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Kasper Morton posted an update 6 years, 9 months ago
Furthermore, we were unable to detect any suppression of LegC7 toxicity in deletions, which may rule out a function of the intact ESCRT-0 complex in this reversal. It is also possible that Vps27p recruits either a secondary protein required for LegC7 function in vivo, or Vps27p plays an as yet undescribed role in an endosomal maturation pathway that LegC7 can exploit. There is a hypothesized link between the ESCRT pathway, which removes membrane surface area of theMVB, and the endocytic fusion pathway, which increases the surface area of theMVB. Perhaps Vps27p, with the earliest function in the yeast ESCRT pathway, serves a role in promoting endosomal fusion or maturation to ensure sufficient surface area of the MVB for proper downstream ESCRT function. It is clear, however, that no other class E protein activity is required for LegC7 toxicity or localization, and we therefore do not believe that LegC7 is directly modulating overall ESCRT function. The modulation of host endosomal traffic would likely be an important goal for Legionella, in both its attempt to evade the normal host endomembrane system, and in the construction of the LCV during infection. It should be noted that Legionella strains lacking LegC7 are not defective in macrophage proliferation studies, and therefore LegC7-specific activities during Legionella infection remain unclear. Identification of the yeast target protein of LegC7 will likely provide essential insight into the role of this effector protein during the intracellular lifecycle of Legionella. Patients with RA sustain an increased risk of CVD. Reduced kidney function development is enhanced in patients with RA compared to non-RA persons and increases the risk of cardiovascular events in RA. The potential impact of impaired kidney function on atherogenic mechanisms including endothelial activation and atherosclerosis in RA requires elucidation. Both traditional and nontraditional cardiovascular risk factors are associated with prevalent and incident CVD in RA. Accordingly, currently reported recommendations on CVD risk MK-1775 955365-80-7 stratification in RA include the use of multiple traditional risk factor assessment equations such as the Framingham score and the Systematic COronary Risk Evaluation score in combination with consideration of RA characteristics. Nevertheless, up to 85% of white RA patients considered to be at moderate CVD risk according to the latter approach were reported to have carotid artery plaque, which represents a CHD equivalent. Importantly in the present context, we recently found that both traditional cardiovascular risk factors and RA characteristics were related to atherosclerosis in white but consistently not in black Africans with RA, this despite a similar atherosclerosis burden amongst the 2 groups. Taken together, these findings call for additional easily available and reliable CVD risk markers in white and even more so in black patients with RA. Creatinine concentrations are unreliable and creatinine clearance is no longer recommended to estimate kidney function as timed urine collections are cumbersome and prone to error. The iothalamate, EDTA, diethylene triamine pentaacetic acid or iohexol clearance most accurately estimate glomerular filtration rate. However, performing these investigations is expensive and complex and not recommended in routine clinical practice. The initially reported Jelliffe estimated glomerular filtration equation in 1973 was a landmark in the assessment of kidney function. Subsequently, a large series of other equations calculated from serum creatinine concentrations as well as age and sex with or without the inclusion of anthropometric measures or race were reported. Amongst these, the Chronic Kidney Disease Epidemiology Collaboration is most recent and was most extensively validated. Both The Modification of Diet in Renal disease and Chronic Kidney Disease Epidemiology Collaboration equations were also validated in non-RA black Africans. To date, only the Cockcroft-Gault actual body weight equation has been validated in a small cohort of white RA patients. The MDRD was reported to be less accurate than the C-G actual body weight as a measure of creatinine clearance in RA. A further complicating factor in patients with RA is that they experience excess body fat for a given body mass index and reduced muscle mass, which can result in an overestimation of kidney function. In this regard, the Salazar-Corcoran equation and the substitution of actual body weight by various other weight measures in the C-G equation can improve kidney function evaluation in persons with an altered adiposity status. In view of these considerations, we evaluated the independent relations of 9 different eGFR equation values with endothelial activation and atherosclerosis in black and white Africans with RA. We further aimed at determining the accuracy of eGFR equation results in identifying patients with carotid plaque or high risk atherosclerosis.