The in vivo expression of actin/salt-resistant hyperactive DNase I inhibits the development of anti-ssDNA and anti-histone autoantibodies in a murine model of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterised by the production of autoantibodies against ubiquitous antigens, especially nuclear components. Evidence makes it clear that the development of these autoantibodies is an antigen-driven process and that immune complexes involving DNA-containing antigens play a key role in the disease process. In rodents, DNase I is the major endonuclease present in saliva, urine and plasma, where it catalyses the hydrolysis of DNA, and impaired DNase function has been implicated in the pathogenesis of SLE. In this study we have evaluated the effects of transgenic overexpression of murine DNase I endonucleases in vivo in a mouse model of lupus. We generated transgenic mice having T-cells that express either wild-type DNase I (wt. DNase I) or a mutant DNase I ( ash. DNase I), engineered for three new properties - resistance to inhibition by G-actin, resistance to inhibition by physiological saline and hyperactivity compared to wild type. By crossing these transgenic mice with a murine strain that develops SLE we found that, compared to control nontransgenic littermates or wt. DNase I transgenic mice, the ash. DNase I mutant provided significant protection from the development of anti-single-stranded DNA and anti-histone antibodies, but not of renal disease. In summary, this is the first study in vivo to directly test the effects of long-term increased expression of DNase I on the development of SLE. Our results are in line with previous reports on the possible clinical benefits of recombinant DNase I treatment in SLE, and extend them further to the use of engineered DNase I variants with increased activity and resistance to physiological inhibitors.

Renal Research

he author overviews two research projects in the School of Pharmacy at the University of Queensland. The first examines how GPs individualise drug doses with respect to renal function. The second looks at two different approaches to monitoring aminoglycoside antibiotics. (non-author abstract)

Dominance hierarchies and health: Constructing personal zones of spiritual power and healing in modern medicine

Ethological studies of animals in groups and sociobiology indicate that hierarchies of dominance amongst some species ensure the survival of the group. When transferred to human groups, dominance hierarchies suggest a crucial role played by recasting the scope of such hierarchies of dominant and subordinate members to included hyper-dominant beings. A recognition of such beings as even more dominant than the socially dominant members of a hierarchy facilitates the empowerment of the socially subordinate members. Religious belief and practice works to establish such hyper-dominant beings (gods, goddesses, and so forth) as superior members of human groups. Doing so is a means of ensuring the survival of the species and, thus, enhancing healing and human health. The doctor-patient relationship is examined from such a point of view, with an emphasis on whether the hierarchy created by the relationship allows consideration of alternative and complementary forms of medical treatment.

Multi-threaded Communicating Agents in Qu-Prolog

In this tutorial paper we summarise the key features of the multi-threaded Qu-Prolog language for implementing multi-threaded communicating agent applications. Internal threads of an agent communicate using the shared dynamic database used as a generalisation of Linda tuple store. Threads in different agents, perhaps on different hosts, communicate using either a thread-to-thread store and forward communication system, or by a publish and subscribe mechanism in which messages are routed to their destinations based on content test subscriptions. We illustrate the features using an auction house application. This is fully distributed with multiple auctioneers and bidders which participate in simultaneous auctions. The application makes essential use of the three forms of inter-thread communication of Qu-Prolog. The agent bidding behaviour is specified graphically as a finite state automaton and its implementation is essentially the execution of its state transition function. The paper assumes familiarity with Prolog and the basic concepts of multi-agent systems.

Phytate: An anti-nutrient factor in animal diets

7th International Symposium on Poisonous Plants