and their correlation with the severity of osteoarthritis. METHODS: Synovial fluid specimens of 78 patients were harvested to detect the levels of interleukin-6 and matrix metaloproteinase-3 using ELISA assay. The severity of osteoarthritis was estimated by the Hospital for Special Surgery (HSS) score. Pearson correlation analysis was adopted to explore the pairwise correlations between

  11. Matrix metalloproteinase-3 inhibitor I accelerates the early-stage repair of full-thickness articular cartilage defects in the knee of rats%膝关节软骨早期缺损修复中的基质金属蛋白酶3抑制剂Ⅰ

    Institute of Scientific and Technical Information of China (English)

    董福; 宋锦旗; 姜楠; 陆春

    2016-01-01

    BACKGROUND:The biomechanical properties of naturaly regenerated damaged articular cartilage that belongs to the fibrovascular tissue are far worse than those of the normal cartilage so that they cannot meet the requirements for joint function, leading to traumatic arthritis and loss of joint function. OBJECTIVE:To evaluate the effects of matrix metaloproteinase-3 (MMP-3) inhibitor I with different concentrations on the early-stage repair of ful-thickness articular cartilage defects in the knee of rats. METHODS: Twenty-four Sprague Dawley rats were randomized into control, defect (DEF), and defect combined with low-(D+L) and high-dose inhibitor (D+H) groups (n=6 for each group), respectively. Full-thickness articular cartilage defects followed by intraarticular injection of low- and high-dose MMP-3 inhibitor I for 4 weeks was administered in the later two groups. Serum MMP-3 was detected using ELISA method before and after experiment, respectively. Femoral trochleas were collected to observe characteristics of repaired tissue by gross appearance scoring and O’Driscoll histological scoring with Safranine O-Fast Green staining, and to measure type II colagen by immunohistochemistry after experiment. RESULTS AND CONCLUSION:Rats in the D+H group had obvious repair similarly to hyaline articular cartilage, while creamy white cartilage tissue and fibrous tissue repair were observed in D+L group and in DEF group. D+H group obtained the best repair results according to gross appearance scoring and O’Driscol histological scoring and the highest content of type II colagen (P  目的:评价不同水平基质金属蛋白酶3抑制剂Ⅰ对大鼠膝关节软骨早期缺损促进修复的作用。  方法:24只SD大鼠随机选取6只作为空白对照组,另18只大鼠制备膝关节软骨缺损模型后随机分为缺损组、缺损+低浓度抑制剂组及缺损+高浓度抑制剂组,后2组大鼠每周分别进行膝关节腔内注射不

  12. Matrix Metalloproteinases And Their Role In Oral Diseases: A Review

    Directory of Open Access Journals (Sweden)

    Anna P. joseph

    2012-01-01

    Full Text Available Matrix metalloproteinases (MMPs are zinc dependent endopeptidases that are capable of degrading extra cellular matrix proteins. The activity of MMPs is seen not only during normal organogenesis and wound healing, but also in pathological conditions like inflammatory diseases and tumor invasion. This review describes the structure, function and regulation of MMPs and also highlights their role in certain oral diseases like oral cancer, periodontitis and dental caries.

  13. Role of work hardening characteristics of matrix alloys in the strengthening of metal matrix composites

    Indian Academy of Sciences (India)

    K T Kashyap; C Ramachandra; C Dutta; B Chatterji

    2000-02-01

    The strengthening of particulate reinforced metal–matrix composites is associated with a high dislocation density in the matrix due to the difference in coefficient of thermal expansion between the reinforcement and the matrix. While this is valid, the role of work hardening characteristics of the matrix alloys in strengthening of these composites is addressed in the present paper. It is found that commercial purity aluminium which has the lowest work hardening rate exhibits the highest strength increment. This effect is due to increased prismatic punching of dislocations. This relationship of decreasing work hardening rate associated with increasing prismatic punching of dislocations in the order 7075, 2014, 7010, 2024, 6061 and commercial purity aluminium leading to increased strength increments is noted.

  14. Glomerular matrix: synthesis, turnover and role in mesangial expansion

    DEFF Research Database (Denmark)

    Couchman, J R; Beavan, L A; McCarthy, K J

    1994-01-01

    The extracellular matrix has an integral role in development, homeostasis and pathology of the glomerulus. Three spatially distinct matrices are present in the glomerulus: the mesangium, and basement membranes of the capillary loops and Bowman's capsule. Each is dominated by basement membrane com...

  15. The Role of Matrix Metalloproteinases in Renal Diseases

    Directory of Open Access Journals (Sweden)

    Funda SAĞLAM

    2011-05-01

    Full Text Available Matrix metalloproteinases (MMPs are a family of zinc dependent proteinases and the main promoters of extracellular matrix degradation. Their role in renal diseases is now being understood better. Several progressive renal diseases are characterized with persistent cell proliferation and abnormal production of extracellular matrix by mesengial cells. Understanding mesengial cell proliferation and the factors regulating extracellular matrix metabolism is therefore becoming more important. MMPs have been shown to be produced and excreted from renal glomerular cells and interstitital fibroblast and tubuloepithelial cells have also been shown to excrete MMPs. MMPs function in expansive cell behaviour, embryonic evolution and tissue fibrosis. Production of MMPs are known to increase in inflammation and restructure processes. Data obtained from both experimental and clinical studies has shown the role of MMPs in proliferative glomerulonephritis, hypertensive nephropathy, diabetic nephropathy, HIV nephropathy, toxic nephropathy, obstructive nephropathy, renal cell carcinoma, chronic allograft nephropathy-related fibrosis and in many other renal diseases. In light of these data, therapy options targeting MMPs have become a current issue. Limited data obtained from recent studies are promising about the clinical use of therapies repressing MMPs in future. The roles of MMPs which increase in inflammation and restructure processes in renal diseases and future therapy options are discussed in this review.

  16. Enamel matrix protein derivatives: role in periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Rathva VJ

    2011-12-01

    Full Text Available Vandana J RathvaDepartment of Periodontics, KM Shah Dental College and Hospital, Sumandeep University, Gujarat, IndiaAbstract: The role of regenerative periodontal therapy is the reconstitution of lost periodontal structures, ie, new formation of root cementum, periodontal ligament, and alveolar bone. The outcome of basic research has pointed to the important role of enamel matrix protein derivative (EMD in periodontal wound healing. Histologic results from animal and human studies have shown that treatment with EMD promotes periodontal regeneration. Moreover, clinical studies have indicated that treatment with EMD positively influences periodontal wound healing in humans. The goal of this paper is to review the existing literature on EMD.Keywords: enamel matrix protein derivative, Emdogain®, periodontal regeneration

  17. miR-181b-5p Modulates Cell Migratory Proteins, Tissue Inhibitor of Metalloproteinase 3, and Annexin A2 During In Vitro Decidualization in a Human Endometrial Stromal Cell Line.

    Science.gov (United States)

    Graham, Amanda; Holbert, Joshua; Nothnick, Warren B

    2016-01-01

    Decidualization is essential for successful embryo implantation and is regulated by concerted actions of growth factors and hormones. More recently, microRNAs, small RNA molecules that regulate posttranscriptional gene expression, have been implicated to play a role in the decidualization process. Of these microRNAs, miR-181b-5p has been associated with decidualization but its precise role and targets are not well established. To address this gap in our knowledge, we assessed the expression of miR-181b-5p, and its target tissue inhibitor of metalloproteinase 3 (TIMP-3), during in vitro decidualization using the well-characterized human endometrial stromal cell line, t-HESC. miR-181b-5p expression was highest prior to decidualization and significantly decreased in response to decidualization stimulus. In contrast, TIMP-3 expression was absent prior to in vitro decidualization and increased during decidualization. Regulation of TIMP-3 expression by miR-181b-5p was confirmed in vitro by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot analysis, and 3' untranslated region reporter constructs. To identify unforeseen targets of miR-181b-5p during in vitro decidualization, t-HESC cells were transfected with pre- miR-181b-5p, and protein profiles were determined by 2-dimensional differential in-gel electrophoresis followed by matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI TOF/TOF) tandem mass spectrometry. Of these proteins, several downregulated proteins associated with cell migration were identified including annexin A2, which we subsequently confirmed by qRT-PCR and Western blot analysis to be regulated by miR-181b-5p. In conclusion, miR-181b-5p is downregulated during the process of in vitro decidualization and may regulate the expression of proteins associated with cell migration including TIMP-3 and annexin A2.

  18. New Insights into the Role of Matrix Metalloproteinases in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Salvador Espino Y. Sosa

    2017-07-01

    Full Text Available Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A decrease in MMP-2 and MMP-9 interferes with the normal remodeling of spiral arteries at early pregnancy stages, leading to the initial pathophysiological changes observed in preeclampsia. Later in pregnancy, an elevation in MMP-2 and MMP-9 induces abnormal release of vasoactive factors conditioning hypertension. Although these two enzymes lead the scene, other MMPs like MMP-1 and MMP-14 seem to have a role in this pathology. This review gathers published recent evidence about the implications of different MMPs in preeclampsia, and the potential use of these enzymes as emergent biomarkers and biological therapeutic targets, focusing on studies involving human subjects.

  19. Tissue inhibitor of metalloproteinase-3 knockout mice exhibit enhanced energy expenditure through thermogenesis.

    Directory of Open Access Journals (Sweden)

    Yohsuke Hanaoka

    Full Text Available Tissue inhibitors of metalloproteinases (TIMPs regulate matrix metalloproteinase activity and maintain extracellular matrix homeostasis. Although TIMP-3 has multiple functions (e.g., apoptosis, inhibition of VEGF binding to VEGF receptor, and inhibition of TNFα converting enzyme, its roles in thermogenesis and metabolism, which influence energy expenditure and can lead to the development of metabolic disorders when dysregulated, are poorly understood. This study aimed to determine whether TIMP-3 is implicated in metabolism by analyzing TIMP-3 knockout (KO mice. TIMP-3 KO mice had higher body temperature, oxygen consumption, and carbon dioxide production than wild-type (WT mice, although there were no differences in food intake and locomotor activity. These results suggest that metabolism is enhanced in TIMP-3 KO mice. Real-time PCR analysis showed that the expression of PPAR-δ, UCP-2, NRF-1 and NRF-2 in soleus muscle, and PGC-1α and UCP-2 in gastrocnemius muscle, was higher in TIMP-3 KO mice than in WT mice, suggesting that TIMP-3 deficiency may increase mitochondrial activity. When exposed to cold for 8 hours to induce thermogenesis, TIMP-3 KO mice had a higher body temperature than WT mice. In the treadmill test, oxygen consumption and carbon dioxide production were higher in TIMP-3 KO mice both before and after starting exercise, and the difference was more pronounced after starting exercise. Our findings suggest that TIMP-3 KO mice exhibit enhanced metabolism, as reflected by a higher body temperature than WT mice, possibly due to increased mitochondrial activity. Given that TIMP-3 deficiency increases energy expenditure, TIMP-3 may present a novel therapeutic target for preventing metabolic disorders.

  20. [Glycation of extracellular matrix proteins and its role in atherosclerosis].

    Science.gov (United States)

    Kuzan, Aleksandra; Chwiłkowska, Agnieszka; Kobielarz, Magdalena; Pezowicz, Celina; Gamian, Andrzej

    2012-10-29

    Glycation consists in formation of advanced glycation end-products (AGE) during non-enzymatic reaction between reducing sugars and proteins, lipids or nucleic acids. This review is focused mainly on glycation of collagen and its role in acceleration of vascular disease. Collagen is an extracellular matrix protein characterized by unique structure forming fibrils with great anti-tensile and anti-breaking strength. The protein builds the connective tissue and is responsible for biomechanical properties of blood vessels. It is reported that higher content of glycated collagen correlates with lower elasticity and greater toughness of the vessel walls and, as a consequence, a faster rate of atherosclerosis development. Numerous mechanisms connected with AGE formation are involved in atherogenesis, among others: receptor-mediated production of free radicals, triggering an inflammatory process, activation of leukocytes and thrombocytes, facilitation of LDL binding, change in level of growth factors, adhesion molecules, MMP and some other proteins' expression. The coverages allow the development of therapeutic strategies to prevent or slow down the pathological processes connected with glycation of collagen and other proteins in the artery wall. The main strategies are based on limitation of exogenous AGE, consumption of products which contain rutin, treatment with drugs which inhibit AGE formation, such as pyridoxamine, and chemicals which are able to cleave already formed AGE protein-protein crosslinks, such as ALT-711.

  1. L-Carnitine supplementation ameliorates serum tumor necrosis factor-alpha and matrix metalloproteinase-3 in knee osteoarthritis women

    Directory of Open Access Journals (Sweden)

    Reza Mahdavi

    2017-03-01

    Full Text Available Seventy-two females with mild to moderate knee osteoarthritis were included in this randomized double-blind placebo-controlled study. Patients in the intervention group (n=36 received L-carnitine supplement (750 mg/day for two months. L-Carnitine supplementation led to decrease in serum TNF-α and MMP-3 levels significantly in comparison with the baseline (p<0.001 and p<0.001, respectively and placebo group (p<0.001 and p=0.03, respectively. In addition, physician’s global assessment of the severity of osteoarthritis decreased significantly in the L-carnitine group (p<0.001 and placebo group (p=0.012 after supplementation. At the end of the study, a significant difference was observed between the two groups for mean physician’s global assessment of the severity of osteoarthritis (p<0.001, adjusted for baseline values and duration of osteoarthritis. L-Carnitine supplementation has beneficial effects in reducing inflammatory biomarkers in knee osteoarthritis patients which subsequently leads to the alleviation of disease symptoms.

  2. The role of perceptual cues in matrix diagrams

    NARCIS (Netherlands)

    van der Meij, Jan; van Amelsvoort, Marije; Anjewierden, A.

    2015-01-01

    An experiment was conducted to assess whether the design of a matrix diagram influences how people study the diagram and whether this has an effect on recall of the presented information. We compared four versions of a matrix diagram on antisocial personality disorder. It consisted of four header ce

  3. The role of perceptual cues in matrix diagrams

    NARCIS (Netherlands)

    van der Meij, Jan; Amelsvoort, Marije; Anjewierden, Anjo Allert

    2015-01-01

    An experiment was conducted to assess whether the design of a matrix diagram influences how people study the diagram and whether this has an effect on recall of the presented information. We compared four versions of a matrix diagram on antisocial personality disorder. It consisted of four header

  4. The role of perceptual cues in matrix diagrams

    NARCIS (Netherlands)

    van der Meij, Jan; van Amelsvoort, Marije; Anjewierden, A.

    An experiment was conducted to assess whether the design of a matrix diagram influences how people study the diagram and whether this has an effect on recall of the presented information. We compared four versions of a matrix diagram on antisocial personality disorder. It consisted of four header

  5. Disease-Specific Effects of Matrix and Growth Factors on Adhesion and Migration of Rheumatoid Synovial Fibroblasts.

    Science.gov (United States)

    Lefèvre, Stephanie; Schwarz, Maria; Meier, Florian M P; Zimmermann-Geller, Birgit; Tarner, Ingo H; Rickert, Markus; Steinmeyer, Jürgen; Sauerbier, Michael; Rehart, Stefan; Müller-Ladner, Ulf; Neumann, Elena

    2017-06-15

    In rheumatoid arthritis (RA), cartilage and bone matrix are degraded, and extracellular matrix (ECM) proteins, acting as cellular activators, are liberated. Similar to ECM proteins, matrix-bound chemokines, cytokines, and growth factors (GFs) influence functional properties of key cells in RA, especially synovial fibroblasts. The role of these molecules on attachment, migration, and proinflammatory and prodestructive activation of RASFs was analyzed. Adhesion/migration of RASFs were examined under GF-enriched (GF(+)) or -reduced (GF(-)) conditions with or without addition of matrix-associated GFs, TGF-β, and platelet-derived GF to GF(-) or culture supernatants. Fibroblast adhesion and alterations in proinflammatory/prodestructive properties (e.g., IL-6/matrix metalloproteinase 3-release) in response to matrix-associated molecules were compared. Effects of GF(+), GF(-), and other ECM components on human RASF-mediated cartilage invasion were examined in the SCID mouse model. RASF adhesion under GF(-) conditions was significantly lower compared with GF(+) conditions (6.8- versus 8.3-fold). This effect was specific for RA because control cells showed opposite effects (e.g., osteoarthritis synovial fibroblasts [SF]; GF(-) versus GF(+): 10.7- versus 8-fold). Addition of TGF-β to GF(-) increased RASF attachment (12.7-fold) compared with other matrices and components. RASF adhesion to GF(+) matrix resulted in the strongest IL-6 and matrix metalloproteinase-3 release, and was even more pronounced compared with supplementation of single GFs. In vivo, GF(-) matrix decreased RASF-mediated cartilage invasion compared with GF(+) matrix. ECM components and especially GFs when bound within ECM actively enhance RASF attraction and cartilage adhesion. This observation was specific for RASFs as a reverse behavior was observed for controls. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. A critical role for matrix metal loproteinases in liver regeneration

    NARCIS (Netherlands)

    Alwayn, Ian P. J.; Verbesey, Jennifer E.; Kim, Sendia; Roy, Roopali; Arsenault, Danielle A.; Greene, Arin K.; Novak, Katherine; Laforme, Andrea; Lee, Sang; Moses, Marsha A.; Puder, Mark

    2008-01-01

    Background. Matrix metalloproteinases (MMPs), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) are mediators of liver regeneration. To determine whether MMPs are required for normal hepatic regeneration, we performed 67% hepatectomies on mice treated with a broad-spectrum MMP-inhibi

  7. Extracellular matrix proteins regulate epithelial-mesenchymal transition in mammary epithelial cells

    Science.gov (United States)

    Chen, Qike K.; Lee, KangAe; Radisky, Derek C.; Nelson, Celeste M.

    2013-01-01

    Mouse mammary epithelial cells undergo transdifferentiation via epithelial-mesenchymal transition (EMT) upon treatment with matrix metalloproteinase-3 (MMP3). In rigid microenvironments, MMP3 upregulates expression of Rac1b, which translocates to the cell membrane to promote induction of reactive oxygen species and EMT. Here we examine the role of the extracellular matrix (ECM) in this process. Our data show that the basement membrane protein laminin suppresses the EMT response in MMP3-treated cells, whereas fibronectin promotes EMT. These ECM proteins regulate EMT via interactions with their specific integrin receptors. α6-integrin sequesters Rac1b from the membrane and is required for inhibition of EMT by laminin. In contrast, α5-integrin maintains Rac1b at the membrane and is required for the promotion of EMT by fibronectin. Understanding the regulatory role of the ECM will provide insight into mechanisms underlying normal and pathological development of the mammary gland. PMID:23660532

  8. A Novel Role for Matrix Metalloproteinases In Regulating Mammary Stem Cell Function via the Wnt Signaling Pathway

    Science.gov (United States)

    Kessenbrock, Kai; Dijkgraaf, Gerrit J. P.; Lawson, Devon A.; Littlepage, Laurie E.; Shahi, Payam; Pieper, Ursula; Werb, Zena

    2013-01-01

    SUMMARY The microenvironment provides cues that control the behavior of epithelial stem and progenitor cells. Here, we identify matrix metalloproteinase-3 (MMP3) as a novel regulator of Wnt signaling and mammary stem cell (MaSC) activity. We show that MMP3 overexpression promotes hyperplastic epithelial growth, surprisingly, in a non-proteolytic manner via its hemopexin (HPX) domain. We demonstrate that MMP3-HPX specifically binds and inactivates Wnt5b, a non-canonical Wnt ligand that inhibits canonical Wnt signaling and mammary epithelial outgrowth in vivo. Indeed, transplants overexpressing MMP3 display increased canonical Wnt signaling, demonstrating that MMP3 is an extracellular regulator of the Wnt signaling pathway. MMP3-deficient mice exhibit decreased MaSC populations and diminished mammary reconstituting activity, while MMP3 overexpression elevates MaSC function indicating that MMP3 is necessary for the maintenance of MaSCs. Our study reveals a novel mechanism by a microenvironmental protease that regulates Wnt signaling and impacts adult epithelial stem cell function. PMID:23871604

  9. The role of matrix metalloproteinases in recurrent tonsillitis.

    Science.gov (United States)

    Acioglu, Engin; Yigit, Ozgür; Alkan, Zeynep; Server, Ela Araz; Uzun, Hafize; Gelisgen, Ramisa

    2010-05-01

    The aim of this study was to investigate the status of matrix metalloproteinases (MMP-2, MMP-7, MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) due to dysregulated turnover of connective tissue matrices in children with recurrent tonsillitis (RT). Forty-four patients with RT were enrolled in the study. All patients with RT were graded according to the hypertrophy degree of the tonsillar tissue from grade I to grade IV. Patients with grade I tonsillar hypertrophy and grade II tonsillar hypertrophy were accepted as group A, patients with grade III tonsillar hypertrophy and grade IV tonsillar hypertrophy were accepted as group B Tonsillectomy was performed via the usual dissection-snare method. Tonsillar specimens of superficial and core region were evaluated for MMP-2, MMP-7, MMP-9 and TIMP-1 analysis. There was no statistical significance according to the MMP-2, MMP-7, MMP-9 and TIMP-1 activity of superficial part and core regions in both groups individually, MMP-9 level of both the superficial and core regions in group B had statistical significant higher results than group A (p=0.026, p=0.06 respectively). MMP-7 level of the superficial part in group B patients also had statistical significant higher results than group A (p=0.025). However, there was no statistical difference found between superficial and core region MMP-2 and TIMP-1 levels of group A and group B. Related to this, balance between MMP-7-9 and TIMP-1 activities tended to slip MMP-7 and MMP-9 sides with increased tonsillar grade. Results from this study suggest that the presence of MMPs in tonsil tissue consolidates the involvement of degraded extracellular matrix proteins in the pathophysiology of chronic tonsillitis. MMPs activity showed diffuse dissemination in the tonsillar tissue and especially MMP-9 and MMP-7 are the main promoters of the extracellular matrix that responded to inflammatory changes in the tonsillar tissue. Further studies are needed concerning the possible

  10. XHAPLN3 plays a key role in cardiogenesis by maintaining the hyaluronan matrix around heart anlage.

    Science.gov (United States)

    Ito, Yuzuru; Seno, Satsuki; Nakamura, Hiroaki; Fukui, Akimasa; Asashima, Makoto

    2008-07-01

    Hyaluronan matrix plays an important role during vertebrate cardiogenesis. Transcripts for the hyaluronan synthase Has2 gene are expressed in heart anlage, and disruption of either Has2 or versican, a hyaluronan matrix component, abrogates normal cardiac morphogenesis. However, the mechanisms by which hyaluronan matrix contributes to early heart development are largely unknown. Here we show that Xenopus hyaluronan and proteoglycan-binding link protein 3 (XHAPLN3) helps to maintain hyaluronan matrix around the cardiac anlage, and thereby contribute to cardiogenesis. XHAPLN3 mRNA transcript localization overlapped with the mRNA expression of both Xhas2 and Xversican at the heart anlage of early tailbud (stage 23) embryos. Furthermore, knockdown of XHAPLN3 or Xhas2 with morpholino antisense oligos caused a heart deficiency in developing tadpoles. Our results show when and how components of the hyaluronan matrix function in cardiogenesis, improving our understanding of how extracellular matrix participates in embryogenesis.

  11. Decoding the Matrix: Instructive Roles of Proteoglycan Receptors.

    Science.gov (United States)

    Neill, Thomas; Schaefer, Liliana; Iozzo, Renato V

    2015-08-01

    The extracellular matrix is a dynamic repository harboring instructive cues that embody substantial regulatory dominance over many evolutionarily conserved intracellular activities, including proliferation, apoptosis, migration, motility, and autophagy. The matrix also coordinates and parses hierarchical information, such as angiogenesis, tumorigenesis, and immunological responses, typically providing the critical determinants driving each outcome. We provide the first comprehensive review focused on proteoglycan receptors, that is, signaling transmembrane proteins that use secreted proteoglycans as ligands, in addition to their natural ligands. The majority of these receptors belong to an exclusive subset of receptor tyrosine kinases and assorted cell surface receptors that specifically bind, transduce, and modulate fundamental cellular processes following interactions with proteoglycans. The class of small leucine-rich proteoglycans is the most studied so far and constitutes the best understood example of proteoglycan-receptor interactions. Decorin and biglycan evoke autophagy and immunological responses that deter, suppress, or exacerbate pathological conditions such as tumorigenesis, angiogenesis, and chronic inflammatory disease. Basement membrane-associated heparan sulfate proteoglycans (perlecan, agrin, and collagen XVIII) represent a unique cohort and provide proteolytically cleaved bioactive fragments for modulating cellular behavior. The receptors that bind the genuinely multifactorial and multivalent proteoglycans represent a nexus in understanding basic biological pathways and open new avenues for therapeutic and pharmacological intervention.

  12. The regulatory roles of small leucine-rich proteoglycans in extracellular matrix assembly.

    Science.gov (United States)

    Chen, Shoujun; Birk, David E

    2013-05-01

    Small leucine-rich proteoglycans (SLRPs) are involved in a variety of biological and pathological processes. This review focuses on their regulatory roles in matrix assembly. SLRPs have protein cores and hypervariable glycosylation with multivalent binding abilities. During development, differential interactions of SLRPs with other molecules result in tissue-specific spatial and temporal distributions. The changing expression patterns play a critical role in the regulation of tissue-specific matrix assembly and therefore tissue function. SLRPs play significant structural roles within extracellular matrices. In addition, they play regulatory roles in collagen fibril growth, fibril organization and extracellular matrix assembly. Moreover, they are involved in mediating cell-matrix interactions. Abnormal SLRP expression and/or structures result in dysfunctional extracellular matrices and pathophysiology. Altered expression of SLRPs has been found in many disease models, and structural deficiency also causes altered matrix assembly. SLRPs regulate assembly of the extracellular matrix, which defines the microenvironment, modulating both the extracellular matrix and cellular functions, with an impact on tissue function.

  13. Cell stiffness, contractile stress and the role of extracellular matrix

    Energy Technology Data Exchange (ETDEWEB)

    An, Steven S., E-mail: san@jhsph.edu [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Kim, Jina [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Ahn, Kwangmi [Division of Biostatistics, Penn State College of Medicine, Hershey, PA 17033 (United States); Trepat, Xavier [CIBER, Enfermedades Respiratorias, 07110 Bunyola (Spain); Drake, Kenneth J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Fredberg, Jeffrey J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205 (United States)

    2009-05-15

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

  14. Cell stiffness, contractile stress and the role of extracellular matrix

    Science.gov (United States)

    An, Steven S.; Kim, Jina; Ahn, Kwangmi; Trepat, Xavier; Drake, Kenneth J.; Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne; Fredberg, Jeffrey J.; Biswal, Shyam

    2010-01-01

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses. PMID:19327344

  15. The Role of Extracellular Matrix Quality in Pulmonary Fibrosis

    DEFF Research Database (Denmark)

    Kristensen, Jacob Hull; Karsdal, Morten Asser; Genovese, Federica

    2014-01-01

    focused on the role of protein quantity in relation to the progression of PF, while the importance of lung ECM quality, defined by the levels of ECM protein modifications and by the protein distribution in lung tissue, has not been properly addressed. The quality and function of proteins may be altered...

  16. The role of host-derived dentinal matrix metalloproteinases in reducing dentin bonding of resin adhesives.

    Science.gov (United States)

    Zhang, Shan-chuan; Kern, Matthias

    2009-12-01

    Dentin matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes trapped within mineralized dentin matrix, which have the ability to hydrolyze the organic matrix of demineralized dentin. After bonding with resins to dentin there are usually some exposed collagen fibrils at the bottom of the hybrid layer owing to imperfect resin impregnation of the demineralized dentin matrix. Exposed collagen fibrils might be affected by MMPs inducing hydrolytic degradation, which might result in reduced bond strength. Most MMPs are synthesized and released from odontoblasts in the form of proenzymes, requiring activation to degrade extracellular matrix components. Unfortunately, they can be activated by modem self-etch and etch-and-rinse adhesives. The aim of this review is to summarize the current knowledge of the role of dentinal host-derived MMPs in dentin matrix degradation. We also discuss various available MMP inhibitors, especially chlorhexidine, and suggest that they could provide a potential pathway for inhibiting collagen degradation in bonding interfaces thereby increasing dentin bonding durability.

  17. Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, R K; Bissell, M J

    2000-06-01

    The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

  18. Causality and dispersion relations and the role of the S-matrix in the ongoing research

    CERN Document Server

    Schroer, Bert

    2011-01-01

    The adaptation of the Kramers-Kronig dispersion relations to the causal localization structure of QFT led to an important project in particle physics, the only one with a successful closure. The same cannot be said about the subsequent attempts to formulate particle physics as a pure S-matrix project. The feasibility of a pure S-matrix approach are critically analyzed and their serious shortcomings are highlighted. Whereas the conceptual/mathematical demands of renormalized perturbation theory are modest and misunderstandings could easily be corrected, the correct understanding about the origin of the crossing property demands the use of the mathematical theory of modular localization and its relation to the thermal KMS condition. These concepts which combine localization, vacuum polarization and thermal properties under the roof of modular theory will be explained and their use in a new constructive (nonperturbative) approach to QFT will be indicated. The S-matrix still plays a predominant role, but differen...

  19. Scytonemin Plays a Potential Role in Stabilizing the Exopolysaccharidic Matrix in Terrestrial Cyanobacteria.

    Science.gov (United States)

    Gao, Xiang

    2017-02-01

    Cyanobacteria are photosynthetic oxygen-evolving prokaryotes that are distributed in diverse habitats. They synthesize the ultraviolet (UV)-screening pigments, scytonemin (SCY) and mycosporine-like amino acids (MAAs), located in the exopolysaccharide (EPS) matrix. Multiple roles for both pigments have gradually been recognized, such as sunscreen ability, antioxidant activity, and heat dissipation from absorbed UV radiation. In this study, a filamentous terrestrial cyanobacterium Nostoc flagelliforme was used to evaluate the potential stabilizing role of SCY on the EPS matrix. SCY (∼3.7 %) was partially removed from N. flagelliforme filaments by rinsing with 100 % acetone for 5 s. The physiological damage to cells resulting from this treatment, in terms of photosystem II activity parameter Fv/Fm, was repaired after culturing the sample for 40 h. The physiologically recovered sample was further desiccated by natural or rapid drying and then allowed to recovery for 24 h. Compared with the normal sample, a relatively slower Fv/Fm recovery was observed in the SCY-partially removed sample, suggesting that the decreased SCY concentration in the EPS matrix caused cells to suffer further damage upon desiccation. In addition, the SCY-partially removed sample could allow the release of MAAs (∼25 %) from the EPS matrix, while the normal sample did not. Therefore, damage caused by drying of the former resulted from at least the reduction of structural stability of the EPS matrix as well as the loss of partial antioxidant compounds. Considering that an approximately 4 % loss of SCY led to this significant effect, the structurally stabilizing potential of SCY on the EPS matrix is crucial for terrestrial cyanobacteria survival in complex environments.

  20. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia

    NARCIS (Netherlands)

    Klein, G.; Vellenga, E.; Fraaije, M.W.; Kamps, W.A.; Bont, E.S.J.M. de

    2004-01-01

    In the past decades, a lot of effort has been put in identifying the role of matrix metalloproteinases (MMPs) in cancer. The main role of MMPs in angiogenesis, tumor growth and metastasis is degradation of extracellular matrix (ECM) and release and/or activation of growth factors through their

  1. Role of three-dimensional matrix stiffness in regulating the chemoresistance of hepatocellular carcinoma cells.

    Science.gov (United States)

    Liu, Chang; Liu, Yang; Xie, Hong-Guo; Zhao, Shan; Xu, Xiao-Xi; Fan, Li-Xin; Guo, Xin; Lu, Ting; Sun, Guang-Wei; Ma, Xiao-Jun

    2015-01-01

    Hepatocellular carcinoma (HCC) was the most common primary liver cancer, and its resistance to anti-tumor drugs often caused the death of patients suffering with HCC. Matrix stiffness was reported to be closely related to tumor chemoresistance; however, the relationship between HCC drug resistance and three-dimensional (3D) matrix stiffness is still unclear at present. In this study, alginate gel (ALG) beads with controllable matrix stiffness were used to mimic tumor tissue rigidity, and the role of 3D matrix stiffness in regulating the chemoresistance of HCC cells was investigated by using these ALG beads. It was found that HCC cells in ALG beads with 105 kPa stiffness had highest resistance to paclitaxel, 5-FU, and cisplatin. Although the mechanism was still uncovered, ABC transporters and endoplasmic reticulum stress-related molecules were highly expressed in ALG bead-encapsulated HCC cells compared with two-dimensional-cultured cells, which suggested a very complex mechanism underlying HCC drug resistance in 3D culture conditions. In addition, to mimic the specific stiffness of HCC tumor tissue, or other tumor tissues in vivo, response surface methodology (RSM) was used to build up a prediction mathematical model so that ALG beads with desired matrix stiffness could be prepared by simply changing three factors: molecular weight, G content, and alginate concentration.

  2. The Role of Structural Extracellular Matrix Proteins in Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Andrea Brunner

    2007-01-01

    Full Text Available The extracellular matrix (ECM plays a key role in the modulation of cancer cell invasion. In urothelial carcinoma of the bladder (UC the role of ECM proteins has been widely studied. The mechanisms, which are involved in the development of invasion, progression and generalization, are complex, depending on the interaction of ECM proteins with each other as well as with cancer cells. The following review will focus on the pathogenetic role and prognostic value of structural proteins, such as laminins, collagens, fi bronectin (FN, tenascin (Tn-C and thrombospondin 1 (TSP1 in UC. In addition, the role of integrins mediating the interaction of ECM molecules and cancer cells will be addressed, since integrin-mediated FN, Tn-C and TSP1 interactions seem to play an important role during tumor cell invasion and angiogenesis.

  3. The matrix Hamiltonian for hadrons and the role of negative-energy components

    OpenAIRE

    Simonov, Yu. A.

    2004-01-01

    The world-line (Fock-Feynman-Schwinger) representation is used for quarks in arbitrary (vacuum and valence gluon) field to construct the relativistic Hamiltonian. After averaging the Green's function of the white $q\\bar q$ system over gluon fields one obtains the relativistic Hamiltonian, which is matrix in spin indices and contains both positive and negative quark energies. The role of the latter is studied in the example of the heavy-light meson and the standard einbein technic is extended ...

  4. Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Prostate Cancer Progression

    Directory of Open Access Journals (Sweden)

    Yixuan Gong

    2014-06-01

    Full Text Available Matrix metalloproteinases (MMPs, a group of zinc-dependent endopeptidases involved in the degradation of the extracellular matrix, play an important role in tissue remodeling associated with various physiological processes such as morphogenesis, angiogenesis, and tissue repair, as well as pathological processes including cirrhosis, arthritis and cancer. The MMPs are well established as mediators of tumor invasion and metastasis by breaking down connective tissue barriers. Although there has been a vast amount of literature on the role of MMPs in invasion, metastasis and angiogenesis of various cancers, the role of these endopeptidases in prostate cancer progression has not been systematically reviewed. This overview summarizes findings on the tissue and blood expression of MMPs, their function, regulation and prognostic implication in human prostate cancer, with a focus on MMP-2, -7, -9, MT1-MMP and tissue inhibitor of metalloproteinase 1 (TIMP-1. This review also summarizes the efficacy and failure of early-generation matrix metalloproteinase inhibitors (MMPIs in the treatment of metastatic prostate cancer and highlights the lessons and challenges for next generation MMPIs.

  5. The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation

    Directory of Open Access Journals (Sweden)

    Sandra Matabi Ayuk

    2016-01-01

    Full Text Available The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI or photobiomodulation (PBM is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

  6. The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation

    Science.gov (United States)

    2016-01-01

    The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM. PMID:27314046

  7. Role of Matrix Metalloproteinase-2, Matrix Metalloproteinase-9, and Vascular Endothelial Growth Factor in the Development of Chronic Subdural Hematoma.

    Science.gov (United States)

    Hua, Cong; Zhao, Gang; Feng, Yan; Yuan, Hongyan; Song, Hongmei; Bie, Li

    2016-01-01

    Chronic subdural hematoma (CSDH) is an inflammatory and angiogenic disease. Vascular endothelial growth factor (VEGF) has an important effect on the pathological progression of CSDH. The matrix metalloproteinases (MMPs) and VEGF also play a significant role in pathological angiogenesis. Our research was to investigate the level of MMPs and VEGF in serum and hematoma fluid. Magnetic Resonance Imaging (MRI) shows the characteristics of different stages of CSDH. We also analyzed the relationship between the level of VEGF in subdural hematoma fluid and the appearances of the patients' MRI. We performed a study comparing serum and hematoma fluid in 37 consecutive patients with primary CSDHs using enzyme-linked immunosorbent assay (ELISA). MMP-2 and MMP-9 activity was assayed by the gelatin zymography method. The patients were divided into five groups according to the appearance of the hematomas on MRI: group 1 (T1-weighted low, T2-weighted low, n=4), group 2 (T1-weighted high, T2-weighted low, n=11), group 3 (T1-weighted mixed, T2-weighted mixed, n=9), group 4 (T1-weighted high, T2-weighted high, n=5), and group 5 (T1-weighted low, T2-weighted high, n=8). Neurological status was assessed by Markwalder score on admission and at follow-up. The mean age, sex, and Markwalder score were not significantly different among groups. The mean concentration of VEGF, MMP-2, and MMP-9 were significantly higher in hematoma fluid than in serum (pMMP-2 was higher in hematoma fluid (pMMP-2 and MMP-9 are significantly elevated in hematoma fluid, suggesting that the MMPs/VEGF system may be involved in the angiogenesis of CSDH. We also demonstrate a significant correlation between the concentrations of VEGF and MRI appearance. This finding supports the hypothesis that high VEGF concentration in the hematoma fluid is of major pathophysiological importance in the generation and steady increase of the hematoma volume, as well as the determination of MRI appearance.

  8. Extracellular matrix molecules play diverse roles in the growth and guidance of central nervous system axons

    Directory of Open Access Journals (Sweden)

    M.A. Pires-Neto

    1999-05-01

    Full Text Available Axon growth and guidance represent complex biological processes in which probably intervene diverse sets of molecular cues that allow for the appropriate wiring of the central nervous system (CNS. The extracellular matrix (ECM represents a major contributor of molecular signals either diffusible or membrane-bound that may regulate different stages of neural development. Some of the brain ECM molecules form tridimensional structures (tunnels and boundaries that appear during time- and space-regulated events, possibly playing relevant roles in the control of axon elongation and pathfinding. This short review focuses mainly on the recognized roles played by proteoglycans, laminin, fibronectin and tenascin in axonal development during ontogenesis.

  9. Causality and dispersion relations and the role of the S-matrix in the ongoing research

    Energy Technology Data Exchange (ETDEWEB)

    Schroer, Bert, E-mail: schroer@cbpf.b [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Freie Univ. , Berlin (Germany). Inst. fur Theoretische Physik

    2011-07-01

    The adaptation of the Kramers-Kronig dispersion relations to the causal localization structure of QFT led to an important project in particle physics, the only one with a successful closure. The same cannot be said about the subsequent attempts to formulate particle physics as a pure S-matrix project. The feasibility of a pure S-matrix approach are critically analyzed and their seri- ous shortcomings are highlighted. Whereas the conceptual/mathematical demands of renormalized perturbation theory are modest and misunderstandings could easily be corrected, the correct understanding about the origin of the crossing property demands the use of the mathematical theory of modular localization and its relation to the thermal KMS condition. These concepts which combine localization, vacuum polarization and thermal properties under the roof of modular theory will be explained and their use in a new constructive (nonperturbative) approach to QFT will be indicated. The S-matrix still plays a predominant role, but different from Heisenberg's and Mandelstam's proposals the new project is not a pure S-matrix approach. (author)

  10. Functional role of EMMPRIN in the formation and mineralisation of dental matrix in mouse molars.

    Science.gov (United States)

    Xie, Ming; Xing, Guofang; Hou, Liwen; Bao, Jing; Chen, Yuqing; Jiao, Ting; Zhang, Fuqiang

    2015-02-01

    Our previous research has shown that the extracellular matrix metalloproteinase inducer (EMMPRIN) is expressed during and may function in the early development of tooth germs. In the present study, we observed the specific expression of EMMPRIN in ameloblasts and odontoblasts during the middle and late stages of tooth germ development using immunohistochemistry. Furthermore, to extend our understanding of the function of EMMPRIN in odontogenesis, we used an anti-EMMPRIN function-blocking antibody to remove EMMPRIN activity in tooth germ culture in vitro. Both the formation and mineralisation of dental hard tissues were suppressed in the tooth germ culture after the abrogation of EMMPRIN. Meanwhile, significant reductions in VEGF, MMP-9, ALPL, ameloblastin, amelogenin and enamelin expression were observed in antibody-treated tooth germ explants compared to control and normal serum-treated explants. The current results illustrate that EMMPRIN may play a critical role in the processing and maturation of the dental matrix.

  11. The role of matrix metalloproteinases in muscle and adipose tissue development and meat quality: A review.

    Science.gov (United States)

    Christensen, Sara; Purslow, Peter P

    2016-09-01

    Matrix metalloproteinases (MMPs) are a group of enzymes that degrade extracellular matrix components but are also important signaling molecules that regulate many biological processes including muscle, adipose and connective tissue development. Most recently it has been discovered that MMPs act as intracellular signaling molecules inducing gene expression and altering related proteins in the nucleus. Several single nucleotide polymorphisms of MMPs and their inhibitors are known to exist and most of the research on MMPs to date has focused on their activity in relation to human health and disease. Nevertheless there is a growing body of evidence identifying important roles of MMPs as regulators of myogenesis, fibrogenesis and adipogenesis. The aim of this review is to highlight the currently known functions of the MMPs that have a direct bearing on the deposition of meat components and their relationship with meat quality. Some central pathways by which these enzymes can affect the tenderness, the amount and type of fatty acids are highlighted.

  12. The extracellular matrix of the lung and its role in edema formation

    Directory of Open Access Journals (Sweden)

    Paolo Pelosi

    2007-06-01

    Full Text Available The extracellular matrix is composed of a three-dimensional fiber mesh filled with different macromolecules such as: collagen (mainly type I and III, elastin, glycosaminoglycans, and proteoglycans. In the lung, the extracellular matrix has several functions which provide: 1 mechanical tensile and compressive strength and elasticity, 2 low mechanical tissue compliance contributing to the maintenance of normal interstitial fluid dynamics, 3 low resistive pathway for an effective gas exchange, d control of cell behavior by the binding of growth factors, chemokines, cytokines and the interaction with cell-surface receptors, and e tissue repair and remodeling. Fragmentation and disorganization of extracellular matrix components comprises the protective role of the extracellular matrix, leading to interstitial and eventually severe lung edema. Thus, once conditions of increased microvascular filtration are established, matrix remodeling proceeds fairly rapidly due to the activation of proteases. Conversely, a massive matrix deposition of collagen fiber decreases interstitial compliance and therefore makes the tissue safety factor stronger. As a result, changes in lung extracellular matrix significantly affect edema formation and distribution in the lung.A matriz extracelular é um aglomerado tridimensional demacromoléculas composta por: fibras colágenas (principalmente, tipos I e III, elastina, glicosaminoglicanos e proteoglicanos. No pulmão, a matriz extracelular tem várias funções, tais como: 1 promover estresse tensil e elasticidade tecidual, 2 contribuir para a manutenção da dinâmica de fluidos no interstício, 3 propiciar efetiva troca gasosa, 4 controlar a função celular através de sua ligação com fatores de crescimento, quimiocinas, citocinas e interação com receptores de superfície, e 5 remodelamento e reparo tecidual. A fragmentação e a desorganização da matriz extracelular pode acarretar edema intersticial e

  13. Matrix Metalloproteinase and Their Inhibitors: Molecular Aspects of their Roles in the Tumor Metastasis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, whose physiological functions include tissue remo-delling and embryogenesis. The importance of this group of proteins in the processes of tumor invasion and metastasis is now widely acknowledged, and has led to the search for MMP inhibitors for use as anticancer treatments in a clinical setting. The review aims to introduce current research relating to MMPs as well as their native and synthetic inhibitor, with particular emphasis on the molecular aspects of their roles in tumor metastasis.

  14. The role of the non-collagenous matrix in tendon function.

    Science.gov (United States)

    Thorpe, Chavaunne T; Birch, Helen L; Clegg, Peter D; Screen, Hazel R C

    2013-08-01

    Tendon consists of highly ordered type I collagen molecules that are grouped together to form subunits of increasing diameter. At each hierarchical level, the type I collagen is interspersed with a predominantly non-collagenous matrix (NCM) (Connect. Tissue Res., 6, 1978, 11). Whilst many studies have investigated the structure, organization and function of the collagenous matrix within tendon, relatively few have studied the non-collagenous components. However, there is a growing body of research suggesting the NCM plays an important role within tendon; adaptations to this matrix may confer the specific properties required by tendons with different functions. Furthermore, age-related alterations to non-collagenous proteins have been identified, which may affect tendon resistance to injury. This review focuses on the NCM within the tensional region of developing and mature tendon, discussing the current knowledge and identifying areas that require further study to fully understand structure-function relationships within tendon. This information will aid in the development of appropriate techniques for tendon injury prevention and treatment. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

  15. A role for matrix stiffness in the regulation of cardiac side population cell function.

    Science.gov (United States)

    Qiu, Yiling; Bayomy, Ahmad F; Gomez, Marcus V; Bauer, Michael; Du, Ping; Yang, Yanfei; Zhang, Xin; Liao, Ronglih

    2015-05-01

    The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration.

  16. The role of the non-collagenous matrix in tendon function

    Science.gov (United States)

    Thorpe, Chavaunne T; Birch, Helen L; Clegg, Peter D; Screen, Hazel RC

    2013-01-01

    Tendon consists of highly ordered type I collagen molecules that are grouped together to form subunits of increasing diameter. At each hierarchical level, the type I collagen is interspersed with a predominantly non-collagenous matrix (NCM) (Connect. Tissue Res., 6, 1978, 11). Whilst many studies have investigated the structure, organization and function of the collagenous matrix within tendon, relatively few have studied the non-collagenous components. However, there is a growing body of research suggesting the NCM plays an important role within tendon; adaptations to this matrix may confer the specific properties required by tendons with different functions. Furthermore, age-related alterations to non-collagenous proteins have been identified, which may affect tendon resistance to injury. This review focuses on the NCM within the tensional region of developing and mature tendon, discussing the current knowledge and identifying areas that require further study to fully understand structure–function relationships within tendon. This information will aid in the development of appropriate techniques for tendon injury prevention and treatment. PMID:23718692

  17. Probing the role of scaffold dimensionality and media composition on matrix production and phenotype of fibroblasts.

    Science.gov (United States)

    Chawla, S; Chameettachal, S; Ghosh, S

    2015-04-01

    Porous sponges, hydrogels, and micro/nanofibrous matrix are most commonly used three dimensional (3D) biomaterials in tissue engineering; however, reciprocal interaction between internal dimensionality of biomaterials and fibroblasts remains largely unexplored. Such studies would have potential to generate valuable insights about wound healing, tissue morphogenesis and homeostasis. To the best of our knowledge this is the first study to evaluate functionality of porous collagen matrix and collagen gels for in vitro culture of fibroblasts while investigating the role of culture media composition in modulating morphology, phenotype, extracellular matrix (ECM)-related gene expression and protein synthesis by fibroblasts. Encapsulation of fibroblasts in collagen gel was found to be more effective for ECM production compared to scaffold-based culture, as evidenced by enhanced collagen type I, elastin, lysyl oxidase, aggrecan gene expression. High glucose media induced spindle like morphology of typical in vivo fibroblasts and enhanced collagen production compared to other media. This variation in biosynthesis in different glucose concentrations was possibly due to endogenous activation of TGF-β or by an increase in ATP consuming anabolic pathways in high glucose concentration.

  18. The roles of biofilm matrix polysaccharide Psl in mucoid Pseudomonas aeruginosa biofilms.

    Science.gov (United States)

    Ma, Luyan; Wang, Shiwei; Wang, Di; Parsek, Matthew R; Wozniak, Daniel J

    2012-07-01

    The opportunistic pathogen Pseudomonas aeruginosa causes life-threatening, persistent infections in patients with cystic fibrosis (CF). Persistence is attributed to the ability of these bacteria to form structured communities (biofilms). Biofilms rely on an extracellular polymeric substances matrix to maintain structure. Psl exopolysaccharide is a key matrix component of nonmucoid biofilms, yet the role of Psl in mucoid biofilms is unknown. In this report, using a variety of mutants in a mucoid P. aeruginosa background, we found that deletion of Psl-encoding genes dramatically decreased their biofilm formation ability, indicating that Psl is also a critical matrix component of mucoid biofilms. Our data also suggest that the overproduction of alginate leads to mucoid biofilms, which occupy more space, whereas Psl-dependent biofilms are densely packed. These data suggest that Psl polysaccharide may have significant contributions in biofilm persistence in patients with CF and may be helpful for designing therapies for P. aeruginosa CF infection. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  19. Regulatory roles of microtubule-associated proteins in neuronal morphogenesis. Involvement of the extracellular matrix

    Directory of Open Access Journals (Sweden)

    Ramírez G.

    1999-01-01

    Full Text Available As a result of recent investigations, the cytoskeleton can be viewed as a cytoplasmic system of interconnected filaments with three major integrative levels: self-assembling macromolecules, filamentous polymers, e.g., microtubules, intermediate filaments and actin filaments, and supramolecular structures formed by bundles of these filaments or networks resulting from cross-bridges between these major cytoskeletal polymers. The organization of this biological structure appears to be sensitive to fine spatially and temporally dependent regulatory signals. In differentiating neurons, regulation of cytoskeleton organization is particularly relevant, and the microtubule-associated protein (MAP tau appears to play roles in the extension of large neuritic processes and axons as well as in the stabilization of microtubular polymers along these processes. Within this context, tau is directly involved in defining neuronal polarity as well as in the generation of neuronal growth cones. There is increasing evidence that elements of the extracellular matrix contribute to the control of cytoskeleton organization in differentiating neurons, and that these regulations could be mediated by changes in MAP activity. In this brief review, we discuss the possible roles of tau in mediating the effects of extracellular matrix components on the internal cytoskeletal arrays and its organization in growing neurons.

  20. Role of matrix metalloproteinase 13 in both endochondral and intramembranous ossification during skeletal regeneration.

    Directory of Open Access Journals (Sweden)

    Danielle J Behonick

    Full Text Available Extracellular matrix (ECM remodeling is important during bone development and repair. Because matrix metalloproteinase 13 (MMP13, collagenase-3 plays a role in long bone development, we have examined its role during adult skeletal repair. In this study we find that MMP13 is expressed by hypertrophic chondrocytes and osteoblasts in the fracture callus. We demonstrate that MMP13 is required for proper resorption of hypertrophic cartilage and for normal bone remodeling during non-stabilized fracture healing, which occurs via endochondral ossification. However, no difference in callus strength was detected in the absence of MMP13. Transplant of wild-type bone marrow, which reconstitutes cells only of the hematopoietic lineage, did not rescue the endochondral repair defect, indicating that impaired healing in Mmp13-/- mice is intrinsic to cartilage and bone. Mmp13-/- mice also exhibited altered bone remodeling during healing of stabilized fractures and cortical defects via intramembranous ossification. This indicates that the bone phenotype occurs independently from the cartilage phenotype. Taken together, our findings demonstrate that MMP13 is involved in normal remodeling of bone and cartilage during adult skeletal repair, and that MMP13 may act directly in the initial stages of ECM degradation in these tissues prior to invasion of blood vessels and osteoclasts.

  1. Novel self-epitopes derived from aggrecan, fibrillin, and matrix metalloproteinase-3 drive distinct autoreactive T-cell responses in juvenile idiopathic arthritis and in health

    NARCIS (Netherlands)

    S.S.M. Kamphuis (Sylvia); K. Hrafnkelsdóttir (Kolbrún); M. Klein (Mark); W. de Jager (Wilco); M.H. Haverkamp (Margje); J.H.M. van Bilsen (Jolanda); S. Albani (Salvatore); W. Kuis (Wietse); M.H.M. Wauben (Marca); B.J. Prakken (Berent)

    2006-01-01

    textabstractJuvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by chronic joint inflammation. Knowing which antigens drive the autoreactive T-cell response in JIA is crucial for the understanding of disease pathogenesis and additionally may provide targets for an

  2. Functional roles of CSPG4/NG2 in chondrosarcoma.

    Science.gov (United States)

    Jamil, Nuor S M; Azfer, Asim; Worrell, Harrison; Salter, Donald M

    2016-04-01

    CSPG4/NG2 is a multifunctional transmembrane protein with limited distribution in adult tissues including articular cartilage. The purpose of this study was to investigate the possible roles of CSPG4/NG2 in chondrosarcomas and to establish whether this molecule may have potential for targeted therapy. Stable knock-down of CSPG4/NG2 in the JJ012 chondrosarcoma cell line by shRNA resulted in decreased cell proliferation and migration as well as a decrease in gene expression of the MMP (matrix metalloproteinase) 3 protease and ADAMTS4 (aggrecanase). Chondrosarcoma cells in which CSPG4/NG2 was knocked down were more sensitive to doxorubicin than wild-type cells. The results indicate that CSPG4/NG2 has roles in regulating chondrosarcoma cell function in relation to growth, spread and resistance to chemotherapy and that anti-CSPG4/NG2 therapies may have potential in the treatment of surgically unresectable chondrosarcoma.

  3. The role of matrix metalloproteinase-2 promoter polymorphisms in coronary artery disease and myocardial infarction.

    Science.gov (United States)

    Alp, Ebru; Menevse, Sevda; Tulmac, Murat; Yilmaz, Akin; Yalcin, Ridvan; Cengel, Atiye

    2011-04-01

    The matrix metalloproteinase (MMP) family are key enzymes involved in the breakdown of the extracellular matrix in normal physiological processes, including tissue remodeling, and disease processes, such as arthritis and metastasis. The promoter polymorphism in the MMP2 gene may be responsible for multiple diseases related to extracellular matrix degradation. Therefore, we aimed to investigate the relationship between genotypes or haplotypes of -1575 G/A, -1306 C/T, -790 T/G, and -735 C/T promoter polymorphisms and coronary artery disease (CAD) with or without myocardial infarction (MI) history. This study included 298 patients with angiographically confirmed CAD and 299 age matched controls. Genomic DNA was isolated from whole blood and genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. No significant associations were found between -1575 G/A, -1306 C/T, and -790 T/G polymorphisms and CAD with or without MI history. However, the frequency of the -735 TT genotype was significantly lower in the controls than in the patients with MI alone when compared with the CC genotype (p=0.021). Only the distribution of the ACGC haplotype in CAD patients exhibited a significant difference than that in controls (p<0.05). The distribution of other haplotypes did not differ between CAD patients and controls. The present investigation is the first report to detect an association between MMP2 promoter polymorphisms and CAD with or without MI history in the Turkish population. Further case-control studies in CAD development might be contributed to clarify the role of these polymorphisms.

  4. The role of Matrix Gla Protein in ossification and recovery of the avian growth plate

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    Harel eDan

    2012-07-01

    Full Text Available ECM mineralization is an essential physiologic process in bone, teeth, and hypertrophic cartilage. Matrix Gla Protein (MGP, an inhibitor of mineralization, is expressed by chondrocytes and vascular smooth muscle cells to inhibit calcification of those soft tissues.Tibial Dyschondroplasia (TD, a skeletal abnormality apparent as a plug of non-vascularized, non-mineralized, white opaque cartilage in the tibial growth plate of avian species can serve as a good model for studying process and genes involved in matrix mineralization and calcification. In this work, we studied the involvement of MGP in the development of TD, as well as in the processes of spontaneous and induced recovery from this syndrome. First, we found that during normal bone development, MGP is expressed in specific time and locations, starting from wide spread expression in the yet un-ossified diaphysis during embryonic development, to specific expression in hypertrophic chondrocytes adjacent to the chondro-osseous junction and the secondary ossification center just prior to calcification. In addition, we show that MGP is not expressed in the impaired TD lesion, however when the lesion begins to heal, it strongly express MGP prior to its calcification. Moreover, we show that when calcification is inhibited, a gap is formed between the expression zones of MGP and BMP2 and that this gap is closed during the healing process. To conclude, we suggest that MGP, directly or through interaction with BMP2, plays a role as ossification regulator, rather then simple inhibitor that acts prior to ossification.

  5. Ionic liquid matrix-enhanced secondary ion mass spectrometry: the role of proton transfer.

    Science.gov (United States)

    Dertinger, Jennifer J; Walker, Amy V

    2013-03-01

    Room temperature ionic liquids (ILs) are effective matrices in secondary ion mass spectrometry (SIMS) and matrix assisted laser desorption ionization (MALDI). In this paper, we examine the role of proton transfer in the mechanism of secondary ion enhancement using IL matrices in SIMS. We employ hydrogenated and deuterated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as analytes to investigate the origin of proton transfer. The data indicate that protons from the IL anion transfer to the analyte in solution leading to an increase in the secondary ion intensity of the protonated molecular ion. The chemical identity of the matrix cation also affects analyte signal intensities. Using deuterated DPPC we observe that protons (deuterium) from the DPPC tail group react with the cation of the IL liquid leading to an increase in (cation + D)(+) ion intensities. Further, the data suggest that the transfer kinetics of deuterium (hydrogen) is correlated with the secondary ion enhancements observed. The highest secondary ion enhancements are observed for the least sterically hindered cation. Neither the proton affinity nor the pKa of the IL cation have a large effect on the analyte ion intensities, suggesting that steric factors are important in determining the efficacy of IL matrices for a given analyte.

  6. Laminins and Nidogens in the Pericellular Matrix of Chondrocytes: Their Role in Osteoarthritis and Chondrogenic Differentiation.

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    Schminke, Boris; Frese, Jenny; Bode, Christa; Goldring, Mary B; Miosge, Nicolai

    2016-02-01

    The aim of this study was to investigate the role of laminins and nidogen-2 in osteoarthritis (OA) and their potential to support chondrogenic differentiation. We applied immunohistochemistry, electron microscopy, siRNA, quantitative RT-PCR, Western blot, and proteome analysis for the investigation of cartilage tissue and isolated chondrocytes in three-dimensional culture obtained from patients with late-stage knee OA and nidogen-2 knockout mice. We demonstrate that subunits of laminins appear in OA cartilage and that nidogen-2-null mice exhibit typical osteoarthritic features. Chondrogenic progenitor cells (CPCs) produced high levels of laminin-α1, laminin-α5, and nidogen-2 in their pericellular matrix, and laminin-α1 enhanced collagen type II and reduced collagen type I expression by cultured CPCs. Nidogen-2 increased SOX9 gene expression. Knockdown of nidogen-2 reduced SOX9 expression, whereas it up-regulated RUNX2 expression. This study reveals that the influence of the pericellular matrix on CPCs is important for the expression of the major regulator transcription factors, SOX9 and RUNX2. Our novel findings that laminins and nidogen-2 drive CPCs toward chondrogenesis may help in the elucidation of new treatment strategies for cartilage tissue regeneration.

  7. The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded

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    Tyagi Suresh C

    2005-06-01

    Full Text Available Abstract The vascular endothelial basement membrane and extra cellular matrix is a compilation of different macromolecules organized by physical entanglements, opposing ionic charges, chemical covalent bonding, and cross-linking into a biomechanically active polymer. These matrices provide a gel-like form and scaffolding structure with regional tensile strength provided by collagens, elasticity by elastins, adhesiveness by structural glycoproteins, compressibility by proteoglycans – hyaluronans, and communicability by a family of integrins, which exchanges information between cells and between cells and the extracellular matrix of vascular tissues. Each component of the extracellular matrix and specifically the capillary basement membrane possesses unique structural properties and interactions with one another, which determine the separate and combined roles in the multiple diabetic complications or diabetic opathies. Metabolic syndrome, prediabetes, type 2 diabetes mellitus, and their parallel companion (atheroscleropathy are associated with multiple metabolic toxicities and chronic injurious stimuli. The adaptable quality of a matrix or form genetically preloaded with the necessary information to communicate and respond to an ever-changing environment, which supports the interstitium, capillary and arterial vessel wall is individually examined.

  8. A potential role for glia-derived extracellular matrix remodeling in postinjury epilepsy.

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    Kim, Soo Young; Porter, Brenda E; Friedman, Alon; Kaufer, Daniela

    2016-09-01

    Head trauma and vascular injuries are known risk factors for acquired epilepsy. The sequence of events that lead from the initial injury to the development of epilepsy involves complex plastic changes and circuit rewiring. In-depth, comprehensive understanding of the epileptogenic process is critical for the identification of disease-modifying targets. Here we review the complex interactions of cellular and extracellular components that may promote epileptogenesis, with an emphasis on the role of astrocytes. Emerging evidence demonstrates that astrocytes promptly respond to brain damage and play a critical role in the development of postinjury epilepsy. Astrocytes have been shown to regulate extracellular matrix (ECM) remodeling, which can affect plasticity and stability of synapses and, in turn, contribute to the epileptogenic process. From these separate lines of evidence, we present a hypothesis suggesting a possible role for astrocyte-regulated remodeling of ECM and perineuronal nets, a specialized ECM structure around fast-spiking inhibitory interneurons, in the development and progression of posttraumatic epilepsies. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations

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    René Buchet

    2013-03-01

    Full Text Available The present review aims to systematically and critically analyze the current knowledge on phospholipases and their role in physiological and pathological mineralization undertaken by mineralization competent cells. Cellular lipid metabolism plays an important role in biological mineralization. The physiological mechanisms of mineralization are likely to take place in tissues other than in bones and teeth under specific pathological conditions. For instance, vascular calcification in arteries of patients with renal failure, diabetes mellitus or atherosclerosis recapitulates the mechanisms of bone formation. Osteoporosis—a bone resorbing disease—and rheumatoid arthritis originating from the inflammation in the synovium are also affected by cellular lipid metabolism. The focus is on the lipid metabolism due to the effects of dietary lipids on bone health. These and other phenomena indicate that phospholipases may participate in bone remodelling as evidenced by their expression in smooth muscle cells, in bone forming osteoblasts, chondrocytes and in bone resorbing osteoclasts. Among various enzymes involved, phospholipases A1 or A2, phospholipase C, phospholipase D, autotaxin and sphingomyelinase are engaged in membrane lipid remodelling during early stages of mineralization and cell maturation in mineralization-competent cells. Numerous experimental evidences suggested that phospholipases exert their action at various stages of mineralization by affecting intracellular signaling and cell differentiation. The lipid metabolites—such as arachidonic acid, lysophospholipids, and sphingosine-1-phosphate are involved in cell signaling and inflammation reactions. Phospholipases are also important members of the cellular machinery engaged in matrix vesicle (MV biogenesis and exocytosis. They may favour mineral formation inside MVs, may catalyse MV membrane breakdown necessary for the release of mineral deposits into extracellular matrix (ECM, or

  10. Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms

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    Vacek TP

    2015-02-01

    Full Text Available Thomas P Vacek, Shahnaz Rehman, Diana Neamtu, Shipeng Yu, Srikanth Givimani, Suresh C Tyagi Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA Abstract: Atherosclerosis is an inflammatory process that involves activation of matrix metalloproteinases (MMPs; MMPs degrade collagen and allow for smooth-muscle cell migration within a vessel. Moreover, this begets an accumulation of other cellular material, resulting in occlusion of the vessel and ischemic events to tissues in need of nutrients. Homocysteine has been shown to activate MMPs via an increase in oxidative stress and acting as a signaling molecule on receptors like the peroxisome proliferator activated receptor- and N-methyl-d-aspartate receptor. Nitric oxide has been shown to be beneficial in some cases of deactivating MMPs. However, in other cases, it has been shown to be harmful. Further studies are warranted on the scenarios that are beneficial versus destructive. Hydrogen sulfide (H2S has been shown to decrease MMP activities in all cases in the literature by acting as an antioxidant and vasodilator. Various MMP-knockout and gene-silencing models have been used to determine the function of the many different MMPs. This has allowed us to discern the role that each MMP has in promoting or alleviating pathological conditions. Furthermore, there has been some study into the MMP polymorphisms that exist in the population. The purpose of this review is to examine the role of MMPs and their polymorphisms on the development of atherosclerosis, with emphasis placed on pathways that involve nitric oxide, hydrogen sulfide, and homocysteine. Keywords: homocysteine, matrix metalloproteinases, oxidative stress, bone remodeling, collagen cross-linking, hydrogen sulfide, nitric oxide

  11. The role of extracellular matrix in lateral transmission of force in skeletal muscle

    Science.gov (United States)

    Gao, Yingxin

    This dissertation describes the role of extracellular matrix (ECM) in the lateral transmission of force. It consists of an experimental studies of the ECM and mathematical modeling of lateral transmission of force. The effect of aging on the structural and mechanical properties of the epimysium of muscle of the rats were examined. No statistically significant differences were found in the ultrastructure, or the thickness of the epimysium. However, from the tensile stress-strain tests, it was found that the epimysium of muscles from old rats was much stiffer than that of the young rats. Based on these observations. It was concluded that the differences in the mechanical properties of the epimysium of the muscles from the old compared with young rats were not associated with the arrangement and size of collagen fibers in the epimysium. Consequently, other methods will be required to identify the structural bases of the mechanical differences. The stress-strain relationships for the epimysiums of the skeletal muscles from both the young and old rats were found to be nonlinear. A mathematical model was developed that showed that the nonlinear behavior results from the waviness and the reorientation of the collagen fibers in the epimysium. The ECM plays an important role in lateral transmission of force in skeletal muscle by providing shear stress between the muscle fibers or fascicles. A mathematical model was developed to investigate the mechanisms of lateral transmission. It was a modification of the shear lag theory for chopped fiber composite materials used in engineering applications. The modified shear lag theory includes an activation strain to account for muscle contraction and a myofibrils-endomysium interfaces that accounts for the molecular lateral linkages. The model was used to simulate the classic experiments of Street. It was demonstrated that lateral transmission of force in the skeletal muscle is affected by the mechanical and structural properties of

  12. The Role of Host-derived Dentinal Matrix Metalloproteinases in Reducing Dentin Bonding of Resin Adhesives

    OpenAIRE

    Zhang, Shan-chuan; Kern, Matthias

    2009-01-01

    Dentin matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes trapped within mineralized dentin matrix, which have the ability to hydrolyze the organic matrix of demineralized dentin. After bonding with resins to dentin there are usually some exposed collagen fibrils at the bottom of the hybrid layer owing to imperfect resin impregnation of the demineralized dentin matrix. Exposed collagen fibrils might be affected by MMPs inducing hydrolytic degradation, which migh...

  13. Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chun; ZHU Zhonghua; LIU Jianshe; YANG Xiao; FU Ling; DENG Anguo

    2007-01-01

    In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transforming growth factor β1 (TGF-β1) and to explore the role of CTGF in the degradation of renal extracellular matrix (ECM), a human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 (5 μg/L), the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may be a novel way in preventing renal fibrosis.

  14. THE ROLE OF MATRIX METALLOPROTEINASES IN PROCESSES OF HEART RE-MODELING IN CHILDREN WITH RESTRICTIVE CARDIOMYOPATHY

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    T.V. Bershova

    2009-01-01

    Full Text Available Restrictive cardiomyopathy (RCMP is heart disorder with unclear etiology; it can be characterized as disease with disorder of diastolic myocardium function of left ventricle, conditioned by restriction. The chronic heart failure as a syndrome of RCMP can develop as a result of disbalance in system of complex biochemical, structural, and geometrical mechanisms of myocardium re-modeling. Extra cellular matrix play significant role in heart structure and geometry breaking. The destruction of heart is realized by matrix metalloproteinases (MMP. The activity of MMP, in its turn, is controlled by its tissue inhibitors. The present study analyzed the role of MMP in process of collagen’s synthesis and catabolism deregulation, myocardium fibrosis, change of heart chambers, and development of diastolic dysfunction in children with RCMP.Key words: children, chronic heart failure, restrictive cardiomyopathy, matrix metalloproteinases.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(5:36-39

  15. Shell matrix proteins of the clam, Mya truncata: Roles beyond shell formation through proteomic study.

    Science.gov (United States)

    Arivalagan, Jaison; Marie, Benjamin; Sleight, Victoria A; Clark, Melody S; Berland, Sophie; Marie, Arul

    2016-06-01

    Mya truncata, a soft shell clam, is presented as a new model to study biomineralization through a proteomics approach. In this study, the shell and mantle tissue were analysed in order to retrieve knowledge about the secretion of shell matrix proteins (SMPs). Out of 67 and 127 shell and mantle proteins respectively, 16 were found in both shell and mantle. Bioinformatic analysis of SMP sequences for domain prediction revealed the presence of several new domains such as fucolectin tachylectin-4 pentraxin-1 (FTP), scavenger receptor, alpha-2-macroglobulin (α2 M), lipocalin and myosin tail along with previously reported SMP domains such as chitinase, carbonic anhydrase, tyrosinase, sushi, and chitin binding. Interestingly, these newly predicted domains are attributed with molecular functions other than biomineralization. These findings suggest that shells may not only act as protective armour from predatory action, but could also actively be related to other functions such as immunity. In this context, the roles of SMPs in biomineralization need to be looked in a new perspective.

  16. The role of myristoylation in the membrane association of the Lassa virus matrix protein Z

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    Eichler Robert

    2006-11-01

    Full Text Available Abstract The Z protein is the matrix protein of arenaviruses and has been identified as the main driving force for budding. Both LCMV and Lassa virus Z proteins bud from cells in the absence of other viral proteins as enveloped virus-like particles. Z accumulates near the inner surface of the plasma membrane where budding takes place. Furthermore, biochemical data have shown that Z is strongly membrane associated. The primary sequence of Z lacks a typical transmembrane domain and until now it is not understood by which mechanism Z is able to interact with cellular membranes. In this report, we analyzed the role of N-terminal myristoylation for the membrane binding of Lassa virus Z. We show that disruption of the N-terminal myristoylation signal by substituting the N-terminal glycine with alanine (Z-G2A mutant resulted in a significant reduction of Z protein association with cellular membranes. Furthermore, removal of the myristoylation site resulted in a relocalization of Z from a punctuate distribution to a more diffuse cellular distribution pattern. Finally, treatment of Lassa virus-infected cells with various myristoylation inhibitors drastically reduced efficient Lassa virus replication. Our data indicate that myristoylation of Z is critical for its binding ability to lipid membranes and thus, for effective virus budding.

  17. Concentric Gel System to Study the Biophysical Role of Matrix Microenvironment on 3D Cell Migration

    Science.gov (United States)

    Kurniawan, Nicholas Agung; Chaudhuri, Parthiv Kant; Lim, Chwee Teck

    2015-01-01

    The ability of cells to migrate is crucial in a wide variety of cell functions throughout life from embryonic development and wound healing to tumor and cancer metastasis. Despite intense research efforts, the basic biochemical and biophysical principles of cell migration are still not fully understood, especially in the physiologically relevant three-dimensional (3D) microenvironments. Here, we describe an in vitro assay designed to allow quantitative examination of 3D cell migration behaviors. The method exploits the cell’s mechanosensing ability and propensity to migrate into previously unoccupied extracellular matrix (ECM). We use the invasion of highly invasive breast cancer cells, MDA-MB-231, in collagen gels as a model system. The spread of cell population and the migration dynamics of individual cells over weeks of culture can be monitored using live-cell imaging and analyzed to extract spatiotemporally-resolved data. Furthermore, the method is easily adaptable for diverse extracellular matrices, thus offering a simple yet powerful way to investigate the role of biophysical factors in the microenvironment on cell migration. PMID:25867104

  18. Matrix Metalloproteinase 9 in Epilepsy: The Role of Neuroinflammation in Seizure Development

    Science.gov (United States)

    2016-01-01

    Matrix metalloproteinase 9 is a proteolytic enzyme which is recently one of the more often studied biomarkers. Its possible use as a biomarker of neuronal damage in stroke, heart diseases, tumors, multiple sclerosis, and epilepsy is being widely indicated. In epilepsy, MMP-9 is suggested to play a role in epileptic focus formation and in the stimulation of seizures. The increase of MMP-9 activity in the epileptic focus was observed both in animal models and in clinical studies. MMP-9 contributes to formation of epileptic focus, for example, by remodeling of synapses. Its proteolytic action on the elements of blood-brain barrier and activation of chemotactic processes facilitates accumulation of inflammatory cells and induces seizures. Also modification of glutamatergic transmission by MMP-9 is associated with seizures. In this review we will try to recapitulate the results of previous studies about MMP-9 in terms of its association with epilepsy. We will discuss the mechanisms of its actions and present the results revealed in animal models and clinical studies. We will also provide a comparison of the results of various studies on MMP-9 levels in the context of its possible use as a biomarker of the activity of epilepsy. PMID:28104930

  19. Matrix Metalloproteinase 9 in Epilepsy: The Role of Neuroinflammation in Seizure Development

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    Elżbieta Bronisz

    2016-01-01

    Full Text Available Matrix metalloproteinase 9 is a proteolytic enzyme which is recently one of the more often studied biomarkers. Its possible use as a biomarker of neuronal damage in stroke, heart diseases, tumors, multiple sclerosis, and epilepsy is being widely indicated. In epilepsy, MMP-9 is suggested to play a role in epileptic focus formation and in the stimulation of seizures. The increase of MMP-9 activity in the epileptic focus was observed both in animal models and in clinical studies. MMP-9 contributes to formation of epileptic focus, for example, by remodeling of synapses. Its proteolytic action on the elements of blood-brain barrier and activation of chemotactic processes facilitates accumulation of inflammatory cells and induces seizures. Also modification of glutamatergic transmission by MMP-9 is associated with seizures. In this review we will try to recapitulate the results of previous studies about MMP-9 in terms of its association with epilepsy. We will discuss the mechanisms of its actions and present the results revealed in animal models and clinical studies. We will also provide a comparison of the results of various studies on MMP-9 levels in the context of its possible use as a biomarker of the activity of epilepsy.

  20. Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression.

    Science.gov (United States)

    Rauvala, M; Aglund, K; Puistola, U; Turpeenniemi-Hujanen, T; Horvath, G; Willén, R; Stendahl, U

    2006-01-01

    The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Umeå University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.

  1. The Role of Filler-Matrix Interaction on Viscoelastic Response of Biomimetic Nanocomposite Hydrogels

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    Alireza S. Sarvestani

    2008-01-01

    Full Text Available The effect of a glutamic acid (negatively charged peptide (Glu6, which mimics the terminal region of the osteonectin glycoprotein of bone on the shear modulus of a synthetic hydorgel/apatite nanocomposite, was investigated. One end of the synthesized peptide was functionalized with an acrylate group (Ac-Glu6 to covalently attach the peptide to the hydrogel phase of the composite matrix. The addition of Ac-Glu6 to hydroxyapatite (HA nanoparticles (50 nm in size resulted in significant reinforcement of the shear modulus of the nanocomposite (∼100% increase in elastic shear modulus. The reinforcement effect of the Glu6 peptide, a sequence in the terminal region of osteonectin, was modulated by the size of the apatite crystals. A molecular model is also proposed to demonstrate the role of polymer-apatite interaction in improving the viscoelastic behavior of the bone mimetic composite. The predictions of the model were compared with the measured dynamic shear modulus of the PLEOF hydrogel reinforced with HA nanoparticles. This predictive model provides a quantitative framework to optimize the properties of reinforced polymer nanocomposites as scaffolds for applications in tissue regeneration.

  2. Cardioprotective Effects of Voluntary Exercise in a Rat Model: Role of Matrix Metalloproteinase-2

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    Anikó Pósa

    2015-01-01

    Full Text Available Background. Regular exercise at moderate intensity reduces cardiovascular risks. Matrix metalloproteinases (MMPs play a major role in cardiac remodeling, facilitating physiological adaptation to exercise. The aim of this study was to examine the influence of voluntary physical exercise on the MMP-2 enzyme activity and to investigate the cardiac performance by measurement of angina susceptibility of the heart, the basal blood pressure, the surviving aorta ring contraction, and the cardiac infarct size after I/R-induced injury. Methods. Male Wistar rats were divided into control and exercising groups. After a 6-week period, the serum level of MMP-2, basal blood pressure, cardiac angina susceptibility (the ST segment depression provoked by epinephrine and 30 s later phentolamine, AVP-induced heart perfusion and aorta ring contraction, infarct size following 30 min ischemia and 120 min reperfusion, and coronary effluent MMP-2 activity were measured. Results. Voluntary wheel-running exercise decreased both the sera (64 kDa and 72 kDa and the coronary effluent (64 kDa MMP-2 level, reduced the development of ST depression, improved the isolated heart perfusion, and decreased the ratio of infarct size. Conclusion. 6 weeks of voluntary exercise training preserved the heart against cardiac injury. This protective mechanism might be associated with the decreased activity of MMP-2.

  3. A role for matrix metalloproteinase-9 in the hemodynamic changes following acute pulmonary embolism.

    Science.gov (United States)

    Fortuna, Geisa M; Figueiredo-Lopes, Lívia; Dias-Junior, Carlos A C; Gerlach, Raquel F; Tanus-Santos, Jose E

    2007-01-02

    Matrix metalloproteinases (MMPs) modulate vascular contractility and may affect acute pulmonary embolism (APE)-induced pulmonary hypertension. We examined the effects of the administration of doxycycline (a MMP inhibitor) following APE in anesthetized dogs. Sham operated dogs (N=5) received only saline. APE was induced by intravenous injections of microspheres in amounts to increase mean pulmonary artery pressure (MPAP) by 20 mm Hg, and embolized dogs received saline (Emb group, N=8), or doxycycline (10 mg/kg, i.v.) 5 or 30 min of APE (Emb+Doxy 5 and Emb+Doxy 30 groups, N=9 and 8, respectively). Hemodynamic evaluation was performed at baseline and 5-120 after APE. Gelatin zymography of MMP-2 and MMP-9 from plasma samples was performed. No significant hemodynamic changes were found in Sham animals. Embolization increased MPAP by 218+/-16% and the pulmonary vascular resistance index (PVRI) by 289+/-42% in Emb group (both PDoxy 30+Emb group. In addition, doxycyline reduced MPAP and PVRI 30 min after APE with maximum effects seen 120 min after APE (25+/-4% decrease in MPAP and 33+/-6% decrease in PVRI; both PDoxy+5 group. Plasma pro-MMP-9 and MMP-9 levels increased only in Emb group and MMP-2 remained unaltered. Our study shows that doxycycline attenuates APE-induced pulmonary hypertension, and indicates that MMP-9 has a role in APE-induced pulmonary hypertension. MMP-9 may be a pharmacological target in APE.

  4. Role of Substratum Stiffness in Modulating Genes Associated with Extracellular Matrix and Mechanotransducers YAP and TAZ

    Science.gov (United States)

    Raghunathan, Vijay Krishna; Morgan, Joshua T.; Dreier, Britta; Reilly, Christopher M.; Thomasy, Sara M.; Wood, Joshua A.; Ly, Irene; Tuyen, Binh C.; Hughbanks, Marissa; Murphy, Christopher J.; Russell, Paul

    2013-01-01

    Purpose. Primary open-angle glaucoma is characterized by increased resistance to aqueous humor outflow and a stiffer human trabecular meshwork (HTM). Two Yorkie homologues, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif, encoded by WWTR1 (TAZ), are mechanotransducers of the extracellular-microenvironment and coactivators of transcription. Here, we explore how substratum stiffness modulates the YAP/TAZ pathway and extracellular matrix genes in HTM cells and how this may be play a role in the onset and progression of glaucoma. Methods. HTM cells from normal donors were cultured on hydrogels mimicking the stiffness of normal (5 kPa) and glaucomatous (75 kPa) HTM. Changes in expression of YAP/TAZ related genes and steroid responsiveness were determined. Additionally, transglutaminase-2 expression was determined after YAP silencing. Results. YAP and TAZ are both expressed in human trabecular meshwork cells. In vitro, YAP and TAZ were inversely regulated by substratum stiffness. YAP and 14-3-3σ were downregulated to different extents on stiffer substrates; TAZ, tissue transglutaminase (TGM2), and soluble frizzled-related protein-1 (sFRP-1) were significantly upregulated. CTGF expression appeared to be altered differentially by both YAP and TAZ. Myocilin and angiopoietin-like 7 expression in response to dexamethasone was more pronounced on stiffer substrates. We demonstrated a direct effect by YAP on TGM2 when YAP was silenced by small interfering RNA. Conclusions. The expression of YAP/TAZ and ECM-related-genes is impacted on physiologically relevant substrates. YAP was upregulated in cells on softer substrates. Stiffer substrates resulted in upregulation of canonical Wnt modulators, TAZ and sFRP-1, and thus may influence the progression of glaucoma. These results demonstrate the importance of YAP/TAZ in the HTM and suggest their role in glaucoma. PMID:23258147

  5. Salivary inflammatory mediators and metalloproteinase 3 in patients with chronic severe periodontitis before and after periodontal phase I therapy

    OpenAIRE

    Reina, Silvia Lorena; Hoyos, Fernando; Carranza, Nelson; Borda, Enri Santiago

    2015-01-01

    The role of IL-1β, PGE2 and MMP-3 in the pathogenesis of periodontal disease is well researched. This study aimed to asses and compared the salivary IL-1β, PGE2 and MMP-3 levels in patients with untreated chronic severe periodontitis and those treated with periodontal phase I therapy and periodontally healthy individuals as controls, in relationship to the presence of salivary anti-β1 IgA. Fil: Reina, Silvia Lorena. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacolo...

  6. Salivary inflammatory mediators and metalloproteinase 3 in patients with chronic severe periodontitis before and after periodontal phase I therapy

    OpenAIRE

    Reina, Silvia Lorena; Hoyos, Fernando; Carranza, Nelson; Borda, Enri Santiago

    2015-01-01

    The role of IL-1β, PGE2 and MMP-3 in the pathogenesis of periodontal disease is well researched. This study aimed to asses and compared the salivary IL-1β, PGE2 and MMP-3 levels in patients with untreated chronic severe periodontitis and those treated with periodontal phase I therapy and periodontally healthy individuals as controls, in relationship to the presence of salivary anti-β1 IgA. Fil: Reina, Silvia Lorena. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacolo...

  7. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    Directory of Open Access Journals (Sweden)

    Alison Gartland

    2016-09-01

    Full Text Available Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

  8. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    DEFF Research Database (Denmark)

    Gartland, Alison; Erler, Janine Terra; Cox, Thomas Robert

    2016-01-01

    and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview......Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating...... of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis....

  9. Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines.

    Science.gov (United States)

    Serra, Raffaele; Grande, Raffaele; Buffone, Gianluca; Molinari, Vincenzo; Perri, Paolo; Perri, Aldina; Amato, Bruno; Colosimo, Manuela; de Franciscis, Stefano

    2016-02-01

    Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non-infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme-linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP-1 and MMP-8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP-2 and MMP-9. We also documented higher levels of interleukin (IL)-1, IL-6, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.

  10. The role of valvular endothelial cell paracrine signaling and matrix elasticity on valvular interstitial cell activation.

    Science.gov (United States)

    Gould, Sarah T; Matherly, Emily E; Smith, Jennifer N; Heistad, Donald D; Anseth, Kristi S

    2014-04-01

    The effects of valvular endothelial cell (VlvEC) paracrine signaling on VIC phenotype and nodule formation were tested using a co-culture platform with physiologically relevant matrix elasticities and diffusion distance. 100 μm thin poly(ethylene glycol) (PEG) hydrogels of 3-27 kPa Young's moduli were fabricated in transwell inserts. VICs were cultured on the gels, as VIC phenotype is known to change significantly within this range, while VlvECs lined the underside of the membrane. Co-culture with VlvECs significantly reduced VIC activation to the myofibroblast phenotype on all gels with the largest percent decrease on the 3 kPa gels (~70%), while stiffer gels resulted in approximately 20-30% decrease. Additionally, VlvECs significantly reduced αSMA protein expression (~2 fold lower) on both 3 and 27 kPa gels, as well as the number (~2 fold lower) of nodules formed on the 27 kPa gels. Effects of VlvECs were prevented when nitric oxide (NO) release was inhibited with l-NAME, suggesting that VlvEC produced NO inhibits VIC activation. Withdrawal of l-NAME after 3, 5, and 7 days with restoration of VlvEC NO production for 2 additional days led to a partial reversal of VIC activation (~25% decrease). A potential mechanism by which VlvEC produced NO reduced VIC activation was studied by inhibiting initial and mid-stage cGMP pathway molecules. Inhibition of soluble guanylyl cyclase (sGC) with ODQ or protein kinase G (PKG) with RBrcGMP or stimulation of Rho kinase (ROCK) with LPA, abolished VlvEC effects on VIC activation. This work contributes substantially to the understanding of the valve endothelium's role in preventing VIC functions associated with aortic valve stenosis initiation and progression.

  11. Identification and Characterization of the Lysine-Rich Matrix Protein Family in Pinctada fucata: Indicative of Roles in Shell Formation.

    Science.gov (United States)

    Liang, Jian; Xie, Jun; Gao, Jing; Xu, Chao-Qun; Yan, Yi; Jia, Gan-Chu; Xiang, Liang; Xie, Li-Ping; Zhang, Rong-Qing

    2016-12-01

    Mantle can secret matrix proteins playing key roles in regulating the process of shell formation. The genes encoding lysine-rich matrix proteins (KRMPs) are one of the most highly expressed matrix genes in pearl oysters. However, the expression pattern of KRMPs is limited and the functions of them still remain unknown. In this study, we isolated and identified six new members of lysine-rich matrix proteins, rich in lysine, glycine and tyrosine, and all of them are basic matrix proteins. Combined with four members of the KRMPs previously reported, all these proteins can be divided into three subclasses according to the results of phylogenetic analyses: KRMP1-3 belong to subclass KPI, KRMP4-5 belong to KPII, and KRMP6-10 belong to KPIII. Three subcategories of lysine-rich matrix proteins are highly expressed in the D-phase, the larvae and adult mantle. Lysine-rich matrix proteins are involved in the shell repairing process and associated with the formation of the shell and pearl. What's more, they can cause abnormal shell growth after RNA interference. In detail, KPI subgroup was critical for the beginning formation of the prismatic layer; both KPII and KPIII subgroups participated in the formation of prismatic layer and nacreous layer. Compared with different temperatures and salinity stimulation treatments, the influence of changes in pH on KRMPs gene expression was the greatest. Recombinant KRMP7 significantly inhibited CaCO3 precipitation, changed the morphology of calcite, and inhibited the growth of aragonite in vitro. Our results are beneficial to understand the functions of the KRMP genes during shell formation.

  12. The extracellular matrix of the lung and its role in edema formation

    OpenAIRE

    Paolo Pelosi; Rocco, Patricia R. M.; Daniela Negrini; Alberto Passi

    2007-01-01

    The extracellular matrix is composed of a three-dimensional fiber mesh filled with different macromolecules such as: collagen (mainly type I and III), elastin, glycosaminoglycans, and proteoglycans. In the lung, the extracellular matrix has several functions which provide: 1) mechanical tensile and compressive strength and elasticity, 2) low mechanical tissue compliance contributing to the maintenance of normal interstitial fluid dynamics, 3) low resistive pathway for an effective gas exchang...

  13. The clinical role of increase of serum matrix metalloproteinase-8 concentration in patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    强华; 周朝霞; 孙超峰; 马爱群; 程华; 周萍

    2008-01-01

    Objective To study the clinical role of the variation of serum matrix metalloproteinase-8 (MMP-8) concentration in patients with acute coronary syndrome (ACS). Methods ELISA method was adopted to detect serum MMP-8 concentration and to observe concentration's differences and features among 80 selected ACS cases (43 acute myocardial infarction and 37 unstable angina pectoris), 43 stable angina pectoris (SAP) cases and 37 control cases. And meanwhile the atherosclerosis risk factors of each case, such as age,...

  14. Expression changes and roles of matrix metalloproteinases in a rat model of traumatic deep vein thrombosis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-bing; LI Wen; YAO Li-qing; ZHAO Xue-ling; WANG Bing; LI Hong-kun; NING Ya; SONG En; ZHANG Xin-xin

    2010-01-01

    Objective:To study the expression changes of matrix metal loproteinases (MMPs) in traumatic deep vein thrombosis (TDVT) in a rat model with the aid of gene chip technology and to explore the roles of MMPs in TDVT.Methods:Totally 150 Sprague Dawley rats were randomly divided into control group (n=10) and model group (n=140). Rat models of TDVT were established by clamping the femoral vein and fixing the bilateral hind limbs. Then fixation of the hip spica with plaster bandage was conducted.According to the observation phases and/or biological situations of the femoral vein thrombosis, the model rats were further divided into 7 groups. Vascular tissues were obtained from each group through noninvasive incision into the femoral vein at corresponding time points. We adopted the Trizoi one-step method for total RNA extraction,Affymetrix RAT 230 2.0 array for detection of RNA expressions and fold change (FC) analysis for changes of differential expressions of MMPs in each group. The main outcome parameters measured included expressions of MMP-2,MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11,MMP- 12, MMP-13, MMP- 14, MMP- 16, MMP-23 and MMP-24. Gene array data of these MMPs were analyzed by the Affymetrix Microarray Analysis software (Version 5.0).Results:FC analysis showed differential expressions of MMPs in each group during the course of TDVT. At the initial period of thrombosis, MMP-2, MMP-3, MMP-7,MMP-8, MMP-9, MMP- 10, MMP-11, and MMP-24 had significantly high expression, while MMP-12, MMP-13,MMP-14, MMP-16 and MMP-23 had relatively low expression. MMPs were all highly expressed at the peak time of thrombosis. In the process of thrombus resolution,MMP-2, MMP-10, MMP-16 and MMP-24 have relatively low expression, while MMP-12, MMP-13, MMP-14,MMP-16 and MMP-23 have significantly high expression.Conclusion:MMPs may affect the process of TDVT through transcription regulation of the fibrinolysis-anti-fibrinolytic system during the course of thrombosis and thrombus resolution.

  15. Dermal Wound Fibroblasts and Matrix Metaloproteinases (MMPs: Their Possible Role in Allergic Contact Dermatitis

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Khorramizadeh

    2004-03-01

    Full Text Available This study was conducted to examine if allergic contact dermatitis (ACD alters the expression of MMPs in human dermal fibroblasts. Fibroblasts are the primary source for MMP and matrix production in skin. MMPs are known to involve in a number of physiological and pathological processes. Some published data indicated a gelatinase-like activity in acute and chronic phases of allergic contact dermatitis. However, no exact source of gelatinase activity was demonstrated. Moreover, little is known about the role of MMPs in immune responses.To study and predict the pathophysiological effects of (MMP-2 in allergic contact dermatitic (ACD patients, we established an in vitro tissue culture survey based on fibroblast explanted from ACD wounds and normal tissues respectively. We also employed a precise proliferation assay [i.e. MTT; 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] to analyze and compare three ACD vs. three normal cell strains. Parallel to MTT assay, we assessed the activity as well as the kinetics of gelatinase (MMP-2 in conditioned media using a zymogeraphy analysis. There was a significant difference in proliferation capacity between mean ACD fibroblast strains vs. mean normal cells, particularly in days 6 to 8 post explantation, 492.5±6.6 vs. 361.75±8.25 respectively. Zymoanalyses indicated significant differences between ACD cells and normal fibroblasts both in time-course and MMP-2 activity per cell fashions, 163.7±16.21 for mean ACD fibroblasts vs. 130±9.09 for normal cells respectively. These data suggest that fibroblasts overproliferated in the process of ACD.  Moreover, simultaneous overexpression of MMPs observed in ACD fibroblasts vs. normal strains, is indicative of altered fibroblast functionality in the process of allergic contactdermatitis. The activity per cell analysis showed that MMP-2 expression in ACD fibroblasts is independent of cell number, suggesting that either intra- or inter-cellular control

  16. Dermal Wound Fibroblasts and Matrix Metaloproteinases (MMPs): Their Possible Role in Allergic Contact Dermatitis.

    Science.gov (United States)

    Khorramizadeh, Mohammad Reza; Falak, Reza; Pezeshki, Mohammad; Safavifar, Farnaz; Mansouri, Parvin; Ghahary, Aziz; Saadat, Farshid; Varshokar, Kamran

    2004-03-01

    This study was conducted to examine if allergic contact dermatitis (ACD) alters the expression of MMPs in human dermal fibroblasts. Fibroblasts are the primary source for MMP and matrix production in skin. MMPs are known to involve in a number of physiological and pathological processes. Some published data indicated a gelatinase-like activity in acute and chronic phases of allergic contact dermatitis. However, no exact source of gelatinase activity was demonstrated. Moreover, little is known about the role of MMPs in immune responses.To study and predict the pathophysiological effects of (MMP-2) in allergic contact dermatitic (ACD) patients, we established an in vitro tissue culture survey based on fibroblast explanted from ACD wounds and normal tissues respectively. We also employed a precise proliferation assay [i.e. MTT; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to analyze and compare three ACD vs. three normal cell strains. Parallel to MTT assay, we assessed the activity as well as the kinetics of gelatinase (MMP-2) in conditioned media using a zymogeraphy analysis. There was a significant difference in proliferation capacity between mean ACD fibroblast strains vs. mean normal cells, particularly in days 6 to 8 post explantation, 492.5+/-6.6 vs. 361.75+/-8.25 respectively. Zymoanalyses indicated significant differences between ACD cells and normal fibroblasts both in time-course and MMP-2 activity per cell fashions, 163.7+/-16.21 for mean ACD fibroblasts vs. 130+/-9.09 for normal cells respectively. These data suggest that fibroblasts overproliferated in the process of ACD. Moreover, simultaneous overexpression of MMPs observed in ACD fibroblasts vs. normal strains, is indicative of altered fibroblast functionality in the process of allergic contactdermatitis. The activity per cell analysis showed that MMP-2 expression in ACD fibroblasts is independent of cell number, suggesting that either intra- or inter-cellular control signals are also

  17. Accounting for the Role of Long Walks on Networks via a New Matrix Function

    CERN Document Server

    Estrada, Ernesto

    2016-01-01

    We introduce a new matrix function for studying graphs and real-world networks based on a double-factorial penalization of walks between nodes in a graph. This new matrix function is based on the matrix error function. We find a very good approximation of this function using a matrix hyperbolic tangent function. We derive a communicability function, a subgraph centrality and a double-factorial Estrada index based on this new matrix function. We obtain upper and lower bounds for the double-factorial Estrada index of graphs, showing that they are similar to those of the single-factorial Estrada index. We then compare these indices with the single-factorial one for simple graphs and real-world networks. In particular, we study the problem of identification of essential proteins in yeast. We conclude that for this practical problem the structural information contained in the longer walks on graphs is not as relevant as the one contained in the shorter ones for characterizing network structure. More practical appl...

  18. Electron transport through SWNT/trans-PA/ SWNT structure (the role of solitons): A t-matrix technique

    Indian Academy of Sciences (India)

    S A Ketabi; H Milani Moghaddam; N Shahtamasebi

    2007-10-01

    Using a tight-binding model and a transfer-matrix technique, we numerically investigate the effects of the coupling strength and the role of solitons on the electronic transmission through a system in which trans-polyacetylene (trans-PA) molecule is sandwiched between two semi-infinite single-walled carbon nanotubes (SWNT). We rely on Landauer formalism as the basis for studying the conductance properties of this system. Our calculations show that the solitons play an important role in the response of this system causing a large enhancement in the conductance. Also our results suggest that the conductance is sensitive to the CNT/molecule coupling strength.

  19. Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions.

    Science.gov (United States)

    Górski, A; Castronovo, V; Stepień-Sopniewska, B; Grieb, P; Ryba, M; Mrowiec, T; Korczak-Kowalska, G; Wierzbicki, P; Matysiak, W; Dybowska, B

    1994-07-01

    Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.

  20. Adhesion of pineapple-leaf fiber to epoxy matrix: The role of surface treatments

    Directory of Open Access Journals (Sweden)

    Yusran Payae

    2009-07-01

    Full Text Available Natural fibers are considered to have potential use as reinforcing agents in polymer composite materials because of their principle benefits: moderate strength and stiffness, low cost, and be an environmental friendly, degradable, and renewablematerial. Due to their inherently hydrophilic nature, they are prone to absorb moisture, which can plasticise or weaken theadhesion of fibers to the surrounding matrix and by this affect the performance of composites used in atmospheric humidity,particularly at elevated temperatures. The surface treatments are often applied to the fiber to improve the bond strengthbetween the fibers and matrix. This work discussed the effect of sodium hydroxide (NaOH treatment and epoxy resin as acompatibilizing agent on interface properties of pineapple leaf fiber (PALF-epoxy composites. A single-fiber fragmentationtest coupled with data reduction technique was employed to assess interface quality in terms of apparent interfacial shearstrength (IFSS or a of untreated, NaOH, and epoxy resin treated PALFs-epoxy composites. Tensile properties of untreatedand treated PALFs were also examined. It was found that both treatments substantially increase a, corresponding to animproved level of adhesion. The improvement in the level of adhesion for the alkali and epoxy treated fiber composites wasdue to an increase in the physical bonding between the alkali treated fibers and the matrix, and due to a promoted compatibilitybetween the epoxy treated fibers and matrix, respectively.

  1. The role of porous matrix in water flow regulation within a karst unsaturated zone: an integrated hydrogeophysical approach

    Science.gov (United States)

    Carrière, Simon D.; Chalikakis, Konstantinos; Danquigny, Charles; Davi, Hendrik; Mazzilli, Naomi; Ollivier, Chloé; Emblanch, Christophe

    2016-05-01

    Some portions of the porous rock matrix in the karst unsaturated zone (UZ) can contain large volumes of water and play a major role in water flow regulation. The essential results are presented of a local-scale study conducted in 2011 and 2012 above the Low Noise Underground Laboratory (LSBB - Laboratoire Souterrain à Bas Bruit) at Rustrel, southeastern France. Previous research revealed the geological structure and water-related features of the study site and illustrated the feasibility of specific hydrogeophysical measurements. In this study, the focus is on hydrodynamics at the seasonal and event timescales. Magnetic resonance sounding (MRS) measured a high water content (more than 10 %) in a large volume of rock. This large volume of water cannot be stored in fractures and conduits within the UZ. MRS was also used to measure the seasonal variation of water stored in the karst UZ. A process-based model was developed to simulate the effect of vegetation on groundwater recharge dynamics. In addition, electrical resistivity tomography (ERT) monitoring was used to assess preferential water pathways during a rain event. This study demonstrates the major influence of water flow within the porous rock matrix on the UZ hydrogeological functioning at both the local (LSBB) and regional (Fontaine de Vaucluse) scales. By taking into account the role of the porous matrix in water flow regulation, these findings may significantly improve karst groundwater hydrodynamic modelling, exploitation, and sustainable management.

  2. The role of porous matrix in water flow regulation within a karst unsaturated zone: an integrated hydrogeophysical approach

    Science.gov (United States)

    Carrière, Simon D.; Chalikakis, Konstantinos; Danquigny, Charles; Davi, Hendrik; Mazzilli, Naomi; Ollivier, Chloé; Emblanch, Christophe

    2016-11-01

    Some portions of the porous rock matrix in the karst unsaturated zone (UZ) can contain large volumes of water and play a major role in water flow regulation. The essential results are presented of a local-scale study conducted in 2011 and 2012 above the Low Noise Underground Laboratory (LSBB - Laboratoire Souterrain à Bas Bruit) at Rustrel, southeastern France. Previous research revealed the geological structure and water-related features of the study site and illustrated the feasibility of specific hydrogeophysical measurements. In this study, the focus is on hydrodynamics at the seasonal and event timescales. Magnetic resonance sounding (MRS) measured a high water content (more than 10 %) in a large volume of rock. This large volume of water cannot be stored in fractures and conduits within the UZ. MRS was also used to measure the seasonal variation of water stored in the karst UZ. A process-based model was developed to simulate the effect of vegetation on groundwater recharge dynamics. In addition, electrical resistivity tomography (ERT) monitoring was used to assess preferential water pathways during a rain event. This study demonstrates the major influence of water flow within the porous rock matrix on the UZ hydrogeological functioning at both the local (LSBB) and regional (Fontaine de Vaucluse) scales. By taking into account the role of the porous matrix in water flow regulation, these findings may significantly improve karst groundwater hydrodynamic modelling, exploitation, and sustainable management.

  3. Superplasticity in ceramic and metal matrix composites and the role of grain size, segregation, interfaces, and second phase morphology

    Energy Technology Data Exchange (ETDEWEB)

    Wadsworth, J.; Nieh, T.G.

    1992-10-01

    Structural ceramics and ceramic composites have been shown to exhibit superplasticity in recent times and this discovery has attracted tremendous interest. Although the number of ceramics exhibits superplasticity is now quite large, there are gaps in understanding the requirements for superplasticity in ceramics. Also, superplastic behavior at very high strain rates (1 s{sup {minus}1}) in metallic-based materials is an area of increasing research. In this case, the phenomenon has been observed quite extensively in aluminum alloy-based metal matrix composites and mechanically alloyed aluminum- and nickel-based materials. Again, the details of the structural requirements of this phenomenon are not yet understood. In the present paper, experimental results on superplasticity in ceramic-based materials and on high strain rate behavior in metallic-based materials are presented. The roles of grain size, grain boundary and interface chemistry, and second phase morphology and compatibility with the matrix material will be emphasized.

  4. The Relationship between Matrix Metalloproteinases and Atherosclerotic Lesions%基质金属蛋白酶与动脉粥样硬化病变的关系

    Institute of Scientific and Technical Information of China (English)

    陈线茹; 豆志伟

    2012-01-01

    在正常生理情况下,基质金属蛋白酶-9能够切断任何细胞外基质成分,调节细胞黏着,作用于细胞外成分或其他蛋白成分而启动潜在生物学功能.病理状态下,潜在型基质金属蛋白酶-9可被激活并参与动脉粥样硬化时的血管壁重构、斑块破裂、血栓形成等过程.研究发现,基质金属蛋白酶-3与动脉粥样硬化过程中纤维帽的形成密切相关,同时基质金属蛋白酶-3可激活包括基质金属蛋白酶-3前体在内的其他基质金属蛋白酶,从而加速动脉粥样硬化病变的发展.%In normal physiological conditions, matrix metalloproteinases-9 not only cut off any extracellular matrix components and adjust cell adhesion, but when in the role of the extracellular matrix components or other protein composition can star) the potential biological function. In the pathologic state, potential matrix metalloproteinases-9 can be activated and participate hemal wall reconstruction, plaque ruptured and thrombosis in the processes of atherosclerosis. Research has found matrix metalloproleinases-3 to be closely related lo the process of the formation of the fibrous cap in atherosclerosis, at the same time matrix metal loproteinases-3 can activate matrix metalloprotein-ases-3 precursor and other matrix metalloproteinases, thus speeding up the development of atherosclerotic lesions.

  5. Matrix Metalloproteinases During Axonal Regeneration, a Multifactorial Role from Start to Finish.

    Science.gov (United States)

    Andries, Lien; Van Hove, Inge; Moons, Lieve; De Groef, Lies

    2017-04-01

    By proteolytic cleavage, matrix metalloproteinases (MMPs) not only remodel the extracellular matrix (ECM) but they also modify the structure and activity of other proteinases, growth factors, signaling molecules, cell surface receptors, etc. Their vast substrate repertoire adds a complex extra dimension of biological control and turns MMPs into important regulatory nodes in the protease web. In the central nervous system (CNS), the detrimental impact of elevated MMP activities has been well-described for traumatic injuries and many neurodegenerative diseases. Nonetheless, there is ample proof corroborating MMPs as fine regulators of CNS physiology, and well-balanced MMP activity is instrumental to development, plasticity, and repair. In this manuscript, we review the emerging evidence for MMPs as beneficial modulators of axonal regeneration in the mammalian CNS. By exploring the multifactorial causes underlying the inability of mature axons to regenerate, and describing how MMPs can help to overcome these hurdles, we emphasize the benign actions of these Janus-faced proteases.

  6. Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix

    Science.gov (United States)

    Subramanian, Arul; Schilling, Thomas F.

    2015-01-01

    Tendons and ligaments are extracellular matrix (ECM)-rich structures that interconnect muscles and bones. Recent work has shown how tendon fibroblasts (tenocytes) interact with muscles via the ECM to establish connectivity and strengthen attachments under tension. Similarly, ECM-dependent interactions between tenocytes and cartilage/bone ensure that tendon-bone attachments form with the appropriate strength for the force required. Recent studies have also established a close lineal relationship between tenocytes and skeletal progenitors, highlighting the fact that defects in signals modulated by the ECM can alter the balance between these fates, as occurs in calcifying tendinopathies associated with aging. The dynamic fine-tuning of tendon ECM composition and assembly thus gives rise to the remarkable characteristics of this unique tissue type. Here, we provide an overview of the functions of the ECM in tendon formation and maturation that attempts to integrate findings from developmental genetics with those of matrix biology. PMID:26672092

  7. Matrix metalloproteinases: a review of their structure and role in systemic sclerosis.

    Science.gov (United States)

    Peng, Wen-jia; Yan, Jun-wei; Wan, Ya-nan; Wang, Bing-xiang; Tao, Jin-hui; Yang, Guo-jun; Pan, Hai-feng; Wang, Jing

    2012-12-01

    Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

  8. Establishing epithelial glandular polarity: interlinked roles for ARF6, Rac1, and the matrix microenvironment.

    Science.gov (United States)

    Monteleon, Christine L; Sedgwick, Alanna; Hartsell, Alyssa; Dai, Michael; Whittington, Catherine; Voytik-Harbin, Sherry; D'Souza-Schorey, Crislyn

    2012-12-01

    Epithelial cysts comprise the structural units of the glandular epithelium. Although glandular inversion in epithelial tumors is thought to be a potential mechanism for the establishment of metastatic disease, little is known about the morphogenic cues and signaling pathways that govern glandular polarity and organization. Using organotypic cultures of Madin-Darby canine kidney cells in reconstituted basement membrane, we show that cellular depletion of the small GTP-binding protein ARF6 promotes the formation of inverted cysts, wherein the apical cell membrane faces the cyst exterior, and the basal domain faces the central lumen, while individual cell polarity is maintained. These cysts are also defective in interactions with laminin at the cyst-matrix interface. This inversion of glandular orientation is accompanied by Rac1 inactivation during early cystogenesis, and temporal activation of Rac1 is sufficient to recover the normal cyst phenotype. In an unnatural collagen I microenvironment, ARF6-depleted, inverted epithelial cysts exhibit some loss of cell polarity, a marked increase in Rho activation and Rac1 inactivation, and striking rearrangement of the surrounding collagen I matrix. These studies demonstrate the importance of ARF6 as a critical determinant of glandular orientation and the matrix environment in dictating structural organization of epithelial cysts.

  9. The role of aragonite matrix surface chemistry on the chondrogenic differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Gross-Aviv, Talia; Vago, Razi

    2009-02-01

    In the present research we study the effects of surface chemistry of an aragonite crystalline biomatrix on the chondrogenesis of mesenchymal stem cells (MSCs). An aragonite matrix obtained from the coral Porites lutea and a gold-coated P. lutea matrix were seeded with MSCs, with and without the addition of growth factors (GFs). Scanning electron microscopy, histochemical staining, immunofluorescence, biochemical analyses and quantitative polymerase chain reaction showed that the chemistry of the matrix influenced the differentiation process of the MSCs. The calcium carbonate composition of the coral promoted osteogenesis, while impeding cell-material contact (by gold coating) altered the differentiation lineage of MSCs towards chondrogenic fate. Supplementation of the culture medium with GFs intensified the influence of the surface composition on the differentiation of MSCs, and the synergistic effect of the biomatrix surface composition and the GFs induced chondrogenesis and facilitated maintenance of the chondrocyte phenotype. Therefore, we suggest that scaffolding material candidates for tissue engineering should be examined for their effects on the MSCs differentiation process and their effect on signal transduction events in the cells.

  10. Artificial biofilms establish the role of matrix interactions in staphylococcal biofilm assembly and disassembly.

    Science.gov (United States)

    Stewart, Elizabeth J; Ganesan, Mahesh; Younger, John G; Solomon, Michael J

    2015-08-14

    We demonstrate that the microstructural and mechanical properties of bacterial biofilms can be created through colloidal self-assembly of cells and polymers, and thereby link the complex material properties of biofilms to well understood colloidal and polymeric behaviors. This finding is applied to soften and disassemble staphylococcal biofilms through pH changes. Bacterial biofilms are viscoelastic, structured communities of cells encapsulated in an extracellular polymeric substance (EPS) comprised of polysaccharides, proteins, and DNA. Although the identity and abundance of EPS macromolecules are known, how these matrix materials interact with themselves and bacterial cells to generate biofilm morphology and mechanics is not understood. Here, we find that the colloidal self-assembly of Staphylococcus epidermidis RP62A cells and polysaccharides into viscoelastic biofilms is driven by thermodynamic phase instability of EPS. pH conditions that induce phase instability of chitosan produce artificial S. epidermidis biofilms whose mechanics match natural S. epidermidis biofilms. Furthermore, pH-induced solubilization of the matrix triggers disassembly in both artificial and natural S. epidermidis biofilms. This pH-induced disassembly occurs in biofilms formed by five additional staphylococcal strains, including three clinical isolates. Our findings suggest that colloidal self-assembly of cells and matrix polymers produces biofilm viscoelasticity and that biofilm control strategies can exploit this mechanism.

  11. [Role of cytokine-matrix metalloproteinase axis on promoting vascular neointima hyperplasia in mice].

    Science.gov (United States)

    Liu, Y; Ning, W H; Shen, X H; Guo, D L; Guo, L

    2016-11-24

    Objective: To observe the effects of tumor necrosis factor-α (TNF-α) and platelet derived growth factor (PDGF) on vascular neointimal hyperplasia on matrix metalloproteinase 9/2 gene knockout (MMP9/2(-/-)) mice and explore related mechanisms. Methods: Mice of control group, MMP9(-/-) group, MMP2(-/-) group and MMP9/2(-/-) group were studied. Femoral artery was injured by transluminal wire, the mRNA expression levels of TNF-α and PDGF on femoral artery were detected by RT-PCR; the protein expression of MMP9 and MMP2 were assessed by Western blot on day 0, 1, 3, 7, 14 and 28 post injury. Mice in control group received TNF-α(5 ng/ml, 0.10 ml), TNF-α(0.05 ml)+ MMP inhibitor SB-3CT(0.50 ng/ml, 0.05 ml) injection, or PDGF-bb (10 ng/ml, 0.10 ml)and PDGF-bb(0.05 ml)+ SB-3CT(0.05 ml)injection around injured artery, intimal hyperplasia at 2 and 4 weeks after injury was observed. Intimal hyperplasia at 2 and 4 weeks after injury was also observed in MMP9/2(-/-) mice. TNF-α(5 ng/ml, 0.10 ml)was injected to MMP2(-/-) mice, PDGF-bb (0.1 ml) was injected to MMP9(-/-) mice around injured artery, intimal hyperplasia at 2 and 4 weeks after injury was observed. The degree of neointimal hyperplasia were observed by the Elastica-van Gieson staining and the area of neointima and media of the arteries were measured by SigmaPlot and intima ratio was calculated. Vascular smooth muscle cell (VSMC) mediums of MMP9(-/-) and MMP2(-/-) mice were stimulated by TNF-α and PDGF-bb, respectively, and migration assay, and proliferation assay were performed, relative migration and proliferation cells numbers were counted. Results: (1) mRNA expression of TNF-α (235.33±23.68) and PDGF-bb (3.30±0.56) in femoral arteries peaked at 1 day after injury, while MMP9 or MMP2 protein expression peaked at 7 or 28 days after injury. (2)In control mice, TNF-α intervention significantly enhanced intimal hyperplasia at 2 weeks after injury (2.21±0.05 vs. 1.55±0.03 in blank control group, Phyperplasia at

  12. Genomic analysis of a spontaneous model of breast cancer metastasis to bone reveals a role for the extracellular matrix.

    Science.gov (United States)

    Eckhardt, Bedrich L; Parker, Belinda S; van Laar, Ryan K; Restall, Christina M; Natoli, Anthony L; Tavaria, Michael D; Stanley, Kym L; Sloan, Erica K; Moseley, Jane M; Anderson, Robin L

    2005-01-01

    A clinically relevant model of spontaneous breast cancer metastasis to multiple sites, including bone, was characterized and used to identify genes involved in metastatic progression. The metastatic potential of several genetically related tumor lines was assayed using a novel real-time quantitative RT-PCR assay of tumor burden. Based on this assay, the tumor lines were categorized as nonmetastatic (67NR), weakly metastatic to lymph node (168FARN) or lung (66cl4), or highly metastatic to lymph node, lung, and bone (4T1.2 and 4T1.13). In vitro assays that mimic stages of metastasis showed that highly metastatic tumors lines were more adhesive, invasive, and migratory than the less metastatic lines. To identify metastasis-related genes in this model, each metastatic tumor was array profiled against the nonmetastatic 67NR using 15,000 mouse cDNA arrays. A significant proportion of genes relating to the extracellular matrix had elevated expression in highly metastatic tumors. The role of one of these genes, POEM, was further investigated in the model. In situ hybridization showed that POEM expression was specific to the tumor epithelium of highly metastatic tumors. Decreased POEM expression in 4T1.2 tumors significantly inhibited spontaneous metastasis to the lung, bone, and kidney. Taken together, our data support a role for the extracellular matrix in metastatic progression and describe, for the first time, a role for POEM in this process.

  13. Dual Roles of the Lysine-Rich Matrix Protein (KRMP-3 in Shell Formation of Pearl Oyster, Pinctada fucata.

    Directory of Open Access Journals (Sweden)

    Jian Liang

    Full Text Available Matrix proteins play important roles in shell formation. Our group firstly isolated three cDNAs encoding lysine-rich matrix protein from Pinctada fucata in 2006. However, the functions of KRMPs are not fully understood. In addition, KRMPs contain two functional domains, the basic domain and the Gly/Tyr domain respectively. Based on the modular organization, the roles of their two domains were poorly characterized. Furthermore, KRMPs were then reported in other two species, P. maxima and P. margaritifera, which indicated that KRMPs might be very important for shell formation. In this study, the characterization and function of KRMP-3 and its two functional domains were studied in vitro through purification of recombinant glutathione S-transferase tagged KRMP-3 and two KRMP-3 deletion mutants. Western blot and immunofluorescence revealed that native KRMP-3 existed in the EDTA-insoluble matrix of the prismatic layer and was located in the organic sheet and the prismatic sheath. Recombinant KRMP-3 (rKRMP-3 bound tightly to chitin and this binding capacity was duo to the Gly/Tyr-rich region. rKRMP-3 inhibited the precipitation of CaCO3, affected the crystal morphology of calcite and inhibited the growth of aragonite in vitro, which was almost entirely attributed to the lysine-rich region. The results present direct evidence of the roles of KRMP-3 in shell biomineralization. The functional rBR region was found to participate in the growth control of crystals and the rGYR region was responsible to bind to chitin.

  14. EGFR and HER2 exert distinct roles on colon cancer cell functional properties and expression of matrix macromolecules.

    Science.gov (United States)

    Ellina, Maria-Ioanna; Bouris, Panagiotis; Aletras, Alexios J; Theocharis, Achilleas D; Kletsas, Dimitris; Karamanos, Nikos K

    2014-08-01

    ErbB receptors, EGFR and HER2, have been implicated in the development and progression of colon cancer. Several intracellular pathways are mediated upon activation of EGFR and/or HER2 by EGF. However, there are limited data regarding the EGF-mediated signaling affecting functional cell properties and the expression of extracellular matrix macromolecules implicated in cancer progression. Functional assays, such as cell proliferation, transwell invasion assay and migration were performed to evaluate the impact of EGFR/HER2 in constitutive and EGF-treated Caco-2 cells. Signaling pathways were evaluated using specific intracellular inhibitors. Western blot was also utilized to examine the phosphorylation levels of ERK1/2. Real time PCR was performed to evaluate gene expression of matrix macromolecules. EGF increases cell proliferation, invasion and migration and importantly, EGF mediates overexpression of EGFR and downregulation of HER2. The EGF-EGFR axis is the main pathway affecting colon cancer's invasive potential, proliferative and migratory ability. Intracellular pathways (PI3K-Akt, MEK1/2-Erk and JAK-STAT) are all implicated in the migratory profile. Notably, MT1- and MT2-MMP as well as TIMP-2 are downregulated, whereas uPA is upregulated via an EGF-EGFR network. The EGF-EGFR axis is also implicated in the expression of syndecan-4 and TIMP-1. However, glypican-1 upregulation by EGF is mainly mediated via HER2. The obtained data highlight the crucial importance of EGF on the expression of both receptors and on the EGF-EGFR/HER2 signaling network, reveal the distinct roles of EGFR and HER2 on expression of matrix macromolecules and open a new area in designing novel agents in targeting colon cancer. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness

    Science.gov (United States)

    Marinković, Aleksandar; Mih, Justin D.; Park, Jin-Ah; Liu, Fei

    2012-01-01

    Lung fibroblast functions such as matrix remodeling and activation of latent transforming growth factor-β1 (TGF-β1) are associated with expression of the myofibroblast phenotype and are directly linked to fibroblast capacity to generate force and deform the extracellular matrix. However, the study of fibroblast force-generating capacities through methods such as traction force microscopy is hindered by low throughput and time-consuming procedures. In this study, we improved at the detail level methods for higher-throughput traction measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent beads to permit autofocusing and automated displacement mapping, and transduction of fibroblasts with a fluorescent label to streamline cell boundary identification. Together these advances substantially improve the throughput of traction microscopy and allow us to efficiently compute the forces exerted by lung fibroblasts on substrates spanning the stiffness range present in normal and fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter the forces they transmit to the extracellular matrix as its stiffness changes, with very low forces generated on matrices as compliant as normal lung tissue. Moreover, exogenous TGF-β1 selectively accentuates tractions on stiff matrices, mimicking fibrotic lung, but not on physiological stiffness matrices, despite equivalent changes in Smad2/3 activation. Taken together, these results demonstrate a pivotal role for matrix mechanical properties in regulating baseline and TGF-β1-stimulated contraction of lung fibroblasts and suggest that stiff fibrotic lung tissue may promote myofibroblast activation through contractility-driven events, whereas normal lung tissue compliance may protect against such feedback amplification of fibroblast activation. PMID:22659883

  16. Role of extracellular matrix remodelling in adipose tissue pathophysiology: relevance in the development of obesity.

    Science.gov (United States)

    Catalán, V; Gómez-Ambrosi, J; Rodríguez, A; Frühbeck, G

    2012-12-01

    Adipose tissue responds dynamically to alterations in nutrient excess through adipocyte hypertrophy and hyperplasia, followed by increased angiogenesis, immune cell infiltration, extracellular matrix (ECM) overproduction, and thus, increased production of proinflammatory adipokines during the progression of chronic inflammation. Adipose tissue remodelling is an ongoing process that is pathologically accelerated in the obese state in large part mediated by ECM proteins and proteases. The ECM is subject to major modifications by adipocytes and other cell types that are infiltrated in the adipose tissue, such as macrophages and vascular cells. In obesity, unusual expression of ECM components and fragments derived from tissue-remodelling processes can influence immune cell recruitment and activation, actively contributing to inflammation. ECM turnover requires a tightly regulated balance between the synthesis of the components and their proteolysis, mainly by fibrinolytic systems and matrix metalloproteases (MMPs). In this review, we discuss the key cellular steps that lead to adipose tissue remodelling and the main molecular mechanisms and mediators in this process. We highlight the importance of hypoxia and angiogenesis in the adipose remodelling process, as well as the cross-talk between adipocytes, macrophages and ECM components.

  17. Tribological performance of self-lubricating aluminum matrix nanocomposites: Role of graphene nanoplatelets

    Directory of Open Access Journals (Sweden)

    Meysam Tabandeh-Khorshid

    2016-03-01

    Full Text Available In the present investigation, aluminum matrix nanocomposites reinforced by graphene nanoplatelets were synthesized by powder metallurgy method. The microstructure of the Al-Graphene nanoplatelets sample was investigated by TEM. The hardness measurements of these samples were investigated using a Rockwell hardness tester. To investigate the tribological behavior of aluminum matrix composites reinforced by graphene nanoplatelets and pure aluminum, pin-on-disk experiments were conducted on the prepared samples. In the experiments, the influence of reinforcement, volume fraction, normal load, and sliding velocity on the tribological performance was investigated. Results showed that the wear rate of Al-1wt.% GNP is increased with increasing normal loads. However, the coefficient of friction (COF of the Al-1wt.% GNP decreased with increasing normal loads. Formation of graphene film on the worn surface of Al-1wt.% GNP sample and morphology of the worn surfaces of aluminum and composite samples were analyzed by Optical Microscope (OM and Scanning Electron Microscope (SEM. It was found that the graphene nanoplatelets reinforced nano-composites showed superior tribological properties and demonstrated the ability of the self-lubricating nature of the composite during tribological conditions.

  18. Role of the Co-based microwires/polymer matrix interface on giant magneto impedance response

    Energy Technology Data Exchange (ETDEWEB)

    Estévez, Diana; Li, Jiawei; Liu, Gang; Man, Qikui, E-mail: Manqk@nimte.ac.cn; Chang, Chuntao; Wang, Xinmin; Li, Run-Wei

    2015-09-15

    Highlights: • Co-based microwires-epoxy interface was modified with silane and GMI was evaluated. • XPS confirmed the adhesion of silane onto the wires by Si–O–Si and Fe–O–Si bonds. • GMI curves for treated samples exhibited two-peak behavior and higher GMI ratio. • GMI variation was explained by the change of the surface magnetic anisotropy. • GMI could potentially be used as a surface scanning technique. - Abstract: The interface of Co-based microwires-epoxy composites was modified by applying silane treatment on the surface of the wires and their magneto impedance (MI) response was evaluated. The aim of the surface treatment was to modify the residual stresses that coexist at the microwires/polymer matrix interface and hence the magnetic anisotropy. X-ray Photoelectron Spectroscopy confirmed the covalent attachment of silane molecule onto the wires surface by the presence of Si–O–Si and Fe–O–Si. The MI curve changed from single peak for untreated samples to double peak behavior for treated samples with a significant improvement of MI ratio. Additionally, the magnitude of the anisotropy field increased with the frequency, which may imply a strongly non-uniform stress distribution towards the surface. The MI variation was explained by the change of the surface magnetic anisotropy owing to the modification of the microwires/polymer matrix interface.

  19. Role of Microvascular Tone and Extracellular Matrix Contraction in the Regulation of Interstitial Fluid: Implications for Aortic Dissection.

    Science.gov (United States)

    Mallat, Ziad; Tedgui, Alain; Henrion, Daniel

    2016-09-01

    The pathophysiology of aortic dissection is poorly understood, and its risk is resistant to medical treatment. Most studies have focused on a proposed pathogenic role of transforming growth factor-β in Marfan disease and related thoracic aortic aneurysms and aortic dissections. However, clinical testing of this concept using angiotensin II type 1 receptor antagonists to block transforming growth factor-β signaling fell short of promise. Genetic mutations that predispose to thoracic aortic aneurysms and aortic dissections affect components of the extracellular matrix and proteins involved in cellular force generation. Thus, a role for dysfunctional mechanosensing in abnormal aortic wall remodeling is emerging. However, how abnormal mechanosensing leads to aortic dissection remains a mystery. Here, we review current knowledge about the regulation of interstitial fluid dynamics and myogenic tone and propose that alteration in contractile force reduces vascular tone in the microcirculation (here, aortic vasa vasorum) and leads to elevations of blood flow, transmural pressure, and fluid flux into the surrounding aortic media. Furthermore, reduced contractile force in medial smooth muscle cells coupled with alteration of structural components of the extracellular matrix limits extracellular matrix contraction, further promoting the formation of intramural edema, a critical step in the initiation of aortic dissection. The concept is supported by several pathophysiological and clinical observations. A direct implication of this concept is that drugs that lower blood pressure and limit interstitial fluid accumulation while preserving or increasing microvascular tone would limit the risk of dissection. In contrast, drugs that substantially lower microvascular tone would be ineffective or may accelerate the disease and precipitate aortic dissection.

  20. The role of graphite morphology and matrix structure on low frequency thermal cycling of cast irons

    Indian Academy of Sciences (India)

    S Y Buni; N Raman; S Seshan

    2004-02-01

    Low frequency thermal cycling tests were carried out on four types of cast iron (viz., austempered ductile iron, pearlitic ductile iron, compacted/vermicular graphite iron and grey cast iron) at predetermined ranges of thermal cycling temperatures. The specimens were unconstrained. Results show that austempered ductile iron has the highest thermal cycling resistance, followed by pearlitic ductile iron and compacted graphite iron, while grey cast iron exhibits the lowest resistance. Microstructural analysis of test specimens subjected to thermal cycling indicates that matrix decomposition and grain growth are responsible for the reduction in hardness while graphite oxidation, de-cohesion and grain boundary separation are responsible for the reduction in the modulus of elasticity upon thermal cycling.

  1. The role of extracellular matrix in glioma invasion: a cellular Potts model approach.

    Science.gov (United States)

    Rubenstein, Brenda M; Kaufman, Laura J

    2008-12-15

    In this work, a cellular Potts model based on the differential adhesion hypothesis is employed to analyze the relative importance of select cell-cell and cell-extracellular matrix (ECM) contacts in glioma invasion. To perform these simulations, three types of cells and two ECM components are included. The inclusion of explicit ECM with an inhomogeneous fibrous component and a homogeneously dispersed afibrous component allows exploration of the importance of relative energies of cell-cell and cell-ECM contacts in a variety of environments relevant to in vitro and in vivo experimental investigations of glioma invasion. Simulations performed here focus chiefly on reproducing findings of in vitro experiments on glioma spheroids embedded in collagen I gels. For a given range and set ordering of energies associated with key cell-cell and cell-ECM interactions, our model qualitatively reproduces the dispersed glioma invasion patterns found for most glioma cell lines embedded as spheroids in collagen I gels of moderate concentration. In our model, we find that invasion is maximized at intermediate collagen concentrations, as occurs experimentally. This effect is seen more strongly in model gels composed of short collagen fibers than in those composed of long fibers, which retain significant connectivity even at low density. Additional simulations in aligned model matrices further elucidate how matrix structure dictates invasive patterns. Finally, simulations that allow invading cells to both dissolve and deposit ECM components demonstrate how Q-Potts models may be elaborated to allow active cell alteration of their surroundings. The model employed here provides a quantitative framework with which to bound the relative values of cell-cell and cell-ECM interactions and investigate how varying the magnitude and type of these interactions, as well as ECM structure, could potentially curtail glioma invasion.

  2. Recent Findings on the Role of Gelatinases (Matrix Metalloproteinase-2 and -9 in Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Olimpio Galasso

    2012-01-01

    Full Text Available Several studies dealing with the pathomechanisms of OA refer to MMP-1, -3, -7, -8, and -13 whereas a smaller number of investigations have pointed out the pathogenic role of gelatinases in OA. These gelatinases are best known for their involvement in pulmonary, myocardial, and neoplastic disease but they are emerging as important proteases implicated in the OA progression. This paper highlights the role of the gelatinases as emerging factors in OA pathogenesis through the regulation of subchondral bone resorption and microvascular invasion. The most significant new findings over the last year that add to our knowledge of the activity of these proteins in OA have been reported.

  3. Planarians as a model to assess in vivo the role of matrix metalloproteinase genes during homeostasis and regeneration.

    Directory of Open Access Journals (Sweden)

    Maria Emilia Isolani

    Full Text Available Matrix metalloproteinases (MMPs are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2 are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi. Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues

  4. The role of proteases in fibronectin matrix remodeling in thyroid epithelial cell monolayer cultures.

    Science.gov (United States)

    Nezi, Luigi; Greco, Dario; Nitsch, Lucio; Garbi, Corrado

    2002-01-01

    Fischer rat thyroid (FRT) cells organize a matrix of extracellular fibronectin (FN) fibrils, which undergoes extensive remodeling according to cell culture confluence. In non-confluent cells FN forms a fibrillar array associated with the ventral cell surface. However, basal FN is progressively removed in confluent cultures and substituted by non-fibrillar FN deposits at lateral cell domains in regions of cell-cell contacts. FRT cells secrete and expose on the plasma membrane the tissue-type plasminogen activator and, in serum-free cultures, plasminogen induces a rapid loss of FN fibrils. Incubation with plasmin inhibitors greatly reduces this effect. FRT cells also express annexin II, a plasminogen receptor, suggesting that plasmin activity is associated with the pericellular enviroment. This is in agreement with the observation that a great reduction in FN degradation is observed if the cells are pre-incubated with carboxypeptidase B, which prevents plasminogen binding to the cells. A gelatinolytic activity with a molecular weigth equivalent to MMP-2 has been demonstrated by zymography of culture media, and the presence of MMP-2 and MT1-MMP on the cell plasma membrane has been detected by immunofluorescence. These results indicate that in the FN remodeling process, occurring during FRT epithelium maturation, both plasmin-dependent (tPA activated) and plasmin-independent proteolytic activities are involved.

  5. The critical role of the cellular thiol homeostasis in cadmium perturbation of the lung extracellular matrix.

    Science.gov (United States)

    Zhao, Yinzhi; Chen, Lijun; Gao, Song; Toselli, Paul; Stone, Phillip; Li, Wande

    2010-01-12

    Cadmium (Cd) inhalation can result in emphysema. Cd exposure of rat lung fibroblasts (RFL6) enhanced levels of metal scavenging thiols, e.g., metallothionein (MT) and glutathione (GSH), and the heavy chain of gamma-glutamylcysteine synthetase (gamma-GCS), a key enzyme for GSH biosynthesis, concomitant with downregulation of lysyl oxidase (LO), a copper-dependent enzyme for crosslinking collagen and elastin in the extracellular matrix (ECM). Cd downregulation of LO in treated cells was closely accompanied by suppression of synthesis of collagen, a major structure component of the lung ECM. Using rats intratracheally instilled with cadmium chloride (30 microg, once a week) as an animal model, we further demonstrated that although 2-week Cd instillation induced a non-significant change in the lung LO activity and collagen synthesis, 4- and 6-week Cd instillation resulted in a steady decrease in the lung LO and collagen expression. The lung MT and total GSH levels were both upregulated upon the long-term Cd exposure. Emphysematous lesions were generated in lungs of 6-week Cd-dosed rats. Increases of cellular thiols by transfection of cells with MT-II expression vectors or treatment of cells with GSH monoethyl ester, a GSH delivery system, markedly inhibited LO mRNA levels and catalytic activities in the cell model. Thus, Cd upregulation of cellular thiols may be a critical cellular event facilitating downregulation of LO, a potential mechanism for Cd-induced emphysema.

  6. Role of salivary matrix metalloproteinase-8 (MMP-8) in chronic periodontitis diagnosis.

    Science.gov (United States)

    Gupta, Namita; Gupta, N D; Gupta, Akash; Khan, Saif; Bansal, Neha

    2015-03-01

    Periodontitis is an inflammatory disease of the periodontium. Any imbalance between the matrix metalloproteinases (MMPs) secreted by neutrophils and tissue inhibitors initiates the destruction of collagen in gum tissue, leading to chronic periodontitis. This study aimed to correlate salivary levels of MMP-8 and periodontal parameters of chronic periodontitis to establish MMP-8 as a noninvasive marker for the early diagnosis of chronic periodontitis. The study involved 40 subjects visiting the periodontic OPD of Dr. Ziauddin Ahmad Dental College and Hospital, located in Aligarh, U.P., India, from 2011 to 2012. The subjects were divided into two groups: group I consisted of 20 periodontally healthy subjects (controls) while group II consisted of 20 patients with chronic periodontitis. Chronic periodontitis was assessed on the basis of several periodontal parameters, including pocket probing depth (PPD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI). Around 3ml of unstimulated and whole expectorated saliva was collected for MMP-8 estimation by ELISA using Quantikine human total MMP-8 immunoassay kits. Data were analyzed using STATISTICA (Windows version 6) software. Salivary MMP-8 levels of groups I and II were 190.91 ± 143.89 ng/ml and 348.26 ± 202.1 ng/ml, respectively. The MMP-8 levels and periodontal status (PPD, CAL, GI, and PI) of groups I and II showed positive and significant correlations (for PPD, r = 0.63, P chronic periodontitis.

  7. The role of microbial-produced extracellular polymeric matrix in the formation and survival of biological soil crusts

    Science.gov (United States)

    Rossi, Federico; Adessi, Alessandra; De Philippis, Roberto

    2016-04-01

    Biological soil crusts (BSCs) are complex communities commonly constituting organo-mineral layers in arid and semiarid environment having a major influence on these ecosystems (Belnap and Lange, 2001). They have high tolerance towards a-biotic stresses and fluctuations in moisture, illumination, salinity and nutrients. The plasticity exhibited by BSCs is hugely contributed by the presence of the extracellular polymeric matrix (EPM) that is synthesized by crustal organisms, notably cyanobacteria and microalgae. This polysaccharidic net plays key roles in biofilm relations with the surrounding constrained environment. Notably, EPM concurs in coping with water scarcity, freezing and salt stress; increases biolayers stability against erosion, and is involved in nutrient provision (Rossi and De Philippis, 2015). We conducted several investigations in a research area located in the Inner Mongolian desert (Inner Mongolia, China) where BSCs were induced over different sites through inoculation-based techniques performed in different years. Our studies were aimed at determining the role of EPM in BSC development and survival in such a hyper-arid system. This presentation will report the results concerning the role of EPM in water capture from non-rainfall sources, water maintenance at the topsoil, and in water infiltrability, the latter being a factor with important ecological implications. In additions we investigated the role of the matrix as a source of carbon for the crustal heterotrophs. Furthermore, EPM was extracted with methods optimized in our lab, aiming at removing tightly bound fractions and loosely bound fractions from BSCs having different ages. The fractions were analyzed in terms of monosaccharidic composition, and molecular weight (MW) distribution. We show how the relative amounts of uronic acids increase in the EPM with the age of the crusts, implying advantages for the community-water relations. In addition, we observed significant differences in MW

  8. Durability of polymer matrix composites for infrastructure: The role of the interphase

    Science.gov (United States)

    Verghese, Kandathil Nikhil Eapen

    1999-12-01

    As fiber reinforced polymer matrix composites find greater use in markets such as civil infrastructure and ground transportation, the expectations placed on these materials are ever increasing. The overall cost and reliability have become the drivers of these high performance materials and have led to the disappearance of resins such as bismaleimides (BMI). cyanate esters and other high performance polyimides and epoxys. In their place polymers, such polyester and vinylester have arisen. The reinforcing fiber scenario has also undergone changes from the high quality and performance assured IM7 and AS4 to cheaper and hybrid systems consisting of both glass and low cost carbon. Manufacturing processes have had their share of changes too with processes such as pultrusion and other mass production techniques replacing hand lay-up and resin transfer molding. All of this has however come with little or no concession on material performance. The motivation of the present research has therefore been to try to improve the properties of these low cost composites by better understanding the constituent materials (fiber and matrix) and the region that lies in-between them namely the interphase. In order to achieve this. working with controls is necessary and the present discourse therefore deals with the AS4 fiber system from Hexcel Corporation and the vinyl ester resin, Derakane 441-400 from The Dow Chemical Company. The following eight chapters sum up the work done thus far on composites made with sized fibers and the above mentioned resin and fiber systems. They are in the form of publications that have either been accepted. submitted or going to be submitted to various peer reviewed journals. The sizings used have been poly(vinylpyrrolidone) PVP and Polyhydroxyether (Phenoxy) thermoplastic polymers and G' an industrial sizing material supplied by Hexcel. A number of issues have been addressed ranging from viscoelastic relaxation to enviro-mechanical durability. Chapter 1

  9. The extracellular matrix of porcine mature oocytes: Origin, composition and presumptive roles

    Directory of Open Access Journals (Sweden)

    Pivko Juraj

    2003-12-01

    Full Text Available Abstract The extracellular matrix (ECM of porcine mature oocytes was revealed by transmission electron microscopy (TEM after treatment with tannic acid and ruthenium red. Present in the perivitelline space (PVS and on the surface of the zona pellucida (ZP, it appeared to be composed of thin filaments and granules at the interconnections of the filaments, which were interpreted respectively as hyaluronic acid chains and bound proteoglycans. In order to determine whether this material is produced by the corona cells (the same ECM was found also on the surface of the zona pellucida and between cumulus cells or by the oocyte itself, the synthesis of glycoproteins and glycosaminoglycans was checked by autoradiography on semi-thin and thin sections observed by light and electron microscopy. Immature oocytes within or without cumulus cells, were incubated with L [3H-] fucose or L [3H-] glucosamine – precursors respectively of glycoproteins and hyaluronic acid or hyaluronan (HA bound to proteoglycans – for various times (with or without chase and at different stages during in vitro maturation. In the first case, incorporation was found in both cumulus cells and ooplasm (notably in the Golgi area for 3H-fucose and labeled material accumulated in the ECM of the PVS and of the ZP surface. Labeling in the PVS with both precursors was maximum between metaphase I (MI and metaphase II (MII and was partially extracted by hyaluronidase but not by neuraminidase. Tunicamycin, an inhibitor of glycoprotein synthesis, significantly decreased the amount of 3H-fucose labeled molecules in the PVS and increased the incidence of polyspermic penetration during subsequent in vivo fertilization. Since cumulus-free oocytes also secreted 3H-glucosamine containing compounds, both oocyte and cumulus cells probably contribute to the production of the ECM found in the PVS of mature oocytes. ECM and particularly its HA moiety present on both sides of the ZP may constitute a

  10. 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.

  11. Role of the extracellular matrix in variations of invasive pathways in lung cancers

    Energy Technology Data Exchange (ETDEWEB)

    Sá, V.K. de [Universidade de São Paulo, Departamento de Patologia, Faculdade de Medicina, São Paulo, SP (Brazil); Carvalho, L.; Gomes, A.; Alarcão, A.; Silva, M.R.; Couceiro, P.; Sousa, V. [Universidade de Coimbra, Coimbra (Portugal); Soares, F.A. [Hospital A.C. Camargo, São Paulo, SP (Brazil); Capelozzi, V.L. [Universidade de São Paulo, Departamento de Patologia, Faculdade de Medicina, São Paulo, SP (Brazil)

    2013-01-11

    Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas (SqCC), is the massive degradation of the extracellular matrix. The remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan synthases (HAS), E-cadherin adhesion molecules, and the transforming growth factor β (TGF-β) may favor invasion, cellular motility, and proliferation. We examined HAase proteins (Hyal), HAS, E-cadherin, and TGF-β profiles in lung AD subtypes and SqCC obtained from smokers and non-smokers. Fifty-six patients, median age 64 years, who underwent lobectomy for AD (N = 31) and SqCC (N = 25) were included in the study. HAS-1, -2 and -3, and Hyal-1 and -3 were significantly more expressed by tumor cells than normal and stroma cells (P < 0.01). When stratified according to histologic types, HAS-3 and Hyal-1 immunoreactivity was significantly increased in tumor cells of AD (P = 0.01) and stroma of SqCC (P = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS-3 immunoreactivity in tumor cells (P < 0.01). Stroma cells of SqCC from non-smokers presented a significant association with HAS-3 (P < 0.01). Hyal, HAS, E-cadherin, and TGF-β modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. HAases in resected AD and SqCC were strongly related to the prognosis. Therefore, our findings suggest that strategies aimed at preventing high HAS-3 and Hyal-1 synthesis, or local responses to low TGF-β and E-cadherin, may have a greater impact in lung cancer prognosis.

  12. Role of extracellular matrix protein CabA in resistance of Vibrio vulnificus biofilms to decontamination strategies.

    Science.gov (United States)

    Park, Jin Hwan; Lee, Byungho; Jo, Youmi; Choi, Sang Ho

    2016-11-07

    Biofilms are recalcitrant and raise safety problems in the food industry. In this study, the role of CabA, an extracellular matrix protein, in the resistance of the biofilms of Vibrio vulnificus, a foodborne pathogen, to decontamination strategies was investigated. Biofilms of the cabA mutant revealed reduced resistance to detachment by vibration and disinfection by sodium hypochlorite compared to the biofilms of the parental wild type in vitro. The reduced resistance of the cabA mutant biofilms was complemented by introducing a recombinant cabA, indicating that the reduced resistance of the cabA mutant biofilms is caused by the inactivation of cabA. The expression of cabA was induced in cells bound to oyster, the primary vehicle of the pathogen. The cabA mutant biofilms on oyster are defective in biomass and resistance to detachment and disinfection. The bacterial cells in the wild-type biofilms are clustered by filaments which are not apparent in the cabA mutant biofilms. The combined results indicated that CabA contributes to the structural integrity of V. vulnificus biofilms possibly by forming filaments in the matrix and thus rendering the biofilms robust, suggesting that CabA could be a target to control V. vulnificus biofilms on oyster. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Combined role of type IX collagen and cartilage oligomeric matrix protein in cartilage matrix assembly: Cartilage oligomeric matrix protein counteracts type IX collagen-induced limitation of cartilage collagen fibril growth in mouse chondrocyte cultures

    NARCIS (Netherlands)

    Blumbach, K.; Bastiaansen-Jenniskens, Y.M.; Groot, J. de; Paulsson, M.; Osch, G.J.V.M. van; Zaucke, F.

    2009-01-01

    Objective. Defects in the assembly and composition of cartilage extracellular matrix are likely to result in impaired matrix integrity and increased susceptibility to cartilage degeneration. The aim of this study was to determine the functional interaction of the collagen fibril-associated proteins

  14. Combined role of type IX collagen and cartilage oligomeric matrix protein in cartilage matrix assembly: Cartilage oligomeric matrix protein counteracts type IX collagen-induced limitation of cartilage collagen fibril growth in mouse chondrocyte cultures

    NARCIS (Netherlands)

    Blumbach, K.; Bastiaansen-Jenniskens, Y.M.; Groot, J. de; Paulsson, M.; Osch, G.J.V.M. van; Zaucke, F.

    2009-01-01

    Objective. Defects in the assembly and composition of cartilage extracellular matrix are likely to result in impaired matrix integrity and increased susceptibility to cartilage degeneration. The aim of this study was to determine the functional interaction of the collagen fibril-associated proteins

  15. Role of the extracellular matrix-located Mac-2 binding protein as an interactor of the Wnt proteins.

    Science.gov (United States)

    Pikkarainen, Timo; Nurmi, Tuomas; Sasaki, Takako; Bergmann, Ulrich; Vainio, Seppo

    2017-09-30

    The Wnt proteins constitute a conserved family of secreted palmitoleate-containing signaling proteins that play important roles in development and tissue homeostasis. Their hydrophobic nature has raised the question of how the proteins are transported outside the cells. Accumulating evidence suggests that several different mechanisms, including transport by lipoprotein particles and exosomes, may contribute to this process. Here, we expressed epitope-tagged Wnt4 in HEK293 cells, and identified Mac-2 binding protein (Mac-2BP) as its binding partner in the serum-free conditioned medium. Serine-to-alanine substitution at the conserved fatty acid-conjugation site did not affect Mac-2BP binding. Subsequent studies showed that Mac-2BP may be a general Wnt interactor. It is found in the extracellular matrix (ECM) of various tissues, where it forms unusual oligomeric ring-like structures. Its functions appear to include interactions with cells and certain ECM components. Intriguingly, both Wnt signaling and Mac-2BP expression are upregulated in many types of cancer. Our studies on the four-domain Mac-2BP indicate a crucial role in Wnt binding for the C-terminal domain that bears no sequence similarity to any other protein. Mac-2BP may have a role in regulating the extracellular spreading and storage of the Wnts, thereby modulating their bioavailability and stability. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Association study for the role of Matrix metalloproteinases 2 and 3 gene polymorphisms in dental caries susceptibility.

    Science.gov (United States)

    Karayasheva, Dobrina; Glushkova, Maria; Boteva, Ekaterina; Mitev, Vanyo; Kadiyska, Tanya

    2016-08-01

    Various exogenous and endogenous risk factors have been described as contributing to dental caries susceptibility. In the last decade it has been established that both pro and active forms of host derived Matrix metalloproteinases (MMPs) are present in the oral cavity. MMPs role in caries development has been hypothesized. The aim of this study was to analyse MMP2 (rs2287074) and MMP3 (rs679620) single nucleotide polymorphisms (SNPs) and their role in caries susceptibility. The two SNPs were analysed by PCR- restriction fragment length polymorphism (RFLP) in a sample of 102 ethnic Bulgarian volunteers (42 males and 60 females), all students in Sofia Medical University. Statistical analysis of the MMP2 SNP showed significant differences for the genotype frequencies between the caries free (CF, DMFT=0) and low caries experience (LCE, DMFT≤5) groups. Analysis for the non-synonymous MMP3 SNP found significant differences between both CF vs caries experience groups (LCE+ high caries experience (HCE, DMFT≥5)) and LCE vs HCE groups. The presence of allele G decreased the risk of HCE about 4 times. MMP2 and MMP3 genes are likely to be involved in caries susceptibility in our population. However, as dental caries is a multifactorial disorder and several genes are likely to have influence on it, it is reasonable to expect that SNPs, even those proven to be functional like rs679620, potentially play a significant, but not major role in the disease outcome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The pel polysaccharide can serve a structural and protective role in the biofilm matrix of Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Kelly M Colvin

    2011-01-01

    Full Text Available Bacterial extracellular polysaccharides are a key constituent of the extracellular matrix material of biofilms. Pseudomonas aeruginosa is a model organism for biofilm studies and produces three extracellular polysaccharides that have been implicated in biofilm development, alginate, Psl and Pel. Significant work has been conducted on the roles of alginate and Psl in biofilm development, however we know little regarding Pel. In this study, we demonstrate that Pel can serve two functions in biofilms. Using a novel assay involving optical tweezers, we demonstrate that Pel is crucial for maintaining cell-to-cell interactions in a PA14 biofilm, serving as a primary structural scaffold for the community. Deletion of pelB resulted in a severe biofilm deficiency. Interestingly, this effect is strain-specific. Loss of Pel production in the laboratory strain PAO1 resulted in no difference in attachment or biofilm development; instead Psl proved to be the primary structural polysaccharide for biofilm maturity. Furthermore, we demonstrate that Pel plays a second role by enhancing resistance to aminoglycoside antibiotics. This protection occurs only in biofilm populations. We show that expression of the pel gene cluster and PelF protein levels are enhanced during biofilm growth compared to liquid cultures. Thus, we propose that Pel is capable of playing both a structural and a protective role in P. aeruginosa biofilms.

  18. Symposium: Role of the extracellular matrix in mammary development. Regulation of milk protein and basement membrane gene expression: The influence of the extracellular matrix

    Energy Technology Data Exchange (ETDEWEB)

    Aggeler, J.; Park, C.S.; Bissell, M.J.

    1988-10-01

    Synthesis and secretion of milk proteins ({alpha}-casein, {beta}-casein, {gamma}-casein, and transferrin) by cultured primary mouse mammary epithelial cells is modulated by the extracellular matrix. In cells grown on released or floating type I collagen gels, mRNA for {beta}-casein and transferrin is increased as much as 30-fold over cells grown on plastic. Induction of {beta}-casein expression depends strongly on the presence of lactogenic hormones, especially prolactin, in the culture. When cells are plated onto partially purified reconstituted basement membrane, dramatic changes in morphology and milk protein gene expression are observed. Cells cultured on the matrix for 6 to 8 d in the presence of prolactin, insulin, and hydrocortisone form hollow spheres and duct-like structures that are completely surrounded by matrix. The cells lining these spheres appear actively secretory and are oriented with their apices facing the lumen. Hybridization experiments indicate that mRNA for {beta}-casein can be increased as much as 70-fold in these cultures. Because > 90% of the cultured cells synthesize immunoreactive {beta}-casein, as compared with only 40% of cells in the late pregnant gland, the matrix appears to be able to induce protein expression in previously silent cells. Synthesis of laminin and assembly of a mammary-specific basal lamina by cells cultured on different extracellular matrices also appears to depend on the presence of lactogenic hormones. These studies provide support for the concept of dynamic reciprocity in which complex interactions between extracellular matrix and the cellular cytoskeleton contribute to the induction and maintenance of tissue-specific gene expression in the mammary gland.

  19. Melting behaviour of lead and bismuth nano-particles in quasicrystalline matrix - The role of interfaces

    Indian Academy of Sciences (India)

    Alok Singh; A P Tsai

    2003-02-01

    Nanomaterials are playing an increasingly important role in modern technologies. Interfaces are crucial in nanotechnology. In this study, we have examined the stability of nanoparticles. Major emphasis is on understanding the effect of interfaces on melting. Melting behaviour of nanocrystalline interfaces, created by embedding lead and bismuth nanoparticles in quasicrystalline matrices, was studied. Sharply faceted and coherent interfaces can be related to sharper melting transitions, while irregularly shaped and incoherent interfaces can be directly correlated with lowering of melting temperatures. It is shown here that solid lead forms a high energy interface with phason strain-free quasicrystal (resulting in a lowering of the melting temperature) while bismuth forms a low energy interface with the quasicrystal (resulting in superheating, unusual for bismuth).

  20. [Role of matrix metalloproteinases and tissue inhibitors of metalloproteinases in hypertension. Pathogenesis of hypertension and obesity].

    Science.gov (United States)

    Trojanek, Joanna B

    2015-01-01

    Hypertension (HT), obesity and related metabolic disorders are increasing cause diseases with risk of premature death in western societies. Both hypertension and obesity are characterized by similar disorders such as chronic low systemic inflammation, changes in the vessel wall, abdominal obesity, insulin-resistance or dyslipidemia. Chronic, untreated HT leads to adverse changes in internal organs like kidney damage, arterial remodeling and hypertrophy of the left ventricle. The important role metalloproteinases and their inhibitors (TIMPs) in the pathophysiology of hypertension is associated with the degradation of vascular wall components, especially collagen and elastin. The activated RAAS system (renin-angiotensin-aldosterone) is displaying direct impact in the pathogenesis and progress of hypertension. Angiotensin II affects the expression and activation of many growth factors, cytokines and MMPs. The fat tissue of obese people is in the state of low intensity chronic inflammation and undergoes continual process of remodeling. Obesity is one of the direct cause of hypertension.

  1. Bifunctional role of the Treponema pallidum extracellular matrix binding adhesin Tp0751.

    Science.gov (United States)

    Houston, Simon; Hof, Rebecca; Francescutti, Teresa; Hawkes, Aaron; Boulanger, Martin J; Cameron, Caroline E

    2011-03-01

    Treponema pallidum, the causative agent of syphilis, is a highly invasive pathogenic spirochete capable of attaching to host cells, invading the tissue barrier, and undergoing rapid widespread dissemination via the circulatory system. The T. pallidum adhesin Tp0751 was previously shown to bind laminin, the most abundant component of the basement membrane, suggesting a role for this adhesin in host tissue colonization and bacterial dissemination. We hypothesized that similar to that of other invasive pathogens, the interaction of T. pallidum with host coagulation proteins, such as fibrinogen, may also be crucial for dissemination via the circulatory system. To test this prediction, we used enzyme-linked immunosorbent assay (ELISA) methodology to demonstrate specific binding of soluble recombinant Tp0751 to human fibrinogen. Click-chemistry-based palmitoylation profiling of heterologously expressed Tp0751 confirmed the presence of a lipid attachment site within this adhesin. Analysis of the Tp0751 primary sequence revealed the presence of a C-terminal putative HEXXH metalloprotease motif, and in vitro degradation assays confirmed that recombinant Tp0751 purified from both insect and Escherichia coli expression systems degrades human fibrinogen and laminin. The proteolytic activity of Tp0751 was abolished by the presence of the metalloprotease inhibitor 1,10-phenanthroline. Further, inductively coupled plasma-mass spectrometry showed that Tp0751 binds zinc and calcium. Collectively, these results indicate that Tp0751 is a zinc-dependent, membrane-associated protease that exhibits metalloprotease-like characteristics. However, site-directed mutagenesis of the HEXXH motif to HQXXH did not abolish the proteolytic activity of Tp0751, indicating that further mutagenesis studies are required to elucidate the critical active site residues associated with this protein. This study represents the first published description of a T. pallidum protease capable of degrading host

  2. Passive mechanical properties of rat abdominal wall muscles suggest an important role of the extracellular connective tissue matrix.

    Science.gov (United States)

    Brown, Stephen H M; Carr, John Austin; Ward, Samuel R; Lieber, Richard L

    2012-08-01

    Abdominal wall muscles have a unique morphology suggesting a complex role in generating and transferring force to the spinal column. Studying passive mechanical properties of these muscles may provide insights into their ability to transfer force among structures. Biopsies from rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA) were harvested from male Sprague-Dawley rats, and single muscle fibers and fiber bundles (4-8 fibers ensheathed in their connective tissue matrix) were isolated and mechanically stretched in a passive state. Slack sarcomere lengths were measured and elastic moduli were calculated from stress-strain data. Titin molecular mass was also measured from single muscle fibers. No significant differences were found among the four abdominal wall muscles in terms of slack sarcomere length or elastic modulus. Interestingly, across all four muscles, slack sarcomere lengths were quite long in individual muscle fibers (>2.4 µm), and demonstrated a significantly longer slack length in comparison to fiber bundles (p muscle lengths. Titin molecular mass was significantly less in TrA compared to each of the other three muscles (p < 0.0009), but this difference did not correspond to hypothesized differences in stiffness.

  3. Extracellular matrix composition significantly influences pancreatic stellate cell gene expression pattern: role of transgelin in PSC function.

    Science.gov (United States)

    Apte, Minoti V; Yang, Lu; Phillips, Phoebe A; Xu, Zhihong; Kaplan, Warren; Cowley, Mark; Pirola, Romano C; Wilson, Jeremy S

    2013-09-15

    Activated pancreatic stellate cells (PSCs) are responsible for the fibrotic matrix of chronic pancreatitis and pancreatic cancer. In vitro protocols examining PSC biology have usually involved PSCs cultured on plastic, a nonphysiological surface. However, PSCs cultured on physiological matrices, e.g., Matrigel (normal basement membrane) and collagen (fibrotic pancreas), may have distinctly different behaviors compared with cells cultured on plastic. Therefore, we aimed to 1) compare PSC gene expression after culture on plastic, Matrigel, and collagen I; 2) validate the gene array data for transgelin, the most highly dysregulated gene in PSCs grown on activating vs. nonactivating matrices, at mRNA and protein levels; 3) examine the role of transgelin in PSC function; and 4) assess transgelin expression in human chronic pancreatitis sections. Culture of PSCs on different matrices significantly affected their gene expression pattern. 146, 619, and 432 genes, respectively, were differentially expressed (P PSC proliferation and also reduced platelet-derived growth factor-induced PSC migration. Notably, transgelin was highly expressed in chronic pancreatitis in stromal areas and periacinar spaces but was absent in acinar cells. These findings suggest that transgelin is a potentially useful target protein to modulate PSC function so as to ameliorate pancreatic fibrosis.

  4. A role for topographic cues in the organization of collagenous matrix by corneal fibroblasts and stem cells.

    Science.gov (United States)

    Karamichos, Dimitrios; Funderburgh, Martha L; Hutcheon, Audrey E K; Zieske, James D; Du, Yiqin; Wu, Jian; Funderburgh, James L

    2014-01-01

    Human corneal fibroblasts (HCF) and corneal stromal stem cells (CSSC) each secrete and organize a thick stroma-like extracellular matrix in response to different substrata, but neither cell type organizes matrix on tissue-culture polystyrene. This study compared cell differentiation and extracellular matrix secreted by these two cell types when they were cultured on identical substrata, polycarbonate Transwell filters. After 4 weeks in culture, both cell types upregulated expression of genes marking differentiated keratocytes (KERA, CHST6, AQP1, B3GNT7). Absolute expression levels of these genes and secretion of keratan sulfate proteoglycans were significantly greater in CSSC than HCF. Both cultures produced extensive extracellular matrix of aligned collagen fibrils types I and V, exhibiting cornea-like lamellar structure. Unlike HCF, CSSC produced little matrix in the presence of serum. Construct thickness and collagen organization was enhanced by TGF-ß3. Scanning electron microscopic examination of the polycarbonate membrane revealed shallow parallel grooves with spacing of 200-300 nm, similar to the topography of aligned nanofiber substratum which we previously showed to induce matrix organization by CSSC. These results demonstrate that both corneal fibroblasts and stromal stem cells respond to a specific pattern of topographical cues by secreting highly organized extracellular matrix typical of corneal stroma. The data also suggest that the potential for matrix secretion and organization may not be directly related to the expression of molecular markers used to identify differentiated keratocytes.

  5. A role for topographic cues in the organization of collagenous matrix by corneal fibroblasts and stem cells.

    Directory of Open Access Journals (Sweden)

    Dimitrios Karamichos

    Full Text Available Human corneal fibroblasts (HCF and corneal stromal stem cells (CSSC each secrete and organize a thick stroma-like extracellular matrix in response to different substrata, but neither cell type organizes matrix on tissue-culture polystyrene. This study compared cell differentiation and extracellular matrix secreted by these two cell types when they were cultured on identical substrata, polycarbonate Transwell filters. After 4 weeks in culture, both cell types upregulated expression of genes marking differentiated keratocytes (KERA, CHST6, AQP1, B3GNT7. Absolute expression levels of these genes and secretion of keratan sulfate proteoglycans were significantly greater in CSSC than HCF. Both cultures produced extensive extracellular matrix of aligned collagen fibrils types I and V, exhibiting cornea-like lamellar structure. Unlike HCF, CSSC produced little matrix in the presence of serum. Construct thickness and collagen organization was enhanced by TGF-ß3. Scanning electron microscopic examination of the polycarbonate membrane revealed shallow parallel grooves with spacing of 200-300 nm, similar to the topography of aligned nanofiber substratum which we previously showed to induce matrix organization by CSSC. These results demonstrate that both corneal fibroblasts and stromal stem cells respond to a specific pattern of topographical cues by secreting highly organized extracellular matrix typical of corneal stroma. The data also suggest that the potential for matrix secretion and organization may not be directly related to the expression of molecular markers used to identify differentiated keratocytes.

  6. Gas transport in metal organic framework–polyetherimide mixed matrix membranes: The role of the polyetherimide backbone structure

    NARCIS (Netherlands)

    Hegde, Maruti; Shahid, S.; Norder, Ben; Dingemans, Theo J.; Nijmeijer, Dorothea C.

    2015-01-01

    We report on how the morphology of the polymer matrix, i.e. amorphous vs. semi-crystalline, affects the gas transport properties in a series of mixed matrix membranes (MMMs) using Cu3(BTC)2 as the metal organic framework (MOF) filler. The aim of our work is to demonstrate how incorporation of

  7. Gas transport in metal organic framework–polyetherimide mixed matrix membranes: The role of the polyetherimide backbone structure

    NARCIS (Netherlands)

    Hegde, Maruti; Shahid, Salman; Norder, Ben; Dingemans, Theo J.; Nijmeijer, Kitty

    2015-01-01

    We report on how the morphology of the polymer matrix, i.e. amorphous vs. semi-crystalline, affects the gas transport properties in a series of mixed matrix membranes (MMMs) using Cu3(BTC)2 as the metal organic framework (MOF) filler. The aim of our work is to demonstrate how incorporation of Cu3(BT

  8. Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma.

    Directory of Open Access Journals (Sweden)

    Christine F Skibola

    Full Text Available BACKGROUND: Non-Hodgkin lymphoma (NHL is the fifth most common cancer in the U.S. and few causes have been identified. Genetic association studies may help identify environmental risk factors and enhance our understanding of disease mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: 768 coding and haplotype tagging SNPs in 146 genes were examined using Illumina GoldenGate technology in a large population-based case-control study of NHL in the San Francisco Bay Area (1,292 cases 1,375 controls are included here. Statistical analyses were restricted to HIV- participants of white non-Hispanic origin. Genes involved in steroidogenesis, immune function, cell signaling, sunlight exposure, xenobiotic metabolism/oxidative stress, energy balance, and uptake and metabolism of cholesterol, folate and vitamin C were investigated. Sixteen SNPs in eight pathways and nine haplotypes were associated with NHL after correction for multiple testing at the adjusted q<0.10 level. Eight SNPs were tested in an independent case-control study of lymphoma in Germany (494 NHL cases and 494 matched controls. Novel associations with common variants in estrogen receptor 1 (ESR1 and in the vitamin C receptor and matrix metalloproteinase gene families were observed. Four ESR1 SNPs were associated with follicular lymphoma (FL in the U.S. study, with rs3020314 remaining associated with reduced risk of FL after multiple testing adjustments [odds ratio (OR = 0.42, 95% confidence interval (CI = 0.23-0.77 and replication in the German study (OR = 0.24, 95% CI = 0.06-0.94. Several SNPs and haplotypes in the matrix metalloproteinase-3 (MMP3 and MMP9 genes and in the vitamin C receptor genes, solute carrier family 23 member 1 (SLC23A1 and SLC23A2, showed associations with NHL risk. CONCLUSIONS/SIGNIFICANCE: Our findings suggest a role for estrogen, vitamin C and matrix metalloproteinases in the pathogenesis of NHL that will require further validation.

  9. Tissue inhibitor of metalloproteinase-3 is up-regulated by transforming growth factor-beta1 in vitro and expressed in fibroblastic foci in vivo in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    García-Alvarez, Jorge; Ramirez, Remedios; Checa, Marco; Nuttall, Robert K; Sampieri, Clara L; Edwards, Dylan R; Selman, Moisés; Pardo, Annie

    2006-05-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by fibroblast expansion and extracellular matrix accumulation. However, the mechanisms involved in matrix remodeling have not been elucidated. In this study, the authors aimed to evaluate the expression of the tissue inhibitors of matrix metalloproteinases (TIMPs) in human fibroblasts and whole tissues from IPF and normal lungs. They also determined the role of mitogen-activated protein kinase (MAPK) in TIMP3 expression. TIMP1, TIMP2, and TIMP3 were highly expressed in lung fibroblasts. Transforming growth factor (TGF)-beta1, a profibrotic mediator, induced strong up-regulation of TIMP3 at the mRNA and protein levels. The authors examined whether the MAPK pathway was involved in TGF-beta1-induced TIMP3 expression. TGF-beta1 induced the phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2. Biochemical blockade of p38 by SB203580, but not of the ERK MAPK pathway, inhibited the effect of this factor. The effect was also blocked by the tyrosine kinase inhibitor genistein and by antagonizing TGF-beta1 receptor type I (activin-linked kinase [ALK5]). In IPF tissues TIMP3 gene expression was significantly increased and the protein was localized to fibroblastic foci and extracellular matrix. Our findings suggest that TGF-beta1-induced TIMP3 may be an important mediator in lung fibrogenesis.

  10. Matrix metalloproteinase production in regenerating axolotl spinal cord.

    Science.gov (United States)

    Chernoff, E A; O'Hara, C M; Bauerle, D; Bowling, M

    2000-01-01

    In urodele amphibian spinal cord regeneration, the ependymal cells lining the central canal remodel the lesion site to favor axonal regrowth. We profiled the production of matrix metalloproteinases by injury-reactive mesenchymal ependymal cells in vivo and in vitro and found that matrix metalloproteinases are involved in this remodeling process in the axolotl (Ambystoma mexicanum). The production of cell-associated matrix metalloproteinases in vivo was shown to be identical to that in our cultured ependymal cell model system. Activated and zymogen forms of matrix metalloproteinases were identified using zymography, chemical inhibitors of matrix metalloproteinases, and cleavage of propeptides by organomercurials. The principal cellular proteinases consisted of matrix metalloproteinase-2 (gelatinase A) and matrix metalloproteinase-1 (type I collagenase), which display characteristic shifts in molecular weight following proenzyme processing by organomercurials. In addition, ependymal cell conditioned medium contained secreted forms of the enzyme undetectable in situ. Matrix metalloproteinase-9 (gelatinase B) as well as matrix metalloproteinase-2 and matrix metalloproteinase-1 were secreted and casein substrate zymography showed the presence of a small amount of a very high molecular weight matrix metalloproteinase-3 (prostromelysin) secreted into the culture medium. Matrix metalloproteinases were still present at 4 weeks post-lesioning when the ependymal cells have just re-epithelialized, but decreased near the completion of regeneration (8 weeks post-lesioning). Zymography showed no detectable matrix metalloproteinases in unlesioned cord but the presence of tissue inhibitor of metalloproteinase-1 in intact cord was seen by Western blotting. This study shows that matrix metalloproteinases are associated with urodele spinal cord regeneration and validates the use of our ependymal cell tissue culture model system to evaluate ependymal cell behavior during spinal cord

  11. The clinical role of increase of serum matrix metalloproteinase-8 concentration in patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    Qiang Hua; Zhou Zhaoxia; Sun Chaofeng; Ma Aiqun; Cheng Hua; Zhou Ping

    2008-01-01

    Objective To study the clinical role of the variation of serum matrix metalloproteinase-8 (MMP-8)concentration in patients with acute coronary syndrome (ACS). Methods ELISA method was adopted to detect serum MMP-8 concentration and to observe concentration's differences and features among 80 selected ACS cases (43 acute myocardial infarction and 37 unstable angina pectoris), 43 stable angina pectoris (SAP) cases and 37 control cases.And meanwhile the atherosclerosis risk factors of each case, such as age, sex, hypertension, body mass index, smoking,family history, diabetes, and hyperlipidemia were collected and analyzed as a whole. Results First, serum MMP-8 concentration reached the highest point in ACS, and there was significant difference between SAP and control groups (P0.05). Third, Logistic regression analysis revealed that serum MMP-8 concentration might be the indicator of ACS (B=4.493, P=0.000), particularly, that of AMI (B=9.961,P=0.000). Fourth, linear correlation and linear regression analysis found that only neutrophil was likely to influence serum MMP-8 concentration (r=0.274, P=0.001). Fifth, in the diagnosis of ACS, the area under ROC curve of MMP-8 was 0.785, the sensitivity and specificity were 68.6% and 76.5%, respectively. Conclusion ① Serum MMP-8 concentration has close relationship with the occurrence of ACS, particularly with AMI;② Serum MMP-8 concentration may be one of the predicting indicators of ACS and particularly of AMI;③ Neutrophil may be correlated with serum MMP-8 concentration;④ MMP-8 is of somewhat valuable in diagnosing ACS.

  12. Quantitative analysis of Nipah virus proteins released as virus-like particles reveals central role for the matrix protein

    Directory of Open Access Journals (Sweden)

    Eaton Bryan T

    2007-01-01

    Full Text Available Abstract Background Nipah virus (NiV is an emerging paramyxovirus distinguished by its ability to cause fatal disease in both animal and human hosts. Together with Hendra virus (HeV, they comprise the genus Henipavirus in the Paramyxoviridae family. NiV and HeV are also restricted to Biosafety Level-4 containment and this has hampered progress towards examining details of their replication and morphogenesis. Here, we have established recombinant expression systems to study NiV particle assembly and budding through the formation of virus-like particles (VLPs. Results When expressed by recombinant Modified Vaccinia virus Ankara (rMVA or plasmid transfection, individual NiV matrix (M, fusion (F and attachment (G proteins were all released into culture supernatants in a membrane-associated state as determined by sucrose density gradient flotation and immunoprecipitation. However, co-expression of F and G along with M revealed a shift in their distribution across the gradient, indicating association with M in VLPs. Protein release was also altered depending on the context of viral proteins being expressed, with F, G and nucleocapsid (N protein reducing M release, and N release dependent on the co-expression of M. Immunoelectron microscopy and density analysis revealed VLPs that were similar to authentic virus. Differences in the budding dynamics of NiV proteins were also noted between rMVA and plasmid based strategies, suggesting that over-expression by poxvirus may not be appropriate for studying the details of recombinant virus particle assembly and release. Conclusion Taken together, the results indicate that NiV M, F, and G each possess some ability to bud from expressing cells, and that co-expression of these viral proteins results in a more organized budding process with M playing a central role. These findings will aid our understanding of paramyxovirus particle assembly in general and could help facilitate the development of a novel vaccine

  13. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in pigmented villonodular synovitis suggests their potential role for joint destruction.

    Science.gov (United States)

    Uchibori, Mitsutoshi; Nishida, Yoshihiro; Tabata, Izuru; Sugiura, Hideshi; Nakashima, Hiroatsu; Yamada, Yoshihisa; Ishiguro, Naoki

    2004-01-01

    Pigmented villonodular synovitis (PVNS) is an uncommon idiopathic, proliferative synovial disease. Since matrix metalloproteinases (MMP) are assumed to play an important role in the pathogenesis of PVNS, we examined the expression and activity of MMP and tissue inhibitor of metalloproteinases (TIMP) in PVNS. Synovial tissue samples were obtained from 10 patients with PVNS (knee 8, ankle 2) and 4 patients each with rheumatoid arthritis (RA) or osteoarthritis (OA) for comparison. Protein deposition and mRNA expression were determined by conventional immunohistochemical studies and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Gelatin zymography was performed for detection of gelatin-degrading activity. The quantity of MMP and TIMP was measured by ELISA. Intense immunostaining for MMP-1 was detected in both the multinucleated giant cells and mononuclear cells, whereas TIMP-1 was weakly positive. MMP-9 immunostained predominantly in the multinucleated cells, whereas other MMP and TIMP were weakly detected. RT-PCR analysis showed that mRNA expression of MMP-9 was stimulated in PVNS, whereas MMP-2 mRNA was not, compared to RA or OA. The gelatin zymogram indicated protease activities predominantly at 92 kDa and 67 kDa. In accord with the immunostaining results, the amount of MMP-1 and MMP-9 protein was significantly higher than that of TIMP-1 and MMP-2, respectively. We characterized the expression and activity of MMP in PVNS and observed that PVNS tissues predominantly produce MMP-1 and MMP-9. Given that PVNS occasionally induces joint destruction, stimulated expression of MMP-1 and MMP-9 may contribute to the invasive activity and the bone and cartilage loss in PVNS.

  14. Role of the HIV-1 Matrix Protein in Gag Intracellular Trafficking and Targeting to the Plasma Membrane for Virus Assembly

    Directory of Open Access Journals (Sweden)

    Ruba H Ghanam

    2012-02-01

    Full Text Available Human immunodeficiency virus type-1 (HIV-1 encodes a polypeptide called Gag that is able to form virus-like particles (VLPs in vitro in the absence of any cellular or viral constituents. During the late phase of the HIV-1 infection, Gag polyproteins are transported to the plasma membrane (PM for assembly. In the past two decades, in vivo, in vitro and structural studies have shown that Gag trafficking and targeting to the PM are orchestrated events that are dependent on multiple factors including cellular proteins and specific membrane lipids. The matrix (MA domain of Gag has been the focus of these studies as it appears to be engaged in multiple intracellular interactions that are suggested to be critical for virus assembly and replication. The interaction between Gag and the PM is perhaps the most understood. It is now established that the ultimate localization of Gag on punctate sites on the PM is mediated by specific interactions between the MA domain of Gag and phosphatidylinositol-4,5-bisphosphate (PI(4,5P2, a minor lipid localized on the inner leaflet of the PM. Structure-based studies revealed that binding of PI(4,5P2 to MA induces minor conformational changes, leading to exposure of the myristyl (myr group. Exposure of the myr group is also triggered by binding of calmodulin, enhanced by factors that promote protein self-association like the capsid domain of Gag, and is modulated by pH. Despite the steady progress in defining both the viral and cellular determinants of retroviral assembly and release, Gag’s intracellular interactions and trafficking to its assembly sites in the infected cell are poorly understood. In this review, we summarize the current understanding of the structural and functional role of MA in HIV replication.

  15. Spectroscopic dimensions of silver nanoparticles and clusters in ZnO matrix and their role in bioinspired antifouling and photocatalysis.

    Science.gov (United States)

    Michael, Robin Jude Vimal; Sambandam, Balaji; Muthukumar, Thangavelu; Umapathy, Manickam J; Manoharan, Periakaruppan T

    2014-05-14

    Silver doped zinc oxide nanoparticles are synthesized by a solution combustion method. The samples characterized by a variety of spectroscopic and other techniques clearly reveal the presence of silver nanoparticles as well as silver clusters. The silver in the two forms was identified by careful deconvolution of X-ray photoelectron spectral results. Their formation was also confirmed by the presence of plasmons, the concentration and energy of which increase on increasing silver input, indicating the presence of perpendicular excitons since aggregates of clusters are known to shift the plasmon resonances depending on their topologies. Further confirmation of clusters came from EPR (electron paramagnetic resonance), HRSEM (high resolution scanning electron microscopy) and HRTEM (high resolution transmission electron microscopy); direct proof for clusters came from matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectral measurements. The antimicrobial activity of the silver doped zinc oxide polymer nanocomposites as biomedical devices are measured by zone of inhibition. Also, samples coated on paper disk with acacia binder are evaluated by a disk diffusion method. While pure zinc oxide does not show any antimicrobial property, the activity of silver-doped zinc oxide is comparable to that of commercial antibiotics and found to be related to nanoparticulate silver. Similarly, the microbial adherence to the surface of polymer nanocomposite which mimics a biomedical device also was influenced by nanoparticles of silver. The photocatalytic water treatment was carried out using silver carrying nanoparticles with Rhodamine-B and 4-chlorophenol as model pollutants. The increased photocatalytic activity of silver containing zinc oxide as compared to pure zinc oxide nanoparticles is attributed to the synergistic display of the properties of silver nanoparticles and clusters in zinc oxide. This activity depends upon the dispersion of silver

  16. Up-regulation of matrix metalloproteinase-8 by betel quid extract and arecoline and its role in 2D motility.

    Science.gov (United States)

    Liu, Shyun-Yeu; Liu, Young-Chau; Huang, Wen-Tsung; Huang, Guan-Cheng; Chen, Tai-Chi; Lin, Mei-Huei

    2007-11-01

    Betel quid (BQ) and matrix metalloproteinase-8 (MMP-8) play roles in oral diseases. Here, we analyzed the regulation of MMP-8 by BQ and its effect on cell migration. We found that BQ extract (BQE) increased the secretion of an 85kDa caseinolytic proteinase, specifically precipitated by an anti-MMP-8 antibody, in the culture medium of OECM-1, an oral squamous cell carcinoma (OSCC) cell line. BQE also stimulated MMP-8 secretion in an esophageal carcinoma cell line, CE81T/VGH, in a dose-dependent manner, and MMP-8 protein was maximally expressed at 24h after BQE treatment in OECM-1. The BQE-induced MMP-8 expression was dose-dependently inhibited by PD98059. Arecoline, the major alkaloid of areca nut, was tested to dose-dependently up-regulate MMP-8 protein level. Moreover, both arecoline- (4.7-fold) and BQE-selected (5.5-fold) CE81T/VGH cells expressed higher MMP-8 protein level and exhibited enhanced two-dimensional (2D) motility (p=0.009 in both cells) than parental cells. The enhanced motility of arecoline- (p=0.006) and BQE-selected (p=0.002) cells was both specifically blocked by an anti-MMP-8 antibody. We conclude that BQ may accelerate tumor migration by stimulating MMP-8 expression through MEK pathway in at least some carcinomas of the upper aerodigestive tract. Furthermore, arecoline may be one of the positive MMP-8 regulators among BQ ingredients.

  17. Role of vertex corrections in the matrix formulation of the random phase approximation for the multiorbital Hubbard model

    Science.gov (United States)

    Altmeyer, Michaela; Guterding, Daniel; Hirschfeld, P. J.; Maier, Thomas A.; Valentí, Roser; Scalapino, Douglas J.

    2016-12-01

    In the framework of a multiorbital Hubbard model description of superconductivity, a matrix formulation of the superconducting pairing interaction that has been widely used is designed to treat spin, charge, and orbital fluctuations within a random phase approximation (RPA). In terms of Feynman diagrams, this takes into account particle-hole ladder and bubble contributions as expected. It turns out, however, that this matrix formulation also generates additional terms which have the diagrammatic structure of vertex corrections. Here we examine these terms and discuss the relationship between the matrix-RPA superconducting pairing interaction and the Feynman diagrams that it sums.

  18. A new method to extract matrix proteins directly from the secretion of the mollusk mantle and the role of these proteins in shell biomineralization.

    Science.gov (United States)

    Liu, Xiaojun; Liu, Chang; Chen, Lei; Sun, Juan; Zhou, Yujuan; Li, Qi; Zheng, Guilan; Zhang, Guiyou; Wang, Hongzhong; Xie, Liping; Zhang, Rongqing

    2011-10-01

    Considering the continuous and substantive secretory ability of the mantle in vitro, we report a new technique to produce shell-matrix proteins by inducing the mantle, after removal from the organism's body, to secrete soluble-matrix proteins into phosphate buffer. By this method, a large amount of matrix proteins could be obtained in 2 h. Experiments involving in vitro calcium carbonate crystallization and organic framework calcium carbonate crystallization indicated that these proteins retain high bioactivity and play key roles in shell biomineralization. Phosphate buffer-soluble proteins secreted by the margin of the mantles (MSPs) were used to reconstruct the stages in the growth of the prismatic layer of the decalcified organic frameworks. The MSPs were observed to aggregate calcites in vitro, and this ability enabled the mollusk to form big calcites in the prismatic layer. During shell biomineralization, an important stage after the self-assembly of the biomacromolecules and the formation of crystals is the assembly of the two parts to form a firm structure. Moreover, a new type of matrix protein, functioning as the binding factor between the crystals and the organic frameworks, was shown to exist in the phosphate buffer-soluble proteins secreted by the central part of mantles (CSPs). Nanoscale-sized bowl-like aragonites, with heights of ∼800 nm, were induced by CSPs in vitro. This method is a successful example of obtaining functional proteins through secretion by animal tissues.

  19. Calcinosis in juvenile dermatomyositis : a possible role for the vitamin K-dependent protein matrix Gla protein

    NARCIS (Netherlands)

    Van Summeren, M. J. H.; Spliet, W. G. M.; Van Royen-Kerkhof, A.; Vermeer, C.; Lilien, M.; Kuis, W.; Schurgers, L. J.

    2008-01-01

    Objectives. The aims of the present study were to investigate whether the calcification inhibitor matrix Gla protein (MGP) is expressed in muscle biopsies of patients with juvenile dermatomyositis (JDM), and whether different forms of MGP are differentially expressed in JDM patients with and without

  20. Collagens and retinal Müller cells in healthy and diseased vitreoretinal interface : the regulatory role of extracellular matrix

    NARCIS (Netherlands)

    Bu, Shao

    2015-01-01

    Collagenen en Retinale Müller Cellen in de Gezonde en Pathologisch Veranderde Vitreoretinale Grenslaag --de regulatoire rol van de extracellulaire matrix De vitreoretinale grenslaag omvat het corticale glasvocht, de membrana limitans interna en de eindvoetjes van de retinale Müller cellen.

  1. The role of advection and dispersion in the rock matrix on the transport of leaking CO2-saturated brine along a fractured zone

    Science.gov (United States)

    Ahmad, Nawaz; Wörman, Anders; Sanchez-Vila, Xavier; Bottacin-Busolin, Andrea

    2016-12-01

    CO2 that is injected into a geological storage reservoir can leak in dissolved form because of brine displacement from the reservoir, which is caused by large-scale groundwater motion. Simulations of the reactive transport of leaking CO2aq along a conducting fracture in a clay-rich caprock are conducted to analyze the effect of various physical and geochemical processes. Whilst several modeling transport studies along rock fractures have considered diffusion as the only transport process in the surrounding rock matrix (diffusive transport), this study analyzes the combined role of advection and dispersion in the rock matrix in addition to diffusion (advection-dominated transport) on the migration of CO2aq along a leakage pathway and its conversion in geochemical reactions. A sensitivity analysis is performed to quantify the effect of fluid velocity and dispersivity. Variations in the porosity and permeability of the medium are found in response to calcite dissolution and precipitation along the leakage pathway. We observe that advection and dispersion in the rock matrix play a significant role in the overall transport process. For the parameters that were used in this study, advection-dominated transport increased the leakage of CO2aq from the reservoir by nearly 305%, caused faster transport and increased the mass conversion of CO2aq in geochemical reactions along the transport pathway by approximately 12.20% compared to diffusive transport.

  2. Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes: role of integrinβ1 and focal adhesion kinase signaling cues.

    Science.gov (United States)

    Prasadam, Indira; Farnaghi, Saba; Feng, Jian Q; Gu, Wenyi; Perry, Samuel; Crawford, Ross; Xiao, Yin

    2013-10-09

    Our recent study indicated that subchondral bone pathogenesis in osteoarthritis (OA) is associated with osteocyte morphology and phenotypic abnormalities. However, the mechanism underlying this abnormality needs to be identified. In this study we investigated the effect of extracellular matrix (ECM) produced from normal and OA bone on osteocytic cells function. De-cellularized matrices, resembling the bone provisional ECM secreted from primary human subchondral bone osteoblasts (SBOs) of normal and OA patients were used as a model to study the effect on osteocytic cells. Osteocytic cells (MLOY4 osteocyte cell line) cultured on normal and OA derived ECMs were analyzed by confocal microscopy, scanning electron microscopy (SEM), cell attachment assays, zymography, apoptosis assays, qRT-PCR and western blotting. The role of integrinβ1 and focal adhesion kinase (FAK) signaling pathways during these interactions were monitored using appropriate blocking antibodies. The ECM produced by OA SBOs contained less mineral content, showed altered organization of matrix proteins and matrix structure compared with the matrices produced by normal SBOs. Culture of osteocytic cells on these defective OA ECM resulted in a decrease of integrinβ1 expression and the de-activation of FAK cell signaling pathway, which subsequently affected the initial osteocytic cell's attachment and functions including morphological abnormalities of cytoskeletal structures, focal adhesions, increased apoptosis, altered osteocyte specific gene expression and increased Matrix metalloproteinases (MMP-2) and -9 expression. This study provides new insights in understanding how altered OA bone matrix can lead to the abnormal osteocyte phenotypic changes, which is typical in OA pathogenesis.

  3. Pigment epithelium derived factor suppresses expression of Sost/Sclerostin by osteocytes: implication for its role in bone matrix mineralization.

    Science.gov (United States)

    Li, Feng; Song, Na; Tombran-Tink, Joyce; Niyibizi, Christopher

    2015-06-01

    Mutations in Serpinf1 gene which encodes pigment epithelium derived factor (PEDF) lead to osteogenesis imperfecta type VI whose hallmark is defective mineralization. Mechanisms by which PEDF regulates matrix mineralization remain unknown. We examined effect of exogenous PEDF on expression of osteoblastic and osteocytic related genes and proteins in mineralizing osteoblast culture. Mineralizing human osteoblasts supplemented with exogenous PEDF for 14 days deposited 47% more mineral than cells cultured without PEDF. Analysis of selected gene expression by cells in mineralizing cultures supplemented with exogenous PEDF showed reduction in expression of Sclerostin (Sost) by 70%, matrix extracellular phosphoglycoprotein (MEPE) by 75% and dentin matrix protein (DMP-1) by 20% at day 14 of culture. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) expression was not affected. Western blotting and immunoprecipitation showed that sclerostin and MEPE synthesis by osteocytes were reduced by 50% and 60% respectively in mineralizing osteoblasts containing exogenous PEDF. Primary osteocytes exposed to PEDF also reduced synthesis of Sost/sclerostin by 50% within 24 h. For osteoblastic genes, Bone sialoprotein (BSP) was expressed at 75% higher by day 7 in cultures containing exogenous PEDF while Col1A1 expression remained high at all-time points. Total beta-catenin was increased in mineralizing osteoblastic cells suggesting increased Wnt activity. Taken together, the data indicate that PEDF suppressed expression of factors that inhibit mineralization while enhancing those that promote mineralization. The findings also suggest that PEDF may regulate Sost expression by osteocytes leading to enhanced osteoblastic differentiation and increased matrix mineralization.

  4. Matrix theory

    CERN Document Server

    Franklin, Joel N

    2003-01-01

    Mathematically rigorous introduction covers vector and matrix norms, the condition-number of a matrix, positive and irreducible matrices, much more. Only elementary algebra and calculus required. Includes problem-solving exercises. 1968 edition.

  5. Biomechanics of isolated tomato (Solanum lycopersicum L.) fruit cuticles: the role of the cutin matrix and polysaccharides.

    Science.gov (United States)

    López-Casado, Gloria; Matas, Antonio J; Domínguez, Eva; Cuartero, Jesús; Heredia, Antonio

    2007-01-01

    The mechanical characteristics of the cuticular membrane (CM), a complex composite biopolymer basically composed of a cutin matrix, waxes, and hydrolysable polysaccharides, have been described previously. The biomechanical behaviour and quantitative contribution of cutin and polysaccharides have been investigated here using as experimental material mature green and red ripe tomato fruits. Treatment of isolated CM with anhydrous hydrogen fluoride in pyridine allowed the selective elimination of polysaccharides attached to or incrusted into the cutin matrix. Cutin samples showed a drastic decrease in elastic modulus and stiffness (up to 92%) compared with CM, which clearly indicates that polysaccharides incorporated into the cutin matrix are responsible for the elastic modulus, stiffness, and the linear elastic behaviour of the whole cuticle. Reciprocally, the viscoelastic behaviour of CM (low elastic modulus and high strain values) can be assigned to the cutin. These results applied both to mature green and red ripe CM. Cutin elastic modulus, independently of the degree of temperature and hydration, was always significantly higher for the ripe than for the green samples while strain was lower; the amount of phenolics in the cutin network are the main candidates to explain the increased rigidity from mature green to red ripe cutin. The polysaccharide families isolated from CM were pectin, hemicellulose, and cellulose, the main polymers associated with the plant cell wall. The three types of polysaccharides were present in similar amounts in CM from mature green and red ripe tomatoes. Physical techniques such as X-ray diffraction and Raman spectroscopy indicated that the polysaccharide fibres were mainly randomly oriented. A tomato fruit CM scenario at the supramolecular level that could explain the observed CM biomechanical properties is presented and discussed.

  6. Ethanol impairs muscarinic receptor-induced neuritogenesis in rat hippocampal slices: Role of astrocytes and extracellular matrix proteins.

    Science.gov (United States)

    Giordano, Gennaro; Guizzetti, Marina; Dao, Khoi; Mattison, Hayley A; Costa, Lucio G

    2011-12-01

    In an in vitro co-culture system of astrocytes and neurons, stimulation of cholinergic muscarinic receptors in astrocytes had been shown to cause neuritogenesis in hippocampal neurons, and this effect was inhibited by ethanol. The present study sought to confirm these earlier findings in a more complex system, in vitro rat hippocampal slices in culture. Exposure of hippocampal slices to the cholinergic agonist carbachol (1mM for 24h) induced neurite outgrowth in hippocampal pyramidal neurons, which was mediated by activation of muscarinic M3 receptors. Specifically, carbachol induced a >4-fold increase in the length of the longest neurite, and a 4-fold increase in the length of minor neurites and in the number of branches. Co-incubation of carbachol with ethanol (50mM) resulted in significant inhibition of the effects induced by carbachol on all parameters measured. Neurite outgrowth in CNS neurons is dependent on various permissive factors that are produced and released by glial cells. In hippocampal slices carbachol increased the levels of two extracellular matrix protein, fibronectin and laminin-1, by 1.6-fold, as measured by Western blot. Co-incubation of carbachol with ethanol significantly inhibited these increases. Carbachol-induced increases in levels of extracellular matrix proteins were antagonized by a M3 muscarinic receptor antagonist. Furthermore, function-blocking fibronectin or laminin-1 antibodies antagonized the effect of carbachol on neurite outgrowth. These results indicate that in hippocampal slices stimulation of muscarinic M3 receptors induces neurite outgrowth, which is mediated by fibronectin and laminin-1, two extracellular matrix proteins released by astrocytes. By decreasing fibronectin and laminin levels ethanol prevents carbachol-induced neuritogenesis. These findings highlight the importance of glial-neuronal interactions as important targets in the developmental neurotoxicity of alcohol.

  7. Hierarchical spatial segregation of two Mediterranean vole species: the role of patch-network structure and matrix composition.

    Science.gov (United States)

    Pita, Ricardo; Lambin, Xavier; Mira, António; Beja, Pedro

    2016-09-01

    According to ecological theory, the coexistence of competitors in patchy environments may be facilitated by hierarchical spatial segregation along axes of environmental variation, but empirical evidence is limited. Cabrera and water voles show a metapopulation-like structure in Mediterranean farmland, where they are known to segregate along space, habitat, and time axes within habitat patches. Here, we assess whether segregation also occurs among and within landscapes, and how this is influenced by patch-network and matrix composition. We surveyed 75 landscapes, each covering 78 ha, where we mapped all habitat patches potentially suitable for Cabrera and water voles, and the area effectively occupied by each species (extent of occupancy). The relatively large water vole tended to be the sole occupant of landscapes with high habitat amount but relatively low patch density (i.e., with a few large patches), and with a predominantly agricultural matrix, whereas landscapes with high patch density (i.e., many small patches) and low agricultural cover, tended to be occupied exclusively by the small Cabrera vole. The two species tended to co-occur in landscapes with intermediate patch-network and matrix characteristics, though their extents of occurrence were negatively correlated after controlling for environmental effects. In combination with our previous studies on the Cabrera-water vole system, these findings illustrated empirically the occurrence of hierarchical spatial segregation, ranging from within-patches to among-landscapes. Overall, our study suggests that recognizing the hierarchical nature of spatial segregation patterns and their major environmental drivers should enhance our understanding of species coexistence in patchy environments.

  8. The relative roles of collagen adhesive receptor DDR2 activation and matrix stiffness on the downregulation of focal adhesion kinase in vascular smooth muscle cells.

    Science.gov (United States)

    Bhadriraju, Kiran; Chung, Koo-Hyun; Spurlin, Tighe A; Haynes, Ross J; Elliott, John T; Plant, Anne L

    2009-12-01

    Cells within tissues derive mechanical anchorage and specific molecular signals from the insoluble extracellular matrix (ECM) that surrounds them. Understanding the role of different cues that extracellular matrices provide cells is critical for controlling and predicting cell response to scaffolding materials. Using an engineered extracellular matrix of Type I collagen we examined how the stiffness, supramolecular structure, and glycosylation of collagen matrices influence the protein levels of cellular FAK and the activation of myosin II. Our results show that (1) cellular FAK is downregulated on collagen fibrils, but not on a non-fibrillar monolayer of collagen, (2) the downregulation of FAK is independent of the stiffness of the collagen fibrils, and (3) FAK levels are correlated with levels of tyrosine phosphorylation of the collagen adhesion receptor DDR2. Further, siRNA depletion of DDR2 blocks FAK downregulation. Our results suggest that the collagen receptor DDR2 is involved in the regulation of FAK levels in vSMC adhered to Type I collagen matrices, and that regulation of FAK levels in these cells appears to be independent of matrix stiffness.

  9. Polymorphisms of the tissue inhibitor of metalloproteinase 3 gene are associated with resistance to high-altitude pulmonary edema (HAPE in a Japanese population: a case control study using polymorphic microsatellite markers.

    Directory of Open Access Journals (Sweden)

    Nobumitsu Kobayashi

    Full Text Available INTRODUCTION: High-altitude pulmonary edema (HAPE is a hypoxia-induced, life-threatening, high permeability type of edema attributable to pulmonary capillary stress failure. Genome-wide association analysis is necessary to better understand how genetics influence the outcome of HAPE. MATERIALS AND METHODS: DNA samples were collected from 53 subjects susceptible to HAPE (HAPE-s and 67 elite Alpinists resistant to HAPE (HAPE-r. The genome scan was carried out using 400 polymorphic microsatellite markers throughout the whole genome in all subjects. In addition, six single nucleotide polymorphisms (SNPs of the gene encoding the tissue inhibitor of metalloproteinase 3 (TIMP3 were genotyped by Taqman® SNP Genotyping Assays. RESULTS: The results were analyzed using case-control comparisons. Whole genome scanning revealed that allele frequencies in nine markers were statistically different between HAPE-s and HAPE-r subjects. The SNP genotyping of the TIMP3 gene revealed that the derived allele C of rs130293 was associated with resistance to HAPE [odds ratio (OR = 0.21, P = 0.0012 and recessive inheritance of the phenotype of HAPE-s (P = 0.0012. A haplotype CAC carrying allele C of rs130293 was associated with resistance to HAPE. DISCUSSION: This genome-wide association study revealed several novel candidate genes associated with susceptibility or resistance to HAPE in a Japanese population. Among those, the minor allele C of rs130293 (C/T in the TIMP3 gene was linked to resistance to HAPE; while, the ancestral allele T was associated with susceptibility to HAPE.

  10. On the Role of Processing Parameters in Producing Recycled Aluminum AA6061 Based Metal Matrix Composite (MMC-AlR) Prepared Using Hot Press Forging (HPF) Process

    Science.gov (United States)

    Ahmad, Azlan; Lajis, Mohd Amri

    2017-01-01

    Solid-state recycling, which involves the direct recycling of scrap metal into bulk material using severe plastic deformation, has emerged as a potential alternative to the conventional remelting and recycling techniques. Hot press forging has been identified as a sustainable direct recycling technique that has fewer steps and maintains excellent material performance. An experimental investigation was conducted to explore the hardness and density of a recycled aluminum-based metal matrix composite by varying operating temperature and holding time. A mixture of recycled aluminum, AA6061, and aluminum oxide were simultaneously heated to 430, 480, and 530 °C and forged for 60, 90, and 120 min. We found a positive increase in microhardness and density for all composites. The hardness increased approximately 33.85%, while density improved by about 15.25% whenever the temperature or the holding time were increased. Based on qualitative analysis, the composite endures substantial plastic deformation due to the presence of hardness properties due to the aluminum oxide embedded in the aluminum matrix. These increases were significantly affected by the operating temperature; the holding time also had a subordinate role in enhancing the metal matrix composite properties. Furthermore, in an effort to curb the shortage of primary resources, this study reviewed the promising performance of secondary resources produced by using recycled aluminum and aluminum oxide as the base matrix and reinforcement constituent, respectively. This study is an outline for machining practitioners and the manufacturing industry to help increase industry sustainability with the aim of preserving the Earth for our community in the future. PMID:28925963

  11. The role of an organic matrix during the formation of siliceous scales in the heliozoon Actinophrys sol (actinophryida, protista).

    Science.gov (United States)

    Newman, P J; Patterson, D J

    1993-07-25

    Actinophrys sol is a freshwater heliozoon which has trophic and encysted body forms. During encystment, siliceous scales are laid down in silica deposition vesicles. The scales form one layer of a multi-layered cyst wall. Scale production is described using light microscopy, transmission electron microscopy, scanning electron microscopy, and X-ray microanalysis. Silica is laid down on an organic matrix which is visible prior to silicification and after removal of silica with hydrofluoric acid. Actinophrys sol can be cultured under silica impoverished conditions, with the result that the siliceous plates are absent. The cysts continue to form but are fragile. Silica is not a prerequisite for the processes of encystment and cyst formation. Copyright © 1993 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  12. [Role of Allelic Genes of Matrix Metalloproteinases and Their Tissue Inhibitors in the Peptic Ulcer Disease Development].

    Science.gov (United States)

    Shaymardanova, E Kh; Nurgalieva, A Kh; Khidiyatova, I M; Gabbasova, L V; Kuramshina, O A; Kryukova, A Ya; Sagitov, R B; Munasipov, F R; Khusnutdinova, E Kh

    2016-03-01

    Peptic ulcer disease is a chronic disease of the gastrointestinal tract, mainly manifesting itself in the formation of the fairly persistent ulcer defect of the mucous membrane of the stomach and/or duodenum. Association analysis of common polymorphisms of matrix metalloproteinases genes MMP-1 (rs1799750, rs494379), MMP-2 (rs2285052), MMP-3 (rs3025058), MMP-9 (rs3918242, rs17576), and MMP-12 (rs2276109) and their tissue inhibitors TIMP-2 (rs8179090) and TIMP-3 (rs9619311) was carried out in 353 patients with a gastric ulcer or duodenal ulcer and in 325 unrelated healthy individuals from the Republic of Bashkortostan. Associations of polymorphic variants rs1799750 and rs494379 of gene MMP-1, rs3025058 of gene MMP-3, rs3918242 and rs17576 of gene MMP-9, and rs9619311 of gene TIMP-3 with the risk of peptic ulcer disease in Russians and Tatars were revealed.

  13. Role of immunohistochemical overexpression of matrix metalloproteinases MMP-2 and MMP-11 in the prognosis of death by ovarian cancer.

    Science.gov (United States)

    Périgny, Martine; Bairati, Isabelle; Harvey, Isabelle; Beauchemin, Michel; Harel, François; Plante, Marie; Têtu, Bernard

    2008-02-01

    Matrix metalloproteinases (MMPs) are enzymes thought to be involved in tumor invasion. We hypothesized that MMP-2 and MMP-11 overexpression was associated with the aggressiveness of ovarian carcinoma. This study was performed on samples from 100 patients with stage III ovarian carcinomas treated surgically between 1990 and 2000. Immunohistochemical staining was performed on ovarian tumors and peritoneal implants using monoclonal antibodies. Overexpression was defined as more than 10% of cells expressing the marker. Multivariate analyses showed that only MMP-2 overexpression by cancer cells in peritoneal implants was associated with a significant risk of death by disease (hazard ratio, 2.65; 95% confidence interval, 1.41-4.97; P =.003). MMP-11 overexpression was not predictive of survival. These results suggest that MMP-2 overexpression by cancer cells in peritoneal implants and not in the primary ovarian cancer is predictive of ovarian cancer prognosis and more likely reflects the presence of particularly aggressive clones of cancer cells.

  14. Role of non-mulberry silk fibroin in deposition and regulation of extracellular matrix towards accelerated wound healing.

    Science.gov (United States)

    Chouhan, Dimple; Chakraborty, Bijayshree; Nandi, Samit K; Mandal, Biman B

    2017-01-15

    Bombyx mori silk fibroin (BMSF) as biopolymer has been extensively explored in wound healing applications. However, limited study is available on the potential of silk fibroin (SF) from non-mulberry (Antheraea assama and Philosamia ricini) silk variety. Herein, we have developed non-mulberry SF (NMSF) based electrospun mats functionalized with epidermal growth factor (EGF) and ciprofloxacin HCl as potential wound dressing. The NMSF based mats exhibited essential properties of wound dressing like biocompatibility, high water retention capacity (440%), water vapor transmission rate (∼2330gm(-2)day(-1)), high elasticity (∼2.6MPa), sustained drug release and antibacterial activity. Functionalized NMSF mats enhanced the proliferation of human dermal fibroblasts and HaCaT cells in vitro as compared to non-functionalized mats (p⩽0.01) showing effective delivery of EGF. Extensive in vivo wound healing assesment demonstrated accelerated wound healing, enhanced re-epithelialization, highly vascularized granulation tissue and higher wound maturity as compared to BMSF based mats. NMSF mats treated wounds showed regulated deposition of mature elastin, collagen and reticulin fibers in the extracellular matrix of skin. Presence of skin appendages and isotropic collagen fibers in the regenerated skin also demonstrated scar-less healing and aesthetic wound repair. A facile fabrication of a ready-to-use bioactive wound dressing capable of concomitantly accelerating the healing process as well as deposition of the extracellular matrix (ECM) to circumvent further scarring complicacies has become a focal point of research. In this backdrop, our present work is based on non-mulberry silk fibroin (NMSF) electrospun antibiotic loaded semi-occlusive mats, mimicking the ECM of skin in terms of morphology, topology, microporous structure and mechanical stiffness. Regulation of ECM deposition and isotropic orientation evinced the potential of the mat as an instructive platform for skin

  15. Matrix Factorization and Matrix Concentration

    OpenAIRE

    Mackey, Lester

    2012-01-01

    Motivated by the constrained factorization problems of sparse principal components analysis (PCA) for gene expression modeling, low-rank matrix completion for recommender systems, and robust matrix factorization for video surveillance, this dissertation explores the modeling, methodology, and theory of matrix factorization.We begin by exposing the theoretical and empirical shortcomings of standard deflation techniques for sparse PCA and developing alternative methodology more suitable for def...

  16. Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand.

    Science.gov (United States)

    Hollander, Wouter den; Boer, Cindy G; Hart, Deborah J; Yau, Michelle S; Ramos, Yolande F M; Metrustry, Sarah; Broer, Linda; Deelen, Joris; Cupples, L Adrienne; Rivadeneira, Fernando; Kloppenburg, Margreet; Peters, Marjolein; Spector, Tim D; Hofman, Albert; Slagboom, P Eline; Nelissen, Rob G H H; Uitterlinden, André G; Felson, David T; Valdes, Ana M; Meulenbelt, Ingrid; van Meurs, Joyce J B

    2017-08-30

    Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the elderly. Of all the joints, genetic predisposition is strongest for OA of the hand; however, only few genetic risk loci for hand OA have been identified. Our aim was to identify novel genes associated with hand OA and examine the underlying mechanism. We performed a genome-wide association study of a quantitative measure of hand OA in 12 784 individuals (discovery: 8743, replication: 4011). Genome-wide significant signals were followed up by analysing gene and allele-specific expression in a RNA sequencing dataset (n=96) of human articular cartilage. We found two significantly associated loci in the discovery set: at chr12 (p=3.5 × 10(-10)) near the matrix Gla protein (MGP) gene and at chr12 (p=6.1×10(-9)) near the CCDC91 gene. The DNA variant near the MGP gene was validated in three additional studies, which resulted in a highly significant association between the MGP variant and hand OA (rs4764133, Betameta=0.83, Pmeta=1.8*10(-15)). This variant is high linkage disequilibrium with a coding variant in MGP, a vitamin K-dependent inhibitor of cartilage calcification. Using RNA sequencing data from human primary cartilage tissue (n=96), we observed that the MGP RNA expression of the hand OA risk allele was significantly lowercompared with the MGP RNA expression of the reference allele (40.7%, p<5*10(-16)). Our results indicate that the association between the MGP variant and increased risk for hand OA is caused by a lower expression of MGP, which may increase the burden of hand OA by decreased inhibition of cartilage calcification. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

    Science.gov (United States)

    Ingram, Jennifer L; Slade, David; Church, Tony D; Francisco, Dave; Heck, Karissa; Sigmon, R Wesley; Ghio, Michael; Murillo, Anays; Firszt, Rafael; Lugogo, Njira L; Que, Loretta; Sunday, Mary E; Kraft, Monica

    2016-01-01

    Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

  18. Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Sassoli, Chiara; Nosi, Daniele; Tani, Alessia; Chellini, Flaminia [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Mazzanti, Benedetta [Dept. of Experimental and Clinical Medicine—Section of Haematology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Quercioli, Franco [CNR-National Institute of Optics (INO), Largo Enrico Fermi 6, 50125 Arcetri-Florence (Italy); Zecchi-Orlandini, Sandra [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Formigli, Lucia, E-mail: formigli@unifi.it [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy)

    2014-05-01

    Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7{sup +} satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration.

  19. Effect of uric acid on gentamicin-induced nephrotoxicity in rats - role of matrix metalloproteinases 2 and 9.

    Science.gov (United States)

    Romero, Freddy; Pérez, Mariela; Chávez, Maribel; Parra, Gustavo; Durante, Paula

    2009-12-01

    In this work, we aimed to study the effect of uric acid on gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were assigned to one of six groups (six rats each) which received intraperitoneal injections for 9 days: (S) saline; (UA) Uric acid alone; (G) Gentamicin alone; (G + UA) Gentamicin + uric acid; (G rec) Gentamicin recovery and (G + UA rec) Gentamicin + uric acid recovery. In (G rec) and (G + UA rec), rats recovered for 7 days after the last injection. Urine and blood samples were taken on day 0 and at the end of every stage. Kidneys were harvested for histological scoring, determination of renal malondialdehyde (MDA), zymography and western blots for matrix metalloprotease (MMP)-2 and MMP-9. Uric acid alone did not provoke changes in biochemical and histological parameters when compared to controls. Gentamicin alone increased significantly plasma creatinine and blood urea nitrogen and caused a moderate histological damage. When combined with uric acid, these conditions worsened. MMP-9 activity and expression was decreased in rats from group G + UA as compared with rats from group G, while activity of MMP-2 was similarly increased in both groups when compared to controls. The increase in renal MDA induced by gentamicin was not altered when it was combined with uric acid. During the recovery stage, all biochemical parameters returned to normal levels, though a trend for delay of tubular damage recovery was observed in group G + UA rec when compared with group G rec. The results indicate that uric acid worsens gentamicin-induced nephrotoxicity. The mechanism is likely to implicate down-regulation of MMP-9.

  20. 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.

  1. The role of up-regulated serine proteases and matrix metalloproteinases in the pathogenesis of a murine model of colitis

    DEFF Research Database (Denmark)

    Tarlton, J F; Whiting, C V; Tunmore, D

    2000-01-01

    was to assess the role of tissue proteases in a mouse model of colitis. Proteolytic activity was analyzed, using gel and in situ zymography, in colonic tissues from severe combined immunodeficient mice with colitis induced by transfer of CD4(+) T lymphocytes. Serine proteinase levels increased in colitic tissue....... Proteinase levels followed a decreasing concentration gradient from proximal to distal colon. Proteolysis was localized to infiltrating leukocytes in diseased severe combined immunodeficient mice. Transmural inflammation was associated with serine proteinase and MMP activity in overlying epithelium......Proteinases are important at several phases of physiological and pathological inflammation, mediating cellular infiltration, cytokine activation, tissue damage, remodeling, and repair. However, little is known of their role in the pathogenesis of inflammatory bowel disease. The aim of this study...

  2. Balance between apoptosis or survival induced by changes in extracellular-matrix composition in human mesangial cells: a key role for ILK-NFκB pathway.

    Science.gov (United States)

    del Nogal, María; Luengo, Alicia; Olmos, Gemma; Lasa, Marina; Rodriguez-Puyol, Diego; Rodriguez-Puyol, Manuel; Calleros, Laura

    2012-12-01

    Renal fibrosis is the final outcome of many clinical conditions that lead to chronic renal failure, characterized by a progressive substitution of cellular elements by extracellular-matrix proteins, in particular collagen type I. The aim of this study was to identify the mechanisms responsible for human mesangial cell survival, conditioned by changes in extracellular-matrix composition. Our results indicate that collagen I induces apoptosis in cells but only after inactivation of the pro-survival factor NFκB by either the super-repressor IκBα or the PDTC inhibitor. Collagen I activates a death pathway, through ILK/GSK-3β-dependent Bim expression. Moreover, collagen I significantly increases NFκB-dependent transcription, IκBα degradation and p65/NFκB translocation to the nucleus; it activates β1 integrin and this is accompanied by increased activity of ILK which leads to AKT activation. Knockdown of ILK or AKT with small interfering RNA suppresses the increase in NFκB activity. NFκB mediates cell survival through the antiapoptotic protein Bcl-xL. Our data suggest that human mesangial cells exposed to abnormal collagen I are protected against apoptosis by a complex mechanism involving integrin β1/ILK/AKT-dependent NFκB activation with consequent Bcl-xL overexpression, that opposes a simultaneously activated ILK/GSK-3β-dependent Bim expression and this dual mechanism may play a role in the progression of glomerular dysfunction.

  3. Matrix Metalloproteinase 2 (MMP-2) Plays a Critical Role in the Softening of Common Carp Muscle during Chilled Storage by Degradation of Type I and V Collagens.

    Science.gov (United States)

    Xu, Chao; Wang, Cheng; Cai, Qiu-Feng; Zhang, Qian; Weng, Ling; Liu, Guang-Ming; Su, Wen-Jin; Cao, Min-Jie

    2015-12-30

    Matrix metalloproteinases (MMPs) are proposed to play important roles in the degradation of collagens, thus causing the post-mortem softening of fish muscle, although the specific mechanism remains largely unresolved. Previously, we reported the existence of gelatinase-like proteinases in common carp (Cyprinus carpio) muscle. The primary structures of these proteinases, however, have never been investigated. In the present study, two MMPs with molecular masses of 66 and 65 kDa were purified to homogeneity from common carp muscle by ammonium sulfate fractionation and a series of column chromatographies. Matrix-assisted laser desorption/ionization-tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS/MS) analysis indicated that they are completely identical to MMP-2 from common carp. During chilled storage of common carp at 4 °C, the enzymatic activity of MMP-2 increased to 212% in 12 h while the texture profile increased over the first 2 h and gradually decreased. On the other hand, type V collagen was purified to homogeneity and a specific polyclonal antibody against this protein was prepared. Both type I and V collagens were effectively hydrolyzed by MMP-2 at 30 °C and even at 4 °C. Furthermore, injection of metalloproteinase proteinase inhibitor EDTA into the blood vessel of live common carp suppressed post-mortem tenderization significantly. All of these results confirmed that MMP-2 is a major proteinase responsible for the degradation of collagens, resulting in the softening of fish muscle during chilled storage.

  4. [The role of Matrix Metaloproteinases in the progression of periodontitis, and the use of specific inhibitors to these enzymes in the treatment of the periodontal disease].

    Science.gov (United States)

    Nasatzky, E; Rubinstein, Y; Goultschin, J; Schwartz, Z

    2003-04-01

    Matrix Metaloproteinases (MMPs) play a crucial role in the pathogenesis of the periodontal disease. This group of enzymes can degrade most of the proteins that compose the extracellular matrix. Recently a new concept of treatment, the "host modulating therapy" (HMT) was developed. The rationale behind this concept is to inhibit the production of the inflammatory mediators and/or to block the production of the host MMPs and thus inhibiting disease production. In the recent years it was found that Tetracyclines (TC) decrease the levels of TNF-alpha, IL-1, Nitric Oxide, and prostaglandins, and via intra and extra cellular mechanisms inhibit the production and activation of the MMPs. A capsule of 20 mg Doxycycline, called later Low Dose Doxycycline (LDD), was the first HMT in the periodontal disease. In a 9 month study it was found that LDD bid after supragingival scaling statistically increased pocket reduction and attachment gain compared to supragingival scaling alone. However, this improvement was found only in pockets of 7 mm or more, and was not compared yet to periodontal supportive therapy every three month. There is a need for more basic and clinical research in the field of HMT in the treatment of periodontal disease, to expand our knowledge and clinical experience that will enable us to decide when and how to use medications to modulate host response.

  5. The role of FGF-2/HGF and fibronectin matrix on pleomorphic adenoma myoepithelial cell morphology and immunophenotype: an in vitro study.

    Science.gov (United States)

    Silva, Carolina Amália Barcellos; Nardello, Laura Cristina Leite; Garcia, Frederico Windlin; Araújo, Ney Soares de; Montalli, Victor Angelo; Araújo, Vera Cavalcanti de; Martinez, Elizabeth Ferreira

    2015-02-01

    Myoepithelial cells play a central role in glandular tumors, regulating the progression of in situ to invasive neoplasias, with the tumor microenvironment being shown to be involved in both initiation and progression. This study aimed to analyze the in vitro effects of fibroblast growth factor-2 (FGF-2) and hepatocyte growth factor (HGF) in myoepithelial cells under the influence of the fibronectin matrix extracellular protein. Benign myoepithelial cells were obtained from pleomorphic adenoma and cultured on a fibronectin substratum. FGF-2 and HGF were supplemented at different concentrations and time intervals, in order to evaluate cell proliferation, morphology and immunophenotype. Individually, FGF-2 and HGF supplementation did not alter myoepithelial cell proliferation, morphology or immunophenotype. The fibronectin substratum provoked an increase in cell proliferation and immunopositivity for α-smooth muscle actin and FGF-2. The myoepithelial cell morphology changed when the fibronectin substratum and FGF-2 acted together, highlighting the importance of the fibronectin extracellular matrix protein on the behavior of these cells.

  6. The multifunctional role of the pallilysin-associated Treponema pallidum protein, Tp0750, in promoting fibrinolysis and extracellular matrix component degradation.

    Science.gov (United States)

    Houston, Simon; Russell, Shannon; Hof, Rebecca; Roberts, Alanna K; Cullen, Paul; Irvine, Kyle; Smith, Derek S; Borchers, Christoph H; Tonkin, Michelle L; Boulanger, Martin J; Cameron, Caroline E

    2014-02-01

    The mechanisms that facilitate dissemination of the highly invasive spirochaete, Treponema pallidum, are incompletely understood. Previous studies showed the treponemal metalloprotease pallilysin (Tp0751) possesses fibrin clot degradation capability, suggesting a role in treponemal dissemination. In the current study we report characterization of the functionally linked protein Tp0750. Structural modelling predicts Tp0750 contains a von Willebrand factor type A (vWFA) domain, a protein-protein interaction domain commonly observed in extracellular matrix (ECM)-binding proteins. We report Tp0750 is a serine protease that degrades the major clot components fibrinogen and fibronectin. We also demonstrate Tp0750 cleaves a matrix metalloprotease (MMP) peptide substrate that is targeted by several MMPs, enzymes central to ECM remodelling. Through proteomic analyses we show Tp0750 binds the endothelial fibrinolytic receptor, annexin A2, in a specific and dose-dependent manner. These results suggest Tp0750 constitutes a multifunctional protein that is able to (1) degrade infection-limiting clots by both inhibiting clot formation through degradation of host coagulation cascade proteins and promoting clot dissolution by complexing with host proteins involved in the fibrinolytic cascade and (2) facilitate ECM degradation via MMP-like proteolysis of host components. We propose that through these activities Tp0750 functions in concert with pallilysin to enable T. pallidum dissemination.

  7. The role of the interaction of the vinculin proline-rich linker region with vinexin α in sensing the stiffness of the extracellular matrix.

    Science.gov (United States)

    Yamashita, Hiroshi; Ichikawa, Takafumi; Matsuyama, Daisuke; Kimura, Yasuhisa; Ueda, Kazumitsu; Craig, Susan W; Harada, Ichiro; Kioka, Noriyuki

    2014-05-01

    Although extracellular matrix (ECM) stiffness is an important aspect of the extracellular microenvironment and is known to direct the lineage specification of stem cells and affect cancer progression, the molecular mechanisms that sense ECM stiffness have not yet been elucidated. In this study, we show that the proline-rich linker (PRL) region of vinculin and the PRL-region-binding protein vinexin are involved in sensing the stiffness of ECM substrates. A rigid substrate increases the level of cytoskeleton-associated vinculin, and the fraction of vinculin stably localizing at focal adhesions (FAs) is larger on rigid ECM than on soft ECM. Mutations in the PRL region or the depletion of vinexin expression impair these responses to ECM stiffness. Furthermore, vinexin depletion impairs the stiffness-dependent regulation of cell migration. These results suggest that the interaction of the PRL region of vinculin with vinexin α plays a crucial role in sensing ECM stiffness and in mechanotransduction.

  8. The role of the microfissuration of the rock matrix in the abrasion resistance of ornamental granitic rocks

    Science.gov (United States)

    Rodríguez-Rey, Angel; Sanchez-Delgado, Nuria; Camino, Clara; Calleja, Lope; Ruiz de Argandoña, Vicente G.; Setien, Alexia

    2015-04-01

    The microcrack density and the abrasion resistance of five ornamental granites (Albero, Gris Alba, Mondariz, Rosa Porriño and Traspieles) from Galicia (NW Spain) have been quantified as part of a research aimed to interpret the cuttability of the rocks in relation to the petrophysical properties of the rock matrix. Large blocks from the quarries have been cut with an industrial saw and the microcrack density and the abrasion resistance have been measured in two surfaces: H, parallel to the cut surface; T, perpendicular both to the cut surface and the cutting direction. Both planes are perpendicular to the rift plane, as it is known in quarry works. The microcrack density has been quantified following an stereological procedure applied to polished sections imaged under scanning electron microscopy. The magnification of the images allowed the study of microcracks as narrow as 2 microns in aperture. The density has been quantified in terms of length of microcrack traces per surface unit so possible anisotropies of the microcrack network could be detected. The obtained values are in the typical range for this type of rocks although the Traspieles granite shows a higher value due to its weathering degree (H: 5.11, T: 5.37 mm/mm2). The values measured in the two surfaces (H and T) are quite similar in four of the rocks; only the Albero granite shows a marked anisotropy (H: 2.76 T: 3.53 mm/mm2). The abrasion resistance of the rocks has been measured following the european standard EN 14157:2004 using the capon method. The rocks can be classified in two groups according to their abrasion resistance. Rosa Porriño, Gris Alba and Mondariz granites are the more resistant to abrasion with values around 16-17 mm. Albero and Traspieles granites are less resistant with values higher than 19 mm. The results show a good correlation between the microcrack density and the abrasion resistance. As can be expected the rocks with high microcrack density show low abrasion resistance. The

  9. Association of topoisomerase II with the hepatoma cell nuclear matrix: the role of intermolecular disulfide bond formation.

    Science.gov (United States)

    Kaufmann, S H; Shaper, J H

    1991-02-01

    Previous studies have resulted in conflicting data regarding the recovery of the nuclear enzymes topoisomerase (topo) II and topo I in the nuclear matrix fraction. In the present study we have assessed the effect of systematically altering a single extraction procedure on the distribution of these enzymes during the subfractionation of nuclei from HTC hepatoma tissue culture cells. When nuclear monolayers (prepared by treating attached cells in situ with the neutral detergent Nonidet-P40 at 4 degrees C) were isolated in the presence of the irreversible sulfhydryl blocking reagent iodoacetamide, subsequent treatment with DNase I and RNase A followed by 1.6 M NaCl resulted in structures which were extensively depleted of intranuclear components as assessed by phase contrast microscopy and conventional transmission electron microscopy. These structures contained 12 +/- 4% of the total protein present in the original nuclear monolayers. The lamins and polypeptides with molecular weights comparable to those of actin and vimentin were the predominant polypeptides present on SDS-polyacrylamide gels. Western blotting revealed that less than 5% of the total nuclear topo II molecules were present in these structures. In contrast, when the sulfhydryl cross-linking reagent sodium tetrathionate (NaTT) was substituted for iodoacetamide, the same extraction procedure yielded structures containing components of the nucleolus and an extensive intranuclear network. These structures contained a wide variety of nonlamin, nonhistone nuclear polypeptides including 23 +/- 4% of the total nuclear topo II. SDS-polyacrylamide gel electrophoresis performed under nonreducing conditions revealed that topo II in these nuclear matrices was present as part of a large disulfide cross-linked complex. Treatment of these structures with reducing agents in 1.6 M NaCl released the topo II. In contrast, topo I did not form disulfide cross-linked oligomers and was not detectable in any of these nuclease

  10. Cloning and characterization of Prisilkin-39, a novel matrix protein serving a dual role in the prismatic layer formation from the oyster Pinctada fucata.

    Science.gov (United States)

    Kong, Yawei; Jing, Gu; Yan, Zhenguang; Li, Changzhong; Gong, Ningping; Zhu, Fangjie; Li, Dongxian; Zhang, Yaorun; Zheng, Guilan; Wang, Hongzhong; Xie, Liping; Zhang, Rongqing

    2009-04-17

    Molluscs form their shells out of CaCO(3) and a matrix of biomacromolecules. Understanding the role of matrices may shed some light on the mechanism of biomineralization. Here, a 1401-bp full-length cDNA sequence encoding a novel matrix protein was cloned from the mantle of the bivalve oyster, Pinctada fucata. The deduced protein (Prisilkin-39), which has a molecular mass of 39.3 kDa and an isoelectric point of 8.83, was fully characterized, and its role in biomineralization was demonstrated using both in vivo and in vitro crystal growth assays. Prisilkin-39 is a highly repetitive protein with an unusual composition of Gly, Tyr, and Ser residues. Expression of Prisilkin-39 was localized to columnar epithelial cells of the mantle edge, corresponding to the calcitic prismatic layer formation. Immunostaining in situ and immunodetection in vitro revealed the presence of a characteristic pattern of Prisilkin-39 in the organic sheet and in sheaths around the prisms. Prisilkin-39 binds tightly with chitin, an insoluble polysaccharide that forms the highly structured framework of the shell. Antibody injection in vivo resulted in dramatic morphological deformities in the inner shell surface structure, where large amounts of CaCO(3) were deposited in an uncontrolled manner. Moreover, Prisilkin-39 strictly prohibited the precipitation of aragonite in vitro. Taken together, Prisilkin-39 is the first protein shown to have dual function, involved both in the chitinous framework building and in crystal growth regulation during the prismatic layer mineralization. These observations may extend our view on the rare group of basic matrices and their functions during elaboration of the molluscan shell.

  11. The Regulation of Matrix Metalloproteinase Expression and the Role of Discoidin Domain Receptor 1/2 Signalling in Zoledronate-treated PC3 Cells.

    Science.gov (United States)

    Reel, Buket; Korkmaz, Ceren Gonen; Arun, Mehmet Zuhuri; Yildirim, Gokce; Ogut, Deniz; Kaymak, Aysegul; Micili, Serap Cilaker; Ergur, Bekir Ugur

    2015-01-01

    Discoidin Domain Receptors (DDR1/DDR2) are tyrosine kinase receptors which are activated by collagen. DDR signalling regulates cell migration, proliferation, apoptosis and matrix metalloproteinase (MMP) production. MMPs degrade extracellular matrix (ECM) and play essential role in tumor growth, invasion and metastasis. Nitrogen-containing bisphosphonates (N-BPs) which strongly inhibit osteoclastic activity are commonly used for osteoporosis treatment. They also have MMP inhibitory effect. In this study, we aimed to investigate the effects of zoledronate in PC3 cells and the possible role of DDR signalling and downstream pathways in these inhibitory effects. We studied messenger RNA (mRNA) and protein expressions of MMP-2,-9,-8, DDR1/DDR2 type I procollagen (TIP) and mRNA levels of PCA-1, MMP-13 and DDR-initiated signalling pathway players including K-Ras oncogene, ERK1, JNK1, p38, AKT-1 and BCLX in PC3 cells in the presence or absence of zoledronate (10-100 μM) for 2-3 days. Zoledronate (100 μM) down-regulated DDR1/ DDR2, TIP mRNAs but did not change MMP-13 (collagenase-3) mRNA. However, zoledronate up-regulated MMP-8 (collagenase-2) mRNA. Zoledronate also inhibited mRNA expressions of K-Ras, ERK1, AKT-1, BCLX and PCA-1; but did not change JNK1, p38 mRNA levels. Zoledronate (100 μM) supressed DDR1/DDR2, TIP expressions; and gelatinase (MMP-2/MMP-9) expressions/activities. Conversely, zoledronate up-regulated MMP-8 expression in PC3 cells. Zoledronate down-regulates MMP-2/-9 expressions in PC3 prostate cancer cells. DDR1/DDR2 signalling and DDR-initiated downstream Ras/Raf/ERK and PI3K/AKT pathways may at least partially responsible for MMP inhibitory effect of zoledronate.

  12. Role of CTGF/CCN2 in reparative dentinogenesis in human dental pulp.

    Science.gov (United States)

    Muromachi, Koichiro; Kamio, Naoto; Matsumoto, Takashi; Matsushima, Kiyoshi

    2012-03-01

    Connective tissue growth factor/CCN family 2 (CTGF/CCN2) has been considered to participate in tooth development. To date, the expression and role of CTGF/CCN2 in reparative dentinogenesis have been unclear. Our previous study revealed that matrix metalloproteinase-3 (MMP-3) stimulates cell migration via CTGF/CCN2 expression and secretion in human dental pulp cells, and that this is dependent on dynamin-related endocytosis and independent of protease activity. The objective of the present study was to determine the expression of CTGF/CCN2 in reparative dentin in human carious teeth and to examine the effect of CTGF/CCN2 on mineralization in cultured human dental pulp cells. Minimal expression of CTGF/CCN2 was evident in odontoblasts subjacent to the dentin-pulp junction in healthy teeth, whereas strong expression was detected in odontoblast-like cells lining the reparative dentin subjacent to dental caries. In human dental pulp cells, CTGF/CCN2 promoted mineralization but failed to induce proliferation, suggesting that this molecule has the ability to induce the differentiation of human dental pulp cells. Taken together, the data suggest that CTGF/CCN2 is likely involved in reparative dentinogenesis through formation of hard tissue in human carious teeth.

  13. Critical role of matrix metalloproteinase-9 in acute cold exposure-induced stroke in renovascular hypertensive rats.

    Science.gov (United States)

    Li, Chunguang; Li, Xiangpen; Shen, Qingyu; Li, Yi; He, Lei; Li, Mei; Tang, Yamei; Wang, Yidong; He, Qingyu; Peng, Ying

    2013-11-01

    Our objectives are to investigate the role of MMP-9 in cold exposure-induced stroke and assess the preventive effect of doxycycline, a total of 200 rats were assigned to a control group, sham group, 2-kidney, 2-clip (2K-2C) group, and doxycycline-received 2K-2C group (2K-2C+doxy) (N=50, each), and subsequently, each group were randomly assigned to 2 groups: acute cold exposure (ACE) and nonacute cold exposure (NACE) (N=25, each). After the blood pressure was stabilized, rats were maintained on a 12-h light (22°C)/dark (4°C) cycle (ACE group) or a 12-h light (22°C)/dark (22°C) cycle (NACE group) for 3 cycles. The results showed that ACE upregulated Ang II and MMP-9 protein levels in brains and aortas and considerably enhanced stroke incidence in 2K-2C rats. In contrast, doxycycline treatment prevented upregulation of MMP-9 protein expression and activity in brains and aortas in response to ACE and significantly decreased stroke incidence. These findings suggest that cold exposure-induced MMP-9 via activation of RAS might play a critical role in the initiation of cold exposure-induced stroke during chronic hypertension and doxycycline shows protective effects against cold exposure-induced stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Matrix calculus

    CERN Document Server

    Bodewig, E

    1959-01-01

    Matrix Calculus, Second Revised and Enlarged Edition focuses on systematic calculation with the building blocks of a matrix and rows and columns, shunning the use of individual elements. The publication first offers information on vectors, matrices, further applications, measures of the magnitude of a matrix, and forms. The text then examines eigenvalues and exact solutions, including the characteristic equation, eigenrows, extremum properties of the eigenvalues, bounds for the eigenvalues, elementary divisors, and bounds for the determinant. The text ponders on approximate solutions, as well

  15. Role of sodium ions in the vitrification process: glass matrix modification, slag structure depolymerization, and influence of metal immobilization.

    Science.gov (United States)

    Kuo, Yi-Ming

    2014-07-01

    This study investigates the role of Na ions, a common flux, in the vitrification process. Artificial glass systems composed of Al2O3, CaO, and SiO2 with various Na concentrations were melted at 1450 degrees C. The specimens were cooled by air cooling and water quenching and the metal mobility was evaluated using a sequential extraction procedure. The X-ray diffraction analysis and scanning electron microscopy observations showed that Na ions governed the air-cooled slag's structure. Na ions initially depolymerized CaSiO3-linked chains into CaSiO3 chains, and further cut them into shorter and nonuniform ones, making the slag structure amorphous. With even more Na ions, CaSiO3 chains were divided into single SiO4 tetrahedrons and formed Na-related crystals (Na2Ca3Si2O8 and NaAlSiO4). The phase distributions of Al, Cr, Cu Mn, and Ni showed that Na has a positive effect on the immobilization of heavy metals at suitable concentrations, but a negative effect when in excess amounts. Implications: Vitrification has been widely used to treat hazardous materials. The Na-bearing additives were often used as a flux to improve the melting process. This study described the role of Na played in the vitrification process. The Na ions acted as glass modifier and depolymerize the chain structure of slag. With adequate addition amount of Na ions, the immobilization of heavy metals was improved. The results provided much information about the crystalline phase variation, metal mobility, and surface characteristics while Na serves as a flux.

  16. Regulation of P21cip1 Expression by Growth Factors and the Extracellular Matrix Reveals a Role for Transient ERK Activity in G1 Phase

    Science.gov (United States)

    Bottazzi, Maria Elena; Zhu, Xiaoyun; Böhmer, Ralph M.; Assoian, Richard K.

    1999-01-01

    We have examined the regulation of p21cip1 by soluble mitogens and cell anchorage as well as the relationship between the expression of p21cip1 and activation of the ERK subfamily of MAP kinases. We find that p21cip1 expression in G1 phase can be divided into two discrete phases: an initial induction that requires growth factors and the activation of ERK, and then a subsequent decline that is enhanced by cell anchorage in an ERK-independent manner. In contrast to the induction of cyclin D1, the induction of p21cip1 is mediated by transient ERK activity. Comparative studies with wild-type and p21cip1-null fibroblasts indicate that adhesion-dependent regulation of p21cip1 is important for proper control of cyclin E–cdk2 activity. These data lead to a model in which mitogens and anchorage act in a parallel fashion to regulate G1 phase expression of p21cip1. They also show that (a) growth factors and growth factor/extracellular matrix cooperation can have different roles in regulating G1 phase ERK activity and (b) both transient and sustained ERK signals have functionally significant roles in controlling cell cycle progression through G1 phase. PMID:10491389

  17. Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing?

    Science.gov (United States)

    Sheets, Anthony R; Demidova-Rice, Tatiana N; Shi, Lei; Ronfard, Vincent; Grover, Komel V; Herman, Ira M

    2016-01-01

    Debridement, the removal of diseased, nonviable tissue, is critical for clinicians to readily assess wound status and prepare the wound bed for advanced therapeutics or downstream active healing. Removing necrotic slough and eschar through surgical or mechanical methods is less specific and may be painful for patients. Enzymatic debridement agents, such as Clostridial collagenase, selectively and painlessly degrade devitalized tissue. In addition to its debriding activities, highly-purified Clostridial collagenase actively promotes healing, and our past studies reveal that extracellular matrices digested with this enzyme yield peptides that activate cellular migratory, proliferative and angiogenic responses to injury in vitro, and promote wound closure in vivo. Intriguingly, while collagenase Santyl® ointment, a sterile preparation containing Clostridial collagenases and other non-specific proteases, is a well-accepted enzymatic debridement agent, its role as an active healing entity has never been established. Based on our previous studies of pure Clostridial collagenase, we now ask whether the mixture of enzymes contained within Santyl® produces matrix-derived peptides that promote cellular injury responses in vitro and stimulate wound closure in vivo. Here, we identify novel collagen fragments, along with collagen-associated peptides derived from thrombospondin-1, multimerin-1, fibronectin, TGFβ-induced protein ig-h3 and tenascin-C, generated from Santyl® collagenase-digested human dermal capillary endothelial and fibroblastic matrices, which increase cell proliferation and angiogenic remodeling in vitro by 50-100% over controls. Using an established model of impaired healing, we further demonstrate a specific dose of collagenase from Santyl® ointment, as well as the newly-identified and chemically-synthesized ECM-derived peptides significantly increase wound re-epithelialization by 60-100% over saline-treated controls. These results not only confirm and

  18. Matrix Thermalization

    CERN Document Server

    Craps, Ben; Nguyen, Kévin

    2016-01-01

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  19. Matrix metalloproteinase-25 has a functional role in mouse secondary palate development and is a downstream target of TGF-β3

    Directory of Open Access Journals (Sweden)

    Brown Graham D

    2010-09-01

    Full Text Available Abstract Background Development of the secondary palate (SP is a complex event and abnormalities during SP development can lead to cleft palate, one of the most common birth disorders. Matrix metalloproteinases (MMPs are required for proper SP development, although a functional role for any one MMP in SP development remains unknown. MMP-25 may have a functional role in SP formation as genetic scans of the DNA of human cleft palate patients indicate a common mutation at a region upstream of the MMP-25 gene. We report on the gene expression profile of MMP-25 in the developing mouse SP and identify its functional role in mouse SP development. Results MMP-25 mRNA and protein are found at all SP developmental stages in mice, with the highest expression at embryonic day (E 13.5. Immunohistochemistry and in situ hybridization localize MMP-25 protein and mRNA, respectively, to the apical palate shelf epithelial cells and apical mesenchyme. MMP-25 knockdown with siRNA in palatal cultures results in a significant decrease in palate shelf fusion and persistence of the medial edge epithelium. MMP-25 mRNA and protein levels significantly decrease when cultured palate shelves are incubated in growth medium with 5 μg/mL of a TGF-β3-neutralizing antibody. Conclusions Our findings indicate: (i MMP-25 gene expression is highest at E12.5 and E13.5, which corresponds with increasing palate shelf growth downward alongside the tongue; (ii MMP-25 protein and mRNA expression predominantly localize in the apical epithelium of the palate shelves, but are also found in apical areas of the mesenchyme; (iii knockdown of MMP-25 mRNA expression impairs palate shelf fusion and results in significant medial edge epithelium remaining in contacted areas; and (iv bio-neutralization of TGF-β3 significantly decreases MMP-25 gene expression. These data suggest a functional role for MMP-25 in mouse SP development and are the first to identify a role for a single MMP in mouse SP

  20. Elementary matrix algebra

    CERN Document Server

    Hohn, Franz E

    2012-01-01

    This complete and coherent exposition, complemented by numerous illustrative examples, offers readers a text that can teach by itself. Fully rigorous in its treatment, it offers a mathematically sound sequencing of topics. The work starts with the most basic laws of matrix algebra and progresses to the sweep-out process for obtaining the complete solution of any given system of linear equations - homogeneous or nonhomogeneous - and the role of matrix algebra in the presentation of useful geometric ideas, techniques, and terminology.Other subjects include the complete treatment of the structur

  1. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

    2014-01-01

    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...... suggest that cholesterol matrix formation may play a pathogenic role in atherosclerotic inflammation, and they indicate a mechanism by which bacteria and/or bacterial products may play a role in processes leading to arteriosclerosis....

  2. Primary structure and phosphorylation of dentin matrix protein 1 (DMP1) and dentin phosphophoryn (DPP) uniquely determine their role in biomineralization.

    Science.gov (United States)

    Deshpande, Atul Suresh; Fang, Ping-An; Zhang, Xiaoyuan; Jayaraman, Thottala; Sfeir, Charles; Beniash, Elia

    2011-08-08

    The SIBLING (small integrin-binding ligand N-linked glycoproteins) family is the major group of noncollagenous proteins in bone and dentin. These extremely acidic and highly phosphorylated extracellular proteins play critical roles in the formation of collagenous mineralized tissues. Whereas the lack of individual SIBLINGs causes significant mineralization defects in vivo, none of them led to a complete cessation of mineralization suggesting that these proteins have overlapping functions. To assess whether different SIBLINGs regulate biomineralization in a similar manner and how phosphorylation impacts their activity, we studied the effects of two SIBLINGs, dentin matrix protein 1 (DMP1) and dentin phosphophoryn (DPP), on mineral morphology and organization in vitro. Our results demonstrate distinct differences in the effects of these proteins on mineralization. We show that phosphorylation has a profound effect on the regulation of mineralization by both proteins. Specifically, both phosphorylated proteins facilitated organized mineralization of collagen fibrils and phosphorylated DMP1-induced formation of organized mineral bundles in the absence of collagen. In summary, these results indicate that the primary structure and phosphorylation uniquely determine functions of individual SIBLINGs in regulation of mineral morphology and organization.

  3. Role of the Emp Pilus Subunits of Enterococcus faecium in Biofilm Formation, Adherence to Host Extracellular Matrix Components, and Experimental Infection.

    Science.gov (United States)

    Montealegre, Maria Camila; Singh, Kavindra V; Somarajan, Sudha R; Yadav, Puja; Chang, Chungyu; Spencer, Robert; Sillanpää, Jouko; Ton-That, Hung; Murray, Barbara E

    2016-05-01

    Enterococcus faecium is an important cause of hospital-associated infections, including urinary tract infections (UTIs), bacteremia, and infective endocarditis. Pili have been shown to play a role in the pathogenesis of Gram-positive bacteria, including E. faecium We previously demonstrated that a nonpiliated ΔempABC::cat derivative of E. faecium TX82 was attenuated in biofilm formation and in a UTI model. Here, we studied the contributions of the individual pilus subunits EmpA, EmpB, and EmpC to pilus architecture, biofilm formation, adherence to extracellular matrix (ECM) proteins, and infection. We identified EmpA as the tip of the pili and found that deletion of empA reduced biofilm formation to the same level as deletion of the empABC operon, a phenotype that was restored by reconstituting in situ the empA gene. Deletion of empB also caused a reduction in biofilm, while EmpC was found to be dispensable. Significant reductions in adherence to fibrinogen and collagen type I were observed with deletion of empA and empB, while deletion of empC had no adherence defect. Furthermore, we showed that each deletion mutant was significantly attenuated in comparison to the isogenic parental strain, TX82, in a mixed-inoculum UTI model (P Emp pilins are important for E. faecium to cause infection in the urinary tract.

  4. Dynamics of matrix-free Ca2+ in cardiac mitochondria: two components of Ca2+ uptake and role of phosphate buffering.

    Science.gov (United States)

    Wei, An-Chi; Liu, Ting; Winslow, Raimond L; O'Rourke, Brian

    2012-06-01

    Mitochondrial Ca(2+) uptake is thought to provide an important signal to increase energy production to meet demand but, in excess, can also trigger cell death. The mechanisms defining the relationship between total Ca(2+) uptake, changes in mitochondrial matrix free Ca(2+), and the activation of the mitochondrial permeability transition pore (PTP) are not well understood. We quantitatively measure changes in [Ca(2+)](out) and [Ca(2+)](mito) during Ca(2+) uptake in isolated cardiac mitochondria and identify two components of Ca(2+) influx. [Ca(2+)](mito) recordings revealed that the first, MCU(mode1), required at least 1 µM Ru360 to be completely inhibited, and responded to small Ca(2+) additions in the range of 0.1 to 2 µM with rapid and large changes in [Ca(2+)](mito). The second component, MCU(mode2), was blocked by 100 nM Ru360 and was responsible for the bulk of total Ca(2+) uptake for large Ca(2+) additions in the range of 2 to 10 µM; however, it had little effect on steady-state [Ca(2+)](mito). MCU(mode1) mediates changes in [Ca(2+)](mito) of 10s of μM, even in the presence of 100 nM Ru360, indicating that there is a finite degree of Ca(2+) buffering in the matrix associated with this pathway. In contrast, the much higher Ca(2+) loads evoked by MCU(mode2) activate a secondary dynamic Ca(2+) buffering system consistent with calcium-phosphate complex formation. Increasing P(i) potentiated [Ca(2+)](mito) increases via MCU(mode1) but suppressed [Ca(2+)](mito) changes via MCU(mode2). The results suggest that the role of MCU(mode1) might be to modulate oxidative phosphorylation in response to intracellular Ca(2+) signaling, whereas MCU(mode2) and the dynamic high-capacity Ca(2+) buffering system constitute a Ca(2+) sink function. Interestingly, the trigger for PTP activation is unlikely to be [Ca(2+)](mito) itself but rather a downstream byproduct of total mitochondrial Ca(2+) loading.

  5. Matrix inequalities

    CERN Document Server

    Zhan, Xingzhi

    2002-01-01

    The main purpose of this monograph is to report on recent developments in the field of matrix inequalities, with emphasis on useful techniques and ingenious ideas. Among other results this book contains the affirmative solutions of eight conjectures. Many theorems unify or sharpen previous inequalities. The author's aim is to streamline the ideas in the literature. The book can be read by research workers, graduate students and advanced undergraduates.

  6. On the role of hydrogel structure and degradation in controlling the transport of cell-secreted matrix molecules for engineered cartilage.

    Science.gov (United States)

    Dhote, Valentin; Skaalure, Stacey; Akalp, Umut; Roberts, Justine; Bryant, Stephanie J; Vernerey, Franck J

    2013-03-01

    Damage to cartilage caused by injury or disease can lead to pain and loss of mobility, diminishing one's quality of life. Because cartilage has a limited capacity for self-repair, tissue engineering strategies, such as cells encapsulated in synthetic hydrogels, are being investigated as a means to restore the damaged cartilage. However, strategies to date are suboptimal in part because designing degradable hydrogels is complicated by structural and temporal complexities of the gel and evolving tissue along multiple length scales. To address this problem, this study proposes a multi-scale mechanical model using a triphasic formulation (solid, fluid, unbound matrix molecules) based on a single chondrocyte releasing extracellular matrix molecules within a degrading hydrogel. This model describes the key players (cells, proteoglycans, collagen) of the biological system within the hydrogel encompassing different length scales. Two mechanisms are included: temporal changes of bulk properties due to hydrogel degradation, and matrix transport. Numerical results demonstrate that the temporal change of bulk properties is a decisive factor in the diffusion of unbound matrix molecules through the hydrogel. Transport of matrix molecules in the hydrogel contributes both to the development of the pericellular matrix and the extracellular matrix and is dependent on the relative size of matrix molecules and the hydrogel mesh. The numerical results also demonstrate that osmotic pressure, which leads to changes in mesh size, is a key parameter for achieving a larger diffusivity for matrix molecules in the hydrogel. The numerical model is confirmed with experimental results of matrix synthesis by chondrocytes in biodegradable poly(ethylene glycol)-based hydrogels. This model may ultimately be used to predict key hydrogel design parameters towards achieving optimal cartilage growth.

  7. THE ROLE OF THE MATRIX METALLOPROTEINASES IN THE DEVELOPMENT OF LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH ARTERIAL HYPERTENSION AND METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2015-09-01

    Full Text Available Aim. To assess the role of the activation of matrix metalloproteinase-1 zymogen (ProMMP-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in the development of left ventricular (LV hypertrophy in patients with arterial hypertension (HT and metabolic syndrome (MS with varying degree of obesity.Material and methods. 108 patients with HT and MS divided into 3 groups according to body mass index, and 28 healthy women were studied. Intracardiac blood flow and ProMMP-1 and TIMP-1 levels were assessed.Results. Disbalance in the ProMMP-1 and TIMP-1 systems  is associated with the severity of left ventricular remodeling and grade of obesity. The changes in LV structure and geometry and activation ProMMP-1 with a deficit of TIMP-1 were most significant in patients with HT and grade 3 obesity (respectively 7.7±0.61 and 183.6±17.2 ng/ml in grade 3 obesity vs 3.5±0.3 and 291.7±22.4 ng/ml in grade 1 obesity; p<0.05. Associations between hemodynamic parameters and levels of ProMMP-1 [withLVmass index (LVMI: r=0.47; p<0.05] and TIMP-1 (with LVMI: r=-0.39;  p<0.05 were determined.Conclusion. Changes in the ProMMP-1 and TIMP-1 system in women with HT and MS are associated with the severity ofLVhypertrophy.

  8. Role of matrix metalloproteinase, tissue inhibitor of metalloproteinase and tumor necrosis factor-α single nucleotide gene polymorphisms in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Martin JW Meijer; Marij AC Mieremet-Ooms; Ruud A van Hogezand; Cornelis BHW Lamers; Daniel W Hommes; Hein W Verspaget

    2007-01-01

    AIM: To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1, -2, -3, -9, tissue inhibitors of metalloproteinases (TIMP)-1, -2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD), that may enhance susceptibility and/or disease severity.METHODS: Genomic DNA from 134 Crohn's disease (CD), 111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR.RESULTS: The TIMP-1 genotype ∏ in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%, P = 0.018 and 67.9% vs 51.6%, P = 0.055, respectively), while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%, P = 0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5TST genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during followup (91.2% vs 71.8%, P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%, P = 0.017).CONCLUSION: Allelic composition at the examined SNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype, i.e., fistulizing disease,stricture pathogenesis and first disease localisation.These findings reinforce the important role of these proteins in IBD.

  9. [The role of disequilibrium of expression of matrix metalloproteinase-2/9 and their tissue inhibitors in pathogenesis of hyperoxia-induced acute lung injury in mice].

    Science.gov (United States)

    Zhang, Xiang-feng; Zhu, Guang-fa; Liu, Shuang; Foda, Hussein D

    2008-10-01

    To investigate the role of matrix metalloproteinase-2/9 (MMP-2/9) and their tissue inhibitors (TIMP-1/2) in pathogenesis of acute lung injury (ALI) induced by hyperoxia. Seventy-two C57BL/6 mice were randomly divided into normal control group, hyperoxia for 24 hours group, hyperoxia for 48 hours group, and hyperoxia for 72 hours group, with 18 mice in each group. The mice in hyperoxia groups were exposed to >98% oxygen in sealed cages, and the normal control group were placed outside of the cage to breathe room air. At the end of the exposure time the animals were euthanized, the right lung was removed and phosphate buffer solution (PBS) was used to lavage the lung through the endotracheal catheter. The wet/dry weight ratio, broncho-alveolar lavage fluid (BALF) protein content and the volume of pleural fluid were measured, the severity of lung injury was assessed; the expression of MMP-2/9 and TIMP-1/2 mRNA in lung tissue at 24, 48 and 72 hours of hyperoxia were assessed by reverse transcript-polymerase chain reaction (RT-PCR); the amount of MMP-2/9 and TIMP-1/2 protein in lung tissue were measured by enzyme-linked immunosorbent assay (ELISA). Hyperoxia caused ALI as evidenced by the increase in lung wet/dry weight ratio, BALF protein content and the volume of pleural fluid as compared with the normal control group (P<0.05 or P<0.01). RT-PCR study showed increased expression of MMP-2/9 and TIMP-1 mRNA in lung tissues (P<0.05 or P<0.01), and ELISA assay also demonstrated upregulation of MMP-2/9 and an increase in TIMP-1 amount in BALF compared with their normal control group (P<0.05 or P<0.01). The ratios of both MMP-2 mRNA/TIMP-2 mRNA and MMP-2 protein/TIMP-2 protein were all increased in hyperoxia groups as compared with their normal control group (all P<0.01). Hyperoxia causes ALI in mice, and disturbance of MMP-2/TIMP-2 balance plays an important role in the development of hyperoxia-induced ALI in mice.

  10. Comparative role of phosphotyrosine kinase domains of c-ros and c-ret protooncogenes in metanephric development with respect to growth factors and matrix morphogens.

    Science.gov (United States)

    Liu, Z Z; Wada, J; Kumar, A; Carone, F A; Takahashi, M; Kanwar, Y S

    1996-08-25

    Receptor-like protooncogenes, with tyrosine kinase catalytic domains, are expressed in neoplastic and fetal tissues and potentially have a role in embryonic development. Which protooncogene may have the dominant role in embryonic renal development during the "postinductive" period, i.e., Day 10 onward, was addressed in this study by utilizing an in vitro organ culture system. The role of various receptor-like protooncogenes, with the emphasis on c-ros and c-ret, was investigated by antisense-oligodeoxynucleotide (ODN) gene-targeting strategies at a point in metanephric development when reciprocal-inductive interactions between the epithelium and mesenchyme have already been initiated and are rampant. Also, their relationship with other morphogens, like extracellular matrix (ECM) proteins and growth factors, was studied. Initial in situ hybridization and RT-PCR analyses revealed a similar spatiotemporal expression for both c-ros and c-ret in the embryonic kidneys. At Day 13, they were mainly expressed in the developing nephrons in the nephrogenic zone and ureteric bud branches, where the signals from the mesenchymal ligands are transduced to the epithelial cell surface receptors. Minimal expression was observed in the newborn kidneys. Inclusion of antisense ODNs, derived from the phosphotyrosine kinase domains, inhibited metanephric growth in the organ culture; the most dramatic effects were observed with the c-ret antisense ODN. The c-ret-induced dysmorphogenetic effects were characterized as a decrease in the population of nephrons, atrophy of the mesenchymal cells, and loss of acuteness of the tips of ureteric bud branches. Interestingly, the ureteric bud branches continue to grow in the atrophic mesenchyme. Both c-ros and c-ret antisense ODNs reduced the gene expression and biosynthesis of various ECM proteins. The proteoglycans, expressed at the epithelial:mesenchymal interface, were most adversely affected, especially by the c-ret antisense. The treatment of

  11. Matrix analysis

    CERN Document Server

    Bhatia, Rajendra

    1997-01-01

    A good part of matrix theory is functional analytic in spirit. This statement can be turned around. There are many problems in operator theory, where most of the complexities and subtleties are present in the finite-dimensional case. My purpose in writing this book is to present a systematic treatment of methods that are useful in the study of such problems. This book is intended for use as a text for upper division and gradu­ ate courses. Courses based on parts of the material have been given by me at the Indian Statistical Institute and at the University of Toronto (in collaboration with Chandler Davis). The book should also be useful as a reference for research workers in linear algebra, operator theory, mathe­ matical physics and numerical analysis. A possible subtitle of this book could be Matrix Inequalities. A reader who works through the book should expect to become proficient in the art of deriving such inequalities. Other authors have compared this art to that of cutting diamonds. One first has to...

  12. Double-stranded DNA breaks hidden in the neutral Comet assay suggest a role of the sperm nuclear matrix in DNA integrity maintenance.

    Science.gov (United States)

    Ribas-Maynou, J; Gawecka, J E; Benet, J; Ward, W S

    2014-04-01

    We used a mouse model in which sperm DNA damage was induced to understand the relationship of double-stranded DNA (dsDNA) breaks to sperm chromatin structure and to the Comet assay. Sperm chromatin fragmentation (SCF) produces dsDNA breaks located on the matrix attachment regions, between protamine toroids. In this model, epididymal sperm induced to undergo SCF can religate dsDNA breaks while vas deferens sperm cannot. Here, we demonstrated that the conventional neutral Comet assay underestimates the epididymal SCF breaks because the broken DNA ends remain attached to the nuclear matrix, causing the DNA to remain associated with the dispersion halo, and the Comet tails to be weak. Therefore, we term these hidden dsDNA breaks. When the Comet assay was modified to include an additional incubation with sodium dodecyl sulfate (SDS) and dithiothreitol (DTT) after the conventional lysis, thereby solubilizing the nuclear matrix, the broken DNA was released from the matrix, which resulted in a reduction of the sperm head halo and an increase in the Comet tail length, exposing the hidden dsDNA breaks. Conversely, SCF-induced vas deferens sperm had small halos and long tails with the conventional neutral Comet assay, suggesting that the broken DNA ends were not tethered to the nuclear matrix. These results suggest that the attachment to the nuclear matrix is crucial for the religation of SCF-induced DNA breaks in sperm. Our data suggest that the neutral Comet assay identifies only dsDNA breaks that are released from the nuclear matrix and that the addition of an SDS treatment can reveal these hidden dsDNA breaks.

  13. Matrix pentagons

    CERN Document Server

    Belitsky, A V

    2016-01-01

    The Operator Product Expansion for null polygonal Wilson loop in planar maximally supersymmetric Yang-Mills theory runs systematically in terms of multiparticle pentagon transitions which encode the physics of excitations propagating on the color flux tube ending on the sides of the four-dimensional contour. Their dynamics was unravelled in the past several years and culminated in a complete description of pentagons as an exact function of the 't Hooft coupling. In this paper we provide a solution for the last building block in this program, the SU(4) matrix structure arising from internal symmetry indices of scalars and fermions. This is achieved by a recursive solution of the Mirror and Watson equations obeyed by the so-called singlet pentagons and fixing the form of the twisted component in their tensor decomposition. The non-singlet, or charged, pentagons are deduced from these by a limiting procedure.

  14. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Nadia Calabriso

    2016-08-01

    Full Text Available Matrix metalloproteinases (MMPs are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases’ activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5–25 μg/mL of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively or their specific components (0.5–25 μmol/L, before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.

  15. The structure of myristoylated Mason-Pfizer monkey virus matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in its membrane binding.

    Science.gov (United States)

    Prchal, Jan; Srb, Pavel; Hunter, Eric; Ruml, Tomáš; Hrabal, Richard

    2012-10-26

    We determined the solution structure of myristoylated Mason-Pfizer monkey virus matrix protein by NMR spectroscopy. The myristoyl group is buried inside the protein and causes a slight reorientation of the helices. This reorientation leads to the creation of a binding site for phosphatidylinositols. The interaction between the matrix protein and phosphatidylinositols carrying C(8) fatty acid chains was monitored by observation of concentration-dependent chemical shift changes of the affected amino acid residues, a saturation transfer difference experiment and changes in (31)P chemical shifts. No differences in the binding mode or affinity were observed with differently phosphorylated phosphatidylinositols. The structure of the matrix protein-phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)] complex was then calculated with HADDOCK software based on the intermolecular nuclear Overhauser enhancement contacts between the ligand and the matrix protein obtained from a (13)C-filtered/(13)C-edited nuclear Overhauser enhancement spectroscopy experiment. PI(4,5)P(2) binding was not strong enough for triggering of the myristoyl-switch. The structural changes of the myristoylated matrix protein were also found to result in a drop in the oligomerization capacity of the protein.

  16. Matrix metalloproteinase and its inhibitor in temporomandibular joint osteoarthrosis after indirect trauma in young goats.

    Science.gov (United States)

    Wang, Yan-Liang; Li, Xin-Jun; Qin, Rui-Feng; Lei, De-Lin; Liu, Yan-Pu; Wu, Gao-Yi; Zhang, Yong-Jie; Yan-Jin; Wang, Da-Zhang; Hu, Kai-Jin

    2008-04-01

    Our aim was to examine the change in expression of matrix metalloproteinases (MMP-13), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the articular cartilage of goats with experimentally-induced osteoarthrosis of the temporomandibular joint (TMJ) at various times. Osteoarthrosis was induced in 20 goats in the bilateral TMJ and 5 goats acted as controls. There were 5 goats in each group, and a group was killed at 7 days, and 1, 3, and 6 months postoperatively. The samples were collected, and the joints evaluated histologically. Immunofluorescence was used to detect the presence of MMPs and TIMP-1 in the articular disc and condylar cartilage. The ultrastructure of the articular disc and condylar surface at 1 month was examined with scanning electron microscopy (SEM). Osteoarthrosis of the TMJ progressed gradually over time. MMP-13, MMP-3, and TIMP-1 were expressed strongly in the TMJ soon after injury; MMP-13 became gradually weakened, and MMP-3 strengthened later. None of these were expressed in the normal condyle. After a month the surface of the arthrotic condyle was uneven, and the underlying collagen fibrils were exposed in irregular fissures on the surface. The secretion of TIMP-1 was related closely to the changes of MMPs during osteoarthrosis of the TMJ. The unbalanced ratio between them caused degradation of the matrix of the cartilage and might be the cause of osteoarthrosis of the TMJ.

  17. Participação das metaloproteinases da matriz na etiopatogenia dos cistos odontogênicos Role of matrix metalloproteinases in the etiopathogeny of odontogenic cysts

    Directory of Open Access Journals (Sweden)

    Éricka Janine Dantas da Silveira

    2007-06-01

    Full Text Available Visando contribuir para um melhor entendimento do crescimento das lesões odontogênicas e do papel das metaloproteinases da matriz (MMPs nesse processo, realizou-se uma análise da expressão imuno-histoquímica das MMPs -1, -2 e -9, em 15 cistos radiculares (CR, 10 cistos radiculares residuais (CRR, 10 cistos dentígeros (CD e 10 ceratocistos odontogênicos (CO. Analisou-se, no epitélio e no mesênquima, a imunopositividade das lesões, atribuindo-se os escores: (- ausência de marcação, (+ marcação focal e (++ marcação difusa. De uma maneira geral verificou-se, no limitante epitelial das lesões, expressão predominantemente difusa da MMP-1 (CRR: 100%, CD: 70% e focal para 53% dos CRs e 60% dos COs. Ela variou de focal (CR: 60% e CO: 100% a difusa (CRR: 60% e CD: 50% para a MMP-2 e marcadamente focal para a MMP-9 (100% dos CR, CRR e CO e 60% dos CD. No mesênquima, detectou-se expressão destacadamente maior nos COs: 100% difusa para a MMP-1, enquanto a grande maioria de todos os cistos foi focal; a MMP-2 expressou-se com escore focal em 100% dos casos, contrastando-se a forte ausência de marcação nos outros cistos; para a MMP-9, 50% foram difusas e 50% focais, enquanto a maioria dos outros cistos não exibiu marcação. Os resultados deste estudo sugerem que o crescimento dos cistos odontogênicos pode ser influenciado pela secreção das MMPs. A expressão mais exuberante das MMPs no mesênquima dos COs confirma sua participação ativa no crescimento da lesão, o que pode justificar em parte sua maior agressividade em relação às outras lesões císticas.In an attempt to contribute to a better understanding about the growth of odontogenic lesions and the role of matrix metalloproteinases (MMPs in this event, the immunoexpression of MMP-1, -2 and -9 was evaluated in 15 radicular cysts (RCs, 10 residual radicular cysts (RRCs, 10 dentigerous cysts (DCs and 10 odontogenic keratocysts (OKs. To the analysis of epithelium and

  18. Riemann Zeta Matrix Function

    OpenAIRE

    Kargın, Levent; Kurt, Veli

    2015-01-01

    In this study, obtaining the matrix analog of the Euler's reflection formula for the classical gamma function we expand the domain of the gamma matrix function and give a infinite product expansion of sinπxP.  Furthermore we define Riemann zeta matrix function and evaluate some other matrix integrals. We prove a functional equation for Riemann zeta matrix function.

  19. 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.

  20. Role of solvent on protein-matrix coupling in MbCO embedded in water-saccharide systems: a Fourier transform infrared spectroscopy study.

    Science.gov (United States)

    Giuffrida, Sergio; Cottone, Grazia; Cordone, Lorenzo

    2006-08-01

    Embedding protein in sugar systems of low water content enables one to investigate the protein dynamic-structure function in matrixes whose rigidity is modulated by varying the content of residual water. Accordingly, studying the dynamics and structure thermal evolution of a protein in sugar systems of different hydration constitutes a tool for disentangling solvent rigidity from temperature effects. Furthermore, studies performed using different sugars may give information on how the detailed composition of the surrounding solvent affects the internal protein dynamics and structural evolution. In this work, we compare Fourier transform infrared spectroscopy measurements (300-20 K) on MbCO embedded in trehalose, sucrose, maltose, raffinose, and glucose matrixes of different water content. At all the water contents investigated, the protein-solvent coupling was tighter in trehalose than in the other sugars, thus suggesting a molecular basis for the trehalose peculiarity. These results are in line with the observation that protein-matrix phase separation takes place in lysozyme-lactose, whereas it is absent in lysozyme-trehalose systems; indeed, these behaviors may respectively be due to the lack or presence of suitable water-mediated hydrogen-bond networks, which match the protein surface to the surroundings. The above processes might be at the basis of pattern recognition in crowded living systems; indeed, hydration shells structural and dynamic matching is first needed for successful come together of interacting biomolecules.

  1. Titanium implants induce expression of matrix metalloproteinases in bone during osseointegration.

    Science.gov (United States)

    Shubayev, Veronica I; Brånemark, Rickard; Steinauer, Joanne; Myers, Robert R

    2004-01-01

    Implanted pure titanium fixtures are able to completely integrate with bone, in part because of the formation of a strong extracellular matrix (ECM) bond at the titanium-bone interface. In this study, we used a rodent femur model of intramedullary osseointegration to analyze the changes in immunoreactivity of ECM-controlling matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase-3 (TIMP-3), and tumor necrosis factor alpha (TNF-alpha) during osseointegration. We observed dramatic increases in MMP-2, MMP-9, MMP-7, TIMP-3, and TNF-alpha in osteocytes, osteoclasts, haversian canals, and the interface matrix in bone ipsilateral to the titanium implant. An increase in TIMP-3, MMP-9, and MMP-7 in hypertrophied chondrocytes and the vascular component of the epiphysial growth plate was also observed in experimental bone. These findings were not seen in contralateral or sham-operated bone, where the titanium fixtures were threaded into the femur and immediately removed. Our data link titanium-induced bone remodeling to changes in expression and distribution of MMPs.

  2. Extracellular localization of galectin-3 has a deleterious role in joint tissues.

    Science.gov (United States)

    Janelle-Montcalm, Audrée; Boileau, Christelle; Poirier, Françoise; Pelletier, Jean-Pierre; Guévremont, Mélanie; Duval, Nicolas; Martel-Pelletier, Johanne; Reboul, Pascal

    2007-01-01

    In this study we examine the extracellular role of galectin-3 (gal-3) in joint tissues. Following intra-articular injection of gal-3 or vehicle in knee joints of mice, histological evaluation of articular cartilage and subchondral bone was performed. Further studies were then performed using human osteoarthritic (OA) chondrocytes and subchondral bone osteoblasts, in which the effect of gal-3 (0 to 10 microg/ml) was analyzed. Osteoblasts were incubated in the presence of vitamin D3 (50 nM), which is an inducer of osteocalcin, encoded by an osteoblast terminal differentiation gene. Genes of interest mainly expressed in either chondrocytes or osteoblasts were analyzed with real-time RT-PCR and enzyme immunoassays. Signalling pathways regulating osteocalcin were analyzed in the presence of gal-3. Intra-articular injection of gal-3 induced knee swelling and lesions in both cartilage and subchondral bone. On human OA chondrocytes, gal-3 at 1 microg/ml stimulated ADAMTS-5 expression in chondrocytes and, at higher concentrations (5 and 10 microg/ml), matrix metalloproteinase-3 expression. Experiments performed with osteoblasts showed a weak but bipolar effect on alkaline phosphatase expression: stimulation at 1 microg/ml or inhibition at 10 microg/ml. In the absence of vitamin D3, type I collagen alpha 1 chain expression was inhibited by 10 microg/ml of gal-3. The vitamin D3 induced osteocalcin was strongly inhibited in a dose-dependent manner in the presence of gal-3, at both the mRNA and protein levels. This inhibition was mainly mediated by phosphatidylinositol-3-kinase. These findings indicate that high levels of extracellular gal-3, which could be encountered locally during the inflammatory process, have deleterious effects in both cartilage and subchondral bone tissues.

  3. Extracellular Matrix Proteins

    Directory of Open Access Journals (Sweden)

    Linda Christian Carrijo-Carvalho

    2012-01-01

    Full Text Available Lipocalin family members have been implicated in development, regeneration, and pathological processes, but their roles are unclear. Interestingly, these proteins are found abundant in the venom of the Lonomia obliqua caterpillar. Lipocalins are β-barrel proteins, which have three conserved motifs in their amino acid sequence. One of these motifs was shown to be a sequence signature involved in cell modulation. The aim of this study is to investigate the effects of a synthetic peptide comprising the lipocalin sequence motif in fibroblasts. This peptide suppressed caspase 3 activity and upregulated Bcl-2 and Ki-67, but did not interfere with GPCR calcium mobilization. Fibroblast responses also involved increased expression of proinflammatory mediators. Increase of extracellular matrix proteins, such as collagen, fibronectin, and tenascin, was observed. Increase in collagen content was also observed in vivo. Results indicate that modulation effects displayed by lipocalins through this sequence motif involve cell survival, extracellular matrix remodeling, and cytokine signaling. Such effects can be related to the lipocalin roles in disease, development, and tissue repair.

  4. 基质金属蛋白酶-2和基质金属蛋白酶-9在胶质瘤侵袭和转移中的作用%Role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in glioma invasion and metastasis

    Institute of Scientific and Technical Information of China (English)

    曾吉玲; 杨振宇; 马千权; 张立芹; 罗学港

    2015-01-01

    Glioma is a malignant tumor with high mortality. Cell invasion and metastasis are important lethal factors of it, which can be caused by matrix metalloproteinases (MMPs) dissolving the extracellular matrix. MMPs are zinc-dependent proteolytic enzymes and widely distributed in various tissues and organs. MMPs participate in the degradation and rebuilding of extracelular matrix, regulating cel adhesion, playing an important role in the tumor invasion and metastasis. In this review, we put emphasis on the role of MMP-2 and MMP-9 in glioma invasion and the mechanism.%胶质瘤是一种中枢神经系统恶性肿瘤,病死率高.胶质瘤细胞的侵袭和转移是其致死的重原因之一,而基质金属蛋白酶通过溶解细胞外基质实现侵袭和转移.基质金属蛋白酶(matrixmetalloproteinase,MMP)是锌离子依赖性蛋白水解酶,广泛分布于人体各组织和器官,参与细胞外基质的降解和重塑,调节细胞粘着,在肿瘤细胞的侵袭中起着重作用.本文就基质金属蛋白酶-2和基质金属蛋白酶-9在胶质瘤中的侵袭作用及其机制进行综述.

  5. Purification and properties of a small latent matrix metalloproteinase of the rat uterus.

    Science.gov (United States)

    Woessner, J F; Taplin, C J

    1988-11-15

    A small metalloproteinase that digests Azocoll was found in the uterus of the rat. Its activity increased to high levels during the postpartum period in parallel with the breakdown of the extracellular matrix exclusive of collagen (Sellers, A., and Woessner, J.F., Jr. (1980) Biochem. J. 189, 521-531). This enzyme has now been purified almost 7,000-fold to homogeneity from 12 g of tissue using molecular sieve chromatography, blue sepharose chromatography, and zinc-chelate chromatography. Gel electrophoresis with sodium dodecyl sulfate and dithiothreitol gives Mr = 28,000 for the latent form of the enzyme and Mr = 19,000 for the active form that arises spontaneously or by treatment with aminophenylmercuric acetate. The enzyme digests components of the extracellular matrix including gelatins of types I, III, IV, and V, fibronectin, and proteoglycan. It digests the alpha 2(I) chain of gelatin in preference to the alpha 1(I) chain and cleaves dinitrophenyl-Pro-Leu-Gly-Ile-Ala-Gly-Pro-D-Arg. It cleaves the B chain of insulin at two points: Ala14-Leu15 and Tyr16-Leu17. It has no action on collagens of types I, III, IV, or V at 26 degrees C and no action on elastin or phenylazo-Pro-Leu-Gly-Pro-D-Arg. The pH optimum is at pH 7 and the pI at 5.9. The enzyme requires zinc and calcium ions for activity; cobalt and strontium can partially replace these metal ions. The enzyme is not inhibited by low levels of phosphoramidon or Zincov. Its properties clearly distinguish it from collagenase, gelatinase (matrix metalloproteinase 2), and stromelysin (matrix metalloproteinase 3); it therefore constitutes a further member of the family of extracellular matrix metalloendopeptidases. The name matrix metalloproteinase 7 is proposed.

  6. Direct inhibition of matrix metalloproteinase-2 (MMP-2) by (-)-epigallocatechin-3-gallate: A possible role for the fibronectin type II repeats.

    Science.gov (United States)

    Jha, Shalinee; Kanaujia, Shankar Prasad; Limaye, Anil M

    2016-11-15

    Matrix metalloproteinases (MMPs) -2 and -9, also called gelatinases, constitute a distinct subgroup within the MMP family of extracellular matrix remodeling proteases. Gelatinases are implicated in tumor cell invasion and metastasis, and are attractive therapeutic targets. Several synthetic small molecule inhibitors of MMPs developed till date have failed in clinical trials. This has prompted explorations into the gamut of dietary compounds and nutraceuticals for specific inhibitors of MMPs with desirable properties. (-)-epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, is popular as a potential chemotherapeutic agent with demonstrable anti-metastatic and MMP inhibitory activities. Here, we have addressed the mechanism of EGCG-mediated inhibition of MMP-2 using in silico molecular docking approach. We show for the first time that EGCG targets the fibronectin type II repeat regions 1 and 3 of MMP-2, binds amino acids that constitute the exosite of this enzyme and hinders proper positioning of the substrate. This study offers a novel insight into the inhibition of MMP-2 by EGCG and presents a starting point for development of novel therapeutic molecules that can specifically target the gelatinases.

  7. A novel nuclear magnetic resonance (NMR) imaging method for measuring the water front penetration rate in hydrophilic polymer matrix capsule plugs and its role in drug release.

    Science.gov (United States)

    Ashraf, M; Iuorno, V L; Coffin-Beach, D; Evans, C A; Augsburger, L L

    1994-05-01

    An NMR imaging method was developed to estimate the rate of water movement in slow-release capsule matrices of pseudoephdrine HCl and hydroxypropyl cellulose (HPC). Test capsules were first placed in a USP method 2 (paddles, 50 rpm) dissolution apparatus. Each plug was removed from the dissolution medium at predetermined times, blotted dry, and placed within the magnetic field of a General Electric 400-MHz wide-bore NMR spectrometer equipped with a microimaging accessory. Images were recorded along the transverse plane of each plug. The water penetration rate was determined by comparison of the cut and weighed contour plots of the images acquired. After 1 hr, the plugs tamped to 200 N exhibited water penetration to the center, while only 45% of the drug was released. The percentage dry matrix was fitted to the Jost equation to obtain a diffusion coefficient of 4.15 x 10(-6) cm2/sec. NMR imaging is set forth as an important and practicable technique to investigate drug formulations. In the HPC matrix system of this study, the NMR imaging results convincingly revealed the rate of hydration front penetration not to be a rate-limiting step in the drug release process.

  8. Role of disulphide linkages between protein-coated lipid droplets and the protein matrix in the rheological properties of porcine myofibrillar protein-peanut oil emulsion composite gels.

    Science.gov (United States)

    Wu, Mangang; Xiong, Youling L; Chen, Jie

    2011-07-01

    The objective of the study was to establish disulphide interaction between protein-coated oil droplets and the surrounding protein matrix in myofibrillar protein (MP)-emulsion composite gels. An MP-stabilized peanut oil emulsion was treated with 0, 1, 3, 5 and 10 mM N-ethylmaleimide (NEM, a sulphydryl-blocking agent) and subsequently incorporated into a bulk MP sol to produce 5%-lipid, 2%-protein composites at pH 6.2. About 69% of sulphydryls in the emulsion (1% protein) were blocked by 1 mM NEM, and almost all were bound at ≥3 mM NEM. The loss of free sulphydryls resulted in a significant drop in the storage modulus (G') and rupture force of the composite gels. Microstructural examination revealed pores and oil leakage from emulsion droplets by NEM treatments, corresponding to declining rheological properties of the MP-emulsion composites. The results supported the hypothesis that disulphide cross-linking between MP-coated oil droplets and protein matrix contributed to the stabilization and reinforcement of protein-emulsion composite gels formed in comminuted muscle foods.

  9. Development and validation of UHPLC-MS/MS method for determination of eight naturally occurring catechin derivatives in various tea samples and the role of matrix effects.

    Science.gov (United States)

    Svoboda, Pavel; Vlčková, Hana; Nováková, Lucie

    2015-10-10

    A complete analytical procedure combining optimized tea infusion preparation and validated UHPLC-MS/MS method was developed for routine quantification of eight naturally occurring catechin derivatives in various tea samples. The preparation of tea infusions was optimized in terms of temperature, time and water-to-tea ratio in green, white and black teas. The catechins were analyzed using ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry in a run of only 4 min including equilibration of the system. The UHPLC-MS/MS method was fully validated in terms of inter/intra-day precision, accuracy, linearity (r(2)>0.9991), range (50-5000 ng/ml), LOD (1.5-7.5 ng/ml) and LOQ (5-25 ng/ml). Validation of the method included also the determination of the matrix effects that were evaluated in both flavored and unflavored green, white and black teas. Dilution of the resulting tea infusions appeared to be crucial for the matrix effects and also for subsequent catechin quantification in real tea samples in order to fit into the linear range of the UHPLC-MS/MS method. This complete procedure for catechin quantification was finally applied to real sample analysis represented by 70 commercial tea samples.

  10. The composition of acids in bitumen and in products from saponification of kerogen: Investigation of their role as connecting kerogen and mineral matrix

    Energy Technology Data Exchange (ETDEWEB)

    Razvigorova, M.; Budinova, T.; Tsyntsarski, B.; Petrova, B. [Bulgarian Academy of Sciences, Institute of Organic Chemistry, 1113 Sofia, Acad. Bonchev Str., bl. 9 (Bulgaria); Ekinci, E. [ISIK University, Kumbaba Mevkii, 34980 Istanbul (Turkey); Atakul, H. [Istanbul Technical University, Department of Chemical Engineering, Maslak, 34469 Istanbul (Turkey)

    2008-11-03

    In order to obtain more information and to understand the nature of relation between organic and mineral matter in oil shales, the compositions of soluble bitumen fractions obtained by extraction from Bulgarian oil shales before and after demineralization with 10% HCl, concentrated HF, and a HF/HCl mixture were investigated. The four extracts were quantitatively examined by IR and {sup 1}H NMR spectroscopy. The investigation of isolated acidic material of the bitumen fractions showed that the fatty acids are present in bitumen fractions as free acids, esters and salts. The amount of free acids in bitumen is very small. The dominant part of bitumen acids is associated with mineral components of the oil shales as well as part of them is included in the mineral matrix, and can be separated only after deep demineralization. The kerogen of the oil shales, obtained after separation of the bitumen fractions and mineral components, was subjected to saponification in order to determine the amount of acids, bound as esters to the kerogen matrix. The major components found were n-carboxylic, {alpha},{omega}-di-carboxylic, and aromatic acids. The connection of kerogen with mineral components is accomplished by the participation of carboxylic and complicated ester bonds. Experimental data for the composition of bitumen acids give evidence that algae and terrestrial materials are initial sources in the formation of soluble organic matter of Bulgarian oil shale. (author)

  11. Myocardial structure and matrix metalloproteinases.

    Science.gov (United States)

    Aggeli, C; Pietri, P; Felekos, I; Rautopoulos, L; Toutouzas, K; Tsiamis, E; Stefanadis, C

    2012-01-01

    Metalloproteinases (MMPs) are enzymes which enhance proteolysis of extracellular matrix proteins. The pathophysiologic and prognostic role of MMPs has been demonstrated in numerous studies. The present review covers a wide a range of topics with regards to MMPs structural and functional properties, as well as their role in myocardial remodeling in several cardiovascular diseases. Moreover, the clinical and therapeutic implications from their assessment are highlighted.

  12. 人胎盘天然金属蛋白酶抑制因子3的分离纯化%Isolation and purification of natural tissue inhibitor of metalloproteinase-3 from human placenta

    Institute of Scientific and Technical Information of China (English)

    徐军; 吴鹏; 韩琳; 张忠

    2006-01-01

    BACKGROUND: Matrix metalloproteinase (MMP) is a kind of protease family, its activity can be inhibited by tissue inhibitor of metalloproteinase (TIMP), especially by TIMP-3.OBJECTIVE: To fully isolate and purify natural TIMP-3, and to create enzyme-linked immunoassay of TIMP-3.DESIGN: Single-sample observation SETTING: Central Laboratory of Shenyang Medical College MATERIALS: Human placenta from Department of Obstetrics & Gynecology, Fengtian Hospital Affiliated to Shenyang Medical College (Informed consent was obtained from the relatives of patients) and MMP-1 from Research Institute. Fuji Chemical Industries, Ltd.METHODS: This experiment was conducted in the Central Laboratory of Shenyang Medical College between March 2001 and May 2002. Firstly,4 mol/L urea Tris-buffer solution (pH8.0) was used to prepare homogenate solution of placenta. Secondly, homogenate solution was performed chromatography through CM52 positive ion-exchange resin and Sephacryl S200 gel filtration. Thirdly, relative molecular weight and purity were detected by SDS- polyacrylamidedel gel electrophoresis (SDS-PAGE).Fourthly, Western blotting was used to identify the characters of purified protein. Fifthly, the inhibitory rate of TIMP-3 to MMP-1 was measured with immumofluorescence method.MAIN OUTCOME MEASURES: ① The relative molecular mass of protein showed by PAGE. ② Results of Western blot. ③ The inhibitory rate of TIMP-3 for MMP-1. ④ The recovery rate of TIMP-3 following purification.RESULTS: ①The isolated and purified TIMP-3 from human placenta consisted of non-glycosylated and glycosylated protein, with relative molecular mass of 24 000 and 27 000, respectively. ② The inhibitory concentration of non-glycosylated and glycosylated TIMP-3 was 1.1×1010 mol/L and 1.2×1010 mol/L respectively to MMP-1. The inhibitory concentration of placenta-derived TIMP-3 was significantly higher than that of recombinant TIMP-3 for MMP-1. ③ The recovery rate of TIMP-3 was 23.4% following two

  13. Creep, Fatigue and Fracture Behavior of Environmental Barrier Coating and SiC-SiC Ceramic Matrix Composite Systems: The Role of Environment Effects

    Science.gov (United States)

    Zhu, Dongming; Ghosn, Louis J.

    2015-01-01

    Advanced environmental barrier coating (EBC) systems for low emission SiCSiC CMC combustors and turbine airfoils have been developed to meet next generation engine emission and performance goals. This presentation will highlight the developments of NASAs current EBC system technologies for SiC-SiC ceramic matrix composite combustors and turbine airfoils, their performance evaluation and modeling progress towards improving the engine SiCSiC component temperature capability and long-term durability. Our emphasis has also been placed on the fundamental aspects of the EBC-CMC creep and fatigue behaviors, and their interactions with turbine engine oxidizing and moisture environments. The EBC-CMC environmental degradation and failure modes, under various simulated engine testing environments, in particular involving high heat flux, high pressure, high velocity combustion conditions, will be discussed aiming at quantifying the protective coating functions, performance and durability, and in conjunction with damage mechanics and fracture mechanics approaches.

  14. The role of nuclear energy in brazilian energy matrix: socioeconomic and environmental aspects; O papel da energia nuclear na matriz energetica brasileira: aspectos socioeconomicos e ambientais

    Energy Technology Data Exchange (ETDEWEB)

    Schirmer, Priscila

    2016-09-01

    With the large increase of energy demand in the world, either for the continued expansion of industrialization, or by the raise of consumption, are increasing the need for energy sources diversification and the search for cleaner alternatives of energy production. Nuclear power has been considered as an option to curb the emission of greenhouse gases and reduce the dependence of fossil fuels. However, nuclear energy is an issue that still causes a lot of doubt and questions, turning the development of this work very important for a better understanding of the lay public as well as to contribute and encourage future research through an assessment of their environmental and socio-economic aspects, discussing the risks, benefits, and an assessment of the expansion of nuclear energy use, including an overview of nuclear energy in Brazil. Concluding that nuclear energy can contribute to the expansion of the Brazilian energy matrix, as the only heat source able to ensure constant supply of energy without emitting greenhouse gases. Considering that Brazil dominates the technology of the nuclear fuel cycle, and has a large reserves of uranium. A larger share of nuclear energy in the Brazilian energy matrix can generate greater diversification of the same, valuing the environmental and economic sustainability of the country and reducing the system's vulnerability. However, nuclear generation should not be considered as the only solution to the energy problems of the country, but make a part of it by the combination with other renewable sources, increasing the diversity and energy security of the country. (author)

  15. A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing.

    Science.gov (United States)

    De Jesus, Aribet M; Aghvami, Maziar; Sander, Edward A

    2016-01-01

    Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours), structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants) were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks) remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient-specific mechanical

  16. A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing.

    Directory of Open Access Journals (Sweden)

    Aribet M De Jesus

    Full Text Available Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours, structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient

  17. Fragmentation of extracellular matrix by hypochlorous acid

    DEFF Research Database (Denmark)

    Woods, Alan A; Davies, Michael Jonathan

    2003-01-01

    The interaction of extracellular matrix with cells regulates their adhesion, migration and proliferation, and it is believed that damage to vascular matrix components is a factor in the development of atherosclerosis. Evidence has been provided for a role for the haem enzyme MPO (myeloperoxidase)...

  18. MMP20, KLK4, and MMP20/KLK4 double null mice define roles for matrix proteases during dental enamel formation.

    Science.gov (United States)

    Hu, Yuanyuan; Smith, Charles E; Richardson, Amelia S; Bartlett, John D; Hu, Jan C C; Simmer, James P

    2016-03-01

    Matrix metalloproteinase 20 (MMP20) and kallikrein-related peptidase 4 (KLK4) are secreted proteinases that are essential for proper dental enamel formation. We characterized and compared enamel formed in wild-type, Mmp20 (-/-), Klk4 (-/-), Mmp20 (+/-) Klk4 (+/-), and Mmp20 (-/-) Klk4 (-/-) mice using dissecting and light microscopy, backscattered scanning electron microscopy (bSEM), SEM, microcomputed tomography (μCT), and energy-dispersive X-ray analysis (EDX). Following eruption, fractures were observed on Mmp20 (-/-), Klk4 (-/-), Mmp20 (+/-) Klk4 (+/-), and Mmp20 (-/-) Klk4 (-/-) molars. Failure of the enamel in the Mmp20 (+/-) Klk4 (+/-) molars was unexpected and suggested that digenic effects could contribute to the etiology of amelogenesis imperfecta in humans. Micro-CT analyses of hemimandibles demonstrated significantly reduced high-density enamel volume in the Mmp20 (-/-) and Klk4 (-/-) mice relative to the wild-type, which was further reduced in Mmp20 (-/-) Klk4 (-/-) mice. bSEM images of 7-week Mmp20 (-/-) and Mmp20 (-/-) Klk4 (-/-) mandibular incisors showed rough, pitted enamel surfaces with numerous indentations and protruding nodules. The Mmp20 (+/-) and Mmp20 (+/-) Klk4 (+/-) incisors showed prominent, evenly spaced, horizontal ridges that were more distinct in Mmp20 (+/-) Klk4 (+/-) incisors relative to Mmp20 (+/-) incisors due to the darkening of the valleys between the ridges. In cross sections, the Mmp20 (-/-) and Mmp20 (-/-) Klk4 (-/-) exhibited three distinct layers. The outer layer exhibited a disturbed elemental composition and an irregular enamel surface covered with nodules. The Mmp20 null enamel was apparently unable to withstand the sheer forces associated with eruption and separated from dentin during development. Cells invaded the cracks and interposed between the dentin and enamel layers. MMP20 and KLK4 serve overlapping and complementary functions to harden enamel by removing protein, but MMP20 potentially serves multiple

  19. Association of poly(ADP-ribose) polymerase with the nuclear matrix: the role of intermolecular disulfide bond formation, RNA retention, and cell type.

    Science.gov (United States)

    Kaufmann, S H; Brunet, G; Talbot, B; Lamarr, D; Dumas, C; Shaper, J H; Poirier, G

    1991-02-01

    The recovery of the enzyme poly(ADP-ribose) polymerase (pADPRp) in the nuclease- and 1.6 M NaCl-resistant nuclear subfraction prepared from a number of different sources was assessed by Western blotting. When rat liver nuclei were treated with DNase I and RNase A followed by 1.6 M NaCl, approximately 10% of the nuclear pADPRp was recovered in the sedimentable fraction. The proportion of pADPRp recovered with the residual fraction decreased to less than 5% of the total nuclear polymerase when nuclei were prepared in the presence of the sulfhydryl blocking reagent iodoacetamide and increased to approximately 50% of the total nuclear pADPRp when nuclei were treated with the sulfhydryl cross-linking reagent sodium tetrathionate (NaTT) prior to fractionation. To determine whether this effect of disulfide bond formation was unique to rat liver nuclei, nuclear matrix/cytoskeleton structures were prepared in situ by sequentially treating monolayers of tissue culture cells with Nonidet-P40, DNase I and RNase A, and 1.6 M NaCl (S.H. Kaufmann and J.H. Shaper (1991) Exp. Cell Res. 192, 511-523). When nuclear monolayers were prepared from HTC rat hepatoma cells, CaLu-1 human lung carcinoma cells, and CHO hamster ovary cells in the absence of NaTT, pADPRp was undetectable in the nuclease- and 1.6 M NaCl-resistant fraction. In contrast, when nuclear monolayers were isolated in the presence of NaTT, from 5% (CaLu-1) to 26% (HTC cells) of the total nuclear pADPRp was recovered with the nuclease- and salt-resistant fraction. Examination of these residual structures by SDS-polyacrylamide gel electrophoresis under nonreducing conditions suggested that pADPRp was present as a component of disulfide cross-linked complexes. Further analysis by immunofluorescence revealed that the pADPRp was diffusely distributed throughout the CaLu-1 or CHO nuclear matrix. In addition, when matrices were prepared in the absence of RNase A, pADPRp was also observed in the residual nucleoli. These

  20. Multiscale Modeling of Ceramic Matrix Composites

    Science.gov (United States)

    Bednarcyk, Brett A.; Mital, Subodh K.; Pineda, Evan J.; Arnold, Steven M.

    2015-01-01

    Results of multiscale modeling simulations of the nonlinear response of SiC/SiC ceramic matrix composites are reported, wherein the microstructure of the ceramic matrix is captured. This micro scale architecture, which contains free Si material as well as the SiC ceramic, is responsible for residual stresses that play an important role in the subsequent thermo-mechanical behavior of the SiC/SiC composite. Using the novel Multiscale Generalized Method of Cells recursive micromechanics theory, the microstructure of the matrix, as well as the microstructure of the composite (fiber and matrix) can be captured.

  1. Sparse Planar Array Synthesis Using Matrix Enhancement and Matrix Pencil

    Directory of Open Access Journals (Sweden)

    Mei-yan Zheng

    2013-01-01

    Full Text Available The matrix enhancement and matrix pencil (MEMP plays important roles in modern signal processing applications. In this paper, MEMP is applied to attack the problem of two-dimensional sparse array synthesis. Firstly, the desired array radiation pattern, as the original pattern for approximating, is sampled to form an enhanced matrix. After performing the singular value decomposition (SVD and discarding the insignificant singular values according to the prior approximate error, the minimum number of elements can be obtained. Secondly, in order to obtain the eigenvalues, the generalized eigen-decomposition is employed on the approximate matrix, which is the optimal low-rank approximation of the enhanced matrix corresponding to sparse planar array, and then the ESPRIT algorithm is utilized to pair the eigenvalues related to each dimension of the planar array. Finally, element positions and excitations of the sparse planar array are calculated according to the correct pairing of eigenvalues. Simulation results are presented to illustrate the effectiveness of the proposed approach.

  2. The role of tetragonal-metal-organic framework-5 loadings with extra ZnO molecule on the gas separation performance of mixed matrix membrane

    Energy Technology Data Exchange (ETDEWEB)

    Arjmandi, Mehrzad; Pakizeh, Majid [Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Pirouzram, Omid [Kurdistan University, Kurdistan (Iran, Islamic Republic of)

    2015-06-15

    The effect of more ZnO molecule in tetragonal structure of MOF-5 than cubic structure on the gas permeation properties of T-MOF-5/polyetherimide mixed matrix membranes was investigated. T-MOF-5 was first successfully synthesized and carefully characterized by XRD, FTIR, SEM and N{sub 2} adsorption technique at 77 K. Novel T-MOF-5/PEI MMMs were prepared using solution casting method and characterized by FTIR and SEM. The SEM pictures of the MMMs showed that T-MOF-5 nanocrystals changed the morphology of PEI and exhibited acceptable contacts between the filler particles and the polymer chains. Gas permeation properties of these membranes with different T-MOF-5 contents were studied for pure H{sub 2}, CO{sub 2}, CH{sub 4} and N{sub 2} gases. Permeation measurement showed that the all gases' permeability, diffusivity and solubility were increased with T-MOF-5 loading. H{sub 2} permeability and the ideal selectivity of H{sub 2}/CO{sub 2} and H{sub 2}/CH{sub 4} in MMM with 25 wt% loading of T-MOF-5 nanocrystals were increased. This behavior was attributed to more ZnO molecule in T-MOF-5 structure. The experimental gas permeations through T-MOF-5/PEI nanocomposite with different filler loadings were fitted on Higuchi model. Good agreement between the experimental data and the predicted gas permeability was obtained.

  3. Role of NF-κB activation in matrix metalloproteinase 9, vascular endothelial growth factor and interleukin 8 expression and secretion in human breast cancer cells.

    Science.gov (United States)

    Li, Caijuan; Guo, Sufen; Shi, Tiemei

    2013-04-01

    The aims of this study were to assess the effects and potential mechanisms of parthenolide on the expression of vascular endothelial growth factor (VEGF), interleukin 8 (IL-8) and matrix metalloproteinase 9 (MMP-9) in human breast cancer cell line MDA-MB-231. After incubation with different concentrations of parthenolide for 24 h, MDA-MB-231 cells were collected, and the expressions of VEGF, IL-8 and MMP-9 were measured by real-time PCR and Western blot. The secretions of VEGF, IL-8 and MMP-9 in culture supernatant of MDA-MB-231 cells were then measured with ELISA assays. The NF-κB DNA-binding activity of breast cancer cells treated with parthenolide was analyzed using electrophoretic mobility assays. The real-time PCR and Western blot data showed that the expressions of VEGF, IL-8 and MMP-9 were significantly inhibited by parthenolide at both transcription level and protein level in MDA-MB-231 cells. ELISA results also confirmed these effects at a secretion level. The electrophoretic mobility assay results demonstrated that parthenolide can inhibit NF-κB DNA-binding activity of the breast cancer cells. Hence, the expression of VEGF, IL-8 and MMP-9 may be suppressed by parthenolide through the inhibition of NF-κB DNA-binding activity in MDA-MB-231 cells.

  4. Progression of kidney disease in non-diabetic patients with coronary artery disease: predictive role of circulating matrix metalloproteinase-2, -3, and -9.

    Directory of Open Access Journals (Sweden)

    Ta-Wei Hsu

    Full Text Available BACKGROUND: Circulating matrix metalloproteinase (MMP-2, -3 and -9 are well recognized in predicting cardiovascular outcome in coronary artery disease (CAD, but their risks for chronic kidney disease (CKD are lacking. Therefore, the present study aimed to investigate whether circulating MMP levels could independently predict future kidney disease progression in non-diabetic CAD patients. METHODS: The prospective study enrolled 251 non-diabetic subjects referred for coronary angiography, containing normal coronary artery (n = 30 and CAD with insignificant (n = 95 and significant (n = 126 stenosis. Estimated glomerular filtration rate (eGFR was calculated using the CKD-EPI formula. eGFR decline rate was calculated and the primary endpoint was a decline in eGFR over 25% from baseline. RESULTS: The eGFR decline rate (ml/min/1.73 m(2 per year in patients with CAD (1.22 [-1.27, 1.05] was greater than that in those with normal coronary artery (0.21 [-2.63, 0.47], P20% in eGFR from baseline or final eGFR < 60 mL/min/1.73 m(2. CONCLUSION: Circulating MMP-2, -3 and -9 are independently associated with kidney disease progression in non-diabetic CAD patients and add incremental predictive power to conventional risk factors.

  5. Molecular insights and therapeutic targets for blood-brain barrier disruption in ischemic stroke: critical role of matrix metalloproteinases and tissue-type plasminogen activator

    Science.gov (United States)

    Jin, Rong; Yang, Guojun; Li, Guohong

    2010-01-01

    Blood-brain barrier (BBB) disruption, mediated through matrix metalloproteinases (MMPs) and other mechanisms, is a critical event during ischemic stroke. Tissue plasminogen activator (tPA) is the only FDA-approved thrombolytic therapy for acute ischemic stroke, but the efficacy and safety of its therapeutic application is limited by narrow treatment time windows and side effects. Thus, there is a pressing need to develop combinational therapy that could offset tPA side effects and improve efficacy in clinical practice. Recent experimental studies indicate that tPA has previously unidentified functions in the brain beyond its well established thrombolytic activity, which might contribute to tPA-related side effects through MMPs (mainly MMP-9) and several signaling pathways involved in LDL receptor-related protein (LRP), activated protein C (APC) and protease-activated receptor 1 (PAR-1), platelet-derived growth factor C (PDGF-C), and N-methyl-D-aspartate (NMDA) receptor. Therapeutic targeting of MMPs and/or tPA-related signaling pathways might offer promising new approaches to combination therapies for ischemic stroke. This review provides an overview of the relationship between structural components and function of the BBB/neurovascular unit with respect to ischemic stroke. We discuss how MMPs and tPA contribute to BBB disruption during ischemic stroke and highlight recent findings of molecular signaling pathways involved in neurotoxicity of tPA therapy. PMID:20302940

  6. Histochemical analysis of the role of class I and class II Clostridium histolyticum collagenase in the degradation of rat pancreatic extracellular matrix for islet isolation

    NARCIS (Netherlands)

    VosScheperkeuter, GH; vanSuylichem, PTR; Wolters, GHJ; vanSchilfgaarde, R

    1997-01-01

    To understand why class II Clostridium histolyticum collagenase is much more effective than class I in the isolation of rat pancreatic islets, we analyzed the role of these collagenases in pancreatic tissue dissociation. Crude collagenase was purified and then fractionated into class I and II with d

  7. Octonionic matrix representation and electromagnetism

    Energy Technology Data Exchange (ETDEWEB)

    Chanyal, B. C. [Kumaun University, S. S. J. Campus, Almora (India)

    2014-12-15

    Keeping in mind the important role of octonion algebra, we have obtained the electromagnetic field equations of dyons with an octonionic 8 x 8 matrix representation. In this paper, we consider the eight - dimensional octonionic space as a combination of two (external and internal) four-dimensional spaces for the existence of magnetic monopoles (dyons) in a higher-dimensional formalism. As such, we describe the octonion wave equations in terms of eight components from the 8 x 8 matrix representation. The octonion forms of the generalized potential, fields and current source of dyons in terms of 8 x 8 matrix are discussed in a consistent manner. Thus, we have obtained the generalized Dirac-Maxwell equations of dyons from an 8x8 matrix representation of the octonion wave equations in a compact and consistent manner. The generalized Dirac-Maxwell equations are fully symmetric Maxwell equations and allow for the possibility of magnetic charges and currents, analogous to electric charges and currents. Accordingly, we have obtained the octonionic Dirac wave equations in an external field from the matrix representation of the octonion-valued potentials of dyons.

  8. A review of decellurization methods caused by an urgent need for quality control of cell-free extracellular matrix' scaffolds and their role in regenerative medicine.

    Science.gov (United States)

    Kawecki, Marek; Łabuś, Wojciech; Klama-Baryla, Agnieszka; Kitala, Diana; Kraut, Malgorzata; Glik, Justyna; Misiuga, Marcelina; Nowak, Mariusz; Bielecki, Tomasz; Kasperczyk, Aleksandra

    2017-02-14

    The natural extracellular matrix (ECM),thanks to its specific properties (e.g., collagenous lattice, a reservoir of growth factors, ECM-cell anchoring areas, an optimal pH and CO2 ),ensures an optimal microenvironment for homeostatic and regenerative cell development. In the context of regenerative medicine, ECM is a lair for residual and infiltrative cells. The aim of the clinical usage of cell-free ECM scaffolds is the enhancement of tissue regeneration with possible minimization of an adverse host reaction on allogeneic or xenogeneic biomaterial. Thus, the objective of decellularization is to obtain acellular grafts characterized by optimal biological properties, such as a lack of remaining cellular elements (e.g., cell membrane phospholipids and proteins, nucleic acids, mitochondria), lack of immunogenicity, lack of calcification promotion and lack of cytotoxicity (e.g., in unrinsed detergents). Furthermore, cell-free ECM scaffolds should present the optimal mechanical and structural properties that may ensure the biocompatibility of the graft. The maintenance of the ultrastructure composition of the ECM is one of the most important goals of decellularization. All physical, chemical, and biological methods proposed (used separately or in combination to extract cells from tissues/organs) are not 100% effective in cell removal and always cause a disruption of the ECM texture, as well as a probable loss of important structure components. Although cell-free ECM scaffolds are generally classified as medical devices, there are no widely accepted or legally defined criteria for quality control/evaluation methods of obtained matrices. Such criteria must be provided. Some of them have been proposed in this manuscript. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  9. The Matrix Cookbook

    DEFF Research Database (Denmark)

    Petersen, Kaare Brandt; Pedersen, Michael Syskind

    Matrix identities, relations and approximations. A desktop reference for quick overview of mathematics of matrices.......Matrix identities, relations and approximations. A desktop reference for quick overview of mathematics of matrices....

  10. Matrix with Prescribed Eigenvectors

    Science.gov (United States)

    Ahmad, Faiz

    2011-01-01

    It is a routine matter for undergraduates to find eigenvalues and eigenvectors of a given matrix. But the converse problem of finding a matrix with prescribed eigenvalues and eigenvectors is rarely discussed in elementary texts on linear algebra. This problem is related to the "spectral" decomposition of a matrix and has important technical…

  11. A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss.

    Science.gov (United States)

    Roumans, Nadia Jt; Vink, Roel G; Fazelzadeh, Parastoo; van Baak, Marleen A; Mariman, Edwin Cm

    2017-05-01

    Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietary intervention (DI). When people are following a diet, the volume of an adipocyte decreases by loss of triglycerides, which creates stress between the cell contents and the surrounding extracellular matrix (ECM). Previously, we observed that genetic variations in ECM genes are associated with an increased risk of weight regain.Objective: We investigated the relation between the expression of ECM genes during WL and a period of weight stabilization (WS) and the risk of weight regain.Design: In this randomized controlled trial, 61 healthy overweight or obese participants followed either a 5-wk very-low-calorie diet (VLCD; 500 kcal/d) or a 12-wk low-calorie diet (1250 kcal/d) (WL period) with a subsequent 4-wk WS period and a 9-mo follow-up. The WL and WS periods combined were considered the DI. Abdominal subcutaneous adipose tissue biopsy samples were collected for microarray analysis. Gene expression changes for a broad set of ECM-related genes were correlated with the weight-regain percentage (WR%).Results: A total of 26 of the 277 genes were significantly correlated with WR% during WL, WS, or the DI periods. Most correlations were observed in the VLCD group during the WS period. Four genes code for leukocyte-specific receptors. These and other genes belong to a group of 26 genes, among which the expression changes were highly correlated (r ≥ 0.7, P ≤ 0.001). This group could be divided into 3 subclusters linking to 2 biological processes-leukocyte integrin gene activity and ECM remodeling-and a link to insulin sensitivity was also apparent.Conclusions: Our present findings indicate the importance of adipose tissue leukocytes for the risk of weight regain. ECM modification also seems to be involved, and we observed a link to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT01559415. © 2017 American Society for Nutrition.

  12. 基质金属蛋白酶9在正常及病理妊娠中的作用%The Role of Matrix Metalloproteinase-9 in Normal and Pathologic Pregnancies

    Institute of Scientific and Technical Information of China (English)

    张晶晶; 侯海燕

    2016-01-01

    Matrix metalloproteinases (MMPs) are zinc proteinases that degrade compounds of the extracellular matrix (ECM), which are inhibited by their natural inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs). MMPs involve in many processes of tissue remolding through degrade ECM. A successful pregnancy depends on trophoblastic invasion of endometrial and implant embryo into uterus, through invasive vascular endothelial to make the vascular remodeling and meet the placental blood supply. MMP-9 plays an important role in trophoblast invasion, placental vascular remodeling and delivery through playing protease function and degrading ECM. The imbalance between MMP-9 and its inhibitor TIMP-1 relates to many pathological pregnancy processes, such as spontaneous abortion, preterm labour, hypertensive disorder complicating pregnancy and gestational diabetes mellitus. This article summarizes the role of MMP-9 in normal pregnancy and pathologic pregnancy. The current knowledge in the field of identified ECM proteases will be contributive to the innovative therapeutic intervention in pathological pregnancy processes.%基质金属蛋白酶(MMPs)是一种分解细胞外基质(ECM)组分的锌依赖性蛋白酶,其活性受金属蛋白酶组织抑制剂(TIMPs)的抑制.MMPs通过降解ECM参与众多组织重塑过程.妊娠过程的顺利进行有赖于滋养细胞侵入子宫内膜并将胚胎植入宫腔内,通过侵入血管内皮使血管重塑,满足胎盘血流供应.MMP-9通过发挥蛋白酶的功能降解ECM,在滋养细胞侵入、胎盘血管重塑以及分娩过程中发挥重要作用.MMP-9与其抑制剂TIMP-1调节失衡与早期自然流产、早产、妊娠期高血压疾病、妊娠期糖尿病等病理妊娠过程有关.综述MMP-9在正常及病理妊娠中的研究进展,明确ECM蛋白酶领域的最新知识将有利于为干预病理妊娠过程提供创新性思路.

  13. Roles of adjuvant and route of vaccination in antibody response and protection engendered by a synthetic matrix protein 2-based influenza A virus vaccine in the mouse

    Directory of Open Access Journals (Sweden)

    Cudic Mare

    2007-10-01

    Full Text Available Abstract Background The M2 ectodomain (M2e of influenza A virus (IAV strains that have circulated in humans during the past 90 years shows remarkably little structural diversity. Since M2e-specific antibodies (Abs are capable of restricting IAV replication in vivo but are present only at minimal concentration in human sera, efforts are being made to develop a M2e-specific vaccine. We are exploring a synthetic multiple antigenic peptide (MAP vaccine and here report on the role of adjuvants (cholera toxin and immunostimulatory oligodeoxynucleotide and route of immunization on Ab response and strength of protection. Results Independent of adjuvants and immunization route, on average 87% of the M2e-MAP-induced Abs were specific for M2e peptide and a variable fraction of these M2e(pep-specific Abs (average 15% cross-reacted with presumably native M2e expressed by M2-transfected cells. The titer of these cross-reactive M2e(pep-nat-specific Abs in sera of parenterally immunized mice displayed a sigmoidal relation to level of protection, with EC50 of ~20 μg Ab/ml serum, though experiments with passive M2e(pep-nat Abs indicated that serum Abs did not fully account for protection in parenterally vaccinated mice, particularly in upper airways. Intranasal vaccination engendered stronger protection and a higher proportion of G2a Abs than parenteral vaccination, and the strength of protection failed to correlate with M2e(pep-nat-specific serum Ab titers, suggesting a role of airway-associated immunity in protection of intranasally vaccinated mice. Intranasal administration of M2e-MAP without adjuvant engendered no response but coadministration with infectious IAV slightly enhanced the M2e(pep-nat Ab response and protection compared to vaccination with IAV or adjuvanted M2e-MAP alone. Conclusion M2e-MAP is an effective immunogen as ~15% of the total M2e-MAP-induced Ab response is of desired specificity. While M2e(pep-nat-specific serum Abs have an important

  14. Beta 1 integrin binding plays a role in the constant traction force generation in response to varying stiffness for cells grown on mature cardiac extracellular matrix.

    Science.gov (United States)

    Gershlak, Joshua R; Black, Lauren D

    2015-01-15

    We have previously reported a unique response of traction force generation for cells grown on mature cardiac ECM, where traction force was constant over a range of stiffnesses. In this study we sought to further investigate the role of the complex mixture of ECM on this response and assess the potential mechanism behind it. Using traction force microscopy, we measured cellular traction forces and stresses for mesenchymal stem cells (MSCs) grown on polyacrylamide gels at a range of stiffnesses (9, 25, or 48 kPa) containing either adult rat heart ECM, different singular ECM proteins including collagen I, fibronectin, and laminin, or ECM mimics comprised of varying amounts of collagen I, fibronectin, and laminin. We also measured the expression of integrins on these different substrates as well as probed for β1 integrin binding. There was no significant change in traction force generation for cells grown on the adult ECM, as previously reported, whereas cells grown on singular ECM protein substrates had increased traction force generation with an increase in substrate stiffness. Cells grown on ECM mimics containing collagen I, fibronectin and laminin were found to be reminiscent of the traction forces generated by cells grown on native ECM. Integrin expression generally increased with increasing stiffness except for the β1 integrin, potentially implicating it as playing a role in the response to adult cardiac ECM. We inhibited binding through the β1 integrin on cells grown on the adult ECM and found that the inhibition of β1 binding led to a return to the typical response of increasing traction force generation with increasing stiffness. Our data demonstrates that cells grown on the mature cardiac ECM are able to circumvent typical stiffness related cellular behaviors, likely through β1 integrin binding to the complex composition. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. The minimum amount of "matrix " needed for matrix-assisted pulsed laser deposition of biomolecules

    DEFF Research Database (Denmark)

    Tabetah, Marshall; Matei, Andreea; Constantinescu, Catalin;

    2014-01-01

    of coarse-grained molecular dynamics simulations are performed for a model lysozyme-water system, where the water serves the role of volatile "matrix" that drives the ejection of the biomolecules. The simulations reveal a remarkable ability of a small (5-10 wt %) amount of matrix to cause the ejection...

  16. The protective role of the -1306C>T functional polymorphism in matrix metalloproteinase-2 gene is associated with cervical cancer: implication of human papillomavirus infection.

    Science.gov (United States)

    Singh, Neha; Hussain, Showket; Sharma, Upma; Suri, Vanita; Nijhawan, Raje; Bharadwaj, Mausumi; Sobti, R C

    2016-04-01

    Cervical cancer is the major reproductive health problem among women caused by persistent infection of high-risk human papillomavirus (HR-HPV). Metalloproteinase-2 (MMP-2) is an endopeptidase highly expressed in cervical cancer; however, the genetic link between aberrant expression of MMP-2 and cervical carcinogenesis is not known. The genotypic distribution, expression pattern of MMP-2 and HPV infection, was analyzed in a total of 300 fresh surgically resected cervical tissue biopsies. The MMP-2 C1306T (rs243865) promoter polymorphism dominant model (CC v/s CT + CT + TT) revealed that the CC genotype had a 4.33-fold significant increased risk for development of cervical cancer (OR = 4.33; 95 % CI = 2.36-4.02, p = 0.0001) compared to those with variant genotypes (-1306 CT + TT). The C allele was associated with 3-fold significant increased risk (OR = 2.95; 95 % CI = 1.90-4.60, p = 0.0002) compared to T allele. Interestingly, a significant correlation was found between high expression of MMP-2 protein and CC genotype in cancer patients (p = 0.001) compared to normal controls (p = 0.012). Further analysis showed that the risk of cancer was extremely pronounced in HPV positive patients (OR = 9.33; 95 % CI = 2.88-30.20, p = 0.0001) compared to HPV negative ones, implicating the possible interaction between -1306CC genotype and HPV infection in increasing the cancer risk (p = 0.0001). The leads from the present study suggest the protective role of gene variant -1306C>T at the promoter region of the MMP-2 against HPV-mediated cervical cancer. These findings substantiate the functional role of MMP-2 C1306T polymorphism in a significant downregulation of MMP-2 protein in women with variant genotype (CT/TT) compared to the normal wild CC genotype.

  17. The requirement of matrix ATP for the import of precursor proteins into the mitochondrial matrix and intermembrane space

    NARCIS (Netherlands)

    Stuart, Rosemary A.; Gruhler, Albrecht; Klei, Ida van der; Guiard, Bernard; Koll, Hans; Neupert, Walter

    1994-01-01

    The role of ATP in the matrix for the import of precursor proteins into the various mitochondrial subcompartments was investigated by studying protein translocation at experimentally defined ATP levels. Proteins targeted to the matrix were neither imported or processed when matrix ATP was depleted.

  18. New Criteria for Judging Generalized Strictly Diagonally Dominant Matrix

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jin-song

    2015-01-01

    Generalized strictly diagonally dominant matrices play a wide and important role in computational mathematics, mathematical physics, theory of dynamical systems, etc. But it is difficult to judge a matrix is or not generalized strictly diagonally dominant matrix. In this paper, by using the properties of α-chain diagonally dominant matrix, we obtain new criteria for judging generalized strictly diagonally dominant matrix, which enlarge the identification range.

  19. Perturbative analysis of gauged matrix models

    Science.gov (United States)

    Dijkgraaf, Robbert; Gukov, Sergei; Kazakov, Vladimir A.; Vafa, Cumrun

    2003-08-01

    We analyze perturbative aspects of gauged matrix models, including those where classically the gauge symmetry is partially broken. Ghost fields play a crucial role in the Feynman rules for these vacua. We use this formalism to elucidate the fact that nonperturbative aspects of N=1 gauge theories can be computed systematically using perturbative techniques of matrix models, even if we do not possess an exact solution for the matrix model. As examples we show how the Seiberg-Witten solution for N=2 gauge theory, the Montonen-Olive modular invariance for N=1*, and the superpotential for the Leigh-Strassler deformation of N=4 can be systematically computed in perturbation theory of the matrix model or gauge theory (even though in some of these cases an exact answer can also be obtained by summing up planar diagrams of matrix models).

  20. Perturbative Analysis of Gauged Matrix Models

    CERN Document Server

    Dijkgraaf, R; Kazakov, V A; Vafa, C; Dijkgraaf, Robbert; Gukov, Sergei; Kazakov, Vladimir A.; Vafa, Cumrun

    2003-01-01

    We analyze perturbative aspects of gauged matrix models, including those where classically the gauge symmetry is partially broken. Ghost fields play a crucial role in the Feynman rules for these vacua. We use this formalism to elucidate the fact that non-perturbative aspects of N=1 gauge theories can be computed systematically using perturbative techniques of matrix models, even if we do not possess an exact solution for the matrix model. As examples we show how the Seiberg-Witten solution for N=2 gauge theory, the Montonen-Olive modular invariance for N=1*, and the superpotential for the Leigh-Strassler deformation of N=4 can be systematically computed in perturbation theory of the matrix model/gauge theory (even though in some of these cases the exact answer can also be obtained by summing up planar diagrams of matrix models).

  1. Extracellular matrix component signaling in cancer

    DEFF Research Database (Denmark)

    Multhaupt, Hinke A. B.; Leitinger, Birgit; Gullberg, Donald

    2016-01-01

    Cell responses to the extracellular matrix depend on specific signaling events. These are important from early development, through differentiation and tissue homeostasis, immune surveillance, and disease pathogenesis. Signaling not only regulates cell adhesion cytoskeletal organization and motil...... as well as matrix constitution and protein crosslinking. Here we summarize roles of the three major matrix receptor types, with emphasis on how they function in tumor progression. [on SciFinder(R)]......Cell responses to the extracellular matrix depend on specific signaling events. These are important from early development, through differentiation and tissue homeostasis, immune surveillance, and disease pathogenesis. Signaling not only regulates cell adhesion cytoskeletal organization...... and motility but also provides survival and proliferation cues. The major classes of cell surface receptors for matrix macromols. are the integrins, discoidin domain receptors, and transmembrane proteoglycans such as syndecans and CD44. Cells respond not only to specific ligands, such as collagen, fibronectin...

  2. Parallelism in matrix computations

    CERN Document Server

    Gallopoulos, Efstratios; Sameh, Ahmed H

    2016-01-01

    This book is primarily intended as a research monograph that could also be used in graduate courses for the design of parallel algorithms in matrix computations. It assumes general but not extensive knowledge of numerical linear algebra, parallel architectures, and parallel programming paradigms. The book consists of four parts: (I) Basics; (II) Dense and Special Matrix Computations; (III) Sparse Matrix Computations; and (IV) Matrix functions and characteristics. Part I deals with parallel programming paradigms and fundamental kernels, including reordering schemes for sparse matrices. Part II is devoted to dense matrix computations such as parallel algorithms for solving linear systems, linear least squares, the symmetric algebraic eigenvalue problem, and the singular-value decomposition. It also deals with the development of parallel algorithms for special linear systems such as banded ,Vandermonde ,Toeplitz ,and block Toeplitz systems. Part III addresses sparse matrix computations: (a) the development of pa...

  3. Phosphine in various matrixes

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Matrix-bound phosphine was determined in the Jiaozhou Bay coastal sediment, in prawn-pond bottom soil, in the eutrophic lake Wulongtan, in the sewage sludge and in paddy soil as well. Results showed that matrix-bound phosphine levels in freshwater and coastal sediment, as well as in sewage sludge, are significantly higher than that in paddy soil. The correlation between matrix bound phosphine concentrations and organic phosphorus contents in sediment samples is discussed.

  4. Formalization of Matrix Theory in HOL4

    Directory of Open Access Journals (Sweden)

    Zhiping Shi

    2014-08-01

    Full Text Available Matrix theory plays an important role in modeling linear systems in engineering and science. To model and analyze the intricate behavior of complex systems, it is imperative to formalize matrix theory in a metalogic setting. This paper presents the higher-order logic (HOL formalization of the vector space and matrix theory in the HOL4 theorem proving system. Formalized theories include formal definitions of real vectors and matrices, algebraic properties, and determinants, which are verified in HOL4. Two case studies, modeling and verifying composite two-port networks and state transfer equations, are presented to demonstrate the applicability and effectiveness of our work.

  5. Matrix metalloproteinases in exercise and obesity

    OpenAIRE

    Jaoude J; Koh Y

    2016-01-01

    Jonathan Jaoude,1 Yunsuk Koh2 1Department of Biology, 2Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA Abstract: Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endoproteinases that have the ability to break down extracellular matrix. The large range of MMPs’ functions widens their spectrum of potential role as activators or inhibitors in tissue remodeling, cardiovascular diseases, and obesity. In particular, MMP-1, -2, and ...

  6. Matrix metalloproteinases in lung biology

    Directory of Open Access Journals (Sweden)

    Parks William C

    2000-12-01

    Full Text Available Abstract Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease.

  7. Patience of matrix games

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Ibsen-Jensen, Rasmus; Podolskii, Vladimir V.;

    2013-01-01

    For matrix games we study how small nonzero probability must be used in optimal strategies. We show that for image win–lose–draw games (i.e. image matrix games) nonzero probabilities smaller than image are never needed. We also construct an explicit image win–lose game such that the unique optimal...

  8. Patience of matrix games

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Ibsen-Jensen, Rasmus; Podolskii, Vladimir V.

    2013-01-01

    For matrix games we study how small nonzero probability must be used in optimal strategies. We show that for image win–lose–draw games (i.e. image matrix games) nonzero probabilities smaller than image are never needed. We also construct an explicit image win–lose game such that the unique optimal...

  9. Transfer function matrix

    Science.gov (United States)

    Seraji, H.

    1987-01-01

    Given a multivariable system, it is proved that the numerator matrix N(s) of the transfer function evaluated at any system pole either has unity rank or is a null matrix. It is also shown that N(s) evaluated at any transmission zero of the system has rank deficiency. Examples are given for illustration.

  10. Role of microRNA 1207-5P and its host gene, the long non-coding RNA Pvt1, as mediators of extracellular matrix accumulation in the kidney: implications for diabetic nephropathy.

    Science.gov (United States)

    Alvarez, M Lucrecia; Khosroheidari, Mahdieh; Eddy, Elena; Kiefer, Jeff

    2013-01-01

    Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage renal disease in the Western World. One of the major characteristics of this disease is the excessive accumulation of extracellular matrix (ECM) in the kidney glomeruli. While both environmental and genetic determinants are recognized for their role in the development of diabetic nephropathy, epigenetic factors, such as DNA methylation, long non-coding RNAs, and microRNAs, have also recently been found to underlie some of the biological mechanisms, including ECM accumulation, leading to the disease. We previously found that a long non-coding RNA, the plasmacytoma variant translocation 1 (PVT1), increases plasminogen activator inhibitor 1 (PAI-1) and transforming growth factor beta 1 (TGF-β1) in mesangial cells, the two main contributors to ECM accumulation in the glomeruli under hyperglycemic conditions, as well as fibronectin 1 (FN1), a major ECM component. Here, we report that miR-1207-5p, a PVT1-derived microRNA, is abundantly expressed in kidney cells, and is upregulated by glucose and TGF-β1. We also found that like PVT1, miR-1207-5p increases expression of TGF-β1, PAI-1, and FN1 but in a manner that is independent of its host gene. In addition, regulation of miR-1207-5p expression by glucose and TGFβ1 is independent of PVT1. These results provide evidence supporting important roles for miR-1207-5p and its host gene in the complex pathogenesis of diabetic nephropathy.

  11. Improved Matrix Uncertainty Selector

    CERN Document Server

    Rosenbaum, Mathieu

    2011-01-01

    We consider the regression model with observation error in the design: y=X\\theta* + e, Z=X+N. Here the random vector y in R^n and the random n*p matrix Z are observed, the n*p matrix X is unknown, N is an n*p random noise matrix, e in R^n is a random noise vector, and \\theta* is a vector of unknown parameters to be estimated. We consider the setting where the dimension p can be much larger than the sample size n and \\theta* is sparse. Because of the presence of the noise matrix N, the commonly used Lasso and Dantzig selector are unstable. An alternative procedure called the Matrix Uncertainty (MU) selector has been proposed in Rosenbaum and Tsybakov (2010) in order to account for the noise. The properties of the MU selector have been studied in Rosenbaum and Tsybakov (2010) for sparse \\theta* under the assumption that the noise matrix N is deterministic and its values are small. In this paper, we propose a modification of the MU selector when N is a random matrix with zero-mean entries having the variances th...

  12. Elementary matrix theory

    CERN Document Server

    Eves, Howard

    1980-01-01

    The usefulness of matrix theory as a tool in disciplines ranging from quantum mechanics to psychometrics is widely recognized, and courses in matrix theory are increasingly a standard part of the undergraduate curriculum.This outstanding text offers an unusual introduction to matrix theory at the undergraduate level. Unlike most texts dealing with the topic, which tend to remain on an abstract level, Dr. Eves' book employs a concrete elementary approach, avoiding abstraction until the final chapter. This practical method renders the text especially accessible to students of physics, engineeri

  13. Rheocasting Al matrix composites

    Energy Technology Data Exchange (ETDEWEB)

    Girot, F.A.; Albingre, L.; Quenisset, J.M.; Naslain, R.

    1987-11-01

    A development status account is given for the rheocasting method of Al-alloy matrix/SiC-whisker composites, which involves the incorporation and homogeneous distribution of 8-15 vol pct of whiskers through the stirring of the semisolid matrix melt while retaining sufficient fluidity for casting. Both 1-, 3-, and 6-mm fibers of Nicalon SiC and and SiC whisker reinforcements have been experimentally investigated, with attention to the characterization of the resulting microstructures and the effects of fiber-matrix interactions. A thin silica layer is found at the whisker surface. 7 references.

  14. Mueller matrix differential decomposition.

    Science.gov (United States)

    Ortega-Quijano, Noé; Arce-Diego, José Luis

    2011-05-15

    We present a Mueller matrix decomposition based on the differential formulation of the Mueller calculus. The differential Mueller matrix is obtained from the macroscopic matrix through an eigenanalysis. It is subsequently resolved into the complete set of 16 differential matrices that correspond to the basic types of optical behavior for depolarizing anisotropic media. The method is successfully applied to the polarimetric analysis of several samples. The differential parameters enable one to perform an exhaustive characterization of anisotropy and depolarization. This decomposition is particularly appropriate for studying media in which several polarization effects take place simultaneously. © 2011 Optical Society of America

  15. Ubiquitination of specific mitochondrial matrix proteins.

    Science.gov (United States)

    Lehmann, Gilad; Ziv, Tamar; Braten, Ori; Admon, Arie; Udasin, Ronald G; Ciechanover, Aaron

    2016-06-17

    Several protein quality control systems in bacteria and/or mitochondrial matrix from lower eukaryotes are absent in higher eukaryotes. These are transfer-messenger RNA (tmRNA), The N-end rule ATP-dependent protease ClpAP, and two more ATP-dependent proteases, HslUV and ClpXP (in yeast). The lost proteases resemble the 26S proteasome and the role of tmRNA and the N-end rule in eukaryotic cytosol is performed by the ubiquitin proteasome system (UPS). Therefore, we hypothesized that the UPS might have substituted these systems - at least partially - in the mitochondrial matrix of higher eukaryotes. Using three independent experimental approaches, we demonstrated the presence of ubiquitinated proteins in the matrix of isolated yeast mitochondria. First, we show that isolated mitochondria contain ubiquitin (Ub) conjugates, which remained intact after trypsin digestion. Second, we demonstrate that the mitochondrial soluble fraction contains Ub-conjugates, several of which were identified by mass spectrometry and are localized to the matrix. Third, using immunoaffinity enrichment by specific antibodies recognizing digested ubiquitinated peptides, we identified a group of Ub-modified matrix proteins. The modification was further substantiated by separation on SDS-PAGE and immunoblots. Last, we attempted to identify the ubiquitin ligase(s) involved, and identified Dma1p as a trypsin-resistant protein in our mitochondrial preparations. Taken together, these data suggest a yet undefined role for the UPS in regulation of the mitochondrial matrix proteins.

  16. Pesticide-Exposure Matrix

    Science.gov (United States)

    The "Pesticide-exposure Matrix" was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years.

  17. Matrix theory of gravitation

    CERN Document Server

    Koehler, Wolfgang

    2011-01-01

    A new classical theory of gravitation within the framework of general relativity is presented. It is based on a matrix formulation of four-dimensional Riemann-spaces and uses no artificial fields or adjustable parameters. The geometrical stress-energy tensor is derived from a matrix-trace Lagrangian, which is not equivalent to the curvature scalar R. To enable a direct comparison with the Einstein-theory a tetrad formalism is utilized, which shows similarities to teleparallel gravitation theories, but uses complex tetrads. Matrix theory might solve a 27-year-old, fundamental problem of those theories (sec. 4.1). For the standard test cases (PPN scheme, Schwarzschild-solution) no differences to the Einstein-theory are found. However, the matrix theory exhibits novel, interesting vacuum solutions.

  18. Matrix comparison, Part 2

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Borlund, Pia

    2007-01-01

    The present two-part article introduces matrix comparison as a formal means for evaluation purposes in informetric studies such as cocitation analysis. In the first part, the motivation behind introducing matrix comparison to informetric studies, as well as two important issues influencing...... such comparisons, matrix generation, and the composition of proximity measures, are introduced and discussed. In this second part, the authors introduce and thoroughly demonstrate two related matrix comparison techniques the Mantel test and Procrustes analysis, respectively. These techniques can compare...... important. Alternatively, or as a supplement, Procrustes analysis compares the actual ordination results without investigating the underlying proximity measures, by matching two configurations of the same objects in a multidimensional space. An advantage of the Procrustes analysis though, is the graphical...

  19. The Matrix Organization Revisited

    DEFF Research Database (Denmark)

    Gattiker, Urs E.; Ulhøi, John Parm

    1999-01-01

    This paper gives a short overview of matrix structure and technology management. It outlines some of the characteristics and also points out that many organizations may actualy be hybrids (i.e. mix several ways of organizing to allocate resorces effectively).......This paper gives a short overview of matrix structure and technology management. It outlines some of the characteristics and also points out that many organizations may actualy be hybrids (i.e. mix several ways of organizing to allocate resorces effectively)....

  20. Optical Coherency Matrix Tomography

    Science.gov (United States)

    2015-10-19

    optics has been studied theoretically11, but has not been demonstrated experimentally heretofore. Even in the simplest case of two binary DoFs6 (e.g...coherency matrix G spanning these DoFs. This optical coherency matrix has not been measured in its entirety to date—even in the simplest case of two...dense coding, etc. CREOL, The College of Optics & Photonics, University of Central Florida, Orlando , Florida 32816, USA. Correspondence and requests

  1. Matrix fractional systems

    Science.gov (United States)

    Tenreiro Machado, J. A.

    2015-08-01

    This paper addresses the matrix representation of dynamical systems in the perspective of fractional calculus. Fractional elements and fractional systems are interpreted under the light of the classical Cole-Cole, Davidson-Cole, and Havriliak-Negami heuristic models. Numerical simulations for an electrical circuit enlighten the results for matrix based models and high fractional orders. The conclusions clarify the distinction between fractional elements and fractional systems.

  2. Hacking the Matrix.

    Science.gov (United States)

    Czerwinski, Michael; Spence, Jason R

    2017-01-05

    Recently in Nature, Gjorevski et al. (2016) describe a fully defined synthetic hydrogel that mimics the extracellular matrix to support in vitro growth of intestinal stem cells and organoids. The hydrogel allows exquisite control over the chemical and physical in vitro niche and enables identification of regulatory properties of the matrix. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The Matrix Organization Revisited

    DEFF Research Database (Denmark)

    Gattiker, Urs E.; Ulhøi, John Parm

    1999-01-01

    This paper gives a short overview of matrix structure and technology management. It outlines some of the characteristics and also points out that many organizations may actualy be hybrids (i.e. mix several ways of organizing to allocate resorces effectively).......This paper gives a short overview of matrix structure and technology management. It outlines some of the characteristics and also points out that many organizations may actualy be hybrids (i.e. mix several ways of organizing to allocate resorces effectively)....

  4. Ubiquitination of specific mitochondrial matrix proteins

    Energy Technology Data Exchange (ETDEWEB)

    Lehmann, Gilad [The Janet and David Polak Tumor and Vascular Biology Research Center and the Technion Integrated Cancer Center (TICC), The Rappaport Faculty of Medicine and Research Institute, Haifa, 31096 (Israel); Ziv, Tamar [The Smoler Proteomics Center, Faculty of Biology – Technion-Israel Institute of Technology, Haifa, 32000 (Israel); Braten, Ori [The Janet and David Polak Tumor and Vascular Biology Research Center and the Technion Integrated Cancer Center (TICC), The Rappaport Faculty of Medicine and Research Institute, Haifa, 31096 (Israel); Admon, Arie [The Smoler Proteomics Center, Faculty of Biology – Technion-Israel Institute of Technology, Haifa, 32000 (Israel); Udasin, Ronald G. [The Janet and David Polak Tumor and Vascular Biology Research Center and the Technion Integrated Cancer Center (TICC), The Rappaport Faculty of Medicine and Research Institute, Haifa, 31096 (Israel); Ciechanover, Aaron, E-mail: aaroncie@tx.technion.ac.il [The Janet and David Polak Tumor and Vascular Biology Research Center and the Technion Integrated Cancer Center (TICC), The Rappaport Faculty of Medicine and Research Institute, Haifa, 31096 (Israel)

    2016-06-17

    Several protein quality control systems in bacteria and/or mitochondrial matrix from lower eukaryotes are absent in higher eukaryotes. These are transfer-messenger RNA (tmRNA), The N-end rule ATP-dependent protease ClpAP, and two more ATP-dependent proteases, HslUV and ClpXP (in yeast). The lost proteases resemble the 26S proteasome and the role of tmRNA and the N-end rule in eukaryotic cytosol is performed by the ubiquitin proteasome system (UPS). Therefore, we hypothesized that the UPS might have substituted these systems – at least partially – in the mitochondrial matrix of higher eukaryotes. Using three independent experimental approaches, we demonstrated the presence of ubiquitinated proteins in the matrix of isolated yeast mitochondria. First, we show that isolated mitochondria contain ubiquitin (Ub) conjugates, which remained intact after trypsin digestion. Second, we demonstrate that the mitochondrial soluble fraction contains Ub-conjugates, several of which were identified by mass spectrometry and are localized to the matrix. Third, using immunoaffinity enrichment by specific antibodies recognizing digested ubiquitinated peptides, we identified a group of Ub-modified matrix proteins. The modification was further substantiated by separation on SDS-PAGE and immunoblots. Last, we attempted to identify the ubiquitin ligase(s) involved, and identified Dma1p as a trypsin-resistant protein in our mitochondrial preparations. Taken together, these data suggest a yet undefined role for the UPS in regulation of the mitochondrial matrix proteins. -- Highlights: •Mitochondrial matrix contains ubiquitinated proteins. •Ubiquitination occurs most probably in the matrix. •Dma1p is a ubiquitin ligase present in mitochondrial preparations.

  5. Microarray Analysis Reveals Increased Expression of Matrix Metalloproteases and Cytokines of Interleukin-20 Subfamily in the Kidneys of Neonate Rats Underwent Unilateral Ureteral Obstruction: A Potential Role of IL-24 in the Regulation of Inflammation and Tissue Remodeling.

    Science.gov (United States)

    Pap, Domonkos; Sziksz, Erna; Kiss, Zoltán; Rokonay, Réka; Veres-Székely, Apor; Lippai, Rita; Takács, István Márton; Kis, Éva; Fekete, Andrea; Reusz, György; Vannay, Adam; Szabó, Attila J

    2017-01-01

    Congenital obstructive nephropathy (CON) is the main cause of pediatric chronic kidney diseases leading to renal fibrosis. High morbidity and limited treatment opportunities of CON urge the better understanding of the underlying molecular mechanisms. To identify the differentially expressed genes, microarray analysis was performed on the kidney samples of neonatal rats underwent unilateral ureteral obstruction (UUO). Microarray results were then validated by real-time RT-PCR and bioinformatics analysis was carried out to identify the relevant genes, functional groups and pathways involved in the pathomechanism of CON. Renal expression of matrix metalloproteinase (MMP)-12 and interleukin (IL)-24 were evaluated by real-time RT-PCR, flow cytometry and immunohistochemical analysis. Effect of the main profibrotic factors on the expression of MMP-12 and IL-24 was investigated on HK-2 and HEK-293 cell lines. Finally, the effect of IL-24 treatment on the expression of pro-inflammatory cytokines and MMPs were tested in vitro. Microarray analysis revealed 880 transcripts showing >2.0-fold change following UUO, enriched mainly in immune response related processes. The most up-regulated genes were MMPs and members of IL-20 cytokine subfamily, including MMP-3, MMP-7, MMP-12, IL-19 and IL-24. We found that while TGF-β treatment inhibits the expression of MMP-12 and IL-24, H2O2 or PDGF-B treatment induce the epithelial expression of MMP-12. We demonstrated that IL-24 treatment decreases the expression of IL-6 and MMP-3 in the renal epithelial cells. This study provides an extensive view of UUO induced changes in the gene expression profile of the developing kidney and describes novel molecules, which may play significant role in the pathomechanism of CON. © 2017 The Author(s)Published by S. Karger AG, Basel.

  6. Highly efficient direct aerobic oxidative esterification of cinnamyl alcohol with alkyl alcohols catalysed by gold nanoparticles incarcerated in a nanoporous polymer matrix: a tool for investigating the role of the polymer host.

    Science.gov (United States)

    Buonerba, Antonio; Noschese, Annarita; Grassi, Alfonso

    2014-04-25

    The selective aerobic oxidation of cinnamyl alcohol to cinnamaldehyde, as well as direct oxidative esterification of this alcohol with primary and secondary aliphatic alcohols, were achieved with high chemoselectivity by using gold nanoparticles supported in a nanoporous semicrystalline multi-block copolymer matrix, which consisted of syndiotactic polystyrene-co-cis-1,4-polybutadiene. The cascade reaction that leads to the alkyl cinnamates occurs through two oxidation steps: the selective oxidation of cinnamyl alcohol to cinnamaldehyde, followed by oxidation of the hemiacetal that results from the base-catalysed reaction of cinnamaldehyde with an aliphatic alcohol. The rate constants for the two steps were evaluated in the temperature range 10-45 °C. The cinnamyl alcohol oxidation is faster than the oxidative esterification of cinnamaldehyde with methanol, ethanol, 2-propanol, 1-butanol, 1-hexanol or 1-octanol. The rate constants of the latter reaction are pseudo-zero order with respect to the aliphatic alcohol and decrease as the bulkiness of the alcohol is increased. The activation energy (Ea) for the two oxidation steps was calculated for esterification of cinnamyl alcohol with 1-butanol (Ea = 57.8±11.5 and 62.7±16.7 kJ mol(-1) for the first and second step, respectively). The oxidative esterification of cinnamyl alcohol with 2-phenylethanol follows pseudo-first-order kinetics with respect to 2-phenylethanol and is faster than observed for other alcohols because of fast diffusion of the aromatic alcohol in the crystalline phase of the support. The kinetic investigation allowed us to assess the role of the polymer support in the determination of both high activity and selectivity in the title reaction.

  7. Implementation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry in Routine Clinical Laboratories Improves Identification of Coagulase-Negative Staphylococci and Reveals the Pathogenic Role of Staphylococcus lugdunensis.

    Science.gov (United States)

    Argemi, Xavier; Riegel, Philippe; Lavigne, Thierry; Lefebvre, Nicolas; Grandpré, Nicolas; Hansmann, Yves; Jaulhac, Benoit; Prévost, Gilles; Schramm, Frédéric

    2015-07-01

    The use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for staphylococcal identification is now considered routine in laboratories compared with the conventional phenotypical methods previously used. We verified its microbiological relevance for identifying the main species of coagulase-negative staphylococci (CoNS) by randomly selecting 50 isolates. From 1 January 2007 to 31 August 2008, 12,479 staphylococci were isolated with phenotypic methods, of which 4,594 were identified as Staphylococcus aureus and 7,885 were coagulase negative staphylococci. Using MALDI-TOF MS from 1 January 2011 to 31 August 2012, 14,913 staphylococci were identified, with 5,066 as S. aureus and 9,847 as CoNS. MALDI-TOF MS allowed the identification of approximately 85% of the CoNS strains, whereas only 14% of the CoNS strains were identified to the species level with phenotypic methods because they were often considered contaminants. Furthermore, the use of MALDI-TOF MS revealed the occurrence of recently characterized Staphylococcus species, such as S. pettenkoferi, S. condimenti, and S. piscifermentans. Microbiological relevance analysis further revealed that some species displayed a high rate of microbiological significance, i.e., 40% of the S. lugdunensis strains included in the analysis were associated with infection risk. This retrospective microbiological study confirms the role of MALDI-TOF MS in clinical settings for the identification of staphylococci with clinical consequences. The species distribution reveals the occurrence of the recently identified species S. pettenkoferi and putative virulent species, including S. lugdunensis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Solution of the Lyapunov matrix equation for a system with a time-dependent stiffness matrix

    DEFF Research Database (Denmark)

    Pommer, Christian; Kliem, Wolfhard

    2004-01-01

    The stability of the linearized model of a rotor system with non-symmetric strain and axial loads is investigated. Since we are using a fixed reference system, the differential equations have the advantage to be free of Coriolis and centrifugal forces. A disadvantage is nevertheless the occurrenc...... of time-dependent periodic terms in the stiffness matrix. However, by solving the Lyapunov matrix equation we can formulate several stability conditions for the rotor system. Hereby the positive definiteness of a certain averaged stiffness matrix plays a crucial role....

  9. Extracellular matrix as a driver for lung regeneration.

    Science.gov (United States)

    Balestrini, Jenna L; Niklason, Laura E

    2015-03-01

    Extracellular matrix has manifold roles in tissue mechanics, guidance of cellular behavior, developmental biology, and regenerative medicine. Over the past several decades, various pre-clinical and clinical studies have shown that many connective tissues may be replaced and/or regenerated using suitable extracellular matrix scaffolds. More recently, decellularization of lung tissue has shown that gentle removal of cells can leave behind a "footprint" within the matrix that may guide cellular adhesion, differentiation and homing following cellular repopulation. Fundamental issues like understanding matrix composition and micro-mechanics remain difficult to tackle, largely because of a lack of available assays and tools for systematically characterizing intact matrix from tissues and organs. This review will critically examine the role of engineered and native extracellular matrix in tissue and lung regeneration, and provide insights into directions for future research and translation.

  10. Novel entries in a fungal biofilm matrix encyclopedia.

    Science.gov (United States)

    Zarnowski, Robert; Westler, William M; Lacmbouh, Ghislain Ade; Marita, Jane M; Bothe, Jameson R; Bernhardt, Jörg; Lounes-Hadj Sahraoui, Anissa; Fontaine, Joël; Sanchez, Hiram; Hatfield, Ronald D; Ntambi, James M; Nett, Jeniel E; Mitchell, Aaron P; Andes, David R

    2014-08-05

    Virulence of Candida is linked with its ability to form biofilms. Once established, biofilm infections are nearly impossible to eradicate. Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. We further explore the function of matrix components, including the impact on drug resistance. We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. Three individual polysaccharides were identified and were suggested to interact physically. Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). Functional matrix proteomic analysis revealed 458 distinct activities. The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed

  11. Expression and biological role of Matrix metalloproteinases 16 in esophagus squamous cell carcinoma%基质金属蛋白酶16在食管鳞癌中的表达及其生物学功能

    Institute of Scientific and Technical Information of China (English)

    吴秋丽; 林碧芸; 吴梦杰; 刘明

    2014-01-01

    Background and purpose:Esophageal carcinoma is one of main malignancies with rapid course and a poor prognosis in China. The reasons of poor overall survival are the invasion and metastasis of the tumor. Matrix metalloproteinase (MMPs) play essential roles in promoting tumor invasion and metastasis. In this study, we aimed to investigate the expression and functional signiifcance of matrix metalloproteinase 16(MMP-16) in esophageal squamous cell carcinoma (ESCC). We expect to ifnd a lead molecule for the beneift of early detecting tumor and the development of novel treatment of ESCC. Methods:The expression levels of MMP-16 protein and mRNA in human ESCC and the matched normal tissues were determined by immunohistochemistry, Western blot and Real-Time PCR (RT-PCR). The stable Ec109 cell line with MMP-16 knockdown and negative controls were established by RNA interference technology. The cell migration, invasion, proliferation and cell apoptosis of MMP-16 in stable interfered Ec109 cell line was examined by cell counting, scratch test, Transwell test and lfow cytometry assays. The data were analyzed by t test. Results:MMP-16 protein was downregulated in cancerous group compared with the matched normal tissue and correlated with the clinical features of histological differentiation (P0.05). Conclusion: MMP-16 is downregulated in human ESCC tissues. The cell migration and invasion is promoted by interference of MMP-16 in Ec109, while the cell apoptosis is inhibited. MMP-16 may be considered as a target gene for therapy of ESCC.%背景与目的:中国是世界上食管癌的高发区,食管癌可发生早期淋巴结及血行转移,这使其表现出临床进展迅速并且预后很差的特性。研究显示癌组织侵袭和转移与其诱导产生的蛋白酶降解细胞外基质、基底膜能力密切相关,因此基质金属蛋白酶(matrix metalloproteinase,MMP)在肿瘤的发生、发展、转移过程中发挥重要作用,本

  12. Matrix Information Geometry

    CERN Document Server

    Bhatia, Rajendra

    2013-01-01

    This book is an outcome of the Indo-French Workshop on Matrix Information Geometries (MIG): Applications in Sensor and Cognitive Systems Engineering, which was held in Ecole Polytechnique and Thales Research and Technology Center, Palaiseau, France, in February 23-25, 2011. The workshop was generously funded by the Indo-French Centre for the Promotion of Advanced Research (IFCPAR).  During the event, 22 renowned invited french or indian speakers gave lectures on their areas of expertise within the field of matrix analysis or processing. From these talks, a total of 17 original contribution or state-of-the-art chapters have been assembled in this volume. All articles were thoroughly peer-reviewed and improved, according to the suggestions of the international referees. The 17 contributions presented  are organized in three parts: (1) State-of-the-art surveys & original matrix theory work, (2) Advanced matrix theory for radar processing, and (3) Matrix-based signal processing applications.  

  13. Notes on Matrix Strings and Fivebranes

    Science.gov (United States)

    Dijkgraaf, R.; Verlinde, E.; Verlinde, H.

    In these notes we review aspects of the matrix formulation of M-theory compactifications. In particular we highlight the appearance of IIA strings and their interactions, and explain the unifying role of the M-theory five-brane for describing the spectrum of the T5 compactification and its duality symmetries.

  14. Notes on matrix strings and fivebranes

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, R.; Verlinde, H. [University of Amsterdam, Amsterdam (Netherlands); Verlinde, E. [CERN, Geneva (Switzerland)

    1998-07-01

    In these notes we review aspects of the matrix formulation of M-theory compactifications. In particular we highlight the appearance of IIA string and their interactions, and explain the unifying role of the M-theory five-brane for describing the spectrum of the T{sup 5} compactification and its duality symmetries. (Author). 41 refs., 3 figs.

  15. Extracellular matrix and tissue engineering applications

    NARCIS (Netherlands)

    Fernandes, Hugo; Moroni, Lorenzo; Blitterswijk, van Clemens; Boer, de Jan

    2009-01-01

    The extracellular matrix is a key component during regeneration and maintenance of tissues and organs, and it therefore plays a critical role in successful tissue engineering as well. Tissue engineers should recognise that engineering technology can be deduced from natural repair processes. Due to a

  16. The extracellular matrix of plants: Molecular, cellular and developmental biology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    A symposium entitled ``The Extracellular Matrix of Plants: Molecular, Cellular and Developmental Biology was held in Tamarron, Colorado, March 15--21, 1996. The following topics were explored in addresses by 43 speakers: structure and biochemistry of cell walls; biochemistry, molecular biology and biosynthesis of lignin; secretory pathway and synthesis of glycoproteins; biosynthesis of matrix polysaccharides, callose and cellulose; role of the extracellular matrix in plant growth and development; plant cell walls in symbiosis and pathogenesis.

  17. Ceramic Matrix Composites .

    Directory of Open Access Journals (Sweden)

    J. Mukerji

    1993-10-01

    Full Text Available The present state of the knowledge of ceramic-matrix composites have been reviewed. The fracture toughness of present structural ceramics are not enough to permit design of high performance machines with ceramic parts. They also fail by catastrophic brittle fracture. It is generally believed that further improvement of fracture toughness is only possible by making composites of ceramics with ceramic fibre, particulate or platelets. Only ceramic-matrix composites capable of working above 1000 degree centigrade has been dealt with keeping reinforced plastics and metal-reinforced ceramics outside the purview. The author has discussed the basic mechanisms of toughening and fabrication of composites and the difficulties involved. Properties of available fibres and whiskers have been given. The best results obtained so far have been indicated. The limitations of improvement in properties of ceramic-matrix composites have been discussed.

  18. Matrix interdiction problem

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Feng [Los Alamos National Laboratory; Kasiviswanathan, Shiva [Los Alamos National Laboratory

    2010-01-01

    In the matrix interdiction problem, a real-valued matrix and an integer k is given. The objective is to remove k columns such that the sum over all rows of the maximum entry in each row is minimized. This combinatorial problem is closely related to bipartite network interdiction problem which can be applied to prioritize the border checkpoints in order to minimize the probability that an adversary can successfully cross the border. After introducing the matrix interdiction problem, we will prove the problem is NP-hard, and even NP-hard to approximate with an additive n{gamma} factor for a fixed constant {gamma}. We also present an algorithm for this problem that achieves a factor of (n-k) mUltiplicative approximation ratio.

  19. Extracellular matrix structure.

    Science.gov (United States)

    Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K

    2016-02-01

    Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented.

  20. Finite Temperature Matrix Theory

    CERN Document Server

    Meana, M L; Peñalba, J P; Meana, Marco Laucelli; Peñalba, Jesús Puente

    1998-01-01

    We present the way the Lorentz invariant canonical partition function for Matrix Theory as a light-cone formulation of M-theory can be computed. We explicitly show how when the eleventh dimension is decompactified, the N=1 eleven dimensional SUGRA partition function appears. From this particular analysis we also clarify the question about the discernibility problem when making statistics with supergravitons (the N! problem) in Matrix black hole configurations. We also provide a high temperature expansion which captures some structure of the canonical partition function when interactions amongst D-particles are on. The connection with the semi-classical computations thermalizing the open superstrings attached to a D-particle is also clarified through a Born-Oppenheimer approximation. Some ideas about how Matrix Theory would describe the complementary degrees of freedom of the massless content of eleven dimensional SUGRA are also discussed.

  1. Matrix proteoglycans as effector molecules for epithelial cell function

    Directory of Open Access Journals (Sweden)

    C. W. Frevert

    2005-12-01

    Full Text Available Matrix proteoglycans are complex molecules composed of a core protein and glycosaminoglycan side chains. Once thought to be the molecular glue providing structural support and imparting biomechanical properties to lung tissue, it is now apparent that proteoglycans are important biological modifiers which regulate processes such as lung development, homeostasis, inflammation and wound healing. The diverse roles of proteoglycans in the extracellular matrix suggest that these molecules play a critical role in normal and diseased lungs. This short article will discuss the role extracellular matrix proteoglycans play in regulating epithelial cell function in the lungs.

  2. Genetic Relationships Between Chondrules, Rims and Matrix

    Science.gov (United States)

    Huss, G. R.; Alexander, C. M. OD.; Palme, H.; Bland, P. A.; Wasson, J. T.

    2004-01-01

    The most primitive chondrites are composed of chondrules and chondrule fragments, various types of inclusions, discrete mineral grains, metal, sulfides, and fine-grained materials that occur as interchondrule matrix and as chondrule/inclusion rims. Understanding how these components are related is essential for understanding how chondrites and their constituents formed and were processed in the solar nebula. For example, were the first generations of chondrules formed by melting of matrix or matrix precursors? Did chondrule formation result in appreciable transfer of chondrule material into the matrix? Here, we consider three types of data: 1) compositional data for bulk chondrites and matrix, 2) mineralogical and textural information, and 3) the abundances and characteristics of presolar materials that reside in the matrix and rims. We use these data to evaluate the roles of evaporation and condensation, chondrule formation, mixing of different nebular components, and secondary processing both in the nebula and on the parent bodies. Our goal is to identify the things that are reasonably well established and to point out the areas that need additional work.

  3. Matrixed business support comparison study.

    Energy Technology Data Exchange (ETDEWEB)

    Parsons, Josh D.

    2004-11-01

    The Matrixed Business Support Comparison Study reviewed the current matrixed Chief Financial Officer (CFO) division staff models at Sandia National Laboratories. There were two primary drivers of this analysis: (1) the increasing number of financial staff matrixed to mission customers and (2) the desire to further understand the matrix process and the opportunities and challenges it creates.

  4. IIB Matrix Model

    CERN Document Server

    Aoki, H; Kawai, H; Kitazawa, Y; Tada, T; Tsuchiya, A

    1999-01-01

    We review our proposal for a constructive definition of superstring, type IIB matrix model. The IIB matrix model is a manifestly covariant model for space-time and matter which possesses N=2 supersymmetry in ten dimensions. We refine our arguments to reproduce string perturbation theory based on the loop equations. We emphasize that the space-time is dynamically determined from the eigenvalue distributions of the matrices. We also explain how matter, gauge fields and gravitation appear as fluctuations around dynamically determined space-time.

  5. Little IIB Matrix Model

    CERN Document Server

    Kitazawa, Y; Saito, O; Kitazawa, Yoshihisa; Mizoguchi, Shun'ya; Saito, Osamu

    2006-01-01

    We study the zero-dimensional reduced model of D=6 pure super Yang-Mills theory and argue that the large N limit describes the (2,0) Little String Theory. The one-loop effective action shows that the force exerted between two diagonal blocks of matrices behaves as 1/r^4, implying a six-dimensional spacetime. We also observe that it is due to non-gravitational interactions. We construct wave functions and vertex operators which realize the D=6, (2,0) tensor representation. We also comment on other "little" analogues of the IIB matrix model and Matrix Theory with less supercharges.

  6. Rheocasting Al Matrix Composites

    Science.gov (United States)

    Girot, F. A.; Albingre, L.; Quenisset, J. M.; Naslain, R.

    1987-11-01

    Aluminum alloy matrix composites reinforced by SiC short fibers (or whiskers) can be prepared by rheocasting, a process which consists of the incorporation and homogeneous distribution of the reinforcement by stirring within a semi-solid alloy. Using this technique, composites containing fiber volume fractions in the range of 8-15%, have been obtained for various fibers lengths (i.e., 1 mm, 3 mm and 6 mm for SiC fibers). This paper attempts to delineate the best compocasting conditions for aluminum matrix composites reinforced by short SiC (e.g Nicalon) or SiC whiskers (e.g., Tokamax) and characterize the resulting microstructures.

  7. Reduced Google matrix

    CERN Document Server

    Frahm, K M

    2016-01-01

    Using parallels with the quantum scattering theory, developed for processes in nuclear and mesoscopic physics and quantum chaos, we construct a reduced Google matrix $G_R$ which describes the properties and interactions of a certain subset of selected nodes belonging to a much larger directed network. The matrix $G_R$ takes into account effective interactions between subset nodes by all their indirect links via the whole network. We argue that this approach gives new possibilities to analyze effective interactions in a group of nodes embedded in a large directed networks. Possible efficient numerical methods for the practical computation of $G_R$ are also described.

  8. Density matrix perturbation theory.

    Science.gov (United States)

    Niklasson, Anders M N; Challacombe, Matt

    2004-05-14

    An orbital-free quantum perturbation theory is proposed. It gives the response of the density matrix upon variation of the Hamiltonian by quadratically convergent recursions based on perturbed projections. The technique allows treatment of embedded quantum subsystems with a computational cost scaling linearly with the size of the perturbed region, O(N(pert.)), and as O(1) with the total system size. The method allows efficient high order perturbation expansions, as demonstrated with an example involving a 10th order expansion. Density matrix analogs of Wigner's 2n+1 rule are also presented.

  9. Complex matrix model duality

    Energy Technology Data Exchange (ETDEWEB)

    Brown, T.W.

    2010-11-15

    The same complex matrix model calculates both tachyon scattering for the c=1 non-critical string at the self-dual radius and certain correlation functions of half-BPS operators in N=4 super- Yang-Mills. It is dual to another complex matrix model where the couplings of the first model are encoded in the Kontsevich-like variables of the second. The duality between the theories is mirrored by the duality of their Feynman diagrams. Analogously to the Hermitian Kontsevich- Penner model, the correlation functions of the second model can be written as sums over discrete points in subspaces of the moduli space of punctured Riemann surfaces. (orig.)

  10. Control of extracellular matrix assembly by syndecan-2 proteoglycan

    DEFF Research Database (Denmark)

    Klass, C M; Couchman, J R; Woods, A

    2000-01-01

    Extracellular matrix (ECM) deposition and organization is maintained by transmembrane signaling and integrins play major roles. We now show that a second transmembrane component, syndecan-2 heparan sulfate proteoglycan, is pivotal in matrix assembly. Chinese Hamster Ovary (CHO) cells were stably...

  11. Universality of the Distribution Functions of Random Matrix Theory. II

    OpenAIRE

    Tracy, Craig A.; Widom, Harold

    1999-01-01

    This paper is a brief review of recent developments in random matrix theory. Two aspects are emphasized: the underlying role of integrable systems and the occurrence of the distribution functions of random matrix theory in diverse areas of mathematics and physics.

  12. Dynamic Matrix Rank

    DEFF Research Database (Denmark)

    Frandsen, Gudmund Skovbjerg; Frandsen, Peter Frands

    2009-01-01

    We consider maintaining information about the rank of a matrix under changes of the entries. For n×n matrices, we show an upper bound of O(n1.575) arithmetic operations and a lower bound of Ω(n) arithmetic operations per element change. The upper bound is valid when changing up to O(n0.575) entri...... closed fields. The upper bound for element updates uses fast rectangular matrix multiplication, and the lower bound involves further development of an earlier technique for proving lower bounds for dynamic computation of rational functions.......We consider maintaining information about the rank of a matrix under changes of the entries. For n×n matrices, we show an upper bound of O(n1.575) arithmetic operations and a lower bound of Ω(n) arithmetic operations per element change. The upper bound is valid when changing up to O(n0.575) entries...... in a single column of the matrix. We also give an algorithm that maintains the rank using O(n2) arithmetic operations per rank one update. These bounds appear to be the first nontrivial bounds for the problem. The upper bounds are valid for arbitrary fields, whereas the lower bound is valid for algebraically...

  13. Empirical codon substitution matrix

    Directory of Open Access Journals (Sweden)

    Gonnet Gaston H

    2005-06-01

    Full Text Available Abstract Background Codon substitution probabilities are used in many types of molecular evolution studies such as determining Ka/Ks ratios, creating ancestral DNA sequences or aligning coding DNA. Until the recent dramatic increase in genomic data enabled construction of empirical matrices, researchers relied on parameterized models of codon evolution. Here we present the first empirical codon substitution matrix entirely built from alignments of coding sequences from vertebrate DNA and thus provide an alternative to parameterized models of codon evolution. Results A set of 17,502 alignments of orthologous sequences from five vertebrate genomes yielded 8.3 million aligned codons from which the number of substitutions between codons were counted. From this data, both a probability matrix and a matrix of similarity scores were computed. They are 64 × 64 matrices describing the substitutions between all codons. Substitutions from sense codons to stop codons are not considered, resulting in block diagonal matrices consisting of 61 × 61 entries for the sense codons and 3 × 3 entries for the stop codons. Conclusion The amount of genomic data currently available allowed for the construction of an empirical codon substitution matrix. However, more sequence data is still needed to construct matrices from different subsets of DNA, specific to kingdoms, evolutionary distance or different amount of synonymous change. Codon mutation matrices have advantages for alignments up to medium evolutionary distances and for usages that require DNA such as ancestral reconstruction of DNA sequences and the calculation of Ka/Ks ratios.

  14. Matrix Embedded Organic Synthesis

    Science.gov (United States)

    Kamakolanu, U. G.; Freund, F. T.

    2016-05-01

    In the matrix of minerals such as olivine, a redox reaction of the low-z elements occurs. Oxygen is oxidized to the peroxy state while the low-Z-elements become chemically reduced. We assign them a formula [CxHyOzNiSj]n- and call them proto-organics.

  15. More on rotations as spin matrix polynomials

    Energy Technology Data Exchange (ETDEWEB)

    Curtright, Thomas L. [Department of Physics, University of Miami, Coral Gables, Florida 33124-8046 (United States)

    2015-09-15

    Any nonsingular function of spin j matrices always reduces to a matrix polynomial of order 2j. The challenge is to find a convenient form for the coefficients of the matrix polynomial. The theory of biorthogonal systems is a useful framework to meet this challenge. Central factorial numbers play a key role in the theoretical development. Explicit polynomial coefficients for rotations expressed either as exponentials or as rational Cayley transforms are considered here. Structural features of the results are discussed and compared, and large j limits of the coefficients are examined.

  16. Change in Cell Shape Is Required for Matrix Metalloproteinase-Induced Epithelial-Mesenchymal Transition of Mammary Epithelial Cells

    Science.gov (United States)

    Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J.; Radisky, Derek C.

    2010-01-01

    Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a “cuboidal” epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase-3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP-3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP-3/Rac1b-induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP-3. These effects are not caused by general disruptions in cell signaling pathways, as TGF-β-induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape-dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT-inducing agents. PMID:18506791

  17. Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J.; Radisky, Derek C.

    2008-06-26

    Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a 'cuboidal' epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase-3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP-3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP-3/Rac1b-induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP-3. These effects are not caused by general disruptions in cell signaling pathways, as TGF-{beta}-induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape-dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT-inducing agents.

  18. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    Directory of Open Access Journals (Sweden)

    Xiaofei Cheng

    2016-01-01

    Full Text Available Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM. Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9, matrix metalloproteinase 3 (MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1, was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  19. Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

    OpenAIRE

    Tracy, Lauren E.; Minasian, Raquel A.; Caterson, E.J.

    2016-01-01

    Significance: Fibroblasts play a critical role in normal wound healing. Various extracellular matrix (ECM) components, including collagens, fibrin, fibronectin, proteoglycans, glycosaminoglycans, and matricellular proteins, can be considered potent protagonists of fibroblast survival, migration, and metabolism.

  20. Dentin matrix degradation by host Matrix Metalloproteinases: inhibition and clinical perspectives towards regeneration.

    Directory of Open Access Journals (Sweden)

    Catherine eChaussain

    2013-11-01

    Full Text Available Bacterial enzymes have long been considered solely accountable for the degradation of the dentin matrix during the carious process. However, the emerging literature suggests that host-derived enzymes, and in particular the matrix metalloproteinases (MMPs contained in dentin and saliva can play a major role in this process by their ability to degrade the dentin matrix from within. These findings are important since they open new therapeutic options for caries prevention and treatment. The possibility of using MMP inhibitors to interfere with dentin caries progression is discussed. Furthermore, the potential release of bioactive peptides by the enzymatic cleavage of dentin matrix proteins by MMPs during the carious process is discussed. These peptides, once identified, may constitute promising therapeutical tools for tooth and bone regeneration.

  1. Decorin modulates matrix mineralization in vitro

    Science.gov (United States)

    Mochida, Yoshiyuki; Duarte, Wagner R.; Tanzawa, Hideki; Paschalis, Eleftherios P.; Yamauchi, Mitsuo

    2003-01-01

    Decorin (DCN), a member of small leucine-rich proteoglycans, is known to modulate collagen fibrillogenesis. In order to investigate the potential roles of DCN in collagen matrix mineralization, several stable osteoblastic cell clones expressing higher (sense-DCN, S-DCN) and lower (antisense-DCN, As-DCN) levels of DCN were generated and the mineralized nodules formed by these clones were characterized. In comparison with control cells, the onset of mineralization by S-DCN clones was significantly delayed; whereas it was markedly accelerated and the number of mineralized nodules was significantly increased in As-DCN clones. The timing of mineralization was inversely correlated with the level of DCN synthesis. In these clones, the patterns of cell proliferation and differentiation appeared unaffected. These results suggest that DCN may act as an inhibitor of collagen matrix mineralization, thus modulating the timing of matrix mineralization.

  2. Abnormal recruitment of extracellular matrix proteins by excess Notch3 ECD: a new pathomechanism in CADASIL.

    Science.gov (United States)

    Monet-Leprêtre, Marie; Haddad, Iman; Baron-Menguy, Céline; Fouillot-Panchal, Maï; Riani, Meriem; Domenga-Denier, Valérie; Dussaule, Claire; Cognat, Emmanuel; Vinh, Joelle; Joutel, Anne

    2013-06-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, or CADASIL, one of the most common inherited small vessel diseases of the brain, is characterized by a progressive loss of vascular smooth muscle cells and extracellular matrix accumulation. The disease is caused by highly stereotyped mutations within the extracellular domain of the NOTCH3 receptor (Notch3(ECD)) that result in an odd number of cysteine residues. While CADASIL-associated NOTCH3 mutations differentially affect NOTCH3 receptor function and activity, they all are associated with early accumulation of Notch3(ECD)-containing aggregates in small vessels. We still lack mechanistic explanation to link NOTCH3 mutations with small vessel pathology. Herein, we hypothesized that excess Notch3(ECD) could recruit and sequester functionally important proteins within small vessels of the brain. We performed biochemical, nano-liquid chromatography-tandem mass spectrometry and immunohistochemical analyses, using cerebral and arterial tissue derived from patients with CADASIL and mouse models of CADASIL that exhibit vascular lesions in the end- and early-stage of the disease, respectively. Biochemical fractionation of brain and artery samples demonstrated that mutant Notch3(ECD) accumulates in disulphide cross-linked detergent-insoluble aggregates in mice and patients with CADASIL. Further proteomic and immunohistochemical analyses identified two functionally important extracellular matrix proteins, tissue inhibitor of metalloproteinases 3 (TIMP3) and vitronectin (VTN) that are sequestered into Notch3(ECD)-containing aggregates. Using cultured cells, we show that increased levels or aggregation of Notch3 enhances the formation of Notch3(ECD)-TIMP3 complex, promoting TIMP3 recruitment and accumulation. In turn, TIMP3 promotes complex formation including NOTCH3 and VTN. In vivo, brain vessels from mice and patients with CADASIL exhibit elevated levels of both insoluble cross

  3. Matrix string theory

    Science.gov (United States)

    Dijkgraaf, Robbert; Verlinde, Erik; Verlinde, Herman

    1997-02-01

    Via compactification on a circle, the matrix mode] of M-theory proposed by Banks et a]. suggests a concrete identification between the large N limit of two-dimensional N = 8 supersymmetric Yang-Mills theory and type IIA string theory. In this paper we collect evidence that supports this identification. We explicitly identify the perturbative string states and their interactions, and describe the appearance of D-particle and D-membrane states.

  4. Matrix string theory

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, R. [Amsterdam Univ. (Netherlands). Dept. of Mathematics; Verlinde, E. [TH-Division, CERN, CH-1211 Geneva 23 (Switzerland)]|[Institute for Theoretical Physics, Universtity of Utrecht, 3508 TA Utrecht (Netherlands); Verlinde, H. [Institute for Theoretical Physics, University of Amsterdam, 1018 XE Amsterdam (Netherlands)

    1997-09-01

    Via compactification on a circle, the matrix model of M-theory proposed by Banks et al. suggests a concrete identification between the large N limit of two-dimensional N=8 supersymmetric Yang-Mills theory and type IIA string theory. In this paper we collect evidence that supports this identification. We explicitly identify the perturbative string states and their interactions, and describe the appearance of D-particle and D-membrane states. (orig.).

  5. Matrix String Theory

    CERN Document Server

    Dijkgraaf, R; Verlinde, Herman L

    1997-01-01

    Via compactification on a circle, the matrix model of M-theory proposed by Banks et al suggests a concrete identification between the large N limit of two-dimensional N=8 supersymmetric Yang-Mills theory and type IIA string theory. In this paper we collect evidence that supports this identification. We explicitly identify the perturbative string states and their interactions, and describe the appearance of D-particle and D-membrane states.

  6. Holomorphic matrix integrals

    CERN Document Server

    Felder, G; Felder, Giovanni; Riser, Roman

    2004-01-01

    We study a class of holomorphic matrix models. The integrals are taken over middle dimensional cycles in the space of complex square matrices. As the size of the matrices tends to infinity, the distribution of eigenvalues is given by a measure with support on a collection of arcs in the complex planes. We show that the arcs are level sets of the imaginary part of a hyperelliptic integral connecting branch points.

  7. Matrix groups for undergraduates

    CERN Document Server

    Tapp, Kristopher

    2016-01-01

    Matrix groups touch an enormous spectrum of the mathematical arena. This textbook brings them into the undergraduate curriculum. It makes an excellent one-semester course for students familiar with linear and abstract algebra and prepares them for a graduate course on Lie groups. Matrix Groups for Undergraduates is concrete and example-driven, with geometric motivation and rigorous proofs. The story begins and ends with the rotations of a globe. In between, the author combines rigor and intuition to describe the basic objects of Lie theory: Lie algebras, matrix exponentiation, Lie brackets, maximal tori, homogeneous spaces, and roots. This second edition includes two new chapters that allow for an easier transition to the general theory of Lie groups. From reviews of the First Edition: This book could be used as an excellent textbook for a one semester course at university and it will prepare students for a graduate course on Lie groups, Lie algebras, etc. … The book combines an intuitive style of writing w...

  8. Metal matrix Composites

    Directory of Open Access Journals (Sweden)

    Pradeep K. Rohatgi

    1993-10-01

    Full Text Available This paper reviews the world wide upsurge in metal matrix composite research and development activities with particular emphasis on cast metal-matrix particulate composites. Extensive applications of cast aluminium alloy MMCs in day-to-day use in transportation as well as durable good industries are expected to advance rapidly in the next decade. The potential for extensive application of cast composites is very large in India, especially in the areas of transportation, energy and electromechanical machinery; the extensive use of composites can lead to large savings in materials and energy, and in several instances, reduce environmental pollution. It is important that engineering education and short-term courses be organized to bring MMCs to the attention of students and engineering industry leaders. India already has excellent infrastructure for development of composites, and has a long track record of world class research in cast metal matrix particulate composites. It is now necessary to catalyze prototype and regular production of selected composite components, and get them used in different sectors, especially railways, cars, trucks, buses, scooters and other electromechanical machinery. This will require suitable policies backed up by funding to bring together the first rate talent in cast composites which already exists in India, to form viable development groups followed by setting up of production plants involving the process engineering capability already available within the country. On the longer term, cast composites should be developed for use in energy generation equipment, electronic packaging aerospace systems, and smart structures.

  9. Advances in biomimetic regeneration of elastic matrix structures.

    Science.gov (United States)

    Sivaraman, Balakrishnan; Bashur, Chris A; Ramamurthi, Anand

    2012-10-01

    Elastin is a vital component of the extracellular matrix, providing soft connective tissues with the property of elastic recoil following deformation and regulating the cellular response via biomechanical transduction to maintain tissue homeostasis. The limited ability of most adult cells to synthesize elastin precursors and assemble them into mature crosslinked structures has hindered the development of functional tissue-engineered constructs that exhibit the structure and biomechanics of normal native elastic tissues in the body. In diseased tissues, the chronic overexpression of proteolytic enzymes can cause significant matrix degradation, to further limit the accumulation and quality (e.g., fiber formation) of newly deposited elastic matrix. This review provides an overview of the role and importance of elastin and elastic matrix in soft tissues, the challenges to elastic matrix generation in vitro and to regenerative elastic matrix repair in vivo, current biomolecular strategies to enhance elastin deposition and matrix assembly, and the need to concurrently inhibit proteolytic matrix disruption for improving the quantity and quality of elastogenesis. The review further presents biomaterial-based options using scaffolds and nanocarriers for spatio-temporal control over the presentation and release of these biomolecules, to enable biomimetic assembly of clinically relevant native elastic matrix-like superstructures. Finally, this review provides an overview of recent advances and prospects for the application of these strategies to regenerating tissue-type specific elastic matrix structures and superstructures.

  10. Matrix Theory of Small Oscillations

    Science.gov (United States)

    Chavda, L. K.

    1978-01-01

    A complete matrix formulation of the theory of small oscillations is presented. Simple analytic solutions involving matrix functions are found which clearly exhibit the transients, the damping factors, the Breit-Wigner form for resonances, etc. (BB)

  11. Matrix Completions and Chordal Graphs

    Institute of Scientific and Technical Information of China (English)

    Kenneth John HARRISON

    2003-01-01

    In a matrix-completion problem the aim is to specifiy the missing entries of a matrix inorder to produce a matrix with particular properties. In this paper we survey results concerning matrix-completion problems where we look for completions of various types for partial matrices supported ona given pattern. We see that thc existence of completions of the required type often depends on thechordal properties of graphs associated with the pattern.

  12. THE GENERALIZED POLARIZATION SCATTERING MATRIX

    Science.gov (United States)

    the Least Square Best Estimate of the Generalized Polarization matrix from a set of measurements is then developed. It is shown that the Faraday...matrix data. It is then shown that the Least Square Best Estimate of the orientation angle of a symmetric target is also determinable from Faraday rotation contaminated short pulse monostatic polarization matrix data.

  13. The cellulose resource matrix.

    Science.gov (United States)

    Keijsers, Edwin R P; Yılmaz, Gülden; van Dam, Jan E G

    2013-03-01

    The emerging biobased economy is causing shifts from mineral fossil oil based resources towards renewable resources. Because of market mechanisms, current and new industries utilising renewable commodities, will attempt to secure their supply of resources. Cellulose is among these commodities, where large scale competition can be expected and already is observed for the traditional industries such as the paper industry. Cellulose and lignocellulosic raw materials (like wood and non-wood fibre crops) are being utilised in many industrial sectors. Due to the initiated transition towards biobased economy, these raw materials are intensively investigated also for new applications such as 2nd generation biofuels and 'green' chemicals and materials production (Clark, 2007; Lange, 2007; Petrus & Noordermeer, 2006; Ragauskas et al., 2006; Regalbuto, 2009). As lignocellulosic raw materials are available in variable quantities and qualities, unnecessary competition can be avoided via the choice of suitable raw materials for a target application. For example, utilisation of cellulose as carbohydrate source for ethanol production (Kabir Kazi et al., 2010) avoids the discussed competition with easier digestible carbohydrates (sugars, starch) deprived from the food supply chain. Also for cellulose use as a biopolymer several different competing markets can be distinguished. It is clear that these applications and markets will be influenced by large volume shifts. The world will have to reckon with the increase of competition and feedstock shortage (land use/biodiversity) (van Dam, de Klerk-Engels, Struik, & Rabbinge, 2005). It is of interest - in the context of sustainable development of the bioeconomy - to categorize the already available and emerging lignocellulosic resources in a matrix structure. When composing such "cellulose resource matrix" attention should be given to the quality aspects as well as to the available quantities and practical possibilities of processing the

  14. Matrix string partition function

    CERN Document Server

    Kostov, Ivan K; Kostov, Ivan K.; Vanhove, Pierre

    1998-01-01

    We evaluate quasiclassically the Ramond partition function of Euclidean D=10 U(N) super Yang-Mills theory reduced to a two-dimensional torus. The result can be interpreted in terms of free strings wrapping the space-time torus, as expected from the point of view of Matrix string theory. We demonstrate that, when extrapolated to the ultraviolet limit (small area of the torus), the quasiclassical expressions reproduce exactly the recently obtained expression for the partition of the completely reduced SYM theory, including the overall numerical factor. This is an evidence that our quasiclassical calculation might be exact.

  15. Matrix vector analysis

    CERN Document Server

    Eisenman, Richard L

    2005-01-01

    This outstanding text and reference applies matrix ideas to vector methods, using physical ideas to illustrate and motivate mathematical concepts but employing a mathematical continuity of development rather than a physical approach. The author, who taught at the U.S. Air Force Academy, dispenses with the artificial barrier between vectors and matrices--and more generally, between pure and applied mathematics.Motivated examples introduce each idea, with interpretations of physical, algebraic, and geometric contexts, in addition to generalizations to theorems that reflect the essential structur

  16. Random matrix theory

    CERN Document Server

    Deift, Percy

    2009-01-01

    This book features a unified derivation of the mathematical theory of the three classical types of invariant random matrix ensembles-orthogonal, unitary, and symplectic. The authors follow the approach of Tracy and Widom, but the exposition here contains a substantial amount of additional material, in particular, facts from functional analysis and the theory of Pfaffians. The main result in the book is a proof of universality for orthogonal and symplectic ensembles corresponding to generalized Gaussian type weights following the authors' prior work. New, quantitative error estimates are derive

  17. Supported Molecular Matrix Electrophoresis.

    Science.gov (United States)

    Matsuno, Yu-Ki; Kameyama, Akihiko

    2015-01-01

    Mucins are difficult to separate using conventional gel electrophoresis methods such as SDS-PAGE and agarose gel electrophoresis, owing to their large size and heterogeneity. On the other hand, cellulose acetate membrane electrophoresis can separate these molecules, but is not compatible with glycan analysis. Here, we describe a novel membrane electrophoresis technique, termed "supported molecular matrix electrophoresis" (SMME), in which a porous polyvinylidene difluoride (PVDF) membrane filter is used to achieve separation. This description includes the separation, visualization, and glycan analysis of mucins with the SMME technique.

  18. Matrix algebra for linear models

    CERN Document Server

    Gruber, Marvin H J

    2013-01-01

    Matrix methods have evolved from a tool for expressing statistical problems to an indispensable part of the development, understanding, and use of various types of complex statistical analyses. This evolution has made matrix methods a vital part of statistical education. Traditionally, matrix methods are taught in courses on everything from regression analysis to stochastic processes, thus creating a fractured view of the topic. Matrix Algebra for Linear Models offers readers a unique, unified view of matrix analysis theory (where and when necessary), methods, and their applications. Written f

  19. Notes on matrix and micro strings

    Science.gov (United States)

    Dijkgraaf, Robbert; Verlinde, E.; Verlinde, H.

    1998-11-01

    We review some recent developments in the study of M-theory compactifications via Matrix theory. In particular we highlight the appearance of IIA strings and their interactions, and explain the unifying role of the M-theory five-brane for describing the spectrum of the T5 compactification and its duality symmetries. The 5+1-dimensional micro-string theory that lives on the fivebrane world-volume takes a central place in this presentation.

  20. Notes on Matrix and Micro Strings

    CERN Document Server

    Dijkgraaf, R; Verlinde, Herman L

    1998-01-01

    We review some recent developments in the study of M-theory compactifications via Matrix theory. In particular we highlight the appearance of IIA strings and their interactions, and explain the unifying role of the M-theory five-brane for describing the spectrum of the T^5 compactification and its duality symmetries. The 5+1-dimensional micro-string theory that lives on the fivebrane world-volume takes a central place in this presentation.

  1. Notes on matrix and micro strings

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, R. [Amsterdam Univ. (Netherlands). Dept. of Mathematics; Verlinde, E. [TH-Division, CERN, 1211 Geneva 23 (Switzerland)]|[Institute for Theoretical Physics, University of Utrecht, 3508 TA Utrecht (Netherlands); Verlinde, H. [Institute for Theoretical Physics, University of Amsterdam, 1018 XE Amsterdam (Netherlands)

    1998-11-01

    We review some recent developments in the study of M-theory compactifications via matrix theory. In particular we highlight the appearance of IIA strings and their interactions, and explain the unifying role of the M-theory five-brane for describing the spectrum of the T{sup 5} compactification and its duality symmetries. The 5+1-dimensionalmicro-string theory that lives on the fivebrane world-volume takes a central place in this presentation. (orig.) 51 refs.

  2. Matrix metalloproteinases (MMPs) and trophoblast invasion

    Institute of Scientific and Technical Information of China (English)

    LI Jing; ZHAO Tianfu; DUAN Enkui

    2005-01-01

    MMPs and their natural tissue inhibitors TIMPs are crucial in coordinated breakdown and remodeling of the extracellular matrix (ECM) in physiological and pathological situations. Placentation is a key event of pregnancy in which MMPs/TIMPs system plays important roles in regulating the extravillus cytotrophoblast (EVTs) invasion. This paper focuses on expression patterns and regulatory mechanisms of MMPs/TIMPs family members during the process of placentation. Their implications in curing pregnancy-related diseases are also discussed.

  3. Matrix Extracellular Phosphoglycoprotein Inhibits Phosphate Transport

    OpenAIRE

    Marks, J; Churchill, L J; Debnam, E. S.; Unwin, R J

    2008-01-01

    The role of putative humoral factors, known as phosphatonins, in phosphate homeostasis and the relationship between phosphate handling by the kidney and gastrointestinal tract are incompletely understood. Matrix extracellular phosphoglycoprotein (MEPE), one of several candidate phosphatonins, promotes phosphaturia, but whether it also affects intestinal phosphate absorption is unknown. Here, using the in situ intestinal loop technique, we demonstrated that short-term infusion of MEPE inhibits...

  4. Cell-material interactions on biphasic polyurethane matrix.

    Science.gov (United States)

    Dicesare, Patrick; Fox, Wade M; Hill, Michael J; Krishnan, G Rajesh; Yang, Shuying; Sarkar, Debanjan

    2013-08-01

    Cell-matrix interaction is a key regulator for controlling stem cell fate in regenerative tissue engineering. These interactions are induced and controlled by the nanoscale features of extracellular matrix and are mimicked on synthetic matrices to control cell structure and functions. Recent studies have shown that nanostructured matrices can modulate stem cell behavior and exert specific role in tissue regeneration. In this study, we have demonstrated that nanostructured phase morphology of synthetic matrix can control adhesion, proliferation, organization and migration of human mesenchymal stem cells (MSCs). Nanostructured biodegradable polyurethanes (PU) with segmental composition exhibit biphasic morphology at nanoscale dimensions and can control cellular features of MSCs. Biodegradable PU with polyester soft segment and hard segment composed of aliphatic diisocyanates and dipeptide chain extender were designed to examine the effect polyurethane phase morphology. By altering the polyurethane composition, morphological architecture of PU was modulated and its effect was examined on MSC. Results show that MSCs can sense the nanoscale morphology of biphasic polyurethane matrix to exhibit distinct cellular features and, thus, signifies the relevance of matrix phase morphology. The role of nanostructured phases of a synthetic matrix in controlling cell-matrix interaction provides important insights for regulation of cell behavior on synthetic matrix and, therefore, is an important tool for engineering tissue regeneration. Copyright © 2012 Wiley Periodicals, Inc.

  5. Cell–material interactions on biphasic polyurethane matrix

    Science.gov (United States)

    Dicesare, Patrick; Fox, Wade M.; Hill, Michael J.; Krishnan, G. Rajesh; Yang, Shuying; Sarkar, Debanjan

    2013-01-01

    Cell–matrix interaction is a key regulator for controlling stem cell fate in regenerative tissue engineering. These interactions are induced and controlled by the nanoscale features of extracellular matrix and are mimicked on synthetic matrices to control cell structure and functions. Recent studies have shown that nanostructured matrices can modulate stem cell behavior and exert specific role in tissue regeneration. In this study, we have demonstrated that nanostructured phase morphology of synthetic matrix can control adhesion, proliferation, organization and migration of human mesenchymal stem cells (MSCs). Nanostructured biodegradable polyurethanes (PU) with segmental composition exhibit biphasic morphology at nanoscale dimensions and can control cellular features of MSCs. Biodegradable PU with polyester soft segment and hard segment composed of aliphatic diisocyanates and dipeptide chain extender were designed to examine the effect polyurethane phase morphology. By altering the polyurethane composition, morphological architecture of PU was modulated and its effect was examined on MSC. Results show that MSCs can sense the nanoscale morphology of biphasic polyurethane matrix to exhibit distinct cellular features and, thus, signifies the relevance of matrix phase morphology. The role of nanostructured phases of a synthetic matrix in controlling cell–matrix interaction provides important insights for regulation of cell behavior on synthetic matrix and, therefore, is an important tool for engineering tissue regeneration. PMID:23255285

  6. Matrix Metalloproteinases-7 and Kidney Fibrosis

    Science.gov (United States)

    Ke, Ben; Fan, Chuqiao; Yang, Liping; Fang, Xiangdong

    2017-01-01

    Matrix metalloproteinase-7 (MMP-7) is a secreted zinc- and calcium-dependent endopeptidase that degrades a broad range of extracellular matrix substrates and additional substrates. MMP-7 playsa crucial role in a diverse array of cellular processes and appears to be a key regulator of fibrosis in several diseases, including pulmonary fibrosis, liver fibrosis, and cystic fibrosis. In particular, the relationship between MMP-7 and kidney fibrosis has attracted significant attention in recent years. Growing evidence indicates that MMP-7 plays an important role in the pathogenesis of kidney fibrosis. Here, we summarize the recent progress in the understanding of the role of MMP-7 in kidney fibrosis. In particular, we discuss how MMP-7 contributes to kidney fibrotic lesions via the following three pathways: epithelial-mesenchymal transition (EMT), transforming growth factor-beta (TGF-β) signaling, and extracellular matrix (ECM) deposition. Further dissection of the crosstalk among and regulation of these pathways will help clinicians and researchers develop effective therapeutic approaches for treating chronic kidney disease.

  7. Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea

    OpenAIRE

    O'Brien Terrence P; Song Jae K; Hakim Melinda A; Reviglio Victor E

    2003-01-01

    Abstract Background Matrix metalloproteinases play an important role in extracellular matrix deposition and degradation. Based on previous clinical observations of corneal perforations during topical fluoroquinolone treatment, we decided to evaluate the comparative effects of various fluoroquinolone eye drops on the expression of matrix metalloproteinases (MMPs) in cornea. Methods Eighty female Lewis rats were divided into two experimental groups: intact and wounded corneal epithelium. Unifor...

  8. Effect of Electro-acupuncture on Matrix Metalloproteinase in Degenerated Cervical Intervertebral Disc of Rats

    Institute of Scientific and Technical Information of China (English)

    SHI Zheng; HUANG Qiang; MA Xiao-peng; LIU Shi-min; LIU Hui-rong; ZHU Zhong-chun

    2007-01-01

    To observe the effect of electro-acupuncture on matrix metalloproteinase in degenerated cervical intervertebral disc rats.Methods:The rat model of cervical intervertebral disc degeneration was induced by unbalanced dynamic and static forces,then the rats were randomly allocated to model group,electro-acupuncture groupⅠ(acupoints Dazhu(BL 11) and Tianzhu(BL 10) were electro-acupunctured),and electro-acupuncture group Ⅱ(acupoints Dazhu (BL 11),Tianzhu(BL 10)and Shenshu(BL 23) were electro-acupunctured),with the normal rats as control.then the HE staining method was adopted to observe the morphological change of cervical intervertebral disc and the immunohistochemical staining method was used to detect the marx metalloproteinases-1(MMP-1) and matrix metalloproteinases-3(MMP-3) in cervical intervertebral disc.Results:The morphological observation showed that after electro-acupuncture treatment,the degrees of cervical intervertebral disc degeneration in electro-acupuncture groupⅠand electro-acupuncture group Ⅱ were alleviated,and the electro-acupuncture group Ⅱ was superior to electro-acupuncture group Ⅰ.The expressions of MMP-1 and MMP-3 in degenerated cervical intervertebral disc were increased(P<0.01),and after electro-acupuncture treatment,the expressions of MMP-1 and MMP-3 in degenerated cervical intervertebral disc were decreased,especially the electro-acupuncture group Ⅱpresented the better effect as compared with electro-acupuncture group Ⅰ(P<0.05).Conclusions:Electro-acupuncture at acupoints Dazhu (BL 11) and Tianzhu (BL 10) had a certain therapeutic effect on cervical intervertebral disc degeneration,and in combination with acupoint Shenshu(BL 23),this therapeutic effect could be enhanced,its action mechanism might be that electro-acupuncture can reduce the expressions of MMP-l and MMP-3 in degenerated cervical intervertebral disc,inhibit the degradation of matrix in intervertebral disc.so as to relieve cervical intervertebral disc

  9. Systematic study on dynamic atomic layer epitaxy of InN on/in +c-GaN matrix and fabrication of fine-structure InN/GaN quantum wells: Role of high growth temperature

    Science.gov (United States)

    Yoshikawa, Akihiko; Kusakabe, Kazuhide; Hashimoto, Naoki; Hwang, Eun-Sook; Imai, Daichi; Itoi, Takaomi

    2016-12-01

    The growth kinetics and properties of nominally 1-ML (monolayer)-thick InN wells on/in +c-GaN matrix fabricated using dynamic atomic layer epitaxy (D-ALEp) by plasma-assisted molecular beam epitaxy were systematically studied, with particular attention given to the effects of growth temperature. Attention was also given to how and where the ˜1-ML-thick InN layers were frozen or embedded on/in the +c-GaN matrix. The D-ALEp of InN on GaN was a two-stage process; in the 1st stage, an "In+N" bilayer/monolayer was formed on the GaN surface, while in the 2nd, this was capped by a GaN barrier layer. Each process was monitored in-situ using spectroscopic ellipsometry. The target growth temperature was above 620 °C and much higher than the upper critical epitaxy temperature of InN (˜500 °C). The "In+N" bilayer/monolayer tended to be an incommensurate phase, and the growth of InN layers was possible only when they were capped with a GaN layer. The InN layers could be coherently inserted into the GaN matrix under self-organizing and self-limiting epitaxy modes. The growth temperature was the most dominant growth parameter on both the growth process and the structure of the InN layers. Reflecting the inherent growth behavior of D-ALEp grown InN on/in +c-GaN at high growth temperature, the embedded InN layers in the GaN matrix were basically not full-ML in coverage, and the thickness of sheet-island-like InN layers was essentially either 1-ML or 2-ML. It was found that these InN layers tended to be frozen at the step edges on the GaN and around screw-type threading dislocations. The InN wells formed type-I band line-up heterostructures with GaN barriers, with exciton localization energies of about 300 and 500 meV at 15 K for the 1-ML and 2-ML InN wells, respectively.

  10. Matrix Quantization of Turbulence

    CERN Document Server

    Floratos, Emmanuel

    2011-01-01

    Based on our recent work on Quantum Nambu Mechanics $\\cite{af2}$, we provide an explicit quantization of the Lorenz chaotic attractor through the introduction of Non-commutative phase space coordinates as Hermitian $ N \\times N $ matrices in $ R^{3}$. For the volume preserving part, they satisfy the commutation relations induced by one of the two Nambu Hamiltonians, the second one generating a unique time evolution. Dissipation is incorporated quantum mechanically in a self-consistent way having the correct classical limit without the introduction of external degrees of freedom. Due to its volume phase space contraction it violates the quantum commutation relations. We demonstrate that the Heisenberg-Nambu evolution equations for the Matrix Lorenz system develop fast decoherence to N independent Lorenz attractors. On the other hand there is a weak dissipation regime, where the quantum mechanical properties of the volume preserving non-dissipative sector survive for long times.

  11. Matrix Graph Grammars

    CERN Document Server

    Velasco, Pedro Pablo Perez

    2008-01-01

    This book objective is to develop an algebraization of graph grammars. Equivalently, we study graph dynamics. From the point of view of a computer scientist, graph grammars are a natural generalization of Chomsky grammars for which a purely algebraic approach does not exist up to now. A Chomsky (or string) grammar is, roughly speaking, a precise description of a formal language (which in essence is a set of strings). On a more discrete mathematical style, it can be said that graph grammars -- Matrix Graph Grammars in particular -- study dynamics of graphs. Ideally, this algebraization would enforce our understanding of grammars in general, providing new analysis techniques and generalizations of concepts, problems and results known so far.

  12. Matrix anticirculant calculus

    Science.gov (United States)

    Dimiev, Stancho; Stoev, Peter; Stoilova, Stanislava

    2013-12-01

    The notion of anticirculant is ordinary of interest for specialists of general algebra (to see for instance [1]). In this paper we develop some aspects of anticirculants in real function theory. Denoting by X≔x0+jx1+⋯+jmxm, xk∈R, m+1 = 2n, and jk is the k-th degree of the matrix j = (0100...00010...00001...0..................-1000...0), we study the functional anticirculants f(X)≔f0(x0,x1,...,xm)+jf1(x0,x1,...,xm)+⋯+jm-1fm-1(x0,x1,...,xm)+jmfm(x0,x1,...,xm), where fk(x0,x1,...,xm) are smooth functions of 2n real variables. A continuation for complex function theory will appear.

  13. Light cone matrix product

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, Matthew B [Los Alamos National Laboratory

    2009-01-01

    We show how to combine the light-cone and matrix product algorithms to simulate quantum systems far from equilibrium for long times. For the case of the XXZ spin chain at {Delta} = 0.5, we simulate to a time of {approx} 22.5. While part of the long simulation time is due to the use of the light-cone method, we also describe a modification of the infinite time-evolving bond decimation algorithm with improved numerical stability, and we describe how to incorporate symmetry into this algorithm. While statistical sampling error means that we are not yet able to make a definite statement, the behavior of the simulation at long times indicates the appearance of either 'revivals' in the order parameter as predicted by Hastings and Levitov (e-print arXiv:0806.4283) or of a distinct shoulder in the decay of the order parameter.

  14. Matrix membranes and integrability

    Energy Technology Data Exchange (ETDEWEB)

    Zachos, C. [Argonne National Lab., IL (United States); Fairlie, D. [University of Durham (United Kingdom). Dept. of Mathematical Sciences; Curtright, T. [University of Miami, Coral Gables, FL (United States). Dept. of Physics

    1997-06-01

    This is a pedagogical digest of results reported in Curtright, Fairlie, {ampersand} Zachos 1997, and an explicit implementation of Euler`s construction for the solution of the Poisson Bracket dual Nahm equation. But it does not cover 9 and 10-dimensional systems, and subsequent progress on them Fairlie 1997. Cubic interactions are considered in 3 and 7 space dimensions, respectively, for bosonic membranes in Poisson Bracket form. Their symmetries and vacuum configurations are explored. Their associated first order equations are transformed to Nahm`s equations, and are hence seen to be integrable, for the 3-dimensional case, by virtue of the explicit Lax pair provided. Most constructions introduced also apply to matrix commutator or Moyal Bracket analogs.

  15. The algebras of large N matrix mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Halpern, M.B.; Schwartz, C.

    1999-09-16

    Extending early work, we formulate the large N matrix mechanics of general bosonic, fermionic and supersymmetric matrix models, including Matrix theory: The Hamiltonian framework of large N matrix mechanics provides a natural setting in which to study the algebras of the large N limit, including (reduced) Lie algebras, (reduced) supersymmetry algebras and free algebras. We find in particular a broad array of new free algebras which we call symmetric Cuntz algebras, interacting symmetric Cuntz algebras, symmetric Bose/Fermi/Cuntz algebras and symmetric Cuntz superalgebras, and we discuss the role of these algebras in solving the large N theory. Most important, the interacting Cuntz algebras are associated to a set of new (hidden!) local quantities which are generically conserved only at large N. A number of other new large N phenomena are also observed, including the intrinsic nonlocality of the (reduced) trace class operators of the theory and a closely related large N field identification phenomenon which is associated to another set (this time nonlocal) of new conserved quantities at large N.

  16. The algebras of large N matrix mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Halpern, M.B.; Schwartz, C.

    1999-09-16

    Extending early work, we formulate the large N matrix mechanics of general bosonic, fermionic and supersymmetric matrix models, including Matrix theory: The Hamiltonian framework of large N matrix mechanics provides a natural setting in which to study the algebras of the large N limit, including (reduced) Lie algebras, (reduced) supersymmetry algebras and free algebras. We find in particular a broad array of new free algebras which we call symmetric Cuntz algebras, interacting symmetric Cuntz algebras, symmetric Bose/Fermi/Cuntz algebras and symmetric Cuntz superalgebras, and we discuss the role of these algebras in solving the large N theory. Most important, the interacting Cuntz algebras are associated to a set of new (hidden!) local quantities which are generically conserved only at large N. A number of other new large N phenomena are also observed, including the intrinsic nonlocality of the (reduced) trace class operators of the theory and a closely related large N field identification phenomenon which is associated to another set (this time nonlocal) of new conserved quantities at large N.

  17. [Matrix metalloproteases as molecular markers in gastric cancer].

    Science.gov (United States)

    de la Peña, Sol; Sampieri, Clara L; León-Córdoba, Kenneth

    2010-02-06

    Gastric cancer is the second leading cause of cancer-associated mortality in the world. Prognosis in patients with gastric cancer is difficult to establish because it is commonly diagnosed when gastric wall invasion and metastasis have occurred. Currently, some members of the extracellular matrix metalloproteinases have been identified, whose expression in gastric tumor tissue is significantly elevated compared to healthy gastric tissue. Matrix metalloproteinases are 24 zinc-dependent endopeptidases that catalyze the proteolysis of the extracellular matrix. This degradation allows the cancer cells invade the surrounding stroma and trigger metastasis. Upregulation of certain matrix metalloproteinases in gastric cancer has been associated with a poor prognosis and elevated invasive capacity. This review compiles evidence about the genetic expression of matrix metalloproteinases in gastric cancer and their role in tumour invasion and metastasis, emphasizing their potential as molecular markers of prognosis. Copyright 2009 Elsevier España, S.L. All rights reserved.

  18. Zeta Potential and Rheological Behavior of ULC Castables Matrix

    Institute of Scientific and Technical Information of China (English)

    XU Yuanchao; WANG Zhanmin; CAO Xiying

    2008-01-01

    Effects of starting materials and four dispersants (STP, SHP, FDN and FS60) on Zeta potential and rheological behavior of alumina based ULC castables matrix were investigated. The results show that: characteristics of silica fume and alumina cements play a very important role in Zeta potential and viscosity of suspensions of the castables matrix; the dispersants STP and SHP can change Zeta potential values of the matrix suspensions remarkably; the four dispersants can effectively improve the rheological properties of matrix suspensions. For the point of lower viscosity of the matrix suspensions, the suitable additions of the three dispersants (SHP, FDN and FS60) are about 0.2% while that of STP is about 0.3%.

  19. Nipah virus matrix protein: expert hacker of cellular machines.

    Science.gov (United States)

    Watkinson, Ruth E; Lee, Benhur

    2016-08-01

    Nipah virus (NiV, Henipavirus) is a highly lethal emergent zoonotic paramyxovirus responsible for repeated human outbreaks of encephalitis in South East Asia. There are no approved vaccines or treatments, thus improved understanding of NiV biology is imperative. NiV matrix protein recruits a plethora of cellular machinery to scaffold and coordinate virion budding. Intriguingly, matrix also hijacks cellular trafficking and ubiquitination pathways to facilitate transient nuclear localization. While the biological significance of matrix nuclear localization for an otherwise cytoplasmic virus remains enigmatic, the molecular details have begun to be characterized, and are conserved among matrix proteins from divergent paramyxoviruses. Matrix protein appropriation of cellular machinery will be discussed in terms of its early nuclear targeting and later role in virion assembly.

  20. Spherical membranes in Matrix theory

    CERN Document Server

    Kabat, D; Kabat, Daniel; Taylor, Washington

    1998-01-01

    We consider membranes of spherical topology in uncompactified Matrix theory. In general for large membranes Matrix theory reproduces the classical membrane dynamics up to 1/N corrections; for certain simple membrane configurations, the equations of motion agree exactly at finite N. We derive a general formula for the one-loop Matrix potential between two finite-sized objects at large separations. Applied to a graviton interacting with a round spherical membrane, we show that the Matrix potential agrees with the naive supergravity potential for large N, but differs at subleading orders in N. The result is quite general: we prove a pair of theorems showing that for large N, after removing the effects of gravitational radiation, the one-loop potential between classical Matrix configurations agrees with the long-distance potential expected from supergravity. As a spherical membrane shrinks, it eventually becomes a black hole. This provides a natural framework to study Schwarzschild black holes in Matrix theory.

  1. Linearized supergravity from Matrix theory

    CERN Document Server

    Kabat, D; Kabat, Daniel; Taylor, Washington

    1998-01-01

    We show that the linearized supergravity potential between two objects arising from the exchange of quanta with zero longitudinal momentum is reproduced to all orders in 1/r by terms in the one-loop Matrix theory potential. The essential ingredient in the proof is the identification of the Matrix theory quantities corresponding to moments of the stress tensor and membrane current. We also point out that finite-N Matrix theory violates the Equivalence Principle.

  2. Lectures on Matrix Field Theory

    Science.gov (United States)

    Ydri, Badis

    The subject of matrix field theory involves matrix models, noncommutative geometry, fuzzy physics and noncommutative field theory and their interplay. In these lectures, a lot of emphasis is placed on the matrix formulation of noncommutative and fuzzy spaces, and on the non-perturbative treatment of the corresponding field theories. In particular, the phase structure of noncommutative $\\phi^4$ theory is treated in great detail, and an introduction to noncommutative gauge theory is given.

  3. Matrix elements of unstable states

    CERN Document Server

    Bernard, V; Meißner, U -G; Rusetsky, A

    2012-01-01

    Using the language of non-relativistic effective Lagrangians, we formulate a systematic framework for the calculation of resonance matrix elements in lattice QCD. The generalization of the L\\"uscher-Lellouch formula for these matrix elements is derived. We further discuss in detail the procedure of the analytic continuation of the resonance matrix elements into the complex energy plane and investigate the infinite-volume limit.

  4. Enhancing an R-matrix

    CERN Document Server

    MacKaay, M A

    1996-01-01

    In order to construct a representation of the tangle category one needs an enhanced R-matrix. In this paper we define a sufficient and necessary condition for enhancement that can be checked easily for any R-matrix. If the R-matrix can be enhanced, we also show how to construct the additional data that define the enhancement. As a direct consequence we find a sufficient condition for the construction of a knot invariant.

  5. Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix

    Directory of Open Access Journals (Sweden)

    M. Paez-Pereda

    2005-10-01

    Full Text Available The extracellular matrix is a three-dimensional network of proteins, glycosaminoglycans and other macromolecules. It has a structural support function as well as a role in cell adhesion, migration, proliferation, differentiation, and survival. The extracellular matrix conveys signals through membrane receptors called integrins and plays an important role in pituitary physiology and tumorigenesis. There is a differential expression of extracellular matrix components and integrins during the pituitary development in the embryo and during tumorigenesis in the adult. Different extracellular matrix components regulate adrenocorticotropin at the level of the proopiomelanocortin gene transcription. The extracellular matrix also controls the proliferation of adrenocorticotropin-secreting tumor cells. On the other hand, laminin regulates the production of prolactin. Laminin has a dynamic pattern of expression during prolactinoma development with lower levels in the early pituitary hyperplasia and a strong reduction in fully grown prolactinomas. Therefore, the expression of extracellular matrix components plays a role in pituitary tumorigenesis. On the other hand, the remodeling of the extracellular matrix affects pituitary cell proliferation. Matrix metalloproteinase activity is very high in all types of human pituitary adenomas. Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.

  6. Matrix Models and Gravitational Corrections

    CERN Document Server

    Dijkgraaf, R; Temurhan, M; Dijkgraaf, Robbert; Sinkovics, Annamaria; Temurhan, Mine

    2002-01-01

    We provide evidence of the relation between supersymmetric gauge theories and matrix models beyond the planar limit. We compute gravitational R^2 couplings in gauge theories perturbatively, by summing genus one matrix model diagrams. These diagrams give the leading 1/N^2 corrections in the large N limit of the matrix model and can be related to twist field correlators in a collective conformal field theory. In the case of softly broken SU(N) N=2 super Yang-Mills theories, we find that these exact solutions of the matrix models agree with results obtained by topological field theory methods.

  7. A matrix model for WZW

    Energy Technology Data Exchange (ETDEWEB)

    Dorey, Nick [Department of Applied Mathematics and Theoretical Physics, University of Cambridge,Wilberforce Road, Cambridge, CB3 OWA (United Kingdom); Tong, David [Department of Applied Mathematics and Theoretical Physics, University of Cambridge,Wilberforce Road, Cambridge, CB3 OWA (United Kingdom); Department of Theoretical Physics, TIFR,Homi Bhabha Road, Mumbai 400 005 (India); Stanford Institute for Theoretical Physics,Via Pueblo, Stanford, CA 94305 (United States); Turner, Carl [Department of Applied Mathematics and Theoretical Physics, University of Cambridge,Wilberforce Road, Cambridge, CB3 OWA (United Kingdom)

    2016-08-01

    We study a U(N) gauged matrix quantum mechanics which, in the large N limit, is closely related to the chiral WZW conformal field theory. This manifests itself in two ways. First, we construct the left-moving Kac-Moody algebra from matrix degrees of freedom. Secondly, we compute the partition function of the matrix model in terms of Schur and Kostka polynomials and show that, in the large N limit, it coincides with the partition function of the WZW model. This same matrix model was recently shown to describe non-Abelian quantum Hall states and the relationship to the WZW model can be understood in this framework.

  8. A Matrix Model for WZW

    CERN Document Server

    Dorey, Nick; Turner, Carl

    2016-01-01

    We study a U(N) gauged matrix quantum mechanics which, in the large N limit, is closely related to the chiral WZW conformal field theory. This manifests itself in two ways. First, we construct the left-moving Kac-Moody algebra from matrix degrees of freedom. Secondly, we compute the partition function of the matrix model in terms of Schur and Kostka polynomials and show that, in the large $N$ limit, it coincides with the partition function of the WZW model. This same matrix model was recently shown to describe non-Abelian quantum Hall states and the relationship to the WZW model can be understood in this framework.

  9. Research Progress on the Role of MMP3 in the Development of Tumor★%MMP3在肿瘤发生发展中作用的新进展★

    Institute of Scientific and Technical Information of China (English)

    胡涂; 曾乐平(综述); 黄菊芳(审校)

    2013-01-01

      Matrix metalloproteinase 3 (MMP3) is attached to the family of Matrix metalloproteinases (MMPs). And the cata-lytic domain, which is located between the propeptide (Pro) and the hinge and has an active site with Zn2+, is the cardinal active site of MMP3. Its change in gene expression and its abnormal activity contribute to the pathologic processing of many diseases, especially to the development of tumor. This review is aimed at introducing and elaborating MMP3 through its structure, func-tion, biochemistry and its contribution in tumor progression.%  基质金属蛋白酶3(matrix metalloproteinase3, MMP3)是MMPs家族的主要成员之一,其前肽区(propeptide, Pro)和铰链(hinge, H)之间的具有Zn2+活性位点的接触反应性核团(catalytic domain)是其核心反应部位。MMP3在机体内表达的变化和活性的异常参与了多种疾病的病理过程,特别是肿瘤的发生与发展过程。本文将从MMP3的结构、功能、生物化学特性及其在肿瘤发生发展中的作用等方面综述其最新研究进展。

  10. Matrix metalloproteinases in wound repair (review).

    Science.gov (United States)

    Ravanti, L; Kähäri, V M

    2000-10-01

    Wound repair is initiated with the aggregation of platelets, formation of a fibrin clot, and release of growth factors from the activated coagulation pathways, injured cells, platelets, and extracellular matrix (ECM), followed by migration of inflammatory cells to the wound site. Thereafter, keratinocytes migrate over the wound, angiogenesis is initiated, and fibroblasts deposit and remodel the granulation tissue. Cell migration, angiogenesis, degradation of provisional matrix, and remodeling of newly formed granulation tissue, all require controlled degradation of the ECM. Disturbance in the balance between ECM production and degradation leads to formation of chronic ulcers with excessive ECM degradation, or to fibrosis, for example hypertrophic scars or keloids characterized by excessive accumulation of ECM components. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which as a group can degrade essentially all ECM components. So far, 20 members of the human MMP family have been identified. Based on their structure and substrate specificity, they can be divided into subgroups of collagenases, stromelysins, stromelysin-like MMPs, gelatinases, membrane-type MMPs (MT-MMPs), and other MMPs. In this review, the role of MMPs in normal wound repair as well as in chronic ulcers is discussed. In addition, the role of signaling pathways, in particular, mitogen-activated protein kinases (MAPKs) in regulating MMP expression is discussed as possible therapeutical targets for wound healing disorders.

  11. Extended Matrix Variate Hypergeometric Functions and Matrix Variate Distributions

    Directory of Open Access Journals (Sweden)

    Daya K. Nagar

    2015-01-01

    Full Text Available Hypergeometric functions of matrix arguments occur frequently in multivariate statistical analysis. In this paper, we define and study extended forms of Gauss and confluent hypergeometric functions of matrix arguments and show that they occur naturally in statistical distribution theory.

  12. Matrix identity and tractional forces influence indirect cardiac reprogramming

    Science.gov (United States)

    Kong, Yen P.; Carrion, Bita; Singh, Rahul K.; Putnam, Andrew J.

    2013-12-01

    Heart regeneration through in vivo cardiac reprogramming has been demonstrated as a possible regenerative strategy. While it has been reported that cardiac reprogramming in vivo is more efficient than in vitro, the influence of the extracellular microenvironment on cardiac reprogramming remains incompletely understood. This understanding is necessary to improve the efficiency of cardiac reprogramming in order to implement this strategy successfully. Here we have identified matrix identity and cell-generated tractional forces as key determinants of the dedifferentiation and differentiation stages during reprogramming. Cell proliferation, matrix mechanics, and matrix microstructure are also important, but play lesser roles. Our results suggest that the extracellular microenvironment can be optimized to enhance cardiac reprogramming.

  13. Update of human and mouse matrix metalloproteinase families

    OpenAIRE

    Jackson Brian C; Nebert Daniel W; Vasiliou Vasilis

    2010-01-01

    Abstract Matrix metalloproteinases (MMPs) are a family of zinc proteases that degrade most of the components of the extracellular matrix (ECM). MMPs also have a number of non-traditional roles in processing factors related to cell growth/proliferation, inflammation and more. There are 23 human MMPs and 23 mouse MMPs, most of which share orthology among most vertebrates; other examples have been found in invertebrates and plants. MMPs are named in order of discovery, but also have been grouped...

  14. Matrix Product Operators, Matrix Product States, and ab initio Density Matrix Renormalization Group algorithms

    CERN Document Server

    Chan, Garnet Kin-Lic; Nakatani, Naoki; Li, Zhendong; White, Steven R

    2016-01-01

    Current descriptions of the ab initio DMRG algorithm use two superficially different languages: an older language of the renormalization group and renormalized operators, and a more recent language of matrix product states and matrix product operators. The same algorithm can appear dramatically different when written in the two different vocabularies. In this work, we carefully describe the translation between the two languages in several contexts. First, we describe how to efficiently implement the ab-initio DMRG sweep using a matrix product operator based code, and the equivalence to the original renormalized operator implementation. Next we describe how to implement the general matrix product operator/matrix product state algebra within a pure renormalized operator-based DMRG code. Finally, we discuss two improvements of the ab initio DMRG sweep algorithm motivated by matrix product operator language: Hamiltonian compression, and a sum over operators representation that allows for perfect computational par...

  15. Ceramic matrix composite article and process of fabricating a ceramic matrix composite article

    Science.gov (United States)

    Cairo, Ronald Robert; DiMascio, Paul Stephen; Parolini, Jason Robert

    2016-01-12

    A ceramic matrix composite article and a process of fabricating a ceramic matrix composite are disclosed. The ceramic matrix composite article includes a matrix distribution pattern formed by a manifold and ceramic matrix composite plies laid up on the matrix distribution pattern, includes the manifold, or a combination thereof. The manifold includes one or more matrix distribution channels operably connected to a delivery interface, the delivery interface configured for providing matrix material to one or more of the ceramic matrix composite plies. The process includes providing the manifold, forming the matrix distribution pattern by transporting the matrix material through the manifold, and contacting the ceramic matrix composite plies with the matrix material.

  16. Hydrogel-Framed Nanofiber Matrix Integrated with a Microfluidic Device for Fluorescence Detection of Matrix Metalloproteinases-9.

    Science.gov (United States)

    Han, Sang Won; Koh, Won-Gun

    2016-06-21

    Matrix metalloproteinases (MMPs) play a pivotal role in regulating the composition of the extracellular matrix and have a critical role in vascular disease, cancer progression, and bone disorders. This paper describes the design and fabrication of a microdevice as a new platform for highly sensitive MMP-9 detection. In this sensing platform, fluorescein isocyanate (FITC)-labeled MMP-9 specific peptides were covalently immobilized on an electrospun nanofiber matrix to utilize an enzymatic cleavage strategy. Prior to peptide immobilization, the nanofiber matrix was incorporated into hydrogel micropatterns for easy size control and handling of the nanofiber matrix. The resultant hydrogel-framed nanofiber matrix immobilizing the peptides was inserted into microfluidic devices consisting of reaction chambers and detection zones. The immobilized peptides were reacted with the MMP-9-containing solution in a reaction chamber, which resulted in the cleavage of the FITC-containing peptide fragments and subsequently generated fluorescent flow at the detection zone. As higher concentrations of the MMP-9 solution were introduced or larger peptide-immobilizing nanofiber areas were used, more peptides were cleaved, and a stronger fluorescence signal was observed. Due to the huge surface area of the nanofiber and small dimensions of the microsystem, a faster response time (30 min) and lower detection limit (10 pM) could be achieved in this study. The hydrogel-framed nanofiber matrix is disposable and can be replaced with new ones immobilizing either the same or different biomolecules for various bioassays, while the microfluidic system can be continuously reused.

  17. Determination of Matrix Pore Size Distribution in Fractured Clayey Till and Assessment of Matrix Migration of Dechlorinationg Bacteria

    DEFF Research Database (Denmark)

    Cong, Lu; Broholm, Mette Martina; Fabricius, Ida Lykke

    2014-01-01

    The pore structure and pore size distribution (PSD) in the clayey till matrix from three Danish field sites were investigated by image analysis to assess the matrix migration of dechlorinating bacteria in clayey till. Clayey till samples had a wide range of pore sizes, with diameters of 0.1–100 μm...... account for approximately 30–60% of the total porosity (20–26%), which is within the range of those reported for clayey soils and other clayey deposits in the literature. The pore size, PSD, and interconnectivity of pores in clayey till matrix may play an important role in evaluation of the migration...

  18. Matrix Theory of pp Waves

    CERN Document Server

    Michelson, J

    2004-01-01

    The Matrix Theory that has been proposed for various pp wave backgrounds is discussed. Particular emphasis is on the existence of novel nontrivial supersymmetric solutions of the Matrix Theory. These correspond to branes of various shapes (ellipsoidal, paraboloidal, and possibly hyperboloidal) that are unexpected from previous studies of branes in pp wave geometries.

  19. How to Study a Matrix

    Science.gov (United States)

    Jairam, Dharmananda; Kiewra, Kenneth A.; Kauffman, Douglas F.; Zhao, Ruomeng

    2012-01-01

    This study investigated how best to study a matrix. Fifty-three participants studied a matrix topically (1 column at a time), categorically (1 row at a time), or in a unified way (all at once). Results revealed that categorical and unified study produced higher: (a) performance on relationship and fact tests, (b) study material satisfaction, and…

  20. Machining of Metal Matrix Composites

    CERN Document Server

    2012-01-01

    Machining of Metal Matrix Composites provides the fundamentals and recent advances in the study of machining of metal matrix composites (MMCs). Each chapter is written by an international expert in this important field of research. Machining of Metal Matrix Composites gives the reader information on machining of MMCs with a special emphasis on aluminium matrix composites. Chapter 1 provides the mechanics and modelling of chip formation for traditional machining processes. Chapter 2 is dedicated to surface integrity when machining MMCs. Chapter 3 describes the machinability aspects of MMCs. Chapter 4 contains information on traditional machining processes and Chapter 5 is dedicated to the grinding of MMCs. Chapter 6 describes the dry cutting of MMCs with SiC particulate reinforcement. Finally, Chapter 7 is dedicated to computational methods and optimization in the machining of MMCs. Machining of Metal Matrix Composites can serve as a useful reference for academics, manufacturing and materials researchers, manu...

  1. Matrix Model Approach to Cosmology

    CERN Document Server

    Chaney, A; Stern, A

    2015-01-01

    We perform a systematic search for rotationally invariant cosmological solutions to matrix models, or more specifically the bosonic sector of Lorentzian IKKT-type matrix models, in dimensions $d$ less than ten, specifically $d=3$ and $d=5$. After taking a continuum (or commutative) limit they yield $d-1$ dimensional space-time surfaces, with an attached Poisson structure, which can be associated with closed, open or static cosmologies. For $d=3$, we obtain recursion relations from which it is possible to generate rotationally invariant matrix solutions which yield open universes in the continuum limit. Specific examples of matrix solutions have also been found which are associated with closed and static two-dimensional space-times in the continuum limit. The solutions provide for a matrix resolution of cosmological singularities. The commutative limit reveals other desirable features, such as a solution describing a smooth transition from an initial inflation to a noninflationary era. Many of the $d=3$ soluti...

  2. Matrix convolution operators on groups

    CERN Document Server

    Chu, Cho-Ho

    2008-01-01

    In the last decade, convolution operators of matrix functions have received unusual attention due to their diverse applications. This monograph presents some new developments in the spectral theory of these operators. The setting is the Lp spaces of matrix-valued functions on locally compact groups. The focus is on the spectra and eigenspaces of convolution operators on these spaces, defined by matrix-valued measures. Among various spectral results, the L2-spectrum of such an operator is completely determined and as an application, the spectrum of a discrete Laplacian on a homogeneous graph is computed using this result. The contractivity properties of matrix convolution semigroups are studied and applications to harmonic functions on Lie groups and Riemannian symmetric spaces are discussed. An interesting feature is the presence of Jordan algebraic structures in matrix-harmonic functions.

  3. Effect of precipitate-matrix interface sinks on the growth of voids in the matrix

    Energy Technology Data Exchange (ETDEWEB)

    Brailsford, A.D.; Mansur, L.K.

    1981-01-01

    A qualitative discussion of the differing roles played by coherent and incoherent precipitates as point defect sinks is presented. Rate theory is used to obtain semiquantitative estimates of the growth of cavities in the matrix when either type of precipitate is present. Methods for deriving the sink strengths of precipitates of arbitrary shape are developed. In three materials where available microstructural information allows an analysis, precipitates are found to cause only a small relative suppression of cavity growth via the mechanisms here considered.

  4. Tumorigenic Potential of Extracellular Matrix Metalloproteinase Inducer

    Science.gov (United States)

    Zucker, Stanley; Hymowitz, Michelle; Rollo, Ellen E.; Mann, Richard; Conner, Cathleen E.; Cao, Jian; Foda, Hussein D.; Tompkins, David C.; Toole, Bryan P.

    2001-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs. PMID:11395366

  5. Interleukin-34 in rheumatoid arthritis: potential role in clinical therapy.

    Science.gov (United States)

    Zhang, Fangze; Ding, Rui; Li, Ping; Ma, Cuili; Song, Ding; Wang, Xuetong; Ma, Tianjiao; Bi, Liqi

    2015-01-01

    To investigate, whether interleukin (IL)-34 can be used as marker for treatment effectiveness in rheumatoid arthritis (RA). Serum samples were collected from 35 healthy participants and 83 patients with RA before as well as 4 weeks and 12 weeks after treatment initiation with the tumor necrosis factor α (TNF-α) inhibitor Etanercept. Related clinical data and hand radiograms of the patients were evaluated and serum IL-34, IL-6, IL-8, TNF-α, matrix metalloproteinase-3 (MMP-3) in addition to anti-cyclic citrullinated peptide (CCP) antibody concentrations were measured by ELISA. Serum concentrations of IL-34, IL-6, IL-8, TNF-α, MMP-3 and anti-CCP antibodies were markedly elevated in RA patients compared with controls (Panti-CCP antibodies in RA patients at baseline (P<0.01) and also with IL-8, MMP-3, IL-6, and DAS28 changes during therapy. Patients in stage III of hand X-ray RA scores had higher IL-34 serum concentrations than in stage II (P<0.05). IL-34 level decreased significantly (P<0.01) starting from 4 weeks after therapy initiation. IL-34 serum concentrations correlated with inflammatory cytokines before and during therapy and were significantly higher in stage III of hand X-ray score patients than in stage II participants. IL-34 might be used both as a biomarker for RA diagnosis and therapy efficiency.

  6. Matrix Metalloproteinases & Implication in Periodontitis- A Short Review

    Directory of Open Access Journals (Sweden)

    Hitesh Desarda

    2013-01-01

    Full Text Available Matrix metalloproteinases (MMPs are a group of enzymes which are responsible for the degradation of extracellular matrix during normal tissue turnover and also during inflammatory processes. The expression and activity of MMPs in adult tissues is normally quite low, but increases significantly in various pathological conditions that may lead into unwanted tissue destruction,such as inflammatory diseases, tumour growth and metastasis. The role of MMP-8 in periodontitis is the well-known example of the unwanted tissue destruction related to increased activity of MMPs. Degradation of the extracellular matrix may involve four distinct pathways. A body of evidence suggests that matrix components may be dissolved by extracellular matrix metalloproteinase (MMP-dependent or plasmin (Pln-dependent cleavage reactions and that larger fragment of matrix may be disposed by a phagocytic pathway by way of cleavage by lysosomal proteinases. Mineralized matrices appear to be degraded by a complex process mediated by osteoclasts which relies on degradation by lysosomal proteinases in a narrow pericellular compartment. Matrix metalloproteinases can specifically cleave and degrade collagens and connective tissue matrix at physiologic pH and temperature. The objective of this review article is to understand the complete mechanisms regulating the expression of MMPs and enzymatic activity is of great importance.Source for all the articles is electronic Pub-Med system, published in between 1997-2011 searched by using keywords like Matrix Metalloproteinases, Periodontitis, Extracellular Matrix, Collagen . Future trend should be directed towards the development of easy, reliable and fast diagnostic tools and the effective therapeutic strategies to reduce the levels of MMPs.

  7. Manufacturing Titanium Metal Matrix Composites by Consolidating Matrix Coated Fibres

    Institute of Scientific and Technical Information of China (English)

    Hua-Xin PENG

    2005-01-01

    Titanium metal matrix composites (TiMMCs) reinforced by continuous silicon carbide fibres are being developed for aerospace applications. TiMMCs manufactured by the consolidation of matrix-coated fibre (MCF) method offer optimum properties because of the resulting uniform fibre distribution, minimum fibre damage and fibre volume fraction control. In this paper, the consolidation of Ti-6Al-4V matrix-coated SiC fibres during vacuum hot pressing has been investigated. Experiments were carried out on multi-ply MCFs under vacuum hot pressing (VHP). In contrast to most of existing studies, the fibre arrangement has been carefully controlled either in square or hexagonal arraysthroughout the consolidated sample. This has enabled the dynamic consolidation behaviour of MCFs to be demonstrated by eliminating the fibre re-arrangement during the VHP process. The microstructural evolution of the matrix coating was reported and the deformation mechanisms involved were discussed.

  8. Bidirectional extracellular matrix signaling during tissue morphogenesis

    Science.gov (United States)

    Gjorevski, Nikolce; Nelson, Celeste M.

    2009-01-01

    Normal tissue development and function are regulated by the interplay between cells and their surrounding extracellular matrix (ECM). The ECM provides biochemical and mechanical contextual information that is conveyed from the cell membrane through the cytoskeleton to the nucleus to direct cell phenotype. Cells, in turn, remodel the ECM and thereby sculpt their local microenvironment. Here we review the mechanisms by which cells interact with, respond to, and influence the ECM, with particular emphasis placed on the role of this bidirectional communication during tissue morphogenesis. We also discuss the implications for successful engineering of functional tissues ex vivo. PMID:19896886

  9. New pole placement algorithm - Polynomial matrix approach

    Science.gov (United States)

    Shafai, B.; Keel, L. H.

    1990-01-01

    A simple and direct pole-placement algorithm is introduced for dynamical systems having a block companion matrix A. The algorithm utilizes well-established properties of matrix polynomials. Pole placement is achieved by appropriately assigning coefficient matrices of the corresponding matrix polynomial. This involves only matrix additions and multiplications without requiring matrix inversion. A numerical example is given for the purpose of illustration.

  10. High temperature polymer matrix composites

    Science.gov (United States)

    Serafini, Tito T. (Editor)

    1987-01-01

    These are the proceedings of the High Temperature Polymer Matrix Composites Conference held at the NASA Lewis Research Center on March 16 to 18, 1983. The purpose of the conference is to provide scientists and engineers working in the field of high temperature polymer matrix composites an opportunity to review, exchange, and assess the latest developments in this rapidly expanding area of materials technology. Technical papers are presented in the following areas: (1) matrix development; (2) adhesive development; (3) Characterization; (4) environmental effects; and (5) applications.

  11. Matrix Elements for Hylleraas CI

    Science.gov (United States)

    Harris, Frank E.

    The limitation to at most a single interelectron distance in individual configurations of a Hylleraas-type multiconfiguration wave function restricts significantly the types of integrals occurring in matrix elements for energy calculations, but even then if the formulation is not handled efficiently the angular parts of these integrals escalate to create expressions of great complexity. This presentation reviews ways in which the angular-momentum calculus can be employed to systematize and simplify the matrix element formulas, particularly those for the kinetic-energy matrix elements.

  12. The extracellular matrix in breast cancer.

    Science.gov (United States)

    Insua-Rodríguez, Jacob; Oskarsson, Thordur

    2016-02-01

    The extracellular matrix (ECM) is increasingly recognized as an important regulator in breast cancer. ECM in breast cancer development features numerous changes in composition and organization when compared to the mammary gland under homeostasis. Matrix proteins that are induced in breast cancer include fibrillar collagens, fibronectin, specific laminins and proteoglycans as well as matricellular proteins. Growing evidence suggests that many of these induced ECM proteins play a major functional role in breast cancer progression and metastasis. A number of the induced ECM proteins have moreover been shown to be essential components of metastatic niches, promoting stem/progenitor signaling pathways and metastatic growth. ECM remodeling enzymes are also markedly increased, leading to major changes in the matrix structure and biomechanical properties. Importantly, several ECM components and ECM remodeling enzymes are specifically induced in breast cancer or during tissue regeneration while healthy tissues under homeostasis express exceedingly low levels. This may indicate that ECM and ECM-associated functions may represent promising drug targets against breast cancer, providing important specificity that could be utilized when developing therapies. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Google matrix, dynamical attractors, and Ulam networks

    Science.gov (United States)

    Shepelyansky, D. L.; Zhirov, O. V.

    2010-03-01

    We study the properties of the Google matrix generated by a coarse-grained Perron-Frobenius operator of the Chirikov typical map with dissipation. The finite-size matrix approximant of this operator is constructed by the Ulam method. This method applied to the simple dynamical model generates directed Ulam networks with approximate scale-free scaling and characteristics being in certain features similar to those of the world wide web with approximate scale-free degree distributions as well as two characteristics similar to the web: a power-law decay in PageRank that mirrors the decay of PageRank on the world wide web and a sensitivity to the value α in PageRank. The simple dynamical attractors play here the role of popular websites with a strong concentration of PageRank. A variation in the Google parameter α or other parameters of the dynamical map can drive the PageRank of the Google matrix to a delocalized phase with a strange attractor where the Google search becomes inefficient.

  14. Matrix metalloproteinase gene polymorphisms and oral cancer.

    Science.gov (United States)

    Pereira, Andresa C; Dias do Carmo, Elaine; Dias da Silva, Marco A; Blumer Rosa, Luiz E

    2012-12-01

    Since oral squamous cell carcinoma (OSCC) is the most prevalent malignant cancer in the oral cavity, several researches have been performed to study the role of important enzymes in this disease. Among them, the matrix metalloproteinases (MMPs) are highlighted, due to the fact that they are proteinases responsible to degrade many extra-cellular matrix components, making possible the invasion of neoplasic cells. Important tools in cancer prognosis have been utilized aiming to correlate high levels of MMPs and OSCC, such as immunohistochemical, zymographic and mRNA detection methods. However, these techniques are usually applied after cancer detection, characterizing a curative but not a preventive medicine. Trying to make interventions before the development of the disease and making possible the identification of people at high risk and, analysis of modifications in MMP genes has been a chance for modern medicine. Recently, polymorphisms in MMP genes have been related to different neoplasias, including OSCC. Despite investigation is beginning, MMP gene polymorphisms seems to have a promising future in oral cancer research and some of the present results have shown that there are MMP polymorphisms related to an increased risk for developing oral cancer. Key words:Oral cancer, polymorphism, matrix metalloproteinase.

  15. Mueller-Jones Matrix measurement in material identification

    Science.gov (United States)

    Xu, Jiang; Qian, Weixian; Wang, Xiao

    2016-09-01

    The uniformity of lattice arrangement plays an important role in industrial processing, science and technology studies and environmental pollution detection. However, there are very little papers to study surface structure by depolarization characteristics. In order to improve the efficiency and accuracy of material identification system by polarization technology, we developed a new method to decompose the Mueller matrix, we studied the mechanism of the scattering of electromagnetic wave, and analyzed the relationship between the characteristics of depolarization and mechanism of scattering. We used the Jones Matrix and Mueller Matrix to set up the physical model, and decomposed the Mueller-Jones Matrix by the characteristics of polarization, then got the depolarization coefficients (ωd) of the surfaces of the samples. By using this theory, we deduced the relation formula of Mueller matrix, Mueller-Jones matrix and Isotropic-Depolarizer matrix. Based on the polarized characteristics of the samples, we analyzed design method of material identification system and gave the results of the experimental test. Finally, we applied the theory of Fresnel formulas to verify the theoretical model. From the results, we found that the depolarization coefficients of the samples' surfaces were related to the scattering, and in the whole measurement process, the depolarization coefficients of the samples were far different; the method could easily to distinguish the metal and nonmetal, and more quickly to analyze the surface roughness of the samples. Therefore, the depolarization technology had a great application value, and the paper had very important significance on the development of surface structure study.

  16. A strategy to quantitate global phosphorylation of bone matrix proteins.

    Science.gov (United States)

    Sroga, Grażyna E; Vashishth, Deepak

    2016-04-15

    Current studies of protein phosphorylation focus primarily on the importance of specific phosphoproteins and their landscapes of phosphorylation in the regulation of different cellular functions. However, global changes in phosphorylation of extracellular matrix phosphoproteins measured "in bulk" are equally important. For example, correct global phosphorylation of different bone matrix proteins is critical to healthy tissue biomineralization. To study changes of bone matrix global phosphorylation, we developed a strategy that combines a procedure for in vitro phosphorylation/dephosphorylation of fully mineralized bone in addition to quantitation of the global phosphorylation levels of bone matrix proteins. For the first time, we show that it is possible to enzymatically phosphorylate/dephosphorylate fully mineralized bone originating from either cadaveric human donors or laboratory animals (mice). Using our strategy, we detected the difference in the global phosphorylation levels of matrix proteins isolated from wild-type and osteopontin knockout mice. We also observed that the global phosphorylation levels of matrix proteins isolated from human cortical bone were lower than those isolated from trabecular bone. The developed strategy has the potential to open new avenues for studies on the global phosphorylation of bone matrix proteins and their role in biomineralization as well for other tissues/cells and protein-based materials.

  17. Matrix product operators, matrix product states, and ab initio density matrix renormalization group algorithms

    Science.gov (United States)

    Chan, Garnet Kin-Lic; Keselman, Anna; Nakatani, Naoki; Li, Zhendong; White, Steven R.

    2016-07-01

    Current descriptions of the ab initio density matrix renormalization group (DMRG) algorithm use two superficially different languages: an older language of the renormalization group and renormalized operators, and a more recent language of matrix product states and matrix product operators. The same algorithm can appear dramatically different when written in the two different vocabularies. In this work, we carefully describe the translation between the two languages in several contexts. First, we describe how to efficiently implement the ab initio DMRG sweep using a matrix product operator based code, and the equivalence to the original renormalized operator implementation. Next we describe how to implement the general matrix product operator/matrix product state algebra within a pure renormalized operator-based DMRG code. Finally, we discuss two improvements of the ab initio DMRG sweep algorithm motivated by matrix product operator language: Hamiltonian compression, and a sum over operators representation that allows for perfect computational parallelism. The connections and correspondences described here serve to link the future developments with the past and are important in the efficient implementation of continuing advances in ab initio DMRG and related algorithms.

  18. Matrix product operators, matrix product states, and ab initio density matrix renormalization group algorithms.

    Science.gov (United States)

    Chan, Garnet Kin-Lic; Keselman, Anna; Nakatani, Naoki; Li, Zhendong; White, Steven R

    2016-07-01

    Current descriptions of the ab initio density matrix renormalization group (DMRG) algorithm use two superficially different languages: an older language of the renormalization group and renormalized operators, and a more recent language of matrix product states and matrix product operators. The same algorithm can appear dramatically different when written in the two different vocabularies. In this work, we carefully describe the translation between the two languages in several contexts. First, we describe how to efficiently implement the ab initio DMRG sweep using a matrix product operator based code, and the equivalence to the original renormalized operator implementation. Next we describe how to implement the general matrix product operator/matrix product state algebra within a pure renormalized operator-based DMRG code. Finally, we discuss two improvements of the ab initio DMRG sweep algorithm motivated by matrix product operator language: Hamiltonian compression, and a sum over operators representation that allows for perfect computational parallelism. The connections and correspondences described here serve to link the future developments with the past and are important in the efficient implementation of continuing advances in ab initio DMRG and related algorithms.

  19. Regulation by the extracellular matrix (ECM) of prolactin-induced alpha s1-casein gene expression in rabbit primary mammary cells: role of STAT5, C/EBP, and chromatin structure.

    Science.gov (United States)

    Jolivet, Geneviève; Pantano, Thaïs; Houdebine, Louis Marie

    2005-05-15

    The aim of the present study was to understand how the extracellular matrix (ECM) regulates at the gene level the prolactin (Prl)-induced signal transducer and activator of transcription 5 (STAT5)-dependent expression of the alpha s1-casein gene in mammary epithelial cells. CCAAT enhancer binding proteins (C/EBPs) are assumed regulators of beta-casein gene expression. Rabbit primary mammary cells express alpha s1-casein gene when cultured on collagen and not on plastic. Similar C/EBPbeta, C/EBPdelta, STAT5, and Prl-activated STAT5 were found under all culture conditions. Thus the ECM does not act through C/EBPs or STAT5. This was confirmed by transfections of rabbit primary mammary cells by a construct sensitive to ovine prolactin (oPrl) and ECM (6i TK luc) encompassing STAT5 and C/EBP binding sites. The mutation of C/EBPs binding sites showed that these sites were not mandatory for Prl-induced expression of the construct. Interestingly, chromatin immunoprecipitation by the anti-acetylhistone H4 antibody (ChIP) showed that the ECM (and not Prl) maintained a high amount of histone H4 acetylation upstream of the alpha s1-casein gene especially at the level of a distal Prl- and ECM-sensitive enhancer. Alpha6 integrin (a membrane receptor of laminin, the principal active component of the mammary ECM) was found at the surface of cells cultured on collagen but not on plastic. In cells cultured on collagen in the presence of anti-alpha6 integrin antibody, Prl-induced transcription of the endogenous alpha s1-casein gene was significantly reduced, without modifying C/EBPs and STAT5. Besides, histone H4 acetylation was reduced. Thus, we propose that the ECM regulates rabbit alpha s1-casein protein expression by local modification of chromatin structure, independently of STAT5 and C/EBPs.

  20. GoM Diet Matrix

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set was taken from CRD 08-18 at the NEFSC. Specifically, the Gulf of Maine diet matrix was developed for the EMAX exercise described in that center...

  1. Linear connections on matrix geometries

    CERN Document Server

    Madore, J; Mourad, J; Madore, John; Masson, Thierry; Mourad, Jihad

    1994-01-01

    A general definition of a linear connection in noncommutative geometry has been recently proposed. Two examples are given of linear connections in noncommutative geometries which are based on matrix algebras. They both possess a unique metric connection.

  2. Matrix Quantum Mechanics from Qubits

    CERN Document Server

    Hartnoll, Sean A; Mazenc, Edward A

    2016-01-01

    We introduce a transverse field Ising model with order N^2 spins interacting via a nonlocal quartic interaction. The model has an O(N,Z), hyperoctahedral, symmetry. We show that the large N partition function admits a saddle point in which the symmetry is enhanced to O(N). We further demonstrate that this `matrix saddle' correctly computes large N observables at weak and strong coupling. The matrix saddle undergoes a continuous quantum phase transition at intermediate couplings. At the transition the matrix eigenvalue distribution becomes disconnected. The critical excitations are described by large N matrix quantum mechanics. At the critical point, the low energy excitations are waves propagating in an emergent 1+1 dimensional spacetime.

  3. The R-matrix theory

    Energy Technology Data Exchange (ETDEWEB)

    Descouvemont, P; Baye, D [Physique Nucleaire Theorique et Physique Mathematique, C.P. 229, Universite Libre de Bruxelles (ULB), B 1050 Brussels (Belgium)], E-mail: pdesc@ulb.ac.be, E-mail: dbaye@ulb.ac.be

    2010-03-15

    The different facets of the R-matrix method are presented pedagogically in a general framework. Two variants have been developed over the years: (i) The 'calculable' R-matrix method is a calculational tool to derive scattering properties from the Schroedinger equation in a large variety of physical problems. It was developed rather independently in atomic and nuclear physics with too little mutual influence. (ii) The 'phenomenological' R-matrix method is a technique to parametrize various types of cross sections. It was mainly (or uniquely) used in nuclear physics. Both directions are explained by starting from the simple problem of scattering by a potential. They are illustrated by simple examples in nuclear and atomic physics. In addition to elastic scattering, the R-matrix formalism is applied to inelastic and radiative-capture reactions. We also present more recent and more ambitious applications of the theory in nuclear physics.

  4. The CKM matrix and flavor physics from lattice QCD

    CERN Document Server

    Van de Water, Ruth S

    2009-01-01

    I discuss the role of lattice QCD in testing the Standard Model and searching for physics beyond the Standard Model in the quark flavor sector. I first review the Standard Model CKM framework. I then present the current status of the CKM matrix, focusing on determinations of CKM matrix elements and constraints on the CKM unitarity triangle that rely on lattice QCD calculations of weak matrix elements. I also show the potential impact of improved lattice QCD calculations on the global CKM unitarity triangle fit. I then describe several hints of new physics in the quark flavor sector that rely on lattice QCD calculations of weak matrix elements, such as evidence of a ~2-3 sigma tension in the CKM unitarity triangle and the "f_{D_s} puzzle". I finish with a discussion of lattice QCD calculations of rare B- and K-decays needed to probe physics beyond the Standard Model at future experiments.

  5. Fabrication of aluminum matrix composite reinforced with carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    1.0 wt.% carbon nanotube (CNT) reinforced 2024A1 matrix composite was fabricated by cold isostatic press and subsequent hot extrusion techniques. The mechanical properties of the composite were measured by a tensile test. Meanwhile, the fracture surfaces were examined using field emission scanning electron microscopy. The experimental results show that CNTs are dispersed homogeneously in the composite and that the interfaces of the Al matrix and the CNT bond well. Although the tensile strength and the Young's modulus of the composite are enhanced markedly, the elongation does not decrease when compared with the matrix material fabricated under the same process. The reasons for the increments may be the extraordinary mechanical properties of CNTs, and the bridging and pulling-out role of CNTs in the Al matrix composite.

  6. Automatic generation of matrix element derivatives for tight binding models

    Science.gov (United States)

    Elena, Alin M.; Meister, Matthias

    2005-10-01

    Tight binding (TB) models are one approach to the quantum mechanical many-particle problem. An important role in TB models is played by hopping and overlap matrix elements between the orbitals on two atoms, which of course depend on the relative positions of the atoms involved. This dependence can be expressed with the help of Slater-Koster parameters, which are usually taken from tables. Recently, a way to generate these tables automatically was published. If TB approaches are applied to simulations of the dynamics of a system, also derivatives of matrix elements can appear. In this work we give general expressions for first and second derivatives of such matrix elements. Implemented in a tight binding computer program, like, for instance, DINAMO, they obviate the need to type all the required derivatives of all occurring matrix elements by hand.

  7. Matrix analysis of electrical machinery

    CERN Document Server

    Hancock, N N

    2013-01-01

    Matrix Analysis of Electrical Machinery, Second Edition is a 14-chapter edition that covers the systematic analysis of electrical machinery performance. This edition discusses the principles of various mathematical operations and their application to electrical machinery performance calculations. The introductory chapters deal with the matrix representation of algebraic equations and their application to static electrical networks. The following chapters describe the fundamentals of different transformers and rotating machines and present torque analysis in terms of the currents based on the p

  8. Titanium dioxide anatase as matrix for matrix-assisted laser desorption/ionization analysis of small molecules.

    Science.gov (United States)

    Castro, Ana L; Madeira, Paulo J Amorim; Nunes, Manuel R; Costa, Fernanda M; Florêncio, M Helena

    2008-12-01

    The use of inorganic species as assisting materials in matrix-assisted laser desorption/ionization (MALDI) analysis is an alternative approach to avoid interfering matrix ions in the low-mass region of the mass spectra. Reports of the application of inorganic species as matrices in MALDI analysis of small molecules are, however, scarce. Nevertheless, titanium dioxide (TiO(2)) powder has been reported to be a promising matrix medium. In this study we further explore the use of TiO(2) as a matrix for the MALDI analysis of low molecular weight compounds. We present results showing that nanosized TiO(2) anatase and TiO(2) rutile perform better as MALDI matrices than a commercial TiO(2) anatase/rutile mixture. Moreover, when using nanosized TiO(2) anatase as a matrix, high-quality mass spectra can be obtained with strong analyte signals and weak or non-existing matrix interference ions. Furthermore, our results show that the phase type plays an important role in the application of TiO(2) as a MALDI matrix.

  9. Molecular Control of Vascular Tube Morphogenesis and Stabilization: Regulation by Extracellular Matrix, Matrix Metalloproteinases, and Endothelial Cell-Pericyte Interactions

    Science.gov (United States)

    Davis, George E.; Stratman, Amber N.; Sacharidou, Anastasia

    Recent studies have revealed a critical role for both extracellular matrices and matrix metalloproteinases in the molecular control of vascular morphogenesis and stabilization in three-dimensional (3D) tissue environments. Key interactions involve endothelial cells (ECs) and pericytes, which coassemble to affect vessel formation, remodeling, and stabilization events during development and postnatal life. EC-pericyte interactions control extracellular matrix remodeling events including vascular basement membrane matrix assembly, a necessary step for endothelial tube maturation and stabilization. ECs form tube networks in 3D extracellular matrices in a manner dependent on integrins, membrane-type metalloproteinases, and the Rho GTPases, Cdc42 and Rac1. Recent work has defined an EC lumen signaling complex of proteins composed of these proteins that controls 3D matrix-specific signaling events required for these processes. The EC tube formation process results in the creation of a network of proteolytically generated vascular guidance tunnels. These tunnels are physical matrix spaces that regulate vascular tube remodeling and represent matrix conduits into which pericytes are recruited to allow dynamic cell-cell interactions with ECs. These dynamic EC-pericyte interactions induce vascular basement membrane matrix deposition, leading to vessel maturation and stabilization.

  10. Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers.

    Science.gov (United States)

    Rempe, Ralf G; Hartz, Anika Ms; Bauer, Björn

    2016-09-01

    Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood-brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood-brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer's disease, Parkinson's disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood-brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood-brain barrier in brain disorders.

  11. SVD row or column symmetric matrix

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new architecture for row or column symmetric matrix called extended matrix is defined, and a precise correspondence of the singular values and singular vectors between the extended matrix and its original (namely, the mother matrix) is derived. As an illustration of potential, we show that, for a class of extended matrices, the singular value decomposition using the mother matrix rather than the extended matrix per se can save the CPU time and memory without loss of numerical precision.

  12. Mecanismos de disfunção da barreira hematoencefálica no paciente criticamente enfermo: ênfase no papel das metaloproteinases de matriz Mechanisms of dysfunction of the blood-brain barrier in critically ill patients: emphasis on the role of matrix metalloproteinases

    Directory of Open Access Journals (Sweden)

    Hugo Rojas

    2011-06-01

    Full Text Available Será descrito a base fisiológica dos componentes da barreira hematoencefálica e suas propriedades. Além disto, pretende-se abordar o efeito particular das metaloproteinases e seu controle sobre as propriedades da matriz extracelular e a relação disto com disfunção da barreira hemotoencefálica. Finalmente se demonstrará o papel da metaloproteinases nas alterações do sistema nervoso central em doenças associadas ao paciente criticamente enfermo.This paper aims to describe the physiological basis of the blood-brain barrier components and its properties. Additionally, the particular effects of metalloproteinases and their control over the extracellular matrix and its relationship with blood-brain barrier dysfunction are discussed. Finally, the role of metalloproteinases on changes in the central nervous system in critically ill patients is discussed.

  13. High-level inducible Smad4-reexpression in the cervical cancer cell line C4-II is associated with a gene expression profile that predicts a preferential role of Smad4 in extracellular matrix composition

    Directory of Open Access Journals (Sweden)

    Schwarz Elisabeth

    2007-11-01

    Full Text Available Abstract Background Smad4 is a tumour suppressor frequently inactivated in pancreatic and colorectal cancers. We have recently reported loss of Smad4 in every fourth carcinoma of the uterine cervix. Smad4 transmits signals from the TGF-β superfamily of cytokines and functions as a versatile transcriptional co-modulator. The prevailing view suggests that the tumour suppressor function of Smad4 primarily resides in its capability to mediate TGF-β growth inhibitory responses. However, accumulating evidence indicates, that the acquisition of TGF-β resistance and loss of Smad4 may be independent events in the carcinogenic process. Through inducible reexpression of Smad4 in cervical cancer cells we wished to shed more light on this issue and to identify target genes implicated in Smad4 dependent tumor suppression. Methods Smad4-deficient human C4-II cervical carcinoma cells were used to establish inducible Smad4 reexpression using the commercial Tet-on™ system (Clontech. The impact of Smad4 reexpression on cell growth was analysed in vitro and in vivo. Transcriptional responses were assessed through profiling on cDNA macroarrays (Clontech and validated through Northern blotting. Results Clones were obtained that express Smad4 at widely varying levels from approximately physiological to 50-fold overexpression. Smad4-mediated tumour suppression in vivo was apparent at physiological expression levels as well as in Smad4 overexpressing clones. Smad4 reexpression in a dose-dependent manner was associated with transcriptional induction of the extracellular matrix-associated genes, BigH3, fibronectin and PAI-1, in response to TGF-β. Smad4-dependent regulation of these secreted Smad4 targets is not restricted to cervical carcinoma cells and was confirmed in pancreatic carcinoma cells reexpressing Smad4 after retroviral transduction and in a stable Smad4 knockdown model. On the other hand, the classical cell cycle-associated TGF-β target genes, c-myc, p

  14. Minimal Realizations of Supersymmetry for Matrix Hamiltonians

    CERN Document Server

    Andrianov, Alexandr A

    2014-01-01

    The notions of weak and strong minimizability of a matrix intertwining operator are introduced. Criterion of strong minimizability of a matrix intertwining operator is revealed. Criterion and sufficient condition of existence of a constant symmetry matrix for a matrix Hamiltonian are presented. A method of constructing of a matrix Hamiltonian with a given constant symmetry matrix in terms of a set of arbitrary scalar functions and eigen- and associated vectors of this matrix is offered. Examples of constructing of $2\\times2$ matrix Hamiltonians with given symmetry matrices for the cases of different structure of Jordan form of these matrices are elucidated.

  15. Matrix metalloproteinase-12 (MMP-12) in osteoclasts

    DEFF Research Database (Denmark)

    Hou, Peng; Troen, Tine; Ovejero, Maria C

    2004-01-01

    and resorption. Furthermore, we investigated the role of MMP-12 in bone resorption and osteoclast recruitment by comparing MMP-12 knockout and wild-type mice in specialized culture models known to depend on MMP activity, as well as in the ovariectomy model, and we did not find any indication for a limiting role......Osteoclasts require matrix metalloproteinase (MMP) activity and cathepsin K to resorb bone, but the critical MMP has not been identified. Osteoclasts express MMP-9 and MMP-14, which do not appear limiting for resorption, and the expression of additional MMPs is not clear. MMP-12, also called....... Northern blots show that highly purified rabbit osteoclasts in culture express MMP-12 at the same level as macrophages, whereas in situ hybridizations performed on rabbit bone do not show any MMP-12 expression in osteoclasts whatever the bone type. In contrast, in situ hybridizations performed on mouse...

  16. Nuclear matrix - structure, function and pathogenesis.

    Science.gov (United States)

    Wasąg, Piotr; Lenartowski, Robert

    2016-12-20

    The nuclear matrix (NM), or nuclear skeleton, is the non-chromatin, ribonucleoproteinaceous framework that is resistant to high ionic strength buffers, nonionic detergents, and nucleolytic enzymes. The NM fulfills a structural role in eukaryotic cells and is responsible for maintaining the shape of the nucleus and the spatial organization of chromatin. Moreover, the NM participates in several cellular processes, such as DNA replication/repair, gene expression, RNA transport, cell signaling and differentiation, cell cycle regulation, apoptosis and carcinogenesis. Short nucleotide sequences called scaffold/matrix attachment regions (S/MAR) anchor the chromatin loops to the NM proteins (NMP). The NMP composition is dynamic and depends on the cell type and differentiation stage or metabolic activity. Alterations in the NMP composition affect anchoring of the S/MARs and thus alter gene expression. This review aims to systematize information about the skeletal structure of the nucleus, with particular emphasis on the organization of the NM and its role in selected cellular processes. We also discuss several diseases that are caused by aberrant NM structure or dysfunction of individual NM elements.

  17. Matrix metalloproteinase imbalance in muscle disuse atrophy.

    Science.gov (United States)

    Giannelli, G; De Marzo, A; Marinosci, F; Antonaci, S

    2005-01-01

    Muscle atrophy commonly occurs as a consequence of prolonged muscle inactivity, as observed after cast immobilization, bed rest or space flights. The molecular mechanisms responsible for muscle atrophy are still unknown, but a role has been proposed for altered permeability of the sarcolemma and of the surrounding connective tissue. Matrix metallo-proteinases (MMPs) are a family of enzymes with proteolytic activity toward a number of extracellular matrix (ECM) components; they are inhibited by tissue inhibitors of MMPs (TIMPs). In a rat tail-suspension experimental model, we show that after fourteen days of non-weight bearing there is increased expression of MMP-2 in the atrophic soleus and gastrocnemius and decreased expression of TIMP-2. In the same experimental model the expression of Collagen I and Collagen IV, two main ECM components present in the muscles, was reduced and unevenly distributed in unloaded animals. The difference was more evident in the soleus than in the gastrocnemius muscle. This suggests that muscle disuse induces a proteolytic imbalance, which could be responsible for the breakdown of basal lamina structures such as Collagen I and Collagen IV, and that this leads to an altered permeability with consequent atrophy. In conclusion, an MMP-2/TIMP-2 imbalance could have a role in the mechanism underlying muscle disuse atrophy; more studies are needed to expand our molecular knowledge on this issue and to explore the possibility of targeting the proteolytic imbalance with MMP inhibitors.

  18. Basic Components of Connective Tissues and Extracellular Matrix

    DEFF Research Database (Denmark)

    Halper, Jaroslava; Kjær, Michael

    2014-01-01

    of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds. Fibronectin with its...... network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin...... and TGFβ activity was observed in fibrotic skin disorders such as keloids and scleroderma. Cartilage oligomeric matrix protein (COMP) or thrombospondin-5 is primarily present in the cartilage. High levels of COMP are present in fibrotic scars and systemic sclerosis of the skin, and in tendon, especially...

  19. The Astrobiology Matrix and the "Drake Matrix" in Education

    Science.gov (United States)

    Mizser, A.; Kereszturi, A.

    2003-01-01

    We organized astrobiology lectures in the Eotvos Lorand University of Sciences and the Polaris Observatory in 2002. We present here the "Drake matrix" for the comparison of the astrobiological potential of different bodies [1], and astrobiology matrix for the visualization of the interdisciplinary connections between different fields of astrobiology. Conclusion: In Hungary it is difficult to integrate astrobiology in the education system but the great advantage is that it can connect different scientific fields and improve the view of students. We would like to get in contact with persons and organizations who already have experience in the education of astrobiology.

  20. A survey of matrix theory and matrix inequalities

    CERN Document Server

    Marcus, Marvin

    2010-01-01

    Written for advanced undergraduate students, this highly regarded book presents an enormous amount of information in a concise and accessible format. Beginning with the assumption that the reader has never seen a matrix before, the authors go on to provide a survey of a substantial part of the field, including many areas of modern research interest.Part One of the book covers not only the standard ideas of matrix theory, but ones, as the authors state, ""that reflect our own prejudices,"" among them Kronecker products, compound and induced matrices, quadratic relations, permanents, incidence

  1. Matrix factorizations and elliptic fibrations

    Science.gov (United States)

    Omer, Harun

    2016-09-01

    I use matrix factorizations to describe branes at simple singularities of elliptic fibrations. Each node of the corresponding Dynkin diagrams of the ADE-type singularities is associated with one indecomposable matrix factorization which can be deformed into one or more factorizations of lower rank. Branes with internal fluxes arise naturally as bound states of the indecomposable factorizations. Describing branes in such a way avoids the need to resolve singularities. This paper looks at gauge group breaking from E8 fibers down to SU (5) fibers due to the relevance of such fibrations for local F-theory GUT models. A purpose of this paper is to understand how the deformations of the singularity are understood in terms of its matrix factorizations. By systematically factorizing the elliptic fiber equation, this paper discusses geometries which are relevant for building semi-realistic local models. In the process it becomes evident that breaking patterns which are identical at the level of the Kodaira type of the fibers can be inequivalent at the level of matrix factorizations. Therefore the matrix factorization picture supplements information which the conventional less detailed descriptions lack.

  2. Matrix factorizations and elliptic fibrations

    Directory of Open Access Journals (Sweden)

    Harun Omer

    2016-09-01

    Full Text Available I use matrix factorizations to describe branes at simple singularities of elliptic fibrations. Each node of the corresponding Dynkin diagrams of the ADE-type singularities is associated with one indecomposable matrix factorization which can be deformed into one or more factorizations of lower rank. Branes with internal fluxes arise naturally as bound states of the indecomposable factorizations. Describing branes in such a way avoids the need to resolve singularities. This paper looks at gauge group breaking from E8 fibers down to SU(5 fibers due to the relevance of such fibrations for local F-theory GUT models. A purpose of this paper is to understand how the deformations of the singularity are understood in terms of its matrix factorizations. By systematically factorizing the elliptic fiber equation, this paper discusses geometries which are relevant for building semi-realistic local models. In the process it becomes evident that breaking patterns which are identical at the level of the Kodaira type of the fibers can be inequivalent at the level of matrix factorizations. Therefore the matrix factorization picture supplements information which the conventional less detailed descriptions lack.

  3. Biofilm recruitment of Vibrio cholerae by matrix proteolysis.

    Science.gov (United States)

    Duperthuy, Marylise; Uhlin, Bernt Eric; Wai, Sun Nyunt

    2015-11-01

    The appearance of bacterial biofilms involves secretion of polysaccharides and proteins that form an extracellular matrix embedding the bacteria. Proteases have also been observed, but their role has remained unclear. Smith and co-workers have now found that proteolysis can contribute to further recruitment of bacteria to Vibrio cholerae biofilms.

  4. A Contemporary Matrix Approach to Defining Shared Governance.

    Science.gov (United States)

    Davenport, Richard; Daniels, Elaine; Jones, James; Kesseler, Roger; Mowrey, Merlyn

    This paper outlines a matrix approach to shared governance developed at Central Michigan University (CMU), designed to help faculty and administrators focus on specific decision areas and to define existing roles more clearly. The process began at CMU in spring 1998 with the formation of an ad hoc committee on governance which surveyed faculty and…

  5. On Geometry and Matrix Models

    CERN Document Server

    Dijkgraaf, R; Dijkgraaf, Robbert; Vafa, Cumrun

    2002-01-01

    We point out two extensions of the relation between matrix models, topological strings and N=1 supersymmetric gauge theories. First, we note that by considering double scaling limits of unitary matrix models one can obtain large N duals of the local Calabi-Yau geometries that engineer N=2 gauge theories. In particular, a double scaling limit of the Gross-Witten one-plaquette lattice model gives the SU(2) Seiberg-Witten solution, including its induced gravitational corrections. Secondly, we point out that the effective superpotential terms for N=1 ADE quiver gauge theories is similarly computed by large multi-matrix models, that have been considered in the context of ADE minimal models on random surfaces. The associated spectral curves are multiple branched covers obtained as Virasoro and W-constraints of the partition function.

  6. On geometry and matrix models

    Science.gov (United States)

    Dijkgraaf, Robbert; Vafa, Cumrun

    2002-11-01

    We point out two extensions of the relation between matrix models, topological strings and N=1 supersymmetric gauge theories. First, we note that by considering double scaling limits of unitary matrix models one can obtain large- N duals of the local Calabi-Yau geometries that engineer N=2 gauge theories. In particular, a double scaling limit of the Gross-Witten one-plaquette lattice model gives the SU(2) Seiberg-Witten solution, including its induced gravitational corrections. Secondly, we point out that the effective superpotential terms for N=1 ADE quiver gauge theories is similarly computed by large- N multi-matrix models, that have been considered in the context of ADE minimal models on random surfaces. The associated spectral curves are multiple branched covers obtained as Virasoro and W-constraints of the partition function.

  7. On geometry and matrix models

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, Robbert E-mail: rhd@science.uva.nl; Vafa, Cumrun

    2002-11-11

    We point out two extensions of the relation between matrix models, topological strings and N=1 supersymmetric gauge theories. First, we note that by considering double scaling limits of unitary matrix models one can obtain large-N duals of the local Calabi-Yau geometries that engineer N=2 gauge theories. In particular, a double scaling limit of the Gross-Witten one-plaquette lattice model gives the SU(2) Seiberg-Witten solution, including its induced gravitational corrections. Secondly, we point out that the effective superpotential terms for N=1 ADE quiver gauge theories is similarly computed by large-N multi-matrix models, that have been considered in the context of ADE minimal models on random surfaces. The associated spectral curves are multiple branched covers obtained as Virasoro and W-constraints of the partition function.

  8. Lectures on matrix field theory

    CERN Document Server

    Ydri, Badis

    2017-01-01

    These lecture notes provide a systematic introduction to matrix models of quantum field theories with non-commutative and fuzzy geometries. The book initially focuses on the matrix formulation of non-commutative and fuzzy spaces, followed by a description of the non-perturbative treatment of the corresponding field theories. As an example, the phase structure of non-commutative phi-four theory is treated in great detail, with a separate chapter on the multitrace approach. The last chapter offers a general introduction to non-commutative gauge theories, while two appendices round out the text. Primarily written as a self-study guide for postgraduate students – with the aim of pedagogically introducing them to key analytical and numerical tools, as well as useful physical models in applications – these lecture notes will also benefit experienced researchers by providing a reference guide to the fundamentals of non-commutative field theory with an emphasis on matrix models and fuzzy geometries.

  9. Noncommutative spaces from matrix models

    Science.gov (United States)

    Lu, Lei

    Noncommutative (NC) spaces commonly arise as solutions to matrix model equations of motion. They are natural generalizations of the ordinary commutative spacetime. Such spaces may provide insights into physics close to the Planck scale, where quantum gravity becomes relevant. Although there has been much research in the literature, aspects of these NC spaces need further investigation. In this dissertation, we focus on properties of NC spaces in several different contexts. In particular, we study exact NC spaces which result from solutions to matrix model equations of motion. These spaces are associated with finite-dimensional Lie-algebras. More specifically, they are two-dimensional fuzzy spaces that arise from a three-dimensional Yang-Mills type matrix model, four-dimensional tensor-product fuzzy spaces from a tensorial matrix model, and Snyder algebra from a five-dimensional tensorial matrix model. In the first part of this dissertation, we study two-dimensional NC solutions to matrix equations of motion of extended IKKT-type matrix models in three-space-time dimensions. Perturbations around the NC solutions lead to NC field theories living on a two-dimensional space-time. The commutative limit of the solutions are smooth manifolds which can be associated with closed, open and static two-dimensional cosmologies. One particular solution is a Lorentzian fuzzy sphere, which leads to essentially a fuzzy sphere in the Minkowski space-time. In the commutative limit, this solution leads to an induced metric that does not have a fixed signature, and have a non-constant negative scalar curvature, along with singularities at two fixed latitudes. The singularities are absent in the matrix solution which provides a toy model for resolving the singularities of General relativity. We also discussed the two-dimensional fuzzy de Sitter space-time, which has irreducible representations of su(1,1) Lie-algebra in terms of principal, complementary and discrete series. Field

  10. Supersymmetry in random matrix theory

    Energy Technology Data Exchange (ETDEWEB)

    Kieburg, Mario

    2010-05-04

    I study the applications of supersymmetry in random matrix theory. I generalize the supersymmetry method and develop three new approaches to calculate eigenvalue correlation functions. These correlation functions are averages over ratios of characteristic polynomials. In the first part of this thesis, I derive a relation between integrals over anti-commuting variables (Grassmann variables) and differential operators with respect to commuting variables. With this relation I rederive Cauchy- like integral theorems. As a new application I trace the supermatrix Bessel function back to a product of two ordinary matrix Bessel functions. In the second part, I apply the generalized Hubbard-Stratonovich transformation to arbitrary rotation invariant ensembles of real symmetric and Hermitian self-dual matrices. This extends the approach for unitarily rotation invariant matrix ensembles. For the k-point correlation functions I derive supersymmetric integral expressions in a unifying way. I prove the equivalence between the generalized Hubbard-Stratonovich transformation and the superbosonization formula. Moreover, I develop an alternative mapping from ordinary space to superspace. After comparing the results of this approach with the other two supersymmetry methods, I obtain explicit functional expressions for the probability densities in superspace. If the probability density of the matrix ensemble factorizes, then the generating functions exhibit determinantal and Pfaffian structures. For some matrix ensembles this was already shown with help of other approaches. I show that these structures appear by a purely algebraic manipulation. In this new approach I use structures naturally appearing in superspace. I derive determinantal and Pfaffian structures for three types of integrals without actually mapping onto superspace. These three types of integrals are quite general and, thus, they are applicable to a broad class of matrix ensembles. (orig.)

  11. Polychoric/Tetrachoric Matrix or Pearson Matrix? A methodological study

    Directory of Open Access Journals (Sweden)

    Dominguez Lara, Sergio Alexis

    2014-04-01

    Full Text Available The use of product-moment correlation of Pearson is common in most studies in factor analysis in psychology, but it is known that this statistic is only applicable when the variables related are in interval scale and normally distributed, and when are used in ordinal data may to produce a distorted correlation matrix . Thus is a suitable option using polychoric/tetrachoric matrices in item-level factor analysis when the items are in level measurement nominal or ordinal. The aim of this study was to show the differences in the KMO, Bartlett`s Test and Determinant of the Matrix, percentage of variance explained and factor loadings in depression trait scale of Depression Inventory Trait - State and the Neuroticism dimension of the short form of the Eysenck Personality Questionnaire -Revised, regarding the use of matrices polychoric/tetrachoric matrices and Pearson. These instruments was analyzed with different extraction methods (Maximum Likelihood, Minimum Rank Factor Analysis, Unweighted Least Squares and Principal Components, keeping constant the rotation method Promin were analyzed. Were observed differences regarding sample adequacy measures, as well as with respect to the explained variance and the factor loadings, for solutions having as polychoric/tetrachoric matrix. So it can be concluded that the polychoric / tetrachoric matrix give better results than Pearson matrices when it comes to item-level factor analysis using different methods.

  12. Symmetries and Interactions in Matrix String Theory

    NARCIS (Netherlands)

    Hacquebord, F.H.

    1999-01-01

    This PhD-thesis reviews matrix string theory and recent developments therein. The emphasis is put on symmetries, interactions and scattering processes in the matrix model. We start with an introduction to matrix string theory and a review of the orbifold model that flows out of matrix string theory

  13. Minimal realizations of supersymmetry for matrix Hamiltonians

    Energy Technology Data Exchange (ETDEWEB)

    Andrianov, Alexander A., E-mail: andrianov@icc.ub.edu; Sokolov, Andrey V., E-mail: avs_avs@rambler.ru

    2015-02-06

    The notions of weak and strong minimizability of a matrix intertwining operator are introduced. Criterion of strong minimizability of a matrix intertwining operator is revealed. Criterion and sufficient condition of existence of a constant symmetry matrix for a matrix Hamiltonian are presented. A method of constructing of a matrix Hamiltonian with a given constant symmetry matrix in terms of a set of arbitrary scalar functions and eigen- and associated vectors of this matrix is offered. Examples of constructing of 2×2 matrix Hamiltonians with given symmetry matrices for the cases of different structure of Jordan form of these matrices are elucidated. - Highlights: • Weak and strong minimization of a matrix intertwining operator. • Criterion of strong minimizability from the right of a matrix intertwining operator. • Conditions of existence of a constant symmetry matrix for a matrix Hamiltonian. • Method of constructing of a matrix Hamiltonian with a given constant symmetry matrix. • Examples of constructing of 2×2 matrix Hamiltonians with a given symmetry matrix.

  14. Properties of the matrix A-XY

    NARCIS (Netherlands)

    Steerneman, A.G.M.; van Perlo -ten Kleij, Frederieke

    2005-01-01

    The main topic of this paper is the matrix V = A - XY*, where A is a nonsingular complex k x k matrix and X and Y are k x p complex matrices of full column rank. Because properties of the matrix V can be derived from those of the matrix Q = I - XY*, we will consider in particular the case where A =

  15. Symmetries and Interactions in Matrix String Theory

    NARCIS (Netherlands)

    Hacquebord, F.H.

    1999-01-01

    This PhD-thesis reviews matrix string theory and recent developments therein. The emphasis is put on symmetries, interactions and scattering processes in the matrix model. We start with an introduction to matrix string theory and a review of the orbifold model that flows out of matrix string theory

  16. Towards Google matrix of brain

    Energy Technology Data Exchange (ETDEWEB)

    Shepelyansky, D.L., E-mail: dima@irsamc.ups-tlse.f [Laboratoire de Physique Theorique (IRSAMC), Universite de Toulouse, UPS, F-31062 Toulouse (France); LPT - IRSAMC, CNRS, F-31062 Toulouse (France); Zhirov, O.V. [Budker Institute of Nuclear Physics, 630090 Novosibirsk (Russian Federation)

    2010-07-12

    We apply the approach of the Google matrix, used in computer science and World Wide Web, to description of properties of neuronal networks. The Google matrix G is constructed on the basis of neuronal network of a brain model discussed in PNAS 105 (2008) 3593. We show that the spectrum of eigenvalues of G has a gapless structure with long living relaxation modes. The PageRank of the network becomes delocalized for certain values of the Google damping factor {alpha}. The properties of other eigenstates are also analyzed. We discuss further parallels and similarities between the World Wide Web and neuronal networks.

  17. Knockdown of the pericellular matrix molecule perlecan lowers in situ cell and matrix stiffness in developing cartilage.

    Science.gov (United States)

    Xu, Xin; Li, Zhiyu; Leng, Yue; Neu, Corey P; Calve, Sarah

    2016-10-15

    The pericellular matrix (PCM) is a component of the extracellular matrix that is found immediately surrounding individual chondrocytes in developing and adult cartilage, and is rich in the proteoglycan perlecan. Mutations in perlecan are the basis of several developmental disorders, which are thought to arise from disruptions in the mechanical stability of the PCM. We tested the hypothesis that defects in PCM organization will reduce the stiffness of chondrocytes in developing cartilage by combining a murine model of Schwartz-Jampel syndrome, in which perlecan is knocked down, with our novel atomic force microscopy technique that can measure the stiffness of living cells and surrounding matrix in embryonic and postnatal tissues in situ. Perlecan knockdown altered matrix organization and significantly decreased the stiffness of both chondrocytes and interstitial matrix as a function of age and genotype. Our results demonstrate that the knockdown of a spatially restricted matrix molecule can have a profound influence on cell and tissue stiffness, implicating a role for outside-in mechanical signals from the PCM in regulating the intracellular mechanisms required for the overall development of cartilage.

  18. Random matrix theory and multivariate statistics

    OpenAIRE

    Diaz-Garcia, Jose A.; Jáimez, Ramon Gutiérrez

    2009-01-01

    Some tools and ideas are interchanged between random matrix theory and multivariate statistics. In the context of the random matrix theory, classes of spherical and generalised Wishart random matrix ensemble, containing as particular cases the classical random matrix ensembles, are proposed. Some properties of these classes of ensemble are analysed. In addition, the random matrix ensemble approach is extended and a unified theory proposed for the study of distributions for real normed divisio...

  19. Matrix theory selected topics and useful results

    CERN Document Server

    Mehta, Madan Lal

    1989-01-01

    Matrices and operations on matrices ; determinants ; elementary operations on matrices (continued) ; eigenvalues and eigenvectors, diagonalization of normal matrices ; functions of a matrix ; positive definiteness, various polar forms of a matrix ; special matrices ; matrices with quaternion elements ; inequalities ; generalised inverse of a matrix ; domain of values of a matrix, location and dispersion of eigenvalues ; symmetric functions ; integration over matrix variables ; permanents of doubly stochastic matrices ; infinite matrices ; Alexander matrices, knot polynomials, torsion numbers.

  20. Sign Patterns That Allow the Given Matrix

    Institute of Scientific and Technical Information of China (English)

    邵燕灵; 孙良

    2003-01-01

    Let P be a property referring to a real matrix. For a sign pattern A, if there exists a real matrix B in the qualitative class of A such that B has property P, then we say A allows P. Three cases that A allows an M-matrix, an inverse M-matrix and a P0-matrix are considered. The complete characterizations are obtained.

  1. The physical meaning of scattering matrix singularities in coupled-channel formalisms

    Energy Technology Data Exchange (ETDEWEB)

    S. Capstick; A. Svarc; L. Tiator; J. Gegelia; M.M. Giannini; E. Santopinto; C. Hanhart; S. Scherer; T.-S.H. Lee; T. Sato; N. Suzuki

    2007-09-04

    The physical meaning of bare and dressed scattering matrix singularities has been investigated. Special attention has been attributed to the role of well known invariance of scattering matrix with respect to the field transformation of the effective Lagrangian. Examples of evaluating bare and dressed quantities in various models are given.

  2. 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

  3. A novel urokinase receptor-targeted inhibitor for plasmin and matrix metalloproteinases suppresses vein graft disease

    NARCIS (Netherlands)

    Eefting, D.; Seghers, L.; Grimbergen, J.M.; Vries, M.R. de; Boer, H.C. de; Lardenoye, J.W.H.P.; Jukema, J.W.; Bockel, J.H. van; Quax, P.H.A.

    2010-01-01

    Aims Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was d

  4. 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

  5. Unravelling the nuclear matrix proteome

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Knol, Jaco C; Jimenez, Connie R

    2009-01-01

    The nuclear matrix (NM) model posits the presence of a protein/RNA scaffold that spans the mammalian nucleus. The NM proteins are involved in basic nuclear function and are a promising source of protein biomarkers for cancer. Importantly, the NM proteome is operationally defined as the proteins...

  6. Parallel Sparse Matrix - Vector Product

    DEFF Research Database (Denmark)

    Alexandersen, Joe; Lazarov, Boyan Stefanov; Dammann, Bernd

    This technical report contains a case study of a sparse matrix-vector product routine, implemented for parallel execution on a compute cluster with both pure MPI and hybrid MPI-OpenMP solutions. C++ classes for sparse data types were developed and the report shows how these class can be used...

  7. Matrix Treatment of Ray Optics.

    Science.gov (United States)

    Quon, W. Steve

    1996-01-01

    Describes a method to combine two learning experiences--optical physics and matrix mathematics--in a straightforward laboratory experiment that allows engineering/physics students to integrate a variety of learning insights and technical skills, including using lasers, studying refraction through thin lenses, applying concepts of matrix…

  8. Sparse Matrix Vector Processing Formats

    NARCIS (Netherlands)

    Stathis, P.T.

    2004-01-01

    In this dissertation we have identified vector processing shortcomings related to the efficient storing and processing of sparse matrices. To alleviate existent problems we propose two storage formats denoted as Block Based Compression Storage (BBCS) format and Hierarchical Sparse Matrix (HiSM) stor

  9. The COMPADRE Plant Matrix Database

    DEFF Research Database (Denmark)

    2014-01-01

    COMPADRE contains demographic information on hundreds of plant species. The data in COMPADRE are in the form of matrix population models and our goal is to make these publicly available to facilitate their use for research and teaching purposes. COMPADRE is an open-access database. We only request...

  10. Hyper-systolic matrix multiplication

    NARCIS (Netherlands)

    Lippert, Th.; Petkov, N.; Palazzari, P.; Schilling, K.

    2001-01-01

    A novel parallel algorithm for matrix multiplication is presented. It is based on a 1-D hyper-systolic processor abstraction. The procedure can be implemented on all types of parallel systems. (C) 2001 Elsevier Science B,V. All rights reserved.

  11. Student Transfer Matrix, Fall 1996.

    Science.gov (United States)

    Oklahoma State Regents for Higher Education, Oklahoma City.

    The Student Transfer Matrix provides data on the numbers of students transferring from Oklahoma public and private institutions of higher education to other Oklahoma institutions, using data from receiving institutions. Among the highlights are: the number of students who transferred to four-year and two-year institutions remained steady at 57.8…

  12. Regularization in Matrix Relevance Learning

    NARCIS (Netherlands)

    Schneider, Petra; Bunte, Kerstin; Stiekema, Han; Hammer, Barbara; Villmann, Thomas; Biehl, Michael

    2010-01-01

    A In this paper, we present a regularization technique to extend recently proposed matrix learning schemes in learning vector quantization (LVQ). These learning algorithms extend the concept of adaptive distance measures in LVQ to the use of relevance matrices. In general, metric learning can displa

  13. Perturbation semigroup of matrix algebras

    OpenAIRE

    Neumann, N.; Suijlekom, W.D. van

    2016-01-01

    In this article we analyze the structure of the semigroup of inner perturbations in noncommutative geometry. This perturbation semigroup is associated to a unital associative *-algebra and extends the group of unitary elements of this *-algebra. We compute the perturbation semigroup for all matrix algebras.

  14. Bilateral matrix-exponential distributions

    DEFF Research Database (Denmark)

    Bladt, Mogens; Esparza, Luz Judith R; Nielsen, Bo Friis

    2012-01-01

    In this article we define the classes of bilateral and multivariate bilateral matrix-exponential distributions. These distributions have support on the entire real space and have rational moment-generating functions. These distributions extend the class of bilateral phasetype distributions of [1]...

  15. Multivariate Modelling via Matrix Subordination

    DEFF Research Database (Denmark)

    Nicolato, Elisa

    stochastic volatility via time-change is quite ineffective when applied to the multivariate setting. In this work we propose a new class of models, which is obtained by conditioning a multivariate Brownian Motion to a so-called matrix subordinator. The obtained model-class encompasses the vast majority...

  16. Neonatal disorders of germinal matrix

    NARCIS (Netherlands)

    Raets, M M A; Dudink, J; Govaert, P

    2015-01-01

    The germinal matrix (GM) is a richly vascularized, transient layer near the ventricles. It produces neurons and glial cells, and is present in the foetal brain between 8 and 36 weeks of gestation. At 25 weeks, it reaches its maximum volume and subsequently withers. The GM is vulnerable to haemorrhag

  17. Adams Operations on Matrix Factorizations

    OpenAIRE

    Brown, Michael K.; Miller, Claudia; Thompson, Peder; Walker, Mark E.

    2016-01-01

    We define Adams operations on matrix factorizations, and we show these operations enjoy analogues of several key properties of the Adams operations on perfect complexes with support developed by Gillet-Soul\\'e in their paper "Intersection Theory Using Adams Operations". As an application, we give a proof of a conjecture of Dao-Kurano concerning the vanishing of Hochster's theta invariant.

  18. Parallel Sparse Matrix - Vector Product

    DEFF Research Database (Denmark)

    Alexandersen, Joe; Lazarov, Boyan Stefanov; Dammann, Bernd

    This technical report contains a case study of a sparse matrix-vector product routine, implemented for parallel execution on a compute cluster with both pure MPI and hybrid MPI-OpenMP solutions. C++ classes for sparse data types were developed and the report shows how these class can be used...

  19. The COMPADRE Plant Matrix Database

    DEFF Research Database (Denmark)

    2014-01-01

    COMPADRE contains demographic information on hundreds of plant species. The data in COMPADRE are in the form of matrix population models and our goal is to make these publicly available to facilitate their use for research and teaching purposes. COMPADRE is an open-access database. We only request...

  20. Multivariate Matrix-Exponential Distributions

    DEFF Research Database (Denmark)

    Bladt, Mogens; Nielsen, Bo Friis

    2010-01-01

    -exponential distributions. We prove a characterization that states that a distribution is an MVME distribution if and only if all non-negative, non-null linear combinations of the coordinates have a univariate matrix-exponential distribution. This theorem is analog to a well-known characterization theorem...