ABSTRACT
A solid target system was developed for a PET cyclotron. The system is compatible with many different target materials in the form of foils and electroplated/sputtered targets which makes it useful for production of a wide variety of different PET radionuclides. The target material is manually loaded into the system. Remote handling of irradiated target material is managed with a pneumatic piston and a vacuum technique which allows the targets to be dropped into a shielded transport container. To test the target performance, proton irradiations (12.8 MeV, 45 µA) of monoisotopic yttrium foils (0.64 mm, direct water cooling) were performed to produce 89Zr. The yields were 2200±200 MBq (1 h, n=13) and 6300±65 MBq (3 h, n=3).
Subject(s)
Cyclotrons/instrumentation , Isotope Labeling/instrumentation , Positron-Emission Tomography/instrumentation , Radioisotopes/chemistry , Robotics/instrumentation , Specimen Handling/instrumentation , Zirconium/chemistry , Equipment Design , Equipment Failure Analysis , Radiation Dosage , Radioisotopes/radiation effects , Radiometry/instrumentation , Zirconium/radiation effectsABSTRACT
We have investigated the effects of inhibition of histone de-acetylase activity on silencing at the silent mating-type loci in fission yeast. Treatment of exponentially growing cells with the histone deacetylase inhibitor, trichostatin A (TSA), resulted in derepression of a marker gene inserted 150 bp distal from the silent mat3-M locus. The natural targets for the silencing mechanism in this region were only partially derepressed and the activation appeared to be asymmetric, i.e. the mat2-P cassette remained silent at concentrations that clearly partially derepressed the mat3-M cassette. We further noted that treatment of wild-type h90 cells resulted in the generation of altered sporulation phenotypes, indicating that the treatment affected the expression of mating-type genes and/or mating-type switching. The results are discussed in the light of recent accumulated data regarding the role of deacetylation for silencing in other species.
Subject(s)
Genes, Fungal/genetics , Genes, Mating Type, Fungal , Histone Deacetylase Inhibitors , Schizosaccharomyces/genetics , Enzyme Inhibitors/pharmacology , Fungal Proteins/genetics , Gene Expression Regulation , Gene Expression Regulation, Fungal/drug effects , Histone Deacetylases/metabolism , Hydroxamic Acids/pharmacology , Recombinant Fusion Proteins/geneticsABSTRACT
hda1+ (histone deacetylase 1) is a fission yeast gene which is highly similar in sequence to known histone deacetylase genes in humans and budding yeast. We have investigated if this putative histone deacetylase contributes to transcriptional silencing in the fission yeast Schizosaccharomyces pombe. A precise deletion allele of the hda1+ open reading frame was created. Cells lacking the hda1+ gene are viable. However, genetic analysis reveals that cells without hda1 + display enhanced gene repression/silencing of marker genes, residing adjacent to telomeres, close to the silent mating-type loci and within centromere I. This phenotype is very similar to that recently reported for rpd3 mutants both in Drosophila and budding yeast. No defects in chromosome segregation or changes in telomere length were detected. Cells lacking the hda1+ gene display reduced sporulation. Growth of hda1 cells is partially inhibited by low concentrations of Trichostatin A (TSA), a known inhibitor of histone deacetylase enzymes. TSA treatment is also able to overcome the enhanced silencing found in heterochromatic regions of hda1 cells. These results indicate a genetic redundancy with respect to deacetylase genes and partially overlapping functions of these in fission yeast. The significance of these results is discussed in the light of recent discoveries from other eukaryotes.
