Immunoglobulin A1 Protease, an Exoenzyme of Pathogenic Neisseriae, Is a Potent Inducer of Proinflammatory Cytokines

A characteristic of human pathogenic Neisseriae is the production and secretion of an immunoglobulin (Ig)A1-specific serine protease (IgA1 protease) that cleaves preferentially human IgA1 and other target proteins. Here we show a novel function for native IgA1 protease, i.e., the induction of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 from peripheral blood mononuclear cells. The capacity of IgA1 protease to elicit such cytokine responses in monocytes was enhanced in the presence of T lymphocytes. IgA1 protease did not induce the regulatory cytokine IL-10, which was, however, found in response to lipopolysaccharide and phytohemagglutinin. The immunomodulatory effects caused by IgA1 protease require a native form of the enzyme, and denaturation abolished cytokine induction. However, the proteolytic activity is not required for the cytokine induction by IgA1 protease. Our results indicate that IgA1 protease exhibits important immunostimulatory properties and may contribute substantially to the pathogenesis of neisserial infections by inducing large amounts of TNF-α and other proinflammatory cytokines. In particular, IgA1 protease may represent a key virulence determinant of bacterial meningitis

Lipoplex-functionalized thin-film surface coating based on extracellular matrix components as local gene delivery system to control osteogenic stem cell differentiation

A gene-activated surface coating is presented as a strategy to design smart biomaterials for bone tissue engineering. The thin-film coating is based on polyelectrolyte multilayers composed of collagen I and chondroitin sulfate, two main biopolymers of the bone extracellular matrix, which are fabricated by layer-by-layer assembly. For further functionalization, DNA/lipid-nanoparticles (lipoplexes) are incorporated into the multilayers. The polyelectrolyte multilayer fabrication and lipoplex deposition are analyzed by surface sensitive analytical methods that demonstrate successful thin-film formation, fibrillar structuring of collagen, and homogenous embedding of lipoplexes. Culture of mesenchymal stem cells on the lipoplex functionalized multilayer results in excellent attachment and growth of them, and also, their ability to take up cargo like fluorescence-labelled DNA from lipoplexes. The functionalization of the multilayer with lipoplexes encapsulating DNA encoding for transient expression of bone morphogenetic protein 2 induces osteogenic differentiation of mesenchymal stem cells, which is shown by mRNA quantification for osteogenic genes and histochemical staining. In summary, the novel gene-functionalized and extracellular matrix mimicking multilayer composed of collagen I, chondroitin sulfate, and lipoplexes, represents a smart surface functionalization that holds great promise for tissue engineering constructs and implant coatings to promote regeneration of bone and other tissues.publishe

Deformation analysis of a metropolis from C- to X-band PSI: proof-of-concept with Cosmo-Skymed over Rome, Italy

Stability of monuments and subsidence of residential quarters in Rome (Italy) are depicted based on geospatial analysis of more than 310,000 Persistent Scatterers (PS) obtained from Stanford Method for Persistent Scatterers (StaMPS) processing of 32 COSMO-SkyMed 3m-resolution HH StripMap ascending mode scenes acquired between 21 March 2011 and 10 June 2013. COSMO-SkyMed PS densities and associated displacement velocities are compared with almost 20 years of historical C-band ERS- 1/2, ENVISAT and RADARSAT-1/2 imagery. Accounting for differences in image processing algorithms and satellite acquisition geometries, we assess the feasibility of ground motion monitoring in big cities and metropolitan areas by coupling newly acquired and legacy SAR in full time series. Limitations and operational benefits of the transition from medium resolution C-band to high resolution X-band PS data are discussed, alongside the potential impact on the management of expanding urban environments

Low collectivity of the 2(1)(+) state of Po-212

International audienceThe lifetime of the $2^+_1$ state of $^{212}$Po was measured in the $^{208}$Pb($^{12}$C,$^{8}$Be)$^{212}$Po transfer reaction by γ -ray spectroscopy employing the recoil distance Doppler shift (RDDS) method. The derived absolute B(E2) value of 2.6(3)W.u. indicates a low collectivity and contradicts previous claims of α-cluster components in the structure of the $2^+_1$ state. It is demonstrated that a consistent description of the properties of the $2^+_1$−$4^+_1$−$6^+_1$−$8^+_1$ sequence in $^{212}$Po cannot be achieved in the framework of a single-j shell-model calculation, either. This puzzle is traced to the properties of the seniority-2 configurations in $^{210}$Pb and $^{210}$Po

Low collectivity of the first 2⁺ states of ²¹²,²¹⁰Po

The lifetimes of the first 2⁺ excited states of ²¹²,²¹⁰Po were measured in two transfer reactions ²⁰⁸Pb(¹²C,⁸Be)²¹²Po and ²⁰⁸Pb(¹²C,¹⁰Be)²¹⁰Po by the Recoil Distance Doppler Shift (RDDS) method and by the Doppler Shift Attenuation method (DSAM), respectively. The derived absolute B(E2) values of 2.6(3) W.u. for ²¹²Po and 1.83(28) W.u. for ²¹⁰Po indicate low collectivity. It is shown that the properties of the yrast 2₁⁺, 4₁⁺, 6₁⁺ and 8₁⁺ states in both nuclei cannot be described consistently in the framework of nuclear shell models. It is also demonstrated in the case of ²¹⁰Po that Quasi-particle Phonon Model (QPM) calculations cannot overcome this problem thus indicating the existence of a peculiarity which is neglected in both theoretical approaches