Impulsivity and Compulsivity in Anorexia Nervosa: Cognitive Systems Underlying Variation in Appetite Restraint from an RDoC Perspective

Contemporary nomenclature for anorexia nervosa (AN) describes the eating disorder as transdiagnostic, with overlapping facets of impulsivity and compulsivity contributing to variations in binge-purge, restrictive eating and maladaptive cognitions. It is important to understand how these facets interact, given that those diagnosed with AN often fluctuate and relapse–as opposed to maintaining a stable diagnosis—between Diagnostic and Statistical Manual version 5 (DSM-5) categories, over the life course. The National Institute of Health’s Research Domain Criteria (NIH RDoC) subscribes to the transdiagnostic view of mental disorders and provides progressive guidelines for neuroscience research. As such, using the RDoC guidelines may help to pinpoint how impulsivity and compulsivity contribute to the cognitive mechanisms underlying variations in appetite restraint in eating disorders and common psychiatric comorbidities such as anxiety and obsessive-compulsive disorder. Exploring impulsivity and compulsivity in AN from the perspective of the RDoC cognitive systems domain is aided by measures of genetic, molecular, cellular, neural, physiological, behavioural and cognitive task paradigms. Thus, from the standpoint of the RDoC measures, this chapter will describe some of the ways in which impulsivity and compulsivity contribute to the cognitive systems associated with appetite restraint in AN, with the aim of further clarifying a model of appetite restraint to improve treatment interventions

Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract

Background: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments. Methods: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum. Results: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors. Conclusions: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions. © 2012 Badiali et al.; licensee BioMed Central Ltd

The G protein-coupled receptor subset of the rat genome

<p>Abstract</p> <p>Background</p> <p>The superfamily of G protein-coupled receptors (GPCRs) is one of the largest within most mammals. GPCRs are important targets for pharmaceuticals and the rat is one of the most widely used model organisms in biological research. Accurate comparisons of protein families in rat, mice and human are thus important for interpretation of many physiological and pharmacological studies. However, current automated protein predictions and annotations are limited and error prone.</p> <p>Results</p> <p>We searched the rat genome for GPCRs and obtained 1867 full-length genes and 739 pseudogenes. We identified 1277 new full-length rat GPCRs, whereof 1235 belong to the large group of olfactory receptors. Moreover, we updated the datasets of GPCRs from the human and mouse genomes with 1 and 43 new genes, respectively. The total numbers of full-length genes (and pseudogenes) identified were 799 (583) for human and 1783 (702) for mouse. The rat, human and mouse GPCRs were classified into 7 families named the <it>Glutamate, Rhodopsin, Adhesion, Frizzled, Secretin, Taste2 and Vomeronasal1 </it>families. We performed comprehensive phylogenetic analyses of these families and provide detailed information about orthologues and species-specific receptors. We found that 65 human <it>Rhodopsin </it>family GPCRs are orphans and 56 of these have an orthologue in rat.</p> <p>Conclusion</p> <p>Interestingly, we found that the proportion of one-to-one GPCR orthologues was only 58% between rats and humans and only 70% between the rat and mouse, which is much lower than stated for the entire set of all genes. This is in mainly related to the sensory GPCRs. The average protein sequence identities of the GPCR orthologue pairs is also lower than for the whole genomes. We found these to be 80% for the rat and human pairs and 90% for the rat and mouse pairs. However, the proportions of orthologous and species-specific genes vary significantly between the different GPCR families. The largest diversification is seen for GPCRs that respond to exogenous stimuli indicating that the variation in their repertoires reflects to a large extent the adaptation of the species to their environment. This report provides the first overall roadmap of the GPCR repertoire in rat and detailed comparisons with the mouse and human repertoires.</p

The amphioxus (Branchiostoma floridae) genome contains a highly diversified set of G protein-coupled receptors

<p>Abstract</p> <p>Background</p> <p>G protein-coupled receptors (GPCRs) are one of the largest families of genes in mammals. <it>Branchiostoma floridae </it>(amphioxus) is one of the species most closely related species to vertebrates.</p> <p>Results</p> <p>Mining and phylogenetic analysis of the amphioxus genome showed the presence of at least 664 distinct GPCRs distributed among all the main families of GPCRs; <it>Glutamate (18)</it>, <it>Rhodopsin (570)</it>, <it>Adhesion (37)</it>, <it>Frizzled (6) </it>and <it>Secretin (16)</it>. Surprisingly, the <it>Adhesion </it>GPCR repertoire in amphioxus includes receptors with many new domains not previously observed in this family. We found many <it>Rhodopsin </it>GPCRs from all main groups including many amine and peptide binding receptors and several previously uncharacterized expansions were also identified. This genome has however no genes coding for bitter taste receptors (TAS2), the sweet and umami (TAS1), pheromone (VR1 or VR2) or mammalian olfactory receptors.</p> <p>Conclusion</p> <p>The amphioxus genome is remarkably rich in various GPCR subtypes while the main GPCR groups known to sense exogenous substances (such as Taste 2, mammalian olfactory, nematode chemosensory, gustatory, vomeronasal and odorant receptors) in other bilateral species are absent.</p

The Limits of Lawyering: Legal Opinions in Structured Finance

Significant controversy surrounds the issuance of legal opinions in structured finance transactions, particularly where accountants separately use these opinions, beyond their traditional primary use, for determining whether to characterize the transactions as debt. Reflecting at its core the unresolved boundaries between public and private in financial transactions, this controversy raises important issues of first impression: To what extent, for example, should lawyers be able to issue legal opinions that create negative externalities? Furthermore, what should differentiate the roles of lawyers and accountants in disclosing information to investors? Resolution of these issues not only helps to demystify the mystique, and untangle the morass, of legal-opinion giving but also affects the very viability of the securitization industry, which dominates American, and increasingly global, financing

Prolactin-releasing peptide receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The precursor (PRLH, P81277) for PrRP generates 31 and 20-amino-acid versions. QRFP43 (named after a pyroglutamylated arginine-phenylalanine-amide peptide) is a 43 amino acid peptide derived from QRFP (P83859) and is also known as P518 or 26RFa. RFRP is an RF amide-related peptide [29] derived from a FMRFamide-related peptide precursor (NPVF, Q9HCQ7), which is cleaved to generate neuropeptide SF, neuropeptide RFRP-1, neuropeptide RFRP-2 and neuropeptide RFRP-3 (neuropeptide NPVF)

Adipose tissue stearoyl-CoA desaturase 1 index is increased and linoleic acid is decreased in obesity-prone rats fed a high-fat diet.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Fatty acid (FA) composition and desaturase indices are associated with obesity and related metabolic conditions. However, it is unclear to what extent desaturase activity in different lipid fractions contribute to obesity susceptibility. Our aim was to test whether desaturase activity and FA composition are linked to an obese phenotype in rats that are either obesity prone (OP) or resistant (OR) on a high-fat diet (HFD). METHODS: Two groups of Sprague-Dawley rats were given ad libitum (AL-HFD) or calorically restricted (HFD-paired; pair fed to calories consumed by chow-fed rats) access to a HFD. The AL-HFD group was categorized into OP and OR sub-groups based on weight gain over 5 weeks. Five different lipid fractions were examined in OP and OR rats with regard to proportions of essential and very long-chain polyunsaturated FAs: linoleic acid (LA), alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and the stearoyl-CoA desaturase 1 (SCD-1) product 16:1n-7. FA ratios were used to estimate activities of the delta-5-desaturase (20:4n-6/20:3n-6), delta-6-desaturase (18:3n-6/18:2n-6), stearoyl-CoA desaturase 1 (SCD-1; 16:1n-7/16:0, SCD-16 and 18:1n-9/18:0, SCD-18), de novo lipogenesis (16:0/18:2n-6) and FA elongation (18:0/16:0). Fasting insulin, glucose, adiponectin and leptin concentrations were measured in plasma. RESULTS: After AL-HFD access, OP rats had a significantly higher SCD-16 index and 16:1n-7 proportion, but a significantly lower LA proportion, in subcutaneous adipose tissue (SAT) triacylglycerols, as well as significantly higher insulin and leptin concentrations, compared with OR rats. No differences were found between the two phenotypes in liver (phospholipids; triacylglycerols) or plasma (cholesterol esters; phospholipids) lipid fractions or for plasma glucose or adiponectin concentrations. For the desaturase indices of the HFD-paired rats, the only significant differences compared with the OP or OR rats were higher SCD-16 and SCD-18 indices in SAT triacylglycerols in OP compared with HFD-paired rats. CONCLUSION: The higher SCD-16 may reflect higher SCD-1 activity in SAT, which in combination with lower LA proportions may reflect higher insulin resistance and changes in SAT independent of other lipid fractions. Whether a lower SCD-16 index protects against diet-induced obesity is an interesting possibility that warrants further investigation

Prolactin-releasing peptide receptor in GtoPdb v.2021.3

The precursor (PRLH, P81277) for PrRP generates 31 and 20-amino-acid versions. QRFP43 (43RFa) (named after a pyroglutamylated arginine-phenylalanine-amide peptide) is a 43 amino acid peptide derived from QRFP (P83859) and is also known as P518 or 26RFa. RFRP is an RF amide-related peptide [31] derived from a FMRFamide-related peptide precursor (NPVF, Q9HCQ7), which is cleaved to generate neuropeptide SF, neuropeptide RFRP-1, neuropeptide RFRP-2 and neuropeptide RFRP-3 (neuropeptide NPVF)

Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae

<p>Abstract</p> <p>Background</p> <p>The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in acyl-malonyl condensing enzyme proteins. In this paper, we present an evolutionary analysis of nucleotide sugar transporters in relation to the entire superfamily of drug/metabolite transporters that considers crucial intra-protein duplication events that have shaped the transporters. We use a method that combines the strengths of hidden Markov models and maximum likelihood to find relationships between drug/metabolite transporter families, and branches within families.</p> <p>Results</p> <p>We present evidence that the triose-phosphate transporters, domain unknown function 914, uracil-diphosphate glucose-N-acetylglucosamine, and nucleotide sugar transporter families have evolved from a domain duplication event before the radiation of <it>Viridiplantae </it>in the EamA family (previously called domain unknown function 6). We identify previously unknown branches in the solute carrier 30, 35 and 39 protein families that emerged simultaneously as key physiological developments after the radiation of <it>Viridiplantae</it>, including the "35C/E" branch of EamA, which formed in the lineage of <it>T. adhaerens </it>(<it>Animalia</it>). We identify a second cluster of DMTs, called the domain unknown function 1632 cluster, which has non-cytosolic N- and C-termini, and thus appears to have been formed from a different domain duplication event. We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains. We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought.</p> <p>Conclusions</p> <p>The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before <it>Viridiplantae</it>, showing for the first time the significance of EamA.</p