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Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic(More)
A series of peptide derivatives based on the transition-state mimetic concept has been designed that inhibit the proteinase from the human immunodeficiency virus (HIV). The more active compounds inhibit both HIV-1 and HIV-2 proteinases in the nanomolar range with little effect at 10 micromolar against the structurally related human aspartic proteinases.(More)
It has become evident that the CD4 subset of lymphocytes is a heterogeneous collection of cells with multiple phenotypes and functions (1-3). Recently, CD4+ lym-phocytes have been subdivided into reciprocal subsets based on their expression of unique isoforms of the leucocyte common antigen (LCA)1 /T200 family of antigens (CD45/CD45R) (4-6) and the CDw29(More)
Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work(More)
Monocarboxylate Transporter 2 (MCT2) is a major pyruvate transporter encoded by the SLC16A7 gene. Recent studies pointed to a consistent overexpression of MCT2 in prostate cancer (PCa) suggesting MCT2 as a putative biomarker and molecular target. Despite the importance of this observation the mechanisms involved in MCT2 regulation are unknown. Through an(More)
Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal(More)
Aspartic proteinase A from yeast is specifically and potently inhibited by a small protein called IA3 from Saccharomyces cerevisiae. Although this inhibitor consists of 68 residues, we show that the inhibitory activity resides within the N-terminal half of the molecule. Structures solved at 2.2 and 1.8 A, respectively, for complexes of proteinase A with(More)
Compared with xenografts from previously established cell lines, patient-derived xenografts may more faithfully recapitulate the molecular diversity, cellular heterogeneity, and histology seen in patient tumors, although other limitations of murine models remain. The ability of these models to inform clinical development and answer mechanistic questions(More)
UNLABELLED The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass(More)
We have compiled a global geological map of Ganymede that represents the most recent understanding of the satellite based on Galileo mission results. This contribution builds on important previous accomplishments in the study of Ganymede utilizing Voyager data and incorporates the many new discoveries that were brought about by examination of Galileo data.(More)