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Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations

Authors: Lars Ole Schwen, Arne Schenk, Clemens Kreutz, Jens Timmer, María Matilde Bartolomé Rodríguez, Lars Kuepfer, Tobias Preusser

DOI: 10.1371/journal.pone.0133653

Date Published: 29th Jul 2015

Projects: C1: The role of blood flow in liver lobule function and morphology, D1: Regulation of Blood Flow and Perfusion in the Liver, E3: Horizontal integration on organ scale, E4: Vertical integration across biological scales

Journal: PLoS ONE

Citation: PLoS ONE 10(7) : e0133653

Scales: Cell, Liver lobule, Liver and Organism

Abstract (Expand)

The mammalian liver plays a key role for metabolism and detoxification of xenobiotics in the body. The corresponding biochemical processes are typically subject to spatial variations at different length ...

Created: 30th Jul 2015 at 09:09 Last updated: 30th Jul 2015 at 09:13

Regulation of Liver Enriched Transcription Factors in Rat Hepatocytes Cultures on Collagen and EHS Sarcoma Matrices

Authors: Jürgen Borlak, Prafull Kumar Singh, Ina Rittelmeyer

PubMed ID: 25901575

Date Published: 22nd Apr 2015

Projects: A3.6: Transcription factor network and links to metabolism in NAFLD

Journal: PLoS ONE

Citation: PLoS ONE 10(4): e0124867

Scales: Cell

Abstract (Expand)

Liver-enriched transcription factors (LETF) play a crucial role in the control of liver-specific gene expression and for hepatocytes to retain their molecular and cellular functions complex interactions ...

Created: 5th May 2015 at 13:28

Role of ABC transporters in fluoropyrimidine-based chemotherapy response

Authors: Anne T Nies, Tarek Magdy, Matthias Schwab, Ulrich M Zanger

PubMed ID: 25640272

Date Published: 8th Jan 2015

Projects: A3.4: Linking signalling to metabolic functions, B5: Cell-cell communication influences detoxifying functions in hepatocytes, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Adv. Cancer Res.

Citation: Adv. Cancer Res. 125: 217-43

Scales: Not specified

Abstract (Expand)

Since over 50 years, 5-fluorouracil (5-FU) is in use as backbone of chemotherapy treatment regimens for a wide range of cancers including colon, breast, and head and neck carcinomas. However, drug ...

Created: 7th Apr 2015 at 14:52

Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload

Authors: Sandro Altamura, Regina Kessler, Hermann-Josef Gröne, Norbert Gretz, Matthias W Hentze, Bruno Galy, Martina U Muckenthaler

PubMed ID: 25100063

Date Published: 8th Aug 2014

Projects: B1.3: Linking modulation of iron metabolism with the impact of macrophag...

Journal: Cell Metab.

Citation: Cell Metab. 20(2): 359-67

Scales: Intercellular, Liver and Organism

Abstract (Expand)

The regulatory axis between the iron hormone hepcidin and its receptor, the iron exporter ferroportin (FPN), is central to iron homeostasis. Mutations preventing hepcidin-mediated degradation of FPN ...

Created: 21st Jan 2015 at 10:21

RPPApipe: A pipeline for the analysis of reverse-phase protein array data

Authors: Johannes Eichner, Yvonne Heubach, Manuel Ruff, Hella Kohlhof, Stefan Strobl, Barbara Mayer, Michael Pawlak, Markus F. Templin, Andreas Zell

DOI: 10.1016/j.biosystems.2014.06.009

Date Published: 1st Aug 2014

Projects: A3.4: Linking signalling to metabolic functions, B5: Cell-cell communication influences detoxifying functions in hepatocytes

Journal: Biosystems

Citation: Biosystems 122 : 19

Scales: Cell and Intercellular

Abstract (Expand)

Background and scope: Today, web-based data analysis pipelines exist for a wide variety of microarray platforms, such as ordinary gene-centered arrays, exon arrays and SNP arrays. However, most of the ...

Created: 17th Nov 2015 at 12:14 Last updated: 17th Nov 2015 at 12:15

Recent advances in live cell imaging of hepatoma cells

Authors: Sandeep Salipalli, Prafull Kumar Singh, Jürgen Borlak

PubMed ID: 25005127

Date Published: 8th Jul 2014

Projects: A1.1: Central liver metabolism and its regulation under nutritional chal...

Journal: BMC Cell Biol.

Citation: BMC Cell Biol. 15(1): 26

Scales: Cell

Abstract (Expand)

Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the ...

Created: 10th Jul 2014 at 12:23

Recent insights into the molecular pathophysiology of lipid droplet formation in hepatocytes

Authors: Nishika Sahini, Jürgen Borlak

PubMed ID: 24607340

Date Published: 13th Mar 2014

Projects: A1.1: Central liver metabolism and its regulation under nutritional chal...

Journal: Prog. Lipid Res.

Citation: Prog. Lipid Res. 54C: 86-112

Scales: Cell

Abstract (Expand)

Triacyglycerols are a major energy reserve of the body and are normally stored in adipose tissue as lipid droplets (LDs). The liver, however, stores energy as glycogen and digested triglycerides in the ...

Created: 31st Mar 2014 at 14:53

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

Authors: Patricio Godoy, Nicola J Hewitt, Ute Albrecht, Melvin E Andersen, Nariman Ansari, Sudin Bhattacharya, Johannes Georg Bode, Jennifer Bolleyn, Christoph Borner, Jan Böttger, Albert Braeuning, Robert A Budinsky, Britta Burkhardt, Neil R Cameron, Giovanni Camussi, Chong-Su Cho, Yun-Jaie Choi, J Craig Rowlands, Uta Dahmen, Georg Damm, Olaf Dirsch, María Teresa Donato, Jian Dong, Steven Dooley, Dirk Drasdo, Rowena Eakins, Karine Sá Ferreira, Valentina Fonsato, Joanna Fraczek, Rolf Gebhardt, Andrew Gibson, Matthias Glanemann, Chris E P Goldring, María José Gómez-Lechón, Geny M M Groothuis, Lena Gustavsson, Christelle Guyot, David Hallifax, Seddik Hammad, Adam Hayward, Dieter Häussinger, Claus Hellerbrand, Philip Hewitt, Stefan Hoehme, Hermann-Georg Holzhütter, J Brian Houston, Jens Hrach, Kiyomi Ito, Hartmut Jaeschke, Verena Keitel, Jens M Kelm, B Kevin Park, Claus Kordes, Gerd A Kullak-Ublick, Edward L LeCluyse, Peng Lu, Jennifer Luebke-Wheeler, Anna Lutz, Daniel J Maltman, Madlen Matz-Soja, Patrick McMullen, Irmgard Merfort, Simon Messner, Christoph Meyer, Jessica Mwinyi, Dean J Naisbitt, Andreas K Nussler, Peter Olinga, Francesco Pampaloni, Jingbo Pi, Linda Pluta, Stefan A Przyborski, Anup Ramachandran, Vera Rogiers, Cliff Rowe, Celine Schelcher, Kathrin Schmich, Michael Schwarz, Bijay Singh, Ernst H K Stelzer, Bruno Stieger, Regina Stöber, Yuichi Sugiyama, Ciro Tetta, Wolfgang E Thasler, Tamara Vanhaecke, Mathieu Vinken, Thomas S Weiss, Agata Widera, Courtney G Woods, Jinghai James Xu, Kathy M Yarborough, Jan G Hengstler

PubMed ID: 23974980

Date Published: 23rd Aug 2013

Projects: CTU SOP Human Hepatocytes, CTU SOP Monolayer/sandwich culture hepatocytes, CTU SOP Mouse Hepatocytes, Virtual Liver

Journal: Arch. Toxicol.

Citation: Arch. Toxicol. 87(8): 1315-530

Scales: Not specified

Abstract (Expand)

This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, ...

Created: 9th Sep 2013 at 15:23 Last updated: 24th Oct 2013 at 16:14

Rapid degradation of solid-phase bound peptides by the 20S proteasome

Authors: Marc Hovestädt, Ulrike Kuckelkorn, Agathe Niewienda, Christin Keller, Andrean Goede, Bernhard Ay, Stefan Günther, Katharina Janek, Rudolf Volkmer, Hermann-Georg Holzhütter

PubMed ID: 23893543

Date Published: 28th Jul 2013

Projects: No Projects

Journal: J. Pept. Sci.

Citation: J. Pept. Sci. 19(9): 588-97

Scales: Not specified

Abstract (Expand)

Proteasomes are cellular proteases involved in the degradation of numerous cellular proteins. The 20S proteasome is a cylindrical 28-mer protein complex composed of two outer heptameric α-rings forming ...

Created: 9th Sep 2013 at 15:19 Last updated: 24th Oct 2013 at 16:14

RNA-binding proteins in Mendelian disease

Authors: Alfredo Castello, Bernd Fischer, Matthias W Hentze, Thomas Preiss

PubMed ID: 23415593

Date Published: 15th Feb 2013

Projects: B1.3: Linking modulation of iron metabolism with the impact of macrophag...

Journal: Trends Genet.

Citation: Trends Genet. 29(5): 318-27

Scales: Not specified

Abstract (Expand)

RNA-binding proteins (RBPs) control all aspects of RNA fate, and defects in their function underlie a broad spectrum of human pathologies. We focus here on two recent studies that uncovered the in vivo ...

Created: 14th Jan 2014 at 14:42

Robustness of signal transduction pathways

Authors: Nils Blüthgen, Stefan Legewie

PubMed ID: 23007845

Date Published: 25th Sep 2012

Projects: A2.4: Linking signalling pathways regulating liver regeneration and orga..., B1.2: Reciprocal effect of cell-cell communication on information proces..., B1.3: Linking modulation of iron metabolism with the impact of macrophag...

Journal: Cell. Mol. Life Sci.

Citation: Cell. Mol. Life Sci. 70(13): 2259-69

Scales: Cell and Intercellular

Abstract (Expand)

Signal transduction pathways transduce information about the outside of the cell to the nucleus, regulating gene expression and cell fate. To reliably inform the cell about its surroundings, information ...

Created: 20th Jan 2014 at 16:31

Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS

Authors: Iwona Stelniec-Klotz, Stefan Legewie, Oleg Tchernitsa, Franziska Witzel, Bertram Klinger, Christine Sers, Hanspeter Herzel, Nils Blüthgen, Reinhold Schäfer

PubMed ID: 22864383

Date Published: 7th Aug 2012

Projects: A2.3: Cross-talk and distinct properties of growth factor signalling reg..., B2.1: Hepatic stellate cells as source and target for hepatocellular gro...

Journal: Mol. Syst. Biol.

Citation: Mol. Syst. Biol. 8: 601

Scales: Cell

Abstract (Expand)

RAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here, we used a ...

Created: 3rd Sep 2012 at 11:20 Last updated: 24th Oct 2013 at 16:16

Rab5 is necessary for the biogenesis of the endolysosomal system in vivo

Authors: Anja Zeigerer, Jerome Gilleron, Roman L Bogorad, Giovanni Marsico, Hidenori Nonaka, Sarah Seifert, Hila Epstein-Barash, Satya Kuchimanchi, Chang Geng Peng, Vera M Ruda, Perla Del Conte-Zerial, Jan G Hengstler, Yannis Kalaidzidis, Victor Koteliansky, Marino Zerial

PubMed ID: 22622570

Date Published: 25th May 2012

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., A3.3: Hepatocyte polarity, A3.5: The impact of cell polarity on metabolism detoxification and endoc..., B3: Intercellular communication through cell adhesion

Journal: Nature

Citation: Nature 485(7399): 465-70

Scales: Cell

Abstract (Expand)

An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this ...

Created: 6th Aug 2012 at 14:00 Last updated: 24th Oct 2013 at 16:16

Rodent animal models for surrogate analysis of cell therapy in acute liver failure

Authors: Bruno Christ, Sandra Brückner

PubMed ID: 22485094

Date Published: 2nd Apr 2012

Projects: C6: Organization and function of the sinusoidal system and the liver lob..., Showcase HGF and Regeneration, Virtual Liver

Journal: Front Physiol

Citation: Front Physiol 3: 78

Scales: Cell and Liver

Abstract (Expand)

Without therapeutic intervention acute liver failure (ALF) is the consequence of a progredient destruction of the liver parenchyma due to metabolic exhaustion of the hepatocytes. Perivenous hepatocytes ...

Created: 19th Nov 2013 at 11:57

Response of sinusoidal mouse liver cells to choline-deficient ethionine-supplemented diet

Authors: Elke Ueberham, Jan Böttger, Uwe Ueberham, Jens Grosche, Rolf Gebhardt

PubMed ID: 20942944

Date Published: 13th Oct 2010

Projects: A: Cellular level, B: Communication of Hepatocytes and Non-Parenchymal Liver Cells, C: Liver lobule level

Journal: Comp Hepatol

Citation: Comp Hepatol 9: 8

Scales: Cell, Intercellular, Liver lobule and Liver

Abstract (Expand)

Proliferation of oval cells, the bipotent precursor cells of the liver, requires impeded proliferation and loss of hepatocytes as well as a specific micro-environment, provided by adjacent sinusoidal ...

Created: 20th Jul 2012 at 10:16 Last updated: 24th Oct 2013 at 16:19

Recurrent design patterns in the feedback regulation of the mammalian signalling network

Authors: Stefan Legewie, Hanspeter Herzel, Hans V Westerhoff, Nils Blüthgen

PubMed ID: 18463614

Date Published: 6th May 2008

Projects: HepatoSys

Journal: Mol. Syst. Biol.

Citation: Mol. Syst. Biol. 4: 190

Scales: Not specified

Abstract (Expand)

Biochemical networks are characterized by recurrent patterns and motifs, but the design principles underlying the dynamics of the mammalian intracellular signalling network remain unclear. We systematically ...

Created: 11th Sep 2012 at 13:02 Last updated: 24th Oct 2013 at 16:22

Reduced modeling of signal transduction - a modular approach

Authors: Markus Koschorreck, Holger Conzelmann, Sybille Ebert, Michael Ederer, Ernst Dieter Gilles

PubMed ID: 17854494

Date Published: 13th Sep 2007

Projects: No Projects

Journal: BMC Bioinformatics

Citation: BMC Bioinformatics 8: 336

Scales: Not specified

Abstract (Expand)

Combinatorial complexity is a challenging problem in detailed and mechanistic mathematical modeling of signal transduction. This subject has been discussed intensively and a lot of progress has been ...

Created: 30th Oct 2012 at 09:04 Last updated: 24th Oct 2013 at 16:23