1. Pleiotropic drug-resistance attenuated genomic library improves elucidation of drug mechanisms
Namal V. C. Coorey, James H. Matthews, David S. Bellows and Paul H. Atkinson*. Mol. BioSyst., 2015, 11, 3129-3136
In order to establish whether the PA-DMA is more eﬀective in determining the MoA of a PDR-substrate, parallel chemo-genomic screens were performed with the PDR-substrate CHX, a translation elongation inhibitor that has been shown to be a substrate for at least one PDR pump, and the PA-DMA and parental MATa DMA. The CHX chemogenomic profile generated with the parental MATa DMA showed that very few translation-related single gene deletion strains displayed hypersensitivity to CHX (Table S6, ESI†) and that there was no enrichment for gene deletions ascribed to translation-related GO terms (Table S7, ESI†). The same GO analysis of the CHX hypersensitive single gene deletion mutants in Parsons et al. 2004 also did not show enrichment for translation related genes.
2. Improved oral bioavailability of docetaxel by nanostructured lipid carriers: in vitro characteristics, in vivo evaluation and intestinal transport studies
Guihua Fang, Bo Tang, Yanhui Chao, Yu Zhang,* Hui Xu and Xing Tang*. RSC Adv.,2015, 5, 96437–96447
Following DNLCs absorption into intestinal enterocytes, they entered the systemic circulation via the portal vein or intestinal lymphatic. In order to elucidate the intestinal transport pathway, rats were treated with the lymphatic transport inhibitor, cycloheximide. It has been reported that cycloheximide can inhibit the lymphatic transport pathway without damaging other passive and active absorption pathways. When the rats were treated with cycloheximide, the peak concentration of DTX was dramatically decreased and the AUC0–12 h was reduced by about 57% (p < 0.05) in comparison with the control group (Fig. 7). This result demonstrated the importance of intestinal lymphatic transport in the oral absorption of DNLCs.
3. A global investigation of gene deletion strains that aﬀect premature stop codon bypass in yeast, Saccharomyces cerevisiae
Bahram Samanfar, Le Hoa Tan, Ashkan Golshani*. Mol. BioSyst., 2014, 10,916-924
We subjected the gene deletion strains identified via our large-scale screening to sensitivity analysis against two antibiotics, cycloheximide and paromomycin. Cycloheximide interferes with the translocation step of protein biosynthesis and paromomycin has been linked to codon misreading. Using serial dilution spot test analysis, decreasing cell concentrations of the 84 target strains were subjected to sub-inhibitory concentrations of drugs; 45 ng ml-1 of cycloheximide and 18 mg ml-1 of paromomycin. Approximately 69% of the identified gene deletion strains showed sensitivity to one or both drugs (File S2, ESI†). This compares to approximately 26% of the entire set of yeast non-essential gene deletion strains that show sensitivity to at least one of these drugs.