Adhesion G protein-coupled receptors (AGPCRs) are a family of thirty-three receptors in humans exhibiting a conserved general structure but diverse expression patterns and physiological functions. The large N-termini characteristic of AGPCRs confer unique properties to each receptor and possess a variety of distinct domains that can bind to a diverse array of extracellular proteins and components of the extracellular matrix. The traditional view of AGPCRs, as implied by their name, is that their core function is the mediation of adhesion. In recent years, though, many surprising advances have been made regarding AGPCR signaling mechanisms, activation by mechanosensory forces, and stimulation by small-molecule ligands such as steroid hormones and bioactive lipids. Thus, a new view of AGPCRs has begun to emerge in which these receptors are seen as massive signaling platforms that are crucial for the integration of adhesive, mechanosensory, and chemical stimuli. This review article describes the recent advances that have led to this new understanding of AGPCR function and also discusses new insights into the physiological actions of these receptors as well as their roles in human disease.
Background: A cross-culturally valid nonverbal assessment of semantic knowledge is needed. Accurately identifying impairment of object semantics is important for diagnosis of several disorders, including distinguishing semantic variant primary progressive aphasia (svPPA), a neurodegenerative condition characterised by progressive impairment in word comprehension, from logopenic and nonfluent agrammatic variants, which are not associated with impaired object semantics. However, current assessments require culturally specific knowledge. Aims: We developed a cross-culturally valid short form of the Pyramids and Palm Trees Test to assess object semantic memory. We investigated its clinical utility in differentiating the semantic variant of primary progressive aphasia, from the logopenic and nonfluent agrammatic variants. Areas of atrophy associated with poor performance were identified. Methods & Procedures: Fourteen items that rely on knowledge of objects' defining features were selected from the original 52-item version. The full and short forms were administered to healthy individuals in the US (N = 18), Argentina (N = 20), and Greece (N = 12) and performance was compared. Seventy-eight individuals with primary progressive aphasia in the US completed the short form. Behavioural performance of the svPPA group (N = 24) was compared to other variants. Atlas-based analysis identified regions where atrophy correlated with poor performance in 39 individuals with primary progressive aphasia who had high-resolution magnetic resonance imaging (MRI) scans. Outcomes & Results: Control performance was classified as normal on the short form significantly more often than on the full version. Across groups with primary progressive aphasia, the group with semantic variant performed significantly worse than the groups with logopenic or nonfluent agrammatic variants. Volume in left anterior and inferior temporal cortex correlated with performance. Conclusions: The short-form Pyramids and Palm Trees Test is a clinically relevant, cross-culturally valid assessment of nonverbal object semantics. It can be used to identify semantic impairments, with poor performance associated with atrophy of the temporal lobes.
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