Bid activation during induction of extrinsic and intrinsic apoptosis in eosinophils

Eosinophils readily undergo apoptosis when removed from a physiological environment via activation of the intrinsic cell death pathway. This can be further enhanced by certain chemicals (for example, glucocorticoid), or by extrinsic means (that is, Fas receptor engagement). In this investigation, we examined the relative importance of these pathways in cultured human peripheral blood eosinophils in the context of expression and activation of the BH3-only Bcl2 homologue Bid. Bid activation was examined under conditions where programmed cell death was either stimulated (via Fas engagement or glucocorticoid treatment) or inhibited (interleukin-5 (IL-5)) relative to control. Full-length Bid was found to be highly expressed in eosinophils, and processed to a similar extent during either agonist anti-Fas or glucocorticoid treatment. IL-5 blocked intrinsic Bid activation during factor withdrawal or glucocorticoid treatment, and partially attenuated that caused by Fas activation. Caspase 8 (but not caspase 9) antagonism partly but significantly affected receptor-mediated Bid activation and cell death; these processes were not altered by either caspase inhibitor during simple factor withdrawal or glucocorticoid treatment. Bid processing appears to be central to both intrinsic and extrinsic pathways of cell death in eosinophils. The role of IL-5 in blocking the intrinsic pathway of eosinophil apoptosis is underscored. Results of specific inhibition support the existence of Bid activation pathways in eosinophils other than those mediated by the classic initiator caspases.     

Gene expression variation in Down's syndrome mice allows prioritization of candidate genes

Background  

Down's syndrome (DS), or trisomy 21, is a complex developmental disorder that exhibits many clinical signs that vary in occurrence and severity among patients. The molecular mechanisms responsible for DS have thus far remained elusive. We argue here that normal variation in gene expression in the population contributes to the heterogeneous clinical picture of DS, and we estimated the amplitude of this variation in 50 mouse orthologs of chromosome 21 genes in brain regions of Ts65Dn (a mouse model of DS). We analyzed the RNAs of eight Ts65Dn and eight euploid mice by real-time polymerase chain reaction.     

Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration.     

Multi-locus variable-number tandem repeat profiling of Salmonella enterica serovar Typhi isolates from blood cultures and gallbladder specimens from Makassar, South-Sulawesi, Indonesia

Multi-locus variable-number tandem repeat analysis differentiated 297 Salmonella enterica serovar Typhi blood culture isolates from Makassar in 76 genotypes and a single unique S. Typhi genotype was isolated from the cholecystectomy specimens of four patients with cholelithiasis. The high diversity in S. Typhi genotypes circulating in Makassar indicates that the number of carriers could be very large, which may complicate disease prevention and control.     

Immunocytochemical localization of factor VIII/von Willebrand factor antigen in human platelets

Specific antibodies against anti-human FVIII/vW protein were isolated by affinity chromatography on glutaraldehyde-activated gel (Ultrogel AcA22). They were coupled directly with peroxidase or visualized with anti-rabbit IgG (sheep)-peroxidase (Institut Pasteur). Fab fragments of the same specific antibodies were prepared to enhance the intracellular penetration and coupled to peroxidase. In washed human platelets, staining was observed on the plasma membrane and in the canalicular system, whereas in previous studies whole specific antibodies incubated with fixed platelets showed the labeling only on the plasma membrane. After thrombin activation, the release of granules containing FVIII/vW protein was better visualized in the surface canalicular system. This localization was discussed in regard to the exocytosis process: membrane fusion, granule labeling.     

Two new records of Oribatula (Zygoribatula) species (Acari: Oribatida) from Turkey, with redescriptions

The oribatid mite fauna of Turkey is still relatively poorly known. The present paper adds two species of oribatid mites to the known Turkish fauna viz., Oribatula (Zygoribatula) debilitranslamellata (Kulijev, 1962) and O. (Z.) exilis (Nicolet, 1855). Both species are characterised by large, prominent lamellar cusps, with the lamellar setae inserted apically on the cusps, and by the presence of distinct translamellae. They can be distinguished, however, by the smaller lamellae, absence of cuspidal teeth, narrowly fusiform sensilli and, 13 pairs of thin, smooth, apically almost flagellate notogastral setae, in O. (Z.) debilitranslamellata, and by the wider lamellae, presence of cuspidal teeth, widely fusiform sensilli, and 14 pairs of thin, smooth notogastral setae, with seta c (1) slightly thicker and minutely barbed in O. (Z.) exilis. The following species have been previously reported from Turkey: O. (Z.) cognata (Oudemans, 1902), O. (Z.) undulata (Berlese, 1917), O. (Z.) terricola Van der Hammen, 1952, and O. (Z.) lanceolata Grobler, Bayram & Cobanoglu, 2004.     

Microbial transformation of 17alpha-ethynyl- and 17alpha-ethylsteroids, and tyrosinase inhibitory activity of transformed products

The microbial transformation of the 17alpha-ethynyl-17beta-hydroxyandrost-4-en-3-one (1) (ethisterone) and 17alpha-ethyl-17beta-hydroxyandrost-4-en-3-one (2) by the fungi Cephalosporium aphidicola and Cunninghamella elegans were investigated. Incubation of compound 1 with C. aphidicola afforded oxidized derivative, 17alpha-ethynyl-17beta-hydroxyandrosta-1,4-dien-3-one (3), while with C. elegans afforded a new hydroxy derivative, 17alpha-ethynyl-11alpha,17beta-dihydroxyandrost-4-en-3-one (4). On the other hand, the incubation of compound 2 with the fungus C. aphidicola afforded 17alpha-ethyl-17beta-hydroxyandrosta-1,4-dien-3-one (5). Two new hydroxylated derivatives, 17alpha-ethyl-11alpha,17beta-dihydroxyandrost-4-en-3-one (6) and 17alpha-ethyl-6alpha,17beta-dihydroxy-5alpha-androstan-3-one (7) were obtained from the incubation of compound 2 with C. elegans. Compounds 1-6 exhibited tyrosinase inhibitory activity, with compound 6 being the most potent member (IC(50)=1.72 microM).