Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 180
Filter
1.
PLoS One ; 18(7): e0289017, 2023.
Article in English | MEDLINE | ID: mdl-37486889

ABSTRACT

Automation inherently removes a certain amount of user control. If perceived as a loss of freedom, users may experience psychological reactance, which is a motivational state that can lead a person to engage in behaviors to reassert their freedom. In an online experiment, participants set up and communicated with a hypothetical smart thermostat. Participants read notifications about a change in the thermostat's setting. Phrasing of notifications was altered across three dimensions: strength of authoritative language, deviation of temperature change from preferences, and whether or not the reason for the change was transparent. Authoritative language, temperatures outside the user's preferences, and lack of transparency induced significantly higher levels of reactance. However, when the system presented a temperature change outside of the user's preferences, reactance was mitigated and user acceptance was higher if the thermostat's operations were transparent. Providing justification may be less likely to induce psychological reactance and increase user acceptance. This supports efforts to use behavioral approaches, such as demand response, to increase sustainability and limit the impacts of climate change.


Subject(s)
Automation , Temperature , Humans , Climate Change , Language , Motivation
2.
Sci Eng Ethics ; 26(3): 1477-1498, 2020 06.
Article in English | MEDLINE | ID: mdl-31970596

ABSTRACT

Bainbridge's well known "Ironies of Automation" (in: Johannsen, Rijnsdorp (eds) Analysis, design and evaluation of man-machine systems. Elsevier, Amsterdam, pp 129-135, 1983. https://doi.org/10.1016/B978-0-08-029348-6.50026-9) laid out a set of fundamental criticisms surrounding the promises of automation that, even 30 years later, remain both relevant and, in many cases, intractable. Similarly, a set of ironies in technologies for sensor driven self-quantification (often referred to broadly as wearables) is laid out here, spanning from instrumental problems in human factors design (such as disagreement over physiological norms) to much broader social problems (such as loss of freedom). As with automation, these ironies stand in the way of many of the promised benefits of these wearable technologies. It is argued here that without addressing these ironies now, the promises of wearables may not come to fruition, and instead users may experience outcomes that are opposite to those which the designers seek to afford, or, at the very least, those which consumers believe they are being offered. This paper describes four key ironies of sensor driven self-quantification: (1) know more, know better versus no more, no better; (2) greater self-control versus greater social control; (3) well-being versus never being well enough; (4) more choice versus erosion of choice.


Subject(s)
Wearable Electronic Devices , Humans
3.
Metabolomics ; 14(8): 105, 2018 08 03.
Article in English | MEDLINE | ID: mdl-30830422

ABSTRACT

INTRODUCTION: Melanoma is a highly aggressive malignancy and is currently one of the fastest growing cancers worldwide. While early stage (I and II) disease is highly curable with excellent prognosis, mortality rates rise dramatically after distant spread. We sought to identify differences in the metabolome of melanoma patients to further elucidate the pathophysiology of melanoma and identify potential biomarkers to aid in earlier detection of recurrence. METHODS: Using 1H NMR and DI-LC-MS/MS, we profiled serum samples from 26 patients with stage III (nodal metastasis) or stage IV (distant metastasis) melanoma and compared their biochemical profiles with 46 age- and gender-matched controls. RESULTS: We accurately quantified 181 metabolites in serum using a combination of 1H NMR and DI-LC-MS/MS. We observed significant separation between cases and controls in the PLS-DA scores plot (permutation test p-value = 0.002). Using the concentrations of PC-aa-C40:3, DL-carnitine, octanoyl-L-carnitine, ethanol, and methylmalonyl-L-carnitine we developed a diagnostic algorithm with an AUC (95% CI) = 0.822 (0.665-0.979) with sensitivity and specificity of 100 and 56%, respectively. Furthermore, we identified arginine, proline, tryptophan, glutamine, glutamate, glutathione and ornithine metabolism to be significantly perturbed due to disease (p < 0.05). CONCLUSION: Targeted metabolomic analysis demonstrated significant differences in metabolic profiles of advanced stage (III and IV) melanoma patients as compared to controls. These differences may represent a potential avenue for the development of multi-marker serum-based assays for earlier detection of recurrences, allow for newer, more effective targeted therapy when tumor burden is less, and further elucidate the pathophysiologic changes that occur in melanoma.


Subject(s)
Biomarkers, Tumor/blood , Melanoma/diagnosis , Metabolome , Serum/metabolism , Aged , Case-Control Studies , Chromatography, Liquid/methods , Cohort Studies , Female , Humans , Lymphatic Metastasis , Male , Melanoma/metabolism , Middle Aged , Prognosis , ROC Curve , Tandem Mass Spectrometry/methods
4.
Public Underst Sci ; 26(2): 251-258, 2017 02.
Article in English | MEDLINE | ID: mdl-26386020

ABSTRACT

Both academic and legal communities have cautioned that laypersons may be unduly persuaded by images of the brain and may fail to interpret them appropriately. While early studies confirmed this concern, a second wave of research was repeatedly unable to find evidence of such a bias. The newest wave of studies paints a more nuanced picture in which, under certain circumstances, a neuroimage bias reemerges. To help make sense of this discordant body of research, we highlight the contextual significance of understanding how laypersons' decision making is or is not impacted by neuroimages, provide an overview of findings from all sides of the neuroimage bias question, and discuss what these findings mean to public use and understanding of neuroimages.


Subject(s)
Comprehension , Decision Making , Neuroimaging , Brain/diagnostic imaging , Humans , Jurisprudence , Observer Variation
5.
Int J Obes (Lond) ; 40(7): 1183-6, 2016 07.
Article in English | MEDLINE | ID: mdl-26975440

ABSTRACT

Binge-eating behavior involves rapid consumption of highly palatable foods leading to increased weight gain. Feeding in binge disorders resembles other compulsive behaviors, many of which are responsive to N-acetylcysteine (NAC), which is a cysteine prodrug often used to promote non-vesicular glutamate release by a cystine-glutamate antiporter. To examine the potential for NAC to alter a form of compulsive eating, we examined the impact of NAC on binge eating in a rodent model. Specifically, we monitored consumption of standard chow and a high-fat, high carbohydrate western diet (WD) in a rodent limited-access binge paradigm. Before each session, rats received either a systemic or intraventricular injection of NAC. Both systemic and central administration of NAC resulted in significant reductions of binge eating the WD without decreasing standard chow consumption. The reduction in WD was not attributable to general malaise as NAC did not produce condition taste aversion. These results are consistent with the clinical evidence of NAC to reduce or reverse compulsive behaviors, such as, drug addiction, skin picking and hair pulling.


Subject(s)
Acetylcysteine/pharmacology , Binge-Eating Disorder/drug therapy , Disease Models, Animal , Feeding Behavior/drug effects , Feeding Behavior/psychology , Animals , Conditioning, Operant/drug effects , Diet, High-Fat , Injections, Intraventricular , Male , Rats , Rats, Sprague-Dawley
6.
Sci Eng Ethics ; 22(1): 93-110, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25649071

ABSTRACT

Objections to the use of assistive technologies (such as prostheses) in elite sports are generally raised when the technology in question is perceived to afford the user a potentially "unfair advantage," when it is perceived as a threat to the purity of the sport, and/or when it is perceived as a precursor to a slippery slope toward undesirable changes in the sport. These objections rely on being able to quantify standards of "normal" within a sport so that changes attributed to the use of assistive technology can be judged as causing a significant deviation from some baseline standard. This holds athletes using assistive technologies accountable to standards that restrict their opportunities to achieve greatness, while athletes who do not use assistive technologies are able to push beyond the boundaries of these standards without moral scrutiny. This paper explores how constructions of fairness and "normality" impact athletes who use assistive technology to compete in a sporting venue traditionally populated with "able-bodied" competitors. It argues that the dynamic and obfuscated construction of "normal" standards in elite sports should move away from using body performance as the measuring stick of "normal," toward alternate forms of constructing norms such as defining, quantifying, and regulating the mechanical actions that constitute the critical components of a sport. Though framed within the context of elite sports, this paper can be interpreted more broadly to consider problems with defining "normal" bodies in a society in which technologies are constantly changing our abilities and expectations of what normal means.


Subject(s)
Disabled Persons , Self-Help Devices/ethics , Social Justice , Social Norms , Sports/ethics , Athletes , Humans , Morals
7.
Cognition ; 129(3): 501-11, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24041836

ABSTRACT

A series of highly-cited experiments published in 2008 demonstrated a biasing effect of neuroimages on lay perceptions of scientific research. More recent work, however, has questioned this bias, particularly within legal contexts in which neuroscientific evidence is proffered by one of the parties. The present research moves away from the legal framework and describes five experiments that re-examine this effect. Experiments 1 through 4 present conceptual and direct replications of some of the original 2008 experiments, and find no evidence of a neuroimage bias. A fifth experiment is reported that confirms that, when laypeople are allowed multiple points of reference (e.g., when directly comparing neuroimagery to other graphical depictions of neurological data), a neuroimage bias can be observed. Together these results suggest that, under the right conditions, a neuroimage might be able to bias judgments of scientific information, but the scope of this effect may be limited to certain contexts.


Subject(s)
Health Knowledge, Attitudes, Practice , Judgment/physiology , Neuroimaging/psychology , Pattern Recognition, Visual/physiology , Adult , Bias , Brain , Humans , Random Allocation
8.
PLoS One ; 8(9): e74449, 2013.
Article in English | MEDLINE | ID: mdl-24040251

ABSTRACT

Several highly-cited experiments have presented evidence suggesting that neuroimages may unduly bias laypeople's judgments of scientific research. This finding has been especially worrisome to the legal community in which neuroimage techniques may be used to produce evidence of a person's mental state. However, a more recent body of work that has looked directly at the independent impact of neuroimages on layperson decision-making (both in legal and more general arenas), and has failed to find evidence of bias. To help resolve these conflicting findings, this research uses eye tracking technology to provide a measure of attention to different visual representations of neuroscientific data. Finding an effect of neuroimages on the distribution of attention would provide a potential mechanism for the influence of neuroimages on higher-level decisions. In the present experiment, a sample of laypeople viewed a vignette that briefly described a court case in which the defendant's actions might have been explained by a neurological defect. Accompanying these vignettes was either an MRI image of the defendant's brain, or a bar graph depicting levels of brain activity-two competing visualizations that have been the focus of much of the previous research on the neuroimage bias. We found that, while laypeople differentially attended to neuroimagery relative to the bar graph, this did not translate into differential judgments in a way that would support the idea of a neuroimage bias.


Subject(s)
Attention/physiology , Decision Making , Neuroimaging/psychology , Punishment/psychology , Visual Perception , Bias , Brain/pathology , Crime , Eye Movements/physiology , Female , Humans , Magnetic Resonance Imaging , Male , Young Adult
9.
J Nanosci Nanotechnol ; 9(5): 2917-22, 2009 May.
Article in English | MEDLINE | ID: mdl-19452949

ABSTRACT

Electrically conductive nanocomposites from cellulose nanofibrils (CNF) were successfully produced by in situ polymerization of aniline onto CNF, and studied by open circuit potential (Voc), four probe direct current (dc) electrical conductivity, ultraviolet-visible (UV-Vis) spectroscopy and scanning electron microscopy (SEM). The oxidative polymerization of aniline using ammonium peroxydisulfate in hydrochloric acid aqueous solutions was realized by the addition of nanofibrils leading to an aqueous suspension of CNF coated with polyaniline (PANI). This procedure lead to stable, green suspensions of CNF coated with PANI in the emeraldine oxidation state as demonstrated by Voc and UV-Vis analyses. Electrically conductive films of this cellulose nanocomposite could be cast from aqueous solutions with conductivity close to the conducting polymer, yet with the potential for more useful flexible films.


Subject(s)
Aniline Compounds/chemistry , Cellulose/chemistry , Electric Conductivity , Nanocomposites/chemistry , Aniline Compounds/chemical synthesis , Cellulose/chemical synthesis , Microscopy, Electron, Scanning , Nanocomposites/ultrastructure , Nanostructures/chemistry , Nanostructures/ultrastructure , Spectrophotometry, Ultraviolet
10.
Neuroscience ; 155(2): 530-7, 2008 Aug 13.
Article in English | MEDLINE | ID: mdl-18601982

ABSTRACT

Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine-glutamate exchange via system xc-, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system xc-. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system xc-. Rats were trained to self-administer cocaine (1 mg/kg/200 microl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0-60 mg/kg, i.p.) in the presence or absence of the system xc- inhibitor (S)-4-carboxyphenylglycine (CPG; 0.5 microM; infused into the nucleus accumbens). N-acetylcysteine attenuated cocaine-primed reinstatement, and this effect was reversed by co-administration of CPG. Secondly, we examined whether reduced system xc- activity is necessary for cocaine-primed reinstatement. To do this, we administered N-acetylcysteine (0 or 90 mg/kg, i.p.) prior to 12 daily self-administration sessions (1 mg/kg/200 microl, i.v.; 6 h/day) since this procedure has previously been shown to prevent reduced activity of system xc-. On the reinstatement test day, we then acutely impaired system xc- in some of the rats by infusing CPG (0.5 microM) into the nucleus accumbens. Rats that had received N-acetylcysteine prior to daily self-administration sessions exhibited diminished cocaine-primed reinstatement; this effect was reversed by infusing the cystine-glutamate exchange inhibitor CPG into the nucleus accumbens. Collectively these data establish system xc- in the nucleus accumbens as a key mechanism contributing to cocaine-primed reinstatement.


Subject(s)
Antiporters/metabolism , Cocaine-Related Disorders/metabolism , Cystine/metabolism , Glutamic Acid/metabolism , Nucleus Accumbens/metabolism , Animals , Behavior, Animal/drug effects , Cocaine/pharmacology , Cocaine-Related Disorders/physiopathology , Cystine/analogs & derivatives , Cystine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Extinction, Psychological/drug effects , Male , Microdialysis , Nucleus Accumbens/drug effects , Rats , Rats, Sprague-Dawley , Self Administration , Synapses/metabolism
11.
Phys Rev Lett ; 96(25): 255501, 2006 Jun 30.
Article in English | MEDLINE | ID: mdl-16907317

ABSTRACT

A new extended x-ray-absorption fine structure spectroscopy study of local bonding identifies for the first time significant concentrations of Ge-Ge bonds in amorphous Ge2Sb2Te5. The study provides a new understanding of the local molecular structure of this phase-change material. Application of bond constraint theory indicates that the amorphous phase is an ideal network structure in which the average number of constraints per atom equals the network dimensionality. Analysis within this framework imparts new and significant insights concerning the nature of the reversible optically driven amorphous-crystalline phase transition of Ge2Sb2Te5.

12.
Genes Brain Behav ; 5(3): 222-39, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16594976

ABSTRACT

Perception of the earth's gravitational force is essential for most forms of animal life. However, little is known of the molecular mechanisms and neuronal circuitry underlying gravitational responses. A forward genetic screen using Drosophila melanogaster that provides insight into these characteristics is described here. Vertical choice mazes combined with additional behavioral assays were used to identify mutants specifically affected in gravitaxic responses. Twenty-three mutants were selected for molecular analysis. As a result, 18 candidate genes are now implicated in the gravitaxic behavior of flies. Many of these genes have orthologs across the animal kingdom, while some are more specific to Drosophila and invertebrates. One gene (yuri) located close to a known locus for gravitaxis has been the subject of more extensive analysis including confirmation by transgenic rescue.


Subject(s)
Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Gravity Sensing/physiology , Maze Learning/physiology , Mutation/genetics , Analysis of Variance , Animals , Animals, Genetically Modified , Base Sequence , Drosophila melanogaster/physiology , Genetic Testing , Humans , Male , Molecular Sequence Data , Polymorphism, Genetic/genetics , Sense Organs/physiology , Transcription Factors/genetics
13.
Mol Ecol ; 12(12): 3303-11, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14629347

ABSTRACT

The effects of recent colonization on the aphid parasitoid, Diaeretiella rapae (M'Intosh) (Hymenoptera: Braconidae: Aphidiidae), in Western Australia were investigated. When compared with populations from the Old World, the results of a microsatellite analysis show that the insects have low allelic length and low allele frequency variation, revealing that these individuals experienced a significant founder effect. Marked genetic differentiation between populations was also revealed, which has potentially important implications for host utilization in this species when introduced to a new geographical area(s). Low genetic variation and gene flow in a founder population could limit evolutionary potential in Australia, including the ability of a population to mount a response to newly introduced hosts, such as the Russian wheat aphid, Diuraphis noxia (Mordvilko). Although the actual importance of genetic diversity in the success of biological control agents is unclear, current theory concerning the potential impact of genetic bottlenecks on additive genetic variance is discussed.


Subject(s)
Aphids/parasitology , Founder Effect , Genetic Variation , Pest Control, Biological , Wasps/genetics , Animals , Australia , DNA Primers , Gene Frequency , Microsatellite Repeats/genetics , Population Density , Wasps/physiology
14.
J Biomed Mater Res A ; 66(1): 146-54, 2003 Jul 01.
Article in English | MEDLINE | ID: mdl-12833441

ABSTRACT

Crosslinked ultrahigh molecular weight polyethylene (UHMWPE) has been recently approved by the Food and Drug Administration for use in orthopedic implants. The majority of commercially available UHMWPE orthopedic components are crosslinked using e-beam or gamma radiation. The level of crosslinking is controlled with radiation dose and free radicals are eliminated through heat treatments to prevent long-term degradation associated with chain scission or oxidation mechanisms. Laboratory studies have demonstrated a substantial improvement in the wear resistance of crosslinked UHMWPE. However, a concern about the resistance to fatigue damage remains in the clinical community, especially for tibial components that sustain high cyclic contact stresses. The objective of this study was to investigate both the initiation and propagation aspects of fatigue cracks in radiation crosslinked medical-grade UHMWPE. This work evaluated three levels of radiation, which induced three crosslink densities, on the fatigue crack propagation and total fatigue life behavior. Both as-received UHMWPE, as well as those that underwent an identical thermal history as the crosslinked UHMWPE were used as controls. Fractured crack propagation specimens were examined using scanning electron microscopy to elucidate fatigue fracture mechanisms. The results of this work indicated that a low crosslink density may optimize the fatigue resistance from both a crack initiation and propagation standpoint.


Subject(s)
Acrylic Resins/chemistry , Biocompatible Materials/chemistry , Orthopedic Equipment , Polyethylenes/chemistry , Acrylic Resins/radiation effects , Biocompatible Materials/radiation effects , Equipment Failure , Equipment Failure Analysis , Hot Temperature , Microscopy, Electron, Scanning , Polyethylenes/radiation effects , Prostheses and Implants , Stress, Mechanical , X-Ray Diffraction
15.
J Biomed Mater Res ; 63(6): 722-8, 2002.
Article in English | MEDLINE | ID: mdl-12418016

ABSTRACT

Hemostasis in the traumatized liver has been achieved by thermally denaturing topically applied albumin. In this article, the mechanical properties of liver and denatured albumin (solder) were measured, and the failure methods of liver repaired with albumin were identified. The ultimate tensile strength and Young's modulus were measured for healthy liver (N = 20) and thermally damaged liver (N = 20). The ultimate tensile strength and Young's modulus were measured for three concentrations of coagulated albumin (25, 38, and 53%) in a single layer and for two layers of denatured 38% albumin. Failure under tension of argon-beam coagulator soldered liver on the parenchymal surface (N = 30) with 38% albumin in two layers had a 70% occurrence for tearing at a mean stress of 39 kPa and a 23% occurrence for shearing at a mean stress of 7 kPa. Liver repaired on the interior surface (N = 11) failed in tension by tearing (64%) at a mean stress of 34 kPa and by shearing (36%) at a mean stress of 6 kPa. Argon-beam coagulator soldering with 38% albumin took 6 s/cm(2) for two layers of solder and gave the best balance of usability, strength, and matching of mechanical properties with those of the liver.


Subject(s)
Albumins/administration & dosage , Electrocoagulation , Liver/injuries , Albumins/isolation & purification , Animals , Biocompatible Materials , Biomechanical Phenomena , Electrocoagulation/instrumentation , Electrocoagulation/methods , Humans , In Vitro Techniques , Materials Testing , Protein Denaturation , Sus scrofa , Tensile Strength
16.
Amino Acids ; 23(1-3): 161-2, 2002.
Article in English | MEDLINE | ID: mdl-12373531

ABSTRACT

Repeated administration of cocaine lowers the basal extracellular levels of glutamate in the nucleus accumbens as measured by microdialysis. The studies presented reveal that this long-term neuroadaptation elicited by repeated cocaine results from a decrease in the activity of cystine/glutamate exchange.


Subject(s)
Cocaine/pharmacology , Cystine/metabolism , Dopamine Uptake Inhibitors/pharmacology , Glutamic Acid/metabolism , Nucleus Accumbens/drug effects , Animals , Biological Transport/drug effects , Biological Transport/physiology , Calcium Channel Blockers/pharmacology , Cocaine/administration & dosage , Diltiazem/pharmacology , Dopamine Uptake Inhibitors/administration & dosage , Microdialysis , Nucleus Accumbens/metabolism , Rats , Tetrodotoxin/pharmacology , omega-Conotoxins/pharmacology
17.
Mol Microbiol ; 42(2): 553-60, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11703675

ABSTRACT

Sex is an obligate step in the life cycle of the malaria parasite and occurs in the midgut of the mosquito vector. With both Plasmodium falciparum and Plasmodium berghei, the tryptophan metabolite xanthurenic acid induces the release of motile male gametes from red blood cells (exflagellation), a prerequisite for fertilization. The addition of cGMP or phosphodiesterase inhibitors to cultures of mature gametocytes has also been shown to stimulate exflagellation. Here, we demonstrate that there is a guanylyl cyclase activity associated with mature P. falciparum gametocyte membrane preparations, which is dependent on the presence of Mg(2+)/Mn(2+) but is inhibited by Ca(2+). Significantly, this activity is increased on addition of xanthurenic acid. In contrast, a xanthurenic acid precursor (3-hydroxykynurenine), which is not an inducer of exflagellation, does not induce this guanylyl cyclase activity. These results therefore suggest that xanthurenic acid-induced exflagellation may be mediated by activation of the parasite cGMP signalling pathway.


Subject(s)
Cell Membrane/enzymology , Guanylate Cyclase/metabolism , Membrane Proteins/metabolism , Plasmodium falciparum/drug effects , Plasmodium falciparum/enzymology , Xanthurenates/pharmacology , Animals , Calcium/pharmacology , Cell Membrane/drug effects , Cyclic GMP/metabolism , Guanylate Cyclase/biosynthesis , Guanylate Cyclase/genetics , Humans , Magnesium/pharmacology , Manganese/pharmacology , Membrane Proteins/biosynthesis , Membrane Proteins/genetics , Plasmodium falciparum/cytology , Plasmodium falciparum/growth & development , Signal Transduction/drug effects
18.
J Neurosci ; 21(22): 9043-52, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11698615

ABSTRACT

The present study aimed to characterize a functional role for group I metabotropic glutamate receptors (mGluRs) in the nucleus accumbens and the capacity of repeated cocaine to elicit long-term changes in group I mGluR function. Reverse dialysis of the group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) into the nucleus accumbens resulted in an increase in extracellular glutamate levels that was mediated by the mGluR1 subtype and depended on voltage-dependent Na(+) and Ca(2+) conductance. At 3 weeks after discontinuing 1 week of daily cocaine injections, the capacity of DHPG to induce glutamate release was markedly reduced. Similarly, DHPG induced an mGluR1-dependent increase in locomotor activity after microinjection into the nucleus accumbens that was significantly blunted 3 weeks after repeated cocaine administration. Signaling through group I mGluRs is regulated, in part, by Homer proteins, and it was found that the blunting of group I mGluR-induced glutamate release and motor activity after repeated cocaine was associated with a reduction in Homer1b/c protein that was selective for the medial nucleus accumbens. These data show that repeated cocaine produces an enduring inhibition of the neurochemical and behavioral consequences of stimulating mGluR1 that is accompanied by changes in the mGluR scaffolding apparatus.


Subject(s)
Carrier Proteins/metabolism , Cocaine/administration & dosage , Glutamic Acid/metabolism , Neuropeptides/metabolism , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Receptors, Metabotropic Glutamate/metabolism , Animals , Brain Chemistry/drug effects , Calcium Channel Blockers/pharmacology , Drug Administration Schedule , Drug Tolerance , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Extracellular Space/chemistry , Extracellular Space/metabolism , Glycine/analogs & derivatives , Glycine/pharmacology , Homer Scaffolding Proteins , Male , Microdialysis , Motor Activity/drug effects , Rats , Rats, Inbred Strains , Rats, Sprague-Dawley , Receptor, Metabotropic Glutamate 5 , Receptors, AMPA/metabolism , Receptors, Metabotropic Glutamate/agonists , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Resorcinols/pharmacology , Tetrodotoxin/administration & dosage
19.
Nature ; 411(6835): 330-4, 2001 May 17.
Article in English | MEDLINE | ID: mdl-11357138

ABSTRACT

The evolutionarily conserved Ras/mitogen-activated protein kinase (MAPK) cascade is an integral part of the processes of cell division, differentiation, movement and death. Signals received at the cell surface are relayed into the nucleus, where MAPK phosphorylates and thereby modulates the activities of a subset of transcription factors. Here we report the cloning and characterization of a new component of this signal transduction pathway called Mae (for modulator of the activity of Ets). Mae is a signalling intermediate that directly links the MAPK signalling pathway to its downstream transcription factor targets. Phosphorylation by MAPK of the critical serine residue (Ser 127) of the Drosophila transcription factor Yan depends on Mae, and is mediated by the binding of Yan to Mae through their Pointed domains. This phosphorylation is both necessary and sufficient to abrogate transcriptional repression by Yan. Mae also regulates the activity of the transcriptional activator Pointed-P2 by a similar mechanism. Mae is essential for the normal development and viability of Drosophila, and is required in vivo for normal signalling of the epidermal growth factor receptor. Our study indicates that MAPK signalling specificity may depend on proteins that couple specific substrates to the kinase.


Subject(s)
Carrier Proteins/metabolism , Drosophila Proteins , Drosophila melanogaster/metabolism , Eye Proteins/metabolism , Insect Proteins/metabolism , Intracellular Signaling Peptides and Proteins , MAP Kinase Signaling System , Mitogen-Activated Protein Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Repressor Proteins/metabolism , Transcription Factors/metabolism , Amino Acid Sequence , Animals , Base Sequence , Body Patterning , Carrier Proteins/chemistry , Carrier Proteins/genetics , DNA/genetics , DNA/metabolism , DNA-Binding Proteins , Drosophila melanogaster/embryology , Drosophila melanogaster/enzymology , Drosophila melanogaster/genetics , ErbB Receptors/metabolism , Eye Proteins/chemistry , Eye Proteins/genetics , Gene Expression Regulation , Genes, Essential/genetics , Genes, Reporter/genetics , Immunohistochemistry , Insect Proteins/chemistry , Insect Proteins/genetics , Molecular Sequence Data , Nerve Tissue Proteins , Phosphorylation , Phosphoserine/metabolism , Phosphothreonine/metabolism , Protein Binding , Protein Structure, Tertiary , Proto-Oncogene Proteins/chemistry , Proto-Oncogene Proteins c-ets , Repressor Proteins/chemistry , Repressor Proteins/genetics , Substrate Specificity , Two-Hybrid System Techniques
20.
Psychopharmacology (Berl) ; 155(1): 18-26, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11374332

ABSTRACT

RATIONALE: Clinical studies examining the efficacy of the selective serotonin reuptake inhibitor, fluoxetine, in decreasing craving and cocaine use have been inconsistent. OBJECTIVE: To understand better the effects of fluoxetine treatment on incentive motivation for cocaine, the present study assessed the effects of chronic fluoxetine treatment on cocaine-seeking behavior in rats following exposure to a cocaine self-administration environment or a cocaine priming injection. METHODS: Rats were trained to press a lever for a cocaine reinforcer (0.5 mg/kg per 0.1 ml, i.v.) or received yoked administration of saline. They were then withdrawn from this regimen and given 20 daily injections of saline or fluoxetine (3.0 mg/kg, i.p.). Twenty-four hours after the last injection, the rats were placed in the self-administration environment and cocaine-seeking behavior (i.e., non-reinforced lever pressing) was measured for 90 min. Reinstatement of extinguished cocaine-seeking behavior was then measured for 60 min following a saline injection and for 90 min following a cocaine priming injection (15 mg/kg, i.p.). RESULTS: Chronic fluoxetine treatment attenuated cocaine-seeking behavior following exposure to the self-administration environment in most rats (n = 16), but enhanced cocaine-seeking behavior in two rats. Furthermore, the treatment failed to alter cocaine-seeking behavior following a cocaine priming injection. Interestingly, the amount of cocaine intake during self-administration training correlated with cocaine-seeking behavior following the cocaine priming injection. In fact, the priming injection reinstated cocaine-seeking behavior only in rats with high, but not low, cocaine intake based on a median split. CONCLUSIONS: These results suggest that chronic fluoxetine treatment decreases motivation for cocaine when animals are in a cocaine-free state. Furthermore, individual differences in cocaine use are related to individual differences in sensitivity to the incentive motivational effects of cocaine priming.


Subject(s)
Behavior, Addictive/drug therapy , Cocaine/administration & dosage , Dopamine Uptake Inhibitors/administration & dosage , Extinction, Psychological/drug effects , Fluoxetine/therapeutic use , Individuality , Selective Serotonin Reuptake Inhibitors/therapeutic use , Animals , Behavior, Addictive/psychology , Extinction, Psychological/physiology , Fluoxetine/pharmacology , Male , Motor Activity/drug effects , Motor Activity/physiology , Rats , Rats, Sprague-Dawley , Reaction Time/drug effects , Reaction Time/physiology , Selective Serotonin Reuptake Inhibitors/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...