Tissue-specific expression Patterns of Microrna during acute graft-versus-host Disease in the rat

MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease. We utilized a rat model of aGvHD with transplantation of fully MHC-mismatched T cell depleted bone marrow, followed by infusion of donor T cells. The expression pattern of 423 rat miRNAs was investigated in skin, gut, and lung tissues and intestinal T cells with the NanoString hybridization platform, in combination with validation by quantitative PCR. MHC-matched transplanted rats were included as controls. In the skin, upregulation of miR-34b and downregulation of miR-326 was observed, while in the intestines, we detected downregulation of miR-743b and a trend toward downregulation of miR-345-5p. Thus, tissue-specific expression patterns of miRNAs were observed. Neither miR-326 nor miR-743b has previously been associated with aGvHD. Moreover, we identified upregulation of miR-146a and miR-155 in skin tissue of rats suffering from aGvHD. Analysis of intestinal T cells indicated 23 miRNAs differentially regulated between aGvHD and controls. Two of these miRNAs were differentially expressed either in skin (miR-326) or in intestinal (miR-345-5p) tissue. Comparison of intestinal and peripheral blood T cells indicated common dysregulated expression of miR-99a, miR-223, miR-326, and miR-345-5p. Analysis of predicted gene targets for these miRNAs indicated potential targeting of an inflammatory network both in skin and in the intestines that may further regulate inflammatory cytokine production. In conclusion, comprehensive miRNA profiling in rats suffering from aGvHD demonstrate tissue-specific differences in the expression patterns of miRNA that may not be detected by profiling of peripheral blood T cells alone. These tissue-specific miRNAs may contribute to distinct pathologic mechanisms and could represent potential targets for therapy

A monotone multigrid solver for two body contact problems in biomechanics

The purpose of the paper is to apply monotone multigrid methods to static and dynamic biomechanical contact problems. In space, a finite element method involving a mortar discretization of the contact conditions is used. In time, a new contact-stabilized Newmark scheme is presented. Numerical experiments for a two body Hertzian contact problem and a biomechanical application are reported

In laboratorio con Cabri 3D. 25 schede di geometria dello spazio

Il volume è composto da 25 schede di laboratorio di geometria dello spazio per la scuola secondaria, suddivise in 8 nuclei tematici (Una panoramica su Cabri 3D; Punti, rette e piani nello spazio; Diedri, triedri e angoloidi; Poliedri; Superfici e solidi di rotazione; Volumi e superfici; Coordinate, vettori ed equazioni nello spazio; Trasformazioni geometriche dello spazio). Nelle schede ci sono anche dei richiami teorici, che permettono di utilizzare il libro in modo autonomo. Il volume è corredato da una Guida per l’insegnante (in Internet), che illustra la struttura di ogni nucleo tematico, le caratteristiche e il possibile utilizzo didattico di ogni scheda in laboratorio con l'uso del software Cabri 3D