Cell-free synthesis and processing of multiple precursors to glucagon

Glucagon, a polypeptide hormone of 29 amino acids, is synthesized in the islets of Langerhans and immunoreactive forms of the molecule have been found in several tissues. Like many other polypeptide hormones, glucagon is synthesized via a larger precursor molecular, proglucagon; however, estimates of its size vary considerably and the biosynthetic relationship between some of the putative precursors and authentic secreted glucagon is unclear. Consequently it was of interest to investigate the primary translation product of glucagon mRNA to relate its size to that of previously described glucagon precursors. Here we provide evidence for three distinct immunoreactive preproglucagon molecules, two of which have an apparent molecular weight (MW) of approximately 16,000 (16K). Furthermore, when microsomal membranes were present during translation, the nascent 14K preproglucagon polypeptides were processed to proglucagon with a higher apparent MW of 15,000. In contrast, the nascent 16K preproglucagon was co-translationally processed to a slightly smaller polypeptide. The data indicate that the 14K and 16K preproglucagons undergo different types of post-translational modification.     

A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells

Metastatic progression of cancer is a complex and clinically daunting process. We previously identified a set of human microRNAs (miRNAs) that robustly suppress breast cancer metastasis to lung and bone and which display expression levels that predict human metastasis. Although these findings revealed miRNAs as suppressors of cell-autonomous metastatic phenotypes, the roles of non-coding RNAs in non-cell-autonomous cancer progression processes remain unknown. Here we reveal that endogenous miR-126, an miRNA silenced in a variety of common human cancers, non-cell-autonomously regulates endothelial cell recruitment to metastatic breast cancer cells, in vitro and in vivo. It suppresses metastatic endothelial recruitment, metastatic angiogenesis and metastatic colonization through coordinate targeting of IGFBP2, PITPNC1 and MERTK--novel pro-angiogenic genes and biomarkers of human metastasis. Insulin-like growth factor binding protein 2 (IGFBP2) secreted by metastatic cells recruits endothelia by modulating IGF1-mediated activation of the IGF type-I receptor on endothelial cells; whereas c-Mer tyrosine kinase (MERTK) receptor cleaved from metastatic cells promotes endothelial recruitment by competitively antagonizing the binding of its ligand GAS6 to endothelial MERTK receptors. Co-injection of endothelial cells with breast cancer cells non-cell-autonomously rescues their miR-126-induced metastatic defect, revealing a novel and important role for endothelial interactions in metastatic initiation. Through loss-of-function and epistasis experiments, we delineate an miRNA regulatory network's individual components as novel and cell-extrinsic regulators of endothelial recruitment, angiogenesis and metastatic colonization. We also identify the IGFBP2/IGF1/IGF1R and GAS6/MERTK signalling pathways as regulators of cancer-mediated endothelial recruitment. Our work further reveals endothelial recruitment and endothelial interactions in the tumour microenvironment to be critical features of metastatic breast cancer.     

新型材料LiFePO4三维电极处理苯酚废水的新应用

本文介绍了一种处理苯酚废水的新方法,LiFePO4作为三维电极处理实际含酚废水,跟单独用二维电极处理实际含酚废水的效率进行比较。通过表征性实验,结果表明,LiFePO4作为三维电极,处理75min,三维电极法处理效率为75.05%,二维电极法为65.6%,平均比二维电极高出10个点,处理效率有所提高。     

砼中有害骨料引发房屋质量问题的分析与处理

目前在房屋质量检测中 ,多次发现由于现浇砼粗骨料中混有方镁石等有害杂质引发房屋裂缝问题。本文通过调查了 5个类似的房屋检测项目 ,进行综合分析 ,并提出解决建议。