Articles by Simone S. E. Nielsen in JoVE
Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells Simone S. E. Nielsen1, Piotr Siupka1, Ana Georgian2, Jane E. Preston2, Andrea E. Tóth1, Siti R. Yusof2,3, N. Joan Abbott2, Morten S. Nielsen1 1Lundbeck Foundation Research Initiative on Brain Barriers and Drug Delivery, Department of Biomedicine, Aarhus University, 2 The aim of the protocol is to present an optimized procedure for the establishment of an in vitro blood-brain barrier (BBB) model based on primary porcine brain endothelial cells (pBECs). The model shows high reproducibility, high tightness, and is suitable for studies of transport and intracellular trafficking in drug discovery.
Other articles by Simone S. E. Nielsen on PubMed
Genetically Based Low Oxygen Affinities of Felid Hemoglobins: Lack of Biochemical Adaptation to High-altitude Hypoxia in the Snow Leopard The Journal of Experimental Biology. Aug, 2015 | Pubmed ID: 26246610 Genetically based modifications of hemoglobin (Hb) function that increase blood-O2 affinity are hallmarks of hypoxia adaptation in vertebrates. Among mammals, felid Hbs are unusual in that they have low intrinsic O2 affinities and reduced sensitivities to the allosteric cofactor 2,3-diphosphoglycerate (DPG). This combination of features compromises the acclimatization capacity of blood-O2 affinity and has led to the hypothesis that felids have a restricted physiological niche breadth relative to other mammals. In seeming defiance of this conjecture, the snow leopard (Panthera uncia) has an extraordinarily broad elevational distribution and occurs at elevations above 6000 m in the Himalayas. Here, we characterized structural and functional variation of big cat Hbs and investigated molecular mechanisms of Hb adaptation and allosteric regulation that may contribute to the extreme hypoxia tolerance of the snow leopard. Experiments revealed that purified Hbs from snow leopard and African lion exhibited equally low O2 affinities and DPG sensitivities. Both properties are primarily attributable to a single amino acid substitution, β2His→Phe, which occurred in the common ancestor of Felidae. Given the low O2 affinity and reduced regulatory capacity of feline Hbs, the extreme hypoxia tolerance of snow leopards must be attributable to compensatory modifications of other steps in the O2-transport pathway.