Medical and long-term care for Alzheimer's disease and related dementias (ADRDs) can impose a large economic burden on individuals and societies. We estimated the per capita cost of ADRDs care in the in the United States in 2016 and projected future aggregate care costs during 2020-2060. Based on a previously published methodology, we used U.
View Article and Find Full Text PDFKRAS is one of the most commonly mutated proteins in cancer, and efforts to directly inhibit its function have been continuing for decades. The most successful of these has been the development of covalent allele-specific inhibitors that trap KRAS G12C in its inactive conformation and suppress tumour growth in patients. Whether inactive-state selective inhibition can be used to therapeutically target non-G12C KRAS mutants remains under investigation.
View Article and Find Full Text PDFActivating mutations in KRAS are the most frequent oncogenic alterations in cancer. The oncogenic hotspot position 12, located at the lip of the switch II pocket, offers a covalent attachment point for KRAS inhibitors. To date, KRAS inhibitors have been discovered by first covalently binding to the cysteine at position 12 and then optimizing pocket binding.
View Article and Find Full Text PDFFarnesyl diphosphate (FPP)-derived isoprenoids represent a diverse group of plant secondary metabolites with great economic potential. To enable their efficient production in the heterologous host , we refined a metabolic engineering strategy using the CRISPR/Cas9 system with the aim of increasing the availability of FPP for downstream reactions. The strategy included the overexpression of mevalonate pathway (MVA) genes, the redirection of metabolic flux towards desired product formation and the knockout of genes responsible for competitive reactions.
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