Mutations in SUFU predispose to medulloblastoma

Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis (Ollier and Maffucci diseases). Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to chondrosarcoma. The extent of skeletal involvement is variable in enchondromatosis and may include dysplasia that is not directly attributable to enchondromas. Enchondromatosis is rare, obvious inheritance of the condition is unusual and no candidate loci have been identified. Enchondromas are usually in close proximity to, or in continuity with, growth-plate cartilage. Consequently, they may result from abnormal regulation of proliferation and terminal differentiation of chondrocytes in the adjoining growth plate. In normal growth plates, differentiation of proliferative chondrocytes to post-mitotic hypertrophic chondrocytes is regulated in part by a tightly coupled signaling relay involving parathyroid hormone related protein (PTHrP) and Indian hedgehog (IHH). PTHrP delays the hypertrophic differentiation of proliferating chondrocytes, whereas IHH promotes chondrocyte proliferation. We identified a mutant PTH/PTHrP type I receptor (PTHR1) in human enchondromatosis that signals abnormally in vitro and causes enchondroma-like lesions in transgenic mice. The mutant receptor constitutively activates Hedgehog signaling, and excessive Hedgehog signaling is sufficient to cause formation of enchondroma-like lesions.     

Apc modulates embryonic stem-cell differentiation by controlling the dosage of beta-catenin signaling

The Wnt signal-transduction pathway induces the nuclear translocation of membrane-bound beta-catenin (Catnb) and has a key role in cell-fate determination. Tight somatic regulation of this signal is essential, as uncontrolled nuclear accumulation of beta-catenin can cause developmental defects and tumorigenesis in the adult organism. The adenomatous polyposis coli gene (APC) is a major controller of the Wnt pathway and is essential to prevent tumorigenesis in a variety of tissues and organs. Here, we have investigated the effect of different mutations in Apc on the differentiation potential of mouse embryonic stem (ES) cells. We provide genetic and molecular evidence that the ability and sensitivity of ES cells to differentiate into the three germ layers is inhibited by increased doses of beta-catenin by specific Apc mutations. These range from a severe differentiation blockade in Apc alleles completely deficient in beta-catenin regulation to more specific neuroectodermal, dorsal mesodermal and endodermal defects in more hypomorphic alleles. Accordingly, a targeted oncogenic mutation in Catnb also affects the differentiation potential of ES cells. Expression profiling of wildtype and Apc-mutated teratomas supports the differentiation defects at the molecular level and pinpoints a large number of downstream structural and regulating genes. Chimeric experiments showed that this effect is cell-autonomous. Our results imply that constitutive activation of the Apc/beta-catenin signaling pathway results in differentiation defects in tissue homeostasis, and possibly underlies tumorigenesis in the colon and other self-renewing tissues.     

Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2

We identified loss-of-function mutations in ATP6V0A2, encoding the a2 subunit of the V-type H+ ATPase, in several families with autosomal recessive cutis laxa type II or wrinkly skin syndrome. The mutations result in abnormal glycosylation of serum proteins (CDG-II) and cause an impairment of Golgi trafficking in fibroblasts from affected individuals. These results indicate that the a2 subunit of the proton pump has an important role in Golgi function.     

Gene expression profiling predicts clinical outcome of breast cancer

Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.     

Analytical Algorithms for the Blend Ratios by Fibre-bundle Tensile Curves Part I. Typical Tensile Curve and the Strength and Work Methods

The blend ratio and tensile properties are vital important characteristics of blended fibre bundles. Fibre-bundle tensile behaviour has been measured by means of the Sirolan-Tensor in order to derive a typical specific stress - extension curve. According to the typical tensile curve, the relationships between the blend ratio and the tensile parameters are discussed and established. Two new algorithms, so-called the strength method and the work method, have been developed for the blend-ratio estimation of blended fibre bundles. The relevant blend-ratios and calculations of the two methods are defined in detail. Also, the characteristics have been explained for every calculation and compared to each others. The experimental results show that the blend ratios estimated from the theoretical methods are high coincidence with the measured results. Meanwhile, the specific stress -- extension curve of blended fibre bundles depends directly on the blend ratios of the fibre bundles,     

添加石灰处理纯碱烧结法赤泥的研究

论述了用石灰烧结法处理纯碱烧结法赤泥的研究，考查了钙比，烧结温度，烧结时间对氧化铝溶出率的影响。实验结果表明，石灰烧结法处理纯碱烧结法赤泥的最佳条件为：钙比2．25，烧结温度为1200，烧结时阃为40min．     

Analytical Algorithms for the Blend Ratios by Fibre-bundle Tensile Curves Part Ⅲ:The Definition Method and the Relationships between the Blend Ratio and Tensile Parameters Calculated from Different Ways

The algorithms of the strength, work, modulus and percentage methods have been introduced and discussed in Part Ⅰ and Part Ⅱ of the series papers. As the following, the percentage-function calculation and the frequency-function calculation of the definition method are defined and developed in detail. Meanwhile, the procedures to find the tensile parameters are analysed experimentally and involve "ED" being the average values of the corresponding tensile parameters of each bundle tensile curve measured; "EC" being the tensile parameters obtained from the averaged experimental tensile curve; and "TC" being the parameters of the theoretical tensile curve according to the corresponding nominal blend ratio. The theoretical and experimental results indicate that the blend ratio estimated by the definition method from wool/polyester blended fibre bundles has a high correlation with the actual blend ratio though the variables to be known in this method are the most of all the methods and there exist the difficulty to solve fibre bundle tensile behaviour without fibre broken in accuracy and that there are high correlations between the EC and TC data and the tensile parameters should be calculated using the EC method rather than the ED method with the exception of the bundle initial modulus. The relationships between blend ratios and the tensile properties of blended fibre bundles can be used to select the optimum blend ratio of blended tops or yarns.