Nucleic acids research
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CryptoDB (http://CryptoDB.org) represents a collaborative effort to locate all genome data for the apicomplexan parasite Cryptosporidium parvum in a single user-friendly database. CryptoDB currently houses the genomic sequence data for both the human type 1 H strain and the bovine type 2 IOWA strain in addition to all other available EST and GSS sequences obtained from public repositories. ⋯ Open reading frames greater than 50 and 100 amino acids have been generated for all sequences and all data are available for bulk download. This database, like other apicomplexan parasite databases, has been built utilizing the PlasmoDB model.
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Nucleic acids research · Feb 2002
Differential requirement for the ATPase domain of the Cockayne syndrome group B gene in the processing of UV-induced DNA damage and 8-oxoguanine lesions in human cells.
Cockayne syndrome (CS) is a rare inherited human genetic disorder characterized by UV sensitivity, developmental abnormalities and premature aging. The cellular and molecular phenotypes of CS include increased sensitivity to oxidative and UV-induced DNA lesions. The CSB protein is thought to play a pivotal role in transcription-coupled repair and CS-B cells are defective in the repair of the transcribed strand of active genes, both after exposure to UV and in the presence of oxidative DNA lesions. ⋯ The transfection of the mutant or wild-type CSB gene into the CS1AN. S3. G2 cells did not alter the expression of the subset of genes examined by cDNA array analysis.
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Nucleic acids research · Jul 2000
Modulation of plasma protein binding and in vivo liver cell uptake of phosphorothioate oligodeoxynucleotides by cholesterol conjugation.
Several studies have shown improved efficacy of cholesteryl-conjugated phosphorothioate antisense oligodeoxynucleotides. To gain insight into the mechanisms of the improved efficacy in vivo, we investigated the disposition of ISIS-9388, the 3'-cholesterol analog of the ICAM-1-specific phosphorothioate oligodeoxynucleotide ISIS-3082, in rats. Intravenously injected [(3)H]ISIS-9388 was cleared from the circulation with a half-life of 49.9 +/- 2.2 min (ISIS-3082, 23.3 +/- 3.8 min). ⋯ Analysis by agarose gel electrophoresis indicated that ISIS-9388 binds more tightly to plasma proteins than ISIS-3082. The different interaction of the oligonucleotides with plasma proteins possibly explains their different dispositions. We conclude that cholesterol conjugation results in high accumulation of phosphorothioate oligodeoxynucleotides in various liver cell types, which is likely to be beneficial for antisense therapy of liver-associated diseases.
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Structure of HIV-1 TAR RNA in the absence of ligands reveals a novel conformation of the trinucleotide bulge F. Aboul-ela J. Karn and G. ⋯ Functional groups which have been identified as critical for Tat binding, including the backbone phosphates, are highlighted by van der Waals spheres. These include; phosphates: 21-22, 22-23, 39-40 and 40-41, U23 HI and 04, G26 and A27 N7. A22 and A27 are highlighted in purple, U23 in green and G26 in yellow.
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Nucleic acids research · Sep 1992
Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication--potential effectiveness against most presently sequenced HIV-1 isolates.
Several mono-, di-, tetra-, penta- and nonaribozymes were developed. These multitarget-ribozymes were targeted to cleave HIV-1 env RNA at up to nine different conserved sites. Each multitarget-ribozyme consisted of a chain of up to nine hammerhead motifs, each flanked by a different targeting sequence. ⋯ A nucleotide sequence comparison of the target sites indicates that the multitarget-ribozymes could potentially be effective against all thirty HIV-1 isolates presently sequenced. Their use may help to slow the selection of viral escape mutants and thereby prolong their effectiveness. We anticipate that multitarget-ribozymes will also be more effective in the successful targeting of less variable cellular RNAs.