Of Natural Killer cells and Hepatitis C Virus

Natural Killer (NK) cells are important effector cells in Hepatitis C Virus (HCV) infection, a virus that chronically infects around 2.5% of the world population and is a major cause of liver disease and hepatocellular carcinoma. The exact mechanisms, however, through which NK cells are activated in response to HCV remain elusive. Using the well-established HCV replicon cell-culture model we show that after co- culture of HCV replicon-carrying hepatocytes with peripheral blood mononuclear cells (PBMCs), NK cells increase expression of the high-affinity IL-2 receptor chain CD25, proliferate rapidly and produce IFN-gamma. Activation of NK cells was dependent on IL-2, most likely produced by T cells and on cell-cell contact mediated signals from monocytes. Monocytes from replicon-carrying co-cultures showed increased expression of OX40L, a member of the tumor necrosis factor family and concurrently its receptor OX40 was increased on NK cells. Blocking of OX40L in those co-cultures, as well as depletion of CD14+ monocytes abrogated the virus-induced activation and effector functions of NK cells. Together, our data reveals a novel mechanism of monocyte mediated NK cell activation against virus-infected cells involving the OX40/OX40L axis with potential relevance for therapeutic intervention by e.g. agonistic antibodies against OX40, which are already tested in cancer therapy

Molecular evolution of Cide family proteins: Novel domain formation in early vertebrates and the subsequent divergence-5

Algorithm. The CIDE-N domain is indicated by a dark line on top of the alignment. The alignment of the most conserved region of 37 amino acids encompassing the EDGT signature motif is framed with a red rectangle. The signatures of Cide and Dff family proteins are framed with a green rectangle. The exon boundaries are marked by black vertical lines. (B) Sequence alignment of the CIDE-C domains of Cide family proteins found in human and mouse using MAFFT algorithm. The CIDE-C domain is indicated by a dark line on top of the alignment. The alignment of most conserved 35 amino acids is framed with a red rectangle. The exon boundaries are marked by black vertical lines.<p><b>Copyright information:</b></p><p>Taken from "Molecular evolution of Cide family proteins: Novel domain formation in early vertebrates and the subsequent divergence"</p><p>http://www.biomedcentral.com/1471-2148/8/159</p><p>BMC Evolutionary Biology 2008;8():159-159.</p><p>Published online 23 May 2008</p><p>PMCID:PMC2426694.</p><p></p

Cell Cycle Network Scheme

<p>aa, amino acids; ∼P, ATP; Pi, inorganic phosphate</p

Figure 4

<p>The Free Energy as a Function of Overlap Parameter Q Relative to the Global Minimum G1 Steady-State Fixed Point at Low Temperature (50,000), Intermediate Temperature (77,500), and High Temperature (100,000)</p

Thermodynamic Phase Diagram for the Yeast Cell–Cycle Network

<p>Native phase with global minimum G0/G1 state or steady state; non-native phase with states less overlapping with global minimum G0/G1 state or steady state; trapping phase with states trapped into the local minimum. The larger of δU/T and smaller of ΔU/T, or the larger <i>δ</i>U/ΔU, the more likely the global minimum G1 state is thermodynamically stable and robust.</p

The Global Structures and Properties of the Underlying Potential Landscape of the Yeast Cell–Cycle Network

<div><p>(A) The histogram or the distribution of the potential U.</p><p>(B) The potential landscape spectrum.</p><p>(C) The funnelled landscape of the yeast cell–cycle network.</p><p>(D) The averaged potential as a function of similarity parameter Q with respect to the global minimum G1 state (or global steady state) of potential U.</p><p>(E) The entropy as a function of similarity order parameter Q with respect to the global minimum G1 state (or global steady state) of the potential U.</p></div

Figure 3

<p>The Averaged Potential U as a Function of Similarity Parameter Q with Respect to the Global Minimum G1 State (or Global Steady State) of Potential U against Perturbations of Chemical Rate Coefficient Parameters with 10% Increase (Decrease), 20% Increase (Decrease)</p

The percentage of known colorectal cancer (CRC) genes in top 50–500 MDMs inferred from German dataset.

<p>Known CRC genes were collected from the PubGene (A) or OMIM (B). The percentages were compared with those in top differentially expressed genes (t-test genes) with the same number of genes in top ranked N modules, or GO gene sets with the same amount of top ranked N modules.</p

Overall Performances of Mammalian Classifiers Based on 5-fold Cross-validation Tests.

<p>(A) The ROC curve illustrating the performance for full transcript mode. (B) The ROC curve illustrating the performance for mature mRNA mode.</p

Performance of RNAMethPre for various stringency thresholds and comparison with SRAMP.

<p>Performance of RNAMethPre for various stringency thresholds and comparison with SRAMP.</p