Shikimate kinase: A potential target for development of novel antitubercular agents

Tuberculosis (TB) remains the leading cause of mortality due to a bacterial pathogen, Mycobacterium tuberculosis. However, no new classes of drugs for TB have been developed in the past 30 years. Therefore there is an urgent need to develop faster acting and effective new antitubercular agents, preferably belonging to new structural classes, to better combat TB, including MDR-TB, to shorten the duration of current treatment to improve patient compliance, and to provide effective treatment of latent tuberculosis infection. The enzymes in the shikimate pathway are potential targets for development of a new generation of antitubercular drugs. The shikimate pathway has been shown by disruption of aroK gene to be essential for the Mycobacterium tuberculosis. The shikimate kinase (SK) catalyses the phosphorylation of the 3-hydroxyl group of shikimic acid (shikimate) using ATP as a co-substrate. SK belongs to family of nucleoside monophosphate (NMP) kinases. The enzyme is an alpha/beta protein consisting of a central sheet of five parallel beta-strands flanked by alpha-helices. The shikimate kinases are composed of three domains: Core domain, Lid domain and Shikimate-binding domain. The Lid and Shikimate-binding domains are responsible for large conformational changes during catalysis. More recently, the precise interactions between SK and substrate have been elucidated, showing the binding of shikimate with three charged residues conserved among the SK sequences. The elucidation of interactions between MtSK and their substrates is crucial for the development of a new generation of drugs against tuberculosis through rational drug design.

Potential scenarios for Internet use in the mathematics classroom

Research on the influence of multiple representations in mathematics education gained new momentum when personal computers and software started to become available in the mid-1980s. It became much easier for students who were not fond of algebraic representations to work with concepts such as function using graphs or tables. Research on how students use such software showed that they shaped the tools to their own needs, resulting in an intershaping relationship in which tools shape the way students know at the same time the students shape the tools and influence the design of the next generation of tools. This kind of research led to the theoretical perspective presented in this paper: knowledge is constructed by collectives of humans-with-media. In this paper, I will discuss how media have shaped the notions of problem and knowledge, and a parallel will be developed between the way that software has brought new possibilities to mathematics education and the changes that the Internet may bring to mathematics education. This paper is, therefore, a discussion about the future of mathematics education. Potential scenarios for the future of mathematics education, if the Internet becomes accepted in the classroom, will be discussed. © FIZ Karlsruhe 2009.

In vivo evaluation of the genetic toxicity of Rubus niveus Thunb. (Rosaceae) extract and initial screening of its potential chemoprevention against doxorubicin-induced DNA damage

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Non-centrosymmetric crystals of new N-benzylideneaniline derivatives as potential materials for non-linear optics

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)