Transient Ureteral Obstruction Prevents against Kidney Ischemia/Reperfusion Injury via Hypoxia-Inducible Factor (HIF)-2α Activation

Although the protective effect of transient ureteral obstruction (UO) prior to ischemia on subsequent renal ischemia/reperfusion (I/R) injury has been documented, the underlying molecular mechanism remains to be understood. We showed in the current study that 24 h of UO led to renal tubular hypoxia in the ipsilateral kidney in mice, with the accumulation of hypoxia-inducible factor (HIF)-2α, which lasted for a week after the release of UO. To address the functions of HIF-2α in UO-mediated protection of renal IRI, we utilized the Mx-Cre/loxP recombination system to knock out target genes. Inactivation of HIF-2α, but not HIF-1α blunted the renal protective effects of UO, as demonstrated by much higher serum creatinine level and severer histological damage. UO failed to prevent postischemic neutrophil infiltration and apoptosis induction in HIF-2α knockout mice, which also diminished the postobstructive up-regulation of the protective molecule, heat shock protein (HSP)-27. The renal protective effects of UO were associated with the improvement of the postischemic recovery of intra-renal microvascular blood flow, which was also dependent on the activation of HIF-2α. Our results demonstrated that UO protected the kidney via activation of HIF-2α, which reduced tubular damages via preservation of adequate renal microvascular perfusion after ischemia. Thus, preconditional HIF-2α activation might serve as a novel therapeutic strategy for the treatment of ischemic acute renal failure

Hybridization as a threat in climate relict Nuphar pumila (Nymphaeaceae)

Field studies and conceptual work on hybridization-mediated extinction risk in climate relicts are extremely rare. Nuphar pumila (Nymphaeaceae) is one of the most emblematic climate relicts in Europe with few isolated populations in the Alpine arc. The extent of introgression with related lowland and generalist species Nupharlutea has never been studied using molecular methods. All biogeographical regions where N.pumila naturally occurs in the neighbourhood of the Alpine arc were sampled and studied using nuclear microsatellite markers. Furthermore, we used forward-in-time simulations and Approximate Bayesian Computation to check whether an introgression scenario fits with the observed admixture patterns and estimated the demographic parameters associated with this process. Our study confirms ongoing hybridization between N.pumila and N.lutea and validates it by the use of population models. More than 40 % of investigated N.pumila individuals were admixed and hybrids were found in over 60 % of studied populations. The introgression is bidirectional and is most likely a result of very recent gene flow. Our work provides strong evidence for rapid extinction risk and demographic swamping between specialized climatic relicts and closely related generalists. The remaining pure populations of N.pumila are rare in the Alpine arc and deserve high conservation priority