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Haynes, J. M.

Publications and source records attributed to Haynes, J. M..

3 recordsLinked to original sources

Quantitative Economon Model of Transactions for Drugs and Other Commodities

BackgroundAn economon is a dyadic economic unit of two participants who exchange mutually reinforcing commodities (e.g., addictive drugs for money). A human economon often consists of a buyer providing money to a supplier, while the supplier reciprocally provides some commodity to the buyer. Here, we develop the Quantitative Economon Model (QEM) by reviewing basic principles of behavioral economics and translating those principles into a quantitative model characterizing transactional behavior between buyers and suppliers that would be applicable to transactions involving drugs specifically, as well as other commodities. According to the model, transactions between a buyer and supplier depend on their respective economic demand for the commodities exchanged. Additionally, the model assumes that demand for commodities fluctuates across sequential transactions due to satiation and deprivation associated with consumption of those commodities, of particular relevance to addictive drugs. MethodsWe used a computational approach to simulate data from the QEM according to four conditions representing parametric manipulations of high or low levels of deprivation crossed with high or low levels of satiation (i.e., a 2x2 matrix of conditions). ResultsSimulations revealed patterns of transactional behavior that may be characteristic of a range of commodities. In particular, when deprivation-effects were high and satiation-effects were low, simulated transaction rates were characteristic of the high consumption rates observed with addictive drugs. In other conditions, transaction rates varied along patterns characteristic of consumption for other commodities like food. In sum, the QEM provides a framework for modeling, investigating, and predicting patterns of human transactional behavior.

bioinformatics↗

The Rodent Electronic Nicotine Delivery System: Description and Validationof an Apparatus for Nose-Only E-Cigarette Aerosol Inhalation in Freely Moving Rats

Tobacco use is the leading cause of death globally and in the U.S. After decades of decline, driven by decreases in combusted tobacco use, nicotine product use has increased due to Electronic Nicotine Delivery Systems, also known as e-cigarettes or vapes. Preclinical models of nicotine self-administration can serve as important lodestars in the search for effective intervention and prevention tactics. Current variants of the task have substantial limitations, however. Therefore, we created the Rodent Electronic Nicotine Delivery System, a novel low-cost non-proprietary nose-only preclinical model of nicotine aerosol self-administration. We confirmed that RENDS sequesters nicotine aerosol in the nose port by measuring fine particulate matter (PM < 2.5 microns) generated by e-cigarettes. We also showed that rats robustly self-administer flavored nicotine aerosol, resulting in high blood levels of cotinine (the major nicotine metabolite) and spontaneous somatic withdrawal symptoms. Thus, we provide strong validation of the operation and function of the RENDS, opening the door to an open-source preclinical aerosol model of nicotine self-administration that is relatively low cost. Four existing operant chambers can be retrofitted with the RENDS for less than $325/chamber. All RENDS diagrams and plans for custom designed components are on Open Science Framework (https://osf.io/x2pqf/?view_only=775b55435b8e428f98e6da384ef7889d).

animal behavior and cognition↗

Mouse and human microglial phenotypes in Alzheimer’s disease are controlled by amyloid plaque phagocytosis through Hif1α

The important role of microglia, the brains resident immune cells, in Alzheimers disease (AD) is now well recognized, however their molecular and functional diversity and underlying mechanisms still remain controversial. To transcriptionally and functionally characterize the diversity of microglia in AD and aging, we isolated the amyloid plaque-containing (XO4+) and non-containing (XO4-) microglia from an AD mouse model. Transcriptomics analysis unveiled independent transcriptional trajectories in ageing and AD. XO4+ microglial transcriptomes linked plaque phagocytosis to altered [Formula] expression of bona fide late onset AD genetic risk factors. We further revealed that the XO4+ transcriptional program is present in a subset of human microglia from AD patients and is a direct and reversible consequence of A{beta} plaque phagocytosis. Conversely, XO4- microglia in AD displayed an accelerated ageing signature and contained more intracellular post synaptic material than plaque-containing microglia, despite reduced active synaptosome phagocytosis. Mechanistically, we predicted HIF1 as a core regulator of the XO4-/XO4+ axis, and further validated the mechanism in vitro using human stem cell-derived microglia like cells and primary human microglia. Together these findings unveiled the molecular mechanism underpinning the functional diversity of microglia in AD, providing opportunities to develop treatments targeted at subset specific manipulation of the microglial niche.

neuroscience↗