Long Non-Coding RNAs in Sjögren's Disease.

Sjögren's disease (SjD) is a heterogeneous autoimmune disease characterized by severe dryness of mucosal surfaces, particularly the mouth and eyes; fatigue; and chronic pain. Chronic inflammation of the salivary and lacrimal glands, auto-antibody formation, and extra-glandular manifestations occur in subsets of patients with SjD. An aberrant expression of long, non-coding RNAs (lncRNAs) has been described in many autoimmune diseases, including SjD. Here, we review the current literature on lncRNAs in SjD and their role in regulating X chromosome inactivation, immune modulatory functions, and their potential as biomarkers.

The epigenetic architecture at gene promoters determines cell type-specific LPS tolerance.

Synovial fibroblasts (SF) drive inflammation and joint destruction in chronic arthritis. Here we show that SF possess a distinct type of LPS tolerance compared to macrophages and other types of fibroblasts. In SF and dermal fibroblasts, genes that were non-tolerizable after repeated LPS stimulation included pro-inflammatory cytokines, chemokines and matrix metalloproteinases, whereas anti-viral genes were tolerizable. In macrophages, all measured genes were tolerizable, whereas in gingival and foreskin fibroblasts these genes were non-tolerizable. Repeated stimulation of SF with LPS resulted in loss of activating histone marks only in promoters of tolerizable genes. The epigenetic landscape at promoters of tolerizable genes was similar in unstimulated SF and monocytes, whereas the basal configuration of histone marks profoundly differed in genes that were non-tolerizable in SF only. Our data suggest that the epigenetic configuration at gene promoters regulates cell-specific LPS-induced responses and primes SF to sustain their inflammatory response in chronic arthritis.

Controlled enzymatic removal of damaging casein layers on medieval wall paintings.

A new, gentle enzymatic method was developed for a controlled removal of casein layers from medieval wall paintings. These casein layers were applied over the last 60 years on wall paintings in order to decrease substantial damage due to a peeling off of the frescoes from the roughcast surface due to environmental effects. However, due to the aging of the casein layers (at 40-50 years), a more drastic peeling occurred and the danger of total destruction of the wall paintings is severe. Thus, screening was performed to find the most suitable enzyme for casein digestion. Alcalase 2.5 DX L was the most appropriate enzyme for an effective proteolysis reaction. The enzyme was immobilized on functionalized cellulose membrane. A membrane pad system with immobilized enzymes was developed which could be pressed on the casein layers on the wall painting. A controlled removal of the casein layers by proteolytic digestion was observed and it was possible to continuously wash off the hydrolyzed casein fragments from the wall painting surface by an aqueous carbonate buffer flowing through the membrane pad. The removal and the digestion was monitored by reverse HPLC. Additionally, an on-line monitoring system was set up in order to continuously follow the casein layer removal and the digestion procedure directly on the wall painting. This technique is based on noninvasive 2D-fluorescence monitoring. Optical fiber systems were used to continuously monitor the fluorescence intensity of casein-bound tryptophan. The off-line data were verified with the on-line 2D-fluorescence data. Based on the scientific result an appropriate technique for the controlled enzymatic removal of damaging casein layers on the surface of medieval wall paintings using immobilized enzyme is now available. It is now applied to remove such casein layers from medieval wall paintings in the Allerheiligen-Kapelle Cloister, Wienhausen, Germany, and the St. Alexander Kirche, Wildeshausen, Germany.