For nearly a decade since the mapping of the multiple endocrine neoplasia type 1 (MEN1) locus to 11q13 and the suggestion that it is a tumour suppressor gene, efforts have been made to identify the gene responsible for this familial cancer syndrome. Recently, we have identified the MEN1 gene by the positional cloning approach. This effort involved construction of a 2.8-Mb physical map (D11S480-D11S913) based primarily on a bacterial clone contig. Using these resources, 20 new polymorphic markers were isolated which helped to reduce the interval for candidate genes by haplotype analysis in families and by loss of heterozygosity (LOH) studies in approximately 200 tumours, utilizing laser-assisted microdissection to obtain tumour cells with minimal or no admixture by normal cells. The interval was narrowed by LOH to only 300 kb, and nearly 20 new transcripts that map to this region of 11q13 were isolated and characterized. One of the transcripts was found by dideoxyfingerprinting and cycle sequencing to harbour deleterious germline mutations in affected individuals from MEN-1 kindreds and therefore identified as the MEN1 gene. The type of germline mutations and the identification of mutations in sporadic tumours support the Knudson's two-hit model of tumorigenesis for MEN-1. Efforts are being made to identify the function of the MEN1 gene-encoded protein, menin, and to study its role in tumorigenesis.
Blind flooding is a popular search mechanism used in current commercial P2P systems because of its simplicity. However, blind flooding among peers or superpeers causes large volume of unnecessary traffic although the response time is short. Some improved statistics-based search mechanisms can reduce the traffic volume but also significantly shrink the query coverage range. In some search mechanisms, not all peers may be reachable creating the so-called partial coverage problem. Aiming at alleviating the partial coverage problem and reducing the unnecessary traffic, we propose an efficient and adaptive search mechanism, Hybrid Periodical Flooding (HPF). HPF retains the advantages of statistics-based search mechanisms, alleviates the partial coverage problem, and provides the flexibility to adaptively adjust different parameters to meet different performance requirements. The effectiveness of HPF is demonstrated through simulation studies.
Pyrroline-5-carboxylate synthetase, (P5CS) is a bifunctional enzyme (EC 2.7.2.11/1.2.1.41) that catalyses the first two steps of glutamate pathway in proline biosynthesis in plant. The JcP5CS was cloned from the leaves of Jatropha curcas L. The lengthen of the cDNA of JcP5CS was 2675 bp, containing a 2148 bp open reading frame, a 117 bp 5'-untranslated region and a 410 bp 3'-untranslated region. The open reading fragment (ORF) encoded a 715 amino acid polypeptide with the molecular weight of 77.54 kDa and the pI value of 6.11. JcP5CS was composed of N-terminal Glutamate-5-kinase (G5K, ProB) and C-terminal glutamic-γ-semialdehyde dehydrogenase (GSA-DH, ProA) domains. The conserved Glu-5-kinase, GSA-DH domains, conserved leucine zipper and the putative ATP and NAD(P)H-binding sites was also found. The JcP5CS protein was successfully expressed in Escherichia coli and showed high enzymatic activities. The real-time quantitative PCR results showed that the JcP5CS was induced by drought and salt stress, but not cold stress.
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