Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9.

Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases

Single versus multiple dose ivermectin regimen in onchocerciasis-infected persons with epilepsy treated with phenobarbital: a randomized clinical trial in the Democratic Republic of Congo

Open data for a randomized clinical trial performed in onchocerciasis-endemic villages of the Logo health zone in Ituri province in the Democratic Republic of Congo where mass ivermectin administration had never been implemented. Ivermectin naïve, persons with epilepsy with Onchocerca volvulus infection were randomly allocated to receive ivermectin once, twice or thrice over a one year period of follow up. At the same time they were treated with the anti-epileptic drug phenobarbital. At baseline, information was collected on seizure semiology, seizure frequency, epilepsy risk factors, relevant medical history, previous AED and ivermectin use. The primary outcome was seizure freedom during the last four months of the 12-month follow up period