Endoplasmic reticulum-associated degradation and protein quality control

Approximately one-third of all polypeptides synthesized in eukaryotes are targeted to the endoplasmic reticulum (ER), and once associated with this compartment they are chemically modified. The folding status of the resulting nascent proteins is then surveyed by molecular chaperones and lectins. To clear the ER of dead-end products, proteins that fail quality control are routed to the cytosol and degraded via ER-associated degradation (ERAD). Although many ERAD-requiring factors have been identified and a basic understanding of this pathway has been achieved, numerous questions remain on the mechanisms that lead to the selection and delivery of ERAD substrates

Variabilidad en las medidas de tensión arterial realizada por estudiantes de 5.º y 6.º de medicina Variability of arterial pressure measurements performed by advanced medical students

Introducción. No se ha definido objetivamente si los estudiantes de medicina avanzados dominan destrezas básicas, como la medida de tensión arterial. Sujetos y métodos. Se determinó la variabilidad de medida de tensión arterial por estudiantes de 5.º y 6.º cursos de medicina. Resultados. Se encontraron coeficientes de variación significativamente más elevados en la tensión arterial diastólica derecha y frecuencia cardíaca, y grupos e individuos con error sistemático de medición. Conclusión. Resulta necesario un refuerzo docente en la medida de tensión arterial diastólica y su realización en los dos brazos.Introduction. No objective data are available to know whether advanced medical students are in command of basic practical skills, ie, arterial pressure measurement. Subjects and methods. Variability of arterial pressure measurements was examined in 5th- and 6th-year medical students. Results. Significantly higher variability coefficients were found in right arm diastolic arterial pressure and heart rate. A systematic measurement error was detected in some groups and individuals. Conclusion. A teaching effort will be necessary to improve arterial pressure measurement skills, with special emphasis in diastolic arterial pressure and bilateral measurements

Variabilidad en las medidas de tensión arterial realizada por estudiantes de 5.º y 6.º de medicina

Introducción. No se ha definido objetivamente si los estudiantes de medicina avanzados dominan destrezas básicas, como la medida de tensión arterial. Sujetos y métodos. Se determinó la variabilidad de medida de tensión arterial por estudiantes de 5.º y 6.º cursos de medicina. Resultados. Se encontraron coeficientes de variación significativamente más elevados en la tensión arterial diastólica derecha y frecuencia cardíaca, y grupos e individuos con error sistemático de medición. Conclusión. Resulta necesario un refuerzo docente en la medida de tensión arterial diastólica y su realización en los dos brazos

Identification and characterization of a high-affinity choline uptake system of Brucella abortus

Phosphatidylcholine (PC), a common phospholipid of the eukaryotic cell membrane, is present in the cell envelope of the intracellular pathogen Brucella abortus, the etiological agent of bovine brucellosis. In this pathogen, the biosynthesis of PC proceeds mainly through the phosphatidylcholine synthase pathway; hence, it relies on the presence of choline in the milieu. These observations imply that B. abortus encodes an as-yet-unknown choline uptake system. Taking advantage of the requirement of choline uptake for PC synthesis, we devised a method that allowed us to identify a homologue of ChoX, the high-affinity periplasmic binding protein of the ABC transporter ChoXWV. Disruption of the choX gene completely abrogated PC synthesis at low choline concentrations in the medium, thus indicating that it is a high-affinity transporter needed for PC synthesis via the PC synthase (PCS) pathway. However, the synthesis of PC was restored when the mutant was incubated in media with higher choline concentrations, suggesting the presence of an alternative low-affinity choline uptake activity. By means of a fluorescence-based equilibrium- binding assay and using the kinetics of radiolabeled choline uptake, we show that ChoX binds choline with an extremely high affinity, and we also demonstrate that its activity is inhibited by increasing choline concentrations. Cell infection assays indicate that ChoX activity is required during the first phase of B. abortus intracellular traffic, suggesting that choline concentrations in the early and intermediate Brucella-containing vacuoles are limited. Altogether, these results suggest that choline transport and PC synthesis are strictly regulated in B. abortus. © 2013, American Society for Microbiology