Tobacco Upregulates P. gingivalis Fimbrial Proteins Which Induce TLR2 Hyposensitivity

Tobacco smokers are more susceptible to periodontitis than non-smokers but exhibit reduced signs of clinical inflammation. The underlying mechanisms are unknown. We have previously shown that cigarette smoke extract (CSE) represents an environmental stress to which P. gingivalis adapts by altering the expression of several virulence factors - including major and minor fimbrial antigens (FimA and Mfa1, respectively) and capsule - concomitant with a reduced pro-inflammatory potential of intact P. gingivalis.We hypothesized that CSE-regulation of capsule and fimbrial genes is reflected at the ultrastructural and functional levels, alters the nature of host-pathogen interactions, and contributes to the reduced pro- inflammatory potential of smoke exposed P. gingivalis. CSE induced ultrastructural alterations were determined by electron microscopy, confirmed by Western blot and physiological consequences studied in open-flow biofilms. Inflammatory profiling of specific CSE-dysregulated proteins, rFimA and rMfa1, was determined by quantifying cytokine induction in primary human innate and OBA-9 cells. CSE up-regulates P. gingivalis FimA at the protein level, suppresses the production of capsular polysaccharides at the ultrastructural level, and creates conditions that promote biofilm formation. We further show that while FimA is recognized by TLR2/6, it has only minimal inflammatory activity in several cell types. Furthermore, FimA stimulation chronically abrogates the pro-inflammatory response to subsequent TLR2 stimulation by other TLR-2-specific agonists (Pam3CSK4, FSL, Mfa1) in an IkappaBalpha- and IRAK-1-dependent manner.These studies provide some of the first information to explain, mechanistically, how tobacco smoke changes the P. gingivalis phenotype in a manner likely to promote P. gingivalis colonization and infection while simultaneously reducing the host response to this major mucosal pathogen

Religion and discrimination in the workplace in Turkey

Discrimination based on grounds such as gender or disability has been widely studied in recent research, but the issue of discrimination on grounds of religion or belief has proven to be far less traceable, less studied and more ideologically charged. In Turkey, a state discourse stating that 99% of the population is comprised of Muslim citizens conceals religious diversity in the country. Our contribution focuses on two main manifestations of discrimination within this framework: discrimination on the basis of wearing a headscarf in (or outside) the workplace and discrimination based on religious affiliation, specifically beliefs other than the majority Sunni-Hanefite Islam, in particular Alevis and non-Muslim minorities. Since there are a number of recent studies dealing with the issue of the headscarf, our primary focus will be on the latter topic. Our findings suggest that in the Turkish case, while the headscarf has dominated the issue of discrimination on religious grounds, a more egregious discrimination takes place against members of belief groups other than the Sunni-Hanefite majority. The issue of discrimination in the Turkish workplace on grounds of religion or belief presents interesting questions and challenges. Firstly, in a non-litigate society, discrimination on the basis of religious affiliation is hard to track and quantify. Secondly, recognition of difference does not always lead to pluralism

Computational Studies of Crystal Structure and Bonding

A review. The anal., prediction, and control of crystal structures are frontier topics in present-day research in view of their importance for materials science, pharmaceutical sciences, and many other chem. processes. Computational crystallog. is nowadays a branch of the chem. and physicals sciences dealing with the study of inner structure, intermol. bonding, and cohesive energies in crystals. This chapter, mainly focused on org. compds., first reviews the current methods for x-ray diffraction data treatment, and the new tools available both for quant. statistical anal. of geometries of intermol. contacts using crystallog. databases and for the comparison of crystal structures to detect similarities or differences. Quantum chem. methods for the evaluation of intermol. energies are then reviewed in detail: atoms-in-mols. and other d.-based methods, ab initio MO theory, perturbation theory methods, dispersion-supplemented DFT, semiempirical methods and, finally, entirely empirical atom-atom force fields. The superiority of analyses based on energy over analyses based on geometry is highlighted, with caveats on improvised definitions of some intermol. chem. bonds that are in fact no more than fluxional approach preferences. A perspective is also given on the present status of computational methods for the prediction of crystal structures: in spite of great steps forward, some fundamental obstacles related to the kinetic-thermodn. dilemma persist. Mol. dynamics and Monte Carlo methods for the simulation of crystal structures and of phase transitions are reviewed. These methods are still at a very speculative stage, but hold promise for substantial future developments