461 research outputs found
Serum levels of tryptase suggest that mast cells might have an antiinflammatory role in rheumatoid arthritis: comment on the article by Rivellese et al Reply
No full textPathophysiology and treatment of rheumatic disease
Human mast cells and basophils-How are they similar how are they different?
No full textMast cells and basophils are key contributors to allergies and other inflammatory diseases since they are the most prominent source of histamine as well as numerous additional inflammatory mediators which drive inflammatory responses. However, a closer understanding of their precise roles in allergies and other pathological conditions has been marred by the considerable heterogeneity that these cells display, not only between mast cells and basophils themselves but also across different tissue locations and species. While both cell types share the ability to rapidly degranulate and release histamine following high-affinity IgE receptor cross-linking, they differ markedly in their ability to either react to other stimuli, generate inflammatory eicosanoids or release immunomodulating cytokines and chemokines. Furthermore, these cells display considerable pharmacological heterogeneity which has stifled attempts to develop more effective anti-allergic therapies. Mast cell- and basophil-specific transcriptional profiling, at rest and after activation by innate and adaptive stimuli, may help to unravel the degree to which these cells differ and facilitate a clearer understanding of their biological functions and how these could be targeted by new therapies
Migrazioni e schiavi in Roma imperiale. Cenni ed episodi
No full textL’autore si concentra su aspetti e problemi di storia del diritto romano connessi ai fenomeni migratori a Roma nell’epoca dell’espansione. Pone peraltro in rilievo che pure alla condizione giuridica personale di schiavo ci si sottoponeva talora non coercitivamente, bensì mediante la vendita di sé stessi come schiavi e la venuta a Roma. Svolge anche alcune considerazioni su flussi e consistenza numerica degli immigrati e della schiavitù nel contesto della mobilità nell’età imperiale, per concludere con rapidi cenni sugli inizi delle invasioni straniere nell’età tardoantica.The author concentrates on aspects and problems of the history of Roman law related to migration phenomena in Rome during the era of expansion. Moreover, he emphasized that the personal legal status of slave, sometimes were not subjected with coercion, but with the sale of themselves as slaves and the coming to Rome. He also makes some observations on the flows and numerical consistency of immigrants and slavery in the context of mobility in the imperial age, to conclude with a brief outline of the beginnings of foreign invasions in the Late Antiquity
Are Basophils and Mast Cells Masters in HIV Infection?
No full textThe World Health Organization AIDS epidemic update estimates that more than 37 million people are living with HIV infection. Despite the unprecedented success of antiretroviral treatments, significant challenges remain in the fight against HIV. In particular, how uninfected cells capture HIV and transmit virions to target cells remains an unanswered question. Tissue mast cells and peripheral blood basophils can be exposed to virions or HIV products during infection. Several HIV proteins (i.e., envelope glycoproteins gp120 and gp41, Tat, and Nef) can interact with distinct surface receptors expressed by human basophils and mast cells and modulate their functional responses at different levels. Additionally, several groups have provided evidence that human mast cells can be infected in vitro, as well as in vivo, by certain strains of HIV. Recently, it has been demonstrated that basophils purified from healthy donors and intestinal mast cells can efficiently capture HIV on their cell surface and, cocultured with CD4+ T cells, they can transfer the virus to the cocultured cells leading to infection. Direct contact between human basophils or intestinal mast cells and CD4+ T cells can mediate viral trans-infection of T cells through the formation of viral synapses. Thus, basophils and mast cells can provide a cellular basis for capturing and then spreading viruses throughout the body. Collectively, these findings suggest that human basophils and mast cells play a complex and possibly distinct role in HIV infection, warranting further investigations
What is Beauty But a Breath? (1984)
No full textSATB a cappella – (text is an anonymous 14th century English author - premiered by members of the Concordia College choirs, Frank Felice, conducting, April 1984; originally published by Moon of Hope Publishing, Galesburg, Illinois, 1996.https://digitalcommons.butler.edu/jca_scores/1040/thumbnail.jp
Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors.
No full textRheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis. Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA. However, despite the availability of multiple therapeutic options, up to 40% of patients do not respond to current treatments, including biologics. Small-molecule therapies offer an alternative to biological therapies for the treatment of inflammatory diseases. In the past 5 years, a number of small-molecule compounds targeting Janus Kinases (JAKs) have been developed. Since JAKs are essential for cell signaling in immune cells, in particular controlling the response to many cytokines, their inhibitors quickly became a promising class of oral therapeutics that proved effective in the treatment of RA. Tofacitinib is the first Janus Kinase (JAK) inhibitor approved for the treatment of RA, followed more recently by baricitinib. Several other JAK inhibitors, are currently being tested in phase II and III trials for the treatment of a different autoimmune diseases. Most of these compounds exhibit an overall acceptable safety profile similar to that of biologic agents, with infections being the most frequent adverse event. Apart from tofacitinib, safety data on other JAK inhibitors are still limited. Long-term follow-up and further research are needed to evaluate the general safety profile and the global risk of malignancy of these small molecules, although no clear association with malignancy has been reported to date. Here, we will review the main characteristics of JAK inhibitors, including details on their molecular targets and on the clinical evidences obtained so far in the treatment of RA
Superantigenic Activation of Human Cardiac Mast Cells. (VARRICCHI PRIMO AUTORE E AUTORE CORRISPONDENTE)
No full textB cell superantigens, also called immunoglobulin superantigens, bind to the variable regions of either the heavy or light chain of immunoglobulins mirroring the lymphocyte-activating properties of classical T cell superantigens. Protein A of Staphylococcus aureus, protein L of Peptostreptococcus magnus, and gp120 of HIV are typical immunoglobulin superantigens. Mast cells are immune cells expressing the high-affinity receptor for IgE (FcεRI) and are strategically located in the human heart, where they play a role in several cardiometabolic diseases. Here, we investigated whether immunoglobulin superantigens induced the activation of human heart mast cells (HHMCs). Protein A induced the de novo synthesis of cysteinyl leukotriene C4 (LTC4) from HHMCs through the interaction with IgE VH3+ bound to FcεRI. Protein L stimulated the production of prostaglandin D2 (PGD2) from HHMCs through the interaction with κ light chains of IgE. HIV glycoprotein gp120 induced the release of preformed (histamine) and de novo synthesized mediators, such as cysteinyl leukotriene C4 (LTC4), angiogenic (VEGF-A), and lymphangiogenic (VEGF-C) factors by interacting with the VH3 region of IgE. Collectively, our data indicate that bacterial and viral immunoglobulin superantigens can interact with different regions of IgE bound to FcεRI to induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from human cardiac mast cells
Diminished expression of the ubiquitin-proteasome system in early treatment-naïve patients with rheumatoid arthritis and concomitant type 2 diabetes may be linked to IL-1 pathway hyper-activity; results from PEAC cohort
No full textOBJECTIVE: Based on the recent evidence of IL-1 inhibition in patients with rheumatoid arthritis (RA) and concomitant type 2 diabetes (T2D), we evaluated the synovial tissue expression of IL-1 related genes in relationship to the ubiquitin-proteasome system and the effects of insulin on ubiquitinated proteins in fibroblast-like synoviocytes (FLSs). METHODS: The synovial expression of IL-1 pathway genes was compared in early (< 1 year) treatment-naïve RA patients with T2D (RA/T2D n = 16) and age- and sex-matched RA patients without T2D (n = 16), enrolled in the Pathobiology of Early Arthritis Cohort (PEAC). The synovial expression of ubiquitin in macrophages and synovial lining fibroblasts was also assessed by Immunohistochemistry/immunofluorescence and correlated with synovial pathotypes. Finally, FLSs from RA patients (n = 5) were isolated and treated with human insulin (200 and 500 nM) and ubiquitinated proteins were assessed by western blot. RESULTS: Synovial tissues of RA/T2D patients were characterised by a consistent reduced expression of ubiquitin-proteasome genes. More specifically, ubiquitin genes (UBB, UBC, and UBA52) and genes codifying proteasome subunits (PSMA2, PSMA6, PSMA7, PSMB1, PSMB3, PSMB4, PSMB6, PSMB8, PSMB9, PSMB10, PSMC1, PSMD9, PSME1, and PSME2) were significantly lower in RA/T2D patients. On the contrary, genes regulating fibroblast functions (FGF7, FGF10, FRS2, FGFR3, and SOS1), and genes linked to IL-1 pathway hyper-activity (APP, IRAK2, and OSMR) were upregulated in RA/T2D. Immunohistochemistry showed a significant reduction of the percentage of ubiquitin-positive cells in synovial tissues of RA/T2D patients. Ubiquitin-positive cells were also increased in patients with a lympho-myeloid pathotype compared to diffuse myeloid or pauci-immune-fibroid. Finally, in vitro experiments showed a reduction of ubiquitinated proteins in RA-FLSs treated with a high concentration of insulin (500 nM). CONCLUSIONS: A different IL-1 pathway gene expression was observed in the synovial tissues of early treatment-naïve RA/T2D patients, linked to decreased expression of the ubiquitin-proteasome system. These findings may provide a mechanistic explanation of the observed clinical benefits of IL-1 inhibition in patients with RA and concomitant T2D
CLiC-it 2020 - Italian Conference on Computational Linguistics 2020 - Proceedings of the Seventh Italian Conference on Computational Linguistics
No full textOn behalf of the Program Committee, a very warm welcome to the Seventh Italian Conference on
Computational Linguistics (CLiC-it 2020). This edition of the conference is held in Bologna and
organised by the University of Bologna. The CLiC-it conference series is an initiative of the Italian
Association for Computational Linguistics (AILC) which, after six years of activity, has clearly
established itself as the premier national forum for research and development in the fields of
Computational Linguistics and Natural Language Processing, where leading researchers and
practitioners from academia and industry meet to share their research results, experiences, and
challenges.
This year CLiC-it received 80 submissions against 64 submissions in 2015, 69 in 2016, 72 in
2017, 70 in 2018 and 82 in 2019 confirming the increasing trend of the past years. The
Programme Committee worked very hard to ensure that every paper received at least three
careful and fair reviews. This process finally led to the acceptance of 19 papers for oral
presentation and 53 papers for poster presentation, with a global acceptance rate of 90%
motivated by the inclusive spirit of the conference. The conference is also receiving considerable
attention from the international community, with 17 (21%) submissions showing at least one
author affiliated to a foreign institution. Regardless of the format of presentation, all accepted
papers are allocated 5 or 6 pages plus 2 pages for references in the proceedings, available as
open access publication. In line with previous editions, the conference is organised around
thematic areas managed by one or two area chairs per area.
In addition to the technical programme, this year we are honoured to have as invited speakers
internationally recognised researchers as Veronique Hoste (Ghent University) and Stefan Kopp
(Bielefeld University). We are very grateful to Veronique and Stefan for agreeing to share with
the Italian community their knowledge and expertise on key topics in Computational Linguistics
The Urokinase/Urokinase Receptor System in Mast Cells: Effects of its Functional Interaction with fMLF Receptors
No full textMast cell and basophils express the high affinity receptor for IgE (FcɛRI) and are primary effector cells of allergic disorders. The urokinase (uPA)-mediated plasminogen activation system is involved in physiological and pathological events based on cell migration and tissue remodelling, such as inflammation, wound healing, angiogenesis and metastasis. uPA is a serine protease that binds uPAR, a high affinity glycosyl-phosphatidyl-inositol (GPI)-anchored receptor. uPAR focuses uPA activity at the cell surface and activates intracellular signaling through lateral interactions with integrins, receptor tyrosine kinases and the G-protein-coupled family of fMLF chemotaxis receptors (FPRs). We investigated the expression of the uPA-uPAR system and its functional interaction with FPRs in human mast cells (MCs). Differently from basophils, MCs produced uPA that was able to induce their chemotaxis. Indeed, MCs also expressed uPAR, both in the intact and in a cleaved form (DII-DIII-uPAR) that can expose, at the N-terminus, the SRSRY sequence, able to interact with FPRs and to mediate cell chemotaxis. MCs also expressed mRNAs for FPRs that were functionally active; indeed, uPA and a soluble peptide (uPAR84-95), containing the SRSRY chemotactic sequence of uPAR and able to interact with FPRs, were able to induce MCs chemotaxis. Thus, uPA is a potent chemoattractant for MCs acting through the exposure of the chemotactic epitope of uPAR, that is an endogenous ligand for FPRs. The same mechanism could be involved in VEGF-A secretion by human MCs, also induced by uPA and uPAR84-95 stimulation
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