"A whole way of life": ontology of culture from Raymond Williams's perspective

An overall understanding of culture, both the culture of community one lives in and the culture of communities one communicates with, seems to be important for people to live their lives under the shelter of peace. This study hands over and foregrounds what people should notice when they face with their own and other nation’s culture in order to understand it better and prevent probable problems. Knowing about the essence of one's own culture, the person can protect it while it is being attacked by other cultures. It is predicted that by being aware of all the criteria just mentioned, people can both protect their own genuine culture and communicate with other communities, with different cultures, without facing with or creating crucial problems; as a result, they can live peacefully and help the matter of globalization. The main goal of this study is to present ontology of culture through which people would be able to get how to know their own and other's cultures. This knowledge helps them to communicate properly by knowing about what aspects of culture they should focus on when facing other cultures in order not to create any crucial problem

Biochemical studies on Francisella tularensis RelA in (p)ppGpp biosynthesis

The bacterial stringent response is induced by nutrient deprivation and is mediated by enzymes of the RSH (RelA/SpoT homologue; RelA, (p)ppGpp synthetase I; SpoT, (p)ppGpp synthetase II) superfamily that control concentrations of the 'alarmones' (p)ppGpp (guanosine penta- or tetra-phosphate). This regulatory pathway is present in the vast majority of pathogens and has been proposed as a potential anti-bacterial target. Current understanding of RelA-mediated responses is based on biochemical studies using Escherichia coli as a model. In comparison, the Francisella tularensis RelA sequence contains a truncated regulatory C-terminal region and an unusual synthetase motif (EXSD). Biochemical analysis of F. tularensis RelA showed the similarities and differences of this enzyme compared with the model RelA from Escherichia coli. Purification of the enzyme yielded a stable dimer capable of reaching concentrations of 10 mg/ml. In contrast with other enzymes from the RelA/SpoT homologue superfamily, activity assays with F. tularensis RelA demonstrate a high degree of specificity for GTP as a pyrophosphate acceptor, with no measurable turnover for GDP. Steady state kinetic analysis of F. tularensis RelA gave saturation activity curves that best fitted a sigmoidal function. This kinetic profile can result from allosteric regulation and further measurements with potential allosteric regulators demonstrated activation by ppGpp (5',3'-dibisphosphate guanosine) with an EC50 of 60±1.9 ?M. Activation of F. tularensis RelA by stalled ribosomal complexes formed with ribosomes purified from E. coli MRE600 was observed, but interestingly, significantly weaker activation with ribosomes isolated from Francisella philomiragia

Biochemical and structural characterization of polyphosphate kinase 2 from the intracellular pathogen Francisella tularensis

The metabolism of polyphosphate is important for the virulence of a wide range of pathogenic bacteria and the enzymes of polyphosphate metabolism have been proposed as an antibacterial target. In the intracellular pathogen Francisella tularensis , the product of the gene FTT1564 has been identified as a polyphosphate kinase from the PPK2 family. The isogenic deletion mutant was defective for intracellular growth in macrophages and was attenuated in mice, indicating an important role for polyphosphate in the virulence of Francisella . Herein we report the biochemical and structural characterization of F. tularensis polyphosphate kinase ( Ft PPK2) with a view to characterizing the enzyme as a novel target for inhibitors. Using an HPLC based activity assay the substrate specificity of Ft PPK2 was found to include purine but not pyrimidine nucleotides. The activity was also measured using 31P NMR. Ft PPK2 has been crystallized and the structure determined to 2.23 Å resolution. The structure consists of a 6- stranded parallel ? sheet surrounded by 12 ? helices, with a high degree of similarity to other members of the PPK2 family and the thymidylate kinase superfamily. Residues proposed to be important for substrate binding and catalysis have been identified in the structure, including a lid-loop and the conserved Walker A and B motifs. The ?FTT1564 strain showed significantly increased sensitivity to a range of antibiotics in a manner independent of the mode of action of the antibiotic. This combination of biochemical, structural and microbiological data provide a sound foundation for future studies targeting the development of PPK2 small molecule inhibitors

Donor T Cells Administered Over HLA Class II Barriers Mediate Antitumor Immunity without Broad Off-Target Toxicity in a NOD/Scid Mouse Model of Acute Leukemia

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease