AB0171 THE IMMUNOMODULATORY AND ANTI-INFLAMMATORY EFFECTS OF BOSENTAN IN SYSTEMIC SCLEROSIS

Background:Plasma endothelin-1 (ET-1) levels are increased in patients with systemic sclerosis (SSc), playing a central role in the development of fibrosis, vasoconstriction and inflammation1. While the beneficial effect of Bosentan, the endothelin receptor antagonists, have been demonstrated on vasoconstriction and fibrosis, its potential anti-inflammatory and immunomodulatory activity needs to be further investigated.Objectives:To assess whether Bosentan can modulate the gene expression profile of immune cells in sample of patients with limited and diffuse SSc and active digital ulcers.Methods:We enrolled 34 patients affected by SSc. Twenty-four patients were affected by limited SSc and 12 by diffuse SSc. Blood samples were collected from patients before and after 24 weeks of treatment with Bosentan, in the absence of immunosuppressive therapies. All patients received Bosentan 125 mg twice a day for 24 weeks. Gene expression profiles were assessed by GeneChip® Human Transcriptome Array 2.0 microarray technology. Significantly (p-value1.5) expressed genes pre/post treatment were obtained by paired t-statistics, as implemented in Partek Genomics Suite ver. 6.6. These genes were subjected to functional enrichment analysis by Ingenuity Pathway Analysis. The effect of Bosentan on patients was studied on the "diffuse" and "limited" sub-cohorts, individually, as well as on the whole cohort.Results:Contrary to the limited cohort where differentially expressed genes resulted to be all non-coding genes which are almost all over-expressed before treatment, the diffuse cohort was characterized by 19 differentially expressed genes that enrich biological functions and pathways related to the immune system and its organic response (in particular T-cells). Comparing the limited to the diffuse cohort, pre- and post- treatment, a distinct genetic fingerprint emerges, that characterizes the response to Bosentan by the latter cohort as increased apoptosis of lymphocytes (z-score=3.28) and a decreased quantity of antigen presenting cells (from z-score=1.06 (pre) to -0.75 (post)).Conclusion:The presence of an inflammatory microenvironment, as occur in SSc, influence the relative expression of ET-1 receptors on immune cells, which in turn further contribute to the amplification of cellular responses to inflammation. The observed difference response to therapy between the two cohorts of patients was attributed to influence of ET-1 levels on the relative expression of ET-1 receptors on immune cells surface. Interestingly Bosentan, beside the already-known effect on promoting antigen presenting cells apoptosis, seem to exert its immunomodulatory activity also by deregulating functions that mainly involves the T cells and by promoting their apoptosis, which in turn reflect also its anti-inflammatory proprieties.References:[1]Tinazzi E, Puccetti A, Patuzzo G, et al. Endothelin receptors expressed by immune cells are involved in modulation of inflammation and in fibrosis: relevance to the pathogenesis of systemic sclerosis. J Immunol Res. 2015;2015:147616.Disclosure of Interests:None declare

Chemical and physical characterization of thermal aggregation of model proteins modulated by zinc (II) and copper (II) ions.

BACKGROUND: Metal ions are implicated in protein aggregation processes of several neurodegenerative pathologies, where the protein deposition occurs, and in the biotechnology field like the food technology where many processes in food manufacturing are based on thermal treatments. OBJECTIVE: The influence of Cu2+ or Zn2+ ions on the thermal aggregation process of Bovine beta-lactoglobulin (BLG) and Bovine Serum Albumin (BSA), two protein models, was studied with the aim of delineating the role of these ions in the protein aggregation kinetics and to clarify the related molecular mechanisms. METHODS: The protein structure changes were monitored by Raman spectroscopy, whereas the aggregate growth was followed by Dynamic Light Scattering measurements. RESULTS: Both metal ions are able to favour the BLG aggregation, whereas only Zn2+ ions have a promoter effect on the thermal aggregation of BSA. The reason of this different behaviour is that the BLG aggregation evolution is manly affected by the redistribution of charges, whereas that of BSA by the metal coordination binding which depends on metal. CONCLUSIONS: Raman spectroscopy, combined with dynamic light scattering experiments, was very useful in identifying the role played by Cu2+ and Zn2+ on the aggregation pathways of BLG and BSA. The results provide evidence for the role of histidine residues both in the redistribution of charges and in the two modes of metal binding that take place in BLG- and BSA-containing systems, respectively

The role of two-stage phase formation for the solid-state runaway reaction in Al/Ni reactive multilayers

While extensively studied for heating rates below 1.7 K/s and above 1000 K/s, the solid-state phase transformations in Al/Ni reactive multilayers have not been examined at intermediate heating rates between 100 K/s and 1000 K/s. Combined nanocalorimetry and time-resolved synchrotron x-ray diffraction studies are utilized to address this range of heating rates for multilayers with an overall composition of 10 at. % Ni and a bilayer thickness of 220 nm. It was found that a two-stage phase formation of Al$_{3}$Ni proceeds up to a heating rate of 1000 K/s. The two growth stages occur in the solid-state and are kinetically separated. The activation energy of the first growth stage is determined to be 137 kJ/mol, which agrees well with the literature data at low heating rates. At 1000 K/s, a transition to a runaway reaction is observed. Unusual for metallic multilayers, the reaction proceeds completely in the solid-state which is also known as “solid flame.” Using nanocalorimetry, a critical input power density for ignition of 5.8 x 10$^{4}$ W/cm$^{3}$ was determined. The rapid succession of the two Al$_{3}$Ni formation stages was identified as the underlying mechanism for the self-sustaining reaction

Tsunamis From Submarine Collapses Along the Eastern Slope of the Gela Basin (Strait of Sicily)

Geophysical surveys in the eastern slope of the Gela Basin (Strait of Sicily, central Mediterranean) contributed to the identification of several episodes of sediment mass transport, recorded by scars and deposits of various dimensions within the Pleistocene succession. In addition to a huge failure called Gela Slide with volume exceeding 600 km3, the most studied events show volumes estimated between 0.5 and 1.5 km3, which is common to many other submarine landslide deposits in this region and that can therefore be considered as a characteristic value. In this work, the tsunamigenic potential of two of such landslides, the so-called Northern Twin Slide and South Gela Basin Slide located about 50 km apart along the eastern slope of the Gela Basin, are investigated using numerical codes that describe the onset and motion of the slide, as well as the ensuing tsunami generation and propagation. The results provide the wave height of these tsunami events on the coast of southern Sicily and Malta and can be taken as representative of the tsunamigenic potential of typical landslides occurring along the slope of the Gela Basin

Polycrystalline diamond films grown by MWPECVD technique and application in photocathodes

Diamond is an extremely interesting material for photoemission applications, due to the negative electron affinity which can be obtained after suitable surface treatments. In the present work, two sets of polycrystalline diamond films, characterized by dif-ferent thickness and deposition conditions, are ana-lyzed. In particular, the relationship among the grain size, the amount of non-diamond carbon (sp2) located at the grain boundaries and the film sensitivity as a photocathode has been found and carefully investi-gated. The photoemission yield in the UV range has been evaluated for all the samples, before and after hydrogenation process, and after air exposure. The critical parameter for the photocathode performances has been found not to be the film thickness, but the properties of polycrystalline diamond films, tunable with the plasma modulation and the methane percent-age in the gas mixture

Tsunami potential source in the eastern Sea of Marmara (NW Turkey), along the North Anatolian Fault system

Based on morphobathymetric and seismic reflection data, we studied a large landslide body from the eastern Sea of Marmara (NW Turkey), along the main strand of the North Anatolian Fault, one of the most seismically active geological structures on Earth. Due to its location and dimensions, the sliding body may cause tsunamis in case of failure possibly induced by an earthquake. This could affect heavily the coasts of the Sea of Marmara and the densely populated Istanbul Metropolitan area, with its exposed cultural heritage assets. After a geological and geometrical description of the landslide, thanks to high-resolution marine geophysical data, we simulated numerically possible effects of its massive mobilization along a basal displacement surface. Results, within significant uncertainties linked to dimensions and kinematics of the sliding mass, suggest generation of tsunamis exceeding 15–20 m along a broad coastal sector of the eastern Sea of Marmara. Although creeping processes or partial collapse of the landslide body could lower the associated tsunami risk, its detection stresses the need for collecting more marine geological/geophysical data in the region to better constrain hazards and feasibility of specific emergency plans

The tsunamigenic potential of landslide-generated tsunamis on the Vavilov seamount

The investigation of submarine volcanoes and the tsunamigenic potential of possible movements on their flanks is arduous. In most cases, the lack of specific information about the eruptions’ history and their consequences does not allow a comprehensive analysis in terms of hazard. Nevertheless, useful clues on the possible occurrence of mass movements on seamounts can be obtained from a series of research fields. These account for morphological studies, observations of hydrothermal activity, collection of geophysical data (for example, detailed DEM, seismic profiles, magnetic data), etc. In this context, this study presents new bathymetric data of the Vavilov submarine volcano (Tyrrhenian Sea, Italy) and a detailed morphological analysis of the structure. The latter allows the identification of zones potentially prone to mass movements and the development of numerical scenarios to investigate the tsunami potential associated to these movements on the Vavilov flanks. Results prove that the waves generated by the mass displacements in the proposed scenarios (involving sliding volumes between 0.32 km3 and 1.7 km3) reach maximum values in the order of centimetres, not considering dispersive effects. Eventually, a scenario involving the partial collapse of the west flank of the Vavilov Seamount is simulated, although the occurrence of such an event in the past is still debated due to the uncertainties related to the origin and development of the volcano dome. In this scenario, water elevation as high as 10 m are found in large portions of the Tyrrhenian coasts: waves are large enough to emplace sizeable tsunami deposits onshore, that could have been preserved until today in some specific stretches of the coast and could be detected by a finalised geological search. This study belongs to a series of works devoted to the submarine structures of the Tyrrhenian Sea aiming to disclose the tsunamigenic potential of submarine mass movements on their flanks

Genetic structure of the long-snouted seahorse, Hippocampus guttulatus, in the Central-Western Mediterranean Sea

The seahorse Hippocampus guttulatus reaches its highest abundance in confined environments, where it has unique biological and ecological traits that suggest significant genetic differentiation among populations. In the present study, we aimed to reveal the genetic structure of this species by analysing eight microsatellite loci and a mitochondrial DNA region (cytochrome b) of eight populations from the Central-Western Mediterranean Sea, including lagoon sites. Levels of genetic diversity, as measured by the total number of alleles, number of private alleles, allelic richness and heterozygosity, ranged from low to moderate. The overall value of inbreeding was high, indicating a deficiency in heterozygotes. The haplotype network had a star-like construction, with the most common haplotype present in all populations. Data from the two molecular markers congruently displayed a similar pattern and revealed low genetic differentiation, notwithstanding predictions based on species traits. The observed genetic structure is probably the result of both historical population demographic events and current gene flow. The investigated lagoons, however, revealed a unique genetic profile, which is especially highlighted by the Taranto population. At this site, the results also showed altered values of observed/expected heterozygosity and allelic richness, a characteristic of marginal populations. Our study suggests that lagoon populations should be managed as distinct genetic units