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.     

Participation of CD4 coreceptor molecules in T-cell repertoire selection.

During thymocyte development, progenitor cells bearing both CD4 and CD8 coreceptor molecules mature into functional T lymphocytes that express these proteins in a mutually exclusive way. Although T-cell specificity is determined primarily by the structure of the T-cell antigen receptor (TCR) heterodimer, a developmentally regulated process acts to ensure that cells bearing class II-restricted TCRs are CD4+ and those bearing class I-restricted TCRs express only CD8. To investigate this maturation process, we have engineered transgenic mice in which CD4 is expressed in all thymocyte subsets and in all peripheral T cells. Peripheral CD4+8+ T lymphocytes from these mice react with both class I and class II alloantigens. Moreover, expression of the CD4 transgene disrupts the positive selection of doubly transgenic thymocytes bearing a class I-restricted TCR specific for the male (H-Y) antigen. Hence the CD4 coreceptor participates directly in T-cell repertoire selection.     

Somatic chromosomes of the flat-headed bats (Tylonycteris spp)

Zusammenfassung Zwei sympatrische, nahverwandte Fledermausarten,Tylonycteris pachypus (Temminck) undT. robustula Thomas, besitzen 46 beziehungsweise 32 Chromosomen, was offenbar den Robertson'schen Translokationen zuzuschreiben ist.     

Cytotoxic effects of an alcoholic extract of a sponge,suberites inconstans

Zusammenfassung Ein alkoholisher Extrakt des SchwammesSuberites inconstans erweist sich als ein Zellgift gegenüber Hela-Zellen. Wachstumsstörungen treten auf, und mikroskopisch sichtbare Veränderungen an Kernen und Membranen werden festgestellt.     

An ARF-GEF acting at the Golgi and in selective endocytosis in polarized plant cells

Circumstantial evidence suggests that intracellular membrane trafficking pathways diversified independently in the plant kingdom, but documented examples are rare. ARF-GEFs (guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases) are essential for vesicular trafficking in all eukaryotic kingdoms, but of the eight ARF-GEF families, only the ancestral BIG and GBF types are found in plants. Whereas fungal and animal GBF proteins perform conserved functions at the Golgi, the Arabidopsis thaliana GBF protein GNOM is thought to act in only the process of recycling from endosomes. We now show that the related Arabidopsis GBF protein GNOM-LIKE1 (GNL1) has an ancestral function at the Golgi but is also required for selective internalization from the plasma membrane in the presence of brefeldin A (BFA). We identified gnl1 mutants that accumulated biosynthetic and recycling endoplasmic reticulum markers in enlarged internal compartments. Notably, in the absence of functional GNL1, Golgi stacks were rendered sensitive to the selective ARF-GEF inhibitor BFA, which caused them to fuse with the endoplasmic reticulum. Furthermore, in BFA-treated gnl1 roots, the internalization of a polar plasma-membrane marker, the auxin efflux carrier PIN2, was selectively inhibited. Thus, GNL1 is a BFA-resistant GBF protein that functions with a BFA-sensitive ARF-GEF both at the Golgi and in selective endocytosis, but not in recycling from endosomes. We propose that the evolution of endocytic trafficking in plants was accompanied by neofunctionalization within the GBF family, whereas in other kingdoms it occurred independently by elaboration of additional ARF-GEF families.     

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes

Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers.     

On classical cloning and no-cloning

It is part of information theory folklore that, while quantum theory prohibits the generic (or universal) cloning of states, such cloning is allowed by classical information theory. Indeed, many take the phenomenon of no-cloning to be one of the features that distinguishes quantum mechanics from classical mechanics. In this paper, we argue that pace conventional wisdom, in the case where one does not include a machine system, there is an analog of the no-cloning theorem for classical systems. However, upon adjoining a non-trivial machine system (or ancilla) one finds that, pace the quantum case, the obstruction to cloning disappears for pure states. We begin by discussing some conceptual points and category-theoretic generalities having to do with cloning, and proceed to discuss no-cloning in both the case of (non-statistical) classical mechanics and classical statistical mechanics.