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The transporter associated with antigen processing (TAP) selectively translocates antigenic peptides into the endoplasmic reticulum. Loading onto major histocompatibility complex class I molecules and proofreading of these bound epitopes are orchestrated within the macromolecular peptide-loading complex, which assembles on TAP. This heterodimeric ABC-binding cassette (ABC) transport complex is therefore a major component in the adaptive immune response against virally or malignantly transformed cells. Its pivotal role predestines TAP as a target for infectious diseases and malignant disorders. The development of therapies or drugs therefore requires a detailed comprehension of structure and function of this ABC transporter, but our knowledge about various aspects is still insufficient. This review highlights recent achievements on the structure and dynamics of antigenic peptides in complex with TAP. Understanding the binding mode of antigenic peptides in the TAP complex will crucially impact rational design of inhibitors, drug development, or vaccination strategies.
Perfectionism nowadays is frequently understood as a multidimensional personality trait with two higher-order dimensions of perfectionistic strivings and perfectionistic concerns. While perfectionistic concerns are robustly found to correlate with negative outcomes and psychological malfunctioning, findings concerning the outcomes of perfectionistic strivings are inconsistent. There is evidence that perfectionistic strivings relate to psychological maladjustment on the one hand but to positive outcomes on the other hand as well. Moreover, perfectionistic strivings and perfectionistic concerns frequently showed substantial overlap. These inconsistencies of differential relations and the substantial overlap of perfectionistic strivings and perfectionistic concerns raise questions concerning the factorial structure of perfectionism and the meaning of its dimensions. In this study, several bifactor models were applied to disentangle the common variance of perfectionistic strivings and perfectionistic concerns at the item level using Hill et al.’s (2004) Perfectionism Inventory (PI). The PI measures a broad range of perfectionism dimensions by four perfectionistic strivings and four perfectionistic concerns subscales. The bifactor-(S – 1) model with one general factor defined by concern over mistakes as the reference facet, four specific perfectionistic strivings factors, and three specific perfectionistic concerns factors showed acceptable fit. The results revealed a clear separation between perfectionistic strivings and perfectionistic concerns, as the general factor represented concern over mistakes, while the perfectionistic strivings factors each explained a substantial amount of reliable variance independent of the general factor. As a result, factor scores of the specific perfectionistic strivings factors and the general factor had differential relationships with achievement motivation, neuroticism, conscientiousness, and self-efficacy that met with theoretical expectations, while results for manifest subscale scores were ambiguous. Our results question the existence of reliable sub-constructs of perfectionistic concerns independent of the general factor when defined by concern over mistakes.
Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice.
Though one should be very careful with reaching conclusions about the social views conveyed in 'The Beach of Falesá', and there are many opinions on the story's social message, one of them is "the exposure of white racism" (Menikoff 1984,57) and imperialism. The logical question, why this country, which is declaring itself a bulwark against the world's imperialism, would disapprove of such novel, reasonably appears. And the censoring of it could seem a complete non sequitur. Which 'ideas' could make this novel not suitable for an average Soviet reader in the eyes of the Soviet censorship?
Although existing research has established that aesthetic pleasure and aesthetic interest are two distinct positive aesthetic responses, empirical research on aesthetic preferences usually considers only aesthetic liking to capture participants’ aesthetic response. This causes some fundamental contradictions in the literature; some studies find a positive relationship between easy-to-process stimulus characteristics and aesthetic liking, while others suggest a negative relationship. The present research addresses these empirical contradictions by investigating the dual character of aesthetic liking as manifested in both the pleasure and interest components. Based on the Pleasure-Interest Model of Aesthetic Liking (PIA Model; Graf and Landwehr, 2015), two studies investigated the formation of pleasure and interest and their relationship with aesthetic liking responses. Using abstract art as the stimuli, Study 1 employed a 3 (stimulus fluency: low, medium, high) × 2 (processing style: automatic, controlled) × 2 (aesthetic response: pleasure, interest) experimental design to examine the processing dynamics responsible for experiencing aesthetic pleasure versus aesthetic interest. We find that the effect of stimulus fluency on pleasure is mediated by a gut-level fluency experience. Stimulus fluency and interest, by contrast, are related through a process of disfluency reduction, such that disfluent stimuli that grow more fluent due to processing efforts become interesting. The second study employed product designs (bikes, chairs, and lamps) as stimuli and a 2 (fluency: low, high) × 2 (processing style: automatic, controlled) × 3 (product type: bike, chair, lamp) experimental design to examine pleasure and interest as mediators of the relationship between stimulus fluency and design attractiveness. With respect to lamps and chairs, the results suggest that the effect of stimulus fluency on attractiveness is fully mediated by aesthetic pleasure, especially in the automatic processing style. Conversely, disfluent product designs can enhance design attractiveness judgments due to interest when a controlled processing style is adopted.
Malignant brain tumors, including gliomas, brain metastases and anaplastic meningiomas, are associated with poor prognosis, and represent an unmet medical need. ASA404 (DMXAA), a vascular disrupting agent, has demonstrated promising results in several preclinical tumor models and early phase clinical trials. However, two phase III trials in non-small cell lung cancer reported insufficient results. The aim of the present study was to determine the effects of ASA404 on brain tumors. The effects of ASA404 were evaluated in vitro and in vivo using subcutaneous, and orthotopical models for malignant glioma (U-87, LN-229, U-251, LN-308 and Tu-2449), brain metastasis (HT-29) and malignant meningioma (IOMM-Lee). The acute effects of ASA404 on tumor tissue were analyzed using conventional and immunohistochemical staining techniques [hematoxylin and eosin, MIB-1 antibody/proliferation maker protein Ki-67, cleaved caspase-8, stimulator of interferon genes (STING), ionized calcium-binding adapter molecule 1]. Furthermore, the sizes of subcutaneous tumors were measured and the symptom-free survival rates of animals with intracranial tumors receiving ASA404 treatment were analyzed. ASA404 demonstrated low toxicity in vitro, but exhibited strong effects on subcutaneous tumors 24 h following a single dose of ASA404 (25 mg/kg). ASA404 induced necrosis, hemorrhages and inhibited the proliferation, and growth of tumors in the subcutaneous glioma models. However, ASA404 failed to demonstrate comparable effects in any of the intracranial tumor models examined and did not result in a prolongation of survival. Expression of STING, the molecular target of ASA404, and infiltration of macrophages, the cells mediating ASA404 activity, did not differ between subcutaneous and intracranial tumors. In conclusion, ASA404 demonstrates clear efficacy in subcutaneous tumor models, but has no relevant activity in orthotopic brain tumor models. The expression of STING and infiltration with macrophages were not determined to be involved in the differential activity observed among tumor models. It is possible that the low penetration of ASA-404 into the brain prevents concentrations sufficient enough reaching the tumor in order to exhibit acute effects in vivo.
Tagungsbericht zu 'Lexikographik als künstlerisch-literarische Schreibweise', Ruhr-Universität Bochum, 27. bis 29. Mai 2010.
Die Form des Lexikons ist nicht nur unter dem Blickwinkel der Wissensproduktion und -vermittlung von Interesse, sondern stellt sich auch als ein Phänomen an der Schnittstelle zwischen Literatur und bildender Kunst dar. Entsprechend vielfältig gestalten sich die Erscheinungsformen der Lexikographik, sei es als reines Ordnungssystem oder als künstlerisch-literarisches Projekt. Diese Vielfalt spiegelte sich auch in der von Monika Schmitz-Emans, Kai Fischer und Christoph Schulz vom Bochumer Lehrstuhl für Komparatistik im Rahmen des DFG-Projekts 'Literarische Darstellungsexperimente' organisierten Tagung wider, die die Lexikographik nicht nur literaturwissenschaftlich in den Blick nahm, sondern auch im Rahmen einer Ausstellung von Arbeiten des Künstlers Paul Mersmann den bildkünstlerischen Aspekt des Themas betonte.
Tagungsbericht zu 'Fusion Culture: Fashion beyond Orientalism and Occidentalism', Universität Potsdam, 5. bis 7. November 2009
Die von Gabriele Mentges (Dortmund) und Gertrud Lehnert (Potsdam) veranstaltete und von der Volkswagen Stiftung geförderte Tagung befasste sich mit dem Thema 'Orientalismus und Mode' zum einen unter historischen Aspekten, zum anderen unter gegenwärtigen Bedingungen, in denen von 'Orientalismus' kaum noch die Rede sein kann. Denn längst haben wechselseitige Bezüge Mode zu einer globalen Angelegenheit gemacht. Vernetzung, Vermischung, Globalisierung, aber auch neue Regionalisierung bestimmt (nicht erst seit) heute die Mode.
Tagungsbericht zu 'Die Räume der Mode'. Internationale Tagung der Universität Potsdam, Kulturforum Berlin, 5. bis 7. Mai 2010
Die von Gertrud Lehnert (Potsdam) im Berliner Kulturforum ausgerichtete Tagung 'Die Räume der Mode' (5.-7. Mai 2010) betrachtete aus kulturwissenschaftlicher und praktischer Perspektive das Wechselverhältnis von Mode und Raum.
Tagungsbericht zu 'Comparative Arts - Neue Ansätze zu einer universellen Ästhetik'. 14. Tagung der DGAVL in Münster, 26. bis 28. November 2008
Unter dem Titel 'Comparative Arts - Ansätze zu einer universellen Ästhetik' veranstaltete die DGAVL vom 26. bis zum 28.11. 2008 in Münster ihre 14. turnusmäßige Tagung.