Summary The mammalian Phospholipase D MitoPLD facilitates mitochondrial fusion by generating the signaling lipid phosphatidic acid (PA). The Drosophila MitoPLD homolog Zucchini (Zuc), a proposed cytoplasmic nuclease, is required for piRNA generation, a critical event in germline development. We show that Zuc localizes to mitochondria and has MitoPLD-like activity. Conversely, MitoPLD−/− mice exhibit the meiotic arrest, DNA damage, and male sterility characteristic of mice lacking piRNAs. The primary function of MitoPLD appears to be the generation of mitochondrial-surface PA. This PA in turn recruits the phosphatase Lipin 1, which converts PA to diacylglycerol and promotes mitochondrial fission, suggesting a mechanism for mitochondrial morphology homeostasis. MitoPLD and Lipin 1 have opposing effects on mitochondria length and on intermitochondrial cement (nuage), a structure found between aggregated mitochondria that is implicated in piRNA generation. We propose that mitochondrial-surface PA generated by MitoPLD / Zuc recruits or activates nuage components critical for piRNA production.
Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs) and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated eph and ephrin expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA) and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between ephA2, ephA4, ephA7, ephB4, and ephB6 and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between ephrin ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment.
Two Ziegler−Natta catalysts supported on molecularadducts, namely, MgCl2·6EtOH (ME) and MgCl2·5EtOH·EtOOCPh (Est-ME), have been prepared. A systematic effort has been made to unravel the molecular level structure−property relationships of the catalysts and adducts. Ethylbenzoate is an internal electron donor, and its in situ formation through EtOH + PhCOCl coupling is successfully achieved. The above adduct has been treated with TiCl4, and the resultant catalyst (Ti/Est-ME) is evaluated for ethylene polymerization activity. IR and 13C CP/MAS NMR of Est-ME (Ti/Est-ME) show carbonyl features at 1730 (1680) cm−1 and 169 (170) δ, respectively, providing direct support for the presence of ester as an integral part. In spite of low surface area, Ti/Est-ME gives higher yield for ethylene polymerization than the one derived from ME. The results indicate that electronic environment is more important than surface area or any other single factor in determining the polymerization activity.
Ultrahigh molecular weight polyethylene was synthesized from traditional Ziegler-Natta type catalysts (ZN), namely, TiCl 4 anchored on MgCl 2 support. This, upon activation with AlRR′ 2 (where R, R′ ) isoprenyl or isobutyl), gave precatalysts (C-2 to C-5) having 16, 21, 25, and 32% trivalent titanium, respectively. The reduction in oxidation states also accompanies the reduction in particle size of the catalysts, which in turn gets reflected in the resulting polymer properties under specified operating conditions. We have demonstrated the effect of process conditions that can surmount the catalyst dependency over the polymer characteristics, and hence, it can result in polymer with consistent polymer properties, which is an important need of the polymer industries. The polymer characteristics such as particle size distribution, average particle size, bulk density, reduced specific viscosity, and concentration of fine and coarse particles were determined and were dependent on various process parameters. Under identical reaction conditions, the polymerization with larger scale yield polymer with different characteristics. The fine-tuning of process conditions yielded polymer with consistent quality.
The concentration of ethylene in the solvent of slurry polymerization process is important as it determines the extent of reaction, reaction temperature, heat duty, and molecular weight. In the present study, gas liquid behavior of ethylene, in the presence and absence of hydrogen, was studied in two process solvents namely, hexane and Varsol at various process pressures and temperatures. Solubility of ethylene increases with increase in pressure and decreases with increase in temperature in both the solvents. Ethylene solubility decreases with increase in carbon number of solvent at identical conditions. The presence of hydrogen strongly influences the solubility of ethylene in hexane and varsol. The solubility of ethylene in hexane decreases in the presence of hydrogen compared to its binary solubility, while the presence of hydrogen increases the solubility of ethylene in varsol compared to its binary solubility. A heterogeneous thermodynamic model based on the Chao−Seader method was adopted for modeling the solubility of ethylene, in the presence and absence of hydrogen, in hexane and varsol. Chao−Seader method uses the Redlich−Kwong equation of state for vapor phase fugacity, Chao−Seader correlation for pure component/reference state fugacity, Scatchard−Hildebrand model for liquid activity coefficient, and Lee−Kesler method for molar volume, Gibbs free energy departure and enthalpy departure of the mixtures. The model could explain the ethylene solubility closely in both solvents with the presence and absence of hydrogen over the entire range of process conditions studied.
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