is the second most common cause of invasive candidiasis and is widely known to have reduced susceptibility to fluconazole relative to many other spp. Upc2A is a transcription factor that regulates ergosterol biosynthesis gene expression under conditions of sterol stress such as azole drug treatment or hypoxia. Through an microevolution experiment, we found that loss-of-function mutants of the ATF/CREB transcription factor suppresses the fluconazole hyper-susceptibility of the ∆ mutant.
View Article and Find Full Text PDFThe privileged fused-ring system comprising the bicyclo[2.2.2]diazaoctane (BDO) core is prevalent in diketopiperazine (DKP) natural products with potent and diverse biological activities, with some being explored as drug candidates.
View Article and Find Full Text PDFCytochromes P450 (CYP) form one of the largest enzyme superfamilies on Earth, with similar structural fold but biological functions varying from synthesis of physiologically essential compounds to metabolism of myriad xenobiotics. Here we determined the crystal structures of Coryphaenoides armatus and human sterol 14α-demethylases (CYP51s). Both structures reveal elements that imply elevated conformational flexibility, uncovering molecular basis for faster catalytic rates, lower substrate selectivity, and resistance to inhibition.
View Article and Find Full Text PDFThere is an increasing demand to boost photosynthesis in rice to increase yield potential. Chloroplasts are the site of photosynthesis, and increasing their number and size is a potential route to elevate photosynthetic activity. Notably, bundle sheath cells do not make a significant contribution to overall carbon fixation in rice, and thus, various attempts are being made to increase chloroplast content specifically in this cell type.
View Article and Find Full Text PDFIntroduction: Effective utilisation of the unregistered support workforce is essential to counter a well-documented imaging workforce crisis, yet it is unclear how imaging departments deploy their support staff. As part of a wider explanatory mixed methods study, this research explored models of support workforce deployment across England, identifying the factors which may encourage or inhibit implementation of these models.
Methods: Imaging support workforce deployment at regional and place (NHS Trust) level was investigated using Framework Analysis to combine interviews with Imaging Network representatives and Radiology Service Managers (RSMs) alongside workforce establishment data.