First, we performed a pesticide-wide association study (PWAS). Responding to this need, here we have developed a field-to-bench paradigm, coupling systematic epidemiologic screening with direct testing in neurons to assess and mechanistically dissect pesticide-PD relationships. A wider screen of commercially applied pesticides in relation to PD, coupled to analysis in tractable human dopaminergic neuron models, may thus identify new disease targets, provide mechanistic insights, and help revise priorities for research and public health policy. Fewer studies still have delved into the effect of co-exposures and whether pesticides may directly exert effects on human dopaminergic neurons that are particularly sensitive to environmental toxicants through oxidative stress 5, 6, 7, 8, 9. Aside from important work in model organisms and cellular models mostly focused on rotenone and paraquat, the specific effects of most common, widely used pesticides remain unexplored 4. While pesticides are important components of modern commercial agriculture that help maximize food production, most pesticides that are applied at industrial scales have not been adequately assessed for their potential role in PD, let alone for their mechanisms of action. In California, which is the largest agricultural producer and exporter in the United States, there are currently 13,092 pesticide products with 1059 different active ingredients registered for use 3. Ample evidence links pesticides in general to PD etiology 2. Etiologic contributors include genetic, environmental factors, and aging 1. The hallmark pathology of PD is aggregation of the protein α-synuclein in Lewy bodies in specific midbrain dopaminergic (mDA) neurons. Parkinson’s disease (PD) is a complex, multi-factorial neurodegenerative disease. Our paradigm may prove useful to mechanistically dissect pesticide exposures implicated in PD risk and guide agricultural policy. We find trifluralin is a driver of toxicity to dopaminergic neurons and leads to mitochondrial dysfunction. Further, we analyze pesticides typically used in combinations in cotton farming, demonstrating that co-exposures result in greater toxicity than any single pesticide. We find that 10 pesticides are directly toxic to these neurons. We then employ a live-cell imaging screening paradigm exposing dopaminergic neurons to 39 PD-associated pesticides. We associate long-term exposure to 53 pesticides with PD and identify co-exposure profiles. Agricultural records enable investigation of 288 specific pesticides and PD risk in a comprehensive, pesticide-wide association study. Here we combine quantitative epidemiologic study of pesticide exposures and PD with toxicity screening in dopaminergic neurons derived from PD patient induced pluripotent stem cells (iPSCs) to identify Parkinson’s-relevant pesticides. Parkinson’s disease (PD) is a complex neurodegenerative disease with etiology rooted in genetic vulnerability and environmental factors. Nature Communications volume 14, Article number: 2803 ( 2023) A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides The eight survivors of Team Mamba.fusion-tabs. Follow USA TODAY NBA writer Mark Medina on Twitter, Facebook and Instagram. * Content Template: Content Template for Clubs Layout - start */ Coming back from down 13, the Lightning took its first lead on Ems reverse layup with a minute left. I was shocked when he took me under his wing like he did, not being on his team, Shamblin says. * - */ We go through the year just trying to live our normal life, Zoies mom says. A select few, he was sure, would play in the WNBA. display: none Bryant, a Harry Potter fan, affectionately referred to the place as Hogwarts. Explore and purchase photos of your local teams. They wanted to make the invitational NBA and WNBA workouts an annual event. Team Mamba, the AAU program, shuttered after Bryants death. He texted many of them with advice, randomly dropping in little nuggets. The bright pink Gerber daisy for Payton Chester. overflow: hidden They looked so happy, playing dummy defense against each other. 25s p.cred-links border-bottom: 0px They laid bushels of flowers. But she attends Sierra Canyon, a basketball power in Los Angeles that is closer to. She played on rival team Cal Storm but considered Gigi a little sister, Kobe a mentor. The five-time NBA champion recently partnered with Nike and the Los Angeles Boys & Girls Club to create the Mamba League. Saiya Sidhu is the same age as Gigi, but shes always looked up to her. } Welcome To The Bay Area Mambas AAU Youth Basketball Program.
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