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.     

Spider mites (Acari: Tetranychidae) of Saudi Arabia: two new species,new records and a key to all known species

A total of 18 spider mite species belonging to 10 genera of the family Tetranychidae (Acari: Prostigmata) are reported from different provinces of Saudi Arabia (SA). Among these, two new species, Sonotetranychus madinahensis sp. nov. and Tetranychus salicornicus sp. nov., belonging to the subfamily Tetranychinae are described and illustrated. Also, five genera and 11 species are new to the mite fauna of SA. The distribution and host data of all recorded species in the current study are provided. A key to all spider mite species of SA is provided as well as a key to the species of the armenychus species group of the genus Tetranychus Dufour, based on males.

www.zoobank.org/urn:lsid:zoobank.org:pub:C41BB3ED-99D5-4DCF-B557-09526FA7D56B     

CONCURRENT PRODUCTION ENGINEERING SYSTEM FOR BUFFER SIZE AND FLEXIBLE TRANSFER LINE LAYOUT DESIGN

In this paper we propose a COncurrent Production Engineering System （COPES） for the flexible transfer line （FTL） layout design in a restricted area. COPES first determines the buffer size in front of the bay of each machine tool in the FTL and then initializes a computer aided design （CAD） system to draw the FTL in a restricted area. We develop a set of modules systems which have been integrated into a single framework, in accordance with the practice of concurrent engineering. Concurrent engineering involves the cooperation of these activities. It＇s expected that the developed COPES can improve the cooperation between production engineers＇ and the plant designer. This can be done by enabling the production engineers＇ to make better decision regarding FTL buffer size.