Lower negative bounds on the static electric susceptibility of nonequilibrium cubic crystals

We use a classical, microscopic model of pointlike dipolarizable entities (a model that is standard in the case of positive polarizability) and investigate its behavior for simple cubic (sc), body-centered cubic (bcc), and face-centered cubic (fcc) crystals with one entity per primitive cell when the static polarizability of the entities is negative and the mutual electrostatic interaction between the entities is taken into account. We find that the static electric susceptibility is bounded below due to an instability towards self-polarization but negative values are possible in each case. The usual Clausius-Mossotti relation between the static polarizability and the static electric susceptibility remains valid in the case of negative parameters but is truncated at the lower bound; the value of the bound depends on the crystal structure and is always unrelated to the asymptote of the Clausius-Mossotti curve. The lower bounds of the static electric susceptibility are found to be -0.906 for sc and -1.00 for bcc and fcc. These results confirm that, although the magnitude of the static electric susceptibility does not diverge in the negative case (as it can in the positive case), the magnitudes attainable in the negative case for condensed media may, nevertheless, be many orders of magnitude greater than those predicted previously for inverted vapors and gases. This is a promising result in relation to the development of potential new technologies that exploit the phenomenon

C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function

We describe a novel localization of C7 as a membrane-bound molecule on endothelial cells (ECs). Data obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis, and mass spectrometry revealed that membrane- associated C7 (mC7) was indistinguish-able from soluble C7 and was associated with vimentin on the cell surface. mC7 interacted with the other late complement components to form membrane-bound TCC (mTCC). Unlike the soluble SC5b-9, mTCC failed to stimulate ECs to express adhesion molecules, to secrete IL-8, and to induce albumin leakage through a monolayer of ECs, and more importantly protected ECs from the proinflammatory effect of SC5b-9. Our data disclose the possibility of a novel role of mC7 that acts as a trap for the late complement components to control excessive inflammation induced by SC5b-9. \ua9 2009 by The American Society of Hematology

The structure of the Shiga toxin 2a A-subunit dictates the interactions of the toxin with blood components

Hemolytic uremic syndrome (eHUS) is a severe complication of human infections with Shiga toxins (Stxs)-producing Escherichia coli. A key step in the pathogenesis of eHUS is the interaction of Stxs with blood components before the targeting of renal endothelial cells. Here, we show that a single proteolytic cleavage in the Stx2a A-subunit, resulting into two fragments (A1 and A2) linked by a disulfide bridge (cleaved Stx2a), dictates different binding abilities. Uncleaved Stx2a was confirmed to bind to human neutrophils and to trigger leukocyte/platelet aggregate formation, whereas cleaved Stx2a was ineffective. Conversely, binding of complement factor H was confirmed for cleaved Stx2a and not for uncleaved Stx2a. It is worth noting that uncleaved and cleaved Stx2a showed no differences in cytotoxicity for Vero cells or Raji cells, structural conformation, and contaminating endotoxin. These results have been obtained by comparing two Stx2a batches, purified in different laboratories by using different protocols, termed Stx2a(cl; cleaved toxin, Innsbruck) and Stx2a(uncl; uncleaved toxin, Bologna). Stx2a(uncl) behaved as Stx2a(cl) after mild trypsin treatment. In this light, previous controversial results obtained with purified Stx2a has to be critically re-evaluated; furthermore, characterisation of the structure of circulating Stx2a is mandatory to understand eHUS-pathogenesis and to develop therapeutic approaches

Stratégiai szövetségek, a vállalati kapcsolati hálók átalakulása és a versenyképesség

Transplantation and autoimmunit

BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration

BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest. Consistent with our clinical observations, BRF1 overexpression in a Pten-deficient mouse (Pten BRF1 ) prostate cancer model accelerated prostate carcinogenesis and shortened survival. In Pten BRF1 tumours, immune and inflammatory processes were altered, with reduced tumoral infiltration of neutrophils and CD4 positive T cells, which can be explained by decreased levels of complement factor D (CFD) and C7 components of the complement cascade, an innate immune pathway that influences the adaptive immune response. We tested if the secretome was involved in BRF1-driven tumorigenesis. Unbiased proteomic analysis on BRF1-overexpresing PC3 cells confirmed reduced levels of CFD in the secretome, implicating the complement system in prostate carcinogenesis. We further identify that expression of C7 significantly correlates with expression of CD4 and has the potential to alter clinical outcome in human prostate cancer, where low levels of C7 associate with poorer prognosis

The Cayapa Indians of Ecuador: a genetically isolated group with unexpected complement C7 M/N allele frequencies

The Cayapa Indians live in north-western Ecuador in close proximity to a Black population of African ancestry. C7 M/N allotyping has proved to be a good technique for plasma genetic analysis in several populations. Investigation of 124 Cayapa plasma samples revealed the highest allele frequency of C7(*)N observed in any population examined so far (0.36 versus 0.225 or lower). The marked difference in frequency compared with several Oriental populations, which are believed to have been derived from the same Asian population as native Amerindians, may reflect the effect of a small founder population followed by a high degree of genetic isolation. The allele frequency of 0.12 for C7(*)N determined for the neighbouring Black population supports the conclusion that there has been a lack of genetic admixture of Cayapas with other populations, confirming the results of ethnohistorical investigations and other protein polymorphism studies