Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.     

Conditioned medium enhances the fusion capability of rat bone marrow mesenchymal stem cells and cardiomyocytes

Mesenchymal stem cells (MSCs) show accelerated regeneration potential when these cells experience hypoxic stress. This “preconditioning” has shown promising results with respect to cardio-protection as it stimulates endogenous mechanisms resulting in multiple cellular responses. The current study was carried out to analyze the effect of hypoxia on the expression of certain growth factors in rat MSCs and cardiomyocytes (CMs). Both cell types were cultured and assessed separately for their responsiveness to hypoxia by an optimized dose of 2,4,-dinitrophenol (DNP). These cells were allowed to propagate under normal condition for either 2 or 24 h and then analyzed for the expression of growth factors by RT-PCR. Variable patterns of expression were observed which indicate that their expression depends on the time of re-oxygenation and extent of hypoxia. To see whether the growth factors released during hypoxia affect the fusion of MSCs with CMs, we performed co-culture studies in normal and conditioned medium. The conditioned medium is defined as the medium in which CMs were grown for re-oxygenation till the specified time period of either 2 or 24 h after hypoxia induction. The results showed that the fusion efficiency of cells was increased when the conditioned medium was used as compared to that in the normal medium. This may be due to the presence of certain growth factors released by the cells under hypoxic condition that promote cell survival and enhance their fusion or regenerating ability. This study would serve as another attempt in designing a therapeutic strategy in which conditioned MSCs can be used for ischemic diseases and provide more specific therapy for cardiac regeneration.     

Oil Palm Empty Fruit Bunch and Sugarcane Bagasse Enhance the Bioremediation of Soil Artificially Polluted by Crude Oil

Contamination of soil by petroleum hydrocarbons is becoming prevalent in Malaysia. Infiltration of soil contamination into groundwater poses a great threat to the ecosystem and human health. Bioremediation can occur naturally or can be enhanced with supplementation of microorganisms and fertilizers. However, fertilizers are expensive and therefore alternative nutrient-rich biomaterials are required. In this study, two organic wastes from agricultural industry (i.e., sugarcane bagasse and oil palm empty fruit bunch) were investigated for possible enhanced bioremediation of soil contaminated with Tapis crude oil. Two bacterial strains isolated and characterized previously (i.e., Pseudomonas aeruginosa UKMP-14T and Acinetobacter baumannii UKMP-12T) were used in this study. Sugarcane bagasse (5% and 15%, w/w) and oil palm empty fruit bunch (20%, w/w) were mixed with soil (500 g) spiked with Tapis crude oil (3%, v/w). The treated soils as well as controls were incubated for 20 days under controlled conditions. Sampling was carried out every four days to measure the number of bacterial colonies (CFU/g) and to determine the percentage of oil degradation by gas chromatography. The two biostimulating agents were able to maintain the soil moisture holding capacity, pH, and temperature at 38-40% volumetric moisture content (VMC), 7.0, and 29–30°C; respectively. The growth of bacteria consortium after 20 days in the treatment with sugarcane bagasse and oil palm empty fruit bunch had increased to 10.3 CFU/g and 9.5 CFU/g, respectively. The percentage of hydrocarbon degradation was higher in the soil amended with sugarcane bagasse (100%) when compared to that of oil palm empty fruit bunch (97%) after 20 days. Our results demonstrated the potential of sugarcane bagasse and oil palm empty fruit bunch as good substrates for enhanced bioremediation of soil contaminated with petroleum crude oil.     

Involvement of glycans in the immunological cross-reaction between α-macroglobulin and hemocyanin of the gastropod Helix pomatia

By tandem-crossed immunoelectrophoresis and ELISA experiments an immunological relationship was observed between α-macroglobulin (αM) and hemocyanin (Hc) of the terrestrial snail Helix pomatia. Both glycoproteins occur in the hemolymph: αM (minor component) as a specific proteinase inhibitor, Hc (consisting of three components: α_D-HpH, α_N-HpH and β-HpH) as oxygen transport protein. The cross-reaction was found to be correlated with glycosylation. (i) With β-HpH, which is richer in carbohydrates than α_D-HpH and α_N-HpH, mainly due to a higher 3-O-methyl-d-galactose content, the cross-reaction with HpαM was highest. (ii) From the 8 functional units, designated a–h, isolated from β-HpH, two that lack carbohydrates (c and f) were not recognized by antibodies against HpαM, while the six glycosylated ones were strongly cross-reacting. The nearly complete loss of the cross-reactivity upon deglycosylation of functional units d and g and the inhibition in competitive ELISA experiments by glycopeptides isolated from both β-HpH and HpαM are further evidence that glycans are involved in the immunological relationship between HpH and HpαM. Carbohydrate analyses indicated that the glycan structures present on HpαM are very similar (or identical) to those found on HpH, suggesting that glycans are common epitopes on both proteins. Especially d-xylose and 3-O-methyl-d-galactose seem to be responsible for the cross-reactivity since the α-macroglobulin and hemocyanin of the cephalopod Sepia officinalis, which lack these two monosaccharides in their glycan structures, do not immunologically cross-react.     

Sequence analysis and structure prediction of type II Pseudomonas sp. USM 4–55 PHA synthase and an insight into its catalytic mechanism

Background  

Polyhydroxyalkanoates (PHA), are biodegradable polyesters derived from many microorganisms such as the pseudomonads. These polyesters are in great demand especially in the packaging industries, the medical line as well as the paint industries. The enzyme responsible in catalyzing the formation of PHA is PHA synthase. Due to the limited structural information, its functional properties including catalysis are lacking. Therefore, this study seeks to investigate the structural properties as well as its catalytic mechanism by predicting the three-dimensional (3D) model of the Type II Pseudomonas sp. USM 4–55 PHA synthase 1 (PhaC1_{P.sp USM 4–55}).     

Bicyclic peptides as potent inhibitors of histone deacetylases: Optimization of alkyl loop length

Bicyclic tetrapeptide hydroxamic acids were prepared as histone deacetylase (HDAC) inhibitors, and the evaluated inhibitory activity shows that they are potent against HDAC1 and HDAC4. The in vivo activity depends on alkyl loop length.     

Molecular Docking Study of Beta-Glucosidase with Cellobiose,Cellotetraose and Cellotetriose

Beta-glucosidase (3.2.1.21) plays an essential role in the removal of non-reducing terminal glucosyl residues from glycosides. Recently, beta-glucosidase has been of interest for biomass conversion that acts in synergy with two other enzymes, endoglucanase and exo-glucanase. However, there is not much information available on the catalytic interactions of beta-glucosidase with its substrates. Thus, this study reports on the binding modes between beta-glucosidase from glycoside hydrolase family 1 namely BglB with cellobiose, cellotetraose and cellotetriose via molecular docking simulation. From the results, the binding affinities of BglB-cellobiose, BglB-cellotetraose, and BglB-cellotetriose complexes were reported to be -6.2kJ/mol , -5.68 kJ/mol and -5.63 kJ/mol, respectively. The detail interactions were also been investigated that revealed the key residues involved in forming hydrogen bonds (h-bond) with the substrates. These findings may provide valuable insigths in designing beta-glucosidase with higher cellobiose-hydrolyzing efficiency.     

The Bemisia tabaci species complex： Additions from different parts of the world

Bemisia tabaci is one of the most threatening pests in many crops. We sequenced part of the mitochondrial cytochrome oxidase I gene from fifty whitefly populations collected in Indonesia, Thailand, India and China. Nineteen unique sequences （haplotypes） of the cytochrome oxidase I were identified in these populations. They were combined with sequences available in databases, resulting in a total of 407 haplotypes and analyzed together with nine outgroup accessions. A phylogenetic tree was calculated using the maximum likelihood method. The tree showed that all groups that were found in previous studies were also present in our study. Additionally, seven new groups were identified based on the new haplotypes. Most B. tabaci haplotypes grouped based on their geographical origin. Two groups were found to have a worldwide distribution. Our results indicate that our knowledge on the species complex around B. tabaci is still far from complete.     

Purification and characterization of a Ca(2+)-dependent novel lectin from Nymphaea nouchali tuber with antiproliferative activities

A lectin (termed NNTL) was purified from the extracts of Nymphaea nouchali tuber followed by anion-exchange chromatography on DEAE-cellulose, hydrophobic chromatography on HiTrap Phenyl HP and by repeated anion-exchange chromatography on HiTrap Q FF column. The molecular mass of the purified lectin was 27.0 ± 1.0 kDa, as estimated by SDS/PAGE both in the presence and in the absence of 2-mercaptoethanol. NNTL was an o-nitrophenyl β-D-galactopyranoside sugar-specific lectin that agglutinated rat, chicken and different groups of human blood cells and exhibited high agglutination activity over the pH range 5-9 and temperatures of 30-60 °C. The N-terminal sequence of NNTL did not show sequence similarity with any other lectin and the amino acid analysis revealed that NNTL was rich in leucine, methionine and glycine residues. NNTL was a glycoprotein containing 8% neutral sugar and showed toxicity against brine shrimp nauplii with an LC(50) value of 120 ± 29 μg/ml and exerted strong agglutination activity against four pathogenic bacteria (Bacillus subtilis, Sarcina lutea, Shigella shiga and Shigella sonnei). In addition, antiproliferative activity of this lectin against EAC (Ehrlich ascites carcinoma) cells showed 56% and 76% inhibition in vivo in mice at 1.5 and 3 mg·kg(-1)·day(-1) respectively. NNTL was a divalent ion-dependent glycoprotein, which lost its activity markedly in the presence of denaturants. Furthermore, measurement of fluorescence spectra in the presence and absence of urea and CaCl(2) indicated the requirement of Ca(2+) for the stability of NNTL.     

Genetic and biochemical characterization of a pathway for the degradation of 2-aminoethylphosphonate in Sinorhizobium meliloti 1021

A variety of microorganisms have the ability to use phosphonic acids as sole sources of phosphorus. Here, a novel pathway for degradation of 2-aminoethylphosphonate in the bacterium Sinorhizobium meliloti 1021 is proposed based on the analysis of the genome sequence. Gene deletion experiments confirmed the involvement of the locus containing phnW, phnA, and phnY genes in the conversion of 2-aminoethylphosphonate to inorganic phosphate. Biochemical studies of the recombinant PhnY and PhnA proteins verified their roles as phosphonoacetaldehyde dehydrogenase and phosphonoacetate hydrolase, respectively. This pathway is likely not limited to S. meliloti as suggested by the presence of homologous gene clusters in other bacterial genomes.