Two new catalogs of blazar candidates in the WISE infrared sky

We present two catalogs of radio-loud candidate blazars whose WISE mid-infrared colors are selected to be consistent with the colors of confirmed gamma-ray emitting blazars. The first catalog is the improved and expanded release of the WIBRaLS catalog presented by D'Abrusco et al. (2014): it includes sources detected in all four WISE filters, spatially cross-matched with radio source in one of three radio surveys and radio-loud based on their q22 spectral parameter. WIBRaLS2 includes 9541 sources classified as BL Lacs, FSRQs or mixed candidates based on their WISE colors. The second catalog, called KDEBLLACS, based on a new selection technique, contains 5579 candidate BL Lacs extracted from the population of WISE sources detected in the first three WISE passbands ([3.4], [4.6] and [12]) only, whose mid-infrared colors are similar to those of confirmed, gamma-ray BL Lacs. KDBLLACS members area also required to have a radio counterpart and be radio-loud based on the parameter q12, defined similarly to q22 used for the WIBRaLS2. We describe the properties of these catalogs and compare them with the largest samples of confirmed and candidate blazars in the literature. We crossmatch the two new catalogs with the most recent catalogs of gamma-ray sources detected by Fermi LAT instrument. Since spectroscopic observations of candidate blazars from the first WIBRaLS catalog within the uncertainty regions of gamma-ray unassociated sources confirmed that ~90% of these candidates are blazars, we anticipate that these new catalogs will play again an important role in the identification of the gamma-ray sky.Comment: 20 pages, 7 figures. Accepted for publication in The Astrophysical Journal Supplement Serie

Effect of TNF-alpha and IL-17 on TLR expression and Langerhans cells phenotype in a three-dimensional model of normal human skin: a morphological study

Toll-like receptors (TLRs) are essential for innate immunity and contribute to create the skin barrier. Their abnormal stimulation is involved in the development of several dermatological diseases, among which psoriasis. Tumor Necrosis Factor (TNF)-alpha and interleukin (IL)-17 play a pivotal role in the pathogenesis of psoriatic plaques and their proinflammatory activity can affect Langerhans cell (LC) phenotype. In a well characterized three-dimensional model of organotypic cultures of normal human skin [1-3] we evaluated the effect of TNF-alpha and IL-17 on the expression of TLR2 and 9 by immunofluorescence, on the ultrastructural morphology of keratinocytes and LCs by transmission electron microscopy (TEM). Human skin explants (n=7) were cultured at the air-liquid interface overnight in a Transwell system and exposed to 50 ng/ml IL-17 or 100 ng/ml TNF-alpha or a combination of both cytokines. Samples were harvested 24 (T24) and 48h (T48) after cytokines incubation. After incubation with IL-17 and IL-17+TNF-alpha, TLR2 immunostaining was not detectable in the basal layer, differently from controls and TNF-alpha-treated samples. Conversely, TLR9 expression was progressively induced in granular keratinocytes in all cytokine-exposed groups. By TEM, enlargements of intercellular spaces were evident especially and, after IL-17 treatment, LCs showed an activated phenotype. At T24 LCs number increased indicating that TNF-alpha and IL-17+TNF-alpha exert a chemoattractant activity, while at T48 only IL-17+TNF-alpha maintained this effect on trapping LCs in epidermis. TNF-alpha and IL-17 differently affect LCs behaviour and TLR expression, with a specific contribution to the inflammatory loop underlying the lesion formation. These results suggest that the simultaneous inhibition of the effect of different cytokines with a defined role in the pathogenesis of psoriasis could improve psoriasis treatment

Langerhans cells and Toll Like Receptors: how do they act and react in an in vitro psoriatic microenvironment?

Tumor Necrosis Factor (TNF)-α, interleukin (IL)-17, IL-22 and IL-23 are involved in the psoriasis pathogenesis and represent a strong proinflammatory stimulus. Both epidermal keratinocytes (KCs) and Langerhans cells (LCs) early respond promoting an early epidermal response [1, 2]. Human skin can count on the cellular response supported by LCs and on innate immunity through the expression of Toll-like Receptors (TLRs) [4]. We aimed at investigate whether the exposure of normal human skin to a combination of TNF-α, IL-17, IL-22, and IL-23 (cytokine mix) affected i) LCs immunophenotype, ii) expression of TLR2 and TLR9 and iii) KC proliferation. Human skin samples were obtained after plastic surgery (n = 5) and exposed to the cytokine mix in a Transwell system at air-liquid interface, with a parallel control group. Samples were harvested 24 and 48 hours after cytokine stimulation, processed in parallel for immunofluorescence or ultrastructural analysis. A decrease of cell proliferation was evident in samples exposed to cytokine mix for 24 hours and this phenomenon was more and more evident later. TLR2 immunopositivity progressively disappeared in the basal layer after cytokine mix exposure compared to the control group, while TLR9 expression was induced in scattered granular keratinocytes. By TEM, LCs showed an activated phenotype. In conclusion, these results suggest that, in a microenvironment mimicking the psoriatic plaque, epidermis early stimulates two important lines of defense, thus proposing that a therapeutic intervention in this direction can interfere with the formation/progression of the psoriatic plaque

Evaluation of protective effect of Thymol on UVBinduced damage in an ex-vivo human skin tissue model: morphological analysis and genotoxic evaluations

insult, among which is the most important solar ultraviolet (UV) radiation (Bernerd et al., 2001). For this reason, the use of human skin tissue obtained from plastic aesthetic surgery represents a simple but efficient experimental approach to reproduce a physiological condition to test the early effects of an exogenous stimulus as UV radiation and the possibility of preventing or reducing the early epidermal effects. Normal human skin explants were obtained from healthy young non smoking women 20-40 years old (n=5) after informed consent and cultured epidermal side up at the air-liquid interface overnight in a Transwell system before treatment (Donetti et al., 2005; Bedoni et al., 2007). They were further divided in two groups: the first was exposed to UVB doses ranging from 0.24 J/cm2 to 0.72 J/cm2 and the other one pretreated for 1 h with Thymol (natural monoterpene phenol, 6.6 μM), before the UVB irradiation. In each experiment a cultured sample was not UVB exposed and represented the internal control. Samples were harvested 24 hours after of UVB exposure. Lactate Dehydrogenase (LDH) assay and alkaline comet and micronucleus tests were used to assess cytotoxicity and genotoxicity, respectively. Bioptic fragments were processed both for transmission electron (TEM) and light (LM) microscopy. Epidermal proliferation was investigated by indirect immunofluorescence after incorporation of 5-Bromo- 2’-deoxyuridine (BrdU). UVB induced evident ultrastructural alterations in nucleus and cytoskeleton, while the pretreatment with Thymol showed a reduction of damage in UVB exposed samples both from the morphological point of view that genotoxic aspects. Cell proliferation was strongly inhibited by UVB exposure, while in Thylom pretreated samples was comparable to control. Furthermore these results strongly support the use of ex vivo human skin as a relevant method for safety evaluation of UV skin exposure

Effect of a psoriatic microenvironment in a threedimensional model of normal human skin

Among the cytokines involved in the pathogenesis and in the progression of the disease, tumor necrosis factor (TNF)-alpha and interleukin (IL)-17 are the most relevant. A three dimensional model of organotypic human skin cultures is a valuable approach for exposing the whole skin to TNF-alpha and IL-17 as specific proinflammatory stimuli, thus mimicking a psoriatic microenvironment. Normal human skin explants were obtained from plastic surgery of healthy 20-40 year-old women (n = 7) after informed consent. Bioptic fragments were cultured overnight in a DMEM medium and further divided before adding either 100 ng/ml TNF-alpha or 50 ng/ml IL-17 or a combination of both cytokines. Samples were harvested 24 hours after cytokine incubation. Each patient was represented in all experimental groups. Epidermal proliferation together with the expression of terminal differentiation biomarkers (keratin 10, K10, and 14, K14) and of intercellular adhesion (occludin for tight junctions and E-cadherin for adherens junctions) were investigated by indirect immunofluorescence. Vibrational spectroscopy analysis by a confocal micro-Raman system (785nm laser) has been carried out in three skin samples to evaluate differences of the spectrum versus normal skin. Both cytokines induced a strong inhibition of keratinocyte proliferation (more than 80% compared with their respective controls). A non-continuous occludin expression in the granular layer was observed after the TNF-alpha and IL-17 exposure. Immunolabelings for E-cadherin in tight junctions, for K10 in the suprabasal layers, and for K14 in the basal layer were similar in all experimental groups. The preliminary Raman results highlighted some biomolecules modifications in TNF-alpha- and IL-17-treated skin samples related to ceramide and amide III (keratin proteins) peaks. These results suggest that in this experimental model we reproduced a psoriatic microenvironment in which TNF-alpha and IL-17 induce an early alteration of the homeostasis of the inner proliferative layer, the upper granular layer, and stratum corneum as shown by cell proliferation inhibition, occludin expression, and the biomolecules Raman bands

Optical characterization of WISE selected blazar candidates

Context. Over the last decade more than five thousand γ-ray sources have been detected by the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope. Given the positional uncertainty of the telescope, nearly 30% of these sources remain without an obvious counterpart at lower energies. This has motivated the release of new catalogs of γ-ray counterpart candidates and several follow up campaigns in the last decade. Aims. Recently, two new catalogs of blazar candidates were released. These are the improved and expanded version of the WISE Blazar-Like Radio-Loud Sources (WIBRaLS2) catalog and the Kernel Density Estimation selected candidate BL Lacs (KDEBLLACS) catalog, both selecting blazar-like sources based on their infrared colors from the Wide-field Infrared Survey Explorer (WISE). In this work we characterize these two catalogs, clarifying the true nature of their sources based on their optical spectra from SDSS data release 15, thus testing their efficiency in selecting true blazars. Methods. We first selected all WIBRaLS2 and KDEBLLACS sources with available optical spectra in the footprint of Sloan Digital Sky Survey data release 15. We then analyzed these spectra to verify the nature of each selected candidate and to measure the fraction of the catalogs composed by spectroscopically confirmed blazars. Finally, we evaluated the impact of selection effects, especially those related to optical colors of WIBRaLS2/KDEBLLACS sources and their optical magnitude distributions. Results. We found that at least ∼30% of each catalog is made up of confirmed blazars, with quasars being the major contaminants in the case of WIBRaLS2 (≈58%) and normal galaxies in the case of KDEBLLACS (≈38.2%). The spectral analysis also allowed us to identify the nature of 11 blazar candidates of uncertain type (BCUs) from the Fermi-LAT fourth Point Source Catalog (4FGL) and to find 25 new BL Lac objects.Fil: de Menezes, Raniere. Universidade Do Sao Paulo. Instituto Astronomia, Geofísica E Ciencias Atmosfericas. Departamento de Astronomia; Brasil. Università degli Studi di Torino; ItaliaFil: Peña Herazo, Harold A.. Instituto Nacional de Astrofísica; México. Università di Torino; Italia. Istituto Nazionale Di Fisica Nucleare.; Italia. Osservatorio Astrofisico di Torino; ItaliaFil: Marchesini, Ezequiel Joaquín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Istituto Nazionale Di Fisica Nucleare.; Italia. Università di Torino; ItaliaFil: D´Abrusco, Raffaele. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Masetti, Nicola. Osservatorio di Astrofisica e Scienza dello Spazio; Italia. Universidad Andrés Bello; ChileFil: Nemmen, Rodrigo. Universidade Do Sao Paulo. Instituto Astronomia, Geofísica E Ciencias Atmosfericas. Departamento de Astronomia; BrasilFil: Massaro, Francesco. Università di Torino; Italia. Istituto Nazionale Di Fisica Nucleare.; Italia. Osservatorio Astrofisico di Torino; Italia. Consorzio Interuniversitario per la Fisica Spaziale ; ItaliaFil: Ricci, Federica. Pontificia Universidad Católica de Chile; ChileFil: Landoni, Marco. Osservatorio Astronomico di Brera; ItaliaFil: Paggi, Alessandro. Università di Torino; ItaliaFil: Smith, Howard A.. Harvard-Smithsonian Center for Astrophysics; Estados Unido

Morphological analysis of the effects of tumor necrosis factor-alpha and interleukin-17 in a three-dimensional organotipic model of normal human skin

Psoriasis is an autoimmune chronic inflammatory disease in which epidermal keratinocytes and innate immunity effector cells play a pivotal role in the lesion formation in genetically predisposed subjects (Bonifati et al., 1999). Among the several cytokines involved in psoriasis pathogenesis, tumor necrosis factor (TNF)-alpha and interleukin (IL)-17 play a relevant role. TNF-alpha stimulates the production of many chemokines, induces cell proliferation, and is proapoptotic. IL-17 is involved in the recruitment/activation of neutrophils and induces keratin 17 (K17) expression in psoriatic lesions. The present study is focussed on the early effects of these proinflammatory cytokines on i) the molecular composition of intercellular junctions (desmocollin (DSC)1/desmoglein (DSG)1, E-cadherin, and occludin) ii) on K17 expression iii) on immunophenotype/number of epidermal Langerhans cells (LCs) after cytokines exposure. Ultrastructural analysis was performed in on all samples. Skin explants obtained from plastic surgery of healthy 20-40 year-old women (n = 7) after informed consent, were cultured overnight in Dulbecco’s modified Eagle’s medium and divided before adding 100 ng/ml TNF-alpha or 50 ng/ml IL-17 or a combination of both cytokines (Donetti et al., 2014). Samples were harvested 24, 48, and 72 hours after cytokine incubation. Occludin immunostaining was non homogeneous in cytokine treated samples, starting from 24 hours of culture. Interestingly, K17 expression was induced only in IL-17-treated samples only. No differences were observed in DSC1, DSG1 and E-cadherin expression by immunofluorescence. LC number was significantly higher in samples treated with both cytokines (216.71±15.10%) than in TNF-alpha (125.74±26.24%) or IL-17 (100.14±38.42%) alone. TEM analysis revealed that spaces were enlarged in the basal and spinous layer, especially upon TNF-alpha treatment, but desmosomes were uniformly distributed. Upon TNF-alpha stimulus LCs appeared with few organelles, mostly mitochondria, lysosomes, and scattered peripherical Birbeck granules. Upon IL-17 stimulus, LCs showed a cytoplasm with many mitochondria and numerous Birbeck granules close to the perinuclear space and Golgi apparatus, but also at the periphery, at the beginning of the dendrites. The addition of both cytokines did not modify LC ultrastructure. Altogether this study strongly suggests that this model is useful to study the early, direct, and specific effects of specific psoriatic cytokines on the different cell population

Diagnostic role of circulating extracellular matrix-related proteins in non-small cell lung cancer.

BACKGROUND: Interactions between cancer cells and the surrounding microenvironment are crucial determinants of cancer progression. During this process, bi-directional communication among tumor cells and cancer associated fibroblasts (CAF) regulate extracellular matrix (ECM) deposition and remodeling. As a result of this dynamic process, soluble ECM proteins can be released into the bloodstream and may represent novel circulating biomarkers useful for cancer diagnosis. The aim of the present study was to measure the levels of three circulating ECM related proteins (COL11A1, COL10A1 and SPARC) in plasma samples of lung cancer patients and in healthy heavy-smokers controls and test whether such measurements have diagnostic or prognostic value. METHODS: Gene expression profiling of lung fibroblasts isolated from paired normal and cancer tissue of NSCLC patients was performed by gene expression microarrays. The prioritization of the candidates for the study of circulating proteins in plasma was based on the most differentially expressed genes in cancer associated fibroblasts. Soluble ECM proteins were assessed by western blot in the conditioned medium of lung fibroblasts and by ELISA assays in plasma samples. RESULTS: Plasma samples from lung cancer patients and healthy heavy-smokers controls were tested for levels of COL11A1 and COL10A1 (n = 57 each) and SPARC (n = 90 each). Higher plasma levels of COL10A1 were detected in patients (p ≤ 0.001), a difference that was driven specifically by females (p < 0.001). No difference in COL11A1 levels between patients and controls was found. SPARC levels were also higher in plasma patients than controls (p < 0.001) with good performance in discriminating the two groups (AUC = 0.744). No significant association was observed between plasma proteins levels and clinicopathological features or survival. CONCLUSION: Soluble factors related to proficient tumor-stroma cross-talk are detectable in plasma of primary lung cancer patients and may represent a valuable complementary diagnostic tool to discriminate lung cancer patients from healthy heavy-smokers individuals as shown for the SPARC protein

Competence Centre ICDI per Open Science, FAIR, ed EOSC - Mission, Strategia e piano d'azione

This document presents the mission and strategy of the Italian Competence Centre on Open Science, FAIR, and EOSC. The Competence Centre is an initiative born within the Italian Computing and Data Infrastructure (ICDI), a forum created by representatives of major Italian Research Infrastructures and e-Infrastructures, with the aim of promoting sinergies at the national level, and optimising the Italian participation to European and global challenges in this field, including the European Open Science Cloud (EOSC), the European Data Infrastructure (EDI) and HPC. This working paper depicts the mission and objectives of the ICDI Competence Centre, a network of experts with various skills and competences that are supporting the national stakeholders on topics related to Open Science, FAIR principles application and participation to the EOSC. The different actors and roles are described in the document as well as the activities and services offered, and the added value each stakeholder can find the in Competence Centre. The tools and services provided, in particular the concept for the portal, though which the Centre will connect to the national landscape and users, are also presented

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections