Sialic acid transporter NanT participates in Tannerella forsythia biofilm formation and survival on epithelial cells

Tannerella forsythia is a periodontal pathogen implicated in periodontitis. This gram-negative pathogen depends on exogenous peptidoglycan amino sugar N-acetylmuramic acid (NAM) for growth. In the biofilm state the bacterium can utilize sialic acid (Neu5Ac) instead of NAM to sustain its growth. Thus, the sialic acid utilization system of the bacterium plays a critical role in the growth and survival of the organism in the absence of NAM. We sought the function of a T. forsythia gene annotated as nanT coding for an inner-membrane sugar transporter located on a sialic acid utilization genetic cluster. To determine the function of this putative sialic acid transporter, an isogenic nanT-deletion mutant generated by allelic replacement strategy was evaluated for biofilm formation on NAM or Neu5Ac, and survival on KB epithelial cells. Moreover, since T. forsythia forms synergistic biofilms with Fusobacterium nucleatum, co-biofilm formation activity in mixed culture and sialic acid uptake in culture were also assessed. The data showed that the nanT-inactivated mutant of T. forsythia was attenuated in its ability to uptake sialic acid. The mutant formed weaker biofilms compared to the wild-type strain in the presence of sialic acid and as co-biofilms with F. nucleatum. Moreover, compared to the wild-type T. forsythia nanT-inactivated mutant showed reduced survival when incubated on KB epithelial cells. Taken together, the data presented here demonstrate that NanT-mediated sialic transportation is essential for sialic acid utilization during biofilm growth and survival of the organism on epithelial cells and implies sialic acid might be key for its survival both in subgingival biofilms and during infection of human epithelial cells in vivo

Численная гидродинамическая модель атмосферной дисперсии загрязнений вокруг зданий

The computational fluid mechanics model of is atmospheric dispersion in the vicinity of buildings is developed. The validation of model against field experiment was performed. The application of model to problem of estimation of concentration near contaminated buildings located at the territory of Pridneprovsky Chemical Plant is presented

Нормування полів розсіювання координованих розмірів глибоких отворів на етапі технологічної підготовки виробництва

Оцінювання якості глибоких координованих отворів на етапі проектування, тобто на етапі прийняття рішення про можливість забезпечення їх повної взаємозамінності, враховуючи існуюче обладнання, інструмент, матеріал та оснащення являється актуальною задачею. Рішення таких питань потребує комплексу теоретичних і експериментальних досліджень. Під координованими (взаємопов'язаними) отворами вважаємо групи отворів, в яких задані міжосьові розміри або розміри від базової поверхні до осей отвору. Під точністю розмірів координованих отворів мається на увазі точність відстаней між отвором і базою та між двома або декількома отворами (позиційне відхилення). Вимоги до точності отворів задаються кресленнями

M5-brane geometries, T-duality and fluxes

We describe a duality relation between configurations of M5-branes in M-theory and type IIB theory on Taub-NUT geometries with NSNS and RR 3-form field strength fluxes. The flux parameters are controlled by the angles between the M5-brane and the (T)duality directions. For one M5-brane, the duality leads to a family of supersymmetric flux configurations which interpolates between imaginary self-dual fluxes and fluxes similar to the Polchinski-Strassler kind. For multiple M5-branes, the IIB configurations are related to fluxes for twisted sector fields in orbifolds. The dual M5-brane picture also provides a geometric interpretation for several properties of flux configurations (like the supersymmetry conditions, their contribution to tadpoles, etc), and for many non-trivial effects in the IIB side. Among the latter, the dielectric effect for probe D3-branes is dual to the recombination of probe M5-branes with background ones; also, a picture of a decay channel for non-supersymmetric fluxes is suggested.Comment: 30 pages, 3 figure

N=1 effective potential from dual type-IIA D6/O6 orientifolds with general fluxes

We consider N=1 compactifications of the type-IIA theory on the T6/(Z2xZ2) orbifold and O6 orientifold, in the presence of D6-branes and general NSNS, RR and Scherk-Schwarz geometrical fluxes. Introducing a suitable dual formulation of the theory, we derive and solve the Bianchi identities, and show how certain combinations of fluxes can relax the constraints on D6-brane configurations coming from the cancellation of RR tadpoles. We then compute, via generalized dimensional reduction, the N=1, D=4 effective potential for the seven main moduli, and comment on the relation with truncated N=4 gaugings. As a byproduct, we obtain a general geometrical expression for the superpotential. We finally identify a family of fluxes, compatible with all Bianchi identities, that perturbatively stabilize all seven moduli in supersymmetric AdS4.Comment: 19 pages, no figures, JHEP3 LaTeX. Published versio

D terms from D-branes, gauge invariance and moduli stabilization in flux compactifications

We elucidate the structure of D terms in N=1 orientifold compactifications with fluxes. As a case study, we consider a simple orbifold of the type-IIA theory with D6-branes at angles, O6-planes and general NSNS, RR and Scherk-Schwarz geometrical fluxes. We examine in detail the emergence of D terms, in their standard supergravity form, from an appropriate limit of the D-brane action. We derive the consistency conditions on gauged symmetries and general fluxes coming from brane-localized Bianchi identities, and their relation with the Freed-Witten anomaly. We extend our results to other N=1 compactifications and to non-geometrical fluxes. Finally, we discuss the possible role of U(1) D terms in the stabilization of the untwisted moduli from the closed string sector.Comment: 1+31 pages, 1 figur

Evidence for a novel Carbohydrate Binding Module (CBM) of Tannerella forsythia NanH sialidase, key to interactions at the host-pathogen interface

Bacterial sialidases cleave terminal sialic acid from a variety of host glycoproteins, and contribute to survival and growth of many human-dwelling bacterial species, including various pathogens.Tannerella forsythia, an oral, Gram-negative, fastidious anaerobe, is a key organism in periodontal disease, and possesses a dedicated sialic acid utilisation and scavenging (nan) operon, including NanH sialidase. Here, we describe biochemical characterisation of recombinant NanH, including its action on host-relevant sialoglycans such as sialyl Lewis A and sialyl Lewis X (SLeA/X), and on human cell-attached sialic acids directly, uncovering that it is a highly active broad specificity sialidase. Furthermore, theN-terminal domain of NanH was hypothesised and proven to be capable of binding to a range of sialoglycans and non-sialylated derivatives withKdin the micromolar range, as determined by steady-state tryptophan fluorescence spectroscopy, but it has no catalytic activity in isolation from the active site. We consider this domain to represent the founding member of a novel subfamily of Carbohydrate Binding Module (CBM), involved in glycosidase-ligand binding. In addition, we created a catalytically inactive version of the NanH enzyme (FRIP→YMAP) that retained its ability to bind sialic acid-containing ligands and revealed for the first time that binding activity of a CBM is enhanced by association with the catalytic domain. Finally, we investigated the importance of Lewis-type sialoglycans onT. forsythia-host interactions, showing that nanomolar amounts of SLeA/Xwere capable of reducing invasion of oral epithelial cells byT. forsythiasuggesting that these are key ligands for bacterial-cellular interactions during periodontal disease

Flux-induced SUSY-breaking soft terms on D7-D3 brane systems

We study the effect of RR and NSNS 3-form fluxes on the effective action of the worldvolume fields of Type IIB D7/D3-brane configurations. The D7-branes wrap 4-cycles on a local Calabi-Yau geometry. This is an extension of previous work on hep-th/0311241, where a similar analysis was applied to the case of D3-branes. Our present analysis is based on the D7- and D3-brane Dirac-Born-Infeld and Chern-Simons actions, and makes full use of the R-symmetries of the system, which allow us to compute explicitly results for the fields lying at the D3-D7 intersections. A number of interesting new properties appear as compared to the simpler case of configurations with only D3-branes. As a general result one finds that fluxes stabilize some or all of the D7-brane moduli. We argue that this is important for the problem of stabilizing Kahler moduli through non-perturbative effects in KKLT-like vacua. We also show that (0,3) imaginary self-dual fluxes, which lead to compactifications with zero vacuum energy, give rise to SUSY-breaking soft terms including gaugino and scalar masses, and trilinear terms. Particular examples of chiral MSSM-like models of this class of vacua, based on D3-D7 brane systems at orbifold singularities are presented.Comment: 58 pages, no figures; v2: numerical factor in section 7.2 correcte