Elemental hydrochemistry assessment on its variation and quality status in Langat River, Western Peninsular Malaysia.

This paper discusses the hydrochemistry variation and its quality status in Langat River, based on the chemistry of major ions, metal concentrations and suitability for drinking purposes. Water samples were collected from 30 different stations to assess their hydrochemical characteristics. The physico-chemical parameters selected were temperature, electrical conductivity, total dissolved solids (TDS), salinity, dissolved oxygen , pH, redox potential, HCO3, Cl, SO4, NO3, Ca, Na, K, Mg, 27Al, 138Ba, 9Be, 111Cd, 59Co, 63Cu, 52Cr, 57Fe, 55Mn, 60Ni, 208Pb, 80Se and 66Zn to investigate the variation of the constituents in the river water. Most of the parameters comply with the Drinking Water Quality Standard of the World Health Organization and the Malaysian National Standard for Drinking Water Quality by the Malaysia Ministry of Health except for EC, TDS, Cl, HCO3, SO4, Na, Mg, Al, Fe and Se. The results show that the Langat River is unsuitable for drinking purposes directly without treatment

Integrated Proteomic and Metabolomic Analysis of an Artificial Microbial Community for Two-Step Production of Vitamin C

An artificial microbial community consisted of Ketogulonicigenium vulgare and Bacillus megaterium has been used in industry to produce 2-keto-gulonic acid (2-KGA), the precursor of vitamin C. During the mix culture fermentation process, sporulation and cell lysis of B. megaterium can be observed. In order to investigate how these phenomena correlate with 2-KGA production, and to explore how two species interact with each other during the fermentation process, an integrated time-series proteomic and metabolomic analysis was applied to the system. The study quantitatively identified approximate 100 metabolites and 258 proteins. Principal Component Analysis of all the metabolites identified showed that glutamic acid, 5-oxo-proline, L-sorbose, 2-KGA, 2, 6-dipicolinic acid and tyrosine were potential biomarkers to distinguish the different time-series samples. Interestingly, most of these metabolites were closely correlated with the sporulation process of B. megaterium. Together with several sporulation-relevant proteins identified, the results pointed to the possibility that Bacillus sporulation process might be important part of the microbial interaction. After sporulation, cell lysis of B. megaterium was observed in the co-culture system. The proteomic results showed that proteins combating against intracellular reactive oxygen stress (ROS), and proteins involved in pentose phosphate pathway, L-sorbose pathway, tricarboxylic acid cycle and amino acids metabolism were up-regulated when the cell lysis of B. megaterium occurred. The cell lysis might supply purine substrates needed for K. vulgare growth. These discoveries showed B. megaterium provided key elements necessary for K. vulgare to grow better and produce more 2-KGA. The study represents the first attempt to decipher 2-KGA-producing microbial communities using quantitative systems biology analysis

Targeting RNA Polymerase Primary σ70 as a Therapeutic Strategy against Methicillin-Resistant Staphylococcus aureus by Antisense Peptide Nucleic Acid

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) causes threatening infection-related mortality worldwide. Currently, spread of multi-drug resistance (MDR) MRSA limits therapeutic options and requires new approaches to "druggable" target discovery, as well as development of novel MRSA-active antibiotics. RNA polymerase primary σ⁷⁰ (encoded by gene rpoD) is a highly conserved prokaryotic factor essential for transcription initiation in exponentially growing cells of diverse S. aureus, implying potential for antisense inhibition. METHODOLOGY/PRINCIPAL FINDINGS: By synthesizing a serial of cell penetrating peptide conjugated peptide nucleic acids (PPNAs) based on software predicted parameters and further design optimization, we identified a target sequence (234 to 243 nt) within rpoD mRNA conserved region 3.0 being more sensitive to antisense inhibition. A (KFF)₃K peptide conjugated 10-mer complementary PNA (PPNA2332) was developed for potent micromolar-range growth inhibitory effects against four pathogenic S. aureus strains with different resistance phenotypes, including clinical vancomycin-intermediate resistance S. aureus and MDR-MRSA isolates. PPNA2332 showed bacteriocidal antisense effect at 3.2 fold of MIC value against MRSA/VISA Mu50, and its sequence specificity was demonstrated in that PPNA with scrambled PNA sequence (Scr PPNA2332) exhibited no growth inhibitory effect at higher concentrations. Also, PPNA2332 specifically interferes with rpoD mRNA, inhibiting translation of its protein product σ⁷⁰ in a concentration-dependent manner. Full decay of mRNA and suppressed expression of σ⁷⁰ were observed for 40 µM or 12.5 µM PPNA2332 treatment, respectively, but not for 40 µM Scr PPNA2332 treatment in pure culture of MRSA/VISA Mu50 strain. PPNA2332 (≥1 µM) essentially cleared lethal MRSA/VISA Mu50 infection in epithelial cell cultures, and eliminated viable bacterial cells in a time- and concentration- dependent manner, without showing any apparent toxicity at 10 µM. CONCLUSIONS: The present result suggested that RNAP primary σ⁷⁰ is a very promising candidate target for developing novel antisense antibiotic to treat severe MRSA infections

The Study on Newly Developed McAb NJ001 Specific to Non-Small Cell Lung Cancer and Its Biological Characteristics

Monoclonal antibody (McAb) is the key tool for cancer immunodiagnosis and immunotherapy. McAb-based immunotherapy that targets tumor antigens has had great achivement. In this study, a cell clone which kept secreting high-titer IgG1-type McAb named NJ001 against human non-small cell lung cancer (NSCLC) cells was obtained. The titer of purified NJ001 was 2×106. The antigen named SP70 of NSCLC specifically identified by NJ001 was proved to be a protein with the relative molecular mass (Mr) of 70 kDa. The results of immunohistochemical staining indicated that NJ001 could positively react to NSCLC, but weak positively or negatively react to human small-cell lung cancer (SCLC), pulmonary pseudotumor and other epithelial tumors. In soft agar assay, the colony formation efficiency in NJ001 groups decreased in a dose-dependent manner. For the concentration of 100 µg/ml, 200 µg/ml and 400 µg/ml, the inhibition ratio of colony formation was 23.4%, 62.5% and 100% respectively. Meanwhile, NJ001 caused significant reduction in tumor volume and tumor weight compared to control mice in lung cancer xenograft model. The tumor growth inhibition ratio in 200 µg, 400 µg and 800 µg NJ001 groups was 10.44%, 37.29% and 44.04%, respectively. NJ001 also led to cytomorphological changes and induced the apoptosis of human lung adenocarcinoma cell line SPC-A1 significantly. The newly developed NJ001 selectively reacted to NSCLC and exhibited anti-tumor activity both in vitro and in vivo. NJ001 is of great value concerning immunodiagnostics and immunotherapy for NSCLC and holds promise for further research regarding the mechanism underlying tumor progression of NSCLC

The association of APE1 −656T > G and 1349 T > G polymorphisms and cancer risk: a meta-analysis based on 37 case-control studies

<p>Abstract</p> <p>Background</p> <p>APE1 (apurinic/apyrimidinic endonuclease 1) is an important DNA repair protein in the base excision repair pathway. Polymorphisms in <it>APE1 </it>have been implicated in susceptibility to cancer; however, results from the published studies remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in <it>APE1 </it>and the risk for cancer.</p> <p>Methods</p> <p>The PubMed and Embase databases were searched for case-control studies published up to June, 2011 that investigated <it>APE1 </it>polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations.</p> <p>Results</p> <p>Two polymorphisms (−656 T > G, rs1760944 and 1349 T > G, rs1130409) in 37 case-control studies including 15, 544 cancer cases and 21, 109 controls were analyzed. Overall, variant genotypes (GG and TG/GG) of −656 T > G polymorphism were associated with significantly decreased cancer risk in homozygote comparison (OR = 0.81, 95%CI: 0.67-0.97), dominant model comparison (OR = 0.89, 95%CI: 0.81-0.97) and recessive model comparison (OR = 0.90, 95%CI: 0.82-0.98), whereas the 1349 T > G polymorphism had no effects on overall cancer risk. In the stratified analyses for −656 T > G polymorphism, there was a significantly decreased risk of lung cancer and among Asian populations.</p> <p>Conclusions</p> <p>Although some modest bias could not be eliminated, the meta-analysis suggests that <it>APE1 −</it>656 T > G polymorphism has a possible protective effect on cancer risk particularly among Asian populations whereas 1349 T > G polymorphism does not contribute to the development of cancer.</p

MicroRNA-145 Regulates Chondrogenic Differentiation of Mesenchymal Stem Cells by Targeting Sox9

Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process still remain to be defined. MicroRNAs (miRNAs) regulate various biological processes by binding target mRNA to attenuate protein synthesis. To investigate the mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-β3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferase reporter gene assay data demonstrated that miR-145 targets a putative binding site in the 3′-UTR of SRY-related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over-expression of miR-145 decreased expression of Sox9 only at protein levels and miR-145 inhibition significantly elevated Sox9 protein levels. Furthermore, over-expression of miR-145 decreased mRNA levels for three chondrogenic marker genes, type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen (Col11a1) in C3H10T1/2 cells induced by TGF-β3, whereas anti-miR-145 inhibitor increased the expression of these chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiation by directly targeting Sox9 at early stage of chondrogenic differentiation

PDK1 and HR46 Gene Homologs Tie Social Behavior to Ovary Signals

The genetic basis of division of labor in social insects is a central question in evolutionary and behavioral biology. The honey bee is a model for studying evolutionary behavioral genetics because of its well characterized age-correlated division of labor. After an initial period of within-nest tasks, 2–3 week-old worker bees begin foraging outside the nest. Individuals often specialize by biasing their foraging efforts toward collecting pollen or nectar. Efforts to explain the origins of foraging specialization suggest that division of labor between nectar and pollen foraging specialists is influenced by genes with effects on reproductive physiology. Quantitative trait loci (QTL) mapping of foraging behavior also reveals candidate genes for reproductive traits. Here, we address the linkage of reproductive anatomy to behavior, using backcross QTL analysis, behavioral and anatomical phenotyping, candidate gene expression studies, and backcross confirmation of gene-to-anatomical trait associations. Our data show for the first time that the activity of two positional candidate genes for behavior, PDK1 and HR46, have direct genetic relationships to ovary size, a central reproductive trait that correlates with the nectar and pollen foraging bias of workers. These findings implicate two genes that were not known previously to influence complex social behavior. Also, they outline how selection may have acted on gene networks that affect reproductive resource allocation and behavior to facilitate the evolution of social foraging in honey bees

The first case of Brucella canis in Sweden: background, case report and recommendations from a northern European perspective

Infection with Brucella canis has been diagnosed in Sweden for the first time. It was diagnosed in a three-year-old breeding bitch with reproductive disturbances. Fifteen in-contact dogs were tested repeatedly and all of them were negative for B. canis. The source of infection could not be defined. The present article describes the case and the measures undertaken and gives a short review over B. canis. Recommendations on how to avoid the infection in non-endemic countries are given

Measurements of the branching fraction and polarization in B+->rho K-+(*0) decays

We present the results of a study of the charmless vector-vector decay B+->rho K-+(*0), based on 253 fb(-1) of data collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. We obtain the branching fraction B(B+->rho K-+(*0))=[8.9 +/- 1.7(stat)+/- 1.2(syst)]x10(-6). We also perform a helicity analysis of the rho and K-* vector mesons, and obtain the longitudinal polarization fraction f(L)(B+->rho K-+(*0))=0.43 +/- 0.11(stat)(-0.02)(+0.05)(syst)