![]() ![]() The present application in one aspect provides methods of identifying compounds that modulate mitochondrial function in human brain using a modified teleost (such as zebrafish). The disclosure of all patents, patent applications, and other publications cited herein are hereby incorporated by reference in their entirety for all purposes. Throughout this specification, various patents, patent applications and other types of publications (e.g., journal articles, electronic database entries, etc.) are referenced. These features make zebrafish an attractive model for human disease. In addition, like humans, zebrafish have a chambered heart, rhythmic pumping of oxygenated blood, exquisitely organized structures of the human brain, eyes, and other neural regions, and peripheral organs including the liver, pancreas, kidneys, and intestines. Many biological pathways are shared between zebrafish and humans. Zebrafish are simple vertebrates that are highly amenable to teleost genetic manipulation and share >80% teleost genetic similarity with humans. Most of the drug screening process to date have been conducted in normal (i.e., non-epileptic) human brain, and in vitro functional read-out assays have almost exclusively focused on plasma membrane-bound ion channels and transporters as targets, and have largely reflected enzymes and substrates critical for cellular homeostasis. ![]() ![]() Drugs remain the mainstay of treatment for epilepsy, yet despite nearly eight decades of research and advent of many newer medications, the efficacy rates have not significantly changed. For example, of the nearly 700,000 Canadian with epilepsy, about 250,000 people will not respond to drugs and will continue to have unremitting recurrent seizures and attendant life-long cognitive, behavioral, and mental health problems. BACKGROUNDĮpilepsy is a common neurological condition that affects about 1-2% of the general population. Provided herein is a novel drug screening platform designed to identify drugs that favorably modulate mitochondrial function and bioenergetics in the human brain via the use of one or more genetically altered teleost gene(s) corresponding to a human gene associated with a human disease. 17, 2014, the entire contents of which are incorporated herein by reference in their entireties and for all purposes. 16, 2015, which claims the benefit of and priority to U.S. The PHBV-PLLA blend appeared to yield the best results regarding cell number increase, their attachment and spreading inside and on the scaffold.This application is a national stage entry, filed under 35 U.S. Conclusion: All scaffolds prepared by electrospinning have implied significant potential for use in further studies leading to bone tissue engineering applications. Surface modification with oxygen plasma treatment slightly improved the improved the results in terms of cell number increase and significantly improved spreading of the cells. In vitro studies using human osteosarcoma cells (Saos-2) revealed that the electrospun scaffolds promoted cell growth and penetration. The blends of PHBV with lactide-based polymers led to fibers with less beads and more uniform diameter. ![]() Increase in potential (from 20 to 50 kV) did not lead to the expected decrease in fiber diameter. Concentration was highly influential on fiber properties as it increased from 5 to 15% (w/v), fiber diameter increased from 284 ± 133 nm to 2200 ± 716 nm. Results: Various processing parameters affected the morphology and the dimensions of beads formed on the fibers. Aims & method: In this study, a microbial polyester, poly(3-hydroxybutyrate-co- 3-hydroxyvalerate) (PHBV), and its blends were electrospun into PHBV (10% w/v), PHBV (15% w/v), PHBV-PLLA (5% w/v), PHBV-PLGA (50:50) (15% w/v) and PHBV-P(L,DL)LA (5% w/v) fibrous scaffolds for tissue engineering. ![]()
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