This study extended the evaluation of microswitch technology (i.e., a position sensor and an optic device), recently introduced for chin and eyelid responses, with two new participants with profound multiple disabilities. The participants were girls of 12.5 and 4.0 years of age who did not possess any specific response that they could profitably use in their environment. The study was conducted according to an ABAB design with a 3-week postintervention check. The results showed that both participants increased their level of responding during the intervention phases and postintervention check compared to the baseline phases. This positive outcome was discussed in terms of (a) the apparent suitability of the technology and responses used in the study, (b) the beneficial implications for the participants, and (c) new developments in the area.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/10400435.2007.10131861 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Early Events in βAR Dimer Dynamics Mediated by Activation-Related Microswitches.
J 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 PDFRevealing the graded activation mechanism of neurotensin receptor 1.
Int J Biol Macromol
October 2024
College of Chemistry and Life Science, Beijing University of Technology, Beijing, China. Electronic address:
Graded activation contributes to the precise regulation of GPCR activity, presenting new opportunities for drug design. In this work, a total of 10 μs enhanced-sampling simulations are performed to provide molecular insights into the binding dynamics differences of the neurotensin receptor 1 (NTSR1) to the full agonist SRI-9829, partial agonist RTI-3a and inverse agonist SR48692. The possible graded activation mechanism of NTSR1 is revealed by an integrated analysis utilizing the reweighted potential of mean force (PMF), deep learning (DL) and transfer entropy (TE).
View Article and Find Full Text PDFStructural insights into ligand recognition, selectivity, and activation of bombesin receptor subtype-3.
Cell Rep
August 2024
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Guangdong 528400, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Guangzhou University of Chinese Medicine, Zhongshan Institute for Drug Discovery, Guangdong 510000, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:
Bombesin receptor subtype-3 (BRS3) is an important orphan G protein-coupled receptor that regulates energy homeostasis and insulin secretion. As a member of the bombesin receptor (BnR) family, the lack of known endogenous ligands and high-resolution structure has hindered the understanding of BRS3 signaling and function. We present two cryogenic electron microscopy (cryo-EM) structures of BRS3 in complex with the heterotrimeric G protein in its active states: one bound to the pan-BnR agonist BA1 and the other bound to the synthetic BRS3-specific agonist MK-5046.
View Article and Find Full Text PDFDynamic Insights into the Self-Activation Pathway and Allosteric Regulation of the Orphan G-Protein-Coupled Receptor GPR52.
J Chem Inf Model
September 2023
Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing 100124, China.
Within over 800 members of G-protein-coupled receptors, there are numerous orphan receptors whose endogenous ligands are largely unknown, providing many opportunities for novel drug discovery. However, the lack of an in-depth understanding of the intrinsic working mechanism for orphan receptors severely limits the related rational drug design. The G-protein-coupled receptor 52 (GPR52) is a unique orphan receptor that constitutively increases cellular 5'-cyclic adenosine monophosphate (cAMP) levels without binding any exogenous agonists and has been identified as a promising therapeutic target for central nervous system disorders.
View Article and Find Full Text PDFPathway selectivity in Frizzleds is achieved by conserved micro-switches defining pathway-determining, active conformations.
Nat Commun
July 2023
Karolinska Institutet, Dept. Physiology & Pharmacology, Sec. Receptor Biology & Signaling, Biomedicum, S-17165, Stockholm, Sweden.
The class Frizzled of G protein-coupled receptors (GPCRs), consisting of ten Frizzled (FZD) paralogs and Smoothened, remains one of the most enigmatic GPCR families. This class mediates signaling predominantly through Disheveled (DVL) or heterotrimeric G proteins. However, the mechanisms underlying pathway selection are elusive.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!