A5029749980- MicroRNA in disease regulation
- Circular RNAs in diseases
- Cancer-related molecular mechanisms research
- Protease and Inhibitor Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Renal Diseases and Glomerulopathies
- Phosphodiesterase function and regulation
- Aortic aneurysm repair treatments
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Ion Channels and Receptors
- Chronic Kidney Disease and Diabetes
- Connective tissue disorders research
- Signaling Pathways in Disease
- Receptor Mechanisms and Signaling
- Aortic Disease and Treatment Approaches
- Atherosclerosis and Cardiovascular Diseases
- Birth, Development, and Health
- Neurobiology and Insect Physiology Research
- Asthma and respiratory diseases
- Cardiac Fibrosis and Remodeling
- Proteoglycans and glycosaminoglycans research
- Dialysis and Renal Disease Management
- Chronic Obstructive Pulmonary Disease (COPD) Research
- 14-3-3 protein interactions
Evotec (Germany)
2022-2024
British Heart Foundation
2013-2019
King's College London
2013-2019
King's College Hospital
2019
University College London
2017
Heart Foundation
2017
Max Delbrück Center
2011-2016
Heinrich Heine University Düsseldorf
2016
Düsseldorf University Hospital
2016
University of Kentucky
2016
MicroRNA-122 (miR-122) is abundant in the liver and involved lipid homeostasis, but its relevance to long-term risk of developing metabolic disorders unknown. We therefore measured circulating miR-122 prospective population-based Bruneck Study (n = 810; survey year 1995). Circulating was associated with prevalent insulin resistance, obesity, syndrome, type 2 diabetes, an adverse profile. Among 92 plasma proteins 135 subspecies quantified mass spectrometry, it correlated inversely...
Rationale: Platelets shed microRNAs (miRNAs). Plasma miRNAs change on platelet inhibition. It is unclear whether plasma miRNA levels correlate with function. Objective: To link small RNAs to reactivity. Methods and Results: Next-generation sequencing of in revealed 2 peaks at 22 23 32 33 nucleotides corresponding YRNAs, respectively. Among predominantly, fragments RNY4 RNY5 were detected. YRNAs measured 125 patients a history acute coronary syndrome who had undergone detailed assessment...
A signaling complex enables the compartmentalized regulation of cyclic AMP by calcium entering through a specific channel.
The identification of patients with high-risk atherosclerotic plaques prior to the manifestation clinical events remains challenging. Recent findings question histology- and imaging-based definitions "vulnerable plaque," necessitating an improved approach for predicting onset symptoms.We performed a proteomics comparison vascular extracellular matrix associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus asymptomatic identify protein signature plaques....
Arginine-vasopressin (AVP) modulates the water channel aquaporin-2 (AQP2) in renal collecting duct to maintain homeostasis of body water. AVP binds vasopressin V2 receptors (V2R), increasing cAMP, which promotes redistribution AQP2 from intracellular vesicles into plasma membrane. cAMP also increases transcription, but whether altered degradation protein levels is not well understood. Here, elevation increased within 30 minutes primary inner medullary (IMCD) cells, human embryonic kidney...
Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement plaque extracellular matrix (ECM) may improve morphology stabilize lesions. Here, we demonstrate that chronic administration LNA-miR-29 into an mouse model improves indices morphology. This occurs due upregulation miR-29 target genes the ECM (col1A col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, necrotic zones. Sustained treatment did not affect...
Accumulating evidence links inflammation and atrial fibrillation (AF).To assess whether markers of systemic are associated with incident AF in the general population.The Bruneck Study is a prospective, population-based cohort study 20-year follow-up (n = 909). The population included random sample community aged 40 to 79 years. Levels 13 were measured at baseline 1990. Findings replicated case-control nested within prospective Salzburg Atherosclerosis Prevention Program Subjects High...
Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which modified post-translationally glycosylation. This study aimed to characterize the glycoproteome of aortic ECM from patients with MFS and relate it aortopathy. Approach Results: extracts aneurysmal ascending tissue without were enriched for glycopeptides. Direct N-glycopeptide analysis mass spectrometry identified 141 glycoforms 47 glycosites within 35 glycoproteins human ECM....
ABSTRACT Background Chronic kidney disease (CKD) is common but heterogenous and associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons CKD referred secondary care. Methods Eligible participants stages G3–4 or G1–2 plus albuminuria >30 mg/mmol were enrolled from 16 nephrology centres England, Scotland Wales 2017 2019. Baseline...
Thrombin signaling promotes atherosclerosis by initiating inflammatory events indirectly through platelet activation and directly via protease-activated receptors. Therefore, endogenous thrombin inhibitors may be relevant modulators of atheroprogression cardiovascular risk. In addition, affect the response to non-vitamin K-dependent oral anticoagulants. Here, question was addressed whether small leucine-rich proteoglycan biglycan acts as an inhibitor in heparin cofactor II.Biglycan...
A-kinase anchoring proteins (AKAPs) include a family of scaffolding that target protein kinase A (PKA) and other signaling to cellular compartments thereby confine the activities associated distinct regions within cells. AKAPs bind PKA directly. The interaction is mediated by dimerization docking domain regulatory subunits PKA-binding AKAPs. Analysis interactions between various domains yielded generalized motif allowing identification Our bioinformatics peptide array screening approaches...
Summary Adenylyl cyclase (AC) isoforms can participate in multimolecular signalling complexes incorporating A-kinase anchoring proteins (AKAPs). We recently identified a direct interaction between Ca2+-sensitive AC8 and plasma membrane-targeted AKAP79/150 (in cultured pancreatic insulin-secreting cells hippocampal neurons), which attenuated the stimulation of by Ca2+ entry (Willoughby et al., 2010). Here, we reveal that AKAP79 recruits cAMP-dependent protein kinase (PKA) to mediate...
Idiopathic nephrotic syndrome (INS) is a heterogenous disease and current classification based on observational responses to therapies or kidney histology. The National Unified Renal Translational Research Enterprise (NURTuRE)-INS cohort aims facilitate novel ways of stratifying INS patients improve understanding, therapeutics design clinical trials.
Neutrophils release reactive oxygen species (ROS) as part of the innate inflammatory immune response. Phosphoinositide 3-kinase gamma (PI3Kgamma), which is induced by bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP), has been identified an essential intracellular mediator ROS production. However, complex signalling reactions that link PI3Kgamma with synthesis NADPH oxidase have not yet described in detail. We found activation neutrophils fMLP triggers association protein...
β2-Agonist inhibitors can relieve chronic obstructive pulmonary disease (COPD) symptoms by stimulating cyclic AMP (cAMP) signaling. A-kinase-anchoring proteins (AKAPs) compartmentalize cAMP signaling establishing protein complexes. We previously reported that the β2-agonist fenoterol, direct activation of kinase A (PKA), and exchange factor directly activated decrease cigarette smoke extract (CSE)-induced release neutrophil attractant interleukin-8 (IL-8) from human airway smooth muscle...
The adult human myocardium is incapable of regeneration; yet, the zebrafish (Danio rerio) can regenerate damaged myocardium. Similar to heart, hearts neonatal, but not mice are capable myocardial regeneration. We performed a proteomics analysis and compared their protein expression profile from neonatal mice. Using difference in-gel electrophoresis (DIGE), there was little overlap between proteome mouse (>8weeks old) (18months hearts. Similarly, significant degree mismatch in Enrichment...
Abstract Chronic kidney diseases (CKD) have genetic associations with function. Univariate genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) associated estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN), two complementary function markers. However, it is unknown whether additional SNPs for can be by multivariate statistical analysis. To address this, we applied canonical correlation analysis (CCA), a method, to individual-level...
Defining the molecular and neuronal basis of associative memories is based upon behavioral preparations that yield high performance due to selection salient stimuli, strong reinforcement, repeated conditioning trials. One those Drosophila aversive olfactory procedure where animals initiate multiple memory components after experience a single cycle training procedure. Here, we explored analysis acquisition dynamics as means define revealed correlations between particular chronologies shock...