Protease-activated-receptor-2 affects protease-activated-receptor-1-driven breast cancer

Mammalian protease-activated-receptor-1 and -2 (PAR₁ and PAR₂) are activated by proteases found in the flexible microenvironment of a tumor and play a central role in breast cancer. We propose in the present study that PAR₁ and PAR₂ act together as a functional unit during malignant and physiological invasion processes. This notion is supported by assessing pro-tumor functions in the presence of short hairpin; shRNA knocked-down hPar2 or by the use of a truncated PAR₂ devoid of the entire cytoplasmic tail. Silencing of hPar2 by shRNA-attenuated thrombin induced PAR₁ signaling as recapitulated by inhibiting the assembly of Etk/Bmx or Akt onto PAR₁-C-tail, by thrombin-instigated colony formation and invasion. Strikingly, shRNA-hPar2 also inhibited the TFLLRN selective PAR₁ pro-tumor functions. In addition, while evaluating the physiological invasion process of placenta extravillous trophoblast (EVT) organ culture, we observed inhibition of both thrombin or the selective PAR₁ ligand; TFLLRNPNDK induced EVT invasion by shRNA-hPar2 but not by scrambled shRNA-hPar2. In parallel, when a truncated PAR₂ was utilized in a xenograft mouse model, it inhibited PAR₁–PAR₂-driven tumor growth in vivo. Similarly, it also attenuated the interaction of Etk/Bmx with the PAR₁-C-tail in vitro and decreased markedly selective PAR₁-induced Matrigel invasion. Confocal images demonstrated co-localization of PAR₁ and PAR₂ in HEK293T cells over-expressing YFP-hPar2 and HA-hPar1. Co-immuno-precipitation analyses revealed PAR₁-PAR₂ complex formation but no PAR₁-CXCR4 complex was formed. Taken together, our observations show that PAR₁ and PAR₂ act as a functional unit in tumor development and placenta-uterus interactions. This conclusion may have significant consequences on future breast cancer therapeutic modalities and improved late pregnancy outcome.     

伊朗西北部Arasbaran生物圈保护区及邻近地区的天牛种类(鞘翅目:天牛科)

天牛(鞘翅目Coleoptera:天牛科Cerambycidae)为树木重要的钻蛀性害虫.本文研究了伊朗西北部Arasbaran生物圈保护区及邻近地区的天牛种类,采集鉴定了5个亚科26属33种,提供了一些种类的植物寄主.     

An integrated semiconductor device enabling non-optical genome sequencing

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.     

Shift-contagion in energy markets and global crisis

This paper presents an analysis of shift-contagion in energy markets, testing whether linkages between returns in energy markets increase during crisis periods. The research presented herein demonstrates how common movement between energy markets increases due to (i) shift-contagion across energy markets, reflected by structural transmission of shocks across markets and (ii) larger common shocks operating through standard cross-market interdependences. A regime-switching model was developed to detect shift-contagion across energy markets. In the approach adopted herein, the occurrence of shift-contagion is endogenously estimated rather than being exogenously assigned. The results show that shift-contagion has been a major feature of energy markets over the last decade. Evidence is presented which demonstrates that the linkages between energy markets do not appear to be stable. These results are remarkably accurate for forecasting Brent and natural gas for horizons for up to 50 days. Conversely, for WTI (West Texas Intermediate oil) and coal, the model performs well only for forecasting very short horizons (up to 20 days). For all products, the model shows significant biases for long horizons.     

Chemically Synthesised Pt Particles on Surface Oxidized Carbon Nanotubes as an Effective Catalyst for Direct Methanol Fuel Cell

1 Results The synthesis, physical characterization and electrochemical analysis of Pt particles prepared using the surface oxidized carbon nanotubes prepared by chemically anchoring Pt onto the surface of the CNTs with 2.0 mol/L HNO3 by refluxing for 10 h to introduce surface functional groups.The particles of Pt are synthesized by reduction with sodium borohydride of H2PtCl6. The electro-oxidation of liquid methanol of this catalyst as a thin layer on glassy carbon electrode is investigated at room te...     

Genetically modified Plasmodium parasites as a protective experimental malaria vaccine

Malaria is a mosquito-borne disease that is transmitted by inoculation of the Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes, transform into liver stages, and subsequent liver-stage development ultimately results in release of pathogenic merozoites. Liver stages of the parasite are a prime target for malaria vaccines because they can be completely eliminated by sterilizing immune responses, thereby preventing malarial infection. Using expression profiling, we previously identified genes that are only expressed in the pre-erythrocytic stages of the parasite. Here, we show by reverse genetics that one identified gene, UIS3 (upregulated in infective sporozoites gene 3), is essential for early liver-stage development. uis3-deficient sporozoites infect hepatocytes but are unable to establish blood-stage infections in vivo, and thus do not lead to disease. Immunization with uis3-deficient sporozoites confers complete protection against infectious sporozoite challenge in a rodent malaria model. This protection is sustained and stage specific. Our findings demonstrate that a safe and effective, genetically attenuated whole-organism malaria vaccine is possible.