Biochemical and structural characterization of Cdc14 phosphatases from pathogenic fungi

Cyclin-dependent kinases (Cdk) drive cell cycle progression and reversal of Cdk phosphorylation is essential for mitotic exit. Cdc14 is a widely conserved family of protein phosphatases that reverse Cdk phosphorylation. Recently, Cdc14 was also found to be essential for pathogenicity of some fungal plant pathogens. Fungal pathogens, like Ustilago maydis, decrease agricultural crop yield costing global agriculture by some accounts $60 billion per year. Since Cdc14 is absent in plants, a fungi specific Cdc14 inhibitor could be made to reduce the pathogenicity of U. maydis and other fungal plant pathogens to increase crop yields. To guide inhibitor development, a three-dimensional structural model of fungal Cdc14 is needed. Therefore, we recombinantly expressed Ustilago maydis Cdc14 (UmCdc14) and a catalytically inactive substrate trapping mutant (UmCdc14C318S) with N-terminal hexa-histidine tags in E. coli. Recombinant UmCdc14 and UmCdc14C318S were successfully purified using immobilized metal affinity chromatography. We screened the purified proteins by sitting drop crystallography. Two conditions yielded small crystals for UmCdc14. One condition yielded a crystal for UmCdc14C318S. These conditions were used for large scale crystal growth by hanging drop crystallography. If ideal conditions are found, UmCdc14C318S will be crystallized bound to a peptide substrate to capture the molecular binding determinants that will help guide inhibitor design. Wild-type UmCdc14 will be crystallized bound to small molecule inhibitors identified by a previous high throughput library screen. In the future, we will also explore crystallization of Cdc14 orthologs from other plant pathogens

Hidden Epidemic of Macrolide-resistant Pneumococci

Community-acquired respiratory tract infections (RTIs) account for a substantial proportion of outpatient antimicrobial drug prescriptions worldwide. Concern over the emergence of multidrug resistance in pneumococci has largely been focused on penicillin-resistant Streptococcus pneumoniae. Macrolide antimicrobial drugs have been widely used to empirically treat community-acquired RTIs because of their efficacy in treating both common and atypical respiratory pathogens, including S. pneumoniae. However, increased macrolide use has been associated with a global increase in pneumococcal resistance, which is leading to concern over the continued clinical efficacy of the macrolides to treat community-acquired RTIs. We provide an overview of macrolide-resistant S. pneumoniae and assess the impact of this resistance on the empiric treatment of community-acquired RTIs

Concert recording 2013-03-28

[Track 01]. Fanfares liturgiques. Procession du Vendredi-Saint / Henri Tomasi -- [Track 02]. The good soldier Schweik suite. Overture / Robert Kurka -- [Track 03]. The good soldier Schweik suite. Lament / Robert Kurka -- [Track 04]. The good soldier Schweik suite. March / Robert Kurka -- [Track 05]. The good soldier Schweik suite. War Dance / Robert Kurka -- [Track 06]. The good soldier Schweik suite. Pastoral / Robert Kurka -- [Track 07]. The good soldier Schweik suite. Finale / Robert Kurka -- [Track 08]. Serenade no. 11 in E flat major, KV 375. Allegro maestoso / Wolfgang Amadeus Mozart -- [Track 09]. Prelude, fugue and riffs / Leonard Bernstein

Dating the detachment fault system of the Ruby Mountains, Nevada: Significance for the kinematics of low‐angle normal faults

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94601/1/tect2138.pd

Speech Communication

Contains table of contents for Part IV, table of contents for Section 1 and reports on five research projects.Apple Computer, Inc.C.J. Lebel FellowshipNational Institutes of Health (Grant T32-NS07040)National Institutes of Health (Grant R01-NS04332)National Institutes of Health (Grant R01-NS21183)National Institutes of Health (Grant P01-NS23734)U.S. Navy / Naval Electronic Systems Command (Contract N00039-85-C-0254)U.S. Navy - Office of Naval Research (Contract N00014-82-K-0727

Registered Ship Notes

https://digitalmaine.com/blue_hill_documents/1179/thumbnail.jp