NMDA receptor up-regulation is a major neuroadaptive process that causes excitatory syndrome upon withdrawal from chronic ethanol exposure. The mechanisms of neuroadaptation of NMDA receptors during withdrawal remain unclear, but several lines of evidence suggest that changed gene expression plays important roles. MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs which are involved in the fine tuning of gene expression in various biological processes.

Bone loss and fracture are leading causes of morbidity with aging. The mechanisms of age-related bone disease have not been defined. Our studies suggest that CSF-1 deficiency and increased Nox4 oxidase expression in osteocytes are key determinants of oxidant stress that impact osteocyte survival/function that is essential for bone remodeling. The long-term goal of this proposal is to delineate mechanistic pathways by which CSF-1/oxidative stress regulate osteocyte homeostasis and identify therapeutic targets to prevent bone loss with age. CSF-1 and CSF-1R are expressed by osteocytes.

Type 2 Diabetes (T2DM) is the seventh leading cause of death in the United States, and is quickly becoming a global pandemic. Its patients suffer either reduced insulin production or insulin sensitivity, the latter of which has been associated with reduced nitric oxide synthase (NOS) activity in T2DM skeletal muscle. NOS proteins produce the gaseous signaling molecule nitric oxide (NO), which has been implicated in glucose uptake and insulin sensitivity. In skeletal muscle, NO is produced by neuronal nitric oxide synthase (nNOS), the tissue's primary NOS isoform.

An adverse intrauterine environment, seen in pregnancies complicated by preeclampsia, obesity or intrauterine growth restriction (IUGR), programs the offspring for disease in later life. Placental function regulates fetal growth and development, transducing the maternal and uterine environment to the fetus, and mediating fetal programming. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through translational repression or mRNA degradation.

With a high attributable mortality rate of 40-50%, Candida species represent the fourth leading cause of hospital-acquired bloodstream infections in the United States. These fungal pathogens are normally found as commensals in mammalian mucosal niches, especially the oral cavity. In immunocompromised patients, Candida overgrowth leads to the formation of biofilms, which play an important role in the development of infection. Biofilms are complex microbial communities that adhere to a surface and are enclosed within an extracellular matrix.

Adipose tissues play key roles in the storage, release, and dispersal of highly energetic molecules to maintain energy homeostasis of the organism in response to environmental and hormonal stimuli. Adipose tissue dysfunction is associated with obesity and various metabolic diseases.

In order to develop a novel restorative system with at least twice the lifetime of Bis-GMA/TEGDMA- based composites, their incomplete cure and susceptibility to hydrolysis and esterase degradation must be overcome. To address these problems, we will develop a novel superhydrophobic, degradation-resistant, dental restorative based on an Oxirane/Acrylate interpenetrating network System (OASys, pronounced Oasis).

TxBiomed will communicate with the Strong Heart Study Steering Committee regarding CALiCo/PAGE administrative issues, actively participate in project and working group conference calls, data analysis and manuscript preparation and attend PAGE Steering Committee calls and in-person meetings.

Intimate partner violence is widespread in the United States and causes serious physical and psychological damage to the victims. Although much of partner violence is reciprocal, women suffer far more damage from victimization than men. Alcohol is implicated in violent relationships, both as a chronic risk factor of and an immediate threat during violent episodes. Little is known about the daily interactional processes between partners, the immediate role of alcohol use in those processes, or the context within which violence and drinking occurs.

The proposed research investigates novel molecular targets and processes that promise to minimize brain damage after cerebral ischemic stroke (CIS) and traumatic brain injury (TBI). Current therapeutic strategies to combat acute brain injuries have been largely unsuccessful. We discovered that the Ca2+ dependent phosphatase calcineurin (CN) can bind to PERK, a stress sensor in the endoplasmic reticulum (ER), increases its auto-phosphorylation and enhance a cellular process called the Unfolded Protein Response (UPR).