To see the other types of publications on this topic, follow the link: ROPE matrix.
Dissertations / Theses on the topic 'ROPE matrix'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'ROPE matrix.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Rodríguez, Escribà Marta. "Role of tRNA modifications in the synthesis of the extracellular matrix." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/668499.
Full textAbstract:
Transfer RNAs (tRNAs) are key adaptor molecules that mediate decoding of messenger RNAs (mRNAs) into proteins by complementary pairing of their anticodons with mRNA codons. tRNAs that undergo adenosine to inosine editing at the wobble base, or position 34, display expanded codon decoding capacity as inosine enables pairing not only with uridine, but also with cytosine and adenosine. The essential heterodimeric enzyme Adenosine Deaminase Acting on Transfer RNA (ADAT) catalyzes this post-transcriptional modification in eukaryotes and is comprised of subunits ADAT2 and ADAT3. Emergence of heterodimeric ADAT has been proposed to have shaped both tRNA gene content and codon composition of eukaryotic genomes in such a way that these two features became mirrored. Although the exact contribution of wobble inosine (I34) to translation elongation has not been established, previous reports have suggested that it might play a role in improving translational efficiency and accuracy of genes enriched in codons recognized by I34-modified tRNAs.
To further understand the role of the inosine modification in translation, we generated cell lines depleted in the catalytic subunit ADAT2. Silencing of ADAT2 lead to impaired cellular proliferation and had a variable impact on the expression of genes coding for extracellular matrix (ECM) proteins such as mucins. Notably, ADAT2 deficiency did not have major effects on the post-translational glycosylation of mucins, neither did it trigger the unfolded protein response. Supported by the absence of clear defects in decoding rates in ADAT2 depleted cells, as measured by ribosome profiling, our findings suggest that a reduced pool of I34-modified tRNAs might suffice to carry out cellular functions in steady-state conditions. However, we found that, under circumstances involving a high demand for these tRNAs such as airway remodeling, ADAT2 is required for the proper translation of an ECM gene enriched in stretches of codons read by I34-tRNAs. Taken together, our results suggest that the inosine modification is particularly relevant for the synthesis of ECM proteins during specialized processes including neural development and airway remodeling.
The importance of the inosine modification has been recently underscored by the identification of pathogenic mutations in the gene encoding ADAT3, all of which share common neurodevelopmental phenotypes. The most prevalent mutation identified to date is a valine to methionine (V144M) substitution that is linked to intellectual disability and strabismus. In the present study we characterized human ADAT in terms of activity and quaternary structure, and investigated the effect of the ADAT3 V144M mutation on the enzyme. We showed that the V144M substitution leads to decreased enzymatic activity of ADAT, which might result from alterations in the tertiary structure and subcellular localization of ADAT3 that were found to be associated to the mutation.Els ARNs de transferència (ARNt) són molècules que tenen un paper clau en el procés de traducció dels ARN missatgers (ARNm) en proteïnes mitjançant la interacció del seu anticodó amb codons d’ARNm. Els ARNt que passen per un procés d’edició d’adenosina a inosina a la base wobble, o posició 34, són capaços de llegir més d’un codó d’ARNm gràcies a la capacitat de la inosina de reconèixer els tres nucleòtids uridina, citidina i adenosina. L’enzim responsable d’aquesta modificació post-transcripcional en eucariotes s’anomena Adenosina Deaminasa específica per l’ARNt (ADAT), es tracta d’un complex heterodimèric format per les subunitats ADAT2 i ADAT3 que és essencial per a la viabilitat de l’organisme. Estudis previs han proposat que l’aparició d’ADAT va determinar el nombre de còpies gèniques de cada ARNt així com la composició de codons presents als genomes eucariòtics de tal manera que aquests dos factors estiguessin mútuament balancejats. Tot i que la contribució precisa de la inosina 34 (I34) a la traducció de proteïnes durant la fase d’elongació encara s’ha determinat experimentalment, algunes investigacions han suggerit que podria jugar un rol en l’eficiència i fidelitat de traducció de gens enriquits en codons reconeguts per ARNt modificats amb I34. Amb l’objectiu d’investigar el rol de la inosina en la traducció, hem generat línies cel·lulars on el gen codificant per ADAT2 ha estat silenciat. La depleció d’ADAT2 comporta un retard en el creixement cel·lular i té un efecte variable en l’expressió gènica de proteïnes de la matriu extracel·lular. El patró de modificacions post-traduccionals de glicosilació d’aquestes proteïnes no resulta alterat per la deficiència d’ADAT2, que tampoc activa la resposta a proteïnes desplegades. Juntament amb l’absència de defectes en la velocitat d’elongació analitzada per ribosome profiling, aquestes observacions suggereixen que la cèl·lula és capaç de dur a terme les seves funcions amb un nombre reduït d’ARNt modificats amb inosina. Hem vist, però, que en condicions que requereixen majors quantitats d’ARNt inosinats, la depleció d’ADAT2 dóna lloc a la traducció ineficient d’un gen de matriu extracel·lular altament enriquit en codons sensibles llegits per ARNt modificats. Així doncs, els nostres resultats indiquen que la inosina pot exercir un rol important en la síntesi de proteïnes de la matriu extracel·lular, particularment durant processos de desenvolupament neuronal i de remodelat de les vies respiratòries. La rellevància de la modificació I34 s’ha vist reforçada recentment per la identificació de mutacions de caire patogènic localitzades al gen que codifica ADAT3. Totes elles tenen en comú la presència de fenotips relacionats amb el desenvolupament neurològic. La mutació d’ADAT3 més comuna consisteix en la substitució d’un residu valina per un metionina (V144M) i està associada a la manifestació de discapacitat intel·lectual i estrabisme. En el present estudi hem caracteritzat l’activitat enzimàtica i l’estructura quaternària de l’ADAT humà, així com l’impacte de la mutació V144M d’ADAT3 en el complex heterdimèric. Els nostres revelen que la substitució V144M dóna lloc a una menor activitat enzimàtica d’ADAT. És possible que aquesta reducció es vegi influïda per les alteracions en l’estructura terciària i en la localització cel·lular d’ADAT3 que indueix la mutació.
2
Stanton, Heather. "The role of matrix metalloproteinases in cell-matrix interactions." Thesis, Open University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284376.
Full text
3
Gregory, Jeremy R. (Jeremy Ryan) 1976. "The role of precipitates on fiber/matrix interfaces in metal matrix composites." Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/89301.
Full text
4
Bear, Harriet Mary. "The role of tyrosine rich acidic matrix protein in the extracellular matrix." Thesis, University of Edinburgh, 1997. http://hdl.handle.net/1842/21534.
Full textAbstract:
A number of purification strategies were performed in an attempt to produce highly purified, active TRAMP free from lysyl oxidase for fibrillogenesis and enzymatic studies. TRAMP was eventually purified by DEAE anion exchange followed by Superdex-75 size exclusion (in the presence of urea) and Mono Q FPLC anion exchange chromatography. Yields of 10μg of TRAMP per g wet weight starting material were obtained. TRAMP purified as above was active in fibrillogenesis assays using the 'warm start' technique, in buffers containing 30mM TES, 30mM Na2HPO4, 135mM NaCl pH 7.4. The acceleratory effect of TRAMP on collagen I fibril formation was also observed when the phosphate concentration was lowered to 10mM and when TES was removed. TRAMP has previously been shown to bind to in vitro reconstituted collagen fibrils if present during their formation. Reducing the phosphate concentration decreased the amount of TRAMP associated with collagen I fibrils in co-sedimentation assays, whilst subsequent removal of TES had no effect on TRAMP binding to collagen I fibrils. Preliminary observations also suggested that treatment of TRAMP with sulphatase had no effect on the ability of TRAMP to accelerate collagen I fibril formation. A solid phase assay showed TRAMP to bind collagen I monomers with a higher affinity than fibrils, suggesting a role for TRAMP in the early, nucleation phase of fibril formation. TRAMP was unable to reverse the inhibitory effect of decorin on fibril formation. The presence of decorin had no effect on TRAMP binding to collagen monomers in solid phase assays but led to an increase in the amount of TRAMP associated with collagen fibrils in co-sedimentation assays. Attempts to identify specific binding sites for TRAMP on in vitro reconstituted collagen I fibrils by immunogold labelling and electron microscopy were unsuccessful. Western blot analysis of murine tissues confirmed previous reports that TRAMP was present in lung and skeletal muscle and absent in brain and spleen.
5
Molik, Bablin. "Role of matrix metalloproteinases in uveoscleral outflow." Thesis, Cardiff University, 2007. http://orca.cf.ac.uk/54613/.
Full textAbstract:
Prostaglandin derivatives form the most widely used medicinal treatments given to glaucoma patients to lower intraocular pressure. Prostaglandins are believed to increase matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) activity, leading to increased in aqueous outflow, via uveoscleral outflow pathway. However, the direct impact of MMPs on the tissues within uveoscleral pathway has not been determined. The aim of this project was to compare the direct effect of prostaglandins and MMPs on the tissues within the uveoscleral outflow pathway. To determine the effect of known inducers of MMP activity, scleral fibroblasts and ciliary muscle cells were cultured in the presence of interleukin-1a, tumour necrosis factor, transforming growth factor p and prostaglandin F2a (PGF2a). The effect of prostaglandin F2a and MMPs on the uveoscleral pathway tissue i.e. sclera, was assessed as a measure of permeability, molecular and supramolecular scleral collagen integrity and proteoglycan composition. A significant induction of MMP 1, 2, 3 and 9 secretion and activity with cytokines and PGF2a, within human scleral fibroblast and ciliary muscle cell cultures (p<0.05). A 3-fold increase in scleral permeability was observed within 24 hour of incubation in PGF2a, whereas upto 10-fold increase was observed in MMP treated. The helical rise per residue (at 1.5nm), lateral packing (at 0.29nm) and D-spacing (at 66nm) of scleral collagen was unaffected by MMP and PGF2a incubation. Significant change in aggrecan degradation was observed within scleral tissue incubated in MMP and PGF2a (p<0.05). However, no significant change in small leucine rich proteoglycans i.e. biglycan, decorin and lumican, within sclera occurred within sclera incubated in MMP or PGF2a.
6
Staines, Katherine Ann. "Role of MEPE in chondrocyte matrix mineralisation." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/8157.
Full textAbstract:
Matrix Extracellular Phosphoglycoprotein (MEPE) is a member of a family of proteins called small integrin-binding ligand, N-linked glycoproteins (SIBLINGs) which play key roles in biomineralisation. Altered MEPE expression is associated with several phosphate and bone-mineral metabolic disorders such as oncogenic osteomalacia and hypophosphatemic rickets. Despite this, it remains undetermined what impact MEPE has on the growth plate; the cartilage anlagen from which endochondral ossification, the process responsible for linear bone growth, occurs. The work of this thesis has characterised the ATDC5 cell line and the metatarsal organ culture as useful in vitro models of endochondral ossification. These will prove vital in the pursuit of underpinning the molecular mechanisms involved in endochondral bone growth. These models form the basis of the further studies in this thesis examining the role of MEPE within this highly orchestrated process. Before such role can be defined, this thesis details the spatial and temporal localisation patterns of MEPE in 10-day- and 4-week-old murine growth plates. More specifically, MEPE protein and mRNA were preferentially expressed by the hypertrophic chondrocytes as shown by immunohistochemistry and in situ hybridisation respectively. Microdissection of the murine growth plate confirmed this. Localisation of the cleavage product of MEPE, a 2.2kDa acidic serine- and aspirate-rich motif (ASARM) peptide, followed a similar pattern of expression. The localisation of MEPE to sites of mineralisation serves to strengthen its potential role in chondrocyte matrix mineralisation. This thesis identified this role in both mineralising ATDC5 cells and the metatarsal organ culture. The ASARM peptide was found to be the functional component of MEPE and this function was dependent upon its post-translational phosphorylation. Phosphorylated (p)ASARM peptides significantly inhibited chondrocyte matrix mineralisation without altering the proliferation or differentiation of the chondrocyte cells, or their ability to produce an extracellular matrix. mRNA analysis by qPCR indicted a feedback system by which the pASARM peptide functions to allow the release of further ASARM peptides. Moreover, the pASARM peptide inhibited mRNA expression of markers of vascular angiogenesis highlighting a novel mechanism by which they may inhibit chondrocyte matrix mineralisation. This thesis also determines the regulatory cross-talk between the chondrocytes of the murine growth plate, with the most abundant bone cell type, the osteocyte. This cross-talk inhibits chondrocyte matrix mineralisation and is attributed to sclerostin, an osteocyte-specific secretory protein. Furthermore, it is shown that sclerostin acts through the MEPE-ASARM axis to regulate chondrocyte matrix mineralisation and thus endochondral ossification. The work described herein has characterised and validated in vitro models of growth plate chondrocyte matrix mineralisation and has used these to identify the role of MEPE within chondrocyte matrix mineralisation.
7
Behzadi, Shabnam. "Role of matrix yield in composite performance." Thesis, University of Sheffield, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434485.
Full text
8
Leonardo, Christopher C. "The Role of Extracellular Matrix and Matrix-Degrading Proteases in Neonatal Hypoxic-Ischemic Injury." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002587.
Full text
9
Lytras, Theodoros 1987. "The Role of occupational exposures in Chronic Obstructive Pulmonary Disease." Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/586017.
Full textAbstract:
Introduction: Occupational exposures are considered to be one of the newer and important risk factors for Chronic Obstructive Pulmonary Disease (COPD) besides tobacco smoking. However, the evidence mostly comes from smaller and cross-sectional studies and important questions remain unanswered, such as which specific exposures are responsible, the magnitude of the risk involved, and how the risk varies between men and women and between smokers and nonsmokers. The aim of this thesis was to examine the association between objectively assessed occupational exposures and changes in COPD-related outcomes over two decades in the European Community Respiratory Health Survey (ECRHS), a large multicentre population-based longitudinal study.
Methods: General population samples aged 20-44 years were randomly enrolled in the ECRHS between 1991 and 1993, and twice followed up over the course of 20 years. Complete job histories during this follow-up were linked to the ALOHA(+) Job-Exposure Matrix, generating occupational exposures to 12 categories of agents. Spirometries were performed at each study visit. The outcomes of interest were: lung function decline, chronic bronchitis incidence and post-bronchodilator COPD incidence.
Results: Exposure to biological dust, gases & fumes and pesticides was associated with higher COPD incidence, with 21% of all COPD cases attributable to these three agents. Pesticides were associated with higher incidence of chronic phlegm but only in women, and gases & fumes and solvents also with chronic phlegm but only in men. Mineral dust exposure was associated with higher chronic phlegm incidence and metals exposure with hicher chronic bronchitis incidence, in both sexes. All studied exposures except solvents were associated with accelerated decline in the FEV1/FVC ratio, particularly in male smokers. Women exposed to biological dust also tended to have higher declines in FVC, as did men exposed to pesticides.
Conclusions: A substantial proportion of the total COPD burden is attributable to occupational exposures. The effect of occupation on COPD-related outcomes is complex, and depends on exposure type, sex and smoking status. Further research is warranted to provide more details about the observed associations.Introducció: Les exposicions ocupacionals es consideren un dels factors de risc importants per a la malaltia pulmonar obstructiva crònica (MPOC) juntament amb tabaquisme. No obstant això, l'evidència prové principalment d'estudis de mida petita i transversals i preguntes importants segueixen sense resposta, per exemple quines exposicions específiques són responsables, la magnitud del risc involucrat i com el risc varia entre homes i dones o entre fumadors i no fumadors. L'objectiu d'aquesta tesi és examinar l'associació entre exposicions ocupacionals objectivament avaluades i els canvis en els resultats relacionats amb la MPOC durant dues dècades en l'Enquesta de Salut Respiratòria de la Comunitat Europea (ECRHS), un gran estudi longitudinal multicèntric poblacional. Mètodes: La mostra de la població general amb edats compreses entre 20 i 44 anys es va seleccionar aleatòriament a l’ECRHS entre 1991 i 1993, i a els participants se’ls hi va fer seguiment dues vegades en el transcurs de 20 anys. L'historial complet de treballs durant el període de seguiment es va vincular amb la Matriu d'Ocupació-Exposició ALOHA (+), generant estimacions d'exposicions ocupacionals a 12 categories d'agents. Les espirometries es van realitzar en cada visita d'estudi. Els resultats d'interès van ser: disminució de la funció pulmonar, incidència de bronquitis crònica i incidència de MPOC després de broncodilatació. Resultats: L'exposició a pols, gasos i fums biològics i pesticides es va associar amb una major incidència de MPOC, amb un 21% de tots els casos de MPOC atribuïbles a aquests tres agents. Els pesticides es van associar amb una major incidència d’expectoració crònica, però només en les dones, i gasos i fums i dissolvents també amb expectoració crònica, però només en els homes. L'exposició a la pols mineral es va associar amb una major incidència d’expectoració crònica i l’exposició a metalls amb incidència de bronquitis crònica, en ambdós sexes. Totes les exposicions estudiades, excepte els dissolvents, es van associar amb una disminució accelerada de la relació FEV1 / CVF, (VEMS/CVF) particularment en fumadors homes. Les dones exposades a la pols d'origen biològic també van tenir majors disminucions en la capacitat vital forçada (CVF), igual que els homes exposats als pesticides. Conclusions: Una proporció important dels casos de MPOC és atribuïble a exposicions ocupacionals. L'efecte de l'ocupació en els resultats relacionats amb la MPOC és complex i depèn del tipus d'exposició, el sexe i el tabaquisme. Es requereix més investigació per proporcionar més infromació sobre les associacions observades
10
Garcia, Puig Anna. "Study of extracellular matrix remodeling and the role of periostin b during zebrafish heart regeneration." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/666564.
Full textAbstract:
Adult zebrafish (Danio rerio), in contrast to mammals, are able to regenerate their hearts in response to injury or experimental amputation. Our understanding of the cellular and molecular bases that underlie this process, although fragmentary, has increased significantly over the last years. However, the role of the extracellular matrix (ECM) during zebrafish heart regeneration has been comparatively rarely explored. A better understanding of all the mechanisms underlying this complex process would help developing strategies to regenerate the human heart. With this aim, here, we set out to characterize the ECM protein composition in adult zebrafish hearts, whether it changed during the regenerative response, and the role of the matricellular protein periostin b.
For this purpose, in the first part of the current thesis, we established a decellularization protocol of adult zebrafish ventricles that significantly enriched the yield of ECM proteins. We then performed proteomic analyses of decellularized control hearts and at different times of regeneration. Our results show a dynamic change in ECM protein composition, most evident at the earliest (7 days post-amputation) time-point analyzed. Regeneration associated with sharp increases in specific ECM proteins, and with an overall decrease in collagens and cytoskeletal proteins. We finally tested by atomic force microscopy that the changes in ECM composition translated to decreased ECM stiffness. Our cumulative results identify changes in the protein composition and mechanical properties of the zebrafish heart ECM during regeneration.
In the second part of the current thesis, we have examined the role of periostin b (postnb) during zebrafish heart regeneration. We found that postnb was abundant in the injury of amputated zebrafish ventricles, and we designed two strategies to suppress postnb during regeneration: 1) a shRNA transgenic knock-down, and 2) a CRISPR/Cas9 postnb-/- zebrafish. Knock-down and knock-out fishes did not exhibit any evident developmental defects, but showed a lack complete cardiac regeneration after amputation. The absence of postnb did not have any effect on leukocyte recruitment, matrix metalloproteinase activation or revascularization after amputation. However, postnb-/- zebrafish developed a softer cardiac ECM due to a reduction of collagen cross- linking, and showed an increase of cardiomyocyte proliferation and a decrease on cardiomyocyte cell death after amputation. The stiffness control by postnb seem to be important to correctly modulate stiffness for a complete cardiac regeneration. Stiffness analysis toguether with proliferation analysis suggest that postnb is needed to increase the stiffness in the injury border to instruct cardiomyocytes to stop proliferating and migrate to the injury site.El peix zebra adult (Danio rerio) és capaç, contràriament als mamífers, de regenerar el seu cor en resposta a una lesió o amputació experimental. La comprensió de les bases cel·lulars i moleculars subjacents a aquest procés ha augmentat significativament en els últims anys, encara que segueix sent fragmentària. Tot i així, el paper de la matriu extracel·lular (MEC) durant la regeneració cardíaca del peix zebra ha estat rarament explorat. Una millor comprensió de tots els mecanismes subjacents a aquest complex procés podria ajudar a desenvolupar estratègies per a regenerar el cor humà. Amb aquest objectiu, es va proposar caracteritzar la composició proteica de la MEC en cors de peix zebra adults, els possibles canvis existents durant la resposta regenerativa, i el paper de la proteïna matricel·lular periostin b (postnb). A aquest efecte, a la primera part de la present tesis, es va establir un protocol de descel·lularització de ventricles de peix zebra adults, que va aconseguir un enriquiment significatiu en el contingut en proteïnes de la MEC. A continuació, es va realitzar un anàlisi proteòmics de cors control descel·lularitzats i en diferents moments del procés de regeneració per avaluar els canvis proteics. Els nostres resultats mostren un canvi dinàmic en la composició proteica de la MEC, més evident a temps més inicial del procés de regeneració analitzat (7 dies després de l'amputació). Així, la regeneració cardíaca es va associar a un increment de proteïnes especifiques de la MEC, i a una reducció generalitzada de col·làgens i proteïnes citoesquelètiques. Finalment, es va analitzar per Atomic Force Microscopy els canvis en la duresa de la MEC produïts per aquests canvis observats de composició. El nostre conjunt de resultats identifiquen canvis en la composició proteica i les propietats mecàniques de la MEC cardíaca durant la regeneració. A la segona part de la present tesis, es va examinar el paper de la periostin b (postnb) durant la regeneració cardíaca del peix zebra. La seva presència era abundant a la ferida de ventricles amputats, i es van dissenyar dues estratègies per a suprimir la postnb durant la regeneració: 1) un knock-down (KD) mitjançant shRNAs, i 2) un knock- out (KO) per CRISPR/Cas9. Ni la línia KD ni la KO exhibien cap defecte del desenvolupament, però demostraven una clara deficiència en el procés de regeneració després de l’amputació del ventricle. La absència de la postnb no va demostrar cap efecte sobre el reclutament de leucòcits, l’activació de les metaloproteases de matriu (MMP), o la revascularització després de l’amputació. Tot i així, els peixos postnb-/- van desenvolupar una MEC més tova degut a una reducció del cross-linking del col·lagen. Alhora, van demostrar un increment de la proliferació i una reducció de l’apoptosi dels cardiomiòcits després de l’amputació. El control de la duresa de la MEC efectuat per la postnb sembla ser important per modular correctament aquesta propietat mecànica per a una regeneració cardíaca completa. Els anàlisis de duresa conjuntament amb els anàlisis de proliferació suggereixen que la postnb és necessària per a un increment de la duresa en la vora de la ferida. Així, seria requerida per a instruir als cardiomiòcits per parar de proliferar i migrar cap a la ferida.
11
Moffett, J. F. "The role of matrix metalloproteinases in cystic fibrosis." Thesis, Queen's University Belfast, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.579760.
Full textAbstract:
Cystic fibrosis (CF) lung disease is characterised by progressive destruction and dilatation of the airways. This occurs in the setting of chronic infection, particularly with Pseudomonas aeruginosa (Pa), and is associated with loss of elastin and cartilage, with progressive submucosal fibrosis. Matrix Metalloproteinases (MMPs) can degrade all components of the extracellular matrix, and are inhibited by the Tissue Inhibitors of Metalloproteinases (TIMPs). High MMP-9 activity has been identified in CF sputum, and correlates inversely with lung function (FEV1). The source and regulation of MMP-9 in CF is unknown. Direct Pa infection of epithelial cells resulted in destruction of TIMP-1, the major inhibitor of MMP-9. Pa infection of inflammatory cells" neutrophils, monocytes and monocyte derived macrophages (MDMs); resulted in an unopposed increase in MMP-9. Conditioned media from Pa infected neutrophils (coNPa), monocytes (coMPa) and MDMs (coMDMPa) drove further secretion of MMP-9 from epithelial cells. This was shown to be regulatecl by Mitogen activated protein kinase (MAPK) pathways. The functional, matrix degrading effects of MMPs produced following conditioned media stimulation were examined and revealed that stimulated epithelial cells were able to invade through a matrigel membrane and drive an invasive phenotype, potentially characterising the involvement of MMPs in extracellular matrix breakdown in CF. Further, MMP-9 secretion in conjunction with cytokines and growth factors found in the CF airway, acted on epithelial cells resulting in loss of epithelial cell contact with basement membrane and subsequent invasion of epithelium into the mesenchyme- a process known as Epithelial to mesenchymal transition (EMT). In summary, infiltrating leukocytes and the lung parenchyma are potential sources of excessive MMP-9 activity in CF, and may contribute to the airway destruction that occurs in response to Pa infection.
12
Shen, Yun, and 沈筠. "The role of extracellular matrix in planarian regeneration." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206722.
Full text
13
Gavrilovic, J. "The role of metalloproteinases in extracellular matrix degradation." Thesis, Anglia Ruskin University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377546.
Full text
14
Hemers, Elaine Marie. "Epithelial-mesenchymal signalling : role of matrix metalloproteinase-7." Thesis, University of Liverpool, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410645.
Full text
15
Bergen, Dylan Jeroen Marcel. "A dual role for the Colgi matrix protein giantin in extracellular matrix secretion and cilia function." Thesis, University of Bristol, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.738238.
Full text
16
Lam, Charlton. "Expression of Matrix Metalloproteinases in Naegleria fowleri and Their Role in Degradation of the Extracellular Matrix." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4962.
Full textAbstract:
Naegleria fowleri is a free-living amoeba found in freshwater lakes and ponds that is the causative agent of Primary Amoebic Meningoencephalitis (PAM). Matrix metalloproteinases (MMPs) have been described in protozoa, such as Plasmodium falciparum, Trypanosoma brucei, and Balamuthia mandrillaris, and have been linked to their increased motility and invasive capability by degrading components of the extracellular matrix (ECM). In addition, MMPs are often upregulated in tumorigenic cells and have been attributed as responsible for the metastasis of certain cancers. In the present study, in vitro experiments indicated that MMPs are linked functionally to the ECM degradation process. Gelatin zymography demonstrated protease activity in N. fowleri whole cell lysates, conditioned media, and media collected from in vitro invasion assays. Western immunoblotting confirmed the presence of the metalloproteinases MMP-2, -9, and -14. The highly virulent mouse-passaged amoebae expressed higher levels of MMPs than the weakly virulent axenically grown amoebae. The functional relevance of MMPs found in media in degradation of ECM components was confirmed through the use of MMP inhibitors. The collective in vitro results suggest that MMPs may play a critical role in the invasion of the CNS. Furthermore, the expression of select metalloproteinases may serve as amenable targets for therapeutic manipulation of expansive PAM.
17
Townley, W. "An investigation into the role of matrix metalloproteinases in matrix remodelling and contraction by Dupuytren's fibroblasts." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445949/.
Full textAbstract:
Dupuytren's disease is a common fibroproliferative condition of the hand that results in disability through progressive digital contracture. Despite advances in operative technique, recurrence remains an unsolved problem. The matrix metalloproteases (MMPs) are a large family of proteolytic enzymes that have been shown to play a critical role in cell-mediated collagen contraction and tissue scarring. The aim of this project was to investigate the effect of ilomastat, a broad-spectrum MMP inhibitor, on matrix contraction and remodelling by Dupuytren's fibroblasts in vitro. Paired nodule and cord-derived fibroblasts were isolated by explant culture from five Dupuytren's patients, carpal ligament fibroblasts acted as the control. We employed two different in vitro models to assess the effect of ilomastat on contraction and remodelling by each cell population. A stress-release fibroblast populated collagen lattice (FPCL) model was employed to assess collagen contraction. Generation of mechanical tension was determined using a culture force monitor (CFM). Following dynamic force generation, treatment with cytochalasin-D was used to assess residual matrix tension (RMT) in the collagen lattice, allowing quantification of matrix remodelling. The expression of a range of MMPs (MMP-1, MMP-2, MT1-MMP) and Tissue Inhibitors of Metalloproteinases (TIMP-1, TIMP-2), was established by RT-PCR. Protein levels and enzyme activity were assessed by western blotting, zymography and ELISA. In the FPCL model, ilomastat significantly (p<0.01) inhibited contraction by all tissue-derived fibroblasts at 100uM. In the CFM model, ilomastat significantly reduced force development by cord and nodule-derived fibroblasts (p<0.01), but did not significantly affect RMT. In both models, treatment with ilomastat suppressed activity of MMP-1 and MMP-2, however gene expression and levels of secreted protein were unaffected. Conversely, the expression and activity of MT1-MMP was upregulated in response to ilomastat, whereas, TIMP-1 and TIMP-2 were unaffected. Our findings demonstrate an important role for MMP activity in matrix processing and organisation by Dupuytren's fibroblasts in vitro and suggest that inhibition of MMP activity may well provide a means of controlling or reducing contracture in vivo, by reducing fibroblast-mediated matrix contraction and remodelling.
18
Dash, Shantoshini. "Role of M1 protein and actin-associated cellular cofactors in Influenza A Virus assembly and release." Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT034.
Full textAbstract:
Le virus de la grippe A (le H1N1) pdm09, généralement connu comme le virus de la grippe porcine, a causé la toute première pandémie du 21e siècle. Le virus de grippe est un virus enveloppé à ARN qui utilise la machinerie cellulaire de l’hôte pour s’assembler à la membrane plasmique de la cellule et être relargué à l’extérieur. Dans cette étude, nous nous sommes intéressés au rôle de la protéine virale de matrice M1 dans ce processus. M1 est la protéine la plus abondante et elle est extrêmement importante pour le virus de la grippe. Les 164 résidus de la protéine M1 situés en N-terminal comprennent deux domaines basiques qui sont : le triplet d’arginine (R76/77/78) sur l'hélice 5 et le signal de localisation nucléaire sur l'hélice 6. Ils sont très bien conservés parmi les sous types de la grippe. Premièrement, pour étudier l'interaction M1-membrane, nous avons développé et standardisé un système minimal regroupant M1+M2+NS1/NEP (±M) dans lequel nous pourrons aussi observer la production de VLPs incorporant M1. En utilisant ce système, nous avons créé des mutations dans le triplet d’arginine de M1 et avons regardé l'accrochage de M1 à la membrane ainsi que l'incorporation de M1 dans les VLPs. La conséquence de ces mutations est que la protéine M1 reste dans le cytosol et qu’il y a une réduction drastique du nombre de VLPs contenant M1 relargués. La mutation du triplet arginine par un triplet alanine inhibe complètement la production de VLPs. De plus, un virus mutant avec ce triplet d’alanine n’est plus capable de produire des virions infectieux. Ainsi nous avons mis en évidence l'importance du triplet arginine dans l'accrochage de M1 à la membrane et la production de virions. Par conséquent, pour étudier l’utilisation de l'actine et de ses cofacteurs par le virus, nous avons utilisé de petits ARN interférents pour inhiber l’expression de gènes dans un système minimal de production de VLPs. Nous avons observé une réduction de la production de VLPs contenant M1 en inhibant Rac1et une augmentation de la libération de VLPs contenant M1 en inhibant RhoA et Cdc42. En utilisant un virus IAV (H3N2)-nanoluciferase sur les cellules A549 pulmonaires, nous avons étudié l'effet de la déplétion des RhoGTPases et de leurs effecteurs sur la production virale. Nous avons observé qu'avec Rac1, l'inhibition de Wave2 et Arp3 réduit aussi le pouvoir infectieux du virus H3N2 au cours des étapes tardives de l'infection sans affecter la phase précoce de d'infection. Les protéines interagissant avec M1 ont été identifiées par LC-MS/MS et incluent la cofiline et l’annexine A2. La cofiline, déjà connue pour participer à la réorganisation de l’actine pendant la phase tardive de l’infection par le virus de la grippe, est aussi un effecteur activé par Rac1, Wave2, Pak1 et LIMK afin de former des lamellipodes. L’annexine A2 est aussi connue pour séquestrer la PS au niveau du feuillet interne de la membrane plasmique cellulaire. La reconnaissance de ces groupes de PS par la protéine virale M1 amorcera finalement le processus d’assemblage viral. Ainsi, nos résultats, en décrivant le mécanisme d'accrochage de M1 à la membrane, montrent aussi que Rac1, Wave2 et Arp3 sont probablement des facteurs pro-viraux de l’assemblage et de la libération des virus de la grippe AThe influenza A(H1N1)pdm09 virus, commonly known as swine flu, caused the very first pandemic of 21st century. Influenza virus, an enveloped RNA virus, uses the host cellular machinery for its assembly and release from the host cell plasma membrane. In this study, we were interested in the role of the viral M1 matrix protein in this process. M1 is the most abundant and vitally important protein present in influenza virus. The N-terminal 164 residues of M1 protein comprise of two basic domains which are the arginine triplet (R76/77/78) on helix 5 and the nuclear localization signal on helix 6, which are very well conserved among the influenza A virus subtypes. Firstly, to study M1-membrane interaction, we developed and standardized a minimal system consisting of M1+M2+NS1/NEP(±M) in which we could also observe production of VLPs incorporating M1. Using this system, we performed mutations in the M1 arginine triplet and looked at changes in M1 membrane attachment and M1 incorporation in VLP. As a result of these mutations, the M1 protein remained cytosolic and there was a drastic reduction in M1 containing VLP release. Mutating the entire arginine triplet to an alanine triplet inhibited VLP production completely. Also, a mutant virus with this alanine triplet failed completely to produce infectious virions. Thus we established the importance of the arginine triplet in M1 membrane attachment and virion production. Consequently, to study manipulation of actin and its cofactors by the virus, we used siRNA mediated gene silencing in the VLP producing minimal system. We observed a reduction in M1 containing VLP production upon inhibition of Rac1 and enhancement of M1 containing VLPs released upon inhibition of RhoA and Cdc42. By using an IAV (H3N2)-nanoluciferase virus on pulmonary A549 cells, we studied effect of depletion of RhoGTPases and their effectors on virus production. We observed that along with Rac1, inhibition of Wave2 and Arp3 also reduces the infectivity of H3N2 virus at the late phase of infection without any effect on the early phase of infection. The proteins interacting with M1 were identified by LC-MS/MS and included cofilin and annexin A2. Cofilin, already known to take part in the actin reorganization during the late phase of influenza A virus infection, is also one of the downstream effector linked to Rac1, Wave2, Pak1 and LIMK, for lamellipodia formation. Annexin A2 is also known to sequester PS at the inner leaflet of the cell plasma membrane. The viral protein M1 is able to recognize these clusters of PS, which ultimately initiates the viral assembly process. Thus, our results, while defining the mechanism of M1 membrane attachment, also indicate the possible involvement of Rac1, Wave2 and Arp3 as pro-viral factors in IAV assembly and release
19
Jamil, Aqeel. "The role of matrix metalloproteinase-2 in liver fibrosis." Thesis, University of Southampton, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445490.
Full text
20
Wong, Tina Tzee Ling. "The role of matrix metalloproteinases in conjunctival wound healing." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405196.
Full text
21
Cockett, Mark I. "The role of matrix metalloproteinases in tumour cell invasion." Thesis, Open University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294559.
Full text
22
Baneyx, Gretchen W. "The role of mechanical tension in fibronectin matrix assembly /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/8059.
Full text
23
Garcia, John Francis. "The role of extracellular matrix proteins in epithelial tumorigenesis /." May be available electronically:, 2008. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Full text
24
Thongnuek, Peerapat. "The role of tendon matrix proteins in muscle adhesion." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709043.
Full text
25
Loftus, Ian Magnus. "The role of matrix mellaproteinases in cartoid plaque morphology." Thesis, University of Leicester, 2001. http://hdl.handle.net/2381/29388.
Full textAbstract:
Thromboembolic disease secondary to atherosclerosis is the commonest cause of myocardial infarction and ischaemic stroke. The atherosclerotic plaque develops into a complex structure consisting of a lipid rich core and a connective tissue matrix. If the plaque undergoes acute change such as rupture or ulceration, exposure of highly thrombogenic material in the plaque core leads to thrombus formation with subsequent embolisation or vessel occlusion. There is considerable evidence to support the theory that such acute changes immediately precede the onset of clinical symptoms. Targeting pharmacotherapy towards preventing acute plaque change could in theory reduce the risk of stroke and myocardial infarction in patients with atherosclerosis. The potential for therapeutic intervention to prevent disease progression is therefore a very attractive option, but the precise cause of acute plaque disruption and thus the target for pharmacotherapy, has been elusive. There is increasing evidence that a group of proteolytic enzymes called matrix metalloproteinases (MMPs) are intimately involved in the atherosclerotic disease process. The plaque is a dynamic structure, undergoing continuous remodelling of the extracellular matrix upon which its structural integrity depends. MMPs represent the main physiological regulators of the extracellular matrix, and any imbalance between the level of MMPs and their inhibitors could cause increased matrix degradation. The hypothesis in this study of was that a localised imbalance in the level of MMPs and their inhibitors may be associated with plaque instability and the onset of clinical events. The aim of the study was to quantify the major MMP/TIMP subtype levels within carotid plaques and to correlate them with clinical and histological features of plaque instability.
26
Chowdhury, Biswajit. "Determining the role of murine hyaluronidase 2 in hyaluronan catabolism." The American Society for Biochemistry and Molecular Biology, 2013. http://hdl.handle.net/1993/31154.
Full textAbstract:
Hyaluronidase 2 (HYAL2) is a GPI-linked protein that is proposed to initiate the degradation of hyaluronan (HA), a major extracellular matrix component of many vertebrate tissues. Hyal2 knockout (KO) mice displayed craniofacial abnormalities and severe preweaning lethality. 54% of the surviving KOs developed a grossly dilated left or right atrium, requiring euthanasia, by 3 months of age. We hypothesize that the absence of HYAL2 leads to the accumulation of HA in organs/tissues where HA is normally abundant resulting in developmental defects and organs dysfunction.
Molecular and histological analysis of HYAL2 KO hearts demonstrated extracellular accumulation of high molecular mass (HMM) HA in the heart valves, myocardium, serum and lungs which was associated with severe cardiopulmonary dysfunction. Further, structural and functional analyses of Hyal2 KO mouse hearts using high-frequency ultrasound revealed atrial dilation accompanied by diastolic dysfunction that was evident as early as 4 weeks of age, and progressed with age. Further, 50% of HYAL2 KO mice exhibited a triatrial heart (cor-triatriatum). Histological analyses revealed that the atrial dilation was the result of excess tissue, and did not correlate with the presence of cor triatrium. Hyal2 KO mice were found to have increased numbers of mesenchymal cells at early stages of development, presumably due to the presence of excess HA, that lead to cardiac dysfunction. Further examination of HYAL2 distribution in a broad range of mouse tissues, and accumulation of HA in its absence demonstrated that HYAL2 is mainly localized to endothelial cells and some specialized epithelial cells, and plays a major role in HMM-HA degradation. These studies demonstrated that HYAL2 is important for HA degradation and organ development. In the longer term, our findings will be valuable for understanding pathologies associated with the disruption of HA catabolism, and potentially in the identification of HYAL2-deficient patients.May 2016
27
Swain, Robert Edward. "The role of the fiber/matrix interphase in the static and fatigue behavior of polymeric matrix composite laminates." Diss., This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-07122007-103938/.
Full text
28
Al-Jallad, Hadil. "Role of transglutaminase enzymes in osteoblast differentiation and matrix deposition." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106326.
Full textAbstract:
Bone formation is an osteoblast-mediated process that is controlled by systemic factors such as hormones, growth factors and local cues that arise from the extracellular matrix (ECM). Bone ECM is elaborated by osteoblasts and therefore they can control their own activity. The ultimate goal of bone matrix formation is to elaborate an extracellular network, consisting mainly of fibronectin and collagen type I, that is capable of mineralizing and forming a strong tissue with appropriate tensile and elastic properties. This thesis describes studies that link transglutaminases (TGs), the protein cross-linking enzymes to type I collagen matrix deposition, osteoblast differentiation and bone formation. Findings here show that MC3T3-E1 osteoblasts require TG-activity for differentiation and proper production of collagenous matrices. We also show that osteoblasts produce two transglutaminase enzymes, transglutaminase 2 (TG2) and Factor XIIIA (FXIIIA), which are both expressed during osteoblast differentiation. The work further defines the roles of the two TGs in osteoblasts and shows that FXIIIA is the main TG-enzyme with transamidating activity in osteoblasts' ECM. Production of FXIIIA is induced during osteoblast differentiation and is externalized to the cell surface, then secreted to the ECM. TG2 was mainly found on the cell surface of osteoblasts with no transamidating activity; however, it is co-localized with FXIIIA on the cell surface. Studies conducted with chemical inhibitors, TG-substrates and activity probes suggest that TG-activity is required for osteoblast differentiation at three different levels. First, by positively affecting microtubule dynamics, delivery and fusion of secretory vesicles carrying cellular collagen type I to the plasma membrane. Second, by promoting fibronectin matrix deposition and collagen type I secretion. And third, by stabilizing the interaction between fibronectin and collagen type I in the ECM. Furthermore, we demonstrated that tubulin and fibronectin are candidate substrates for FXIIIA in osteoblasts. In summary, our studies are the first to describe FXIIIA transglutaminase expression in osteoblasts in vitro and in vivo, and first to link it to collagen secretion and osteoblast differentiation. Furthermore, these studies were the first to suggest a role for cellular FXIIIA in microtubule dynamics. We conclude that transglutaminase activity arising from FXIIIA can regulate osteoblast differentiation affecting extracellular matrix deposition.La formation et le développement de l'os est un processus complexe dirigé par les ostéoblastes. Contrôlés par des hormones systémiques, des cytokines et d'autres facteurs locaux, les ostéoblastes sécrètent et assemblent la matrice extracellulaire (MEC) des tissus osseux. L'aboutissement de ce processus sera la génération d'un réseau extracellulaire constitué notamment de la fibronectine et du collagene de type I qui va se minéraliser en formant le tissu dur de l'os avec d'excellent propriétés mécaniques. Cette thèse présente des études liées aux transglutaminases (TGs) – une classe des enzymes responsables de la polymérisation (cross-linking) des protéines et d'autres composée biomacromoléculaires - en relation avec le collagène de type I secrété pendant l'élaboration de la MEC, la différentiation des ostéoblastes et l'élaboration du tissu osseux. Les principaux résultats de ces études portent sur l'observation que l'activité polymérisante de la TG est un facteur crucial pour la différentiation des cellules ostéoblastiques MC3T3-E1 et pour la production normale de la matrice collagénique. Un résultat essentiel de la présente recherche porte sur la découverte que les ostéoblastes synthétisent deux types d'enzymes TG, i.e. la transglutaminase 2 (TG2) et le facteur XIIIA (FXIIIA), qui sont tous les deux secrétés pendant la différentiation des ostéoblastes. Les résultats suivants éclaircirent les rôles des deux enzymes TG (TG2 et FXIIIA) dans l'activité des ostéoblastes en montrant que c'est le FXIIIA qui est l'enzyme TG dominante avec une activité de transamidation importante dans la MEC des ostéoblastes. FXIIIA est produit pendant la différentiation des ostéoblastes en s'externalisant vers la surface des cellules pour être par la suite sécrété dans la MEC. L'enzyme TG2 a été localisé seulement à la surface des cellules osteoblastiques. Même si le TG2 a été trouvé colocalisé avec le FXIIIA à la surface des cellules, aucune activité de transamidation n'est identifiée pour le TG2. Des études comportant des inhibiteurs chimiques, de substrats TG et de sondes d'activité TG suggèrent que l'activité TG est nécessaire pour la différentiation des ostéoblastes sur trois plans distincts, à savoir : (i) par une action bénéfique sur la dynamique des microtubules, l'acheminement et la fusion des vésicules sécrétoires qui transportent le collagène I cellulaire vers la membrane plasmatique; (ii) par l'accélération du dépôt de la matrice de fibronectine et la sécrétion du collagène de type I; (iii) par la stabilisation de l'interaction de la fibronectine avec le collagène I dans la MEC. De plus, nous avons démontré que la tubuline and la fibronectine ce sont de candidats substrat pour le facteur FXIIIA dans les ostéoblastes. En résumé, notre recherche décrit pour la première fois l'expression de l'enzyme transglutaminase FXIIIA dans les ostéoblastes, tant in vitro qu'in vivo, en corrélant l'expression du FXIIIA à la sécrétion et la différentiation des ostéoblastes. De plus, notre étude est la première en attribuant un rôle au facteur FXIIIA relative à la dynamique des microtubules. On conclut de notre étude que l'activité transglutaminase du facteur FXIIIA exerce une influence décisive dans les processus de différentiation des ostéoblastes avec un effet régulateur crucial à la sécrétion et au dépôt de la matrice extracellulaire.
29
Moore, Anthony G., University of Western Sydney, and School of Science. "The role of the extracellular matrix in wool follicle development." THESIS_XXXX_SS_Moore_A.xml, 1999. http://handle.uws.edu.au:8081/1959.7/389.
Full textAbstract:
Molecular and behavioural characterisation of ovine dermal papilla cells performed in this study indicate they synthesise a highly specialised extracellular matrix (ECM). This is conserved between different species and distinguishes papilla cells from dermal fibroblasts with which they have a common origin. The composition of the dermal papilla ECM is temporally and spatially regulated during wool follicle development. It was shown that the ECM associated with dermal papilla cells in foetal sheep skin becomes specialised in regard to chondroitin sulphate synthesis prior to the appearance of follicle primordia. Chrondroitin sulphate and fibronectin were present in the ECM of dermal papilla cells throughout follicle development and during fibre production. Cellular differentiation antigen 44 was present in the ECM od papilla cells exclusively during the formation of dermal papilla, while laminin was present in the dermal papilla ECM of fibre producing follicles only. Co-operation between chondroitin sulphate, fibronectin, and CD44 in regulating the agrregative and proliferative behaviour of papilla cells was demonstrated in culture. Finally, the inhibition of proteoglycan synthesis in newborn mouse skin was found to disrupt the growth of existing follicles and the generation of new ones. Together these findings demonstrate that chondroitin sulphate is intimately associated with the earliest interactions between epithelial and mesenchymal cells during the formation of follicle primordia. It is likely that the interactions specifically involve fibronectin and CD44, and possibly other ECM molecules which have he effect of regulating the behaviour of papilla cellsDoctor of Philosophy (PhD)
30
Ells, Barbara. "Role of the matrix in bandbroadening on polymeric HPLC packings." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ34759.pdf.
Full text
31
Moore, Anthony G. "The role of the extracellular matrix in wool follicle development /." View thesis, 1999. http://library.uws.edu.au/adt-NUWS/public/adt-NUWS20030901.152349/index.html.
Full textAbstract:
Thesis (Ph.D) -- University of Western Sydney, Nepean, 1999.Thesis submitted for degree of Doctor of Philosophy, University of Western Sydney, Nepean and CSIRO Division of Animal Production. Includes bibliographical references.
32
Sonbol, Hala Salim. "Extracellular matrix interactions of polycystin-1 : a role for laminin?" Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414495.
Full text
33
Al, Shammari Basim Raddam K. "Defining the role of matrix metalloproteinases in TB granuloma formation." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/43938.
Full textAbstract:
Tuberculosis (TB) remains a global health emergency and one third of the global population harbour latent infection. A central tenet of TB pathology is that caseation of TB granuloma leads to matrix degradation and pulmonary cavitation, resulting in Mtb transmission and disease progression. However, lung destruction must involve activity of MMPs which are emerging as key proteases contributing to lung tissue pathology in TB. MMP-1 is the dominant collagenase in human pulmonary TB, but mice do not express an orthologue of human MMP-1 in the lung. The precise relationship between the formation of caseous necrosis and lung matrix destruction has not been systematically examined, nor how the extracellular matrix (ECM) regulates the host-pathogen interaction. I investigated the effect of transgenic expression of human MMP-1 and -9 in the mouse on TB pathology and studied lung matrix integrity in human TB granulomas by ECM stains. In cell culture systems, I developed a standard in vitro granuloma model and then progressed to 3D and engineered models of TB granuloma and investigated the effect of modulating cell-matrix interaction by introducing matrix components. In the mouse model, transgenic expression of human MMP-1 caused collagen destruction and caseous necrosis, suggesting that the initial event in caseation is collagen breakdown. In human granulomas, ECM destruction and caseous necrosis co-localise, with loss of collagen fibres in areas of caseous necrosis. Consistent with the hypothesis that matrix degradation is a key initial event in TB pathogenesis, I demonstrated that in cell culture models collagen improves survival of Mtb-infected cells. I have re-considered the sequence of events underlying TB immunopathology and demonstrated that collagen destruction driven by MMP-1 is a critical initial event. This challenges current paradigms of disease pathology. These data demonstrate that the ECM regulates the host-pathogen interaction in TB.
34
Shalaby, Usama A. "The role of matrix metallproteinases in pathogenesis of proliferative vitreoretinopathy." Thesis, University of Aberdeen, 2001. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU145724.
Full textAbstract:
Cellular migration and membrane contraction are two vital steps in pathogenesis of proliferative vitreoretinopathy (PVR). Several factors, related to cell activity, are involved in induction of cell migration and cell-induced membrane contraction. However, the roles of some of these factors in PVR pathophysiology are still to be clarified. The studies described in this thesis were undertaken to investigate the factors affecting cellular migration, mainly HRPE cells, which may modify cellular migration during proliferative vitreoretinopathy. The mechanisms of cell-induced collagen gel contraction, which resembles membrane contraction in PVR, was studied. The role of matrix metallproteinases (MMPs) in induction or inhibition of cell migration and cell-mediated gel contraction is one major goal; this study tried to clarify. In chapter III, HRPE cells were cultured from human male eyes, aged 43 years, and passed several times to create a cell line. To study the effect of different ECMs (fibronectin, laminin and different subtypes of collagen) on cell migration, I developed a cell migration assay "agarose droplet". This assay was established by incorporating HRPE cells into small amount of agarose and the solution was left to set as a gel. The drops were observed, photographed and scanned for 48 hours. The distance migrated by the cells, on plastic or substrate coated plastic, was estimated using both microscopic scale and computer analysis program (Coral Xara) by converting the pixels into metric unites. The results showed that fibronectin at a dose of 10 ,g/ml significantly enhanced cell migration in comparison with cells migrated on plastic. On the other hand, laminin at a dose of 10 g/ml markedly inhibited cell migration and this inhibition was statistically significant. These results suggest that HRPE cells require fibronecin but not laminin to migrate out of agarose droplet. This alteration in cell reaction to different ECM substrates may represent a similar phenomenon of cell-matrix interactions, which stimulate cell migration and survival in PVR environment. Cell migration assay was used again in Chapter IV to determine the role of matrix metalloproteinases (MMPs) 1, 2 9 in directing the behaviour of HRPE cells during migration from agarose droplets. Expression of MMP-1,2 9 by HRPE cells was determined by immunocytochemistry using monoclonal antibodies. In addition, expression of MMPs in cultured HRPE cells was confirmed by western blotting in the absence and in the presence of MMP synthetic inhibitor: Batimastat (BB-94). Finally, cell migration from the agarose was studied in presence of Batimastat. The results showed that MMP-2 9 were expressed by primary HRPE cell cultures and the strong expression of the duplex bands of the same enzymes were shown by western blotting technique. Expression of the MMP-2 9 bands was inhibited completely after treatment of the HRPE cells with BB-94 (500nM and 5 M). BB-94, also inhibited cellular migration from agarose droplets in a dose dependent manner. These results suggest that expression of MMP-2 9 by HRPE cells during their migration from the agarose might resemble the expression of the same enzymes during migration of the cells in the PVR and the inhibition of these enzymes by BB-94 might prevent cellular migration, a critical step in PVR pathogenesis. Therefore, we concluded that migration of HRPE cells from their resident basement membrane into periretinal surfaces requires an interplay between certain ECMs and enzymes as, MMPs to permit cellular invasion. There was an intention to use this assay to study the effect of MMPs on the cellular migration in the presence of these ECMs but because of the tiny size of the drop, it was very difficult to retrieve any materials from the drops. In chapter V, I used cell-mediated collagen gel contraction model to determine the effect of HRPE cells, seeded on the surface of 3-D collagen gels, on the integrity of the gel and to observe the behaviour of human retinal pigment epithelial (HRPE) cells during this time. A comparison between the effect of the HRPE cells on the collagen gel integrity and other cell types as human skin fibroblasts (HSF) and human monocytic cell line (THP-1) has been performed after standardisation of the HRPE cell-mediated collagen gel contraction assay. Also, the effects of coating the collagen gel with different ECM proteins on the cell-mediated collagen gel contraction were studied. The extent of cellular invasion and the degree of gel contraction were quantified for up to three days using phase contrast microscopy and digital image analysis. These experiments showed that HRPE cells mostly proliferated as sheets of cells on the surface of the collagen gel and only minimally invaded the gel, some cells were seen to invade the gel as single cells and invaded the gel to a depth of several tens of microns.
35
Coleman, Gary John. "The role of the extracellular matrix in retinal vascular disease." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486056.
Full textAbstract:
Originally believed to serve as a selective barrier and scaffold to which cells adhere, it has become evident that the individual components of the basement membrane (BM) are regulators of biological activities such as cell growth, differentiation, and migration, and that they influence tissue development and repair (Erickson and Couchman, 2000). Based on the emerging importance ofBM's in critical aspects of cellular activity, this thesis was undertaken in an attempt to further elucidate the role of these biologically-active regulatory proteins in the context of.retinal microvascular disease. The salient findings of this investigation were as follows; The a2(IV)NCl domain of typ~ IV human collagen inhibits angiogenesis in the retinal microvasculature in both in vitro (p
36
Xu, Zhenyuan. "The Role of the Extracellular Matrix in Schwann Cell Phenotype." University of Cincinnati / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1623251473003085.
Full text
37
吳令瞻 and Ling-jim Ng. "Expression of extracellular matrix genes during skeletogenesis: the role of type II collagen." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1997. http://hub.hku.hk/bib/B31237575.
Full text
38
Ng, Ling-jim. "Expression of extracellular matrix genes during skeletogenesis : the role of type II collagen /." Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19050306.
Full text
39
Ponte, Monica. "Calcium homeostasis in articular chondrocytes and its role in matrix synthesis." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318864.
Full text
40
Afzal, Saliha. "Extracellular matrix interactions in ovarian cancer : an investigation into the role of integrins and matrix metalloproteinases in ovarian tumour progression." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299857.
Full text
41
Hou, Peng. "Matrix metalloproteinases in the osteoclast, with special emphasis on the molecular cloning and the functional role of matrix metalloproteinase-12." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287350.
Full text
42
Mah, Wesley Brandon. "The role of fibroblast phenotype and pericellular matrix in wound healing." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44093.
Full textAbstract:
Scar formation as a result of wound healing in skin is associated with increased deposition of extracellular matrix (ECM) and reduced ECM turnover by fibroblasts. Remarkably, wound healing in the human oral mucosa results in scarless healing, while wound healing in the skin can often result in scarring. Therefore comparing fibroblast phenotype and interactions with their ECM niche in the gingiva and skin may provide novel information about the factors that regulate scar formation. To this end, a novel 3D cell culture model was utilized to yield a cellular microenvironment (niche) that closely mimics the in vivo situation and primary gingival (GFBL) and skin fibroblasts (SFBL) phenotype was characterized. Furthermore, fibroblasts were reseeded on cell-free 3D ECM derived from GFBL and SFBL and the effects of the 3D ECM on cell phenotype were analyzed. Interestingly, SFBL in 3D cultures had greater expression of ECM deposition associated genes, including collagens, matricellular proteins, SLRPs, TGF-β1 and CTGF, intracellular ECM degradation and myofibroblast differentiation and function-associated genes, while GFBL had a greater expression of matrix remodeling associated genes (MMPs). We also found that the 3D cultures showed a significant difference in expression of certain genes (MMPs and myofibroblast function-associated genes) between GFBL and SFBL compared to cells reseeded on the 3D ECM or 2D control substrate. Thus, the 3D culture conditions may differentially regulate expression of a subset of genes in these cells. Interestingly, SFBL had a greater expression of matrix deposition associated genes (collagens, SLRPs, tenascins) irrespective of the culture conditions, suggesting that expression of these genes is inherently distinct between GFBL and SFBL. This was associated with greater autogenous TGF-β expression and SMAD3 phosphorylation in SFBL than GFBL, which may partly explain the innate difference in gene expression. In addition, there was greater ERK1/2 phosphorylation in fibroblasts when seeded on 3D ECM compared to 2D substrate. Greater ERK1/2 phosphorylation may have promoted greater expression of AP-1-dependent MMPs seen in SFBL and GFBL on 3D ECM. In conclusion, reduced expression of matrix deposition associated genes and greater expression of matrix remodeling genes in GFBL may contribute to scarless healing in gingiva.
43
Jani, Klodiana. "The role of integrin-dependent cell matrix adhesion in muscle development /." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115688.
Full textAbstract:
Cell adhesion is essential to cell motility and tissue integrity and is regulated by the Integrin family of transmembrane receptors. Integrin binds to ligand extracellularly and provide anchor to the intracellular cytoskeleton via adhesion scaffolding proteins. In order to link cell to the surrounding matrix Integrin needs to be activated. Intracellular activation signals induce perturbations in Integrin cytoplasmic domain that are translated into a conformational change in extracellular region for high affinity ligand binding. Integrin engagement by matrix, in turn, triggers the assembly of adhesion complexes. Such early adhesions promote cytoskeletal organization with subsequent contractile activity that exerts forces against initial Integrin-matrix adhesions. In response to force, Integrin strengthens the interaction with matrix through its clustering and successive recruitment of additional adhesion components. These bidirectional regulatory loops mediated by such interactions are largely dependent on the unique function of Integrin adhesion components.We demonstrate a novel role for the PDZ/LIM domain protein Zasp as a core component of Integrin adhesions. Specifically, Zasp colocalizes with Integrins at focal adhesion in cultured cells and myotendinous junctions in Drosophila embryos. In both cases elimination of Zasp modifies Integrin function causing consequently defects in cell spreading and muscle attachment. Zasp supports Integrin adhesion to the extracellular matrix that is required to withstand tensile forces exerted during cell spreading and muscle contraction. Furthermore, we found that the distribution of Zasp in muscle Z-lines is essential to orchestrate the cross-linking of alpha-Actinin and Actin filaments. Disruption of Zasp leads to loss of muscle cytoarchitecture, pointing to a larger role for Zasp in sarcomere assembly. Finally, we demonstrate that Zasp, in addition to alpha-Actinin, physically interacts with the Integrin- and Actin-bound cytoskeletal protein Talin.
Collectively, our results point to a dual role for Zasp as a structural scaffold. First it regulates Integrin adhesion to the extracellular matrix by interacting with the head domain of Talin at the myotendinous junctions. Second, Zasp controls sarcomere assembly by tethering the presarcomeric alpha-Actinin component to the tail domain of Talin. Zasp finding as a crucial adhesion component provides further insights on the mechanism underlying Integrin-mediated adhesion.
44
Christofidou, Elena D. "Novel mechanism and role of thrombospondin-1 in extracellular matrix organisation." Thesis, University of Bristol, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619255.
Full textAbstract:
Thrombospondins (TSPs) are conserved, multi-domain, extracellular glycoproteins that participate in many biological processes. TSP-1 is present in low levels in the extracellular matrix (ECM) of healthy vessel walls and is up-regulated during neointima and plaque formation. TSP-1 induces vascular smooth muscle cell (SMC) proliferation and migration upon vascular injury or during atherosclerosis. The aims of this' dissertation were: 1) to identify molecular mechanisms and interactions of the C-terminal, L-Iectin domain that mediates ECM deposition of TSP-1; 2) to examine the functional role of ECM-deposited TSP-1 in vessel wall ECM assembly. From cell culture experiments to identify how TSPs accumulate in ECM, a novel mechanism of trans inter-molecular interactions between TSP molecules within ECM is proposed. This mechanism depends on a specific motif in the L-Iectin domain and can act through either homophilic (TSP-1- TSP-1) or heterophilic (TSP-1-TSP-5) interactions to mediate ECM accumulation of TSPs as puncta. Fibrillar collagen may stabilise these puncta in ECM, as inhibition of fibrillar collagen production in fibroblasts decreased the level of TSP-1 in ECM but did not alter puncta patterning. Because only trimeric TSP-1 is retained in ECM, the basis of trimerisation was investigated by use of synthetic peptides derived from the coil-coiled region of TSP-1. Biophysical methodologies proved that a coiled-coil domain peptide, without any N-terminal cysteines, was stably trimeric in solution. Lastly, the role of TSP-1 in healthy aortae was examined with reference to the organisation of aortic walls in wild-type mice, Thbsl -/- mice and mice with transgenic overexpression of TSP-1 in vascular SMC. 10 to 12-week old mice of both genders were included in each set and measurements were made from the ascending and the thoracic aorta. The total width of elastin layers was increased in Thbs1 -/- mice and layers were more irregular. Similar perturbations were identified in aortae from the TSP-1 transgene overexpression mice. Thus, either increasing or decreasing TSP-1 perturbs the aortic wall ECM. The new mechanisms identified might also have implications for atherosclerosis and cardiovascular disease.
45
Kondylis, Evangelos. "Role of Drosophila golgi matrix proteins in the early exocytic pathway." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/11007.
Full textAbstract:
During the course of this study, the role of Drosophila homologues of Golgi matrix proteins in the organisation of the early exocytic pathway (tER and Golgi) was investigated. dp115, dGM130 and dGRASP were depleted from Drosophila S2 cells by RNA interference. Using electron and immunofluorescence microscopy, dp115 depletion was shown to result in Golgi stack breakdown and tER dispersion. The effect on tER organisation was specific for dp115, as depletion of the other Golgi matrix proteins did not have a similar effect. Although, dGRASP or dGM130 single depletion did not lead to a quantitative disruption of the Golgi morphology, dGM130/dp115 and dGM130/dGRASP double depletions pointed to genetic interactions for building and/or maintenance of the Golgi stacks. Considering the key role of the Golgi apparatus in protein transport along the exocytic pathway, anterograde transport of plasma membrane protein Delta, from its site of synthesis (ER) to its final destination, was monitored in cell depleted of the above mentioned Golgi matrix proteins. Surprisingly, none of the depletions, including dp115 that alters considerably the organisation of the exocytic pathway, led to a significant inhibition of intracellular transport. Anterograde intracellular transport in the absence of Golgi stacks exists physiologically during Drosophila development. In a morphological study performed in imaginal discs during the transition from early 3rd instar larva to white pupa, the biogenesis of the Golgi stacks from vesicular-tubular larval clusters was described. These larval clusters were shown to contain several Golgi-specific markers and, therefore seem capable of carrying out proper Golgi functions.
46
Bord, Sharyn. "The role of matrix metalloproteinases in human bone modelling and remodelling." Thesis, Anglia Ruskin University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243631.
Full text
47
Al-Hizab, Fahad A. "The role of matrix metalloproteinases in cartilage destruction in equine arthropathies." Thesis, University of Liverpool, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272750.
Full text
48
Rich, Kirsty. "Matrix metalloproteinases in asthma : the role of mast cells and basophils." Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285664.
Full text
49
Parkin, Ben. "The role of matrix metalloproteinase-2 and its inhibitors in keratoconus." Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343282.
Full text
50
Dinglasan, Lu Anne Velayo. "The role of matrix metalloproteinases in axon guidance and neurite outgrowth." [New Haven, Conn. : s.n.], 2008. http://ymtdl.med.yale.edu/theses/available/etd-12022008-104438/.
Full text