Characterization of the Interaction between the Herpes Simplex Virus Type I Fc Receptor and Immunoglobulin G

Herpes simplex virus type I (HSV-1) virions and HSV-1-infected cells bind to human immunoglobulin G (hIgG) via its Fc region. A complex of two surface glycoproteins encoded by HSV-1, gE and gI, is responsible for Fc binding. We have co-expressed soluble truncated forms of gE and gI in Chinese hamster ovary cells. Soluble gE-gI complexes can be purified from transfected cell supernatants using a purification scheme that is based upon the Fc receptor function of gE-gI. Using gel filtration and analytical ultracentrifugation, we determined that soluble gE-gI is a heterodimer composed of one molecule of gE and one molecule of gI and that gE-gI heterodimers bind hIgG with a 1:1 stoichiometry. Biosensor-based studies of the binding of wild type or mutant IgG proteins to soluble gE-gI indicate that histidine 435 at the CH2-CH3 domain interface of IgG is a critical residue for IgG binding to gE-gI. We observe many similarities between the characteristics of IgG binding by gE-gI and by rheumatoid factors and bacterial Fc receptors such as Staphylococcus aureus protein A. These observations support a model for the origin of some rheumatoid factors, in which they represent anti-idiotypic antibodies directed against antibodies to bacterial and viral Fc receptors

RNAase III-Type Enzyme Dicer Regulates Mitochondrial Fatty Acid Oxidative Metabolism in Cardiac Mesenchymal Stem Cells

Cardiac mesenchymal stem cells (C-MSC) play a key role in maintaining normal cardiac function under physiological and pathological conditions. Glycolysis and mitochondrial oxidative phosphorylation predominately account for energy production in C-MSC. Dicer, a ribonuclease III endoribonuclease, plays a critical role in the control of microRNA maturation in C-MSC, but its role in regulating C-MSC energy metabolism is largely unknown. In this study, we found that Dicer knockout led to concurrent increase in both cell proliferation and apoptosis in C-MSC compared to Dicer floxed C-MSC. We analyzed mitochondrial oxidative phosphorylation by quantifying cellular oxygen consumption rate (OCR), and glycolysis by quantifying the extracellular acidification rate (ECAR), in C-MSC with/without Dicer gene deletion. Dicer gene deletion significantly reduced mitochondrial oxidative phosphorylation while increasing glycolysis in C-MSC. Additionally, Dicer gene deletion selectively reduced the expression of β-oxidation genes without affecting the expression of genes involved in the tricarboxylic acid (TCA) cycle or electron transport chain (ETC). Finally, Dicer gene deletion reduced the copy number of mitochondrially encoded 1,4-Dihydronicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase core subunit 6 (MT-ND6), a mitochondrial-encoded gene, in C-MSC. In conclusion, Dicer gene deletion induced a metabolic shift from oxidative metabolism to aerobic glycolysis in C-MSC, suggesting that Dicer functions as a metabolic switch in C-MSC, which in turn may regulate proliferation and environmental adaptation

The Value of Online Information Privacy: An Empirical Investigation

Concern over online information privacy is widespread and rising. However, prior research is silent about the value of information privacy in the presence of potential benefits from sharing personally identifiable information. Analyzing individuals' trade-offs between the benefits and costs of providing personal information to websites revealed that benefits, monetary reward and future convenience, significantly affect individuals' preferences over websites with differing privacy policies. Quantifying the value of website privacy protection revealed that among U.S. subjects, protection against errors, improper access, and secondary use of personal information is worth US $30.49 - 44.62. Finally, three distinct segments of Internet consumers were determined: privacy guardians, information sellers and convenience seekers.

Co-delivery of human cancer-testis antigens with adjuvant in protein nanoparticles induces higher cell-mediated immune responses.

Nanoparticles have attracted considerable interest as cancer vaccine delivery vehicles for inducing sufficient CD8+ T cell-mediated immune responses to overcome the low immunogenicity of the tumor microenvironment. Our studies described here are the first to examine the effects of clinically-tested human cancer-testis (CT) peptide epitopes within a synthetic nanoparticle. Specifically, we focused on two significant clinical CT targets, the HLA-A2 restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging strategy. Our data shows that simultaneous delivery of a NY-ESO-1 epitope (SLLMWITQV) and CpG using the E2 subunit assembly of pyruvate dehydrogenase (E2 nanoparticle), resulted in a 25-fold increase in specific IFN-γ secretion in HLA-A2 transgenic mice. This translated to a 15-fold increase in lytic activity toward target cancer cells expressing the antigen. Immunization with a MAGE-A3 epitope (FLWGPRALV) delivered with CpG in E2 nanoparticles yielded an increase in specific IFN-γ secretion and cell lysis by 6-fold and 9-fold, respectively. Furthermore, combined delivery of NY-ESO-1 and MAGE-A3 antigens in E2 nanoparticles yielded an additive effect that increased lytic activity towards cells bearing NY-ESO-1+ and MAGE-A3+. Our investigations demonstrate that formulation of CT antigens within a nanoparticle can significantly enhance antigen-specific cell-mediated responses, and the combination of the two antigens in a vaccine can preserve the increased individual responses that are observed for each antigen alone

Study of orientation effect on nanoscale polarization in BaTiO3 thin films using piezoresponse force microscopy

We have investigated the effect of texture on in-plane (IPP) and out- of plane (OPP) polarizations of pulsed-laser-deposited BaTiO3 thin films grown on Pt and La0.5Sr0.5CoO3 (LSCO) buffered Pt electrodes. The OPP and IPP polarizations were observed by piezoresponse force microscopy (PFM) for three-dimensional polarization analyses in conjunction with conventional diffraction methods using x-ray diffraction and reflection high energy electron diffraction measurements. BaTiO3 films grown on Pt electrodes exhibited highly (101) preferred orientation with higher IPP component whereas BaTiO3 film grown on LSCO/Pt electrodes showed (001) and (101) orientations with higher OPP component. Measured effective d(33) values of BaTiO3 films deposited on Pt and LSCO/ Pt electrodes were 14.3 and 54.0 pm/ V, respectively. Local piezoelectric strain loops obtained by OPP and IPP-PFM showed that piezoelectric properties were strongly related to film orientation

On the Origin of Radial Magnetic Fields in Young Supernova Remnants

We study the radio emission from young supernova remnants by means of 3D numerical MHD simulations of the Rayleigh-Taylor instability in the shell of the remnant. The computation is carried out in spherical polar coordinates ($r, \theta, \phi$) by using a moving grid technique which allows us to finely resolve the shell. Three-dimensional result shows more turbulent (complex) structures in the mixing region than the two-dimensional result, and the instability is found to deform the reverse shock front. Stokes parameters (I,Q, and U) are computed to study the radio properties of the remnant. The total intensity map shows two distinctive regions (inner and outer shells). The inner shell appears to be complex and turbulent exhibiting loop structures and plumes as a result of the Rayleigh-Taylor instability, while the outer shell is faint and laminar due to the shocked uniform ambient magnetic fields. The inner shell resembles the observed radio structure in the main shell of young SNRs, which is evidence that the Rayleigh-Taylor instability is an ongoing process in young SNRs. When only the peculiar components of the magnetic fields generated by the instability are considered, the polarization B-vector in the inner radio shell is preferentially radial with about $20 \sim 50\%$ of fractional polarization which is higher than the observed value. The fractional polarization is lowest in the turbulent inner shell and increases outward, which is attributed to the geometric effect. The polarized intensity is found to be correlated with the total intensity. We demonstrate that the polarized intensity from the turbulent region can dominate over the polarized intensity from the shocked uniform fields if the amplified field is sufficiently strong. Therefore, we conclude that the Rayleigh-Taylor instability can explain the dominant radial magneticComment: 26 pages, Latex, 13 Postscript figures. Figures obtainable by email to [email protected]. Accepted for publication in the Astrophysical Journa

Theory of Luminescent Emission in Nanocrystal ZnS:Mn with an Extra Electron

We consider the effect of an extra electron injected into a doped quantum dot $ZnS:Mn^{2+}$. The Coulomb interaction and the exchange interaction between the extra electron and the states of the Mn ion will mix the wavefunctions, split the impurity energy levels, break the previous selection rules and change the transition probabilities. Using this model of an extra electron in the doped quantum dot, we calculated the energy and the wavefunctions, the luminescence probability and the transition lifetime and compare with the experiments. Our calculation shows that two orders of magnitudes of lifetime shortening can occur in the transition $^4T_1-^6A_1$ when an extra electron is present.Comment: 15 pages, 2 Figs No change in Fig