Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease?

Biomolecules are susceptible to many different post-translational modifications that have important effects on their function and stability, including glycosylation, glycation, phosphorylation and oxidation chemistries. Specific conversion of aspartic acid to its isoaspartyl derivative or arginine to citrulline leads to autoantibody production in models of rheumatoid disease, and ensuing autoantibodies cross-react with native antigens. Autoimmune conditions associate with increased activation of immune effector cells and production of free radical species via NADPH oxidases and nitric oxide synthases. Generation of neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS) may contribute to epitope spreading in autoimmunity. The oxidation of amino acids by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS) increases the antigenicity of DNA, LDL and IgG, generating ligands for which autoantibodies show higher avidity. This review focuses on the evidence for ROS and RNS in promoting the autoimmune responses observed in diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or repair ROS/RNS damaged biomolecules and suggests that an associated defect, probably in T cell signal processing or/or antigen presentation, is required for the development of disease.

8-Hydroxydeoxyguanosine. A marker of oxidative DNA damage in systemic lupus erythematosus

8-Hydroxydeoxyguanosine (80HDG) is a specific marker of oxidative damage to DNA. We have observed that patients with SLE (systemic lupus erythematosus), have undetectable levels of urinary 80HDG by HPLC. Further analysis by GC-MS confirmed that levels of 80HDG in SLE urine were 10(3)-fold lower than in an age- and sex-matched control group. Experiments utilising cultures of SLE and normal lymphocytes exposed to H2O2 confirmed the impaired ability of SLE lymphocytes to repair 80HDG. We subsequently observed in SLE patients that 80HDG had accumulated in low molecular weight DNA associated with circulating immune complexes. We suggest that oxygen radicals may induce pathology in SLE by maintaining the presence of an antigenic form of DNA in the circulation.

Content-based VLE designs improve learning efficiency in constructivist statistics education

Background: We introduced a series of computer-supported workshops in our undergraduate statistics courses, in the hope that it would help students to gain a deeper understanding of statistical concepts. This raised questions about the appropriate design of the Virtual Learning Environment (VLE) in which such an approach had to be implemented. Therefore, we investigated two competing software design models for VLEs. In the first system, all learning features were a function of the classical VLE. The second system was designed from the perspective that learning features should be a function of the course's core content (statistical analyses), which required us to develop a specific-purpose Statistical Learning Environment (SLE) based on Reproducible Computing and newly developed Peer Review (PR) technology. Objectives: The main research question is whether the second VLE design improved learning efficiency as compared to the standard type of VLE design that is commonly used in education. As a secondary objective we provide empirical evidence about the usefulness of PR as a constructivist learning activity which supports non-rote learning. Finally, this paper illustrates that it is possible to introduce a constructivist learning approach in large student populations, based on adequately designed educational technology, without subsuming educational content to technological convenience. Methods: Both VLE systems were tested within a two-year quasi-experiment based on a Reliable Nonequivalent Group Design. This approach allowed us to draw valid conclusions about the treatment effect of the changed VLE design, even though the systems were implemented in successive years. The methodological aspects about the experiment's internal validity are explained extensively. Results: The effect of the design change is shown to have substantially increased the efficiency of constructivist, computer-assisted learning activities for all cohorts of the student population under investigation. The findings demonstrate that a content-based design outperforms the traditional VLE-based design. © 2011 Wessa et al.

Effects of solid poly (ethylene glycols) addition to the solutions of aniline or N,N-dimethylaniline with water:experimental measurements and modelling

In this work, the liquid-liquid and solid-liquid phase behaviour of ten aqueous pseudo-binary and three binary systems containing polyethylene glycol (PEG) 2050, polyethylene glycol 35000, aniline, N,N-dimethylaniline and water, in the temperature range 298.15-350.15 K and at ambient pressure of 0.1 MPa, was studied. The obtained temperature-composition phase diagrams showed that the only functional co-solvent was PEG2050 for aniline in water, while PEG35000 even showed a clear anti-solvent effect in the N,N-dimethylaniline aqueous system. The experimental solid-liquid equilibria (SLE) data have been correlated by the non-random two-liquid (NRTL) model, and the correlation results are in accordance with the experimental results.