RESUMEN
In the original publication [...].
RESUMEN
A promising approach to targeted drug delivery is the remote control of magnetically sensitive objects using an external magnetic field source. This method can assist in the accumulation of magnetic carriers in the affected area for local drug delivery, thus providing magnetic nanoparticles for MRI contrast and magnetic hyperthermia, as well as the magnetic separation of objects of interest from the bloodstream and liquid biopsy samples. The possibility of magnetic objects' capture in the flow is determined by the ratio of the magnetic field strength and the force of viscous resistance. Thus, the capturing ability is limited by the objects' magnetic properties, size, and flow rate. Despite the importance of a thorough investigation of this process to prove the concept of magnetically controlled drug delivery, it has not been sufficiently investigated. Here, we studied the efficiency of polyelectrolyte capsules' capture by the external magnetic field source depending on their size, the magnetic nanoparticle payload, and the suspension's flow rate. Additionally, we estimated the possibility of magnetically trapping cells containing magnetic capsules in flow and evaluated cells' membrane integrity after that. These results are required to prove the possibility of the magnetically controlled delivery of the encapsulated medicine to the affected area with its subsequent retention, as well as the capability to capture magnetically labeled cells in flow.
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Sistemas de Liberación de Medicamentos , Magnetismo , Cápsulas/química , Campos Magnéticos , PolielectrolitosRESUMEN
When the yeast Saccharomyces cerevisiae shifts from rapid growth on glucose to slow growth on ethanol, it undergoes profound changes in cellular metabolism, including the destruction of most of the translational machinery. We have examined the effect of this metabolic change, termed the diauxic shift, on the frequency of translational errors. Recoding sites are mRNA sequences that increase the frequency of translational errors, providing a convenient reporter of translational accuracy. We found that the diauxic shift causes no overall change in translational accuracy but does cause a strong reduction in the frequency of one type of programmed error: Ty +1 frameshifting. Genetic data suggest that this effect may be due to changes in the relative amounts of tRNA participating in translation elongation. We discuss possible implications for expression strategies that use recoding.
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Sistema de Lectura Ribosómico/fisiología , Biosíntesis de Proteínas , Saccharomyces cerevisiae/genética , Codón/fisiología , Etanol/metabolismo , Glucosa/metabolismo , Aminoacil-ARN de Transferencia/fisiología , Retroelementos/fisiología , Saccharomyces cerevisiae/crecimiento & desarrollo , Saccharomyces cerevisiae/fisiologíaRESUMEN
Using mutants (tgt, mnmA(asuE, trmU), mnmE(trmE), miaA, miaB, miaE, truA(hisT), truB) of either Escherichia coli or Salmonella enterica serovar Typhimurium and the trm5 mutant of Saccharomyces cerevisiae, we have analyzed the influence by the modified nucleosides Q34, mnm(5)s(2)U34, ms(2)io(6)A37, Psi39, Psi55, m(1)G37, and yW37 on -1 frameshifts errors at various heptameric sequences, at which at least one codon is decoded by tRNAs having these modified nucleosides. The frequency of -1 frameshifting was the same in congenic strains only differing in the allelic state of the various tRNA modification genes. In fact, in one case (deficiency of mnm(5)s(2)U34), we observed a reduced ability of the undermodified tRNA to make a -1 frameshift error. These results are in sharp contrast to earlier observations that tRNA modification prevents +1 frameshifting suggesting that the mechanisms by which -1 and +1 frameshift errors occur are different. Possible mechanisms explaining these results are discussed.