Lernstrategien und Lernerfolg im Studium : zur Validierung des LIST bei berufstätigen Studierenden

Das von Wild und Schiefele (1994) vorgestellte Inventar zur Erfassung von Lernstrategien im Studium (LIST) wird an einer Stichprobe von N = 577 berufstätigen Studierenden vier unterschiedlicher Hochschulen untersucht. Die von Wild und Schiefele angenommene Struktur der kognitiven, ressourcenbezogenen und metakognitiven Lernstrategien wird hier erstmals faktorenanalytisch überprüft. Darüber hinaus wird erstmals die dreifaktorielle Struktur der metakognitiven Lernstrategien mit dem LISTInventar nachgewiesen. Schließlich sind im Sinne einer Außenvalidierung des LIST Zusammenhänge zwischen Lernstrategien und Lernerfolg der Studierenden nachweisbar

The Mu-Opioid Receptor Variant N190K is Unresponsive to Peptide Agonists Yet Can be Rescued by Small Molecule Drugs MOL #64188 2 Running Title: Small molecules rescue function of an inactive MOR variant

MOL #64188 3 Abstract The mu-opioid receptor (MOR) plays an important role in modulating analgesia, feeding behavior and a range of autonomic functions. In the current study, we investigated the degree to which thirteen naturally-occurring missense mutations affect the pharmacological properties of the human MOR. Following expression of each receptor in HEK293 cells, signaling (Gα i/omediated) induced by peptide agonists was assessed utilizing luciferase reporter gene assays. Multiple mutants (S66F, S147C, R260H, R265C, R265H and S268P) show a significant reduction in agonist potency. At the N190K variant, agonist-mediated signaling was essentially absent. ELISA, microscopic analysis and radioligand binding assays revealed that this mutant shows markedly reduced cell surface expression, whereas all other receptor variants were expressed at normal levels. Surface expression of the N190K variant could be increased by incubation with the alkaloid agonist buprenorphine, or with either of the structurally related MOR antagonists, naltrexone or naloxone. Surprisingly, both putative antagonists, despite being inactive at the wild type MOR, triggered a concentration-dependent increase in N190K receptor mediated signaling. In contrast, peptidic ligands failed to promote expression or rescue function of the N190K mutant. Subsequent analysis of the N190K variant in an ethnically diverse cohort identified this isoform in a subgroup of African Americans. Taken together, our studies reveal that the N190K mutation leads to severe functional alterations and, in parallel, changes the response to established MOR ligands. The extent to which this mutation results in physiological abnormalities or affects drug sensitivity in selected populations (e.g. those with chronic pain or addiction) remains to be investigated

The μ-Opioid Receptor Variant N190K Is Unresponsive to Peptide Agonists yet Can be Rescued by Small-Molecule DrugsS⃞

The μ-opioid receptor (MOR) plays an important role in modulating analgesia, feeding behavior, and a range of autonomic functions. In the current study, we investigated the degree to which 13 naturally occurring missense mutations affect the pharmacological properties of the human MOR. After expression of each receptor in human embryonic kidney 293 cells, signaling (Gαi/o-mediated) induced by peptide agonists was assessed using luciferase reporter gene assays. Multiple mutants (S66F, S147C, R260H, R265C, R265H, and S268P) show a significant reduction in agonist potency. At the N190K variant, agonist-mediated signaling was essentially absent. Enzyme-linked immunosorbent assay, microscopic analysis, and radioligand binding assays revealed that this mutant shows markedly reduced cell-surface expression, whereas all other receptor variants were expressed at normal levels. Surface expression of the N190K variant could be increased by incubation with the alkaloid agonist buprenorphine or with either naltrexone or naloxone, structurally related MOR antagonists. We were surprised to find that both putative antagonists, despite being inactive at the wild-type MOR, triggered a concentration-dependent increase in N190K receptor-mediated signaling. In contrast, peptidic ligands failed to promote expression or rescue function of the N190K mutant. Subsequent analysis of the N190K variant in an ethnically diverse cohort identified this isoform in a subgroup of African Americans. Taken together, our studies reveal that the N190K mutation leads to severe functional alterations and, in parallel, changes the response to established MOR ligands. The extent to which this mutation results in physiological abnormalities or affects drug sensitivity in selected populations (e.g., those with chronic pain or addiction) remains to be investigated

Neuropeptide substance P and the immune response

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of activity of immune cells. This Review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immuno-biology of substance P and we discuss the clinical implications of its ability to modulate the immune response