The SOS screen in Arabidopsis: a search for functions involved in DNA metabolism.

The SOS screen, as originally described by Perkins et al. (1999) [7], was setup with the aim of identifying Arabidopsis functions that might potentially be involved in the DNA metabolism. Such functions, when expressed in bacteria, are prone to disturb replication and thus trigger the SOS response. Consistently, expression of AtRAD51 and AtDMC1 induced the SOS response in bacteria, even affecting E. coli viability. 100 SOS-inducing cDNAs were isolated from a cDNA library constructed from an Arabidopsis cell suspension that was found to highly express meiotic genes. A large proportion of these SOS(+) candidates are clearly related to the DNA metabolism, others could be involved in the RNA metabolism, while the remaining cDNAs encode either totally unknown proteins or proteins that were considered as irrelevant. Seven SOS(+) candidate genes are induced following gamma irradiation. The in planta function of several of the SOS-inducing clones was investigated using T-DNA insertional mutants or RNA interference. Only one SOS(+) candidate, among those examined, exhibited a defined phenotype: silenced plants for DUT1 were sensitive to 5-fluoro-uracil (5FU), as is the case of the leaky dut-1 mutant in E. coli that are affected in dUTPase activity. dUTPase is essential to prevent uracil incorporation in the course of DNA replication.

Pharmacological treatment of heterotopic ossification following hip and acetabular surgery.

Heterotopic ossification is a common complication following total hip arthroplasty and surgery following acetabular trauma. It is associated with pain and a decreased range of movement. Prophylaxis is achieved by either non-steroidal anti-inflammatory drug treatment or localised irradiation therapy. The objective of this study was to evaluate the evidence for pharmacological agents used for the prophylaxis of heterotopic ossification following hip and acetabular surgery. The study used a comprehensive literature search to identify all major clinical studies investigating the pharmacological agents used in the prophylaxis of heterotopic ossification following hip and acetabular surgery. It was concluded that indometacin remains the 'gold standard' for heterotopic ossification prophylaxis following total hip arthroplasty and is the only drug proven to be effective against heterotopic ossification following acetabular surgery. Following total hip arthroplasty, other non-steroidal anti-inflammatory drugs, including naproxen and diclofenac, are equally as effective as indometacin and can be considered as alternative first-line treatments. Celecoxib is also of equal efficacy to indometacin and is associated with significantly fewer gastrointestinal side effects. However, serious concerns were raised over the safety of selective cyclooxygenase-2 inhibitors for the cardiovascular system and these should be used cautiously.