Project description:Transcriptional profiling of four growth phases S. Typhimurium comparing immobilised growth with planktonic growth. Each array used labelled cDNA against a common genomic DNA reference. Triplicate or quadruple arrays were carried out for each of the 8 conditions as well as the inoculum culture: inoculum, planktonic MEP, planktonic LEP, planktonic ESP, planktonic LSP, immobilised MEP, immobilised LEP, immobilised ESP and immobilised LSP
Project description:Proteomic data from dengue virus infected U-937 cells. PVD_C samples were infected via antibody-mediated or DC-SIGN receptor mediated entry routes with wild-type DENV-4 or mock inoculum; time points 2, 8, 16, and 24 hours; 5 biological replicates. PVD_L samples were infected via antibody-mediated or DC-SIGN receptor mediated entry routes with wild-type DENV-1 or mock inoculum; time points 2, 6, 10, 18, 24, and 30 hours; 5 biological replicates.
Project description:To better characterize placentitis, we examined the sRNA expression patterns occurring in the endometrium, chorioallantois and serum of mares. Disease was induced in 10 mares via intracervical inoculation of Streptococcus equi ssp. zooepidemicus, either with moderate or high levels of inoculum; three un-inoculated gestationally-matched mares were used as controls. Matched chorioallantois and endometrium were sampled in two locations: region 1 - main lesion by cervical star with placental separation; and region 2 - gross inflammation without placental separation.
Project description:Malaria remains a global health threat as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome beta5 active-site. A potent analog (SW584) showed efficacy in a mouse model of human malaria after oral dosing. SW584 had a low propensity to generate resistance (Minimum Inoculum of Resistance >109) and was synergistic with dihydroartemisinin. Pf_proteasome purification was facilitated by His8-tag introduction onto beta7. Inhibition of Pfbeta5 correlated with parasite killing, without inhibiting the human proteasome or showing cytotoxicity. The Pf_proteasome_SW584 cryo-EM structure showed SW584 bound non-covalently distal from the catalytic threonine, in an unexplored pocket at the beta5/beta6/beta3 subunit interface that shows species differences between Pf and human proteasomes. Identification of a reversible, species selective, orally active series with low resistance propensity, provides a path for drugging this essential target.