A5068112587- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Erythrocyte Function and Pathophysiology
- Blood properties and coagulation
- Genetic Syndromes and Imprinting
- Lipid Membrane Structure and Behavior
- Genomics and Rare Diseases
- Health Systems, Economic Evaluations, Quality of Life
- Epigenetics and DNA Methylation
- Cardiovascular Syncope and Autonomic Disorders
- Chronic Kidney Disease and Diabetes
- Pharmaceutical studies and practices
- Connexins and lens biology
- Dialysis and Renal Disease Management
- Ethics in Clinical Research
- Blood Pressure and Hypertension Studies
- Porphyrin and Phthalocyanine Chemistry
- Sphingolipid Metabolism and Signaling
- Vascular Malformations and Hemangiomas
- Gastroesophageal reflux and treatments
- Supramolecular Self-Assembly in Materials
- Diabetes and associated disorders
- Hearing, Cochlea, Tinnitus, Genetics
- Immunodeficiency and Autoimmune Disorders
- Prenatal Screening and Diagnostics
Sheffield Kidney Institute
2016-2024
Sheffield Teaching Hospitals NHS Foundation Trust
2016-2024
University of Sheffield
2016-2024
University of Leeds
2019-2022
Northern General Hospital
2018
University College London
2012
UCL Australia
2007
Endogenous PIEZO1 channels of native endothelium lack the hallmark inactivation often seen when these are overexpressed in cell lines. Because prior work showed that force shear stress activates sphingomyelinase endothelium, we considered if is relevant to endogenous PIEZO1. Patch clamping was used quantify PIEZO1-mediated signals freshly isolated murine exposed mechanical forces caused by and membrane stretch. Neutral inhibitors genetic disruption sphingomyelin phosphodiesterase 3 (SMPD3)...
Our main objective was to identify baseline prognostic factors predictive of rapid disease progression in a large unselected clinical autosomal dominant polycystic kidney (ADPKD) cohort.
To investigate the prevalence of biallelic PKD1 and PKD2 variants underlying very early onset (VEO) polycystic kidney disease (PKD) in a large international pediatric cohort referred for clinical indications over 10-year period (2010-2020).All samples were tested by Sanger sequencing multiplex ligation-dependent probe amplification (MLPA) genes and/or next-generation panel 15 additional cystic including PKHD1 HNF1B. Two patients underwent exome or genome sequencing.Likely causative detected...
Piezo1 forms a mechanically activated calcium-permeable nonselective cation channel that is functionally important in many cell types. Structural data exist for C-terminal regions, but we lack information about N-terminal regions and how the entire interacts with lipid bilayer. Here, use computational approaches to predict three-dimensional structure of full-length simulate it an asymmetric membrane. A number novel insights are suggested by model: 1) creates trilobed dome membrane extends...
Birth weight is an important indicator of both perinatal and adult health, but little known about the genetic factors contributing to its variability. Intrauterine growth restriction a leading cause morbidity mortality also associated with disease. A significant correlation has been reported between lower birth increased expression maternal PHLDA2 allele in term placenta (the normal imprinting pattern was maintained). However, mechanism that explains transcriptional regulation on utero yet...
<ns4:p>The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16<ns4:sup>th</ns4:sup>century. Advances in understanding presentation and pathophysiology have mirrored progress medicine anatomy, pathology, physiology, cell biology, genetics. The identification of<ns4:italic>PKD1</ns4:italic>and<ns4:italic>PKD</ns4:italic>2, major genes mutated ADPKD, has stimulated advances, which turn led approved drug for this disorder...
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is thought to affect about 1 in 1000 people the UK. ADPKD causes a progressive decline kidney function, with failure tending occur middle age. Children and young may not have any symptoms. However they high blood pressure, which accelerate progression later stages of chronic disease. There uncertainty variation how health professionals manage children confirmed or family history ADPKD, because lack evidence. For example, be unsure when...
Current classification systems do not specify a healthy normal range for urinary albumin excretion. Occult microvascular disease induced by Western lifestyle may mean that values apparently adults exceed optimal levels defined mortality risk.Using national population sample [the US Third National Health and Nutrition Examination Survey (NHANES III) cohort; n = 11 887], the distributions of albumin:creatinine ratio (ACR) fractional excretion (FEalb) were studied in young [ages 20-40 years,...
Tolvaptan, a vasopressin V2 receptor antagonist, was approved in 2015 by the UK National Institute for Health and Care Excellence use patients with autosomal dominant polycystic kidney disease (ADPKD) rapid progression. Simultaneous guidance issued Kidney Association (UKKA) to facilitate national implementation. Data on tolvaptan prescribing England obtained through Service (NHS) Digital, survey of all 77 adult units, implementation UKKA evaluated at an expert PKD centre. A regional...
ABSTRACT Piezo1 is a critical mechanical sensor in many cells. It activated by force thus allowing cells to sense the physical environment and respond stress. Structural data have suggested that has curved shape. Here, we use computational approaches model, for first time, 3D structure of full-length an asymmetric membrane. A number novel insights emerge: (i) creates dome membrane with trilobed topology extends beyond radius protein, (ii) changes lipid its vicinity via specific interactions...
ABSTRACT Piezo1 channels are determinants of vascular responses to fluid flow. They importantly provide sustained response flow, but this property contrasts with the rapid inactivation that has become a hallmark in heterologous overexpression studies. Here we reveal mechanism by which blood vessels disable enable physiological response. Creation molecular model channel defined lipid membranes suggested potential modulation sphingomyelin and its product ceramide. Biological relevance was...
interactor.Figure 6 shows ATP synthase localizes to cilia, and involved in polycystin signaling pathway.Figure7,8 tells us F1Fo beta subunit (F1b) other subunits of mitochondrial respiratory chain complexes are present on cilia NMC cells.ATP co-localizes with polycystin-1,and was detected exosomes(Fig9).PKD-2 is mislocalized pde-1 mutant C.elegans(Fig10).C.elegans PKA homolog, KIN-1, middle segment cilium (A,), does not affect PKD-2 localization (B), but pathway (C)(Fig11).CONCLUSIONS: In...
Autosomal dominant polycystic kidney disease (ADPKD) is generally an adult onset disorder; however rare very early (VEO) cases under the age of 2 years are reported and have a high recurrence risk in subsequent pregnancies. Elucidation underlying mechanism causing phenotype has significant benefits for genetic reproductive counselling.