This study assessed microswitch and computer technology to enable two participants with multiple disabilities, 32 and 19 years of age, to choose among environmental stimuli and request their repetition whenever they so desired. Within each session, 18 stimuli (12 preferred and 6 nonpreferred) were available. For each stimulus, a computer system provided a sample of 3 sec. duration. During the intervention, participants' vocal responding in relation to a stimulus sample activated a microswitch and a computer system turned on that stimulus for 15-30 sec. When participants did not vocally respond, the computer system paused briefly and then presented the next scheduled stimulus sample. When participants vocally responded at the end of a stimulus presentation, the stimulus was repeated. Intervention data showed that the participants learned to choose preferred stimuli and bypass nonpreferred ones as well as to request repetitions of the preferred stimuli. This performance was maintained at a 1-mo. postintervention check and transferred to sets of stimuli not used in the intervention. The implications of these results were discussed.
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http://dx.doi.org/10.2466/pms.103.2.354-362 | DOI Listing |
Structure
January 2025
Computational Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK; Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK. Electronic address:
Negative allosteric modulation of G-protein coupled receptors (GPCRs) by Na ions was first described in the 1970s for opioid receptors (ORs) and has subsequently been detected for most class A GPCRs. In high-resolution structures of inactive-state class A GPCRs, a Na ion binds to a conserved pocket near residue D2.50, whereas active-state structures of GPCRs are incompatible with Na binding.
View Article and Find Full Text PDFJ Membr Biol
December 2024
HPC-Medical & Bioinformatics Applications Group, Centre for Development of Advanced Computing (C-DAC), Innovation Park, Panchawati, Pashan, Pune, India, 411008.
G-Protein-Coupled Receptors (GPCRs) make up around 3-4% of the human genome and are the targets of one-third of FDA-approved drugs. GPCRs typically exist as monomers but also aggregate to form higher-order oligomers, including dimers. βAR, a pharmacologically relevant GPCR, is known to be targeted for the treatment of asthma and cardiovascular diseases.
View Article and Find Full Text PDFNat Commun
August 2024
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are distinct, with the TAARs being most similar to the aminergic receptors such as those activated by adrenaline, serotonin, dopamine and histamine. To elucidate the structural determinants of ligand recognition by TAARs, we have determined the cryo-EM structure of a murine receptor, mTAAR7f, coupled to the heterotrimeric G protein G and bound to the odorant N,N-dimethylcyclohexylamine (DMCHA) to an overall resolution of 2.
View Article and Find Full Text PDFJ Mol Biol
August 2024
Department of Chemistry, School of Physical and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom. Electronic address:
GPR68 is a proton-sensing G-protein Coupled Receptor (GPCR) involved in a variety of physiological processes and disorders including neoplastic pathologies. While GPR68 and few other GPCRs have been shown to be activated by a decrease in the extracellular pH, the molecular mechanism of their activation remains largely unknown. In this work, we used a combined computational and in vitro approach to provide new insight into the activation mechanism of the receptor.
View Article and Find Full Text PDFHum Genomics
June 2024
Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmaceutical target under investigation for the treatment of several neuropsychiatric conditions. TAAR1 single nucleotide variants (SNV) have been found in patients with schizophrenia and metabolic disorders. However, the frequency of variants in geographically diverse populations and the functional effects of such variants are unknown.
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