RESUMO
Many laboratory strains of Escherichia coli are resistant to methotrexate (MTX), a folate analogue that binds dihydrofolate reductase (DHFR). Mutations that inactivate either tolC or acrA confer MTX sensitivity. Further, overexpression of a fusion protein with DHFR activity reverses this sensitivity by titrating out intracellular MTX. These results suggest that MTX accumulates in cells where mutations in acrA or tolC have inactivated the TolC-dependent AcrAB multidrug resistance efflux pump.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Proteínas de Bactérias/metabolismo , Inibidores Enzimáticos/farmacologia , Proteínas de Escherichia coli , Escherichia coli/efeitos dos fármacos , Lipoproteínas/metabolismo , Metotrexato/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/genética , Transporte Biológico , Resistência Microbiana a Medicamentos/fisiologia , Escherichia coli/enzimologia , Escherichia coli/metabolismo , Antagonistas do Ácido Fólico/farmacologia , Lipoproteínas/genética , Proteínas de Membrana Transportadoras , Mutação , Tetra-Hidrofolato Desidrogenase/metabolismoRESUMO
In the period of the late-1980s, before the construction of multi-GeV third-generation storage rings with their intense insertion-device sources, the perceived number one problem for X-ray instrumentation was proper cooling of the first optical element in the beamline. This article, first given as an acceptance speech for the Compton Award ceremony at the Advanced Photon Source, presents a somewhat historical and anecdotal overview of how cryogenically cooled monochromator optics have been developed to provide a monochromator cooling solution adequate for today's power levels. A series of workshops and international collaborations were the key components for the progress and final success of this development.
RESUMO
The EXAFS technique is a powerful new structural tool, particularly useful for studies of disordered or otherwise complex materials for which x-ray diffraction techniques are difficult or unfeasible. At the present time, most EXAFS experiments are carried out at a synchrotron facility because of the larger fluxes available. We have developed an in-laboratory apparatus utilizing a focusing crystal technique which increases available fluxes two to three orders of magnitude over previous laboratory facilities, so that EXAFS measurements can be carried out quickly and accurately in the laboratory. We will discuss the principles of the focusing monochromator and we will also illustrate the experimental method with examples, including studies of chemical solutions, defect crystalline solids, and high-temperature superconductors.
