Overlapping, Additive and Counterregulatory Effects of Type II and I Interferons on Myeloid Dendritic Cell Functions

Dendritic cells (DCs) are central player in immunity by bridging the innate and adaptive arms of the immune system (IS). Interferons (IFNs) are one of the most important factors that regulate both innate and adaptive immunity too. Thus, the understanding of how type II and I IFNs modulate the immune-regulatory properties of DCs is a central issue in immunology. In this paper, we will address this point in the light of the most recent literature, also highlighting the controversial data reported in the field. According to the wide literature available, type II as well as type I IFNs appear, at the same time, to collaborate, to induce additive effects or overlapping functions, as well as to counterregulate each one's effects on DC biology and, in general, the immune response. The knowledge of these effects has important therapeutic implications in the treatment of infectious/autoimmune diseases and cancer and indicates strategies for using IFNs as vaccine adjuvants and in DC-based immune therapeutic approaches

Verifying liquidity of recursive Bitcoin contracts

Smart contracts - computer protocols that regulate the exchange of crypto-assets in trustless environments - have become popular with the spread of blockchain technologies. A landmark security property of smart contracts is liquidity: in a non-liquid contract, it may happen that some assets remain frozen, i.e. not redeemable by anyone. The relevance of this issue is witnessed by recent liquidity attacks to Ethereum, which have frozen hundreds of USD millions. We address the problem of verifying liquidity on BitML, a DSL for smart contracts with a secure compiler to Bitcoin, featuring primitives for currency transfers, contract renegotiation and consensual recursion. Our main result is a verification technique for liquidity. We first transform the infinite-state semantics of BitML into a finite-state one, which focusses on the behaviour of a chosen set of contracts, abstracting from the moves of the context. With respect to the chosen contracts, this abstraction is sound, i.e. if the abstracted contract is liquid, then also the concrete one is such. We then verify liquidity by model-checking the finite-state abstraction. We implement a toolchain that automatically verifies liquidity of BitML contracts and compiles them to Bitcoin, and we assess it through a benchmark of representative contracts.Comment: arXiv admin note: text overlap with arXiv:2003.0029

CD3+CD4+LAP+Foxp3-regulatory cells of the colonic lamina propria limit disease extension in ulcerative colitis

Background and Aims: In ulcerative colitis (UC), inflammation begins in the rectum and can extend proximally throughout the entire colon. The extension of inflammation is an important determinant of disease course, and may be limited by the action of regulatory T cells (Tregs). In this cross-sectional study, we evaluated the relationship between UC extension and the proportions of CD3+CD4+Foxp3+ and CD3+CD4+LAP+Foxp3- Tregs in the colonic lamina propria (LP) of 79 UC patients and 29 controls. The role of these cells in UC extension was also investigated in the murine oxazolone-induced colitis model. Methods: Patients: Disease extension was classified according to the Montreal classification. Where possible, endoscopic biopsies of involved and uninvolved tissue were obtained from UC patients. Mouse model: Colitis was induced by intrarectal oxazolone administration. Lamina propria mononuclear cells were isolated from patient biopsies and mouse colon tissue using enzymatic method and the percentage of CD3+CD4+Foxp3+ and CD3+CD4+LAP+Foxp3-cells evaluated by immunofluorescence. Confocal microscopy was applied for the visualization and quantification of CD4+LAP+ cells on tissue histological sections. Results: In UC patients with distal colitis the proportion of LP CD3+CD4+Foxp3+ Tregs was significantly higher in inflamed tissue than uninvolved tissue. As opposite, the proportion of LP CD3+CD4+LAP+ Tregs was significantly higher in uninvolved tissue than involved tissue. Both LP CD3+CD4+Foxp3+ and LP CD3+CD4+LAP+ Tregs proportion in involved tissue was significantly higher than in controls irrespective of the extension of inflammation. In mice with oxazolone-induced distal colitis, treatment with LAP-depleting antibody was associated with the development of extensive colitis. Conclusions: Our findings suggest that CD3+CD4+LAP+Foxp3-Tregs limit the extension of inflammatory lesions in UC patients

Verifying liquidity of recursive Bitcoin contracts

Smart contracts - computer protocols that regulate the exchange of crypto-assets in trustless environments - have become popular with the spread of blockchain technologies. A landmark security property of smart contracts is liquidity: in a non-liquid contract, it may happen that some assets remain frozen, i.e. not redeemable by anyone. The relevance of this issue is witnessed by recent liquidity attacks to Ethereum, which have frozen hundreds of USD millions. We address the problem of verifying liquidity on BitML, a DSL for smart contracts with a secure compiler to Bitcoin, featuring primitives for currency transfers, contract renegotiation and consensual recursion. Our main result is a verification technique for liquidity. We first transform the infinite-state semantics of BitML into a finite-state one, which focusses on the behaviour of a chosen set of contracts, abstracting from the moves of the context. With respect to the chosen contracts, this abstraction is sound, i.e. if the abstracted contract is liquid, then also the concrete one is such. We then verify liquidity by model-checking the finite-state abstraction. We implement a toolchain that automatically verifies liquidity of BitML contracts and compiles them to Bitcoin, and we assess it through a benchmark of representative contracts

Generation of IL-23 Producing Dendritic Cells (DCs) by Airborne Fungi Regulates Fungal Pathogenicity via the Induction of TH-17 Responses

Interleukin-17 (IL-17) producing T helper cells (TH-17) comprise a newly recognized T cell subset with an emerging role in adaptive immunity to a variety of fungi. Whether different airborne fungi trigger a common signaling pathway for TH-17 induction, and whether this ability is related to the inherent pathogenic behavior of each fungus is currently unknown. Here we show that, as opposed to primary pathogenic fungi (Histoplasma capsulatum), opportunistic fungal pathogens (Aspergillus and Rhizopus) trigger a common innate sensing pathway in human dendritic cells (DCs) that results in robust production of IL-23 and drives TH-17 responses. This response requires activation of dectin-1 by the fungal cell wall polysaccharide b-glucan that is selectively exposed during the invasive growth of opportunistic fungi. Notably, unmasking of b-glucan in the cell wall of a mutant of Histoplasma not only abrogates the pathogenicity of this fungus, but also triggers the induction of IL-23 producing DCs. Thus, b-glucan exposure in the fungal cell wall is essential for the induction of IL-23/TH-17 axis and may represent a key factor that regulates protective immunity to opportunistic but not pathogenic fungi

Liquid-crystalline ordering of antimicrobial peptide-DNA complexes controls TLR9 activation.

Double-stranded DNA (dsDNA) can trigger the production of type I interferon (IFN) in plasmacytoid dendritic cells (pDCs) by binding to endosomal Toll-like receptor-9 (TLR9; refs 1-5). It is also known that the formation of DNA-antimicrobial peptide complexes can lead to autoimmune diseases via amplification of pDC activation. Here, by combining X-ray scattering, computer simulations, microscopy and measurements of pDC IFN production, we demonstrate that a broad range of antimicrobial peptides and other cationic molecules cause similar effects, and elucidate the criteria for amplification. TLR9 activation depends on both the inter-DNA spacing and the multiplicity of parallel DNA ligands in the self-assembled liquid-crystalline complex. Complexes with a grill-like arrangement of DNA at the optimum spacing can interlock with multiple TLR9 like a zipper, leading to multivalent electrostatic interactions that drastically amplify binding and thereby the immune response. Our results suggest that TLR9 activation and thus TLR9-mediated immune responses can be modulated deterministically.This work is supported by NSF grants DMR1411329 and DMR1106106, EU grants ARG-ERC-COLSTRUCTION 227758 and ITN-COMPLOIDS 234810, by the Herchel Smith Fund, and by the Slovenian Research Agency through Grant P1-0055, and the Swiss National Science Foundation (FN 310030-144072). X-ray research was conducted at Stanford Synchrotron Radiation Lightsource, SLAC National Laboratory, supported by the US DOE Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515, the Advanced Light Source, supported by the US DOE Office of Basic Energy Sciences under Contract No. DE-AC02-05CH11231, and at the UCLA CNSI.This is the author accepted manuscript. The final version is available from NPG at http://www.nature.com/nmat/journal/v14/n7/full/nmat4298.html

Sector Mataderos-Villa Lugano: Ciudad de Buenos Aires

Presentación del 1er. premio del Concurso Nacional de ideas urbanísticas para el área sur, eje de desarrollo Avenida Eva Perón en el sector Mataderos-Villa Lugano.Material digitalizado en SEDICI gracias a la Facultad de Arquitectura y Urbanismo (UNLP).Facultad de Arquitectura y Urbanism