Abstract: This disclosure provides new animal models for studying Usher syndrome and developing new therapy. The technology is implemented in pigs, and other large animals in which the ophthalmic architecture and function more closely resembles architecture and function of the human eye. The animals have a genetic modification in which all or a portion of a human gene known to cause Usher syndrome in human patients replaces the host gene. Animals can be cloned or bred to be homozygous at the targeted locus, whereupon they manifest symptoms and signs of Usher syndrome. Since a substantial portion of the targeted gene has been humanized, the animals can be used to develop and test pharmacological agents such as gene therapy that are sequence dependent.

Abstract: A method is described for the characterization of a tested substance, particularly useful in the study of its toxicity, and in particular immunotoxicity. Also described are cell lines and nucleic acids useful in its procurement, which may be used to embody said method, particularly in obtaining cell-chip collections destined for immunotoxicity assays.

Abstract: Use of a compound of formula (I): wherein each R, which are the same or different, is H or C1–C6 alkyl, and X completes a ring which is a substituted triazine having one of the following formulae (II) to (IV): wherein R? is H or C1–C6 alkyl; or an enol tautomer of a compound of formula (I) in which any of the groups R or R? is hydrogen; in the manufacture of a medicament for use as a protein tyrosine phosphatase (PTP) inhibitor. Formula (I) embraces 2-methylfervenulone, which can be produced by fermentation of a novel microbial strain. Fermentation of the said strain also produces novel precursors to 2-methylfervenulone having utility as prodrugs.

Abstract: Detection of Plasmodium ssp. by analysis of extrachromosomal DNA. It has been found that the molecular composition, physical arrangements, and nucleotide sequences of the extrachromosomal plastid-like element and mitochondrial element are highly conserved in different Plasmodium ssp. The high degree of homology has been used to design genera-specific or species specific diagnostic assays with a low frequency of false negatives. Plastid and mitochondrial DNA sequences are disclosed. The use of the sequences is claimed for detection, prophylactic, and therapeutic treatment of Plasmodium ssp. infection in human or other animals.

Abstract: The invention provides agents and compounds (see (I) and (II)) for use in the treatment or prophylaxis of disease conditions caused or exacerbated by mammalian papillomaviruses, such as human papillomaviruses, as well as methods for the treatment or prevention thereof. In said formulae, R1–R4 and n are as defined herein.

Abstract: A method for determining whether a compound inhibits or disrupts an interaction between a first polypeptide comprising a transcriptional adaptor motif (TRAM) and a second polypeptide comprising a TRAM-interaction motif. The first polypeptide and/or second polypeptide may be Mdm-2, p53, TBP, E2F, YY1, CBP/p300 or TF11B, or a viral polypeptide such as a human papillomavirus (HPV) E6 polypeptide from HPV strain (16) or (18).

Abstract: Flavivirus, rhabdovirus and paramyxovirus infections may be treated by administering an inhibitor of the enzyme dihydroorotate dehydrogenase such as 6-fluoro-2-(2?-fluoro-1,1?-biphenyl-4-yl)-3-methyl-4-quinolinearcarboxylic acid sodium salt (Brequinar). A synergistic effect can be obtained if an interferon such as interferon ?2, interferon ?8 or interferon ?, or an inhibitor of a second enzyme selected from inosine monophosphate dehydrogenase, guanosine monophosphate synthetase, cytidine triphosphate synthetase and S-adenosylhomocysteine hydrolase, is also administered.

Abstract: Proteins such as human &bgr;-interferon or human erythropoietin are prepared by culturing mammalian cells which harbour a nucleic acid sequence comprising: (i) a coding sequence which encodes the desired protein and which is operably linked to a promoter capable of directing expression of the coding sequence in a mammalian cell in the presence of a heavy metal ion; and (ii) a first selectable marker sequence comprises a metallothionein gene and which is operably linked to a promoter capable of directing expression of the metallothionein gene in a mammalian cell in the presence of a heavy metal ion; and optionally (iii) a second selectable marker sequence which comprises a neo gene and which is operably linked to a promoter capable of directing expression of the neo gene in a mammalian cell.

Abstract: DENI-S275/90 (ECACC V92042111) is a new strain of Dengue virus serotype 1. The complete cDNA sequence of this virus has been cloned and protein-coding fragments thereof have been used in the construction of expression plasmids. DEN1-S275/90 in inactivated form, DEN1-S275/90 polypeptides or fusion proteins thereof can be incorporated into vaccines for immunisation against DEN1-S275/90 and other DEN1 viruses. The invention further provides diagnostic reagents e.g. labelled antibodies to DEN1-S275/90 proteins, and kits to detect DEN1 virus.

Abstract: A method for diagnosis or prognosis of a cancer is disclosed. The method comprises (i) detecting in a first biological sample protein tyrosine phosphate .alpha. (PTP.alpha.) or PTP.alpha. nucleic acid, and (ii) comparing the level of PTP.alpha. or PTP.alpha. nucleic acid in the first sample with the level in a second biological sample known to be from normal tissue. Any overexpression of PTP.alpha. or PTP.alpha. nucleic acid in the first sample compared to the second sample is indicative that the first sample is from a cancerous tissue.