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PubMed1999

Molecular characterization of the melanin-concentrating-hormone receptor.

Orphan G-protein-coupled receptors (GPCRs) are cloned proteins with structural characteristics common to the GPCRs but that bind unidentified ligands. Orphan GPCRs have been used as targets to identify novel transmitter molecules. Here we describe the isolation from brain extracts and the characterization of the natural ligand of a particular orphan GPCR (SLC-1) that is sequentially homologous to the somatostatin receptors. We show that the natural ligand of this receptor is the neuropeptide melanin-concentrating hormone (MCH). MCH is a cyclic peptide that regulates a variety of functions in the mammalian brain, in particular feeding behaviour. We demonstrate that nanomolar concentrations of MCH strongly activate SLC-1-related pathways through G(alpha)i and/or G(alpha)q proteins. We have analysed the tissue localization of the MCH receptor and find that it is expressed in several brain regions, in particular those involved in olfactory learning and reinforcement mechanisms, indicating that therapies targeting the MCH receptor should act on the neuronal regulation of food consumption.

Amino Acid Sequence↗
PubMed2006

The short-latency dopamine signal: a role in discovering novel actions?

An influential concept in contemporary computational neuroscience is the reward prediction error hypothesis of phasic dopaminergic function. It maintains that midbrain dopaminergic neurons signal the occurrence of unpredicted reward, which is used in appetitive learning to reinforce existing actions that most often lead to reward. However, the availability of limited afferent sensory processing and the precise timing of dopaminergic signals suggest that they might instead have a central role in identifying which aspects of context and behavioural output are crucial in causing unpredicted events.

Animals↗
PubMed2005

Orbitofrontal cortex activity related to emotional processing changes across the menstrual cycle.

The orbitofrontal cortex (OFC) has been implicated in the representation of emotional stimuli, assignment of emotional valence/salience to stimuli, stimulus-reinforcement association learning, motivation, and socio-emotional control. Using functional magnetic resonance imaging in female subjects without premenstrual mood symptoms, we found that OFC activity to emotional linguistic stimuli varies depending on the menstrual cycle phase. Specifically, anterior-medial OFC activity for negative vs. neutral stimuli was increased premenstrually and decreased postmenstrually. The inverse pattern was seen in the lateral OFC. These findings suggest that specific subregional OFC activity to emotional stimuli is modulated across the menstrual cycle. The data also demonstrate that menstrual cycle phase is an important consideration in further studies attempting to elucidate the neural substrates of affective representation.

Adult↗
PubMed2000

Redox aspects of signaling by catecholamines and their metabolites.

This review covers certain novel aspects of catecholamine signaling in neurons that involve redox systems and synaptic plasticity. The redox hypothesis suggests that one important factor in neurocomputation is the formation of new synapses and the removal of old ones (synaptic plasticity), which is modulated in part by the redox balance at the synapse between reactive oxygen species (ROS) (such as hydrogen peroxide and the nitric oxide radical) and neuroprotective antioxidants (such as ascorbate, glutathione, and catecholamines). Catecholamines, in particular dopamine, which signals positive reinforcement, may play a key role in this activity. Dopamine has powerful antioxidant properties by several separate mechanisms-direct ROS scavenging, activation of the synthesis of antioxidant proteins, and possibly via dismuting complexes with iron inside endosomes or in catecholaminergic synaptic vesicles. This may contribute to synaptic growth and reinforcement-directed learning. On the other hand, catecholamines are easily oxidized to toxic quinones on the neuromelanin pathway. This might contribute under certain circumstances to synaptic deletion. Evidence is presented that abnormalities in this system may contribute to the pathogenesis of Parkinson's disease and schizophrenia.

Animals↗
PubMed1980

Clinical laboratory proficiency test performance. Its relationship to structural, process and environmental variables.

This comparative analysis of clinical laboratories was intended to develop a more quantitative understanding of environmental, structural, and process variables and their relationships to the quality of laboratory services. The quality of laboratory services was defined as analytic capability demonstrated on proficiency-test specimens of the College of American Pathologists. Independent variables describing the laboratory environment, as well as structural and process aspects of management, were obtained from management reports, staffing records, and workload reports. Although correlations between the eight proficiency testing indices and the independent variables were generally low, a number of significant correlates were evident in three areas: bacteriology, parasitology, and qualitative hematology. Environmental variables describing organizational size were related to proficiency, as were variables dealing with accreditation by the College of American Pathologists and time accredited by the College of American Pathologists. The education and experience of personnel and the percentage of specialized supervisors were related to proficiency-testing success in bacteriology and parasitology. Empirical evidence suggests that the size of the laboratory indirectly affects proficiency in these three tested areas. Presumably, this relationship is mediated through specialization of work and reinforcement of learning. Few significant correlates were evident in the five remaining areas tested: chemistry, quantitative hematology, blood bank, immunology, and syphilis serology. Despite the concentration of personnel resources and other assets in larger laboratories, size appeared to have no effect on proficiency-testing performance in these five areas.

Bacteriology↗
PubMed2002

Teaching and learning: an update for the orthodontist.

Developments in teaching and learning have implications for every orthodontist. This paper describes some of the theories of teaching and learning that have led to a quiet revolution in higher education. Developments have included the incorporation of self-directed and problem-based learning concepts, together with a more active and interactive role for the learner. The importance of these changes for orthodontic education is discussed.

Feedback↗
PubMed1999

The effects of neurocognitive remediation on executive processing in patients with schizophrenia.

Approaches to cognitive remediation have differed across studies. Most of the larger studies have concentrated on group treatments designed without the benefit of recent laboratory-based studies. The current study describes a randomized trial of an intensive cognitive remediation program involving individual daily sessions of 1 hour for up to 3 months. It targets executive functioning deficits (cognitive flexibility, working memory, and planning) that are known to be problematic in people with schizophrenia. Procedural learning, as well as the principles of errorless learning, targeted reinforcement, and massed practice, was the basis of the intervention. The program was compared with an alternative therapy (intensive occupational therapy) to control for some of the effects of therapeutic contact. Some improvements in cognition followed both therapies. A differential effect in favor of cognitive remediation therapy was found for tests in the cognitive flexibility and the memory subgroups. There was a trend for those receiving atypical antipsychotic medication to benefit more from cognitive remediation for tests of cognitive flexibility. Although there were no consistent changes in symptoms or social functioning between groups, if improvement in cognitive flexibility tasks reached a threshold then there is some evidence that social functioning improved, even over the short duration of the trial. In addition, cognitive remediation differentially improved self-esteem. This study supports the view that cognitive remediation can reduce cognitive deficits and that this reduction may affect social outcome, at least in the short term.

Adult↗