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Asad U Khan

Publications and source records attributed to Asad U Khan.

8 recordsLinked to original sources
PubMed2006

Ribozyme: a clinical tool.

Catalytic RNAs (ribozymes) are capable of specifically cleaving RNA molecules, a property that enables them to act as potential antiviral and anti-cancer agents, as well as powerful tools for functional genomic studies. Recently, ribozymes have been used successfully to inhibit gene expression in a variety of biological systems in vitro and in vivo. Phase I clinical trials using ribozyme gene therapy to treat AIDS patients have been conducted. Despite initial success, there are many areas that require further investigation. These include stability of ribozymes in cells and designing highly active ribozymes in vivo, identification of target sequence sites and co-localization of ribozymes and substrates, and their delivery to specific tissues and maintenance of its stable long-term expression. This review gives a brief introduction to ribozyme structure, catalysis and its potential applications in biological systems as therapeutic agents.

Animals↗
PubMed2006

In silico analysis of genes nucleoprotein, neuraminidase and hemagglutinin: a comparative study on different strains of influenza A (Bird flu) virus sub-type H5N1.

The avian influenza (bird flu) is an infectious disease of birds, ranging from a mild to a severe form of illness. Influenza viruses pose significant challenges to both human and animal health. The proteins, nucleoprotein (NP), neuraminidase (NA) and hemagglutinin (HA) of influenza A virus (Bird flu virus) sub-type A/Hatay/2004/(H5N1) from chicken were selected for this study. Our in silico analysis predicted that HA of influenza A virus is highly sensitive to mutations and hence it is significant for its pathogenic nature. None of the mutations was detected as an important change except in NA where K332R was at a PKC phosphorylation site. Analysis of the sequence comparison showed that the maximum number of mutations were observed in HA. These mutations are significant as they are involved in change in polarity or hydrophobicity as well as in propensity of each amino acid residue to stabilize the secondary structure. The program MAPMUTATION can be used to monitor the mutations, and predict the trend of mutations.

Amino Acid Sequence↗
PubMed2005

Histone modifications as key regulators of transcription.

Covalent modifications of the amino-termini of the core histones in nucleosomes have been shown to be one of the key regulatory mechanisms in transcription regulation. Recently, new roles for histone modifications have been uncovered for the efficient functioning of RNA Pol II. Besides acetylation, which is the most characterized to date these modifications comprise phosphorylation, methylation, and ubiquitination. This review gives comprehensive view of all the major histone modifications and their effect on transcriptional regulation, in Saccharomyces cerevisiae.

Acetylation↗
PubMed2004

Plasmid-mediated multiple antibiotic resistance in Proteus mirabilis isolated from patients with urinary tract infection.

BACKGROUND: Worldwide surveillance of antimicrobial resistance among urinary tract pathogens is useful to determine important trends and geographical variation for common Gram negative and positive species. We initiated this study to learn the drug resistance pattern and its location (genomic or plasmid-borne) among the strains of Proteus mirabilis, one of the most common causative agents of urinary tract infection (UTI). MATERIAL/METHODS: A total of 200 urine samples were collected from UTI patients, followed by isolation and identification of Proteus milabilis strains. Antibiotic sensitivity and resistance analysis was performed by the disc diffusion method, employing multiple antibiotic discs. The sensitivity was monitored by visualizing the zone of inhibition around the disc. Plasmid isolation was performed by the method of Kado and Liu. Transfer of the R-Plasmid to recipient E.coli C600 cells was achieved using the method of Lederberg and Cohen. RESULTS: Clinical study revealed that this infection is more common in young pregnant women. Various strains of Proteus mirabilis isolated during the course of the study were found to show multiple antibiotic resistance, which was further characterized as plasmid-borne drug resistance. CONCLUSIONS: Proteus mirabilis is one of the important causative agents of urinary tract infection in young women especially during the state of pregnancy. Multiple antibiotic resistance markers of Proteus strains were identified as plasmid mediated.

Adolescent↗
PubMed2003

Functional interactions between the transcription and mRNA 3' end processing machineries mediated by Ssu72 and Sub1.

Transcription and processing of pre-mRNA are coupled events. By using a combination of biochemical, molecular, and genetic methods, we have found that the phylogenetically conserved transcription factor Ssu72 is a component of the cleavage/polyadenylation factor (CPF) of Saccharomyces cerevisiae. Our results demonstrate that Ssu72 is required for 3' end cleavage of pre-mRNA but is dispensable for poly(A) addition and RNAP II termination. The in vitro cleavage defect caused by depletion of Ssu72 from cells can be rescued by addition of recombinant Ssu72. Ssu72 interacts physically and genetically with the Pta1 subunit of CPF. Overexpression of PTA1 causes synthetic lethality in an ssu72-3 mutant. Moreover, Sub1, which has been implicated in transcription initiation and termination, also interacts with Pta1, and overexpression of SUB1 suppresses the growth and processing defect of a pta1 mutation. Physical interactions of Ssu72 and Sub1 with Pta1 are mutually exclusive. Based on the interactions of Ssu72 and Sub1 with both the Pta1 of CPF and the TFIIB component of the initiation complex, we present a model describing how these novel connections between the transcription and 3' end processing machineries might facilitate transitions in the RNAP II transcription cycle.

3' Untranslated Regions↗
PubMed2002

Connecting the DOTs: covalent histone modifications and the formation of silent chromatin.

Histone methylation has emerged as a significant regulator of chromatin structure and function. Two different classes of histone methyltransferase (HMT) have been described, which target either lysine or arginine residues in the histone N-terminal tails. A flurry of recent papers now describe a third class of HMT that affects chromatin silencing indirectly, not by methylation of histone tails, but instead by targeting a conserved lysine residue in the core domain of the nucleosome.

Animals↗
PubMedDate not supplied

Ribozymes: a modern tool in medicine.

Since the discovery of ribozymes and self-splicing introns, it has been estimated that this biological property of RNA combined with other recombinant DNA technologies would become a tool to combat viral diseases and control oncogenes. These goals seem like a distinct possibility now. However, there is still a lot to be learned about the mobility of RNA inside the cells and the cellular factors that can impede ribozyme action in order to capitalize fully on the targeted RNA inactivation property of ribozymes. The most effective approach to maximize ribozyme function in a complex intracellular environment is to understand as much as possible about the intracellular fate of the RNA that is being targeted. As new techniques in cell biology become available, such understanding will be less problematic. Fundamental studies of ribozyme structure and mechanism of catalysis are flourishing both at the academic and industrial level and it can be expected that many new developments will continue to take place in these areas in the near future. Here, we review the design, stability and therapeutic application of these technologies illustrating relevant gene targets and applications in molecular medicine. Relevant problems in implementation of the technology, group I and II introns and the differences in applications, ribozyme structure and the application of this technology to virus attack and oncogene downregulation are discussed. Also some of the latest RNA-based technologies such as siRNA, RNA/DNA duplexes and RNA decoys have been introduced.

Animals↗