Inhibiting the mitochondrial pyruvate carrier does not ameliorate synucleinopathy in the absence of inflammation or metabolic deficits

Epidemiological studies suggest a link between type-2 diabetes and Parkinson’s disease (PD) risk. Treatment of type-2 diabetes with insulin sensitizing drugs lowers the risk of PD. We previously showed that the insulin sensitizing drug, MSDC-0160, ameliorates pathogenesis in some animal models of PD. MSDC-0160 reversibly binds the mitochondrial pyruvate carrier (MPC) protein complex, which has an anti-inflammatory effect and restores metabolic deficits. Since PD is characterized by the deposition of α-synuclein (αSyn), we hypothesized that inhibiting the MPC might directly inhibit αSyn aggregation in vivo in mammals. To answer if modulation of MPC can reduce the development of αSyn assemblies, and reduce neurodegeneration, we treated two chronic and progressive mouse models; a viral vector-based αSyn overexpressing model and a pre-formed fibril (PFF) αSyn seeding model with MSDC-0160. These two models present distinct types of αSyn pathology but lack inflammatory or autophagy deficits. Contrary to our hypothesis, we found that a modulation of MPC in these models did not reduce the accumulation of αSyn aggregates or mitigate neurotoxicity. Instead, MSDC-0160 changed the post-translational modification and aggregation features of αSyn. These results are consistent with the lack of a direct effect of MPC modulation on synuclein clearance in these models

Development of Integrated Pest Management in Texas Citrus.

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Models for Minimizing Risks of Dangerous Pests: The Pink Hibiscus Mealybug and Papaya Mealybug

The pink hibiscus mealybug (PHM), Maconellicoccus hirsutus (Green), and the papaya mealybug (PM), Paracoccus marginatus Williams & Granara de Willink, biological control programs were cooperatively developed in the Caribbean by various local and international agencies and organizations. Both programs served as models of proactive program action in the early stages of each invasive pest's introduction into a Caribbean island, and for minimizing losses to the U.S. and neighboring countries. The biological control technology for the PHM developed in St. Kitts and Nevis, W.I., between 1995 and 1997, has been successfully transferred within the last six years to the US Virgin Islands, Puerto Rico, Bahamas, Belize, California, and most recently to Florida, Haiti, and the Dominican Republic. The PM biological control technology developed in the Dominican Republic in 1999 has been transferred to Puerto Rico, Florida, Bahamas, and Guam within the last four years. In both programs, the introduction of exotic parasitoid species resulted in mealybug population density reductions ranging from 82 to 97%. Early program development allowed for swift technology transfer to newly infested islands and to the U.S. Mainland (California and Florida) within thirty days of being found infested. This swift transfer in turn significantly reduced the potentially high rate of geographical dispersal and averted disastrous economic losses in the Caribbean countries, and in the U.S. and its island territories

Microglia affect α\alpha-synuclein cell-to-cell transfer in a mouse model of Parkinson’s disease

International audienceBackground: Cell-to-cell propagation of α-synuclein ($\alpha$-syn) aggregates is thought to contribute to the pathogenesis of Parkinson's disease (PD) and underlie the spread of α-syn neuropathology. Increased pro-inflammatory cytokine levels and activated microglia are present in PD and activated microglia can promote α-syn aggregation. However, it is unclear how microglia influence α-syn cell-to-cell transfer