Hijacking of Host Cell Signaling by Theileria

The apicomplexan parasites Theileria annulata and T. parva possess the ability to transform the infected host cell and induce uncontrolled proliferation. Residing free in the cytosol of its host leukocyte, the schizont is in a perfect position to manipulate host cell signaling pathways involved in regulating apoptosis, proliferation, and cell motility. While extensive Theileria-induced changes in host cell protein phosphorylation patterns have been reported, no Theileria-encoded kinases or phosphatases have been demonstrated - or are even predicted - to be associated with the schizont surface or secreted into the host cell. Instead, it seems that Theileria has evolved the capacity to modulate kinases of the host cell. In certain cases this involves “hijacking” pivotal kinases, such as the IκB kinase complex or the mitotic kinase polo-like kinase 1, recruiting them to the schizont surface. In this chapter the current understanding of Theileria-induced changes in host cell kinase activation is reviewed, and an attempt is made to link these events to phenotypic changes that occur in the cell in response to Theileria infection.

Application of in vivo induced antigen technology (IVIAT) to Bacillus anthracis.

In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase NarG, and three proteins of unknown function. Using quantitative real-time PCR comparing RNA isolated from in vitro cultured B. anthracis to RNA isolated from BALB/c mice infected with virulent Ames strain B. anthracis, we confirmed induced expression in vivo for a subset of B. anthracis genes identified by IVIAT, including L-alanine amidases BA3767, BA4073, and amiA (pXO2-42); the bacteriophage holin gene BA4074; and pagA (pXO1-110). The exogenous addition of two purified putative autolysins identified by IVIAT, N-acetylmuramoyl-L-alanine amidases BA0485 and BA2446, to vegetative B. anthracis cell suspensions induced a species-specific change in bacterial morphology and reduction in viable bacterial cells. Many of the proteins identified in our screen are predicted to affect peptidoglycan re-modeling, and our results support significant cell wall structural remodeling activity during B. anthracis infection. Identification of L-alanine amidases with B. anthracis specificity may suggest new potential therapeutic targets.

Wohnen und die Ökonomie des Raumes – L’habitat et l’économie de l’espace

Wohnen und Habitat sind entscheidende Aspekte des Alltagslebens in mikrohistorischer Hinsicht. korrespondierend mit der Ökonomie des Raumes stellen sie relevante Dimensionen und Produkte des Handelns in Gesellschaften auf der Makroebene dar. Die hier versammelten Beiträge zeugen von der Notwendigkeit der Erneuerung des Themenfeldes Wohnen in vielfältigen gesellschaftlichen, kulturellen und praxeologischen Perspektiven. Sie spannen den Bogen vom Spätmittelalter bis zur Gegenwart, von der entlegenen Burg bis zur Metropole. Sie stellen dabei Bezüge her zu den zeitgenössischen «turns and trends» der Forschung, zu den Debatten über Wohn-, Wirtschafts- und Haushaltsformen bis hin zu den Spannungen zwischen Raumökonomie und Sozialreform, Öffentlichkeit und privater Raum sowie Mobilität und Häuslichkeit.

On the Limits of Greenwich Mean Time, or The Failure of a Modernist Revolution

On the Limits of Greenwich Mean Time, or The Failure of a Modernist Revolution From the introduction of World Standard Time in 1884 to Einstein’s theory of relativity, the nature and regulation of time was a highly contested issue in modernism, with profound political, social and epistemological consequences. Modernist aesthetic sensibilities widely revolted against the increasingly strict rule of the clock, which, as Georg Simmel observed in “The Metropolis and Mental Life,” was established as the necessary basis of a capitalist, urban life. This paper will focus on the contending conceptions of time arising in key modernist texts by authors like Joyce, Woolf and Conrad. I will argue that the uniformity and regularity of time necessary to a rising capitalist society came under attack in a similar way by both modernist literary aesthetics and new scientific discoveries. However, while Einstein’s theory of relativity may have led to a subsequent change of paradigm in scientific thought, it has failed to significantly alter social and popular conceptions of time. Although alternative ways of thinking and living with time are proposed by modernist authors, they remain isolated aesthetic experiments, ineffectual against the regulatory pressure of economic and social structures. In this struggle about the nature of time, so I suggest, science and literature join force against a society that is increasingly governed by economic reason. The fact that they lost this struggle can serve as a striking illustration of an increasing shift of social influence from science and art towards economy.

Über das jetzige Verhältnis der Jüdischen Nation zu dem christlichen Bürgervereine, und dessen künftige Umgestaltung : 2 Abhandlungen

von C. F. von Schmidt-Phiseldek

Wir sind die Juden : eine biblische Studie

von Arthur Maria Baron von Lüttwitz

Chrétiens ›Roman de Perceval ou le Conte du Graal‹ und Wolframs ›Parzival‹. Ihre Überlieferung und textkritische Erschließung

This article discusses the manuscript transmission of Chrétien’s Roman de Perceval ou le Conte du Graal and Wolfram’s Parzival in terms of their textual tradition and editorial criticism. It shows that the most recent edition of the Old French Perceval (K. Busby 1993) can be viewed as a landmark of the art of conventional editing that appeared at the peak of the discussion of ‘New Philology’ and took its own position in this context. At the same time, the Perceval was subject of critical studies based on the principle of ‘unrooted trees’ that questioned the genealogical concept of traditional ‘Lachmannian’ stemmatology. Conversely, a new edition of Wolfram’s Parzival, based on all known manuscripts, remained a desideratum for decades in German studies. Specific research on the textual tradition played a rather marginal role for a long time, but has been reinforced in the recent years in the context of a new critical edition presenting the totality of manuscripts as well as different textual versions in electronic form. The concept of ‘unrooted trees’ visualizing relationships of manuscript readings can be integrated in this concept. The article gives an overview of these methods, presents examples of editorial techniques, and develops ideas on how to combine the research on the manuscript tradition of both the German text and its French counterpart.

BPAG1a and b Associate with EB1 and EB3 and Modulate Vesicular Transport, Golgi Apparatus Structure, and Cell Migration in C2.7 Myoblasts.

BPAG1a and BPAG1b (BPAG1a/b) constitute two major isoforms encoded by the dystonin (Dst) gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5' end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3' end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts.