Interferon-mediated intracellular signalling Modulation of different phospholipase activities in Burkitt lymphoma cells

AbstractThe effect of interferon-α on Daudi lymphoma cells either sensitive or resistant to the action of this cytokine has been analysed in terms of phospholipase C (PLC) and D (PLD) activities. Results have shown a combined modulation of PIP2-specific phospholipase C and phospholipase D. In particular, a decreased activity of PIP2-specific PLC has been found, concomitant to a PLD-mediated phosphatidylcholine hydrolysis, suggesting that the intracellular signaling activated by interferon in Daudi cells involves a phospholipase D/phosphohydrolase pathway

Theoretical analysis and numerical verification of the consistency of viscous smoothed-particle-hydrodynamics formulations in simulating free-surface flows

The theoretical formulation of the smoothed particle hydrodynamics (SPH) method deserves great care because of some inconsistencies occurring when considering free-surface inviscid flows. Actually, in SPH formulations one usually assumes that (i) surface integral terms on the boundary of the interpolation kernel support are neglected, (ii) free-surface conditions are implicitly verified. These assumptions are studied in detail in the present work for free-surface Newtonian viscous flow. The consistency of classical viscous weakly compressible SPH formulations is investigated. In particular, the principle of virtual work is used to study the verification of the free-surface boundary conditions in a weak sense. The latter can be related to the global energy dissipation induced by the viscous term formulations and their consistency. Numerical verification of this theoretical analysis is provided on three free-surface test cases including a standing wave, with the three viscous term formulations investigated

miR-217 is an oncogene that enhances the germinal center reaction.

microRNAs are a class of regulators of gene expression that have been shown critical for a great number of biological processes; however, little is known of their role in germinal center (GC) B cells. Although the GC reaction is crucial to ensure a competent immune response, GC B cells are also the origin of most human lymphomas, presumably due to bystander effects of the immunoglobulin gene remodeling that takes place at these sites. Here we report that miR-217 is specifically upregulated in GC B cells. Gain- and loss-of-function mouse models reveal that miR-217 is a positive modulator of the GC response that increases the generation of class-switched antibodies and the frequency of somatic hypermutation. We find that miR-217 down-regulates the expression of a DNA damage response and repair gene network and in turn stabilizes Bcl-6 expression in GC B cells. Importantly, miR-217 overexpression also promotes mature B-cell lymphomagenesis; this is physiologically relevant as we find that miR-217 is overexpressed in aggressive human B-cell lymphomas. Therefore, miR-217 provides a novel molecular link between the normal GC response and B-cell transformation.S

MicroRNA signatures in B-cell lymphomas

Accurate lymphoma diagnosis, prognosis and therapy still require additional markers. We explore the potential relevance of microRNA (miRNA) expression in a large series that included all major B-cell non-Hodgkin lymphoma (NHL) types. The data generated were also used to identify miRNAs differentially expressed in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) samples. A series of 147 NHL samples and 15 controls were hybridized on a human miRNA one-color platform containing probes for 470 human miRNAs. Each lymphoma type was compared against the entire set of NHLs. BL was also directly compared with DLBCL, and 43 preselected miRNAs were analyzed in a new series of routinely processed samples of 28 BLs and 43 DLBCLs using quantitative reverse transcription-polymerase chain reaction. A signature of 128 miRNAs enabled the characterization of lymphoma neoplasms, reflecting the lymphoma type, cell of origin and/or discrete oncogene alterations. Comparative analysis of BL and DLBCL yielded 19 differentially expressed miRNAs, which were confirmed in a second confirmation series of 71 paraffin-embedded samples. The set of differentially expressed miRNAs found here expands the range of potential diagnostic markers for lymphoma diagnosis, especially when differential diagnosis of BL and DLBCL is required

Role of MicroRNA Profile Modifications in Hepatitis C Virus-Related Mixed Cryoglobulinemia

Hepatitis C virus infection is closely related to lymphoproliferative disorders (LPDs), including mixed cryoglobulinemia (MC) and some lymphomas. Modification of the expression of specific microRNAs (miRNAs) has been associated with different autoimmune diseases and/or LPDs. No data exist about the modifications in miRNA expression in HCV-associated LPDs. The aim of this study was to analyze the expression levels of a panel of miRNAs previously associated with autoimmune/LPDs in a large population of HCV patients with and without MC or non-Hodgkin’s lymphoma (NHL), to identify potential markers of evolution of HCV infection. PBMC expression of miR-Let-7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 was evaluated by real-time PCR in 167 HCV patients (75 with MC [MC-HCV], 11 with HCV-associated NHL [NHL-HCV], 81 without LPD [HCV]) and in 35 healthy subjects (HS). A significant increase in miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression was detected in PBMCs from only NHL patients whereas a significant decrease in miR-26b was detected in both MC and NHL subjects (p<0.01) when compared to HS and HCV groups. A restoration of miR-26b levels was observed in the post-treatment PBMCs of 35 HCV-MC patients experiencing complete virological and clinical response following antiviral therapy. This study, for the first time, shows that specific microRNAs in PBMC from HCV patients who developed MC and/or NHL are modulated differently. The specific, reversible downregulation of miR-26b strongly suggests the key role it plays in the pathogenesis of HCV-related LPDs and its usefulness as a biomarker of the evolution of HCV infection to these disorders

MicroRNA expression in tumor cells from Waldenstrom's macroglobulinemia reflects both their normal and malignant cell counterparts

MicroRNAs (miRNAs) are involved in the regulation of many cellular processes including hematopoiesis, with the aberrant expression of differentiation-stage specific miRNA associated with lymphomagenesis. miRNA profiling has been essential for understanding the underlying biology of many hematological malignancies; however the miRNA signature of the diverse tumor clone associated with Waldenstrom's macroglobulinemia (WM), consisting of B lymphocytes, plasmacytes and lymphoplasmacytic cells, has not been characterized. We have investigated the expression of over 13 000 known and candidate miRNAs in both CD19+ and CD138+ WM tumor cells, as well as in their malignant and non-malignant counterparts. Although neither CD19+ nor CD138+ WM cells were defined by a distinct miRNA profile, the combination of all WM cells revealed a unique miRNA transcriptome characterized by the dysregulation of many miRNAs previously identified as crucial for normal B-cell lineage differentiation. Specifically, miRNA-9*/152/182 were underexpressed in WM, whereas the expression of miRNA-21/125b/181a/193b/223/363 were notably increased (analysis of variance; P<0.0001). Future studies focusing on the effects of these dysregulated miRNAs will provide further insight into the mechanisms responsible for the pathogenesis of WM

A criterion for the choice of the interpolation kernel in Smoothed Particle Hydrodynamics

We study the problem of the appropriate choice of the interpolating kernel to be used in the evaluation of gradients of functions. Such interpolation technique is often used in applications, e.g., it is typical for Smoothed Particle Hydrodynamics (SPH). We propose a minimization procedure for selecting kernels in View the MathML source , in the class of regular, normalizable, symmetric functions having finite moments up to a sufficiently high order; the method is valid when the kernel width is position-dependent and allows to recover conservation laws at the same order of approximation that SPH, as interpolation technique, has when the kernel size is constant