Abstract: In a study of HIV-1 integrase (IN) complexes derived from nuclei of human cells stably expressing the viral protein from a synthetic gene it was demonstrated that in the nuclear extracts IN exists as part of a large distinct complex with apparent Stokes radius of 61 ?, which dissociates upon dilution yielding a core molecule of 41 ?. The IN complexes were isolated from cells expressing FLAG-tagged IN. By present invention it was demonstrated that the 41 ? core is tetramer of IN, whereas 61 ? molecules are composed of IN tetramers associated with a cellular protein with an apparent molecular weight of 76 kDa. This integrase interacting protein (Inip76) was found to be identical to LEDGF/DFS70/p75 a protein implicated in regulation of gene expression and cellular stress-response. HIV-1 IN and Inip76 co-localized in the nuclei of human cells stably expressing IN. Furthermore, it has been demonstrated by present invention that recombinant Inip76 strongly promoted strand-transfer activity of HIV-1 IN in vitro.

Abstract: The invention involves a method of stereotactic and viral vector-mediated gene transfer to produce animals harboring in their neural tissue a polynucleotide sequence, an allelic variant, minigene or a homolog thereof, that encodes for &agr;-synuclein or functional homnologues thereof and overexpresses ccsynuclein or functional homologues thereof locoregional in said neural tissue. Overexpression of &agr;-synuclein is associated with locoregional pathology in the neural tissue as evidenced by histology and neurodegeneration as evidenced by histology. These animals can be used in pharmaceutical screening and for in vivo modelling of &agr;-synuclein biochemistry.

Abstract: The invention provides the use of a pyrano[2,3-d:6,5-d′] dipyrimidine derivative for the manufacture of a medicine for the treatment of a retroviral infection in a mammal. It also provides a product containing: (a) one or more derivatives of a pyrano[2,3-d:6,5-d′] dipyrimidine; and (b) one or more anti-retroviral drugs, including drugs effective against one or more retroviral or cellular proteins involved in the entry and/or replication of a retrovirus, in respective proportions such as to provide a synergistic effect against a retroviral infection in a mammal, as a combined preparation for simultaneous, separate or sequential use in retroviral infection therapy.