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: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.
Project description:Vongsangnak2008 - Genome-scale metabolic
network of Aspergillus oryzae (iWV1314)
This model is described in the article:
Improved annotation through
genome-scale metabolic modeling of Aspergillus oryzae.
Vongsangnak W, Olsen P, Hansen K,
Krogsgaard S, Nielsen J.
BMC Genomics 2008; 9: 245
Abstract:
BACKGROUND: Since ancient times the filamentous fungus
Aspergillus oryzae has been used in the fermentation industry
for the production of fermented sauces and the production of
industrial enzymes. Recently, the genome sequence of A. oryzae
with 12,074 annotated genes was released but the number of
hypothetical proteins accounted for more than 50% of the
annotated genes. Considering the industrial importance of this
fungus, it is therefore valuable to improve the annotation and
further integrate genomic information with biochemical and
physiological information available for this microorganism and
other related fungi. Here we proposed the gene prediction by
construction of an A. oryzae Expressed Sequence Tag (EST)
library, sequencing and assembly. We enhanced the function
assignment by our developed annotation strategy. The resulting
better annotation was used to reconstruct the metabolic network
leading to a genome scale metabolic model of A. oryzae.
RESULTS: Our assembled EST sequences we identified 1,046 newly
predicted genes in the A. oryzae genome. Furthermore, it was
possible to assign putative protein functions to 398 of the
newly predicted genes. Noteworthy, our annotation strategy
resulted in assignment of new putative functions to 1,469
hypothetical proteins already present in the A. oryzae genome
database. Using the substantially improved annotated genome we
reconstructed the metabolic network of A. oryzae. This network
contains 729 enzymes, 1,314 enzyme-encoding genes, 1,073
metabolites and 1,846 (1,053 unique) biochemical reactions. The
metabolic reactions are compartmentalized into the cytosol, the
mitochondria, the peroxisome and the extracellular space.
Transport steps between the compartments and the extracellular
space represent 281 reactions, of which 161 are unique. The
metabolic model was validated and shown to correctly describe
the phenotypic behavior of A. oryzae grown on different carbon
sources. CONCLUSION: A much enhanced annotation of the A.
oryzae genome was performed and a genome-scale metabolic model
of A. oryzae was reconstructed. The model accurately predicted
the growth and biomass yield on different carbon sources. The
model serves as an important resource for gaining further
insight into our understanding of A. oryzae physiology.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180056.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.