- Cellular transport and secretion
- Chronic Kidney Disease and Diabetes
- RNA and protein synthesis mechanisms
- Nerve injury and regeneration
- Signaling Pathways in Disease
- Pancreatic function and diabetes
- Hereditary Neurological Disorders
- Renin-Angiotensin System Studies
- Renal Diseases and Glomerulopathies
- Lipid Membrane Structure and Behavior
- Electrolyte and hormonal disorders
- Cancer, Lipids, and Metabolism
- Diabetes Treatment and Management
- Birth, Development, and Health
- Kidney Stones and Urolithiasis Treatments
- Monoclonal and Polyclonal Antibodies Research
- Gastroesophageal reflux and treatments
- Biochemical and Molecular Research
- Calcium signaling and nucleotide metabolism
- Glycogen Storage Diseases and Myoclonus
- Systemic Sclerosis and Related Diseases
- Ubiquitin and proteasome pathways
- Lipoproteins and Cardiovascular Health
- Eicosanoids and Hypertension Pharmacology
- Clinical Nutrition and Gastroenterology
National Institutes of Health
2014-2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2018-2024
National Institute of Diabetes and Digestive and Kidney Diseases
2016
Hospital Universitario de Gran Canaria Doctor Negrín
2011-2012
Interstitial fibrosis is commonly measured by histology. The Masson trichrome stain widely used, with semiquantitative scores subjectively assigned trained operators. We have developed an objective technique combining Sirius Red staining, polarization contrast microscopy, and automated analysis. Repeated analysis of the same sections operator (r = 0.99) or different operators 0.98) was highly consistent for Red, while performed less consistently 0.61 0.72, respectively). These techniques...
Chronic kidney disease (CKD) is associated with persistent low-grade inflammation and immunosuppression. In this study we tested the role of Toll-like receptor 4, main for endotoxin (LPS), in a mouse model renal fibrosis progressive CKD that better resembles human disease. C3HeJ (TLR4 mutant) mice have missense point mutation TLR4 gene, rendering nonfunctional. after folic acid injection, mutant developed less interstititial comparison to wild-type (WT) mice. Furthermore, 4 weeks 5/6...
Active membrane remodeling during myelination relies on phospholipid synthesis and polarization, both of which are known to depend inositol phospholipids. Here, we show that sciatic nerves mice lacking phosphatidylinositol 4-kinase alpha (PI4KA) in Schwann cells (SCs) substantially reduced myelin thickness with grave consequences nerve conductivity motor functions. Surprisingly, prolonged inhibition PI4KA immortalized mouse SCs failed decrease plasma 4,5-bisphosphate (PI(4,5)P
The lipid kinase phosphatidylinositol 4 III α (PI4KIIIα/PI4KA) is a master regulator of the composition and asymmetry plasma membrane. PI4KA exists primarily in heterotrimeric complex with its regulatory proteins TTC7 FAM126. Fundamental to activity targeted recruitment membrane by lipidated EFR3A EFR3B. Here, we report cryogenic electron microscopy structure C terminus bound PI4KA-TTC7B-FAM126A complex, extensive validation using both hydrogen deuterium exchange mass spectrometry,...
Significance We identify PI4KB, a phosphoinositide kinase that controls the functions of Golgi compartment, as critical regulator myelination peripheral nerves. Genetic inactivation specifically in Schwann cells mice, causes hypomyelination large diameter axons and impairs engulfment small fibers by nonmyelinating cells. Sciatic nerves mutant mice show depletion cholesterol, sphingomyelin phosphatidylethanolamine, well defects protein glycosylation.
The lipid kinase phosphatidylinositol 4 III alpha (PI4KIIIa/PI4KA) is a master regulator of the composition and asymmetry plasma membrane. PI4KA exists primarily in heterotrimeric complex with its regulatory proteins TTC7 FAM126. Fundamental to activity targeted recruitment membrane by lipidated EFR3A EFR3B. Here, we report cryo-EM structure C-terminus bound PI4KA-TTC7B-FAM126A complex, extensive validation using both hydrogen deuterium exchange mass spectrometry (HDX-MS), mutational...
Angiotensin receptor 1 blockers (ARB) are standard nephroprotective drugs in chronic kidney disease. There is less evidence for a effect of HMG-CoA reductase inhibitors (statins) and much known about potential benefits combination therapy. We evaluated the therapeutic statin alone or with an ARB experimental disease.Subtotally nephrectomized (5/6 Nx) rats were treated early vehicle, losartan, cerivastatin losartan/cerivastatin. Expression messenger RNA (mRNA) was assessed by real-time...
AbstractCompensatory hyperhidrosis is an adverse effect of thoracic sympathectomy that can be debilitating, which why efficient treatment demanded. Botulinum toxin emerging treatment, not well known yet. We report two cases compensatory following were both treated with low doses botulinum A. The patients, a male and female, noted high level satisfaction the abolishment sweating was maintained up to 10 months. consider A tolerated, safe effective for should offered as alternative...