10 research outputs found
Recommended from our members
Identification of and Structural Insights into Hit Compounds Targeting N‑Myristoyltransferase for Cryptosporidium Drug Development
Each year, approximately 50,000 children under 5 die as a result of diarrhea caused by Cryptosporidium parvum, a protozoan parasite. There are currently no effective drugs or vaccines available to cure or prevent Cryptosporidium infection, and there are limited tools for identifying and validating targets for drug or vaccine development. We previously reported a high throughput screening (HTS) of a large compound library against Plasmodium N-myristoyltransferase (NMT), a validated drug target in multiple protozoan parasite species. To identify molecules that could be effective against Cryptosporidium, we counter-screened hits from the Plasmodium NMT HTS against Cryptosporidium NMT. We identified two potential hit compounds and validated them against CpNMT to determine if NMT might be an attractive drug target also for Cryptosporidium. We tested the compounds against Cryptosporidium using both cell-based and NMT enzymatic assays. We then determined the crystal structure of CpNMT bound to Myristoyl-Coenzyme A (MyrCoA) and structures of ternary complexes with MyrCoA and the hit compounds to identify the ligand binding modes. The binding site architectures display different conformational states in the presence of the two inhibitors and provide a basis for rational design of selective inhibitors
Gold(III) Macrocycles: Nucleotide-Specific Unconventional Catalytic Inhibitors of Human Topoisomerase I
DNA Topoisomerase 1α Promotes Transcriptional Silencing of Transposable Elements through DNA Methylation and Histone Lysine 9 Dimethylation in Arabidopsis
Money matters: exploiting the data from outcomes research for quality improvement initiatives
In recent years, there has been an increase in studies that have sought to identify predictors of treatment outcome and to examine the efficacy of surgical and non-surgical treatments. In addition to the scientific advancement associated with these studies per se, the hospitals and clinics where the studies are conducted may gain indirect financial benefit from participating in such projects as a result of the prestige derived from corporate social responsibility, a reputational lever used to reward such institutions. It is known that there is a positive association between corporate social performance and corporate financial performance. However, in addition to this, the research findings and the research staff can constitute resources from which the provider can reap a more direct benefit, by means of their contribution to quality control and improvement. Poor quality is costly. Patient satisfaction increases the chances that the patient will be a promoter of the provider to friends and colleagues. As such, involvement of the research staff in the improvement of the quality of care can ultimately result in economic revenue for the provider. The most advanced methodologies for continuous quality improvement (e.g., six-sigma) are data-driven and use statistical tools similar to those utilized in the traditional research setting. Given that these methods rely on the application of the scientific process to quality improvement, researchers have the adequate skills and mind-set to embrace them and thereby contribute effectively to the quality team. The aim of this article is to demonstrate by means of real-life examples how to utilize the findings of outcome studies for quality management in a manner similar to that used in the business community. It also aims to stimulate research groups to better understand that, by adopting a different perspective, their studies can be an additional resource for the healthcare provider. The change in perspective should stimulate researchers to go beyond the traditional studies examining predictors of treatment outcome and to see things instead in terms of the “bigger picture”, i.e., the improvement of the process outcome, the quality of the service