Plectin interacts with the rod domain of type III intermediate filament proteins desmin and vimentin

Plectin is a versatile cytolinker protein critically involved in the organization of the cytoskeletal filamentous system. The muscle-specific intermediate filament (IF) protein desmin, which progressively replaces vimentin during differentiation of myoblasts, is one of the important binding partners of plectin in mature muscle. Defects of either plectin or desmin cause muscular dystrophies. By cell transfection studies, yeast two-hybrid, overlay and pull-down assays for binding analysis, we have characterized the functionally important sequences for the interaction of plectin with desmin and vimentin. The association of plectin with both desmin and vimentin predominantly depended on its fifth plakin repeat domain and downstream linker region. Conversely, the interaction of desmin and vimentin with plectin required sequences contained within the segments 1A-2A of their central coiled-coil rod domain. This study furthers our knowledge of the interaction between plectin and IF proteins important for maintenance of cytoarchitecture in skeletal muscle. Moreover, binding of plectin to the conserved rod domain of IF proteins could well explain its broad interaction with most types of IFs.

Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance

Abstract Alteration of the surface glycosylation pattern on malignant cells potentially affects tumor immunity by directly influencing interactions with glycan-binding proteins (lectins) on the surface of immunomodulatory cells. The sialic acid-binding Ig-like lectins Siglec-7 and -9 are MHC class I-independent inhibitory receptors on human NK cells that recognize sialic acid-containing carbohydrates. Here, we found that the presence of Siglec-9 defined a subset of cytotoxic NK cells with a mature phenotype and enhanced chemotactic potential. Interestingly, this Siglec-9+ NK cell population was reduced in the peripheral blood of cancer patients. Broad analysis of primary tumor samples revealed that ligands of Siglec-7 and -9 were expressed on human cancer cells of different histological types. Expression of Siglec-7 and -9 ligands was associated with susceptibility of NK cell-sensitive tumor cells and, unexpectedly, of presumably NK cell-resistant tumor cells to NK cell-mediated cytotoxicity. Together, these observations have direct implications for NK cell-based therapies and highlight the requirement to consider both MHC class I haplotype and tumor-specific glycosylation.

Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense

Aberrant glycosylation is a key feature of malignant transformation and reflects epigenetic and genetic anomalies among the multitude of molecules involved in glycan biosynthesis. Although glycan biosynthesis is not template bound, altered tumor glycosylation is not random, but associated with common glycosylation patterns. Evidence suggests that acquisition of distinct glycosylation patterns evolves from a ‘microevolutionary’ process conferring advantages in terms of tumor growth, tumor dissemination, and immune escape. Such glycosylation modifications also involve xeno- and hypersialylation. Xeno-autoantigens such as Neu5Gc-gangliosides provide potential targets for immunotherapy. Hypersialylation may display ‘enhanced self’ to escape immunosurveillance and involves several not mutually exclusive inhibitory pathways that all rely on protein–glycan interactions. A better understanding of tumor ‘glycan codes’ as deciphered by lectins, such as siglecs, selectins, C-type lectins and galectins, may lead to novel treatment strategies, not only in cancer, but also in autoimmune disease or transplantation.

The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites.

Despite the paradigm that carbohydrates are T cell-independent antigens, isotype-switched glycan-specific immunoglobulin G (IgG) antibodies and polysaccharide-specific T cells are found in humans. We used a systems-level approach combined with glycan array technology to decipher the repertoire of carbohydrate-specific IgG antibodies in intravenous and subcutaneous immunoglobulin preparations. A strikingly universal architecture of this repertoire with modular organization among different donor populations revealed an association between immunogenicity or tolerance and particular structural features of glycans. Antibodies were identified with specificity not only for microbial antigens but also for a broad spectrum of host glycans that serve as attachment sites for viral and bacterial pathogens and/or exotoxins. Tumor-associated carbohydrate antigens were differentially detected by IgG antibodies, whereas non-IgG2 reactivity was predominantly absent. Our study highlights the power of systems biology approaches to analyze immune responses and reveals potential glycan antigen determinants that are relevant to vaccine design, diagnostic assays, and antibody-based therapies.

Indigene Repräsentation im neuen Venezolanischen Fernsehen

Die politischen Transformationen in Venezuela, im Zuge derer Hugo Chavez Frias eine neue Ära 'sozialer Kommunikation' ankündigte, haben zu einer extremen Polarisierung der Medien, im Speziellen des Fernsehens, geführt. In diesem Buch werden aus kultur- und sozialanthropologischer Perspektive gesellschaftliche Dynamiken unter dem Kriterium der medialen Präsenz, Ausbreitung und Wirkung in den Mittelpunkt gestellt. Am Beispiel der indigenen Warao werden bolivarianische Konzepte partizipativer Repräsentation vorgestellt und diskutiert. Dabei sollen Vorgehensweisen und Prozesse audio-visueller Repräsentation mit der Selbst- und Fremdwahrnehmung der zu Repräsentierenden in Beziehung gesetzt werden.

Otium et negotium. Reading processes and their cultural backgrounds in early Italian and German humanism

Reading and reading habits have radically changed in the digital age. Readers are no longer physically bound to textual objects and libraries, they deal with texts by copying, altering, and annotating them, and they mix established textual forms with other semiotic systems such as pictograms, icons and images. These circumstances also provoke a renewed research interest in the history of reading. In this talk, I will concentrate on reading processes as to how they were enacted and practised in early Italian and German humanism. I will start with some paradigmatic scenes described in Petrarch’s letters (among others the famous visit of the Mont Ventoux, where Petrarch, after having enjoyed a spectacular panorama, withdraws into the contemplative reading of St-Augustine). The transmission of Petrarch’s writings in humanist circles of Southern Germany (e.g. with the Schedel and Gossembrot families in Nurnberg, Augsburg and Strasburg) will then lead to specific reading practices documented in manuscripts that once belonged to coherent libraries and are nowadays spread all over Europe. In the case of the former tradesman and mayor Sigismund Gossembrot, complex habits of textual annotating and cross-referencing can be observed. The dichotomy of the Latin terms otium (‘rest’ and ‘leisure’) and negotium (‘activity’, but also ‘practice’, ‘negotiation’, ‘circulation of social energy’ in the sense of New Historicism) will be used as an ideal-type outline to describe the occurring processes of reading.