3F). Sox9-EGFP High cells were also highly enriched (+3.46-+101.8-fold change vs. Sox9-EGFP Negative cells) in multiple genes encoding gastrointestinal hormones including neurotensin, substance P, ChgA, chromogranin-B, cholecystokinin, glucagon, secretin, gastric inhibitory peptide, and ghrelin (Table 3). These findings strongly support prior data (17, thereby 21) that the Sox9-EGFP High cells are highly enriched for EECs (Table 3). Unexpectedly, microarray data also revealed that BMI1 and HOPX, which mark +4 slowly cycling or quiescent ISCs (54, 61), were significantly and exclusively enriched in Sox9-EGFP High cells vs. all other Sox9-EGFP cell types (+2.65- and +4.15-fold change vs. Sox9-EGFP Negative cells, respectively; P = 4.04E-11 and P = 9.25E-15, respectively) (Table 3).
Several lines of evidence suggest that Dclk1, also called DCAMKL-1, may represent another putative marker of slowly cycling/quiescent ISCs (39). Immunofluorescence studies clearly demonstrated that DCAMKL-1 colocalized with cells expressing high levels of Sox9-EGFP (Fig. 4) and quantitative PCR revealed that DCAMKL-1 mRNA was dramatically enriched in Sox9-EGFP High cells (+147.0 �� 61.9-fold change vs. Sox9-EGFP Negative cells; P < 0.05). Table 3. Genes upregulated specifically in Sox9-EGFP High cells Fig. 4. DCAMKL-1 colocalizes with Sox9-EGFP High cells. Immunostaining for Sox9-EGFP (green) and DCAMKL-1 (red) demonstrates that in intestinal epithelial crypts, DCAMKL-1 colocalizes with high levels of Sox9-EGFP [nuclei staining, 4,6-diamidino-2-phenylindole ... Sox9-EGFP Negative cells and phenotype of differentiated IEC lineages.
A number of genes that were specifically expressed at significantly higher levels in Sox9-EGFP Negative cells vs. all other Sox9-EGFP cell populations are known markers of absorptive enterocytes including trehalase, lactase, aminopeptidase N, alkaline phosphatase, and glucoamylase, which are all enterocyte brush border enzymes (Table 4). Furthermore, Sox9-EGFP Negative cells exhibited specific upregulation of FABP1, FABP2, and SLC2A5 genes, coding for liver and intestinal fatty acid-binding protein and GLUT5, which are all well-accep
Malaria is a major disease burden in 106 countries, causing an estimated 225 million cases and, as reported for 2010, 665,000 to 1,133,000 human deaths each year in tropical and sub-tropical regions [1].
Despite recent progress [2], drug resistance remains a major obstacle to the effective and sustainable control of malaria. Cellular redox Cilengitide reactions play important roles not only in redox regulatory processes and antioxidant defense but also in the mechanisms of drug action and drug resistance in malaria parasites [3], [4]. Recent advances in parasite biology suggest a compartmentalization of redox metabolism [5] as well as of cellular processes that are sites of drug action [6]. Indeed, several antimalarial drugs have been reported to act through the induction of oxidative [7] or nitrosative stress [8].