Transmitting the energy: interdomain cross-talk in Pdr5

ABC (ATP-binding cassette) transporters are ubiquitous integral membrane proteins catalyzing the active export or import of structurally and functionally unrelated compounds. In humans, these proteins are clinically and economically important, as their dysfunction is responsible for a number of diseases. In the case of multidrug resistance (MDR) ABC exporters, they particularly confer resistance to a broad spectrum of toxic compounds, placing them in the focus of clinical research. However, ABC-mediated drug resistance is not only restricted to humans. In yeast for example, MDR is called pleiotropic drug resistance (PDR). Important and well-studied members of the PDR subfamily of ABC transporters are Pdr5 from Saccharomyces cerevisiae and its homolog Cdr1 from Candida albicans. Mutational studies of these two transporters provided many insights into the complexity and conceivable mechanism of the interdomain cross-talk that transmits the energy gained from ATP hydrolysis to the substrate translocation process across the membrane. In this review, we summarize and discuss our current knowledge of the interdomain cross-talk as well as new results obtained for asymmetric ABC transporters and derive possible structural and functional implications for Pdr5.

Cerebral Aneurysm Sac Growth as the Etiology of Recurrence After Successful Coil Embolization

Cerebral aneurysm recurrence is characterized by the recanalization of an aneurysm lumen after treatment with embolization coils, necessitating additional interventional measures. Recurrence rates of ≤ 34% have been reported (with major recurrence rates of ≤ 21% cited).1 The etiology of cerebral aneurysm recurrence remains unclear; however, compaction of embolization coils within a treated aneurysm lumen has been referenced in the literature as the primary mechanism of recurrence.2–4 Nevertheless, it should be noted that the evidence presented has been observational in nature and thus qualitative.2–4 While coil compaction is a conceivable mechanism of cerebral aneurysm recanalization (allowing for increased luminal volume), it is hypothesized by the authors that growth of the sac itself is the primary recurrence mechanism. Previous studies concerning aneurysm sac growth have been limited to qualitative observations of 2D angiographic data.5–6 In these studies the ability to accurately measure aneurysm sac and coil mass size was vital; however, changes in scan magnification and patient orientation between initial and follow-up angiographic scans makes the reliable discernment of aneurysm sac and coil mass size over time difficult, and therefore limits the ability to rigorously assess the temporal evolution of both the coil mass and the aneurysm sac. The objective of this study was to utilize 3D image processing methods to quantify both aneurysm sac growth and coil mass volume in order to assess the association of each mechanism with recurrence. A study population of patients presenting with recurrent cerebral aneurysms post treatment with embolization coils at The University of Iowa Hospitals and Clinics (UIHC) were examined.

One conceivable mechanism of UV-light induced SO₂ Oxidation to H₂SO₄

The electron-excited chemistry of sulfur dioxide oxidation induced by UV irradiation of air with trace O3 and SO2 is considered. The importance of this mechanism is evaluated based on recent laboratory experiments on SO2 oxidation in a laminar tube with air induced by UV irradiation. Results show that under respective conditions the route of SO2 oxidation involving electron excited oxygen molecules may present an additional source of gaseous H2SO4 production to known OH-radical mechanism.

Cell-wall thickness: possible mechanism of acriflavine resistance in meticillin-resistant Staphylococcus aureus

Acriflavine resistance in the clinical meticillin-resistant Staphylococcus aureus isolate KT24 was found not to be mediated by multidrug efflux pumps encoded by qacA/B, smr, qacE, qacG, qacH, qacJ or norA. Early uptake and accumulation of ethidium bromide in MRSA KT24 was significantly lower than that in a susceptible strain, although the efflux rates were similar. Therefore, a permeability barrier in MRSA KT24 may be the conceivable mechanism of acriflavine resistance. Interestingly, it was found that MRSA KT24 had a significantly thickened cell wall, and that cell-wall thickness increased gradually during bacterial growth. In contrast, cell size and surface area in MRSA KT24 were not different from those in the susceptible strain. Moreover, MRSA KT24 exposure to sub-MIC concentrations of acriflavine resulted in a thicker cell wall. These results indicate that cell-wall thickness may be responsible for acriflavine resistance in S. aureus.

Interstrain Gene Transfer in Chlamydia trachomatis In Vitro: Mechanism and Significance

ABSTRACT The high frequency of between-strain genetic recombinants of Chlamydia trachomatis among isolates obtained from human sexually transmitted infections suggests that lateral gene transfer (LGT) is an important means by which C. trachomatis generates variants that have enhanced relative fitness. A mechanism for LGT in C. trachomatis has not been described, and investigation of this phenomenon by experimentation has been hampered by the obligate intracellular development of this pathogen. We describe here experiments that readily detected LGT between strains of C. trachomatis in vitro. Host cells were simultaneously infected with an ofloxacin-resistant (Ofxr) mutant of a serovar L1 strain (L1:Ofxr-1) and a rifampin-resistant (Rifr) mutant of a serovar D strain (D:Rifr-1). Development occurred in the absence of antibiotics, and the progeny were subjected to selection for Ofxr Rifr recombinants. The parental strains differed at many polymorphic nucleotide sites, and DNA sequencing was used to map genetic crossovers and to determine the parental sources of DNA segments in 14 recombinants. Depending on the assumed DNA donor, the estimated minimal length of the transferred DNA was ≥123 kb in one recombinant but was ≥336 to ≥790 kb in all other recombinants. Such trans-DNA lengths have been associated only with conjugation in known microbial LGT systems, but natural DNA transformation remains a conceivable mechanism. LGT studies can now be performed with diverse combinations of C. trachomatis strains, and they could have evolutionary interest and yield useful recombinants for functional analysis of allelic differences between strains.

EXCHANGE REACTIONS OF Co++, Co+++, AND THEIR HEXAMMINO COMPLEXES

In a study of the exchange of radioactive cobalt between Co++ and Co(NH3)6+++ it was found that no exchange within experimental error occurred within seven days at 25 °C., or two days at 50 °C. The various steps involved in a conceivable mechanism by which exchange might have been expected to occur were then investigated separately. From the results obtained it appears that dissociation of the complex is one limiting factor. The exchange between the two hexammino complexes of divalent and trivalent cobalt was found to be very slow at 25 °C.