Project description:Concerns about impending failure of artemisinin compounds (ART) have grown with global use of ART-based combination therapy (ACT) against malaria. WHO has defined Plasmodium falciparum resistance to ART as prolonged parasite clearance half-life in vivo (t1/2) plus the presence of certain K13 Kelch-propeller substitutions, e.g. C580Y. Recrudescences and fever clearance times after ART monotherapy, however, have not correlated well with these criteria. We have crossed K13 C580 wild-type and 580Y-mutant parasites for ART studies in Aotus. Artesunate treated C580- but not 580Y-infections recrudesced requiring retreatment, and K13 type had little or no effect on t1/2. These results challenge K13 and t1/2 variations as markers of increased resistance to ART per se and emphasize the need for effective partner drugs in ACTs.
Project description:Intervention type:DRUG. Intervention1:Huaier, Dose form:GRANULES, Route of administration:ORAL, intended dose regimen:20 to 60/day by either bulk or split for 3 months to extended term if necessary. Control intervention1:None.
Primary outcome(s): For mRNA libraries, focus on mRNA studies. Data analysis includes sequencing data processing and basic sequencing data quality control, prediction of new transcripts, differential expression analysis of genes. Gene Ontology (GO) and the KEGG pathway database are used for annotation and enrichment analysis of up-regulated genes and down-regulated genes.
For small RNA libraries, data analysis includes sequencing data process and sequencing data process QC, small RNA distribution across the genome, rRNA, tRNA, alignment with snRNA and snoRNA, construction of known miRNA expression pattern, prediction New miRNA and Study of their secondary structure Based on the expression pattern of miRNA, we perform not only GO / KEGG annotation and enrichment, but also different expression analysis.. Timepoint:RNA sequencing of 240 blood samples of 80 cases and its analysis, scheduled from June 30, 2022..
Project description:The northern white rhinoceros (Ceratotherium simum cottoni) genome and annotation were previously published, but the annotation contained few genes, with many annotation misalignments, and nomenclature not matching HGNC/VGNC naming conventions, making transcriptional studies very difficult. We used in vivo collected granulosa cells for RNA sequencing and de novo transcript assembly through StringTie to identify all nucleotide gene sequences in our samples. Through extensive manual curation we were able to generate a greatly improved genome annotation increasing gene numbers by 81%. This will greatly enable researchers in this field to utilize the genome and annotation to complete transcriptional studies with this species.
Project description:Unlike in Asia and Latin America, Plasmodium vivax infections were rare in Sub-Saharan Africa due to the absence of the Duffy blood group antigen (Duffy Antigen), the only known erythrocyte receptor for the P. vivax merozoite invasion ligand, Duffy Binding Protein 1 (DBP1). However, P. vivax infections have been documented in Duffy-negative individuals throughout Africa, suggesting that P. vivax may use ligands other than DBP1 to invade Duffy-negative erythrocytes through other receptors. To identify potential P. vivax ligands, we compared parasite gene expression in Saimiri and Aotus monkey erythrocytes infected with P. vivax Salvador I (Sal I). DBP1 binds Aotus but does not bind to Saimiri erythrocytes, and thus P. vivax Sal I must invade Saimiri erythrocytes independently of DBP1. Comparing RNA sequencing (RNAseq) data for late stage infections in Saimiri and Aotus erythrocytes when invasion ligands are expressed, we identified genes that belong to tryptophan-rich antigen and MSP3 families that were more abundantly expressed in Saimiri infections as compared to Aotus infections. These genes may encode potential ligands responsible for P. vivax infections of Duffy-negative Africans.