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onents from CIM for processes such as neurite-like outgrowth, marker gene expression and TH phosphorylation. IBMX and db-cAMP increase levels of intracellular cAMP which can result in PKA activation. cAMP modulates neural February Differentiation Cord Blood MSC differentiation, neuroendocrine differentiation, neuronal differentiation of glioma cells, neurite like outgrowth in medulloblastomas and neural differentiation of bone marrow MSC. Activation of PKA as well as PKC agonists were known to result in DA differentiation. In our experiments, IBMX and db-cAMP were both required for morphological differentiation of MSChUCB possibly act by perturbing calcium homeostasis of the intracellular parasite. SERCA, the calcium pump of sarcoplasmic reticulum responsible for refilling calcium in the ER stores is critically important for cellular homeostasis and calcium signalling BIBW2992 web functions. Unlike vertebrates that possess three serca genes, P. falciparum has a single SERCA, originally described as PfATPaseFebruary Polymorphism of Pf-SERCA conformational changes during activation, involving a cooperative binding of two Ca large sequence diversity in comparison to other so-called house keeping genes, such as the lactate dehydrogenase locus studied in the same lines. To further explore Pfserca sequence diversity and to look for possible causes and geographical structuring, we sequenced a large panel of field isolates from various malariaendemic geographic areas before widespread deployment of ACT. Our data show clear evidence for geographic structuring and indicate that as yet unknown evolutionary mechanisms are contributing to the large field polymorphism of this locus in some areas. Results Pfserca Polymorphism in the Field We sequenced pfserca in Continent AFRICA Collection area Equatorial Guinea Senegal No samples Year of collection Sequenced Partial Full-length Partial partial Full-length Full-length partial Reference of sample collection unpublished Jambou et al. Legend: NS: non synonymous. Syn: synonymous. All nucleotide, codon and corresponding amino acid positions in the table are adjusted to correspond to positions in the reference catalytic activity of the protein. No mutation was identified in the amino acids described as of major importance for the SERCA function in animal species. PfSERCA Polymorphism and Its Relationship with In Vitro Susceptibility to Artemisinins In the set of February Polymorphism of Pf-SERCA S French Guiana Para Amazonas Senegal Eq. Guinea Thailand Cambodia America Africa Asia All samples h Hd K p D ns D ns ns ns ns ns ns ns ns ns F ns ns ns ns ns ns ns ns ns ns ns ns ns ns ns ns ns Legend: The extent of pfserca gene sequence analysed here correspond to nucleotide coordinates February Polymorphism of Pf-SERCA Genetic Diversity and Geographic Distribution A total of were detected in the samples of French Guiana and Senegal. These tests were not considered significant after applying Bonferroni corrections for multiple tests. Overall, genetic differentiation of pfserca reflected the geographic origin of samples. Highly significant FST estimates were obtained for the three pair wise comparisons: America vs. Africa, America vs. Asia, Africa 7370771 vs. Asia. In Asia, all comparisons involving the monomorphic sample of Cambodia were significant, with the exception of the neighbour sample from Thailand. In Africa, no significant genetic differentiation was observed between the two samples of this continent,. In contrast, American

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