Human DNA Polymerase Gamma for Testing the Effect of Drugs on Mitochondrial Function

One of the primary means for treating HIV infection is the use of antiviral nucleotide or nucleoside analogs. These analogs work by inhibiting the activity of reverse transcriptase, the enzyme responsible for preparing the HIV genome for integration into the DNA of the host cell. Although these analogs do not have an effect on the polymerases responsible for replicating the human genome, the polymerase responsible for replicating the mitochondrial genome is sensitive to these analogs.

Java Applet for Modeling Human Metabolism and Energy Expenditure for Adaptive Dieting and Exercise Regimens

Known methods for predicting weight loss fail to account for slowing of metabolism as weight is lost and therefore overestimate the degree of weight loss. While this limitation of the 3500 Calorie per pound rule has been known for some time, it was not clear how to dynamically account for the metabolic slowing. The invention provides a Java applet for modeling of human metabolism to improve the weight change predictions. The model has been validated using previously published human data and the model equations have been published.

Antagonist of A3 Adenosine Receptor Fluorescent Probes for the Study of Diseases that Involve A3 Signaling

This molecular probe may serve as a companion tool to identify and stratify patient populations based on the prevalence of the target A3 adenosine receptors.

Small molecule drugs, A3AR-selective agonists, are currently in advanced clinical trials for the treatment of hepatocellular carcinoma, autoimmune inflammatory diseases, such as rheumatoid arthritis, psoriasis, and dry eye disease, and other conditions.

GLI-Similar 3(GLIS3) Knock Out (KO) Mice as Models to Screen Therapeutics for Diabetes, Polycystic Kidney Disease, and Hypothyroidism

GLI-similar (Glis) 1-3 proteins constitute a subfamily of the Krüppel-like zinc finger transcription factors that are closely related to the Gli family. Mutations in human GLIS3 have been implicated in a syndrome characterized by neonatal diabetes and congenital hypothyroidism (NDH) and in some patients accompanied by polycystic kidney disease, glaucoma, and liver fibrosis. To further identify and study the physiological functions of GLIS3, NIEHS investigators generated mice in which GLIS3 is ubiquitously knocked out (GLIS3-KO) or conditionally knocked out in a cell type-specific manner.

Treatment of Viral Infection by Blocking Interleukin-21

Blocking interleukin (IL-21) may be an effective method to treat or prevent various viral infections. In the course of an immune response to a virus, IL-21, produced primarily by CD4+ T cells, can inhibit or stimulate (regulate), immune cell function (B cells, T cells, natural killer cells, dendritic cells). IL-21 regulation may be either protective or pathological; autoimmune disease pathology has been associated with IL-21 promoted inflammation (in: type 1 diabetes, lupus, and multiple sclerosis).

Endothelial Cell Line to Study Prevention of Atherosclerosis

Atherosclerosis underlies most cases of cardiovascular disease (CVD), which is now the major cause of morbidity and mortality in developed countries. An inflammatory reaction is an essential component in the appearance and development of an atherosclerotic lesion. The inflammatory process is associated with the expression of adhesion molecules such as vascular cell adhesion molecule (VCAM) at the surface of endothelial cells. Antiatherogenic lipoprotein, high density lipoprotein (HDL), is known to down regulate the expression of VCAM.

Salen-Manganese Compounds for Therapy of Viral Infections

Salen-manganese compounds are synthetic, stable, low toxicity, low cost agents that may provide protection from immune reaction-related oxidative cell damage associated with many illnesses. In particular, oxidative cell damage has been associated with many viral infections including influenza. This invention demonstrates that treating mice with salen-manganese compounds, after lethal pandemic influenza virus infection, significantly enhances survival. Salen-manganese treatment also reduces lung pathology and also improved cellular recovery and repair.

Plasmid Useful in Transplantation Therapy for Age-Related Eye Disease

Researchers have developed a green fluorescent protein (GFP) based plasmid that can be used to detect differentiated retinal pigment epithelium (RPE) cells. RPE is a layer of cells located behind the eye that becomes damaged in age-related macular degeneration (AMD). Current cell based therapies for treating AMD focus on generating RPE cells from stem cells. This GPF-based plasmid can be inserted into growing stem cells, and the fluorescence marker can be used to detect and purify stem cells differentiating into RPE cells.

A Method to Expand a Population of Regulatory T Cells Optimal for the Treatment of Autoimmune Diseases

The transfusion of regulatory T cells (Tregs) has been used in the clinic to successfully prevent graft vs. host disease and is currently being evaluated in the treatment of other autoimmune diseases, such as organ graft rejection, type 1 diabetes and multiple sclerosis. Prior to transfusion, adoptive regulatory T cell transfer requires the expansion of regulatory T cells in culture; this results in a mixed population of regulatory T cells that limits the effectiveness of the transferred cells.