Upper respiratory tract infection is a frequent cause of morbidity worldwide. Although the course of infection is usually mild, it is responsible for enormous social and economic costs. Immunostimulation with bacterial extracts consisting of ribosomal RNA and proteoglycans, such as Ribomunyl(®), was introduced into the clinic in the 1980s as a new treatment concept, but did not achieve widespread application. Ribomunyl(®) has been proposed to activate innate immunity, but the contribution of its RNA content as well as its antiviral potential has not been studied. Peripheral blood mononuclear cells from healthy donors and immune cells from adenoids were incubated with Ribomunyl(®) either by itself or formulated in a complex with cationic polypeptides such as poly-l-arginine or protamine, and induction of cytokines was quantified by ELISA. Ribomunyl(®) in complex with either poly-l-arginine or protamine, but not on its own, was able to strongly induce interferon-α (P<0.01) and interleukin-12 (P<0.01) in peripheral blood mononuclear cells, whereas induced tumour necrosis factor-α and interleukin-6 levels were independent of the formulation. Comparable results were obtained in immune cells from adenoids, suggesting efficacy also in virus-affected tissue. Cell sorting, RNase digests and selective receptor expression show that the RNA in Ribomunyl(®) acts as an agonist of Toll-like receptor (TLR)7 and TLR8. Ribomunyl(®) is, in principle, able to potently induce antiviral interferon-α and interleukin-12 via TLR7 and TLR8, respectively, but only when formulated in a complex with cationic polypeptides.

Epigenetics and transplantation seem an odd couple. The influence of epigenetic changes on the immune response of the host following an organ graft is not one of the more obvious connections. However, modifying host immunity to a graft via epigenetic changes of immune related genes could have unexpected ramifications for therapy post transplantation. This review discusses various studies concerning the effects of epigenetic alterations on transplantation-associated pathologies. We present tools for improving transplantation outcome, such as histone deacetylase inhibition, DNA methyltransferase inhibition or venous systemic oxygen persufflation. This will allow a reduction of immunosuppressive medication, leading to fewer side effects. We also show, however, that much effort needs to be put into the elucidation of the molecular mechanisms underlying these advantageous effects. Taken together, altering epigenetics in transplanted organs will ultimately lead to a higher quality of life for transplant patients.

What we believe to be the first demonstration of isotope-specific detection of a low-Z and low density object shielded by a high-Z and high-density material using monoenergetic gamma rays is reported. The isotope-specific detection of LiH shielded by Pb and Al is accomplished using the nuclear resonance fluorescence line of L7i at 478 keV. Resonant photons are produced via laser-based Compton scattering. The detection techniques are general, and the confidence level obtained is shown to be superior to that yielded by conventional x-ray and gamma-ray techniques in these situations.

Antiviral immunity is triggered by immunorecognition of viral nucleic acids. The cytosolic helicase RIG-I is a key sensor of viral infections and is activated by RNA containing a triphosphate at the 5' end. The exact structure of RNA activating RIG-I remains controversial. Here, we established a chemical approach for 5' triphosphate oligoribonucleotide synthesis and found that synthetic single-stranded 5' triphosphate oligoribonucleotides were unable to bind and activate RIG-I. Conversely, the addition of the synthetic complementary strand resulted in optimal binding and activation of RIG-I. Short double-strand conformation with base pairing of the nucleoside carrying the 5' triphosphate was required. RIG-I activation was impaired by a 3' overhang at the 5' triphosphate end. These results define the structure of RNA for full RIG-I activation and explain how RIG-I detects negative-strand RNA viruses that lack long double-stranded RNA but do contain blunt short double-stranded 5' triphosphate RNA in the panhandle region of their single-stranded genome.