Defective nucleotide modifications of mitochondrial tRNAs have been associated with several human diseases, but their pathophysiology remains poorly understood. In this report, we investigated the pathogenic molecular mechanism underlying a hypertension-associated 4435A→G mutation in mitochondrial tRNA The m.4435A→G mutation affected a highly conserved adenosine at position 37, 3' adjacent to the tRNA's anticodon, which is important for the fidelity of codon recognition and stabilization. We hypothesized that the m.4435A→G mutation introduced an mG37 modification of tRNA, altering its structure and function. Primer extension and methylation activity assays indeed confirmed that the m.4435A→G mutation created a tRNA methyltransferase 5 (TRMT5)-catalyzed mG37 modification of tRNA We found that this mutation altered the tRNA structure, indicated by an increased melting temperature and electrophoretic mobility of the mutated tRNA compared with the wildtype molecule. We demonstrated that cybrid cell lines carrying the m.4435A→G mutation exhibited significantly decreased efficiency in aminoacylation and steady-state levels of tRNA, as compared with those of control cybrids. The aberrant tRNA metabolism resulted in variable decreases in mitochondrial DNA (mtDNA)-encoded polypeptides in the mutant cybrids. Furthermore, we found that the m.4435A→G mutation caused respiratory deficiency, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in mutant cybrids. These results demonstrated that an aberrant mG37 modification of mitochondrial tRNA affected the structure and function of its tRNA and consequently altered mitochondrial function. Our findings provide critical insights into the pathophysiology of maternally inherited hypertension, which is manifested by the deficient tRNA nucleotide modification.

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Aluminum-based water treatment residue (Al-WTR) generated during the drinking water treatment process is a readily available recycled material with high phosphorus (P) adsorption capacity. The P adsorption capacity of Al-WTR generated from Singapore's water treatment plant was evaluated with reference to particle size range, adsorption pH and temperature. Column tests, with WTR amendments in sand with and without compost, were used to simulate the bioretention systems. The adsorption rate decreased with increasing WTR sizes. Highest P adsorption capacity, 15.57 mg PO4 3− -P/g WTR, was achieved using fine WTR particles (>50% particles at less than 0.30 mm). At pH 4, the contact time required to reduce effluent P concentration to below the detectable range was half compared with pH 7 and 9. The adsorption rate observed at 40 ± 2 °C was 21% higher compared with that at 30 ± 2 °C. Soil mixes amended with 10% WTR and compost were able to maintain consistently high (90%) total phosphorus (TP) removal efficiency at a TP load up to 6.45 g/m 3 . In contrast, TP removal efficiencies associated with columns without WTR amendment decreased to less than 45% as the TP load increased beyond 4.5 g/m 3. The results showed that WTR application is beneficial for enhanced TP removal in bioretention systems.