Environmental pollutants directly affect the liver X receptor alpha activity: Kinetic and thermodynamic characterization of binding.

Liver X receptor is a ligand-activated transcription factor, which is mainly involved in cholesterol homeostasis, bile acid and triglycerides metabolism, and, as recently discovered, in the glucose metabolism by direct regulation of liver glucokinase. Its modulation by exogenous factors, such as drugs, industrial by-products, and chemicals is documented. Owing to the abundance of these synthetic molecules in the environment, and to the established target role of this receptor, a number of representative compounds of phthalate, organophosphate and fibrate classes were tested as ligands/modulators of human liver X receptor, using an integrated approach, combining an in silico molecular docking technique with an optical SPR biosensor binding study. The compounds of interest were predicted and proved to target the oxysterols-binding site of human LXRα with measurable binding kinetic constants and with affinities ranging between 4.3 × 10(-7) and 4.3 × 10(-8)M. Additionally, non-cytotoxic concentration of these chemicals induced relevant changes in the LXRα gene expression levels and other target genes (SREBP-1c and LGK) in human liver hepatocellular carcinoma cell line (HepG2), as demonstrated by q-RT-PCR.

Post-coma persons with extensive multiple disabilities use microswitch technology to access selected stimulus events or operate a radio device.

The present two studies extended research evidence on the use of microswitch technology by post-coma persons with multiple disabilities. Specifically, Study I examined whether three adults with a diagnosis of minimally conscious state and multiple disabilities could use microswitches as tools to access brief, selected stimulus events. Study II assessed whether an adult, who had emerged from a minimally conscious state but was affected by multiple disabilities, could manage the use of a radio device via a microswitch-aided program. Results showed that the participants of Study I had a significant increase of microswitch responding during the intervention phases. The participant of Study II learned to change radio stations and seemed to spend different amounts of session time on the different stations available (suggesting preferences among the programs characterizing them). The importance of microswitch technology for assisting post-coma persons with multiple disabilities to positively engage with their environment was discussed.

Genetic differentiation at the 3'UTR of PROS-Ag25: a cDNA homologue of Drosophila melanogaster proteasome subunit PROS-Dm25 in the malaria vector Anopheles gambiae.

The Anopheles gambiae cDNA encoding the homologue of the Drosophila melanogaster proteasome PROS-Dm25 was identified and analysed in terms of nucleotide sequence, and chromosomal localisation. In the 3' untranslated region, a GA-rich sequence was mapped which was found to be widely polymorphic among taxa belonging to the A. gambiae complex.

The SAG5 locus of Toxoplasma gondii encodes three novel proteins belonging to the SAG1 family of surface antigens.

We have identified three novel Toxoplasma gondii proteins showing close structural similarity to molecules of the SAG1 family, a group of glycosylphosphatidylinositol-anchored surface antigens expressed by the invasive stages of T. gondii. The novel proteins, denominated SAG5A, SAG5B and SAG5C, are encoded by tandemly arrayed and tightly clustered genes containing no introns. The 367 amino acid-long SAG5B and SAG5C are 97.5% identical to each other, whereas SAG5A (362 amino acids) consists of a C-terminal domain sharing 98% identity with SAG5B and SAG5C, and an N-terminal domain whose identity to the other SAG5 polypeptides is only 42%. Expression analysis of the T. gondii strains RH (virulent) and 76 K (avirulent) showed that all members of the SAG5 cluster are transcribed in T. gondii tachyzoites and bradyzoites. However, immunoblot studies on the RH strain revealed that the synthesis of SAG5A does not occur in tachyzoites and is possibly controlled at the post-transcriptional level. On the contrary, SAG5B and SAG5C were detected by immunoblot in tachyzoite lysates and found to migrate in the 40-45 kDa range under reducing conditions or at approximately 34 kDa under unreduced conditions. Triton X-114 partitioning of tachyzoite protein lysates treated with phosphatidylinositol-specific phospholipase C indicated that SAG5B and SAG5C are glycosylphosphatidylinositol-anchored membrane-associated molecules. Consistently, immunofluorescence analysis of transformed tachyzoites over-expressing SAG5B or SAG5C showed that these molecules are targeted to the parasite surface. The characterisation of the SAG5 locus sheds further light on the complex repertoire of SAG1-related genes in T. gondii, that now comprises 14 highly homologous members and five distantly related genes belonging to the SAG2 family.