Abstract: The present invention relates to the engineering an animal model, preferably mammalian models, more preferably a rat model representing Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in a severe, early-onset axonal neuropathy. A model having the p.Arg364Trp Mfn2 mutation is based on a mutation made using zinc finger endonuclease technology in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized behaviorally and shown to develop multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type rats sacrificed at 7, 40, and 48 weeks and analyzed by light microscopy showed a reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks.

Abstract: Various aspects of the present disclosure are directed toward apparatuses, systems, and methods that include a plurality of absorbable filaments arranged in a support structure and configured degrade within a defined time period and a membrane arranged about the plurality of absorbable filaments and configured to contain fragments of the plurality of absorbable filaments in response to a fracture or degradation of a filament.

Abstract: The present invention relates to Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in severe, early-onset axonal neuropathy for p.Arg364Trp Mfn2 mutation in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized with multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type at 7, 40, and 48 weeks showed reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks not present in 7-week-old cohort Mfn2 mutants, or wild type at 7 or 40 weeks. The p.His361Tyr Mfn2 mutation using CRISPR/Cas9 showed abnormalities in gait dynamics at 8 weeks and lengthening of gait cycle at 16 weeks. The invention provides progressive axonal neuropathy for examining pathogenesis and treatment of CMT2A.

Abstract: The present invention relates to the engineering an animal model, preferably mammalian models, more preferably a rat model representing Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in a severe, early-onset axonal neuropathy. A model having the p.Arg364Trp Mfn2 mutation is based on a mutation made using zinc finger endonuclease technology in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized behaviorally and shown to develop multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type rats sacrificed at 7, 40, and 48 weeks and analyzed by light microscopy showed a reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks.

Abstract: An animal model for Parkinson's disease has a disrupted Mfn2 gene in dopaminergic neurons. The Mfn2 gene disruption results in severe movement disorder attributed to progressive degeneration of the nigrostriatal circuit as found in Parkinson's disease. The animal model having exogenous suppression of the Mfn2 gene in dopaminergic neurons is a suitable animal model for studying Parkinson's disease.

Abstract: An animal model includes a photo-activatable fluorescent protein that can conditionally label the mitochondria throughout the animal or in selective animal cells and tissues, allowing for effective studying of the mitochondria and tracking of mitochondrial dynamics.

Abstract: An animal model for Parkinson's disease has a disrupted Mfn2 gene in dopaminergic neurons.

Abstract: Five-Helix protein, which comprises the three N-helices and at least two, but not three, of the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, such as amino acid residue linkers, is disclosed. Six-Helix protein, which includes the three N-helices and the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, is also disclosed.

Abstract: Inhibitors of HIV membrane fusion and a method of identifying drugs or agents which inhibit binding of the N-helix coiled-coil and the C helix of HIV gp41 envelope protein.

Abstract: Five-Helix protein, which comprises the three N-helices and at least two, but not three, of the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, such as amino acid residue linkers, is disclosed. Six-Helix protein, which includes the three N-helices and the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, is also disclosed.

Abstract: Five-Helix protein, which comprises the three N-helices and at least two, but not three, of the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, such as amino acid residue linkers, is disclosed. Six-Helix protein, which includes the three N-helices and the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, is also disclosed.

Abstract: Described are the crystal structure of the ?-helical domain of the gp41 component of HIV-1 envelope glycoprotein which represents the core of fusion-active gp41, methods of identifying and designing drugs which inhibit gp41 function and drugs which do so.

Abstract: Five-Helix protein, which comprises the three N-helices and at least two, but not three, of the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, such as amino acid residue linkers, is disclosed. Six-Helix protein, which includes the three N-helices and the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, is also disclosed.

Abstract: Inhibitors of HIV membrane fusion and a method of identifying drugs or agents which inhibit binding of the N-helix coiled-coil and the C helix of HIV gp41 envelope protein.

Abstract: Inhibitors of HIV membrane fusion and a method of identifying drugs or agents which inhibit binding of the N-helix coiled-coil and the C helix of HIV gp41 envelope protein.

Abstract: Described are the crystal structure of the &agr;-helical domain of the gp41 component of HIV-1 envelope glycoprotein which represents the core of fusion-active gp41, methods of identifying and designing drugs which inhibit gp41 function and drugs which do so.

Abstract: Five-Helix protein, which comprises the three N-helices and at least two, but not three, of the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, such as amino acid residue linkers, is disclosed. Six-Helix protein, which includes the three N-helices and the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, is also disclosed.

Abstract: Described are the crystal structure of the &agr;-helical domain of the gp41 component of HIV-1 envelope glycoprotein which represents the core of fusion-active gp41, methods of identifying and designing drugs which inhibit gp41 function and drugs which do so.

Abstract: Inhibitors of HIV membrane fusion and a method of identifying drugs or agents which inhibit binding of the N-helix coiled-coil and the C helix of HIV gp41 envelope protein.

Abstract: Five-Helix protein, which comprises the three N-helices and at least two, but not three, of the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, such as amino acid residue linkers, is disclosed. Six-Helix protein, which includes the three N-helices and the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, is also disclosed.