As the elimination of LegC7 toxicity in our study is fairly specific, we suspect that significant structural changes are induced in LegC7N242I, but will not be fully appreciated until crystallographic data are obtained. Recently, the N-terminal portion of a related Legionella effector protein, LegC3, was crystallized, resulting in a structure that did not share close homology with any currently known structure. As this crystal structure did not match in silico predictions, the structure of LegC7 may provide a new role for the N242 residue in LegC7 function. Finally, we find that deletions of VPS27, and ESCRT-0 complex member, partially reversed the toxic effects of LEGC7 expression. This effect is not the result of mislocalization of LegC7, but could be explained by the reduction of LegC7 levels through enhanced proteolytic turnover or reduced LegC7 expression in vps27�� backgrounds; direct interactions between Vps27p and LegC7 in vitro were not detected. Furthermore, we were unable to detect any suppression of LegC7 toxicity in hse1�� deletions, which may rule out a Ibrutinib 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 Vismodegib 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.