Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture

Full-length mRNAs transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (the 'transferome') is unknown. Here, we analyzed the transferome in an human-mouse cell co-culture model using RNA-sequencing. We found that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells. Typically, <1% of endogenous mRNAs undergo transfer. Non-selective, expression-dependent RNA transfer was further validated using synthetic reporters. RNA transfer appears contact-dependent via TNTs, as exemplified for several mRNAs. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions

Template-Directed Synthesis of Multiply Mechanically Interlocked Molecules Under Thermodynamic Control

The template-directed construction of crown-ether-like macrocycles around secondary dialkylammonium ions (R2NH2+) has been utilized for the expedient (one-pot) and highyielding synthesis of a diverse range of mechanically interlocked molecules. The clipping together of appropriately designed dialdehyde and diamine compounds around R2NH2+-containing dumbbell-shaped components proceeds through the formation, under thermodynamic control, of imine bonds. The reversible nature of this particular reaction confers the benefits of “errorchecking” and “proof-reading”, which one usually associates with supramolecular chemistry and strict self-assembly processes, upon these wholly molecular systems. Furthermore, these dynamic covalent syntheses exploit the efficient templating effects that the R2NH2+ ions exert on the macrocyclization of the matched dialdehyde and diamine fragments, resulting not only in rapid rates of reaction, but also affording near-quantitative conversion of starting materials into the desired interlocked products. Once assembled, these “dynamic” interlocked compounds can be “fixed” upon reduction of the reversible imine bonds (by using BH3·THF) to give kinetically stable species, a procedure that can be performed in the same reaction vessel as the inital thermodynamically controlled assembly. Isolation and purification of the mechanically interlocked products formed by using this protocol is relatively facile, as no column chromatography is required. Herein, we present the synthesis and characterization of 1) a [2]rotaxane, 2) a [3]rotaxane, 3) a branched [4]rotaxane, 4) a bis [2]rotaxane, and 5) a novel cyclic [4]rotaxane, demonstrating, in incrementally more complex systems, the efficacy of this one-pot strategy for the construction of interlocked molecules

Strategies in Translating Multi-Word Verbs Found in U.S President Barack Obama�s Speech at University of Indonesia

The objectives of this research entitled Strategies in Translating Multi- Word Verbs Found in U.S President Barack Obama�s Speech at University of Indonesia are to find out the types of multi-word verbs in Obama�s speech and strategies that are used by translators to translate the multi-word verbs found in the speech as idiomatic expression. The strategies are suggested by Baker (1992). The data of this study are first collected by finding the types of multi-word verbs in Obama�s speech as idiomatic expressions. From the analysis that has been done, types of multi word verbs are found such as 16 data and (42.10%) in percentage ofphrasal verbs, 21 data or(55.27%) in percentage ofprepositional verbs and 1 dataor (2.63%) in percentageof phrasal prepositional verbs. From all the types of multi-word verbs that were found 38 are idiomatic expressions. The highest number is strategy of similar meaning but dissimilar form with 23 data or (60.52%) in percentage. The second strategy is similar in meaning and form with 13 data or (34.21%) in percentage. The third is translation by paraphrase with 1 data or (2.63%) in percentage and the last is translation by omission with 1 data or (2.63%) in percentage