764 research outputs found

    Homeostatic mechanisms in dopamine synthesis and release: a mathematical model

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Dopamine is a catecholamine that is used as a neurotransmitter both in the periphery and in the central nervous system. Dysfunction in various dopaminergic systems is known to be associated with various disorders, including schizophrenia, Parkinson's disease, and Tourette's syndrome. Furthermore, microdialysis studies have shown that addictive drugs increase extracellular dopamine and brain imaging has shown a correlation between euphoria and psycho-stimulant-induced increases in extracellular dopamine <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. These consequences of dopamine dysfunction indicate the importance of maintaining dopamine functionality through homeostatic mechanisms that have been attributed to the delicate balance between synthesis, storage, release, metabolism, and reuptake.</p> <p>Methods</p> <p>We construct a mathematical model of dopamine synthesis, release, and reuptake and use it to study homeostasis in single dopaminergic neuron terminals. We investigate the substrate inhibition of tyrosine hydroxylase by tyrosine, the consequences of the rapid uptake of extracellular dopamine by the dopamine transporters, and the effects of the autoreceoptors on dopaminergic function. The main focus is to understand the regulation and control of synthesis and release and to explicate and interpret experimental findings.</p> <p>Results</p> <p>We show that the substrate inhibition of tyrosine hydroxylase by tyrosine stabilizes cytosolic and vesicular dopamine against changes in tyrosine availability due to meals. We find that the autoreceptors dampen the fluctuations in extracellular dopamine caused by changes in tyrosine hydroxylase expression and changes in the rate of firing. We show that short bursts of action potentials create significant dopamine signals against the background of tonic firing. We explain the observed time courses of extracellular dopamine responses to stimulation in wild type mice and mice that have genetically altered dopamine transporter densities and the observed half-lives of extracellular dopamine under various treatment protocols.</p> <p>Conclusion</p> <p>Dopaminergic systems must respond robustly to important biological signals such as bursts, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of tyrosine hydroxylase, the dopamine transporters, and the dopamine autoreceptors.</p

    The effect of impact angle on craters formed by hypervelocity particles

    Get PDF
    The Space Power Institute (SPI) at Auburn University has conducted experiments on the effects of impact angle on crater morphology and impactor residue retention for hypervelocity impacts. Copper target plates were set at angles of 30 deg, 45 deg, 60 deg, and 75 deg from the particle flight path. For the 30 deg and 45 deg impacts, in the velocity regime greater than 8 km s(exp -1) the resultant craters are almost identical to normal incidence impacts. The only difference found was in the apparent distribution of particle residue within the crater, and further research is needed to verify this. The 60 deg and 75 deg impacts showed marked differences in crater symmetry, crater lip shape, and particle residue distribution in the same velocity regime. Impactor residue shock fractionation effects have been quantified in first-order. It is concluded that a combination of analysis techniques can yield further information on impact velocity, direction, and angle of incidence

    Direct radio discovery of a cold brown dwarf

    Get PDF
    Magnetospheric processes seen in gas-giants such as aurorae and circularly-polarized cyclotron maser radio emission have been detected from some brown dwarfs. However, previous radio observations targeted known brown dwarfs discovered via their infrared emission. Here we report the discovery of BDR J1750+3809, a circularly polarized radio source detected around 144 MHz with the LOFAR telescope. Follow-up near-infrared photometry and spectroscopy show that BDR J1750+3809 is a cold methane dwarf of spectral type T6.5±16.5\pm 1 at a distance of 65−8+9 pc65^{+9}_{-8}\,{\rm pc}. The quasi-quiescent radio spectral luminosity of BDR J1750+3809 is ≈5×1015 erg s−1 Hz−1\approx 5\times 10^{15}\,{\rm erg}\,{\rm s}^{-1}\,{\rm Hz}^{-1} which is over two orders of magnitude larger than that of the known population of comparable spectral type. This could be due to a preferential geometric alignment or an electrodynamic interaction with a close companion. In addition, as the emission is expected to occur close to the electron gyro-frequency, the magnetic field strength at the emitter site in BDR J1750+3809 is B≳25 GB\gtrsim 25\,{\rm G}, which is comparable to planetary-scale magnetic fields. Our discovery suggests that low-frequency radio surveys can be employed to discover sub-stellar objects that are too cold to be detected in infrared surveys.Comment: Accepted for publication in ApJ

    Social group membership before treatment for substance dependence predicts early identification and engagement with treatment communities

    Get PDF
    Social relationships play a major role in recovery from substance dependence. To date, greater attention has been paid to the role of important individuals in a person’s life and their contribution to recovery following treatment. This study is the first to examine both individual and wider group-based social connections in the lead up to residential treatment for substance misuse in a therapeutic community (TC), and their influence both on a person’s readiness to engage with the treatment community and with a recovery pathway. Participants were 307 adults interviewed early in treatment about their individual- and group-based social relationships prior to treatment entry, their social identification with the TC, as ‘a user’ and a person ‘in recovery’, their current recovery capital and quality of life. Correlational analysis showed that only pre-treatment group-based, and not individual, relationships, were significantly associated with developing social identification with the TC early in treatment. Moreover, results of hierarchical regression analyses indicated that identification with the TC was best predicted by the extent to which people saw themselves as being in recovery. Finally, mediation analysis indicated that TC identification was the mechanism through which social group memberships prior to treatment commencement protected quality of life in the early phases of treatment. These findings highlight the protective role that group memberships play in building early identification with the TC and supporting well-being in a critical period of transitioning to treatment

    First circumglobal assessment of Southern Hemisphere humpback whale mitochondrial genetic variation and implications for management

    Get PDF
    The description of genetic population structure over a species\u27 geographic range can provide insights into its evolutionary history and also support effective management efforts. Assessments for globally distributed species are rare, however, requiring significant international coordination and collaboration. The global distribution of demographically discrete populations for the humpback whale Megaptera novaeangliae is not fully known, hampering the definition of appropriate management units. Here, we present the first circumglobal assessment of mito - chondrial genetic population structure across the species\u27 range in the Southern Hemisphere and Arabian Sea. We combine new and existing data from the mitochondrial (mt)DNA control region that resulted in a 311 bp consensus sequence of the mtDNA control region for 3009 individuals sampled across 14 breeding stocks and subpopulations currently recognized by the International Whaling Commission. We assess genetic diversity and test for genetic differentiation and also estimate the magnitude and directionality of historic matrilineal gene flow between putative populations. Our results indicate that maternally directed site fidelity drives significant genetic population structure between breeding stocks within ocean basins. However, patterns of connectivity differ across the circumpolar range, possibly as a result of differences in the extent of longitudinal movements on feeding areas. The number of population comparisons observed to be significantly differentiated were found to diminish at the subpopulation scale when nucleotide differences were examined, indicating that more complex processes underlie genetic structure at this scale. It is crucial that these complexities and uncertainties are afforded greater consideration in management and regulatory efforts

    FR II radio galaxies at low frequencies I : morphology, magnetic field strength and energetics

    Get PDF
    This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. ©: 2016 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Due to their steep spectra, low-frequency observations of FR II radio galaxies potentially provide key insights in to the morphology, energetics and spectrum of these powerful radio sources. However, limitations imposed by the previous generation of radio interferometers at metre wavelengths has meant that this region of parameter space remains largely unexplored. In this paper, the first in a series examining FR IIs at low frequencies, we use LOFAR observations between 50 and 160 MHz, along with complementary archival radio and X-ray data, to explore the properties of two FR II sources, 3C452 and 3C223. We find that the morphology of 3C452 is that of a standard FR II rather than of a double-double radio galaxy as had previously been suggested, with no remnant emission being observed beyond the active lobes. We find that the low-frequency integrated spectra of both sources are much steeper than expected based on traditional assumptions and, using synchrotron/inverse-Compton model fitting, show that the total energy content of the lobes is greater than previous estimates by a factor of around 5 for 3C452 and 2 for 3C223. We go on to discuss possible causes of these steeper than expected spectra and provide revised estimates of the internal pressures and magnetic field strengths for the intrinsically steep case. We find that the ratio between the equipartition magnetic field strengths and those derived through synchrotron/inverse-Compton model fitting remains consistent with previous findings and show that the observed departure from equipartition may in some cases provide a solution to the spectral versus dynamical age disparity.Peer reviewe

    In vivo Hippocampal Serotonin Dynamics in Male and Female Mice: Determining Effects of Acute Escitalopram Using Fast Scan Cyclic Voltammetry

    Get PDF
    Depression is a highly prevalent psychiatric disorder, impacting females at a rate roughly twice that of males. This disparity has become the focus of many studies which are working to determine if there are environmental or biological underpinnings to depression pathology. The biology of depression is not well understood, but experts agree that a key neurotransmitter of interest is serotonin. Most research on basic serotonin neurochemistry, by us and others, has predominantly focused on male models. Thus, it is now critical to include female models to decipher possible fundamental differences between the sexes that may underlie this disorder. In this paper, we seek to determine any such differences using fast-scan cyclic voltammetry (FSCV) and fast-scan controlled adsorption voltammetry. These techniques allow us to probe the serotonergic system via measurement of evoked and ambient serotonin at carbon fiber microelectrodes (CFMs). Our data reveal no statistical differences, in the hippocampus, in female serotonin chemistry during the different stages of the estrous cycle compared to the mean female response. Furthermore, no difference was observed in evoked serotonin release and reuptake, nor ambient extracellular serotonin levels between male and female mice. We applied a previously developed mathematical model that fits our serotonin signals as a function of several synaptic processes that control the extracellular levels of this transmitter. We used the model to study potential system differences between males and females. One hypothesis brought fourth, that female mice exhibit tighter autoreceptor control of serotonin, is validated via literature and methiothepin challenge. We postulate that this tight regulation may act as a control mechanism against changes in the serotonin signal mediated by estrogen spikes. Importantly, this safety mechanism has no consequence for acutely administered escitalopram’s (ESCIT’s) ability to increase extracellular serotonin between the sexes. This work demonstrates little fundamental differences in in vivo hippocampal serotonin between the sexes, bar control mechanisms in female mice that can be observed under extraneous circumstances. We thus highlight the importance of considering sex as a biological factor in determining pharmacodynamics for personalized medical treatments that involve targeting serotonin receptors

    A within-attribute model of variety-seeking behavior

    Full text link
    Existing models view variety seeking as the result of differences in the level of attribute satiation across attributes. An alternative within-attribute variety-seeking (WAVS) model is proposed. The model posits that variety seeking occurs among the nested features, or meaningful value ranges, of an underlying dimension. The resulting pattern of consumption is represented as an oscillation about a consumer's ideal point on the dimension. An empirical study that illustrates different oscillation patterns is reported.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47181/1/11002_2004_Article_BF00995114.pd
    • 

    corecore