Project description:Evolving resistance to artemisinin-based compounds in SE Asia threatens to derail attempts to control and eliminate malaria. Resistance has been confirmed in western Cambodia, has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CR) from the blood following treatment. We used a two-phase approach to identify the genes underlying this ongoing selective event. Comparison of geographical differentiation and haplotype structure at 6,969 polymorphic SNPs in 91 parasites from western Cambodia, western Thailand and Laos identified 33 strongly selected genome regions. We screened SNPs and microsatellites within these genome regions in 718 parasites from western Thailand, and identified a 35kb region of chr 13 showing strong association (P=10-6 to 10-11) with slow CR. This region contains several compelling candidate loci, such as HSP70, for assessment by transfection. These results illustrate the efficacy of targeted association for identifying the genetic basis of adaptive traits.
Project description:Evolving resistance to artemisinin-based compounds in SE Asia threatens to derail attempts to control and eliminate malaria. Resistance has been confirmed in western Cambodia, has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CR) from the blood following treatment. We used a two-phase approach to identify the genes underlying this ongoing selective event. Comparison of geographical differentiation and haplotype structure at 6,969 polymorphic SNPs in 91 parasites from western Cambodia, western Thailand and Laos identified 33 strongly selected genome regions. We screened SNPs and microsatellites within these genome regions in 718 parasites from western Thailand, and identified a 35kb region of chr 13 showing strong association (P=10-6 to 10-11) with slow CR. This region contains several compelling candidate loci, such as HSP70, for assessment by transfection. These results illustrate the efficacy of targeted association for identifying the genetic basis of adaptive traits. 91 malaria parasite isolates assayed for single nucleotide polymorphisms across 45K loci
Project description:We used Affymetrix SNP6.0 microarray profiling to analyze Copy Number Variation in tumor and paired non-tumor tissue of HCC and CCA patients. We used copy number data to confirm molecular subgroups of HCC and CCA patients from Thailand
Project description:Human immunodeficiency virus (HIV) disproportionately affects men who have sex with men (MSM) and transgender women (TGW). Safe and acceptable topical HIV prevention methods that target the rectum are needed. MTN-017 was a phase 2, 3-period, randomized sequence, open-label, expanded safety and acceptability crossover study comparing rectally applied reduced-glycerin (RG) 1% tenofovir (TFV) and oral emtricitabine/TFV disoproxil fumarate (FTC/TDF). In each 8-week study period participants were randomized to RG-TFV rectal gel daily, or RG-TFV rectal gel before and after receptive anal intercourse (RAI; or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. MSM and TGW (n = 195) were enrolled from 8 sites in the United States, Thailand, Peru, and South Africa with mean age of 31.1 years (range 18-64). The clinical results were reported here https://www.ncbi.nlm.nih.gov/pubmed/27986684. For the gene expression study, rectal biopsies were obtained from a subset of participants (n = 36) in the United States (Pittsburgh) and Thailand (Bangkok). Biopsies were provided at baseline and after each study period.
Project description:The transcriptome profilling of an Aedes aegypti strain from Thailand resistant to Permethrin and Temephos (Nakhon Sawan 2, NS2) was compared to a susceptible strain of Thailand: Phatthalung (P). A experimental loop design was used : NS2 larvae unexposed vs P, NS2 Exposed (larvae survivors of a temephos bioassay inducing 65% mortality) vs P and NS2 Exposed vs NS2 Unexposed.
