Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI+]

Prions are proteins that can access multiple conformations, at least one of which is beta-sheet rich, infectious and self-perpetuating in nature. These infectious proteins show several remarkable biological activities, including the ability to form multiple infectious prion conformations, also known as strains or variants, encoding unique biological phenotypes, and to establish and overcome prion species (transmission) barriers. In this Perspective, we highlight recent studies of the yeast prion [PSI+], using various biochemical and structural methods, that have begun to illuminate the molecular mechanisms by which self-perpetuating prions encipher such biological activities. We also discuss several aspects of prion conformational change and structure that remain either unknown or controversial, and we propose approaches to accelerate the understanding of these enigmatic, infectious conformers

Outcome of Patients With Small Vessel Vasculitis After Renal Transplantation: National Database Analysis

Background. Small vessel vasculitis commonly affects the kidney and can progress to end-stage renal disease. The goal of this study is to compare outcomes of patients who received a renal transplant as a result of small vessel vasculitis (group A) with those who received kidney transplants because of other causes (group B). Methods. This is a retrospective analysis of United Network for Organ Sharing registry data for adult primary kidney transplants from January 2000 to December 2014. Group A patients (N = 2196) were compared with a group B (N = 6588); groups were case matched for age, race, sex, donor type, and year of transplant in a 1:3 ratio. Results. Renal and patient survivals were better in the group A (P < 0.001). New-onset diabetes after transplant developed in 8.3% of the group A and 11.3% of group B (P < 0.001). Seventeen (0.8%) patients in group A developed recurrent disease. Of these, 7 patients had graft failure, 3 of which were due to disease recurrence. Group A patients had significantly higher risk of developing posttransplant solid organ malignancies (11.3% vs 9.3%, P = 0.006) and lymphoproliferative disorder (1.3% vs 0.8%, P = 0.026). Independent predictors of graft failure and patient mortality were recipients' morbid obesity, diabetes, age, and dialysis duration (hazard ratio of 1.7, 1.4, 1.1/10 years, and 1.1/year for graft failure, and 1.7, 1.7, 1.6/10 years and 1.1/year for patient mortality, respectively). Conclusions. Renal transplantation in patients with small vessel vasculitis has favorable long-term graft and patient outcomes with a low disease recurrence rate. However, they may have a higher risk of developing posttransplant malignancies