AAV2-mediated gene transfer of GDNF to the striatum of MPTP monkeys enhances the survival and outgrowth of co-implanted fetal dopamine neurons

Neural transplantation offers the potential of treating Parkinson’s disease by grafting fetal dopamine neurons to depleted regions of the brain. However, clinical studies of neural grafting in Parkinson’s disease have produced only modest improvements. One of the main reasons for this is the low survival rate of transplanted neurons. The inadequate supply of critical neurotrophic factors in the adult brain is likely to be a major cause of early cell death and restricted outgrowth of fetal grafts placed into the mature striatum. Glial derived neurotrophic factor (GDNF) is a potent neurotrophic factor that is crucial to the survival, outgrowth and maintenance of dopamine neurons, and so is a candidate for protecting grafted fetal dopamine neurons in the adult brain. We found that implantation of adeno-associated virus type 2 encoding GDNF (AAV2-GDNF) in the normal monkey caudate nucleus induced over-expression of GDNF that persisted for at least 6 months after injection. In a 6-month within-animal controlled study, AAV2-GDNF enhanced the survival of fetal dopamine neurons by 4-fold, and increased the outgrowth of grafted fetal dopamine neurons by almost 3-fold in the caudate nucleus of MPTP-treated monkeys, compared with control grafts in the other caudate nucleus. Thus, the addition of GDNF gene therapy to neural transplantation may be a useful strategy to improve treatment for Parkinson’s disease

Kepler-22b: A 2.4 Earth-radius Planet in the Habitable Zone of a Sun-like Star

A search of the time-series photometry from NASA's Kepler spacecraft reveals a transiting planet candidate orbiting the 11th magnitude G5 dwarf KIC 10593626 with a period of 290 days. The characteristics of the host star are well constrained by high-resolution spectroscopy combined with an asteroseismic analysis of the Kepler photometry, leading to an estimated mass and radius of 0.970 +/- 0.060 MSun and 0.979 +/- 0.020 RSun. The depth of 492 +/- 10ppm for the three observed transits yields a radius of 2.38 +/- 0.13 REarth for the planet. The system passes a battery of tests for false positives, including reconnaissance spectroscopy, high-resolution imaging, and centroid motion. A full BLENDER analysis provides further validation of the planet interpretation by showing that contamination of the target by an eclipsing system would rarely mimic the observed shape of the transits. The final validation of the planet is provided by 16 radial velocities obtained with HIRES on Keck 1 over a one year span. Although the velocities do not lead to a reliable orbit and mass determination, they are able to constrain the mass to a 3{\sigma} upper limit of 124 MEarth, safely in the regime of planetary masses, thus earning the designation Kepler-22b. The radiative equilibrium temperature is 262K for a planet in Kepler-22b's orbit. Although there is no evidence that Kepler-22b is a rocky planet, it is the first confirmed planet with a measured radius to orbit in the Habitable Zone of any star other than the Sun.Comment: Accepted to Ap

Weisgerber (Jean). Faulkner et Dostoïevski. Confluences et influences.

Elsworth J.D. Weisgerber (Jean). Faulkner et Dostoïevski. Confluences et influences. . In: Revue belge de philologie et d'histoire, tome 48, fasc. 1, 1970. Antiquité — Oudheid. pp. 66-67

Weisgerber (Jean). Faulkner et Dostoïevski. Confluences et influences.

Elsworth J.D. Weisgerber (Jean). Faulkner et Dostoïevski. Confluences et influences. . In: Revue belge de philologie et d'histoire, tome 48, fasc. 1, 1970. Antiquité — Oudheid. pp. 66-67

Purification and characterization of tribulin, an endogenous inhibitor of monoamine oxidase and of benzodiazepine receptor binding

A low molecular weight fraction of human urine (less than 500 daltons) which both inhibits monoamine oxidase and benzodiazepine binding to central and peripheral receptors has been purified by ethyl acetate extractions, HPLC and thin layer chromatography. This material extracted equally well at acid and basic pH and was insoluble in heptane. It competitively inhibited binding of 3H-clonazepam, a central benzodiazepine receptor agonist and, in addition, displaced 3H-Ro 5-4864, a specific peripheral benzodiazepine receptor ligand, from its binding sites. It showed no GABA shift with the benzodiazepine receptor antagonist, Ro-15 1788. MAO A and B were inhibited approximately equipotently and the material competitively inhibited tyramine oxidation by rat liver. It was stable on boiling and is unlikely to be a peptide

Reduced locomotor responses to cocaine in ghrelin-deficient mice

Ghrelin, an orexigenic hormone produced by the stomach, increases food intake and enhances the locomotor and rewarding effects of cocaine. Consistent with these behavioral effects, ghrelin increases dopamine cell activity in the mesolimbic system resulting in elevat

Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function

Uncoupling protein 2 (UCP2) is known to promote neuroprotection in many forms of neurological pathologies including Parkinson's disease. Here, we examined the hypothesis that UCP2 also mediates aspects of normal nigrostriatal dopamine (DA) function. Mice lacking UCP2 exhibited reduced dopamine turnover in the striatum as measured by the 3,4-dihydoxyphenylacetic acid/dopamine (DOPAC/DA) ratio, reduced tyrosine hydroxylase immunoreactivity (TH IR) in the substantia nigra pars compacta (SNc) and reticulata, striatum and nucleus accumbens. UCP2-knockout (KO) mice also had reduced dopamine transporter immunoreactivity (DAT IR) in the SNc but not other brain regions examined. In order to determine if these biochemical deficits are transcribed into behavioural deficits, we examined locomotor function in UCP2-KO mice compared to wild-type (WT) controls. UCP2-KO mice exhibited significantly reduced total movement distance, movement velocity and increased rest time compared to wild-type controls. These results suggest that UCP2 is an important mitochondrial protein that helps to maintain normal nigrostriatal dopamine neuronal function and a reduction in UCP2 levels may predispose individuals to environmental causes of Parkinson's disease