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Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells.
The transcription factor T-bet (Tbx21) plays a major role in adaptive immunity and is required for optimal IFN-gamma production by DCs. Here we demonstrate an essential function for T-bet in DCs in controlling inflammatory arthritis. We show that collagen antibody-induced arthritis (CAIA), a model of human RA, is a bipartite disease characterized by an early innate immune system component intac...
Previously, defined naturally occurring isoforms of allergenic proteins were classified as hypoallergens and therefore suggested as an agent for immunotherapy in the future. In this paper, we report for the first time the molecular background of hypoallergenicity by comparing the immunological behavior of hyperallergenic Betula verrucosa major Ag 1a (Bet v 1a) and hypoallergenic Bet v 1d, two i...
The protein Bet v 1 represents the main cause for allergic reactions to birch pollen in Europe and North America. Structurally homologous isoforms of Bet v 1 can have different properties regarding allergic sensitization and Th2 polarization, most likely due to differential susceptibility to proteolytic cleavage. Using NMR relaxation experiments and molecular dynamics simulations, we demonstrat...
Elusive bugs can be particularly expensive because they often survive testing and are released in a deployed system. They are characterized as involving a combination of properties. One approach to their detection is bounded exhaustive testing (BET). This paper describes how to implement BET using a variation of JUnit, called BETUnit. The idea of a BET pattern is also introduced. BET patterns d...
Background Birch pollen-allergic subjects often develop Bet v 1-specific IgE that cross-reacts with homologous food allergens. Bet v 1 and its homologs in pollen and food display exclusively conformational epitopes. We established a system to specifically analyze epitope cross-reactivity of Bet v 1-related allergens. The enzyme norcoclaurine synthase (NCS) from Thalictrum flavum is structurally...
Malignant brain tumors are the most common solid tumors in children. The overall prognosis for this group of patients is still poor, emphasizing the importance of more effective therapies. Betulinic acid (Bet A) has been described as a novel cytotoxic compound active against melanoma and neuroblastoma cells. Here we report that Bet A was active against medulloblastoma and glioblastoma cell line...
The basic principles of Bounded Exhaustive Testing (BET) are reviewed, as well as the concept of an Elusive Bug (EB). Initial work on the application of BET to EB's previously indicated that it provides a new and promising approach to this problem. A four-part BET/EB oriented test framework involving: fault model development, BET test generation design, failure model identification and automate...
The transcription factor T-bet regulates the production of interferon-γ and cytotoxic molecules in effector CD8 T cells, and its expression correlates with improved control of chronic viral infections. However, the role of T-bet in infections with differential outcome remains poorly defined. Here, we report that high expression of T-bet in virus-specific CD8 T cells during acute hepatitis B vir...
Despite the recognized role of the T-bet transcription factor in the differentiation of Th1 cells, T-bet-deficient mice can develop small numbers of IFN-gamma-producing CD4 T cells. Although these are not sufficient to allow normal handling of some pathogens, T-bet-deficient mice do resolve infection with the intracellular pathogen Listeria monocytogenes. In contrast, we report that expression ...
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