A5013031763- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Cystic Fibrosis Research Advances
- Proteoglycans and glycosaminoglycans research
- Parasites and Host Interactions
- Asthma and respiratory diseases
- Osteoarthritis Treatment and Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Cell Adhesion Molecules Research
- Inhalation and Respiratory Drug Delivery
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Tracheal and airway disorders
- Salivary Gland Disorders and Functions
- Parasitic Infections and Diagnostics
- Helminth infection and control
- Gut microbiota and health
- Psychopathy, Forensic Psychiatry, Sexual Offending
- Polysaccharides and Plant Cell Walls
- Respiratory and Cough-Related Research
- Protist diversity and phylogeny
- IL-33, ST2, and ILC Pathways
- Advanced Drug Delivery Systems
- Hepatitis C virus research
Wellcome Centre for Cell-Matrix Research
2015-2024
University of Manchester
2015-2024
Manchester Academic Health Science Centre
2017-2023
Boston University
2003-2020
VA Boston Healthcare System
2011-2020
Boston Medical Center
2003-2019
Centre for Inflammation Research
2019
Harvard University
2019
Institut Pasteur
2018
Health Sciences Centre
2018
The study compared the predictive accuracy of three sex offender risk-assessment measures: RRASOR (Hanson, 1997), Thornton's SACJ-Min (Grubin, 1998), and a new scale, Static-99, created by combining items from SACJ-Min. Predictive was tested using four diverse datasets drawn Canada United Kingdom (total n = 1301). showed roughly equivalent accuracy, combination two scales more accurate than either original scale. Static-99 moderate for both sexual recidivism (r 0.33, ROC area 0.71) violent...
MUC2 mucin produced by intestinal goblet cells is the major component of mucus barrier. The inflammatory bowel disease ulcerative colitis characterized depleted and a reduced layer, but aetiology remains obscure. In this study we used random mutagenesis to produce two murine models disease, characterised basis nature inflammation in these mice, compared pathology with human colitis.By N-ethyl-N-nitrosourea identified distinct noncomplementing missense mutations Muc2 causing an colitis-like...
De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced cecum mice resistant to Trichuris muris infection. In this study, we investigated role which detected shortly before worm expulsion and associated with production interleukin-13 (IL-13), resistance nematode. Muc5ac-deficient were incapable expelling T. from intestine harbored long-term chronic infections, despite developing strong T(H)2 responses. had elevated levels IL-13 and, surprisingly, an...
Respiratory mucus contains a mixture of gel-forming mucins but the functional significance these different mucin species is unknown. To help gain better understanding in airways we therefore need to ascertain concentration each within respiratory secretions. Thus aim this study was determine amounts specific directly from solubilized secretions and purified preparations. We investigated feasibility using direct-binding ELISA employing mucin-specific antisera were unable obtain reliable data...
Respiratory mucus contains a mixture of gel-forming mucins but the functional significance these different mucin species is unknown. To help gain better understanding in airways we therefore need to ascertain concentration each within respiratory secretions. Thus aim this study was determine amounts specific directly from solubilized secretions and purified preparations. We investigated feasibility using direct-binding ELISA employing mucin-specific antisera were unable obtain reliable data...
Background. Several reports have suggested an increased risk of coronary disease in human immunodeficiency virus (HIV)–infected patients receiving protease inhibitors (PIs). Impaired endothelium-dependent vasodilation is a putative surrogate marker atherosclerotic disease. Methods. The present study evaluated the effect HIV infection and antiretroviral treatment on endothelial vasomotor function, by assessing brachial artery flow-mediated dilation (FMD). A total 75 HIV-infected were compared...
Background & AimsHyperplasia of mucin-secreting intestinal goblet cells accompanies a number enteric infections, including infections by nematode parasites. Nevertheless, the precise role mucins in host defense infection is not known. We investigated mucin (Muc2) worm expulsion and immunity model infection.MethodsResistant (BALB/c, C57BL/6), susceptible (AKR), Muc2-deficient mouse strains were infected with nematode, Trichuris muris, expulsion, energy status whipworms, changes mucus/mucins,...
At least eight mucin apoproteins are expressed by the tracheobronchial epithelium, but it is not known which, if any, of these major constituents respiratory secretions responsible for formation mucus gel. To address this we have isolated mucins from normal, asthmatic and chronic bronchitic secretions. The reduced subunits were fractionated into four populations (I–IV) anion-exchange HPLC. Amino acid monosaccharide compositional analysis, as well Mr size measurements, indicate that two (I...
Human tracheobronchial epithelial cells grown in air-liquid interface culture have emerged as a powerful tool for the study of airway biology. In this study, we investigated whether system produces “mucus” with protein composition similar to that vivo, induced secretions. Previous compositional studies mucous secretions greatly underrepresented contribution mucins, which are major structural components normal mucus. To overcome limitation, used mass spectrometry-based approach centered on...
Pathologies caused by mutations in extracellular matrix proteins are generally considered to result from the synthesis of matrices that defective. Mutations type X collagen cause metaphyseal chondrodysplasia Schmid (MCDS), a disorder characterised dwarfism and an expanded growth plate hypertrophic zone. We generated knock-in mouse model MCDS-causing mutation (COL10A1 p.Asn617Lys) investigate pathogenic mechanisms linking genotype phenotype. Mice expressing had shortened limbs Chondrocytes...
The rheological characteristics of gastric and duodenal mucin solutions, the building blocks mucus layer that covers epithelia two organs, were investigated using particle tracking microrheology. We used biochemically well characterized purified porcine mucins (MUC5AC MUC2) as models for human mucins, to probe their viscoelasticity a function concentration pH. Furthermore, we both reducing (dithiothreitol, DTT) chaotropic agents (guanidinium chloride urea) mesoscopic forces mediate integrity...
The polymeric mucin component of the intestinal mucus barrier changes during nematode infection to provide not only physical protection but also directly affect pathogenic nematodes and aid expulsion. Despite this, direct interaction with mucins has previously been addressed. We used well-established Trichuris muris model investigate effect on complex mixture immunogenic proteins secreted by called excretory/secretory products (ESPs). Different regimes T. were simulate chronic (low dose) or...
To understand the mucociliary clearance system, mucins were visualized by light, confocal and electron microscopy, mucus was stained Alcian blue tracked video microscopy on tracheal explants of newborn piglets. We observed long linear bundles that appeared at submucosal gland openings transported cephalically. The shown mass spectrometry immunostaining to have a core made MUC5B mucin coated with MUC5AC produced surface goblet cells. transport speed slower than airway liquid flow. suggest...
Rationale: Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of concentration in pathogenesis these abnormalities has not been characterized.Objectives: This study was designed to: 1) measure biophysical properties mucus; 2) identify secreted mucins contained 3) relate to epithelial mucin RNA/protein expression; 4) explore relationships between hyperconcentration disease severity.Methods: Sputum samples were collected from...
It has been demonstrated previously that respiratory secretions contain three oligomeric, gel-forming mucins; one of these was identified as the product MUC5AC gene (1). Here we demonstrate other two mucins are glycoforms MUC5B product. This accomplished by trypsin treatment purified reduced mucin subunit populations and N-terminal sequencing liberated peptides. The products digestion were separated gel filtration into high molecular weight glycopeptides low tryptic latter fractionated...
One hundred eighty human immunodeficiency virus (HIV)– and hepatitis C (HCV)–coinfected patients were prospectively evaluated for suitability interferon ribavirin therapy. Of the 149 with chronic HCV infection who completed evaluation, 44 (30%) eligible treatment 105 (70%) ineligible, main barriers being missed clinic visits, active psychiatric illness, drug or alcohol use, decompensated liver disease, medical illness.