The European dimension for the mouse genome mutagenesis program

The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.     

LKB1 modulates lung cancer differentiation and metastasis

Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis.     

On the Discrepancy Measures for the Optimal Equal Probability Partitioning in Bayesian Multivariate Micro-Aggregation

Data holders, such as statistical institutions and financial organizations, have a very serious and demanding task when producing data for official and public use. It’s about controlling the risk of identity disclosure and protecting sensitive information when they communicate data-sets among themselves, to governmental agencies and to the public. One of the techniques applied is that of micro-aggregation. In a Bayesian setting, micro-aggregation can be viewed as the optimal partitioning of the original data-set based on the minimization of an appropriate measure of discrepancy, or distance, between two posterior distributions, one of which is conditional on the original data-set and the other conditional on the aggregated data-set. Assuming d-variate normal data-sets and using several measures of discrepancy, it is shown that the asymptotically optimal equal probability m-partition of , with m ^1/d ∈ , is the convex one which is provided by hypercubes whose sides are formed by hyperplanes perpendicular to the canonical axes, no matter which discrepancy measure has been used. On the basis of the above result, a method that produces a sub-optimal partition with a very small computational cost is presented. Published online xx, xx, xxxx.     

The High-quality Development of China's Economy:Theory and Applications Special Issue

The world has undergone many changes unseen in a century because of the influence of COVID-19 pandemic and the change of international political and economic re...     

Habitat and plant distributions in hanging gardens of the Narrows, Zion National Park, Utah

Hanging gardens are insular plant communities of the Colorado Plateau. This study examines hanging gardens in the Narrows, Zion National Park, Utah. The floristic similarity of gardens and the presence of species in classes of variables which characterize the habitat are disclosed. Although the gardens are isolated and dissimilar, the individual species are not restricted in the range of habitat found. Floristic dissimilarity cannot be attributed to differences in habitat. These results are compared to studies of hanging gardens in eastern Utah.       

Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking

Cranio-lenticulo-sutural dysplasia (CLSD) is an autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects mapped to chromosome 14q13-q21 (ref. 1). Here we show, using a positional cloning approach, that an F382L amino acid substitution in SEC23A segregates with this syndrome. SEC23A is an essential component of the COPII-coated vesicles that transport secretory proteins from the endoplasmic reticulum to the Golgi complex. Electron microscopy and immunofluorescence show that there is gross dilatation of the endoplasmic reticulum in fibroblasts from individuals affected with CLSD. These cells also exhibit cytoplasmic mislocalization of SEC31. Cell-free vesicle budding assays show that the F382L substitution results in loss of SEC23A function. A phenotype reminiscent of CLSD is observed in zebrafish embryos injected with sec23a-blocking morpholinos. Our observations suggest that disrupted endoplasmic reticulum export of the secretory proteins required for normal morphogenesis accounts for CLSD.