Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer

Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.     

Fe^2＋和CO2对番木瓜ACC氧化酶活性的影响

１－氨基环丙烷－１－羧酸（ＡＣＣ）氧化酶催化ＡＣＣ氧化成为乙烯．通过ＤＥＡＥ－Ｓｅｐｈａｒｏｓｅ和Ｐｈｅｎｙｌ－Ｓｅｐｈａｒｏｓｅ柱层析后，ＡＣＣ氧化酶被纯化１９．５倍．在体外分析中，ＡＣＣ氧化酶活性被Ｆｅ２＋和ＣＯ２促进；Ｃｏ２＋、Ｎｉ２＋和Ｍｎ２＋抑制ＡＣＣ氧化酶的活性，但这种抑制效应能部分地被Ｆｅ２＋所拮抗．ＣＯ２对ＡＣＣ氧化酶活性的促进作用与反应体系中氧的浓度有关，在２１％的氧浓度下，ＣＯ２的促进作用较显著     

ACC氧化酶的测定方法

利用番木瓜ＣａｒｉｃａＰａｐａｙａＬ．果实为材料，研究了１－氨基环丙烷－１－羧酸（ＡＣＣ）氧化酶的体内和体外测定方法．在ＡＣＣ氧化酶的体外分析中，甘油体积分数为１０％～３０％时能稳定酶的活性；φ（ＣＯ２）为０．３％～２０％（反应体系气相中）和０．５～１２ｍｍｏｌ／ＬＡＣＣ提高酶的活性；较适宜的ｐＨ值为７．２．     

Forecasting Online Auctions via Self‐Exciting Point Processes

Modeling online auction prices is a popular research topic among statisticians and marketing analysts. Recent research mainly focuses on two directions: one is the functional data analysis (FDA) approach, in which the price–time relationship is modeled by a smooth curve, and the other is the point process approach, which directly models the arrival process of bidders and bids. In this paper, a novel model for the bid arrival process using a self‐exciting point process (SEPP) is proposed and applied to forecast auction prices. The FDA and point process approaches are linked together by using functional data analysis technique to describe the intensity of the bid arrival point process. Using the SEPP to model the bid arrival process, many stylized facts in online auction data can be captured. We also develop a simulation‐based forecasting procedure using the estimated SEPP intensity and historical bidding increment. In particular, prediction interval for the terminal price of merchandise can be constructed. Applications to eBay auction data of Harry Potter books and Microsoft Xbox show that the SEPP model provides more accurate and more informative forecasting results than traditional methods. Copyright © 2014 John Wiley & Sons, Ltd.     

Leonurine,an improved synthesis

Summary Leonurine (1) is the uterotonic principle ofLeonurus artemisia. We have developed a simple, high-yield synthetic procedure of1 that is adaptable to large scale preparation. The synthesis involves the condensation of syringic acid and 4-guanidino-1-butanol hydrochloride in the presence of DDC using 11 HMPT-ether as solvent. The synthetic leonurine showed uterotonic activity in vivo and in vitro.Acknowledgment. This work was partly supported by World Health Organization, Geneva, Switzerland.     

Late retroperitoneal recurrence of hepatocellular carcinoma 12 years after initial diagnosis

Hepatocellular carcinoma (HCC) is an aggressive tumor with poor long-term prognosis.Here,we present an unusual patient with a solitary recurrence of HCC in the right kidney 12 years after the initial diagnosis.This illustrates the importance of considering late recurrence in patients with a history of HCC and the management of these metastases.