MicroRNAs (miRNAs) post-transcriptionally regulate the expression of target genes, and may behave as oncogenes or tumor suppressors. Human malignant mesothelioma is an asbestos-related cancer, with poor prognosis and low median survival. Here we report, for the first time, a cross-evaluation of miRNA expression in mesothelioma (MPP-89, REN) and human mesothelial cells (HMC-telomerase reverse transcriptase). Microarray profiling, confirmed by real-time quantitative RT-PCR, revealed a differential expression of miRNAs between mesothelioma and mesothelial cells. In addition, a computational analysis combining miRNA and gene expression profiles allowed the accurate prediction of genes potentially targeted by dysregulated miRNAs. Several predicted genes belong to terms of Gene Ontology (GO) that are associated with the development and progression of mesothelioma. This suggests that miRNAs may be key players in mesothelioma oncogenesis. We further investigated miRNA expression on a panel of 24 mesothelioma specimens, representative of the three histotypes (epithelioid, biphasic, and sarcomatoid), by quantitative RT-PCR. The expression of miR-17-5p, miR-21, miR-29a, miR-30c, miR-30e-5p, miR-106a, and miR-143 was significantly associated with the histopathological subtypes. Notably, the reduced expression of two miRNAs (miR-17-5p and miR-30c) correlated with better survival of patients with sarcomatoid subtype. Our preliminary analysis points at miRNAs as potential diagnostic and prognostic markers of mesothelioma, and suggests novel tools for the therapy of this malignancy.

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The classical action for pure Yang-Mills gauge theory can be formulated as a deformation of the topological BF theory where, beside the two-form field B, one has to add one extra-field η given by a one-form which transforms as the difference of two connections. The ensuing action functional gives a theory that is both classically and quantistically equivalent to the original Yang-Mills theory. In order to prove such an equivalence, it is shown that the dependency on the field η can be gauged away completely. This gives rise to a field theory that, for this reason, can be considered as semi-topological or topological in some but not all the fields of the theory. The symmetry group involved in this theory is an affine extension of the tangent gauge group acting on the tangent bundle of the space of connections. A mathematical

Immune thrombocytopaenic purpura (ITP) is an autoimmune systemic disease detectable by the presence of low blood platelets count (<10(5)/µl) and the production of autoantibodies against glycoproteins expressed on the platelet surface. The clinical course is often acute, and life-threatening events may occur especially in children, with 52% of paediatric patients recovering either spontaneously or after treatment. A chronic ITP evolution is observed in 64% of adults, of whom 12% will develop an overlapping autoimmune disease. Several microbial agents such as CagA-positive Helicobacter pylori or Candida albicans and a number of viruses including CMV, EBV or HIV can potentially trigger ITP through molecular mimicry. Moreover, ITP improves after treatment of the underlying infection. Similarly, vaccines such as MMR may prompt ITP (IRR 5.48, 1.61-18.64, p < 0.006). Early recognition of the underlying microbial trigger and the removal of modifiable aetiopathogenetic factors should be integrated as a complementary treatment strategy in all patients who do not readily improve with standard ITP care.

Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer's aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn's disease years later. Our results strongly suggest that ASCAs' role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.

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We study the differential geometry of principal G-bundles whose base space is the space of free paths (loops) on a manifold M . In particular we consider connections defined in terms of pairs (A, B), where A is a connection for a fixed principal bundle P (M, G) and B is a 2-form on M . The relevant curvatures, parallel transports and holonomies are computed and their expressions in local coordinates are exhibited. When the 2-form B is given by the curvature of A, then the so-called non-abelian Stokes formula follows.For a generic 2-form B, we distinguish the cases when the parallel transport depends on the whole path of paths and when it depends only on the spanned surface. In particular we discuss generalizations of the non-abelian Stokes formula. We study also the invariance properties of the (trace of the) holonomy under suitable transformation groups acting on the pairs (A, B).In this way we are able to define observables for both topological and non-topological quantum field theories of the BF type. In the non topological case, the surface terms may be relevant for the understanding of the quark-confinement problem. In the topological case the (perturbative) fourdimensional quantum BF -theory is expected to yield invariants of imbedded (or immersed) surfaces in a 4-manifold M .

Abstract. Consider the familyof semilinear Neumann boundary value problems, where, for ε > 0 small, the set Ω ε is a thin domain in R l , possibly with holes, which collapses, as ε → 0 + , onto a (curved)We identify a "limit" equation for the family (E ε ), prove convergence of trajectories and establish an upper semicontinuity result for the family A ε as ε → 0 + .