Prevention of arthritis by interleukin 10-producing B cells

In this study we have shown that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 gives raise to a B cell population that produce high levels of interleukin (IL)-10 and low levels of interferon (IFN)-{gamma}. Transfer of these B cells into DBA/1-TcR-ß-Tg mice, immunized with bovine collagen (CII) emulsified in complete Freund's adjuvant inhibited T helper type 1 differentiation, prevented arthritis development, and was also effective in ameliorating established disease. IL-10 is essential for the regulatory function of this subset of B cells, as the B cells population isolated from IL-10 knockout mice failed to mediate this protective function. Furthermore, B cells isolated from arthritogenic splenocytes treated in vitro with anti–IL-10/anti–IL-10R were unable to protect recipient mice from developing arthritis. Our results suggest a new role of a subset of B cells in controlling T cell differentiation and autoimmune disorders

IGFBP-3 inhibits Wnt signaling in metastatic melanoma cells.

In previous works, we have shown that insulin-like growth factor-binding protein-3 (IGFBP-3), a tissue and circulating protein able to bind to IGFs, decreases drastically in the blood serum of patients with diffuse metastatic melanoma. In agreement with the clinical data, recombinant IGFBP-3 was found to inhibit the motility and invasiveness of cultured metastatic melanoma cells and to prevent growth of grafted melanomas in mice. The present work was aimed at identifying the signal transduction pathways underlying the anti-tumoral effects of IGFBP-3. We show that the anti-tumoral effect of IGFBP-3 is due to inhibition of the Wnt pathway and depends upon the presence of CD44, a receptor protein known to modulate Wnt signaling. Once it has entered the cell, IGFBP-3 binds the Wnt signalosome interacting specifically with its component GSK-3β. As a consequence, the β-catenin destruction complex dissociates from the LRP6 Wnt receptor and GSK-3β is activated through dephosphorylation, becoming free to target cytoplasmic β-catenin which is degraded by the proteasomal pathway. Altogether, the results suggest that IGFBP-3 is a novel and effective inhibitor of Wnt signaling. As IGFBP-3 is a physiological protein which has no detectable toxic effects either on cultured cells or live mice, it might qualify as an interesting new therapeutic agent in melanoma, and potentially many other cancers with a hyperactive Wnt signaling

Early assembly proteins of the large ribosomal subunit of the thermophilic archaebacterium Sulfolobus. Identification and binding to heterologous rRNA species.

Studies of ribosome structure in thermophilic archaebacteria may provide valuable information on (i) the mechanisms involved in the stabilization of nucleic acid-protein complexes at high temperatures and (ii) the degree of evolutionary conservation of the ribosomal components in the primary kingdoms of cell descent. In this work we investigate certain aspects of RNA/protein interaction within the large ribosomal subunits of the extremely thermophilic archaebacterium Sulfolobus solfataricus. The ribosomal proteins involved in the early reactions leading to in vitro particle assembly have been identified; it is shown that they can interact with the RNA in a temperature-independent fashion, forming a thermally stable "core" particle that can subsequently be converted into complete 50 S ribosomes. Among the protein components of the core particle, those capable of independently binding to 23 and 5 S RNA species have also been identified. Finally, we show that the early assembly proteins of Sulfolobus large ribosomal subunits are able to interact cooperatively with 23 S RNAs from other archaebacteria or from eubacteria, thereby suggesting that RNA/protein recognition sites are largely conserved within prokaryotic ribosomes. By contrast, no specific binding of the archaebacterial proteins to eukaryotic RNA could be demonstrated

Epicutaneous Immunization with Type II Collagen Inhibits both Onset and Progression of Chronic Collagen-Induced Arthritis

Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII) inhibited development and progression of CCIA and, importantly, also ameliorated ongoing disease as indicated by clinical scores of disease severity, paw swelling and joints histology. Treated mice show reduced CII-driven T cell proliferation and IFN-gamma production, as well as significantly lower levels of CII-specific IgG2a serum antibodies. In contrast, CII-driven IL-4 production and IgE antibody levels were increased consistent with skewing of the CII response from Th1 to Th2 in treated mice. IL-4 production in treated mice was inversely correlated with disease severity. Moreover, T cells from treated mice inhibited proliferation and IFN-gamma production by T cells from CCIA mice, suggesting induction of regulatory T cells that actively inhibit effector responses in arthritic mice. The levels of CD4(+)CD25(+) T cells were however not increased following epicutaneous CII treatment. Together, these results suggest that epicutaneous immunization may be used as an immune-modulating procedure to actively re-programme pathogenic Th1 responses, and could have potential as a novel specific and simple treatment for chronic autoimmune inflammatory diseases such as rheumatoid arthritis

Emergency Department as an epidemiological observatory of Human Mobility: the experience of the Moroccan population

We conducted a retrospective study of the accesses to the Emergency Department registered from January 2000 to December 2014 in 5 major hospitals in the Metropolitan Area of Rome. We extrapolated data relating to patients of Moroccan origin from about 5 million total accesses, so we compared with Italians data which, in the same period, came to ED. The Moroccan population is distinguished by a larger number of diagnoses belonging to the ICD-9 code of Infectious Diseases and, more precisely, to Respiratory Infectious Diseases. There are also no differences in the assignment of such diagnoses to Moroccans with Italian citizenship, and this led to think that this could play an important role in the use of the ED and moreover that enrollment to the National Health Service may reduce its inappropriate use. Regarding to Degenerative Disorders, the result of our analysis is quite emblematic, showing that the accesses to the ED is due to Cardiovascular Diseases: 6.33% of Italians' accesses against 1.81% of Moroccans and 2.36% of Moroccans with Italian citizenship. The main explanation for this difference is, obviously, due to the age of the population: about 60% of Moroccans who accessed to ED was less than 40 years old. It is interesting how, in the field of ​​Cardiovascular Diseases, Moroccans have a lower percentage of diagnosis compared to Italians for acute diseases and a greater percentage of diagnoses for chronic diseases, suggesting once again that accesses to ED for migrants often is due to the inability to use the general services of the National Health Service. In conclusion, from the point of view of the Emergency Department, Migration Medicine still has Infectious Diseases as the main reason for access. Degenerative Disorders remain a prerogative of the Italians, but we could certainly assume that the Moroccan population would develop at some point with the aging

Artificial Sequences and Complexity Measures

In this paper we exploit concepts of information theory to address the fundamental problem of identifying and defining the most suitable tools to extract, in a automatic and agnostic way, information from a generic string of characters. We introduce in particular a class of methods which use in a crucial way data compression techniques in order to define a measure of remoteness and distance between pairs of sequences of characters (e.g. texts) based on their relative information content. We also discuss in detail how specific features of data compression techniques could be used to introduce the notion of dictionary of a given sequence and of Artificial Text and we show how these new tools can be used for information extraction purposes. We point out the versatility and generality of our method that applies to any kind of corpora of character strings independently of the type of coding behind them. We consider as a case study linguistic motivated problems and we present results for automatic language recognition, authorship attribution and self consistent-classification.Comment: Revised version, with major changes, of previous "Data Compression approach to Information Extraction and Classification" by A. Baronchelli and V. Loreto. 15 pages; 5 figure