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Biology subjects

Goodey, N. M.

Publications and source records attributed to Goodey, N. M..

2 recordsLinked to original sources

Modeling the Impact of Contamination on Microbial-Enzyme Dynamics and Soil Function

Globally, contaminated soils pose serious risks to agriculture, biodiversity of ecosystems, and human health. Although a variety of monitoring and remediation methods have been developed over the years, there remains a lack of theoretical modelling to better understand the impact of contamination on soil carbon in a microbially-mediated system. In this study, we develop a model which incorporates contaminated soil organic carbon, uncontaminated soil organic carbon, dissolved organic carbon, microbes, extracellular enzymes, and CO2, to explore how different amounts of contamination and modes of contamination (pulse and press) affect microbially-mediated carbon flux within both vegetated and barren environments. The model represents contamination as a pool of contaminated soil organic carbon that is more resistant to microbial degradation than uncontaminated soil organic carbon. The results show that, in barren environments, the amount and type of contamination has no notable impact on the soil system. In contrast to this, in vegetated environments, plants mitigate the impact of large contamination inputs with differences in outcome depending on the amount and type of contamination.

ecology↗

Characterization of novel competitive inhibitors of P. falciparum cGMP-dependent protein kinase

P. falciparum cGMP-dependent protein kinase (PfPKG) is an enticing anti-malarial drug target. Structurally novel isoxazole-based compounds were shown to be ATP competitive inhibitors of PfPKG. Isoxazoles 3 and 5 had Ki values of 0.7 {+/-} 0.2 and 2.3 {+/-} 0.9 nM, respectively, that are comparable to a known standard, 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H pyrrol-3-yl] pyridine (1.4 {+/-} 0.5 nM). They also exhibited excellent selectivity for PfPKG over the human ortholog and the gatekeeper mutant T618Q PfPKG, which mimics the less accessible binding site of the human ortholog. The human orthologs larger binding site volume was predicted to explain the selectivity of the inhibitors for the P. falciparum enzyme. Analogs 4 and 6 were at least 20-fold less potent compared to 3 and 5, suggesting that removing the carbonyl group in 3 or altering the diethylamino moiety in 5 reduced affinity.

biochemistry↗