STRATEGIES FOR ALTERATION OF PRO-INFLAMMATORY GENE EXPRESSION IN CYSTIC FIBROSIS.

Cystic fibrosis (CF) is an autosomal recessive disorder caused by defective function of the cystic fibrosis transmembrane receptor (CFTR) gene product, a cAMP-regulated chloride channel. The main cause of morbidity and mortality in CF patients is a lung chronic inflammation due to several infections from pathogens like Pseudomonas aeruginosa. Chronic inflammatory process leads to elevated concentrations of several pro-inflammatory cytokines (i.e. IL-6, TNFα, IL1β) and chemokines (i.e. IL-8) released from airway epithelial cells and found in the bronchoalveolar fluid of CF patients. We studied the cytokines expression in IB3-1 cells, the cellular model for CF, when inflammation was induced by Pseudomonas aeruginosa infection or TNFα treatment. IL-8 was significantly more expressed compared to all cytokines studied. So far, therapies have been directed at improving airway clearance of secretions and treating pulmonary infection. Recently, among several new therapeutic approaches, a strategy to directly reduce the excessive inflammatory response in the airways has been proposed. In this respect, we focused our attention on two different strategies aiming at the down-regulation of the pro-inflammatory gene expression: · transcription factor decoy (TFD) · natural products as source of new anti-inflammatory compounds Pseudomonas aeruginosa lung infection is known to induce the expression of innate immunity genes by activating different transcription factors (TFs), such as NF-kB, AP-1, Elk-1, and NF-IL-6. Since NF-kB plays a well known pivotal role in inflammatory processes, we chose it as the first molecular target for the TF decoy approach. We show here that NF-kB oligodeoxynucleotide (ODN) decoy on IL-8 promoter partially inhibited the Pseudomonas aeruginosa-dependent transcription of IL-8. The use of ‘‘decoy’’ molecules to inhibit IL-8 driven inflammation represents a promising strategy for CFTR related lung disease. The second approach focused on the natural anti-inflammatory effect of some medicinal plant extracts, including Bergamot from Lebanon, Emblica officinalis and Saraca asoka from Bangladesh and on the identification of the constituents addressing this effect. We show here that all three plant extracts reduced IL-8 gene expression in IB3-1 cells induced to hyper secretion of pro-inflammatory chemokines by TNF-a. The results sustain the anti-inflammatory properties of these plant extracts and suggest a possible use to control the inflammatory process associated with the cystic fibrosis airway pathology

Il progetto Clavius On The Web entra nelle scuole

Clavius on the web is a Digital Humanities project dedicated to the manuscripts of Christophorus Clavius – an important jesuit mathematician and one of most influential scholars of his time – preserved by the Historical Archive of the Pontifical Gregorian University. This paper describes Clavius@School, an initiative within the same project in which students from three high schools partecipate. Clavius@School aims not only to spread knowledge about Clavius’ works, but also to alert to a conscientious and aware use of digital techno

CLAVIUS@SCHOOL IL PROGETTO CLAVIUS ON THE WEB ENTRA NELLE SCUOLE

Clavius on the web is a Digital Humanities project dedicated to the manuscripts of Christophorus Clavius – an important jesuit mathematician and one of most influential scholars of his time – preserved by the Historical Archive of the Pontifical Gregorian University. This paper describes Clavius@School, an initiative within the same project in which students from three high schools partecipate. Clavius@School aims not only to spread knowledge about Clavius’ works, but also to alert to a conscientious and aware use of digital technology, according to the perspective proposed by the French philosopher Bernard Stiegle

Lecturas territoriales: nuevas cartografías interpretativas de la quebrada de Humahuaca

El trabajo ensaya el redibujo y construcción de nuevas cartografías de la Quebrada de Humahuaca (Jujuy, Argentina)como un instrumento de conocimiento del territorio a fin de interpretar los procesos de transformación de este PaisajeCultural antes y después de la Declaratoria UNESCO (2003). La lectura intencionada del territorio, desde diferentesescalas de observación y layers (capas) de información, nos permite indagar en torno a los elementos estructurantesy los patrones del cambio: la asimetría en la forma del relieve y de los cursos de agua, la transversalidad de los ejesde comunicación, la transformación de los tejidos existentes y el crecimiento urbano reciente en pueblos y loteos,así como la evolución en la valoración de los recursos patrimoniales y sitios turísticos. Por último, se abre la discusiónen torno a algunos ámbitos y temas renovados de propuesta que surgen a partir del análisis cartográfico y queplantean interrogantes sobre los límites del territorio; el entendimiento de la quebrada como itinerario cultural y lavaloración de ciertos subsistemas transversales; así como sobre los patrones recientes del crecimiento discontinuoen nuevos barrios o loteos.Fil: Vecslir, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Geografia "Romualdo Ardissone"; ArgentinaFil: Tommei, Constanza Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Arquitectura y Urbanismo. Instituto de Arte Americano e Investigación Estéticas "Mario Buschiazzo"; ArgentinaFil: Mancini, Clara Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Noceti, Irene. No especifica

Sharing Cultural Heritage: the Clavius on the Web Project

In the last few years the amount of manuscripts digitized and made available on the Web has been constantly increasing. However, there is still a considarable lack of results concerning both the explicitation of their content and the tools developed to make it available. The objective of the Clavius on the Web project is to develop a Web platform exposing a selection of Christophorus Clavius letters along with three different levels of analysis: linguistic, lexical and semantic. The multilayered annotation of the corpus involves a XML-TEI encoding followed by a tokenization step where each token is univocally identified through a CTS urn notation and then associated to a part-of-speech and a lemma. The text is lexically and semantically annotated on the basis of a lexicon and a domain ontology, the former structuring the most relevant terms occurring in the text and the latter representing the domain entities of interest (e.g. people, places, etc.). Moreover, each entity is connected to linked and non linked resources, including DBpedia and VIAF. Finally, the results of the three layers of analysis are gathered and shown through interactive visualization and storytelling techniques. A demo version of the integrated architecture was developed

Sulfate Aerosols from Non-Explosive Volcanoes: Chemical-Radiative Effects in the Troposphere and Lower Stratosphere

SO2 and H2S are the two most important gas-phase sulfur species emitted by volcanoes, with a global amount from non-explosive emissions of the order 10 Tg-S/yr. These gases are readily oxidized forming SO42− aerosols, which effectively scatter the incoming solar radiation and cool the surface. They also perturb atmospheric chemistry by enhancing the NOx to HNO3 heterogeneous conversion via hydrolysis on the aerosol surface of N2O5 and Br-Cl nitrates. This reduces formation of tropospheric O3 and the OH to HO2 ratio, thus limiting the oxidation of CH4 and increasing its lifetime. In addition to this tropospheric chemistry perturbation, there is also an impact on the NOx heterogeneous chemistry in the lower stratosphere, due to vertical transport of volcanic SO2 up to the tropical tropopause layer. Furthermore, the stratospheric O3 formation and loss, as well as the NOx budget, may be slightly affected by the additional amount of upward diffused solar radiation and consequent increase of photolysis rates. Two multi-decadal time-slice runs of a climate-chemistry-aerosol model have been designed for studying these chemical-radiative effects. A tropopause mean global net radiative flux change (RF) of −0.23 W·m−2 is calculated (including direct and indirect aerosol effects) with a 14% increase of the global mean sulfate aerosol optical depth. A 5–15 ppt NOx decrease is found in the mid-troposphere subtropics and mid-latitudes and also from pole to pole in the lower stratosphere. The tropospheric NOx perturbation triggers a column O3 decrease of 0.5–1.5 DU and a 1.1% increase of the CH4 lifetime. The surface cooling induced by solar radiation scattering by the volcanic aerosols induces a tropospheric stabilization with reduced updraft velocities that produce ice supersaturation conditions in the upper troposphere. A global mean 0.9% decrease of the cirrus ice optical depth is calculated with an indirect RF of −0.08 W·m−2

Impact of Stratospheric Volcanic Aerosols on Age-of-Air and Transport of Long-Lived Species

The radiative perturbation associated to stratospheric aerosols from major explosive volcanic eruptions may induce significant changes in stratospheric dynamics. The aerosol heating rates warm up the lower stratosphere and cause a westerly wind anomaly, with additional tropical upwelling. Large scale transport of stratospheric trace species may be perturbed as a consequence of this intensified Brewer–Dobson circulation. The radiatively forced changes of the stratospheric circulation during the first two years after the eruption of Mt. Pinatubo (June 1991) may help explain the observed trend decline of long-lived greenhouse gases at surface stations (approximately −8 and −0.4 ppbv/year for CH4 and N2O, respectively). This decline is partly driven by the increased mid- to high-latitude downward flux at the tropopause and also by an increased isolation of the tropical pipe in the vertical layer near the tropopause, with reduced horizontal eddy mixing. Results from a climate-chemistry coupled model are shown for both long-lived trace species and the stratospheric age-of-air. The latter results to be younger by approximately 0.5 year at 30 hPa for 3–4 years after the June 1991 Pinatubo eruption, as a result of the volcanic aerosols radiative perturbation and is consistent with independent estimates based on long time series of in situ profile measurements of SF6 and CO2. Younger age of air is also calculated after Agung, El Chichon and Ruiz eruptions, as well as negative anomalies of the N2O growth rate at the extratropical tropopause layer. This type of analysis is made comparing the results of two ensembles of model simulations (1960–2005), one including stratospheric volcanic aerosols and their radiative interactions and a reference case where the volcanic aerosols do not interact with solar and planetary radiation

Stratospheric Aerosols from Major Volcanic Eruptions: A Composition-Climate Model Study of the Aerosol Cloud Dispersal and e-folding Time

Large explosive volcanic eruptions are capable of injecting considerable amounts of particles and sulfur gases above the tropopause, causing large increases in stratospheric aerosols. Five major volcanic eruptions after 1960 (i.e., Agung, St. Helens, El Chichon, Nevado del Ruiz and Pinatubo) have been considered in a numerical study conducted with a composition-climate coupled model including an aerosol microphysics code for aerosol formation and growth. Model results are compared between an ensemble of numerical simulations including volcanic aerosols and their radiative effects (VE) and a reference simulations ensemble (REF) with no radiative impact of the volcanic aerosols. Differences of VE-REF show enhanced diabatic heating rates; increased stratospheric temperatures and mean zonal westerly winds; increased planetary wave amplitude; and tropical upwelling. The impact on stratospheric upwelling is found to be larger when the volcanically perturbed stratospheric aerosol is confined to the tropics, as tends to be the case for eruptions which were followed by several months with easterly shear of the quasi-biennial oscillation (QBO), e.g., the Pinatubo case. Compared to an eruption followed by a period of westerly QBO, such easterly QBO eruptions are quite different, with meridional transport to mid- and high-latitudes occurring later, and at higher altitude, with a consequent decrease in cross-tropopause removal from the stratosphere, and therefore longer decay timescale. Comparing the model-calculated e-folding time of the volcanic aerosol mass during the first year after the eruptions, an increase is found from 8.1 and 10.3 months for El Chichon and Agung (QBO westerly shear), to 14.6 and 30.7 months for Pinatubo and Ruiz (QBO easterly shear). The corresponding e-folding time of the global-mean radiative flux changes goes from 9.1 and 8.0 months for El Chichon and Agung, to 28.7 and 24.5 months for Pinatubo and Ruiz