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Mechanisms of Sex Determination in Zebrafish
The Problem: Differences in (or Disorders of) Sex Development (DSD) are complex medical issues that involve multiple interacting cell types and organ systems. DSDs impact disease...
Regulatory mechanisms of the Hsp90 chaperone machinery
PROJECT SUMMARY The molecular chaperone Heat Shock Protein-90 (Hsp90) is essential for the folding and activity of an array of `client' proteins involved in signal transduction p...
A Leukemia Cell-Specific Coiled-Coil Protein for Treatment of Chronic Myeloid Leukemia
Project Summary/Abstract The long-term goals of this proposal are to explore the protein dimerization interface as an area for therapeutic intervention. Protein dimerization/olig...
Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans
Project Summary The vast majority of cardiovascular diseases (CVD) occur in men and women ≥60 years of age. Changes in the demographics of aging in the U.S. predict progressive...
Neurally targeted group intervention to reduce early childhood anxiety
Clinically significant anxiety affects 20% of preschoolers and can become chronic, leading to depression, substance abuse, school-drop out and even suicide. To reduce anxiety and...
Genetic and molecular correlates of white matter pathology in Alzheimers disease
PROJECT SUMMARY: Although Alzheimer's disease (AD) is typically defined by the accumulation of beta- amyloid and hyperphosphorylated tau proteins, synaptic loss and neuronal degen...
MICROBIOTA-DEPENDENT CONTROL OF CLOSTRIDIUM DIFFICILE: THE ROLE OF ACETATE AND IL-22 BINDING PROTEIN
PROJECT SUMMARY The overall goal of this application is to establish avenues through which we can harness the intestinal microbiota to enhance mucosal immune responses against Cl...
Using Genetic Diversity to Manage Neurological Disease
Project Summary/Abstract Understanding and treating genome abnormalities that lead to rare genetic neurodegenerative diseases such as Niemann-Pick C1 globally managing cholestero...
Development of biophysical approaches to investigate high-resolution structure and dynamics of membrane proteins
Abstract Functional reconstitution of membrane proteins has been the major roadblock for the application of NMR and other biophysical techniques to investigate their high-resolut...
Ribonucleotide Reductase in Hepatoblastoma Progression and Drug Resistance
PROJECT SUMMARY Hepatoblastoma (HB) is a rare liver cancer that occurs exclusively in young children. Although most HB tumors can be removed by surgery after chemotherapy, a smal...
Next generation deep tissue quantitative optical imaging
PROJECT SUMMARY Nearly 20 years of clinical research has shown that near-infrared optical imaging based upon frequency domain diffuse optical spectroscopy (FD-DOS) can be a power...
Place-Based Mapping in Electric-Acoustic Stimulation Listeners
Abstract Cochlear implant (CI) recipients with acoustic hearing in the implanted ear are fit with a hearing aid and CI in the same ear, a configuration described as electric-acou...
Identifying mechanisms that detect and eliminate aneuploid cells
Age-related macular degeneration, glaucoma and cataract are major causes of vision loss and all three diseases are age-related. Each is associated with the accumulation of senesc...
Project 1: Megakaryocytes as Organizers of the Hematopoietic Environment
Insufficient megakaryopoiesis and thrombopoiesis remain the main cause of persistent thrombocytopenia after hematopoietic stem and progenitor cell (HSPC) transplantation and after...
Project 2: Extracellular Glycosylation and Blood Cell Production
Project 2 – Project Summary Maintaining hematopoiesis is critical for life. Generating the proper numbers of functional blood cells across all lineages requires cell-intrinsic de...
Project 3: Role of Glycosaminoglycans in Hematopoiesis
Project 3 – Project Summary/Abstract Glycosaminoglycans (GAGs) contribute to myriad, and very often opposing, functions such as cellular proliferation as well as apoptosis, self-...
Improving Access and Affordability of Adult Hearing Healthcare: Effectiveness of Community-based Interventions in West Central and South Alabama
Abstract Mounting evidence suggests that hearing loss is associated with social isolation, depression and cognitive decline. Loss of hearing has become a growing public health c...
Coupled Protons and Electrons in Biological Systems
Project Summary/Abstract Controlling the movement of electrons and protons is critical for a wide range of biological processes, including cellular respiration, DNA biosynthesis,...
Targeting antibiotic resistance genes in Vibrio cholerae using a phage-encoded CRISPR-Cas system to improve efficacy of phage prophylaxis
PROJECT SUMMARY The incessant rise of multidrug resistance in bacterial pathogens has created a dire situation that necessitates development of new modalities for preventing and...
Dynamics of calcium signals control neurotransmitter release in retinal ribbon synapses
Retinal bipolar cells are the first 'projection neurons' of the vertebrate visual system and transmit all of the information needed for vision. Bipolar cells can signal change in...