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You searched for subject:(Muc5b Muc5ac). Showing records 1 – 3 of 3 total matches.

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1. Hughes, Gareth William. INVESTIGATING THE SUPRAMOLECULAR ORGANISATION OF RESPIRATORY MUCINS IN HEALTH AND DISEASE.

Degree: 2018, University of Manchester

The polymeric mucins, MUC5B and MUC5AC provide the structural and functional backbone of the respiratory mucus barrier, conferring both viscoelastic and antimicrobial properties onto these complex secretions. Within the mucus barrier, polymeric mucins are believed to be highly organised, arranged in a network-like formation. Structural details regarding how mucins are packaged, secreted and expand to form a functional barrier remain elusive. In addition, despite recent investigations into mucin secondary structure, it is unclear as to how the heavy glycosylation found within mucin domains can influence polymer conformation. Through the use of electron microscopy techniques in combination with biophysical analyses we performed an in depth structural analysis on purified MUC5B and MUC5AC, we then utilised these same techniques to investigate mucin packaging and expansion in response to changes in calcium concentration and pH levels. Finally through structural investigations into the native organisation of the salivary mucus barrier we aimed to investigate the hierarchical mucin topology present within mucosal systems, thus enabling us to draw conclusions about how this organisation may be compromised in disease states such as Cystic Fibrosis (CF). Through transmission electron microscopy (TEM) combined with single particle analysis, we provide evidence to suggest that MUC5B contains bead-like structures, which repeat along the polymer axis and suggest that MUC5B may consist of repeating motifs derived from distinct glycosylation patterns, rather than the disorganised random coil conformation previously assumed. Moreover, through TEM and rate zonal centrifugation, we demonstrate that respiratory mucins form highly entangled linear polymers, the structures of which are sensitive to calcium concentration and fluctuations in pH. In the presence of Ca2+ at pH 5.0, MUC5B adopted a compact conformation which was lost upon removal of calcium, via EGTA, and through increasing the pH to 7.4. We further suggest that the expansion of mucins following secretion occurs via two-step process, with an initial rapid expansion followed by a slower protease-independent maturation process, which is driven by distinct changes to the mucin interactome. Through isolation of mucins derived from CF sputum we have assessed the structural and biophysical changes that occur to the mucin network during CF progression, we suggest that the CF mucin network is severely degraded, with mucin glycopeptides predominating. Furthermore, we suggest that poly (acetyl, arginyl) glucosamine (PAAG) may represent an attractive treatment for CF lung disease, here we highlight its ability to directly bind MUC5B and induce its linearisation, resulting in a less viscous mucin network. Here we provide novel insights into the structural organisation of MUC5B and MUC5AC on both intra- and intermolecular levels, and shed light onto the processes required for mucin packaging and expansion, which have allowed us to understand the mechanisms behind aberrant mucus transport… Advisors/Committee Members: FORD, ROBERT RC, Thornton, David, Ford, Robert.

Subjects/Keywords: Mucus; Mucin; MUC5B; MUC5AC; Cystic Fibrosis; Electron Microscopy; Saliva

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APA (6th Edition):

Hughes, G. W. (2018). INVESTIGATING THE SUPRAMOLECULAR ORGANISATION OF RESPIRATORY MUCINS IN HEALTH AND DISEASE. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:312990

Chicago Manual of Style (16th Edition):

Hughes, Gareth William. “INVESTIGATING THE SUPRAMOLECULAR ORGANISATION OF RESPIRATORY MUCINS IN HEALTH AND DISEASE.” 2018. Doctoral Dissertation, University of Manchester. Accessed September 26, 2020. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:312990.

MLA Handbook (7th Edition):

Hughes, Gareth William. “INVESTIGATING THE SUPRAMOLECULAR ORGANISATION OF RESPIRATORY MUCINS IN HEALTH AND DISEASE.” 2018. Web. 26 Sep 2020.

Vancouver:

Hughes GW. INVESTIGATING THE SUPRAMOLECULAR ORGANISATION OF RESPIRATORY MUCINS IN HEALTH AND DISEASE. [Internet] [Doctoral dissertation]. University of Manchester; 2018. [cited 2020 Sep 26]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:312990.

Council of Science Editors:

Hughes GW. INVESTIGATING THE SUPRAMOLECULAR ORGANISATION OF RESPIRATORY MUCINS IN HEALTH AND DISEASE. [Doctoral Dissertation]. University of Manchester; 2018. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:312990


University of Manchester

2. Williams, Adele. Polymeric Airway Mucins in Equine Recurrent Airway Obstruction.

Degree: 2014, University of Manchester

In healthy airways, mucus forms part of the innate immune response protecting therespiratory epithelium from damage by pathogens and environmental debris (Rose and Voynow, 2006). Conversely, in many respiratory diseases, mucus becomes part of the airway disease pathology. Mucus hypersecretion along with reduced clearance can cause blockage of the small airways, impairing gas exchange, promoting inflammation and becoming a culture medium for bacterial colonisation (Thornton et al., 2008).Recurrent airway obstruction (RAO) is a common yet poorly understood equine chronic respiratory disease where such altered mucus properties and clearance have been identified as major factors in the disease pathology (Davis and Rush, 2002; Gerber et al., 2000; Kaup et al., 1990; Robinson, 2001). The gel-forming mucins are largely responsible for the transport properties of mucus. The major equine airway gel-forming mucin in health is Muc5b and to a lesser extent Muc5ac; produced in specialised respiratory epithelial goblet cells and sub-mucosal glands (Rousseau et al., 2011b). Changes in mucin relative and net amounts and their macromolecular properties and interactions have been attributed to the altered physical properties of airway mucus in airways disease (Groneberg et al., 2002a; Jefcoat et al., 2001; Kirkham et al., 2002; Robinson et al., 2003; Sheehan et al., 1995).The project investigates the biochemical properties of mucins present in mucus from healthy horses and horses with RAO. This project identifies the anatomical presence of mucin-producing goblet cells and glands in fixed tissues from the respiratory tracts of healthy horses and subsequently examines mucin-production sites in respiratory tracts from horses with RAO. Finally the project investigates a methodology for the study of mucin production in airway cells harvested from live horses suffering from RAO.Our investigations confirmed that horses with RAO have more endotracheal mucus than healthy controls, and that Muc5b is the predominant mucin with Muc5ac also present in RAO horse mucus, both during symptomatic disease and when horses are asymptomatic. Mucins are produced in epithelial goblet cells and sub-mucosal glands dispersed throughout the length and circumference of the equine trachea and bronchi. Goblet cell hyperplasia occurs in symptomatic exposed RAO horse airways, although goblet cells are smaller than in asymptomatic RAO horse airways. Exposure to a dusty stable environment is associated with more goblet cells per length of bronchial compared to tracheal epithelium in all horses. RAO horses have larger sub-mucosal glands containing more mucin than control horses.Primary epithelial cell cultures grown at an air liquid interface are an alternative approach to study equine airway mucus, although the use of this culture system is in its early stages. We have developed novel ways to harvest equine airway epithelial cells (tracheal brushing) and shown it is possible to freeze cells collected via tracheal epithelial brushing in 20 % FBS and then culture to ALI… Advisors/Committee Members: BOOT-HANDFORD, RAYMOND RP, Boot-Handford, Raymond, Thornton, David.

Subjects/Keywords: Recurrent airway obstruction, RAO, heaves; Equine, horse; Mucin(s); Muc5b, Muc5ac; airway mucus; glycoprotein

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Williams, A. (2014). Polymeric Airway Mucins in Equine Recurrent Airway Obstruction. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:218611

Chicago Manual of Style (16th Edition):

Williams, Adele. “Polymeric Airway Mucins in Equine Recurrent Airway Obstruction.” 2014. Doctoral Dissertation, University of Manchester. Accessed September 26, 2020. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:218611.

MLA Handbook (7th Edition):

Williams, Adele. “Polymeric Airway Mucins in Equine Recurrent Airway Obstruction.” 2014. Web. 26 Sep 2020.

Vancouver:

Williams A. Polymeric Airway Mucins in Equine Recurrent Airway Obstruction. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2020 Sep 26]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:218611.

Council of Science Editors:

Williams A. Polymeric Airway Mucins in Equine Recurrent Airway Obstruction. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:218611

3. Davies, Heather. Mucins in the alimentary canal: their structure and interactions with polyphenols.

Degree: 2014, University of Manchester

The polymeric gel-forming mucins provide the structural framework of saliva and the mucus barriers that cover the mucosal surfaces of the alimentary canal. Dietary compounds may influence the barrier properties of these protective layers. The effects of green tea polyphenols, which have many health benefits but have low bioavailability and contribute to the astringency of green tea, on the structural properties of the mucins in the alimentary canal are investigated here. Using well characterised, highly purified salivary mucins MUC5B and MUC7, and porcine gastric mucins, the effects of the green tea polyphenol epigallocatechin-3-gallate (EGCG) on mucins were studied here.Using rate-zonal centrifugation coupled to agarose gel electrophoresis, atomic force microscopy and particle tracking microrheology, EGCG, at concentrations found in a cup of green tea, caused increased aggregation of MUC5B in human whole saliva, and increased aggregation and viscosity of purified MUC5B. It was revealed using recombinant proteins of the N- and C-terminal regions of MUC5B that EGCG had these effects by aggregating the terminal globular protein domains of MUC5B. In contrast, MUC5B trypsin-resistant high molecular weight glycopeptides were not aggregated by EGCG, demonstrating that the oligosaccharide-rich, highly-glycosylated regions of mucins are not involved in the EGCG-induced aggregation of mucins. EGCG also caused the majority of MUC7 in human whole saliva to aggregate, and purified MUC7 also showed substantial aggregation in the presence of EGCG.Porcine gastric mucins were also used in order to model human gastric mucins. First, the identity of the porcine gastric mucins was explored using tandem mass spectrometry and immunohistochemistry. This revealed that Muc5ac was expressed by the surface epithelium and was the prominent mucin in porcine gastric mucus. Muc6 was expressed by gastric submucosal glands, but was not a major component of the secreted mucus barrier. Porcine Muc5ac and Muc6 were shown to be aggregated by EGCG. These data demonstrate that mucins from both saliva and the stomach are substantially altered by EGCG. This may contribute to the astringency and low bioavailability of EGCG. In contrast, the green tea polyphenol epicatechin (EC) did not cause aggregation of salivary mucins or porcine gastric mucins, suggesting that the galloyl ring of EGCG (which is absent in EC) is important for its aggregation of mucins, and that EC has different mechanisms of astringency.The structure of the mucins in the alimentary canal was studied using Raman spectroscopy, Raman optical activity (ROA) and Tip-enhanced Raman spectroscopy (TERS). The secondary structure of the oligosaccharide-rich regions of mucins was shown to be largely disordered, with some contribution of poly-proline II helix. The N- and C-terminal regions of MUC5B were largely β-sheet in structure, with some disordered structure also present in the C-terminal region. Raman spectroscopy could reliably distinguish between MUC5B glycoforms, demonstrating the… Advisors/Committee Members: BLANCH, EWAN EW, Thornton, David, Blanch, Ewan.

Subjects/Keywords: Mucin; Stomach; Mucus; Saliva; MUC5B; MUC7; Muc5ac; Muc6; Green tea polyphenols; Epigallocatechin-3-gallate; EGCG; Raman spectroscopy; Raman optical activity; Tip-enhanced Raman spectroscopy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Davies, H. (2014). Mucins in the alimentary canal: their structure and interactions with polyphenols. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:239764

Chicago Manual of Style (16th Edition):

Davies, Heather. “Mucins in the alimentary canal: their structure and interactions with polyphenols.” 2014. Doctoral Dissertation, University of Manchester. Accessed September 26, 2020. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:239764.

MLA Handbook (7th Edition):

Davies, Heather. “Mucins in the alimentary canal: their structure and interactions with polyphenols.” 2014. Web. 26 Sep 2020.

Vancouver:

Davies H. Mucins in the alimentary canal: their structure and interactions with polyphenols. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2020 Sep 26]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:239764.

Council of Science Editors:

Davies H. Mucins in the alimentary canal: their structure and interactions with polyphenols. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:239764

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