Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3beta.

The type IA topoisomerases have been implicated in the repair of dsDNA breaks by homologous recombination and in the resolution of stalled or damaged DNA replication forks; thus, these proteins play important roles in the maintenance of genomic stability. We studied the functions of one of the two mammalian type IA enzymes, Top3beta, using murine embryonic fibroblasts (MEFs) derived from top3beta(-/-) embryos. top3beta(-/-) MEFs proliferated more slowly than TOP3beta(+/+) control MEFs, demonstrated increased sensitivity to DNA-damaging agents such as ionizing and UV radiation, and had increased DNA double-strand breaks as manifested by increased gamma-H2-AX phosphorylation.

Anti-HLA-DR-triggered monocytes mediate in vitro T cell anergy.

Monomorphic MHC class II determinants are attractive targets for immunomodulation. HLA-DR ligation on antigen-presenting cells (APCs) can dramatically alter their function or induce cell death. In monocytes, HLA-DR triggering diminishes their capacity to stimulate T cell proliferation.

Defective signal transduction in B lymphocytes lacking presenilin proteins.

The mammalian presenilin (PS) proteins mediate the posttranslational cleavage of several protein substrates, including amyloid precursor protein, Notch family members, and CD44, but they have also been suggested to function in diverse cellular processes, including calcium-dependent signaling and apoptosis. We carried out an integrative computational study of multiple genomic datasets, including RNA expression, protein interaction, and pathway analyses, which implicated PS proteins in Toll-like receptor signaling. To test these computational predictions, we analyzed mice carrying a conditional allele of PS1 and a germ line-inactivating allele of PS2, together with Cre site-specific recombinase expression under the influence of CD19 control sequences.

Members of the low-molecular-mass rhoptry protein complex of Plasmodium falciparum bind to the surface of normal erythrocytes.

The destruction of erythrocytes is one of the most frequently observed causes of severe malarial anemia. Recently, we showed that tagging normal erythrocytes and cells of erythroid precursors with rhoptry-derived proteins can trigger their destruction. In the present study, we used rhoptry-associated protein (RAP)-1 and RAP-3 gene-disruption mutant Plasmodium falciparum parasites and showed that 2 members of a rhoptry protein complex, RAP-1 and RAP-2, bind to the surface of normal erythrocytes.

Changes in key odorants of raw coffee beans during storage under defined conditions.

During storage of raw coffee beans (green coffee) atypical odors may develop, which are suggested to influence the aroma of particularly the coffee beverage. To gain insight into the aroma compounds responsible for such odor changes, a comparative aroma extract dilution analysis was applied on unstored, raw Arabica coffee beans from Colombia (water content=11.75%) and on the same beans with a water content of 13.