Exome sequencing of liver fluke-associated cholangiocarcinoma

Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.     

Localization of Golgi-resident glycosyltransferases

For many glycosyltransferases, the information that instructs Golgi localization is located within a relatively short sequence of amino acids in the N-termini of these proteins comprising: the cytoplasmic tail, the transmembrane spanning region, and the stem region (CTS). Also, one enzyme may be more reliant on a particular region in the CTS for its localization than another. The predominance of these integral membrane proteins in the Golgi has seen these enzymes become central players in the development of membrane trafficking models of transport within this organelle. It is now understood that the means by which the characteristic distributions of glycosyltransferases arise within the subcompartments of the Golgi is inextricably linked to the mechanisms that cells employ to direct the flow of proteins and lipids within this organelle.     

Ca<Superscript>2+</Superscript> signals,cell membrane disintegration,and activation of TMEM16F during necroptosis

Activated receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain like (MLKL) are essential components of the necroptotic pathway. Phosphorylated MLKL (pMLKL) is thought to induce membrane leakage, leading to cell swelling and disintegration of the cell membrane. However, the molecular identity of the necroptotic membrane pore remains unclear, and the role of pMLKL for membrane permeabilization is currently disputed. We observed earlier that the phospholipid scramblase and ion channel TMEM16F/anoctamin 6 cause large membrane currents, cell swelling, and cell death when activated by a strong increase in intracellular Ca²⁺. We, therefore, asked whether TMEM16F is also central to necroptotic cell death and other cellular events during necroptosis. Necroptosis was induced by TNFα, smac mimetic, and Z-VAD (TSZ) in NIH3T3 fibroblasts and the four additional cell lines HT₂₉, 16HBE, H441, and L929. Time-dependent changes in intracellular Ca²⁺, cell morphology, and membrane currents were recorded. TSZ induced a small and only transient oscillatory rise in intracellular Ca²⁺, which was paralleled by the activation of outwardly rectifying Cl^? currents, which were typical for TMEM16F/ANO6. Ca²⁺ oscillations were due to Ca²⁺ release from endoplasmic reticulum, and were independent of extracellular Ca²⁺. The initial TSZ-induced cell swelling was followed by cell shrinkage. Using typical channel blockers and siRNA-knockdown, the Cl^? currents were shown to be due to the activation of ANO6. However, the knockdown of ANO6 or inhibitors of ANO6 did not inhibit necroptotic cell death. The present data demonstrate the activation of ANO6 during necroptosis, which, however, is not essential for cell death.     

管式填料反应器合成无水过氧乙酸用于柴油均相氧化脱硫

采用管式填料反应器在丙酮溶剂中进行乙醛液相氧化合成无水过氧乙酸,用所制备的过氧乙酸对加氢柴油进行均相氧化脱硫,并考察了氧化脱硫的温度、时间以及萃取剂乙酸溶液(含5%的水)和过氧乙酸产品用量对脱硫效果的影响.试验结果表明,当过氧乙酸产品用量为理论用量的2倍、脱硫氧化反应温度为50 ℃、脱硫氧化反应时间为30 min、萃取剂用量为氧化柴油的2倍时,氧化脱硫后加氢柴油的硫含量可从295.8 mg/kg降到13.4 mg/kg,脱硫效率达95.5%,柴油收率达93.8%.用过氧乙酸对加氢柴油进行均相氧化脱硫,可使柴油的硫含量小于15 mg/kg的最新国际指标.     

The records of coastline changes reflected by mangroves on the Sunda Shelf since the last 40 ka

This paper presents a 40000-year-long high-resolution mangrove record from sediments of Core 18300, 18302 and 18323 on the continental shelf of the southern South China Sea and reconstructs the coastline changes on Sunda Shelf since the last 40000 years. In the period Marine Isotope 3, the old Sunda Shelf had low sea level, and it was partly exposed. Flourishing vegetations grew on the exposed old land. Mangroves developed along the coastline. On the Last Glacial Maximum, the sea level dropped greatly, coastline moved from inner shelf to outer shelf, the Old Sunda Land exposed further, and the lowering sea level induced the gradual disappearing of mangroves from the inner Sunda Shelf to the outer Sunda Shelf. And pioneer vegetation ferns covered the broadly exposed old land immediately. At the time of the last Deglaciation, sea level rose greatly, the coastline moved to the sea and the Sunda Shelf was drown again. Mangroves were emergent again from outer shelf to inner shelf and developed quickly.