0000000000114860
AUTHOR
David Baker
Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.
The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis. Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB(1) and CB(2) cannabinoid receptors in regulating CNS autoimmunity. We found that CB(1) receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB(2) receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB(2)-deficient T cells in the CNS during EAE exhibited reduced levels of apoptosis, a higher…
Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists
The purpose of this study was the generation of central nervous system (CNS)-excluded cannabinoid receptor agonists to test the hypothesis that inhibition of spasticity, due to CNS autoimmunity, could be controlled by affecting neurotransmission within the periphery. Procedures included identification of chemicals and modeling to predict the mode of exclusion; induction and control of spasticity in the ABH mouse model of multiple sclerosis; conditional deletion of CB1 receptor in peripheral nerves; side-effect profiling to demonstrate the mechanism of CNS-exclusion via drug pumps; genome-wide association study in N2(129×ABH) backcross to map polymorphic cannabinoid drug pump; and sequencing…
Politics of Dark Tourism: The Case of Cromañón and ESMA, Buenos Aires, Argentina
Tourism has been recently catalogued as a key global industry (Shaw et al. 1990; Buckley and Witt, 1990; Lee and Chang, 2008). The influx of visitors not only potentially revitalises cultural resources but also generates economic resources of specific destinations. Recently, even spaces of mass-death or disasters such as Ground Zero in New York (9/11 terrorist attack), the Tsunami on Sri Lanka, or Katrina Hurricane hitting New Orleans, USA, can be ‘recycled’ by adopting tourism policies that take death as a main attraction (Klein, 2007). Although this type of tourism has attracted criticism of post-Marxist sociologists, as the sign of sadist spectacle (Bloom 2000; Baudrillard 1996, 2006; Ko…
Protein NMR Structures Refined with Rosetta Have Higher Accuracy Relative to Corresponding X-ray Crystal Structures
We have found that refinement of protein NMR structures using Rosetta with experimental NMR restraints yields more accurate protein NMR structures than those that have been deposited in the PDB using standard refinement protocols. Using 40 pairs of NMR and X-ray crystal structures determined by the Northeast Structural Genomics Consortium, for proteins ranging in size from 5-22 kDa, restrained Rosetta refined structures fit better to the raw experimental data, are in better agreement with their X-ray counterparts, and have better phasing power compared to conventionally determined NMR structures. For 37 proteins for which NMR ensembles were available and which had similar structures in solu…