Data availability For the yeast Ribo-Seq data underlying Fig. 1, all accession numbers for publicly available datasets were listed in Supplementary Table 1. For the human Ribo-Seq data underlying Fig. 2, the original dataset is available from NCBI SRA under accession number SRR3623932 and SRR3623937. The raw data underlying Fig. 3 is shown in Supplementary Figure 6 and Supplementary Table 3. The species identified as virus or its natural/symptomatic hosts were listed in Supplementary Table 5, with their genomic sequences obtained from NCBI GenBank.
Zoledronic acid (ZA) has been shown to inhibit prostate tumor growth in vitro and have beneficial effects in patients with advanced prostate cancer (CaP). The aim of this study was to determine whether ZA exhibits direct anti-tumor effects on CaP cells in vivo. To distinguish the effects of inhibition of osteolysis and direct antitumor activity of ZA in vivo, we compared the results of treatment with ZA and osteoprotegerin (Fc-OPG), which inhibits osteolysis, but without significant direct anti-tumor effects. In vitro Fc-OPG had no significant effects on C4-2 proliferation, whereas ZA decreased proliferation. However, both agents decreased tumor growth in bone. Moreover, both increased bone volume and prevented the overall decreases in BMD associated with growth of C4-2 cells in bone. Our study provides novel and significant observations that the in vivo effects of ZA are consistent with indirect effects mediated by osteoclasts.
Fluorescence in situ hybridization (FISH) has become an increasingly important method for assessing chromosome rearrangement. The reciprocal translocation constituting the Philadelphia (Ph) chromosome [t(9;22)(q34;q11)] characterizes more than 90% of patients with chronic myelogenous leukemia (CML). However, in the remaining cases the Ph chromosome (genetically characterized by the fusion of the BCR-ABL genes) is thought to arise through complex translocations that are often not readily apparent using routine chromosome-banding analysis. For this reason we have developed unique band-specific probes for two- color FISH that detect unequivocally the Ph chromosome, and its derivatives. Results of the application of these probes are illustrated by analysis of 11 cases of CML (9 of which contain “variant” translocations). The probes were generated by chromosome microdissection and in vitro amplification of the bands involved in the Ph translocation, leading to an extremely fast and sensitive approach to identify this alteration in leukemic cell populations.
The budding yeast Saccharomyces cerevisiae is the best studied eukaryote in molecular and cell biology, but its utility for understanding the genetic basis of natural phenotypic variation is limited by the inefficiency of association mapping owing to strong and complex population structure. To facilitate association mapping, we analyzed 190 high-quality genomes of diverse strains, including 85 newly sequenced ones, to uncover yeast's population structure that varies substantially among genomic regions. We identified 181 yeast genes that are absent from the reference genome and demonstrated their expression and role in important functions such as drug resistance. We then simultaneously measured the growth rates of over 4500 lab strains each deficient of a nonessential gene and 81 natural strains across multiple environments using unique DNA barcode present in each strain. We combined the genome-wide reverse genetic information with genome-wide association analysis to determine potential genomic regions of importance to environmental adaptations, and for a subset experimentally validated their role by reciprocal hemizygosity tests. The resources provided permit efficient and reliable association mapping in yeast and significantly enhances its value as a model for understanding the genetic mechanisms of phenotypic polymorphism and evolution.
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