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Researchers at NIAMS have developed a technology for treatment of lysosomal storage diseases by inhibition of autophagy. Pompe disease is an example of a genetic lysosomal storage disease caused by a reduction or absence of acid alpha-glucosidase (GAA). Patients with Pompe disease have a lysosomal buildup of glycogen in cardiac and skeletal muscle cells and severe cardiomyopathy and skeletal muscle myopathy. Treatment of Pompe disease by GAA enzyme replacement therapy is quite ineffective for the skeletal muscle myopathy.

Microglia activation leads to inflammation mediated dopaminergic degeneration in the brain of patients with Parkinson and Alzheimer's Disease. Thus Identification of drugs that reduce microglia activation could prevent or reverse neuronal degeneration in these diseases and other degenerative CNS disorders.

This invention involves ApoA-1 mimetic peptides with multiple amphipathic alpha-helical domains that promote lipid efflux from cells and are useful in the treatment and prevention of dyslipidemic, inflammatory and vascular disorders. IND-enabling studies for one of the peptides, named Fx-5A, are completed in preparation for an IND filing at the FDA, to be followed by a Phase I clinical trial planned for 2017.

Estrogen related receptor alpha (ERRalpha) is a family member of the steroid/thyroid nuclear receptor superfamily. Estrogen related receptors are thought to regulate similar target genes in the absence of known ligands. For example, the inventors previously cloned the human estrogen receptor-related orphan receptor alpha1 cDNA and demonstrated that it enhances estrogen responsiveness of the lactoferrin gene promoter in transfected human endometrial carcinoma cells.

Lactoferrin, an iron-binding glycoprotein, kills bacteria and modulates inflammatory and immune responses. It is expressed in mucosa membrane and is present in saliva, tears, vaginal secretion and neutrophils. It modulates immune and inflammatory response by down-regulating several cytokines. Therefore, lactoferrin is an important protein in first line of defense and protecting health. Changes in lactoferrin expression could also be used as a marker of gene activation, especially estrogen-induced gene activity in the uterus.

This invention relates to a strain of Moraxella catarrhalis containing a gene mutation that prevents endotoxic lipooligosaccharide (LOS) synthesis and potential use of the mutant for developing novel vaccines against the pathogen, for which there is currently no licensed vaccine. M. catarrhalis is one of the causative agents of otitis media (middle ear infection), sinusitis, and lung infections. The mutant is defective in the lpxA gene, whose enzyme product is relevant in lipid A biosynthesis (lipid A is part of the LOS).

The invention relates to monoclonal antibodies that bind to the transcription factor NCOA6 (ASC-2, AIB-3, TRB, TRAP250, NRC). The antibodies have proven successful reagents for Western blotting and for purifying complexes containing NCOA6. The Western blot experiments revealed that NCOA6 is over-expressed in several breast cancer cell lines, and the purification experiments identified a protein complex containing NCOA6 (the ASCOM complex). The monoclonal antibodies may be useful reagents for studying the role of NCOA6 in transcription and for studying the ASCOM complex.

Available for licensing and commercial development is a new scheme for sensitive spatially resolved and spectrally resolved laser-induced fluorescence detection from multiple microfluidic channels. The prototype instrument has been developed and is versatile in that it contains only fixed optical parts and has simultaneous five-color detection from eight microchannels in a plastic microchip for DNA analysis. The detection scheme could be applied to fluorescence detection for any microchip-based analysis in a transparent substrate.

The identified technologies describe self-replicating infectious recombinant paramyxoviruses with one or more attenuating mutations, such as a separate variant polynucleotide encoding a P protein and a separate monocistronic polynucleotide encoding a V protein, or at least one temperature sensitive mutation and one non-temperature sensitive mutation. Compositions and methods for recovering, making and using the infectious, recombinant paramyxoviruses as described are also included (e.g. recombinant human parainfluenza virus type 2 (HPIV2)).

This invention relates to materials and methods associated with polymorphic variants in two enzymes involved in folate-dependent and one-carbon metabolic pathways important in pregnancy-related complications and neural tube birth defects: MTHFD1 (5,10-methylenetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthase) and methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L). These enzymes are extremely important in the promotion of DNA synthesis, a process that is critical for normal placental and fetal development.