TY  - JOUR
A1  - Okoro, Chinyere K.
A1  - Barquist, Lars
A1  - Connor, Thomas R.
A1  - Harris, Simon R.
A1  - Clare, Simon
A1  - Stevens, Mark P.
A1  - Arends, Mark J.
A1  - Hale, Christine
A1  - Kane, Leanne
A1  - Pickard, Derek J.
A1  - Hill, Jennifer
A1  - Harcourt, Katherine
A1  - Parkhill, Julian
A1  - Dougan, Gordon
A1  - Kingsley, Robert A.
T1  - Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa
JF  - PLoS Neglected Tropical Diseases
N2  - Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population.
KW  - genome sequence
KW  - infection
KW  - pathogenicity
KW  - children
KW  - disease
KW  - adults
KW  - identification
KW  - Escherichia coli
KW  - virulence
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143779
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Ramachandran, Sarada Devi
A1  - Schirmer, Katharina
A1  - Münst, Bernhard
A1  - Heinz, Stefan
A1  - Ghafoory, Shahrouz
A1  - Wölfl, Stefan
A1  - Simon-Keller, Katja
A1  - Marx, Alexander
A1  - Øie, Cristina Ionica
A1  - Ebert, Matthias P.
A1  - Walles, Heike
A1  - Braspenning, Joris
A1  - Breitkopf-Heinlein, Katja
T1  - In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells
JF  - PLoS One
N2  - In this study we used differentiated adult human upcyte (R) cells for the in vitro generation of liver organoids. Upcyte (R) cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte (R) process). Proliferating upcyte (R) cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte (R) cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel\(^{TM}\), they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.
KW  - adults
KW  - enzyme metabolism
KW  - albumins
KW  - primary cells
KW  - induction
KW  - expression
KW  - human heptocytes
KW  - mesenchymal stem cells
KW  - oragnoids
KW  - heptaocytes
KW  - drug metabolism
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139552
VL  - 10
IS  - 10
ER  -