A Yersinia pseudotuberculosis protein which cross-reacts with HLA-B27

The most-debated question in the investigation of the spondyloarthropathies has been whether there is molecular mimicry between host HLA-B27 antigens and the arthritis-causing pathogens. We have generated a monoclonal anti-HLA-B27 antibody in our laboratory and have used a radioimmunoassay to screen a panel of bacterial species. Two strains of Yersinia pseudotuberculosis were found to be highly reactive. The cross-reactive Yersinia component was identified by Western blot to be a 19,000 component. A preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis chromatography apparatus was constructed to isolate milligram quantities of this component. To verify that the component carried the HLA-B27-specific epitope, rabbits were hyperimmunized with the purified materials. Affinity-purified antibodies from one of the immunized rabbits indeed carried anti-HLA-B27 activity. Last, antibodies generated against synthetic peptides derived from the HLA-B27.1 amino acid sequence were tested against the Yersinia component. Positive reactivity was found with antibodies generated against a peptide spanning residues 69-83 of the HLA-B27.1 protein. Since this resides in the segment responsible for the allotypic specificity of the antigen, these experiments establish the presence of molecular mimicry to a high degree of confidence.     

Cleavage of dT8 and dT8 phosphorothioyl analogues by Escherichia coli DNA topoisomerase I: product and rate analysis

Escherichia coli DNA topoisomerase I catalyzes the cleavage of short, single-stranded oligodeoxynucleotides with dT8 as the shortest cleavable oligo(thymidylic acid). The 5'-32P-labeled products formed from the cleavage of [5'-32P]dT8 are dT5, dT4, and dT3 with over 70% of the substrate cleaved to dT4. Mg(II) ions affect this product distribution by increasing the percentage of dT4 formed. The substitution of a sulfur atom for a nonbridging oxygen atom in a phosphodiester linkage yields oligodeoxynucleotide phosphorothioyl (PS) analogues. The epimers of the analogues were separated, and the position and stereochemistry of the phosphorothiodiester bond were determined. Topoisomerase I is stereospecific in its reactivity toward these analogues. With the oligodeoxynucleotide PS analogue substrates, the rate of cleavage, the stereospecificity, and the product distribution depend upon the position and the stereochemistry of the phosphorothiodiester linkage.     

A Simple Survival Model for Combined Action of Two Damaging Agents

The aim of this study was mathematical formalization of the development of two damage processes in response to the combined action of two different damaging agents. The model allows to obtain the parametric family of distributions for the life-span when the organism's death is due to joint effect of two damage processes. Differing by their probabilistic meaning the notions of a priori (M (t)) and a posteriori (M(y)) conditional mean contributions of each damage process to the final effect of combined injury are introduced. The formulas permitting to compute the M and M values on the basis of survival data parametric analysis are given.     

Cytotoxic and antiprotozoal activity of flavonoids from Lonchocarpus spp.

A number of flavonoids isolated from Lonchocarpus spp. were evaluated for their antiprotozoal and cytotoxic activity. Flavone 6 and chalcone 7 were found to be the most active against Leishmania parasites and against cell cultures of Leukemia P388DI and adenocarcinoma prostate PC-3.     

Possible involvement of DNA breaks in epigenetic regulation of cell differentiation

The review summarizes the authors’ and literature data on accumulation of DNA breaks in differentiating cells. Large 50-kb free DNA fragments were observed by several research teams in non-apoptotic insect, mammal, and plant cells. More intense DNA breakage was observed during maturation of spermatides, embryo development, and differentiation of myotubes, epidermal cells, lymphocytes, and neutrophils. In general, accumulation of DNA breaks in differentiating cells cannot be attributed to a decrease in the DNA repair efficiency. Poly(ADP)ribose synthesis often follows the DNA breakage in differentiating cells. We hypothesize that DNA fragmentation is an epigenetic tool for regulating the differentiation process. Scarce data on localization of the differentiation-associated DNA breaks indicate their preferable accumulation in specific DNA sequences including the nuclear matrix attachment sites. The same sites are degraded at early stages of apoptosis. Recent data on non-apoptotic function of caspases provide more evidence for possible existence of a DNA breakage mechanism in differentiating cells, resembling the initial stage of apoptosis. Excision of methylated cytosine and recombination are other possible explanations of the phenomenon. Elucidation of mechanisms of differentiation-induced DNA breaks appears to be a prospective research direction.     

Extending the Cellulosome Paradigm: the Modular Clostridium thermocellum Cellulosomal Serpin PinA Is a Broad-Spectrum Inhibitor of Subtilisin-Like Proteases

Clostridium thermocellum encodes a cellulosomal, modular, and thermostable serine protease inhibitor (serpin), PinA. PinA stability but not inhibitory activity is affected by the Fn(III) and Doc(I) domains, and PinA is a broad inhibitor of subtilisin-like proteases and may play a key role in protecting the cellulosome from protease attack.     

Mysterious bio-duck sound attributed to the Antarctic minke whale (Balaenoptera bonaerensis)

For decades, the bio-duck sound has been recorded in the Southern Ocean, but the animal producing it has remained a mystery. Heard mainly during austral winter in the Southern Ocean, this ubiquitous sound has been recorded in Antarctic waters and contemporaneously off the Australian west coast. Here, we present conclusive evidence that the bio-duck sound is produced by Antarctic minke whales (Balaenoptera bonaerensis). We analysed data from multi-sensor acoustic recording tags that included intense bio-duck sounds as well as singular downsweeps that have previously been attributed to this species. This finding allows the interpretation of a wealth of long-term acoustic recordings for this previously acoustically concealed species, which will improve our understanding of the distribution, abundance and behaviour of Antarctic minke whales. This is critical information for a species that inhabits a difficult to access sea-ice environment that is changing rapidly in some regions and has been the subject of contentious lethal sampling efforts and ongoing international legal action.