Kidney Transplant Outcomes in Indigenous People of the Northern Great Plains of the United States.

BACKGROUND: Indigenous people experience higher rates of end-stage renal disease as well as negative predictive factors that undermine kidney transplantation (KT) success. Despite these inequalities, data suggest that short-term outcomes are comparable to those of other groups, but few studies have examined this effect in the Northern Great Plains (NGP) region. METHODS: We performed a retrospective database review to determine outcomes of KT in Indigenous people of the NGP. White and Indigenous people receiving a KT between 2000 and 2018 at a single center were examined. RESULTS: A total of 622 KT recipients were included (117 Indigenous and 505 White). Indigenous patients were more likely to smoke, have diabetes, have higher immunologic risk, receive fewer living donor kidneys, and have longer waitlist times. In the 5 years after KT there were no significant differences in renal function, rejection events, cancer, graft failure, or patient survival. At 10 years posttransplant, Indigenous patients had twice the all-cause graft failure (odds ratio = 2.06; 95% confidence interval, 1.25-3.39) and half the survival rate (odds ratio = 0.47; 95% confidence interval, 0.29-0.76); however, this effect was not maintained once the effects of race, sex, smoking status, diabetes, preemptive transplant, high panel reactive antibody status, and transplant type were adjusted for. CONCLUSIONS: KT outcomes in Indigenous patients in the NGP region are similar to those of White patients 5 years posttransplant, with differences emerging at 10 years that could be diminished with greater emphasis on correcting modifiable risk factors.

A phosphoramidate substrate analog is a competitive inhibitor of the Tetrahymena group I ribozyme.

BACKGROUND: Phosphoramidate oligonucleotide analogs containing N3'-P5' linkages share many structural properties with natural nucleic acids and can be recognized by some RNA-binding proteins. Therefore, if the N-P bond is resistant to nucleolytic cleavage, these analogs may be effective substrate analog inhibitors of certain enzymes that hydrolyze RNA. We have explored the ability of the Tetrahymena group I intron ribozyme to bind and cleave DNA and RNA phosphoramidate analogs. RESULTS: The Tetrahymena group I ribozyme efficiently binds to phosphoramidate oligonucleotides but is unable to cleave the N3'-P5' bond. Although it adopts an A-form helical structure, the deoxyribo-phosphoramidate analog, like DNA, does not dock efficiently into the ribozyme catalytic core. In contrast, the ribo-phosphoramidate analog docks similarly to the native RNA substrate, and behaves as a competitive inhibitor of the group I intron 5' splicing reaction. CONCLUSIONS: Ribo-N3'-P5' phosphoramidate oligonucleotides are useful tools for structural and functional studies of ribozymes as well as protein-RNA interactions.

A magnesium ion core at the heart of a ribozyme domain.

Large ribozymes require divalent metal ions to fold. We show here that the tertiary structure of the Tetrahymena group I intron P4-P6 domain nucleates around a magnesium ion core. In the domain crystal structure, five magnesium ions bind in a three-helix junction at the centre of the molecule. Single atom changes in any one of four magnesium sites in this three-helix junction destroy folding of the entire 160-nucleotide P4-P6 domain. The magnesium ion core may be the RNA counterpart to the protein hydrophobic core, burying parts of the RNA molecule in the native structure.