A5090465124- Cystic Fibrosis Research Advances
- COVID-19 Clinical Research Studies
- Neonatal Respiratory Health Research
- Pediatric health and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Tracheal and airway disorders
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Respiratory viral infections research
- Peptidase Inhibition and Analysis
- Nematode management and characterization studies
- Dermatological and COVID-19 studies
- Genetic and Kidney Cyst Diseases
- Immune responses and vaccinations
- Diet and metabolism studies
- Mechanisms of cancer metastasis
- Peripheral Neuropathies and Disorders
- Infection Control and Ventilation
- Inflammatory Myopathies and Dermatomyositis
- Congenital Ear and Nasal Anomalies
- Respiratory Support and Mechanisms
- Cardiovascular Conditions and Treatments
- Olfactory and Sensory Function Studies
- Inflammation biomarkers and pathways
- Parkinson's Disease and Spinal Disorders
University of Dundee
2016-2025
Ninewells Hospital
2011-2023
Dundee and Angus College
2020
NHS Tayside
2008-2019
University of Bristol
2009
Hartford Hospital
1995
University of Connecticut
1995
University of Wales
1981
Acadia University
1975
Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce selective protein degradation by linking an E3 ubiquitin ligase enzyme to a target protein. This approach allows scope for "undruggable" proteins, and several PROTACs have reached the stage of clinical candidates. However, roles cellular transmembrane transporters in PROTAC uptake efflux remain underexplored. Here, we utilized transporter-focused genetic screens identify ATP-binding cassette transporter...
Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct form cell type– and context-specific microtubule structures is poorly understood. Based on a cohort 12 patients with primary ciliary dyskinesia as well mouse mutants, we identified characterized variants TUBB4B isotype that specifically perturbed centriole cilium biogenesis. Distinct differentially affected dynamics cilia formation...
Rationale: PZP (pregnancy zone protein) is a broad-spectrum immunosuppressive protein believed to suppress T-cell function during pregnancy prevent fetal rejection. It has not previously been reported in the airway.Objectives: To characterize bronchiectasis airway, including its relationship with disease severity.Methods: Label-free liquid chromatography/mass spectrometry was performed for sputum profiling of patients confirmed by high-resolution computed tomography. Results and without...
Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) important host defence against microbes can be proinflammatory chronic lung disease.To determine pulmonary and systemic levels of AMP their relationship with disease severity future risk exacerbations bronchiectasis.A total 135 adults bronchiectasis were prospectively enrolled at three European centres. Levels cathelicidin LL-37,...
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP and protein kinase A (PKA)-regulated Cl(-) channel in the apical membrane of epithelial cells. metabolically regulated adenosine monophosphate-stimulated (AMPK) colocalized with CFTR attenuates its function. However, sites for phosphorylation precise mechanism inhibition by AMPK remain obscure. We demonstrate that normally remains closed at baseline, but nevertheless, opens after AMPK. phosphorylates vitro two essential...
This study was undertaken to describe and compare the forward lateral trunk flexion strength of 20 patients with stroke hemiparesis matched controls. Trunk measured a hand-held dynamometer while subjects were seated upright. Analysis variance procedures showed strength, whether or forward, be decreased significantly in relative The greatest difference between groups strength. also demonstrated weakness on paretic nonparetic side. results show that muscle is impaired multidirectionally...
Background Mutation of the cystic fibrosis transmembrane-conductance regulator (CFTR) causes (CF) but not all CF aspects can easily be explained by deficient ion transport. CF-inflammation provides one example its pathogenesis remains controversial. Here, we tested simple fundamental hypothesis that wild-type CFTR is needed to suppress NF-κB activity. Methodology/Principal Findings In lung epithelial (H441) and engineered (H57) cell lines; report inflammatory markers are significantly...
Healthcare workers (HCWs) are believed to be at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is not known what extent the natural production antibodies SARS-CoV-2 protective against re-infection.A prospective observational study HCWs in Scotland (UK) from May September 2020 was performed. The Siemens total antibody assay used establish seroprevalence this cohort. Controls, matched for age and sex general local population, were studied...
Background Neutrophils are important in the pathophysiology of coronavirus disease 2019 (COVID-19), but molecular changes contributing to altered neutrophil phenotypes following severe acute respiratory syndrome 2 (SARS-CoV-2) infection not fully understood. We used quantitative mass spectrometry-based proteomics explore immediately SARS-CoV-2 and during recovery. Methods Prospective observational study hospitalised patients with PCR-confirmed (May December 2020). Patients were enrolled...
Background: Deletion of phenylalanine-508 (ΔF508) from the first nucleotide-binding domain (NBD1) in wild-type cystic fibrosis (CF) transmembrane-conductance regulator (wtCFTR) causes CF. However, mechanistic relationship between ΔF508-CFTR and diversity CF disease is unexplained. The surface location F508 on NBD1 creates potential for protein-protein interactions nearby, lies a consensus sequence (SYDE) reported to control pleiotropic protein kinase CK2. Methods: Electrophysiology,...
Precision medicine aims to combat the variability of therapeutic response a given by delivering right patient. However, application precision is predicated on prior quantitation variance reference range normality. Airway pathophysiology provides good example due very variable first line defence against airborne assault. Humans differ in their susceptibility inhaled pollutants and pathogens part magnitude trans-epithelial resistance that determines degree epithelial penetration submucosal...
Chickens exhibiting "flip-over" syndrome were found on necropsy to have a blood structure in the heart chamber. Histological studies showed that this is formed of erythrocytes, leucocytes, fibrin and serum. Fibroblasts, collagen fibers, thrombocyte agglutination not observed. These observations indicate structures studied are post-mortem clots.
Abstract Introduction Healthcare workers are believed to be at increased risk of SARS-CoV-2 infection. The extent that compared the general population and groups most have not been extensively studied. Methods A prospective observational study health social care in NHS Tayside (Scotland, UK) from May September 2020. Siemens total antibody assay was used establish seroprevalence this cohort. Patients provided clinical information including demographics workplace information. Controls, matched...
Most CF (cystic fibrosis) results from deletion of a phenylalanine (F508) in the CFTR {CF transmembrane-conductance regulator; ABCC7 [ABC (ATP-binding cassette) sub-family C member 7]} which causes ER (endoplasmic reticulum) degradation mutant. Using stably CFTR-expressing BHK (baby-hamster kidney) cell lines we demonstrated that wild-type CTFR and F508delCFTR mutant are cleaved into differently sized N- C-terminal-bearing fragments, with each hemi-CFTR carrying its nearest NBD...
Cystic fibrosis results from mutations in the cystic transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate B (NDPK-B, NM23-H2) forms functional complex with CFTR. In airway epithelia forskolin/IBMX significantly increases NDPK-B co-localisation CFTR whereas PKA inhibitors attenuate formation. Furthermore, an derived peptide (but not its NDPK-A equivalent) disrupts NDPK-B/CFTR...
Metformin use in diabetes can cause acidosis and might be linked to pancreatitis. Here, we mechanistically focus on this relationship via a point mutation the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7). CFTR is an ATP-hydrolyzing, cAMP/PKA-activated anion channel regulating pancreatic bicarbonate/chloride secretion across duct-facing apical membranes epithelia. has two nucleotide binding domains (NBD1/2) which clamp ATP molecules their opposed, inverted interfacial...
The most debilitating feature of cystic fibrosis (CF) disease is uncontrolled inflammation respiratory epithelium. relationship between the commonest mutated form CFTR (F508del or ΔF508) and has not yet been elucidated. Here, we present a new paradigm suggesting that can interact with intra‐epithelial IgG, establishing direct link normal immune system. Further, our data show amino‐acid sequence local to F508 bind IgG high affinity, dependent on F508, such loss abolishes this both in vitro...
Background: Healthcare workers (HCW) are believed to be at increased risk of SARS-CoV-2 infection. The extent that compared the general population and groups most have not been extensively studied. It is also known what natural production antibodies protective against re-infection.Methods: A prospective observational study health social care in NHS Tayside (Scotland, UK) from May September 2020. Siemens total antibody assay was used establish seroprevalence this cohort. Controls, matched for...
Although bone pain is common in multiple myeloma (MM), muscular symptoms, especially myalgias, may be rare. We describe a patient who presented with generalised myopathy and elevated creatine kinase (CK) suggestive of polymyositis. Routine blood tests showed raised viscosity marked rouleaux formation the peripheral film. A serum protein electrophoresis IgG Lambda paraproteinemia immunoparesis. sternal marrow aspirate biopsy concurrently obtained from right posterior iliac crest considerable...