Novel tocopherol derivatives and tocopheryl quinone derivatives useful in the decrease of lysosomal substrate accumulation, the restoration of normal lysosomal size, and the treatment of lysosomal storage disorders (LSDs) are provided. The inventors have discovered that tocopherol and tocopheryl quinone derivatives with side chain modifications (such as terminal tri-halogenated methyl groups) exhibit improved pharmacokinetics, modulation of mitochondrial potential and restoration of some LSDs phenotypes.

Five human induced pluripotent stem cells (iPSC) lines are generated using lentivirus-based reprogramming technology. These lines are pluripotent, meaning they have the potential to differentiate into all cells in the body, and theoretically can proliferate/self-renew indefinitely. The iPSC lines are: NC1 (derived from female's fibroblasts), NC2 (derived from female's fibroblasts ), NC3 (derived from male's HUVECS), NC4 (derived from male's fibroblasts) and NC5 (derived from female's fibroblasts). Further details of these cells are available upon request.

The invention is directed to small molecule mimetics of apolipoproteins that have an inter-helical hydrocarbon bond, which stabilizes helix formation.

Apolipoproteins facilitate the transport of lipids and cholesterol in the body. Mimetics of apolipoproteins have been used to treat cholesterol-related disorders. However, these mimetics are susceptible to degradation in biological fluids and as a result, their ability to bind cholesterol becomes diminished over time.

This technology describes a series of small-molecule activators of the pyruvate kinase M2 isoform (PK-M2).

The present invention is directed to a transgenic rat model of Alzheimer's Disease (AD) termed TgF344-19+/-. The invention rat overexpresses two human genes (APPswe and PS1deltaE9 genes), each of which are believed to be independent dominant causes of early-onset AD. The hemizygote exhibits major features of AD pathology (i.e., dense and diffuse amyloid plaques, neurofibrillary tangles, cerebral amyloid angiopathy, hyperphosphorylated tau, paired-helical filaments, Hirano bodies, granulovacuolar degeneration, cognitive impairment, and cortical neuronal loss).

Researchers at NIH have developed islet beta cell M3 muscarinic acetylcholine receptor knockout mouse. The mice were generated by crossing floxed mouse M3 muscarinic acetylcholine receptor mice with mice in which Cre recombinase was controlled by the beta-cell specific rat insulin promoter (RIP-Cre mice).

Q490L point mutation was introduced into the rat M3 muscarinic receptor cDNA to confer persistent, constitutive (ligand-independent) activity. Expression of the M3 receptor mutant was placed under the control of a 650 bp fragment of the rat insulin promoter II (RIP II) to limit expression to the islet beta cell.

Researchers at NIH have generated transgenic mice in which the M3 muscarinic receptor is overexpressed in pancreatic beta cells. This was done by placing the receptor gene under the control of the 650 bp rat insulin promoter II (RIP II). The resulting mice show a pronounced increase in glucose tolerance and enhanced plasma insulin levels. Strikingly, these mutant mice were resistant to diet-induced glucose intolerance and hyperglycemia.

Mosquitoes are responsible for spreading many viruses that can make people sick, including dengue, Zika, chikungunya, yellow fever, and more. The Centers for Disease Control and Prevention's (CDC's) new autocidal gravid ovitrap (AGO) mosquito trap is an inexpensive, simple-to-assemble, and easy-to-maintain trap that targets female mosquitoes looking for a place to lay eggs. The current trap model stands 18 inches (45cm) tall and is made of a 5-gallon (18L) bucket. The AGO trap's unique design lures mosquitoes by using water and an all-natural, organic hay attractant.

The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway. Researchers at NIH injected rabbits with the C-terminal peptide of the mouse S1P lyase — 551-TTDPVTQGNQMNGSPKPR-568 — to develop an antibody that can be used in western blotting to study this pathway.