ABSTRACT
In this study, biomarkers and transcriptional factor motifs were identified in order to investigate the etiology and phenotypic severity of Down syndrome. GSE 1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus (GEO). A robust multiarray analysis (RMA) algorithm was applied to detect differentially expressed genes (DEGs). In order to screen for biological pathways and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, the database for annotation, visualization, and integrated discovery (DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs. Finally, a transcriptional regulatory network was constructed, and a hypergeometric distribution test was applied to select for significantly enriched transcriptional factor motifs. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were each up-regulated two-fold in Down syndrome samples compared to normal samples; of these, SON and TTC3 were newly reported. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were located on human chromosome 21 (mouse chromosome 16). The DEGs were significantly enriched in macromolecular complex subunit organization and focal adhesion pathways. Eleven significantly enriched transcription factor motifs (PAX5, EGR1, XBP1, SREBP1, OLF1, MZF1, NFY, NFKAPPAB, MYCMAX, NFE2, and RP58) were identified. The DEGs and transcription factor motifs identified in our study provide biomarkers for the understanding of Down syndrome pathogenesis and progression.
Subject(s)
Animals , Humans , Mice , Rats , Amino Acid Motifs/genetics , Computational Biology/methods , Down Syndrome/genetics , Gene Regulatory Networks/genetics , Transcription Factors/analysis , Algorithms , Biomarkers/analysis , Databases, Genetic , Down Syndrome/etiology , Gene Expression , Gene Ontology , Molecular Sequence Annotation/methods , Phenotype , Protein Array Analysis/methods , Up-Regulation/geneticsABSTRACT
With the construction of the Three Gorges high dam on the Yangtze River in China in mind, a serious of ecological environmental factors that might affect the transmission of Schistosoma japonicum in Jian Han Plain were investigated by means of data collection, field surveys and observation in Hubei Province. Several ecological factors including water level of the Yangtze River; riparian water table, annual rainfall and yearly evaporation were investigated in relation to the prevalence of schistosomiasis. The results suggest that after the dam construction, middle water level flows (ie between flood flows and dry-weather flows) will persist in the flood season due to a rise in the water table. The investigation indicated that snail distribution and human schistosomiasis prevalence differed significantly between years which had typically high, middle and low typical water levels in the Yangzte. Moreover, the prevalence of the disease showed a significant linear regression relationship with density of snail intermediate hosts, water table, annual rainfall, yearly evaporation and ground altitude in the survey area. Systematic and careful monitoring and surveillance is necessary to investigate the impact of the environmental changes brought about by the dam construction on schistosomiasis transmission.
Subject(s)
Animals , China/epidemiology , Environment , Fresh Water , Humans , Linear Models , Population Density , Prevalence , Rain , Schistosomiasis japonica/epidemiology , Snails/parasitology , Water Movements , WeatherABSTRACT
In order to explore the possible occurrence of inducing resistance of Schistosoma japonicum to praziquantel (PZQ), a set of animal experiments were carried out. Outbred mice (NIH strain), Anhui isolates of S. japonicum and Oncomelania hupensis were used. In one protocol five weeks after being infected with 48-52 cercariae, mice were orally dosed with PZQ 300 mg/kg, and killed 82 days later to isolate eggs from the liver. Snails were exposed to miracidia released from egg-hatching. F1 progeny were thus obtained through cercarial inoculation. The same scheme was applied for the establishment of the F2 generation. In another protocol two weeks after infection, PZQ 50 mg/kg/day was given to mice for 5 days. Eggs were collected 26-27 days post treatment and the identical procedures were adopted for F1 and F2 generations successively. Analysis of total worm and female worm reduction rates indicated that there was no significant difference between the sensitivity to PZQ of F1 and F2 progenies of S. japonicum and the parent worms.