Cyclin-dependent kinase 18 controls trafficking of aquaporin-2 and its abundance through ubiquitin ligase STUB1, which functions as an AKAP

Arginine-vasopressin (AVP) facilitates water reabsorption in renal collecting duct principal cells through regulation of the water channel aquaporin-2 (AQP2). The hormone binds to vasopressin V2 receptors (V2R) on the surface of the cells and stimulates cAMP synthesis. The cAMP activates protein kinase A (PKA), which initiates signaling that causes an accumulation of AQP2 in the plasma membrane of the cells facilitating water reabsorption from primary urine and fine-tuning of body water homeostasis. AVP-mediated PKA activation also causes an increase in the AQP2 protein abundance through a mechanism that involves dephosphorylation of AQP2 at serine 261 and a decrease in its poly-ubiquitination. However, the signaling downstream of PKA that controls the localization and abundance of AQP2 is incompletely understood. We carried out an siRNA screen targeting 719 kinase-related genes, representing the majority of the kinases of the human genome and analyzed the effect of the knockdown on AQP2 by high-content imaging and biochemical approaches. The screening identified 13 hits whose knockdown inhibited the AQP2 accumulation in the plasma membrane. Amongst the candidates was the so far hardly characterized cyclin-dependent kinase 18 (CDK18). Our further analysis revealed a hitherto unrecognized signalosome comprising CDK18, an E3 ubiquitin ligase, STUB1 (CHIP), PKA and AQP2 that controls the localization and abundance of AQP2. CDK18 controls AQP2 through phosphorylation at serine 261 and STUB1-mediated ubiquitination. STUB1 functions as an A-kinase anchoring protein (AKAP) tethering PKA to the protein complex and bridging AQP2 and CDK18. The modulation of the protein complex may lead to novel concepts for the treatment of disorders which are caused or are associated with dysregulated AQP2 and for which a satisfactory treatment is not available, e.g., hyponatremia, liver cirrhosis, diabetes insipidus, ADPKD or heart failure

Retrieval Contexts and the Concreteness Effect: Dissociations in Memory of Concrete and Abstract Words

Decades of research on the concreteness effect, namely better memory for concrete as compared with abstract words, suggest it is a fairly robust phenomenon. Nevertheless, little attention has been given to limiting retrieval contexts. Two experiments evaluated intentional memory for concrete and abstract word lists in three retrieval contexts: free recall, explicit word-stem completion, and implicit word-stem completion. Concreteness effects were observed in free recall and in explicit word-stem completion, but not in implicit word-stem completion. These findings are consistent with both a bidirectional version of the relational-distinctiveness processing framework (Ruiz-Vargas, Cuevas, & Marschark, 1996) and a second framework combining insights from dual coding theory (Paivio, 1971, 1986) and the transfer appropriate processing framework (Roediger, Weldon, & Challis, 1989). Also, consistent with the relational-distinctiveness framework, the second experiment suggested that concreteness effects might depend on relational processing at encoding: Concreteness effects were observed in explicit memory for related word lists but not for unrelated word lists. © 2005 Psychology Press Ltd

Defensive properties of pyrrolizidine alkaloids against microorganisms

The understanding of the selection factors that drive chemical diversification of secondary metabolites of constitutive defence systems in plants, such as pyrrolizidine alkaloids (PAs), is still incomplete. Historically, plants always have been confronted with microorganisms. Long before herbivores existed on this planet, plants had to cope with microbial pathogens. Therefore, plant pathogenic microorganisms may have played an important role in the early evolution of the secondary metabolite diversity. In this review, we discuss the impact that plant-produced PAs have on plant-associated microorganisms. The objective of the review is to present the current knowledge on PAs with respect to anti-microbial activities, adaptation and detoxification by microorganisms, pathogenic fungi, root protection and PA induction. Many in vitro experiments showed effects of PAs on microorganisms. These results point to the potential of microorganisms to be important for the evolution of PAs. However, only a few in vivo studies have been published and support the results of the in vitro studies. In conclusion, the topics pointed out in this review need further exploration by carrying out ecological experiments and field studies

Towards a taxonomy of personality descriptors in German: a psycho-lexical study

Angleitner A, Ostendorf F, John OP. Towards a taxonomy of personality descriptors in German: a psycho-lexical study. European Journal of Personality. 1990;4(2):89-118.We present two studies aimed at developing a comprehensive taxonomy of German personality-descriptive terms. In the first study, all personality-descriptive adjectives (e.g. cynical), type nouns (e.g. cynic), and attribute nouns (e.g. cynicism) were extracted from a German dictionary. We found that almost half of all German adjectives were potentially personality-relevant, as contrasted with only 8% of the nouns. Moreover, there were more attribute nouns than type nouns, the latter appearing more slangy, metaphorical, concrete, and rich in imagery (e.g. Big-mouth, Wooden-head). In the second study, we discuss basic conceptual distinctions among units ofpersonality description, develop a category system basedon a prototype conception, and present a classification of 5092 adjectives into 13 categories. The classifications were generalizable across both judges and a two-year time interval, and agreed with a priori expert classifications. An analysis of the prototypical category cores suggested that Evaluations, Temperament and character traits, and Experiential states were represented most extensively in German, whereas Social effects, Roles and relationships, and Appearance were rather infrequent. These findings, though generally similar, differ from Norman's (1967) American taxonomy in the number of Evaluative terms and of Activity descriptors. Our studies provide comprehensive and representative lists of German words for personality traits, moods and emotions, social roles, effects, evaluations, and physical appearance, and may serve as the basis for taxonomies, dimensional analyses, and assessment instruments. We emphasize the need to standardize procedures in taxonomic research and outline suggestions for future studies of other languages

Influences of context on memory for routes

Possible influences of contexts on memory for routes are investigated. Route knowledge was established by learning a route which was presented on a computer screen. Activation of knowledge of items along the route was tested. The main goal was to decide whether the surrounding context in the learning and the test phase has an effect on memory for routes. Beyond general context effects, we looked for a possible indirect or mediated context effect. Such a mediate context effect would occur, when memory improves also in cases where context and the to-be-remembered items are separated by a spatial distance. The results reported here provide evidence for immediate context effects. A mediate context effect is not very strongly supported