Comparative Aspects of Ricin Toxicity by Inhalation.

The pathogenesis of ricin toxicity following inhalation has been investigated in many animal models, including the non-human primate (predominantly the rhesus macaque), pig, rabbit and rodent. The toxicity and associated pathology described in animal models are broadly similar, but variation appears to exist. This paper reviews the published literature and some of our own unpublished data and describes some of the possible reasons for this variation.

A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response.

Vaccines are arguably the most important medical technology developed to date. However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2 or neu.

Direct Detection and Discrimination of Nucleotide Polymorphisms Using Anthraquinone Labeled DNA Probes.

A novel electrochemical detection approach using DNA probes labeled with Anthraquinone (AQ) as a reporter moiety has been successfully exploited as a method for the direct detection of DNA targets. This assay uses simple voltammetry techniques (Differential Pulse Voltammetry) to exploit the unique responsiveness of AQ to its chemical environments within oxygenated aqueous buffers, providing a specific detection mechanism as a result of DNA hybridization. This measurement is based on a cathodic shift of the reduction potential of the AQ tag and the concurrent reduction in peak current upon DNA binding.

Evaluation of a novel electrochemical detection method for Chlamydia trachomatis: application for point-of-care diagnostics.

Atlas Genetics has developed a point-of-care device for Chlamydia trachomatis utilizing a novel electrochemical detection principle. The assay has a time-to-result of less than 25 min. An independent preclinical validation study using 306 pretyped clinical samples determined a clinical sensitivity of 98.

Thioredoxins function as deglutathionylase enzymes in the yeast Saccharomyces cerevisiae.

Background: Protein-SH groups are amongst the most easily oxidized residues in proteins, but irreversible oxidation can be prevented by protein glutathionylation, in which protein-SH groups form mixed disulphides with glutathione. Glutaredoxins and thioredoxins are key oxidoreductases which have been implicated in regulating glutathionylation/deglutathionylation in diverse organisms. Glutaredoxins have been proposed to be the predominant deglutathionylase enzymes in many plant and mammalian species, whereas, thioredoxins have generally been thought to be relatively inefficient in deglutathionylation.

Gcn4 is required for the response to peroxide stress in the yeast Saccharomyces cerevisiae.

An oxidative stress occurs when reactive oxygen species overwhelm the cellular antioxidant defenses. We have examined the regulation of protein synthesis in Saccharomyces cerevisiae in response to oxidative stress induced by exposure to hydroperoxides (hydrogen peroxide, and cumene hydroperoxide), a thiol oxidant (diamide), and a heavy metal (cadmium). Examination of translational activity indicates that these oxidants inhibit translation at the initiation and postinitiation phases.

Global translational responses to oxidative stress impact upon multiple levels of protein synthesis.

Global inhibition of protein synthesis is a common response to stress conditions. We have analyzed the regulation of protein synthesis in response to oxidative stress induced by exposure to H(2)O(2) in the yeast Saccharomyces cerevisiae. Our data show that H(2)O(2) causes an inhibition of translation initiation dependent on the Gcn2 protein kinase, which phosphorylates the alpha-subunit of eukaryotic initiation factor-2.

Protein S-thiolation targets glycolysis and protein synthesis in response to oxidative stress in the yeast Saccharomyces cerevisiae.

The irreversible oxidation of cysteine residues can be prevented by protein S-thiolation, a process by which protein SH groups form mixed disulphides with low-molecular-mass thiols such as glutathione. We report here the target proteins which are modified in yeast cells in response to H(2)O(2). In particular, a range of glycolytic and related enzymes (Tdh3, Eno2, Adh1, Tpi1, Ald6 and Fba1), as well as translation factors (Tef2, Tef5, Nip1 and Rps5) are identified.

Regulation of protein S-thiolation by glutaredoxin 5 in the yeast Saccharomyces cerevisiae.

The irreversible oxidation of cysteine residues can be prevented by protein S-thiolation, a process by which protein -SH groups form mixed disulfides with low molecular weight thiols such as glutathione. We report here that this protein modification is not a simple response to the cellular redox state, since different oxidants lead to different patterns of protein S-thiolation. SDS-polyacrylamide gel electrophoresis shows that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is the major target for modification following treatment with hydroperoxides (hydrogen peroxide or tert-butylhydroperoxide), whereas this enzyme is unaffected following cellular exposure to the thiol oxidant diamide.