Momentum Entanglement for Atom Interferometry.

Compared to light interferometers, the flux in cold-atom interferometers is low and the associated shot noise is large. Sensitivities beyond these limitations require the preparation of entangled atoms in different momentum modes. Here, we demonstrate a source of entangled atoms that is compatible with state-of-the-art interferometers. Entanglement is transferred from the spin degree of freedom of a Bose-Einstein condensate to well-separated momentum modes, witnessed by a squeezing parameter of -3.1(8) dB. Entanglement-enhanced atom interferometers promise unprecedented sensitivities for quantum gradiometers or gravitational wave detectors.

Atom-Chip Fountain Gravimeter.

We demonstrate a quantum gravimeter by combining the advantages of an atom chip for the generation, delta-kick collimation, and coherent manipulation of freely falling Bose-Einstein condensates (BECs) with an innovative launch mechanism based on Bloch oscillations and double Bragg diffraction. Our high-contrast BEC interferometer realizes tens of milliseconds of free fall in a volume as little as a one centimeter cube and paves the way for measurements with sub-µGal accuracies in miniaturized, robust devices.

Cell-mediated reduction of human ß-defensin 1: a major role for mucosal thioredoxin.

Human ß-defensin 1 (hBD-1) is an antimicrobial peptide expressed by epithelia and hematopoietic cells. We demonstrated recently that hBD-1 shows activity against enteric commensals and Candida species only after its disulfide bonds have been reduced by thioredoxin (TRX) or a reducing environment. Here we show that besides TRX, glutaredoxin (GRX) is also able to reduce hBD-1, although with far less efficacy. Moreover, living intestinal and lymphoid cells can effectively catalyze reduction of extracellular hBD-1. By chemical inhibition of the TRX system or specific knockdown of TRX, we demonstrate that cell-mediated reduction is largely dependent on TRX. Quantitative PCR in intestinal tissues of healthy controls and inflammatory bowel disease patients revealed altered expression of some, although not all, redox enzymes, especially in ulcerative colitis. Reduced hBD-1 and TRX localize to extracellular colonic mucus, suggesting that secreted or membrane-bound TRX converts hBD-1 to a potent antimicrobial peptide in vivo.

Innate immune dysfunction in inflammatory bowel disease.

The pathogenetic mechanisms that cause the two types of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are still under investigation. Nevertheless, there is broad agreement that luminal microbes are of particular relevance in the development of these conditions. In recent years, increasing evidence has shown that defects in the innate immunity are at the centre of both types of IBD. The innate intestinal barrier is provided by the epithelium which secretes antimicrobial peptides (so-called defensins) that are retained in the mucus layer. In ileal CD, the alpha-defensins are lacking owing to several Paneth cell defects. In colonic CD, the expression of beta-defensins is inadequate. This may be related to downregulation of the transcription factor peroxisome proliferator-activated receptor-gamma and in some cohorts is associated with a reduced HBD2 gene copy number. In UC, the mucus layer, which protects the host from the enormous amounts of luminal microbes, is defective. This is accompanied by an insufficient differentiation from intestinal stem cells towards goblet cells. All these disturbances in the gut barrier shift the balance from epithelial defence towards bacterial offence. The current treatment for CD and UC is based on suppression of this secondary inflammatory process. In future, patients may benefit from new therapeutic approaches stimulating the protective innate immune system.

Influence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn's disease.

BACKGROUND: Crohn's Disease (CD), a chronic intestinal inflammation, is currently treated primarily by therapeutics which are directed against inflammatory responses. Recent findings though suggest a central role of the innate immune barrier in the pathophysiology. Important factors providing this barrier are antimicrobial peptides like the alpha- and beta-defensins. Little is known about in vivo effects of common drugs on their expression. AIM: To analyse the influence of corticosteroids, azathioprine and aminosalicylate treatment on ileal and colonic antimicrobial peptides in active CD and also assess the role of inflammation. METHODS: We measured the expression of antimicrobial peptides and pro-inflammatory cytokines in 75 patients with active CD. RESULTS: Ileal and colonic alpha- and beta-defensins as well as LL37 remained unaffected by corticosteroids, azathioprine or aminosalicylate treatment. Additionally, we did not observe a negative coherency between Paneth cell alpha-defensins and any measured cytokines. HBD2 and LL37 unlike HBD1 levels were linked to inflammatory cytokines and increased in highly inflamed samples. CONCLUSIONS: Current oral drug treatment seems to have no major effect on the expression of antimicrobial peptides. In contrast to HBD2 and LL37, ileal levels of HD5 and HD6 and colonic HBD1 level are independent of current inflammation. Innovative drugs should aim to strengthen protective innate immunity.