Genome-wide detection of LOH in prostate cancer using human SNP microarray technology

Loss of heterozygosity (LOH) of chromosomal regions is crucial in tumor progression. In this study we assessed the potential of the Affymetrix GeneChip HuSNP mapping assay for detecting genome-wide LOH in prostate tumors. We analyzed two human prostate cell lines, P69SV40Tag (P69) and its tumorigenic subline, M12, and 11 prostate cancer cases. The M12 cells showed LOH in chromosomes 3p12.1-p22.1, 11q22.1-q24.2, 19p13.12, and 19q13.42. All of the prostate cases with informative single-nucleotide polymorphism (SNP) markers showed LOH in 1p31.2, 10q11.21, 12p13.1, 16q23.1-q23.2, 17p13.3, 17q21.31, and 21q21.2. Additionally, a high percentage of cases showed LOH at 6p25.1-p25.3 (75%), 8p22-p23.2, and 10q22.1 (70%). Several tumor suppressor genes (TSGs) have been mapped in these loci. These results demonstrate that the HuSNP mapping assay can serve as an alternative to comparative genomic hybridization for assessing genome-wide LOH and can identify chromosomal regions harboring candidate TSGs implicated in prostate cancer.     

Synthesis of some N-galactosides of 3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones of expected biological activity

The 1-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones were prepared via galactosidation of 3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide. The structure of the new galactosyl derivatives was based on both spectroscopic and chemical evidences.     

Synthesis of some new 2-alpha-L-arabinopyranosyl-1,2,4-triazines as potential antitumor chemotherapeutics

Synthetic routes towards different 2-alpha-L-arabinopyranosyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-/ones or thiones were investigated. Primary human anticancer screening of two selected compounds resulted in an active compound against SF-268 (CNS) cell line.     

The Escherichia coli UVM response is accompanied by an SOS-independent error-prone DNA replication activity demonstrable in vitro

UVM is an SOS-independent inducible response characterized by elevated mutagenesis at a site-specific 3, N4-ethenocytosine (epsilonC) residue borne on M13 single-stranded DNA transfected into Escherichia coli cells pretreated with DNA-damaging agents. By constructing and using E. coli strain AM124 (polA polB umuDC dinB lexA1[Ind-]), we show here that the UVM response is manifested in cells deficient for SOS induction, as well as for all four of the 'non-replicative' DNA polymerases, namely DNA polymerase I (polA), II (polB), IV (dinB) and V (umuDC). These results confirm that UVM represents a novel, previously unidentified cellular response to DNA-damaging agents. To address the question as to whether the UVM response is accompanied by an error-prone DNA replication activity, we applied a newly developed in vitro replication assay coupled to an in vitro mutation analysis system. In the assay, circular M13 single-stranded DNA bearing a site-specific lesion is converted to circular double-stranded replicative-form DNA in the presence of cell extracts and nucleotide precursors under conditions that closely mimic M13 replication in vivo. The newly synthesized (minus) DNA strand is selectively amplified by ligation-mediated polymerase chain reaction (LM-PCR), followed by a multiplex sequence analysis to determine the frequency and specificity of mutations. Replication of DNA bearing a site-specific epsilonC lesion by cell extracts from uninduced E. coli AM124 cells results in a mutation frequency of about 13%. Mutation frequency is elevated fivefold (to 58%) in cell extracts from UVM-induced AM124 cells, with C --> A mutations predominating over C --> T mutations, a specificity similar to that observed in vivo. These results, together with previously reported data, suggest that the UVM response is mediated through the induction of a transient error-prone DNA replication activity and that a modification of DNA polymerase III or the expression of a previously unidentified DNA polymerase may account for the UVM phenotype.     

Maintaining blood–brain barrier integrity: Pericytes perform better than astrocytes during prolonged oxygen deprivation

The blood–brain barrier (BBB), consisting of specialized endothelial cells surrounded by astrocytes and pericytes, plays a crucial role in brain homeostasis. Many cerebrovascular diseases are associated with BBB breakdown and oxygen (O₂) deprivation constitutes a critical factor that onsets its disruption. We investigated the impact of astrocytes and pericytes on brain endothelial cell permeability and survival during different degrees of O₂ deprivation. Prolonged exposure to 1% O₂ caused barrier breakdown and exposure to 0.1% O₂ dramatically accelerated disruption and induced cell death, mediated at least in part via caspase‐3 activation. Reoxygenation allowed only cells exposed to 1% O₂ to re‐establish barrier function. Notably co‐culture with astrocytes and pericytes substantially enhanced barrier function under normoxic conditions, and produced differential responses during O₂ deprivation. At 1% O₂ astrocytes partially maintained barrier integrity whereas pericytes accelerated its disruption in the short‐term, having positive effects only after prolonged exposure. Unexpectedly, at 0.1% O₂ pericytes were more effective than astrocytes in preserving barrier function although the protection afforded by both cells involved inhibition of caspase‐3 pathways. Furthermore, cell‐specific regulation of auto‐ and paracrine VEGF signaling pathways were also in part responsible for the differential modulation of barrier function. Our data suggests that cellular cross‐talk within the neurovascular unit is crucial for preservation of barrier integrity and that pericytes, not astrocytes, play a significant role during severe and prolonged O₂ deprivation. J. Cell. Physiol. 218: 612–622, 2009. © 2008 Wiley‐Liss, Inc.     

Different natural biomasses for lead cation removal

It is believed that some wastes play an important role on the pollution prevention. In this paper, three different natural biomasses were investigated as biosorbent. Salsola green plant which grown at Jubail (industrial area) in KSA, it is phyto remediation plant. Salsola is metal hyper accumulation plant, it adsorbed (23.5, 25.7 mg lead per gram stem or leaf) from soil. Also it can be reused as ion exchanger for pb²⁺ from solution. Shrimp shell’s used for extraction of chitosan in laboratory with degree of substitution 81%. Chitosan and crosslinked carboxymethyl chitosan were investigated for pb²⁺ adsorption and compared with crosslinked carboxymethyl corn cob. The adsorption experiments demonstrated that the three biomasses have high adsorption capacity for pb²⁺, good reusability and stability for three cycles.