Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis

Introduction  

The glucocorticoid receptor (GR) plays an important regulatory role in the immune system. Four polymorphisms in the GR gene are associated with differences in glucocorticoid (GC) sensitivity; the minor alleles of the polymorphisms N363 S and BclI are associated with relative hypersensitivity to GCs, while those of the polymorphisms ER22/23EK and 9β are associated with relative GC resistance. Because differences in GC sensitivity may influence immune effector functions, we examined whether these polymorphisms are associated with the susceptibility to develop Rheumatoid Arthritis (RA) and RA disease severity.     

Aspects of early arthritis. Definition of disease states in early arthritis: remission versus minimal disease activity

With regard to rheumatoid arthritis, remission as currently used in the literature can have two meanings: either a state with persistent absence of clinical and radiological signs of disease activity without being treated for a specific time period, or it may point to a disease state with minimal disease activity during antirheumatic treatment. A risk factor for the first is absence of autoantibodies, with the anti-CCP-antibodies as best predictors, whereas risk factors for achieving a drug-induced state of minimal disease activity are not well defined. These definitions of remission refer to different disease states; therefore, we propose that the term remission is reserved for patients that are not treated with antirheumatic drugs.     

Bioaccumulation of selected metals in the gill,liver and muscle tissue of rednose labeo Labeo rosae from two impoundments on the Olifants River,Limpopo river system,South Africa

Metal concentrations in the gill, muscle and liver tissues of Labeo rosae from two impoundments, Loskop and Flag Boshielo dams on the Olifants River, were evaluated in 2011 to detect patterns in metal associations between tissues and impoundments. Elevated concentrations of Ba, Zn, B, Al, Si and Fe, relative to a pristine site in the catchment, were found in the muscle, liver and gill tissues at both impoundments. Molybdenum concentrations were exceptionally high in all tissues at Loskop Dam and in liver at Flag Boshielo Dam. No definite pattern in the ratio metal concentrations within, or between, fish tissues was identified. The expected trend, liver > gills > muscle, was found at both impoundments, but was less prominent at Loskop Dam. Metal concentrations in muscle of Loskop Dam fish were significantly higher than in those at Flag Boshielo Dam. The inverse was true for liver. The long-term impact of elevated metal concentrations on fish health at both impoundments raises concern.     

Practical and reliable FRET/FLIM pair of fluorescent proteins

Background  

In spite of a great number of monomeric fluorescent proteins developed in the recent years, the reported fluorescent protein-based FRET pairs are still characterized by a number of disadvantageous features, complicating their use as reporters in cell biology and for high-throughput cell-based screenings.     

Stable coexistence of two <Emphasis Type="Italic">Caldicellulosiruptor</Emphasis> species in a <Emphasis Type="Italic">de novo</Emphasis> constructed hydrogen-producing co-culture

Background  

Mixed culture enrichments have been used frequently for biohydrogen production from different feedstock. In spite of the several advantages offered by those cultures, they suffer poor H₂ yield. Constructing defined co-cultures of known H₂ producers may offer a better performance than mixed-population enrichments, while overcoming some of the limitations of pure cultures based on synergies among the microorganisms involved.     

Polyinosinic polycytidylic acid prevents efficient antigen expression after mRNA electroporation of clinical grade dendritic cells

Tumor-derived peptides are used frequently as antigen (Ag) source in dendritic cell (DC) therapy in cancer patients. An alternative is to load DC with tumor-associated Ag (TAA)-encoding RNA. RNA-loading obviates prior knowledge of CTL and Th epitopes in the Ag. Multiple epitopes for many HLA alleles (both MHC class I and class II) are encoded by the RNA and loading is independent of the patient’s HLA make-up. Herein, we determined the optimal conditions for mRNA-electroporation of monocyte-derived DC for clinical application in relation to different maturation cocktails. The data demonstrate that TAA carcinoembryonic antigen, gp100 and tyrosinase are expressed already 30 min after electroporation with the encoding mRNA. Moreover, gp100-specific CTL are activated by gp100 mRNA-electroporated DC. Importantly, we show here that the presence of polyinosinic–polycytidylic acid [poly(I:C)] in the maturation cocktail prevents effective protein expression of the electroporated mRNA as well as subsequent CTL recognition. This effect of poly(I:C) correlates with the induction of IFN-induced genes and innate anti-viral effector molecules in DC. Together these data show that electroporation of mature DC with TAA-encoding mRNA is attractive for use in DC vaccination protocols in cancer patients, but protein expression should be tested for each maturation cocktail. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.