Mechanisms Regulating the Dopamine Transporter and Their Impact on Behavior

Dopamine (DA) is central to movement, reward, learning, sleep, and anxiety. The dopamine transporter (DAT) spatially and temporally controls extracellular dopamine levels by taking DA back up into the presynaptic neuron. Multiple lines of evidence from studies using pharmacological DAT blockade or genetic DAT deletion demonstrate that DAT availability at the plasma membrane is required for maintenance of homeostatic DA levels and DA tone. Therefore, intrinsic mechanisms that regulate the transporter’s availability at the plasma membrane may directly impact downstream DA signaling cascades and DA-dependent behavior. Acute, regulated DAT internalization in response to protein kinase C (PKC) activation has been well documented, however the physiological importance of this mechanism remains untested. Due to DAT’s critical role in regulating DA levels, It is essential to understand mechanisms that acutely regulate DAT function and surface expression, and further, how these mechanisms contribute to DA related behaviors. DAT has intracellular amino and carboxy termini, which contain domains for transporter phosphorylation, recruitment to and from the plasma membrane, and sites for protein-protein interactions. To test whether these domains work synergistically for DAT function and regulated endocytosis I made DAT/SERT chimeras, in which I switched DAT’s amino, carboxy, or both termini with that of SERT, a homologous transporter with highly divergent intracellular domains. I demonstrated that DAT’s amino and carboxy termini synergistically contribute to substrate and select competitive inhibitor affinities. Additionally, I demonstrated that the amino terminus is required for PKC-stimulated DAT endocytosis, and that both N- and C-termini are required for downstream Ack1-dependent regulation of DAT endocytosis. To test the physiological importance of PKC-stimulated DAT endocytosis in vivo, I knocked down Rin, a GTPase required for PKC-stimulated DAT trafficking, in mouse DA neurons. This study was the first to achieve AAV-mediated, conditional, and inducible gene silencing in neurons. Using this AAV approach, I demonstrated a critical role for Rin GTPase signaling and DAT trafficking in both anxiety and locomotor response to cocaine. Taken together, this thesis 1) adds to the understanding of DAT functional and endocytic mechanisms and 2) is the first to report the physiological impact of Rin signaling and DAT endocytosis in DA behavior

Counting the costs of crime in Australia: a 2011 estimate

This report estimates the costs of crime for the calendar year 2011. Executive summary This report seeks to estimate how much crime costs the Australian economy by calculating the number of crimes that come to the attention of the authorities and, using crime victimisation survey data, the number of crimes that are not recorded officially. A dollar figure is then calculated for each estimated crime event and an indication given of the total cost of each specific crime type in terms of actual loss, intangible losses, loss of output caused through the criminal conduct and other related costs such as medical expenses, where relevant. Added to these costs are the costs of preventing and responding to crime in the community including the costs of maintaining the criminal justice system agencies of police, prosecution, courts and correctional agencies, as well as a proportion of the costs of Australian and state and territory government agencies that have crime-related functions. Finally, a deduction is made for the value of property recovered in the case of property crime, as well as the amount of funds recovered from criminals under federal, state and territory proceeds of crime legislation. More detailed information about how each of these estimates was derived is provided in the main body of the report. Official attention paid to specific crime types, particularly drug-related crime and organised crime, affects both the reporting rate and also the cost of policing and correctional responses. In this sense, individual crime type costs and prevention and response costs are not mutually exclusive. Arguably, as individual crime types attract more attention, reporting rates increase and prevention and control of the crimes in question are seen as being deserving of increased resource

Ben Jonson's Modern Literary Reputation as a Dramatist (1925-1958)

Thesis (Ph.D)--Boston Universit

Economics and operation of alternating-current and direct-current systems; a comparative study

This item was digitized by the Internet Archive. Thesis (M.B.A.)--Boston Universityhttps://archive.org/details/economicsoperati00lun

The cost of systemic corticosteroid-induced morbidity in severe asthma : a health economic analysis

The study data-set was supported by the Respiratory Effectiveness Group through their academic partnership with Optimum Patient Care. Ciaran O'Neill was funded under a HRB Research Leader Award (RL/13/16).Peer reviewedPublisher PD

The use of Multiple Displacement Amplification to increase the detection and genotyping of <i>Trypanosoma</i> samples immobilised on FTA filters.

Whole genome amplification methods are a recently developed tool for amplifying DNA from limited template. We report its application in trypanosome infections, characterized by low parasitemias. Multiple displacement amplification (MDA) amplifies DNA with a simple in vitro step and was evaluated on mouse blood samples on FTA filter cards with known numbers of Trypanosoma brucei parasites. The data showed a 20-fold increase in the number of PCRs possible per sample, using primers diagnostic for the multicopy ribosomal ITS region or 177-bp repeats, and a 20-fold increase in sensitivity over nested PCR against a single-copy microsatellite. Using MDA for microsatellite genotyping caused allele dropout at low DNA concentrations, which was overcome by pooling multiple MDA reactions. The validity of using MDA was established with samples from Human African Trypanosomiasis patients. The use of MDA allows maximal use of finite DNA samples and may prove a valuable tool in studies where multiple reactions are necessary, such as population genetic analyses

A Risk Analysis of Carbon Sequestration in Claypan Soil with Conservation Tillage Systems and Nitrogen Fertilizers for Grain Sorghum and Soybean

Replaced with revised version of paper 02/15/06.carbon sequestration, carbon credits, nitrogen, risk, tillage, Crop Production/Industries, Risk and Uncertainty, Q12,

Estimation of the Composition of Three Component Liquid Mixtures

While carrying out research on the extraction of oil from soybeans using mixtures of various solvents, it was quite often necessary to know the composition of a mixture of liquids containing three components. A search of the literature for ways of obtaining the composition of such mixtures by the use of physical constants revealed a very convenient method employing a combination of density and refractive index. Before this method can be used, however, solutions covering the entire ternary system must be made up accurately, their refractive indices and densities taken and plotted in such a manner that the composition of solutions of constant refractive index and solutions of constant specific gravity can be determined. Finally a triangular diagram must be constructed showing the lines of constant refractive index and constant specific gravity as related to the composition (1, 2)