1.Mesothelin's minimal MUC16 binding moiety converts TR3 into a potent cancer therapeutic via hierarchical binding events at the plasma membrane.
Su Y1,2, Tatzel K1, Wang X1, Belt B1, Binder P3, Kuroki L3, Powell MA3,4, Mutch DG3,4, Hawkins WG1,4, Spitzer D1,4. Oncotarget. 2016 Apr 22. doi: 10.18632/oncotarget.8925. [Epub ahead of print]
TRAIL has been extensively explored as a cancer drug based on its tumor-selective activity profile but it is incapable per se of discriminating between death receptors expressed by normal host cells and transformed cancer cells. Furthermore, it is well documented that surface tethering substantially increases its biologic activity. We have previously reported on Meso-TR3, a constitutive TRAIL trimer targeted to the biomarker MUC16 (CA125), in which the entire ectodomain of human mesothelin was genetically fused to the TR3 platform, facilitating attachment to the cancer cells via the MUC16 receptor. Here, we designed a truncation variant, in which the minimal 64 amino acid MUC16 binding domain of mesothelin was incorporated into TR3. It turned out that the dual-domain biologic Meso64-TR3 retained its high MUC16 affinity and bound to the cancer cells quickly, independent of the TR3/death receptor interaction. Furthermore, it was substantially more potent than Meso-TR3 and TR3 in vitro and in a preclinical xenograft model of MUC16-dependent ovarian cancer.
2.Comparison of multi-enzyme and thermophilic bacteria on the hydrolysis of mariculture organic waste (MOW).
Guo L1, Sun M2, Zong Y2, Zhao Y2, Gao M2, She Z2. Water Sci Technol. 2016 Apr;73(8):1978-1985.
Mariculture organic waste (MOW) is rich in organic matter, which is a potential energy resource for anaerobic digestion. In order to enhance the anaerobic fermentation, the MOW was hydrolyzed by multi-enzyme and thermophilic bacteria. It was advantageous for soluble chemical oxygen demand (SCOD) release at MOW concentrations of 6 and 10 g/L with multi-enzyme and thermophilic bacteria pretreatments. For multi-enzyme, the hydrolysis was not obvious at substrate concentrations of 1 and 3 g/L, and the protein and carbohydrate increased with hydrolysis time at substrate concentrations of 6 and 10 g/L. For thermophilic bacteria, the carbohydrate was first released at 2-4 h and then consumed, and the protein increased with hydrolysis time. The optimal enzyme hydrolysis for MOW was determined by measuring the changes of SCOD, protein, carbohydrate, ammonia and total phosphorus, and comparing with acid and alkaline pretreatments.
3.Bicarbonate Values for Healthy Residents Living in Cities Above 1500 Meters of Altitude: A Theoretical Model and Systematic Review.
Ramirez-Sandoval JC1, Castilla-Peón MF2, Gotés-Palazuelos J1, Vázquez-García JC3, Wagner MP4, Merelo-Arias CA2, Vega-Vega O1,5, Rincón-Pedrero R1, Correa-Rotter R1. High Alt Med Biol. 2016 Apr 27. [Epub ahead of print]
Ramirez-Sandoval, Juan C., Maria F. Castilla-Peón, José Gotés-Palazuelos, Juan C. Vázquez-García, Michael P. Wagner, Carlos A. Merelo-Arias, Olynka Vega-Vega, Rodolfo Rincón-Pedrero, and Ricardo Correa-Rotter. Bicarbonate values for healthy residents living in cities above 1500 m of altitude: a theoretical model and systematic review. High Alt Med Biol 00:000-000, 2016-Plasma bicarbonate (HCO3-) concentration is the main value used to assess the metabolic component of the acid-base status. There is limited information regarding plasma HCO3- values adjusted for altitude for people living in cities at high altitude defined as 1500 m (4921 ft) or more above sea level. Our aim was to estimate the plasma HCO3- concentration in residents of cities at these altitudes using a theoretical model and compare these values with HCO3- values found on a systematic review, and with those venous CO2 values obtained in a sample of 633 healthy individuals living at an altitude of 2240 m (7350 ft).
4.Viral protein suppresses oxidative burst and salicylic acid-dependent autophagy and facilitates bacterial growth on virus-infected plants.
Zvereva AS1, Golyaev V1, Turco S1, Gubaeva EG1, Rajeswaran R1, Schepetilnikov MV2, Srour O2, Ryabova LA2, Boller T1, Pooggin MM1. New Phytol. 2016 Apr 27. doi: 10.1111/nph.13967. [Epub ahead of print]
Virus interactions with plant silencing and innate immunity pathways can potentially alter the susceptibility of virus-infected plants to secondary infections with nonviral pathogens. We found that Arabidopsis plants infected with Cauliflower mosaic virus (CaMV) or transgenic for CaMV silencing suppressor P6 exhibit increased susceptibility to Pseudomonas syringae pv. tomato (Pst) and allow robust growth of the Pst mutant hrcC-, which cannot deploy effectors to suppress innate immunity. The impaired antibacterial defense correlated with the suppressed oxidative burst, reduced accumulation of the defense hormone salicylic acid (SA) and diminished SA-dependent autophagy. The viral protein domain required for suppression of these plant defense responses is dispensable for silencing suppression but essential for binding and activation of the plant target-of-rapamycin (TOR) kinase which, in its active state, blocks cellular autophagy and promotes CaMV translation.