Recessively inherited loss-of-function mutations in the PTEN-induced putative kinase 1(Pink1), DJ-1 (Park7) and Parkin (Park2) genes are linked to familial cases of early-onset Parkinson's disease (PD). As part of its strategy to provide more tools for the research community, The Michael J. Fox Foundation for Parkinson's Research (MJFF) funded the generation of novel rat models with targeted disruption ofPink1, DJ-1 or Parkin genes and determined if the loss of these proteins would result in a progressive PD-like phenotype. Pathological, neurochemical and behavioral outcome measures were collected at 4, 6 and 8months of age in homozygous KO rats and compared to wild-type (WT) rats. Both Pink1 and DJ-1 KO rats showed progressive nigral neurodegeneration with about 50% dopaminergic cell loss observed at 8 months of age. ThePink1 KO and DJ-1 KO rats also showed a two to three fold increase in striatal dopamine and serotonin content at 8 months of age. Both Pink1 KO and DJ-1 KO rats exhibited significant motor deficits starting at 4months of age. However, Parkin KO rats displayed normal behaviors with no neurochemical or pathological changes. These results demonstrate that inactivation of the Pink1 or DJ-1 genes in the rat produces progressive neurodegeneration and early behavioral deficits, suggesting that these recessive genes may be essential for the survival of dopaminergic neurons in the substantia nigra (SN). These MJFF-generated novel rat models will assist the research community to elucidate the mechanisms by which these recessive genes produce PD pathology and potentially aid in therapeutic development.

Approaches to improve resolution in chiral separation of several basic pharmaceutical compounds by capillary electrophoresis (CE) via a cyclodextrin (CD) inclusion complexation are described. Tetraalkylammonium reagents, including long-chain cationic surfactants and short-chain alkylammonium hydroxides, are examined for controlling the electroosmotic flow in order to improve resolution of the cationic enantiomers. In this regard, short-chain tetraalkylammonium cations (such as tetrabutylammonium and tetramethylammonium are more effective. First, the short-chain tetraalkylammonium cations can be used at much higher concentrations than the long-chain cationic surfactants, which form micelles in the few millimolar concentration range. As a result, a better capillary wall coverage is provided with the short-chain reagents, which leads to reduction or reversal of the direction of the electroosmotic flow at the acidic pH 2.5. Second, the short-chain tetraalkylammonium cations are relatively less hydrophobic and less likely to occupy the hydrophobic cavity of beta-CD than the long-chain cationic surfactants, leaving the enantioselective interaction sites more available for the analytes. The presence of these tetraalkylammonium cations was essential in many chiral separations that were reportedly not achieved by using the buffer electrolytes containing only the beta-CD as a chiral selector. In addition, a mechanism of chiral recognition by beta-CD for a group of stereoisomers is discussed.

Previously, the use of phenomenological models to describe the migration behavior of acidic solutes in micellar electrokinetic chromatography (MEKC) was reported. In this paper, the phenomenological approach is further extended by including both acidic and basic solutes and simultaneously taking two important experimental factors (pH and micelle concentration) into consideration. In addition, a general method is described to model the migration behavior of ionizable (both acidic and basic) solutes in MEKC with anionic and cationic micelles. The practical implication of the phenomenological approaches is that they will provide quantitative relationships between solute migration and experimental factors such that the migration behavior can be predicted on the basis of a few initial experiments and that physicochemical parameters of solutes can also be estimated from model fitting. Through computer-assisted modeling, migration behavior of several acidic and basic solutes over a pH-micelle concentration factor space was successfully predicted on the basis of only five experiments. Furthermore, this phenomenological approach was used to predict the separation of a group of aromatic amines in MEKC with anionic micelles, which resulted in a successful separation of 18 aromatic amines in less than 15 min.

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