447 research outputs found
Phyla lanceolata (Michx.) Greene
https://thekeep.eiu.edu/herbarium_specimens_byname/19021/thumbnail.jp
Verbena canadensis Britton
https://thekeep.eiu.edu/herbarium_specimens_byname/19088/thumbnail.jp
Verbena canadensis Britton
https://thekeep.eiu.edu/herbarium_specimens_byname/19088/thumbnail.jp
Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers.
Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER(-) breast cancer, AR(-) prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated anticodon cleavage, which is promoted by sex hormones and their receptors. Resultant 5\u27- and 3\u27-SHOT-RNAs, corresponding to 5\u27- and 3\u27-tRNA halves, bear a cyclic phosphate (cP) and an amino acid at the 3\u27-end, respectively. By devising a cP-RNA-seq method that is able to exclusively amplify and sequence cP-containing RNAs, we identified the complete repertoire of 5\u27-SHOT-RNAs. Furthermore, 5\u27-SHOT-RNA, but not 3\u27-SHOT-RNA, has significant functional involvement in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis of hormone-dependent cancers and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets
Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an exosite-binding glycosylated substrate
ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection. As a result of this uHTS effort, a selective, time-dependent, non-zinc-binding inhibitor of ADAM10 with Ki = 883 nM was discovered. This compound exhibited low cell toxicity and was able to selectively inhibit shedding of known ADAM10 substrates in several cell-based models. We hypothesize that differential glycosylation of these cognate substrates is the source of selectivity of our novel inhibitor. The data indicate that this novel inhibitor can be used as an in vitro and, potentially, in vivo, probe of ADAM10 activity. Additionally, results of the present and prior studies strongly suggest that glycosylated substrate are applicable as screening agents for discovery of selective ADAM probes and therapeutics
Consequential considerations when mapping tRNA fragments
We examine several of the choices that went into the design of tDRmapper, a recently reported tool for identifying transfer RNA (tRNA) fragments in deep sequencing data, evaluate them in the context of currently available knowledge, and discuss their potential impact on the output that the tool generates
Massive subsurface ice formed by refreezing of ice-shelf melt ponds
Surface melt ponds form intermittently on several Antarctic ice shelves. Although implicated in ice-shelf break up, the consequences of such ponding for ice formation and ice-shelf structure have not been evaluated. Here we report the discovery of a massive subsurface ice layer, at least 16 km across, several kilometres long and tens of metres deep, located in an area of intense melting and intermittent ponding on Larsen C Ice Shelf, Antarctica. We combine borehole optical televiewer logging and radar measurements with remote sensing and firn modelling to investigate the layer, found to be ∼10 C warmer and ∼170 kg m¯³ denser than anticipated in the absence of ponding and hitherto used in models of ice-shelf fracture and flow. Surface ponding and ice layers such as the one we report are likely to form on a wider range of Antarctic ice shelves in response to climatic warming in forthcoming decades
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