The fermentative model yeast Saccharomyces cerevisiae has been extensively used to study the genetic basis of stress response and homeostasis. In this study, we performed quantitative trait loci (QTL) analysis of the high-temperature fermentation trait of the progeny from the mating of the S. cerevisiae natural isolate BCC39850 (haploid#17) and the laboratory strain CEN.
View Article and Find Full Text PDFA new superior bacteria complementation model was achieved for testing antifolate compounds and investigating antifolate resistance in the dihydrofolate reductase (DHFR) enzyme of the malaria parasite. Earlier models depended on the addition of trimethoprim (TMP) to chemically suppress the host Escherichia coli (Ec) DHFR function. However, incomplete suppression of EcDHFR and potential interference of antibiotics needed to maintain plasmids for complementary gene expression can complicate the interpretations.
View Article and Find Full Text PDFThe sustainable production of natural compounds is increasingly important in today's industrial landscape. This study investigates the metabolic engineering of for the efficient biosynthesis of valuable carotenoids: canthaxanthin, zeaxanthin, and astaxanthin. Utilizing a tailored parental yeast strain, Sp_Bc, we optimized the carotenoid pathway by screening and identifying CrtW and CrtZ enzymatic variants.
View Article and Find Full Text PDFPara-amino salicylic acid (PAS) was first reported by Lehmann in 1946 and used for tuberculosis treatment. However, due to its adverse effects, it is now used only as a second line anti-tuberculosis drug for treatment of multidrug resistant or extensively drug resistant M. tuberculosis.
View Article and Find Full Text PDFThe impact of either Zn or Ce substituted with Ca in bioactive glasses based on the 45SiO - 6PO - 11SrO - (38-(x + y) CaO) - xZnO or yCeO (xZn-yCeBGs) system on bone regeneration has not yet been reported. The aim of this study was to develop new formulations of sol-gel-derived bioactive glass to use as a synthetic bone graft. xZn-yCeBGs were synthesized through the sol-gel process with 0.
View Article and Find Full Text PDFIn the fight towards eradication of malaria, identifying compounds active against new drug targets constitutes a key approach. 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK) has been advanced as a promising target, as being part of the parasite essential folate biosynthesis pathway while having no orthologue in the human genome. However, no drug discovery efforts have been reported on this enzyme.
View Article and Find Full Text PDFAntimicrob Agents Chemother
February 2022
Antifolates targeting dihydrofolate reductase (DHFR) are antimalarial compounds that have long been used for malaria treatment and chemoprevention (inhibition of infection from mosquitoes to humans). Despite their extensive applications, a thorough understanding of antifolate activity against hepatic malaria parasites, especially resistant parasites, has yet to be achieved. Using a transgenic Plasmodium berghei harboring quadruple mutant from Plasmodium falciparum (::-4M), we demonstrated that quadruple mutations on confer complete chemoprevention resistance to pyrimethamine, the previous generation of antifolate, but not to a new class of antifolate designed to overcome the resistance, such as P218.
View Article and Find Full Text PDFEukaryotic messenger RNA is translated via a 5' cap-dependent initiation mechanism. Experimental evidence for proteins involved with translation initiation among eukaryotic parasites is lacking, including Plasmodium falciparum, the human malaria parasite. Native P.
View Article and Find Full Text PDFDihydrofolate reductase-thymidylate synthase of Plasmodium falciparum (PfDHFR-TS) is an important target of antifolate antimalarial drugs. However, drug resistant parasites are widespread in malaria endemic regions. The unique bifunctional property of PfDHFR-TS could be exploited for the design of allosteric inhibitors that interfere with the active dimer conformation.
View Article and Find Full Text PDFBiological robustness allows mutations to accumulate while maintaining functional phenotypes. Despite its crucial role in evolutionary processes, the mechanistic details of how robustness originates remain elusive. Using an evolutionary trajectory analysis approach, we demonstrate how robustness evolved in malaria parasites under selective pressure from an antimalarial drug inhibiting the folate synthesis pathway.
View Article and Find Full Text PDFRecently, we have demonstrated that DNA hybridization using acoustic streaming induced by two piezoelectric transducers provides higher DNA hybridization efficiency than the conventional method. In this work, we refine acoustic streaming system for DNA hybridization by inserting an additional piezoelectric transducer and redesigning the locations of the transducers. The Comsol® Multiphysics was used to design and simulate the velocity field generated by the piezoelectric agitation.
View Article and Find Full Text PDFIn conventional DNA microarray hybridization, delivery of target cDNAs to surface-bounded probes depends solely on diffusion, which is notoriously slow, and thus typically requires 6-20 h to complete. In this study, piezoelectric microagitation through a liquid coupling medium is employed to enhance DNA hybridization efficiency and the results are compared with the standard static hybridization method. DNA hybridization was performed in a sealed aluminium chamber containing DNA microarray glass chip, coupling medium and piezoelectric transducers.
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