Increased expression of interleukin-22 in patients with giant cell arteritis

GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis

Effects of the passage of Comet C/2013 A1 (Siding Spring) observed by the Shallow Radar (SHARAD) on Mars reconnaissance orbiter

The close passage of Comet C/2013 A1 (Siding Spring) to Mars provided a unique opportunity to observe the interaction of cometary materials with the Martian ionosphere and atmosphere using the sounding radar SHARAD (SHAllow RADar) aboard Mars Reconnaissance Orbiter. In two nightside observations, acquired in the 10 h following the closest approach, the SHARAD data reveal a significant increase of the total electron content (TEC). The observed TEC values are typical for daylight hours just after dawn or before sunset but are unprecedented this deep into the night. Results support two predictions indicating that cometary pickup O+ ions, or ions generated from the ablation of cometary dust, are responsible for the creation of an additional ion layer

Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis

Objectives To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Methods Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. Results ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-ß, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. Conclusions ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised

Reversal of gastrointestinal carcinoma-induced immunosuppression and induction of antitumoural immunity by a combination of cyclophosphamide and gene transfer of IL-12

Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC.Fil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Ingolotti, Mariana. Universidad Austral; ArgentinaFil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Bayo Fina, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Atorrasagasti, María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Espinoza, Jaime A.. Universidad Adolfo Ibañez; Chile. Universidad de La Frontera; ChileFil: Gidekel, Manuel. Universidad Adolfo Ibañez; ChileFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Matar, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentin

Properties of recombinant human cytosolic sialidase HsNEU2. The enzyme hydrolyzes monomerically dispersed GM1 ganglioside molecules

Recombinant human cytosolic sialidase (HsNEU2), expressed in Escherichia coli, was purified to homogeneity, and its substrate specificity was studied. HsNEU2 hydrolyzed 4-methylumbelliferyl alpha-NeuAc, alpha 2-->3 sialyllactose, glycoproteins (fetuin, alpha-acid glycoprotein, transferrin, and bovine submaxillary gland mucin), micellar gangliosides GD1a, GD1b, GT1b, and alpha 2-->3 paragloboside, and vesicular GM3. alpha 2-->6 sialyllactose, colominic acid, GM1 oligosaccharide, whereas micellar GM2 and GM1 were resistant. The optimal pH was 5.6, kinetics Michaelis-Menten type, V(max) varying from 250 IU/mg protein (GD1a) to 0.7 IU/mg protein (alpha(1)-acid glycoprotein), and K(m) in the millimolar range. HsNEU2 was activated by detergents (Triton X-100) only with gangliosidic substrates; the change of GM3 from vesicular to mixed micellar aggregation led to a 8.5-fold V(max) increase. HsNEU2 acted on gangliosides (GD1a, GM1, and GM2) at nanomolar concentrations. With these dispersions (studied in detailed on GM1), where monomers are bound to the tube wall or dilutedly associated (1:2000, mol/mol) to Triton X-100 micelles, the V(max) values were 25 and 72 microIU/mg protein, and K(m) was 10 and 15 x 10(-9) m, respectively. Remarkably, GM1 and GM2 were recognized only as monomers. HsNEU2 worked at pH 7.0 with an efficiency (compared with that at pH 5.6) ranging from 4% (on GD1a) to 64% (on alpha(1)-acid glycoprotein), from 7% (on GD1a) to 45% (on GM3) in the presence of Triton X-100, and from 30 to 40% on GM1 monomeric dispersion. These results show that HsNEU2 differentially recognizes the type of sialosyl linkage, the aglycone part of the substrate, and the supramolecular organization (monomer/micelle/vesicle) of gangliosides. The last ability might be relevant in sialidase interactions with gangliosides under physiological conditions

Time-stability of a Single-crystal Diamond Detector for fast neutron beam diagnostic under alpha and neutron irradiation

Single-crystal Diamond Detectors (SDDs), due to their good charge carrier transport properties, low leakage and therefore good energy resolution, are good candidates for fast neutron measurement on pulsed spallation sources and fusion plasma experiments. Moreover, diamonds are known to be resistant to neutron irradiation. Nevertheless, measurements show transient effects during irradiation with ionizing particles, as the alpha particle calibration sources. The decrease of the detector counting rate of a counting chain and the pulse height are interpreted as due to a charge trapping inside the detector, which modifies the drift electric field. These instabilities are strongly dependent on the specific type of the interaction. Measurements have been carried out with both alpha particles in the laboratory and neutrons at the ISIS neutron spallation source. We show that these polarization effects are not permanent: the detector performances can be restored by simply inverting the detector bias high voltage. Prime Novelty Statement The measurements described in the paper were performed in order to study the polarization effect in Single-crystal Diamond Detector. This effect was observed under alpha particle and neutron irradiation. With the Transient Current Technique an interpretation of the effect is given

An overview of the design, construction and performance of large area triple-GEM prototypes for future upgrades of the CMS forward muon system

GEM detectors are used in high energy physics experiments given their good spatial resolution, high rate capability and radiation hardness. An international collaboration is investigating the possibility of covering the 1.6 < vertical bar eta vertical bar < 2.4 region of the CMS muon endcaps with large-area triple-GEM detectors. The CMS high-eta area is actually not fully instrumented, only Cathode Strip Chamber (CSC) are installed. The vacant area presents an opportunity for a detector technology able to to cope with the harsh radiation environment; these micropattern gas detectors are an appealing option to simultaneously enhance muon tracking and triggering capabilities in a future upgrade of the CMS detector. A general overview of this feasibility study is presented. Design and construction of small (10cm x 10cm) and full-size trapezoidal (1m x 0.5m) triple-GEM prototypes is described. Results from measurements with x-rays and from test beam campaigns at the CERN SPS is shown for the small and large prototypes. Preliminary simulation studies on the expected muon reconstruction and trigger performances of this proposed upgraded muon system are reported

Depositional architecture of a mixed travertine-terrigenous system in a fault-controlled continental extensional basin (Messinian, Southern Tuscany, Central Italy)

The extensional Neogene Albegna Basin (Southern Tuscany, Italy) includes several thermogene travertine units dating from the Miocene to Holocene time. During the late Miocene (Messinian), a continental fault-controlled basin (of nearly 500-km2 width) was filled by precipitated travertine and detrital terrigenous strata, characterized by a wedge-shaped geometry that thinned northward, with a maximum thickness of nearly 70m. This mixed travertine-terrigenous succession was investigated in terms of lithofacies types, depositional environment and architecture and the variety of precipitated travertine fabrics. Deposited as beds with thickness ranging from centimetres to a few decimetres, carbonates include nine travertine facies types: F1) clotted peloidal micrite and microsparite boundstone, F2) raft rudstone/floatstone, F3) sub-rounded radial coated grain grainstone, F4) coated gas bubble boundstone, F5) crystalline dendrite cementstone, F6) laminated boundstone, F7) coated reed boundstone and rudstone, F8) peloidal skeletal grainstone and F9) calci-mudstone and microsparstone. Beds of terrigenous deposits with thickness varying from a decimetre to > 10 m include five lithofacies: F10) breccia, F11) conglomerate, F12) massive sandstone, F13) laminated sandstone and F14) claystone. The succession recorded the following three phases of evolution of the depositional setting: 1) At the base, a northward-thinning thermogene travertine terraced slope (Phase I, travertine slope lithofacies association, F1-F6) developed close to the extensional fault system, placed southward with respect to the travertine deposition. 2) In Phase II, the accumulation of travertines was interrupted by the deposition of colluvial fan deposits with a thickness of several metres (colluvial fan lithofacies association, F10 and F12), which consisted of massive breccias, adjacent to the alluvial plain lithofacies association (F11-F14) including massive claystone and sandstone and channelized conglomerates. Travertine lenses, of 2-3-m thickness, appeared intermittently alternating with the colluvial fan breccias. 3) In the third phase, the filled fault-controlled basin evolved into an alluvial plain with ponds rich in coated reed travertines, which record the influence of freshwater (travertine flat lithofacies association, F7-F9). This study shows the stratigraphic architecture and sedimentary evolution of a continental succession, wherein the hydrothermal activity and consequent travertine precipitation were driven by the extensional tectonic regime, with faults acting as fluid paths for the thermal water. Fault activity created the accommodation space for travertine and colluvial fan accumulation. Erosion of the uplifted footwall blocks provided the source of sediments for the colluvial fan breccias, which alternated with the thermogene travertine precipitation. Climatic oscillations might have led to the recharge of the aquifer that fed the hydrothermal vents. The studied continental succession in an extensional basin provides valuable information about the interplay between thermogene travertine and alluvial/colluvial deposition, which in turn might improve the understanding of similar fault-controlled continental depositional systems in outcrops and the subsurface