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The nucleotide-binding oligomerization domain 2 (NOD2) protein plays a key role in innate immunity as a sensor of muramyl dipeptide (MDP), a breakdown product of bacterial peptidoglycan. Bacterial peptidoglycan promotes the innate immune response through the activation of Toll-like receptor 2 (TLR2), which ultimately provokes inflammation. Activation of NOD2 by MDP negatively regulates the activity of TLR2, and thus reduces inflammation.

The inventions described herein are antimalarial small molecule inhibitors of the plasmodial surface anion channel (PSAC), an essential nutrient acquisition ion channel expressed on human erythrocytes infected with malaria parasites. These inhibitors were discovered by high-throughput screening of chemical libraries and analysis of their ability to kill malaria parasites in culture. Two separate classes of inhibitors were found to work synergistically in combination against PSAC and killed malaria cultures at markedly lower concentrations than separately.

This invention offers technology to help treat certain brain diseases, such as Alzheimer's disease and Parkinson's, and may lead to more effective and personalized treatments. P-glycoprotein transporter (P-gp) acts as a pump at the blood-brain barrier to exclude a wide range of xenobiotics (e.g., toxins, drugs, etc.) from the brain and is also expressed in a tumor in response to exposure to established/prospective chemotherapeutics (a phenomenon known as multidrug resistance; MDR).

Many individuals with ongoing and severe dental problems are faced with the prospect of permanent tooth loss. Examples include dentinal degradation due to caries or periodontal disease; (accidental) injury to the mouth; and surgical removal of teeth due to tumors associated with the jaw. Clearly, a technology that offers a possible alternative to artificial dentures by designing and transplanting a set of living teeth fashioned from the patient's own pulp cells would greatly improve the individual's quality of life.

The current invention provides nucleic acid sequences comprising the genomes of infectious hepatitis C viruses (HCV) of genotype 1a and 1b. It covers the use of these sequences, and polypeptides encoded by all or part of the sequences, in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV.

Monoclonal antibodies (mAbs) have become a mainstay of therapy for many cancers. However, antibody therapy is not completely effective in some applications due to loss of the target surface antigen on cancer cells. Such mAb-induced “escape variants” are no longer sensitive to the therapeutic mAb therapy. It was observed that the escape variants carried covalently bound complement activation fragments, especially C3d. NIH inventors have generated several C3d-specific mouse and rabbit monoclonal antibodies to re-target cells that have escaped from mAb therapy.

Enteric viruses like norovirus, rotavirus and astrovirus mainly transmit through fecal-oral route by ingestion of contaminated food and water and productively replicate in the intestines. Recently, researchers at National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Dental and Craniofacial Research (NIDCR) identified a second route of enteric viral transmission by demonstrating that these viruses also productively and persistently infect salivary glands, reaching titers comparable to that in intestines.

Feedback vasodilation by endothelium-derived nitric oxide (NO) is under the regulation of globins. NIH Researchers discovered that not only the alpha globin but also the beta globin subunits of hemoglobin are expressed in the human artery wall, with beta globin interacting directly with endothelial nitric oxide synthase (eNOS).

Local inflammation processes are crucially important in the host defense against pathogens and for successful immunization because proinflammatory cytokines are necessary for initiation and propagation of an immune response. However, normal inflammatory responses are eventually terminated by physiological termination mechanisms, thereby limiting the strength and duration of immune responses, especially to weak antigens. The inventors have shown that adenosine A2a and A3a receptors play a critical role in down-regulation of inflammation in vivo.

Patient conditioning is a critical initial step in hematopoietic stem and progenitor cell (HSPC) transplantation procedures to enable marrow engraftment of infused cells. Conditioning regimens have traditionally been achieved by delivering cytotoxic doses of chemotherapeutic agents and radiation. However, these regimens are associated with significant morbidity and mortality, and cannot be used safely in elderly or subjects with comorbidities.