Leukemia virus long terminal repeat activates NFκB pathway by a TLR3-dependent mechanism

AbstractThe long terminal repeat (LTR) region of leukemia viruses plays a critical role in tissue tropism and pathogenic potential of the viruses. We have previously reported that U3-LTR from Moloney murine and feline leukemia viruses (Mo-MuLV and FeLV) upregulates specific cellular genes in trans in an integration-independent way. The U3-LTR region necessary for this action does not encode a protein but instead makes a specific RNA transcript. Because several cellular genes transactivated by the U3-LTR can also be activated by NFκB, and because the antiapoptotic and growth promoting activities of NFκB have been implicated in leukemogenesis, we investigated whether FeLV U3-LTR can activate NFκB signaling. Here, we demonstrate that FeLV U3-LTR indeed upregulates the NFκB signaling pathway via activation of Ras-Raf-IκB kinase (IKK) and degradation of IκB. LTR-mediated transcriptional activation of genes did not require new protein synthesis suggesting an active role of the LTR transcript in the process. Using Toll-like receptor (TLR) deficient HEK293 cells and PKR−/− mouse embryo fibroblasts, we further demonstrate that although dsRNA-activated protein kinase R (PKR) is not necessary, TLR3 is required for the activation of NFκB by the LTR. Our study thus demonstrates involvement of a TLR3-dependent but PKR-independent dsRNA-mediated signaling pathway for NFκB activation and thus provides a new mechanistic explanation of LTR-mediated cellular gene transactivation

Genetic and phenotype analysis of Borrelia valaisiana sp.nov. (Borrelia genomic groups VS116 and M19)

To clarify the taxonomic status of two recently described Borrelia genomic groups, groups VS116 and M19, three group VS116 strains and eight group M19 strains isolated from Ixodes ricinus ticks in Switzerland, The Netherlands, and the United Kingdom were characterized. PCR-restriction fragment length polymorphism (RFLP) analysis of the 5S-23S intergenic spacer amplicon, rRNA gene restriction analysis, 16S rRNA gene sequence analysis, randomly amplified polymorphic DNA (RAPD) fingerprinting, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and immunoblotting with monoclonal antibodies were used for genetic and phenotypic analysis. The PCR-RFLP and RAPD patterns of three group VS116 strains and eight group M19 strains were identical but differed from those of Borrelia burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii, and Borrelia japonica. DNAs from all group VS116 and M19 strains yielded three fragments (6.9, 3.2, and 1.4 kb) and four fragments (2.1, 1.2, 0.8, and 0.6 kb) after digestion with EcoRV and HindIII, respectively, hybridizing with an Escherichia coli 16S + 23S cDNA probe. The SDS-PAGE protein profiles of group VS116 and M19 strains were heterogeneous. Phylogenetic analysis of the partial 16S rRNA gene sequences showed that group VS116 and M19 spirochetes were members of a Borrelia species distinct from previously characterized members of the genus Borrelia. Based on our present study and data from previous DNA-DNA hybridizations, a new Borrelia species, Borrelia valaisiana sp.nov., in the B. burgdorferi complex, is proposed. Strain VS116 is the type strain of this new specie

Дослідження підходів до оцінки стану конкурентоспроможності підприємств

Мета статті – наведення підходів до оцінки стану конкурентоспроможності підприємств

Charge redistribution at Pd surfaces: ab initio grounds for tight-binding interatomic potentials

A simplified tight-binding description of the electronic structure is often necessary for complex studies of surfaces of transition metal compounds. This requires a self-consistent parametrization of the charge redistribution, which is not obvious for late transition series elements (such as Pd, Cu, Au), for which not only d but also s-p electrons have to be taken into account. We show here, with the help of an ab initio FP-LMTO approach, that for these elements the electronic charge is unchanged from bulk to the surface, not only per site but also per orbital. This implies different level shifts for each orbital in order to achieve this orbital neutrality rule. Our results invalidate any neutrality rule which would allow charge redistribution between orbitals to ensure a common rigid shift for all of them. Moreover, in the case of Pd, the power law which governs the variation of band energy with respect to coordination number, is found to differ significantly from the usual tight-binding square root.Comment: 6 pages, 2 figures, Latex; Phys.Rev. B 56 (1997

Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals

The aim of this study was to identify retrospectively trends in fungal bloodstream infections in The Netherlands in the period from 1987 to 1995. Results of over 395,000 blood cultures from five Dutch university hospitals were evaluated. Overall, there were more than 12 million patient days of care during the nine-year study period. The rate of candidemia doubled in the study period, reaching an incidence of 0.71 episodes per 10,000 patient days in 1995. The general increase in candidemia was paralleled by an increase in non-Candida albicans bloodstream infections, mainly due toCandida glabrata. However, more than 60% of the infections were caused byCandida albicans. Fluconazoleresistant species such asCandida krusei did not emerge during the study period. The increasing rate of candidemia found in Dutch university hospitals is similar to the trend observed in the USA, but the rate is lower and the increase is less pronounced

Nonperturbative Evaluation of the Sphaleron Transition Rate

We review nonperturbative calculations of the rate of sphaleron transitions on the lattice in $1+1$-dimensional field theories and introduce a way to perform the gauge-invariant Gibbs averages in the classical non-Abelian Higgs theories.Comment: 4 pages, uuencoded Postscript file. Talk given at NATO Advanced Research Workshop on Electroweak Physics and the Early Universe, Sintra, Portugal, 23-25 March 199

Type II compactifications on manifolds with SU(2) x SU(2) structure

We study compactifications of type II theories on SU(2) x SU(2) structure manifolds to six, five and four spacetime dimensions. We use the framework of generalized geometry to describe the NS-NS sector of such compactifications and derive the structure of their moduli spaces. We show that in contrast to SU(3) x SU(3) structure compactifications, there is no dynamical SU(2) x SU(2) structure interpolating between an SU(2) structure and an identity structure. Furthermore, we formulate type II compactifications on SU(2) x SU(2) structures in the context of exceptional generalized geometry which makes the U-duality group manifest and naturally incorporates the scalar degrees of freedom arising in the Ramond-Ramond sector. Via this formalism we derive the structure of the moduli spaces as it is expected from N=4 supergravity.Comment: 69 pages, v2 published versio