Lysophosphatidic acid up-regulates vascular endothelial growth factor-C and lymphatic marker expressions in human endothelial cells

Lysophosphatidic acid (LPA) is a low-molecular-weight lipid growth factor, which binds to G-protein-coupled receptors. Previous studies have shown that LPA enhances vascular endothelial growth factor-A (VEGF-A) expression in cancer cells and promotes angiogenesis process. However, the roles of LPA in lymphatic vessel formation and lymphangiogenesis have not been investigated. Here, we demonstrated that LPA up-regulated VEGF-C mRNA and protein expressions in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression levels of lymphatic markers, including Prox-1, LYVE-1 and podoplanin, were enhanced in LPA-stimulated tube forming endothelial cells in vitro and in vivo. Moreover, we showed that pretreatment with MAZ51, a VEGFR-3 kinase inhibitor, and introduction of VEGFR-3 siRNA suppressed LPA-induced HUVEC tube formation and lymphatic marker expressions. These results demonstrated that LPA enhances expression of lymphatic markers through activating VEGF-C receptors in endothelial cells. This study provides basic information that LPA might be a target for therapeutics against lymphangiogenesis and tumor metastasis.     

A single gene network accurately predicts phenotypic effects of gene perturbation in Caenorhabditis elegans

The fundamental aim of genetics is to understand how an organism's phenotype is determined by its genotype, and implicit in this is predicting how changes in DNA sequence alter phenotypes. A single network covering all the genes of an organism might guide such predictions down to the level of individual cells and tissues. To validate this approach, we computationally generated a network covering most C. elegans genes and tested its predictive capacity. Connectivity within this network predicts essentiality, identifying this relationship as an evolutionarily conserved biological principle. Critically, the network makes tissue-specific predictions-we accurately identify genes for most systematically assayed loss-of-function phenotypes, which span diverse cellular and developmental processes. Using the network, we identify 16 genes whose inactivation suppresses defects in the retinoblastoma tumor suppressor pathway, and we successfully predict that the dystrophin complex modulates EGF signaling. We conclude that an analogous network for human genes might be similarly predictive and thus facilitate identification of disease genes and rational therapeutic targets.     

Ultraconservation identifies a small subset of extremely constrained developmental enhancers

Extended perfect human-rodent sequence identity of at least 200 base pairs (ultraconservation) is potentially indicative of evolutionary or functional uniqueness. We used a transgenic mouse assay to compare the embryonic enhancer activity of 231 noncoding ultraconserved human genome regions with that of 206 extremely conserved regions lacking ultraconservation. Developmental enhancers were equally prevalent in both populations, suggesting instead that ultraconservation identifies a small, functionally indistinct subset of similarly constrained cis-regulatory elements.     

Metamorphosed mafic rocks with N-type MORE geochemical features in Hainan Island-Remnants of the Paleo-Tethys Oceanic Crust?

A number of metamorphosed mafic rocks occurred within the Paleozoic strata in the Chenxing and Bangxi regions at the northern side of the Changjiang-Qionghai Fault in Central Hainan Island. These metamorphosed mafic rocks are tholeiites in chemistry. They are characterized by extreme depletion of Th, Nb, Ta and LREEs, resembling the depleted N-type mid-ocean ridge basalts (MORB). Field relations suggest that the protolith of the metamorphosed mafic rocks were likely formed in Paleozoic. These metamorphosed mafic rocks with N-type MORB geochemical features were probably the remnants of the Paleo-Tethys oceanic crust.     

TGA-MS联合技术研究煤中氯含量与氯的析出特征之间的关系

借助TGA-MS技术研究了煤中的氯含量(高氯、中氯、低氯煤)对煤在燃烧时氯的析出特征的影响.MS的结果表明,HCl第一个析出峰是一个热作用过程,这部分氯是以离子状态存在于煤的内表面上,第二个HCl析出峰与煤的变质程度有关,而氯则是与煤的有机结构相连,当煤燃烧时,以HCl形式与CO2、SO2、H2O一起析出.第三个HCl析出峰是由于煤中无机氯化物而导致的.     

Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.

Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels, which are densely localized in nerve terminals. Because neurotransmitter release is proportional to the fourth power of calcium concentration, regulation of its entry can profoundly influence neurotransmission. N- and P/Q-type calcium channels are inhibited by G proteins, and recent evidence indicates feedback regulation of P/Q-type channels by calcium. Although calcium-dependent inactivation of L-type channels is well documented, little is known about how calcium modulates P/Q-type channels. Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the alpha1A subunit of P/Q-type channels. In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current. These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain. Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity.     

Himalayan tectonics explained by extrusion of a low-viscosity crustal channel coupled to focused surface denudation.

Recent interpretations of Himalayan-Tibetan tectonics have proposed that channel flow in the middle to lower crust can explain outward growth of the Tibetan plateau, and that ductile extrusion of high-grade metamorphic rocks between coeval normal- and thrust-sense shear zones can explain exhumation of the Greater Himalayan sequence. Here we use coupled thermal-mechanical numerical models to show that these two processes-channel flow and ductile extrusion-may be dynamically linked through the effects of surface denudation focused at the edge of a plateau that is underlain by low-viscosity material. Our models provide an internally self-consistent explanation for many observed features of the Himalayan-Tibetan system.     

Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids

Fusions between the mouse mammary tumour virus long terminal repeat and a mouse dihydrofolate reductase cDNA have been constructed in a SV40 vector. When these plasmids are transferred into recipient cells, the production of dihydrofolate reductase is regulated by glucocorticoid hormones. These results define a hormonally responsive region of the viral genome.